@article {pmid40243472, year = {2025}, author = {Beyoğlu, D and Idle, JR}, title = {The Microbiome and Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {International journal of molecular sciences}, volume = {26}, number = {7}, pages = {}, pmid = {40243472}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; Animals ; Dysbiosis/microbiology ; *Fatty Liver/microbiology/metabolism/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Liver/microbiology/metabolism/pathology ; Bile Acids and Salts/metabolism ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition wherein excessive fat accumulates in the liver, leading to inflammation and potential liver damage. In this narrative review, we evaluate the tissue microbiota, how they arise and their constituent microbes, and the role of the intestinal and hepatic microbiota in MASLD. The history of bacteriophages (phages) and their occurrence in the microbiota, their part in the potential causation of MASLD, and conversely, "phage therapy" for antibiotic resistance, obesity, and MASLD, are all described. The microbiota metabolism of bile acids and dietary tryptophan and histidine is defined, together with the impacts of their individual metabolites on MASLD pathogenesis. Both periodontitis and intestinal microbiota dysbiosis may cause MASLD, and how individual microorganisms and their metabolites are involved in these processes is discussed. Novel treatment opportunities for MASLD involving the microbiota exist and include fecal microbiota transplantation, probiotics, prebiotics, synbiotics, tryptophan dietary supplements, intermittent fasting, and phages or their holins and endolysins. Although FDA is yet to approve phage therapy in clinical use, there are multiple FDA-approved clinical trials, and this may represent a new horizon for the future treatment of MASLD.}, } @article {pmid40243365, year = {2025}, author = {Ismeurt-Walmsley, C and Giannoni, P and Servant, F and Mekki, L-N and Baranger, K and Rivera, S and Marin, P and Lelouvier, B and Claeysen, S}, title = {The same but different: impact of animal facility sanitary status on a transgenic mouse model of Alzheimer's disease.}, journal = {mBio}, volume = {}, number = {}, pages = {e0400124}, doi = {10.1128/mbio.04001-24}, pmid = {40243365}, issn = {2150-7511}, abstract = {UNLABELLED: The gut-brain axis has emerged as a key player in the regulation of brain function and cognitive health. Gut microbiota dysbiosis has been observed in preclinical models of Alzheimer's disease and patients. Manipulating the composition of the gut microbiota enhances or delays neuropathology and cognitive deficits in mouse models. Accordingly, the health status of the animal facility may strongly influence these outcomes. In the present study, we longitudinally analyzed the fecal microbiota composition and amyloid pathology of 5XFAD mice housed in a specific opportunistic pathogen-free (SOPF) and a conventional facility. The composition of the microbiota of 5XFAD mice after aging in conventional facility showed marked differences compared to WT littermates that were not observed when the mice were bred in SOPF facility. The development of amyloid pathology was also enhanced by conventional housing. We then transplanted fecal microbiota (FMT) from both sources into wild-type (WT) mice and measured memory performance, assessed in the novel object recognition test, in transplanted animals. Mice transplanted with microbiota from conventionally bred 5XFAD mice showed impaired memory performance, whereas FMT from mice housed in SOPF facility did not induce memory deficits in transplanted mice. Finally, 18 weeks of housing SOPF-born animals in a conventional facility resulted in the reappearance of specific microbiota compositions in 5XFAD vs WT mice. In conclusion, these results show a strong impact of housing conditions on microbiota-associated phenotypes and question the relevance of breeding preclinical models in specific pathogen-free (SPF) facilities.

IMPORTANCE: Housing conditions affect the composition of the gut microbiota. Gut microbiota of 6-month-old conventionally bred Alzheimer's mice is dysbiotic. Gut dysbiosis is absent in Alzheimer's mice housed in highly sanitized facilities. Transfer of fecal microbiota from conventionally bred mice affects cognition. Microbiota of mice housed in highly sanitized facilities has no effect on cognition.}, } @article {pmid40243343, year = {2025}, author = {Olesen, RH and Larsen, EB and Rubak, T and Baunwall, SMD and Paaske, SE and Gregersen, M and Foss, CH and Erikstrup, C and Krogh, CB and Ehlers, LH and Hvas, CL}, title = {Cost-Effectiveness of Hospital-at-Home and Fecal Microbiota Transplantation in Treating Older Patients With Clostridioides difficile.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaf104}, pmid = {40243343}, issn = {1537-6591}, support = {NNF22OC0074080//Novo Nordisk Foundation/ ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) primarily affects older patients with comorbid conditions and has a high mortality rate. Fecal microbiota transplantation (FMT) is effective and cost-effective for CDI. In a recent study, we demonstrated the clinical benefits of combining hospital-at-home care with FMT for older patients with CDI, but its cost-effectiveness remains unknown. The current study aimed to evaluate the cost-effectiveness of the intervention in patients aged ≥70 years with CDI, compared with standard treatment.

METHODS: The cost-utility analysis was conducted using data from a randomized clinical trial enrolling 217 patients, assessing the cost-effectiveness of the intervention over 90 days. Resource use was assessed from a healthcare sector perspective. Missing data were handled with proxy replacement and multiple imputation. Sensitivity analyses included probabilistic analysis, complete case analysis, adjustment of key unit prices, and a hospital perspective. A willingness-to-pay threshold was set to €22 994 or $24 863 per quality-adjusted life year (QALY).

RESULTS: In the base case analysis, the intervention was dominant, with mean cost savings of €2556 ($2764) and a mean gain of 0.004 QALY. Although resource use was higher, the intervention resulted in an average reduction of 6 hospital admission days per patient and increased odds of clinical resolution. The results remained robust across different perspectives, the exclusion of patients with missing data, and variations in hospital admission costs.

CONCLUSIONS: In patients aged ≥70 years with CDI, an intervention combining hospital-at-home care and FMT is cost-effective compared with standard treatment. The cost-effectiveness is mainly driven by fewer hospital admission days.}, } @article {pmid40237231, year = {2025}, author = {Saeedi, N and Pourabdolhossein, F and Dadashi, M and Suha, AJ and Janahmadi, M and Behzadi, G and Hosseinmardi, N}, title = {Faecal Microbiota Transplantation Modulates Morphine Addictive-Like Behaviours Through Hippocampal Metaplasticity.}, journal = {Addiction biology}, volume = {30}, number = {4}, pages = {e70034}, pmid = {40237231}, issn = {1369-1600}, support = {//Vice President of Research and Technology of Shahid Beheshti University of Medical Sciences/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Male ; Rats, Wistar ; Rats ; *Morphine/pharmacology ; *Morphine Dependence/therapy/physiopathology ; *Neuronal Plasticity/drug effects/physiology ; *Hippocampus/drug effects/physiopathology ; Substance Withdrawal Syndrome ; Naloxone/pharmacology ; Gastrointestinal Microbiome ; Narcotic Antagonists/pharmacology ; Analgesics, Opioid/pharmacology ; }, abstract = {The microbiota-gut-brain axis has been implicated in the pathology of substance use disorders (SUDs). In light of the brain's capability to reorganize itself in response to intrinsic and extrinsic stimuli, opioid-induced dysbiosis is likely to contribute to addictive behaviour through modulating neuroplasticity. In this study, a faecal microbiota transplantation (FMT) from a saline-donor was performed on morphine-treated rats to evaluate the effects of gut microbiota on morphine-induced metaplasticity and addictive behaviours. Male Wistar rats were treated with subcutaneous injections of 10 mg/kg morphine sulphate every 12 h for 9 days in an effort to induce dependence. The withdrawal syndrome was precipitated by injecting naloxone (1.5 mg/kg, ip) after the final dose of morphine. The tolerance was induced by repeated morphine injections over a period of 7 days (10 mg/kg, once a day, ip). FMT was applied daily through gavage of processed faeces 1 week before and during the morphine treatment. Field potential recordings (i.e., fEPSP) were carried out to assess short-term and long-term synaptic plasticity in the CA1 area of the hippocampus following Schaffer-collateral stimulation. Animals subjected to FMT exhibited significant reductions in naloxone-precipitated withdrawal syndrome (one-way ANOVA, p < 0.05). Tolerance to the analgesic effects of morphine was not affected by FMT (two-way ANOVA, p > 0.05). Following high-frequency stimulation (HFS) to induce long-term potentiation (LTP), a greater fEPSP slope was observed in morphine-treated animals (unpaired t test, p < 0.05). FMT from saline-donor rats diminished morphine-induced augmented LTP (unpaired t test, p < 0.05). These results highlighted the alleviating effects of FMT from saline-donors on morphine-induced metaplasticity and dependence potentially by modulating the dysbiosis of gut microbiota.}, } @article {pmid40237060, year = {2025}, author = {Li, H and Lai, H and Xing, Y and Zou, S and Yang, X}, title = {Microbiota-gut-brain axis: Novel Potential Pathways for Developing Antiepileptogenic Drugs.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/1570159X23666250414094040}, pmid = {40237060}, issn = {1875-6190}, abstract = {The treatment of epilepsy remains imperfect due to a lack of understanding of its pathogenesis. Although antiseizure medications can control most seizures, up to 30% of patients experience uncontrolled seizures, leading to refractory epilepsy. Therefore, elucidating the pathogenesis of epilepsy and exploring new avenues to design antiepileptic drugs may improve epilepsy treatment. Recent studies have identified an imbalance of the gut microbiota (GM) in both patients with epilepsy and various animal models of epilepsy. In response to this phenomenon, an increasing number of studies have focused on controlling seizures by regulating GM homeostasis, utilizing methods such as dietary restrictions, fecal microbiota transplantation, and the use of prebiotics. Surprisingly, these interventions have shown promising antiepileptic effects, suggesting that GM, through the regulatory role of the microbiota-gut-brain axis (gut-brain axis), may emerge as a novel strategy for treating epilepsy. This review aims to discuss the research progress on the relationship between GM and epilepsy, incorporating the latest clinical studies and animal experiments. We will specifically concentrate on the potential key role of the gut-brain axis in epileptogenesis, epilepsy development, and outcomes of epilepsy. Through a detailed analysis of the underlying mechanisms of the gut-brain axis, we aim to provide a more comprehensive perspective on understanding the pathophysiology of epilepsy and lay the groundwork for the development of new antiepileptic drugs in the future.}, } @article {pmid40235083, year = {2025}, author = {Brown, R and Barko, P and Ruiz Romero, JDJ and Williams, DA and Gochenauer, A and Nguyen-Edquilang, J and Suchodolski, JS and Pilla, R and Ganz, H and Lopez-Villalobos, N and Gal, A}, title = {The effect of lyophilised oral faecal microbial transplantation on functional outcomes in dogs with diabetes mellitus.}, journal = {The Journal of small animal practice}, volume = {}, number = {}, pages = {}, doi = {10.1111/jsap.13865}, pmid = {40235083}, issn = {1748-5827}, support = {//University of Illinois at Urbana-Champaign Companion Animal Research Grant Program/ ; }, abstract = {OBJECTIVES: We aimed to determine if oral faecal microbiota transplantation improves indices of glycaemic control, changes the faecal dysbiosis indices, alters faecal short-chain fatty acid and bile acid profiles and increases serum glucagon-like-peptide 1 concentrations in diabetic dogs.

MATERIALS AND METHODS: In this prospective randomised, placebo-controlled, double-blinded pilot study, we recruited nine diabetic dogs (five faecal microbiota transplantation and four placebo) and nine healthy controls.

RESULTS: Compared to healthy dogs, diabetic dogs had altered faecal short-chain fatty acid and bile acid profiles. In the first 30 days, the faecal microbiota transplantation group had a more rapid decline in interstitial glucose; however, the mean interstitial glucose of the faecal microbiota transplantation recipients did not differ from the placebo recipients at the end of the study. Compared with placebo, faecal microbiota transplantation recipients had a decreased 24-hour water intake at day 60 and increased faecal abundance of Faecalibacterium.

CLINICAL SIGNIFICANCE: This study provides a proof of concept for faecal microbiota transplantation in canine diabetes, and its data could inform the design of future large-scale studies. Further investigation is required to determine whether faecal microbiota transplantation would have any role as an adjunctive therapy in canine diabetes and to elucidate the mechanisms by which faecal microbiota transplantation may provide a beneficial clinical effect in canine diabetes.}, } @article {pmid40235010, year = {2025}, author = {Chen, M and Pan, J and Song, Y and Liu, S and Sun, P and Zheng, X}, title = {Effect of inulin supplementation in maternal fecal microbiota transplantation on the early growth of chicks.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {98}, pmid = {40235010}, issn = {2049-2618}, support = {20170204043NY2//key technology research. project of Changchun Key R&D Program, and the Outstanding Talents in Science and Technology Innovation/ ; 32472995//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Inulin/administration & dosage/pharmacology ; *Chickens/growth & development/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/drug effects ; Female ; Dietary Supplements ; Feces/microbiology ; Prebiotics/administration & dosage ; }, abstract = {BACKGROUND: Fecal microbial transplantation (FMT) is an important technology for treating diarrhea and enteritis. Additionally, FMT has been applied to improve productivity, alter abnormal behavior, relieve stress, and reduce burdens. However, some previous studies have reported that FMT may cause stress in acceptor animals. Inulin, a prebiotic, can promote growth, enhance immunity, and balance the gut microbiota. Currently, there are limited reports on the effects of combining FMT with inulin on early growth performance in chicks.

RESULTS: In this study, a total of 90 1-day-old chicks were randomly divided into the control group (CON), FMT group, and inulin group (INU). The CON group was fed a basic diet, whereas the FMT and INU groups received fecal microbiota transplantation and FMT with inulin treatment, respectively. Compared with the FMT and CON groups, the INU group presented significantly greater average daily gain (ADG) and average daily feed intake (ADFI) values (P < 0.05). However, the organ indices did not significantly change (P > 0.05). The ratio of the villi to crypts in the ileum significantly differed at 21 and 35 days (P < 0.05). In addition, the cecum concentrations of acetic acid and butyric acid significantly increased in the INU group (P < 0.05). In addition, gut inflammation and serum inflammation decreased in the INU group, and immune factors increased after inulin supplementation. (P < 0.05). Firmicutes and Bacteroidetes were the dominant phyla, with more than 90% of all sequences being identified as originating from these two phyla. Inulin supplementation during mother-sourced microbial transplantation significantly increased the abundance of Rikenella, Butyricicoccus, and [Ruminococcus], which contributed positively to the promotion of early intestinal health and facilitated the early growth of chicks.

CONCLUSION: The results of this study suggest that inulin supplementation in maternal fecal microbiota transplantation can effectively promote early growth and probiotic colonization, which favors the health of chicks. Video Abstract.}, } @article {pmid40234859, year = {2025}, author = {Senthilkumar, H and Arumugam, M}, title = {Gut microbiota: a hidden player in polycystic ovary syndrome.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {443}, pmid = {40234859}, issn = {1479-5876}, mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/physiopathology/therapy ; *Gastrointestinal Microbiome ; Female ; Animals ; Dysbiosis ; }, abstract = {Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects reproductive-aged women worldwide, causing hormonal imbalances and ovarian dysfunction. PCOS affects metabolic health and increases the risk of obesity, insulin resistance, and cardiovascular disease, in addition to infertility. This review delves deeper into the connections of gut microbiota with PCOS pathophysiology, particularly into its impact on hormone metabolism, obesity, inflammation, and insulin resistance by way of short-chain fatty acids, lipopolysaccharides, and gut-brain axis. Studies also show that changes in the metabolic processes and immune responses are seen in changes in the gut microbiota in PCOS subjects, such as changes in the Bacteroidetes and Firmicutes groups. Some bacteria, like Escherichia and Shigella, have been associated with dysbiosis in patients with PCOS, leading to systemic inflammation and changed hormone levels, which further worsen the clinical symptoms. Therapeutic interventions targeting the gut microbiota comprise probiotics, prebiotics, and fecal microbiota transplantation; these have potential to alleviate the symptoms of PCOS. Other precision microbiome-based therapies include postbiotics, and CRISPR-Cas9 genome editing, which are relatively new avenues toward precision treatment. This complex interlink of gut microbiota and PCOS pathophysiology will open the avenues for possible treatments for hormonal imbalances and metabolic problems that characterize these complex disorders. The review here focuses on the requirement of further studies to be able to elucidate the specific pathways relating gut microbiota dysregulation to PCOS and, thus, improve microbiome-based therapies for better clinical outcomes in affected individuals.}, } @article {pmid40234406, year = {2025}, author = {Sui, Y and Zhang, T and Ou, S and Li, G and Liu, L and Lu, T and Zhang, C and Cao, Y and Bai, R and Zhou, H and Zhao, X and Yuan, Y and Wang, G and Chen, H and Kong, R and Sun, B and Li, L}, title = {Statin therapy associated Lactobacillus intestinalis attenuates pancreatic fibrosis through remodeling intestinal homeostasis.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {59}, pmid = {40234406}, issn = {2055-5008}, support = {82270665//National Natural Science Foundation of China/ ; 82270666//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Homeostasis/drug effects ; Fibrosis ; Fecal Microbiota Transplantation ; Male ; *Pancreas/pathology/drug effects ; Macrophages/immunology ; Mice, Inbred C57BL ; CD8-Positive T-Lymphocytes/immunology ; *Intestines/microbiology/drug effects ; *Lactobacillus ; Disease Models, Animal ; *Probiotics/administration & dosage ; }, abstract = {Chronic pancreatitis (CP) is characterized by irreversible fibrotic destruction and impaired pancreatic function. CP disrupts lipid metabolism and causes the imbalance of gut microbiota which in turn exacerbates pancreatic fibrosis. Statins alter gut microbiota and exert anti-inflammatory effects, but its role in CP has not been fully elucidated. Here, we found that statins-associated higher abundance of Lactobacillus intestinalis (L.intestinalis) maintained gut homeostasis that restrained bacteria translocation from gut to the pancreas, which eventually aggravated pancreatic fibrosis through inhibiting CD8[+]T cells-dependent immunity. Fecal microbiota transplantation (FMT) or L.intestinalis administration inhibited the infiltration of CD8[+]T cells and macrophages that delayed CP progression. L.intestinalis restrained the recruitment of M1 macrophages and limited the release of Ccl2/7 in the colon, which prevented epithelial damage and epithelial barrier dysfunction through blocking Ccl2/7-Ccr1 signaling. Our findings elucidate that the utilization of statin therapy or supplementation of L.intestinalis can be potential approach for the therapies of CP.}, } @article {pmid40233040, year = {2025}, author = {Pomej, K and Frick, A and Scheiner, B and Balcar, L and Pajancic, L and Klotz, A and Kreuter, A and Lampichler, K and Regnat, K and Zinober, K and Trauner, M and Tamandl, D and Gasche, C and Pinter, M}, title = {Study protocol: Fecal Microbiota Transplant combined with Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma who failed to achieve or maintain objective response to Atezolizumab/Bevacizumab - the FAB-HCC pilot study.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0321189}, pmid = {40233040}, issn = {1932-6203}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; *Antibodies, Monoclonal, Humanized/therapeutic use/administration & dosage ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; *Bevacizumab/therapeutic use/administration & dosage ; *Carcinoma, Hepatocellular/therapy/drug therapy ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; *Liver Neoplasms/therapy/drug therapy ; Pilot Projects ; Clinical Trials, Phase II as Topic ; }, abstract = {BACKGROUND: The gut microbiota is often altered in chronic liver diseases and hepatocellular carcinoma (HCC), and increasing evidence suggests that it may influence response to cancer immunotherapy. Strategies to modulate the gut microbiome (i.e., fecal microbiota transplant (FMT)) may help to improve efficacy of immune checkpoint inhibitors (ICIs) or even overcome resistance to ICIs. Here, we describe the design and rationale of FAB-HCC, a single-center, single-arm, phase II pilot study to assess safety, feasibility, and efficacy of FMT from patients with HCC who responded to PD-(L)1-based immunotherapy or from healthy donors to patients with HCC who failed to achieve or maintain a response to atezolizumab plus bevacizumab.

METHODS: In this single-center, single-arm, phase II pilot study (ClinicalTrials.gov identifier: NCT05750030), we plan to include 12 patients with advanced HCC who failed to achieve or maintain a response to atezolizumab/bevacizumab. Patients will receive a single FMT via colonoscopy from donors with HCC who responded to PD-(L)1-based immunotherapy or from healthy individuals, followed by atezolizumab/bevacizumab every 3 weeks. The primary endpoint is safety, measured by incidence and severity of treatment-related adverse events. The main secondary endpoint is efficacy, as assessed by best radiological response according to RECISTv1.1 and mRECIST. Additional exploratory endpoints include data on the effect of FMT on recipient gut microbiota, as well as metagenomic analysis of stool samples, analyses of circulating immune cells and serum and stool proteomic, metabolomic and lipidomic signatures.

DISCUSSION: The results of this study will help to define the potential of FMT as add-on intervention in the systemic treatment of advanced HCC, with the potential to improve efficacy of immunotherapy or even overcome resistance.

TRIAL REGISTRATION: EudraCT Number: 2022-000234-42 Clinical trial registry & ID: ClinicalTrials.gov identifier: NCT05750030 (Registration date: 16.01.2023).}, } @article {pmid40232107, year = {2025}, author = {Ravizza, T and Volpedo, G and Riva, A and Striano, P and Vezzani, A}, title = {Intestinal microbiome alterations in pediatric epilepsy: Implications for seizures and therapeutic approaches.}, journal = {Epilepsia open}, volume = {}, number = {}, pages = {}, doi = {10.1002/epi4.70037}, pmid = {40232107}, issn = {2470-9239}, support = {PE0000006/DN.1553//National Recovery and Resilience Plan (NRRP)/ ; //AICE-FIRE/ ; }, abstract = {The intestinal microbiome plays a pivotal role in maintaining host health through its involvement in gastrointestinal, immune, and central nervous system (CNS) functions. Recent evidence underscores the bidirectional communication between the microbiota, the gut, and the brain and the impact of this axis on neurological diseases, including epilepsy. In pediatric patients, alterations in gut microbiota composition-called intestinal dysbiosis-have been linked to seizure susceptibility. Preclinical models revealed that gut dysbiosis may exacerbate seizures, while microbiome-targeted therapies, including fecal microbiota transplantation, pre/pro-biotics, and ketogenic diets, show promise in reducing seizures. Focusing on clinical and preclinical studies, this review examines the role of the gut microbiota in pediatric epilepsy with the aim of exploring its implications for seizure control and management of epilepsy. We also discuss mechanisms that may underlie mutual gut-brain communication and emerging therapeutic strategies targeting the gut microbiome as a novel approach to improve outcomes in pediatric epilepsy. PLAIN LANGUAGE SUMMARY: Reciprocal communication between the brain and the gut appears to be dysfunctional in pediatric epilepsy. The composition of bacteria in the intestine -known as microbiota- and the gastrointestinal functions are altered in children with drug-resistant epilepsy and animal models of pediatric epilepsies. Microbiota-targeted interventions, such as ketogenic diets, pre-/post-biotics administration, and fecal microbiota transplantation, improve both gastrointestinal dysfunctions and seizures in pediatric epilepsy. These findings suggest that the gut and its microbiota represent potential therapeutic targets for reducing drug-resistant seizures in pediatric epilepsy.}, } @article {pmid40231893, year = {2025}, author = {Vargas-Castellanos, E and Rincón-Riveros, A}, title = {Microsatellite Instability in the Tumor Microenvironment: The Role of Inflammation and the Microbiome.}, journal = {Cancer medicine}, volume = {14}, number = {8}, pages = {e70603}, pmid = {40231893}, issn = {2045-7634}, support = {C-012-2023//Hospital Universitario Mayor Méderi/ ; }, mesh = {Humans ; *Tumor Microenvironment/immunology/genetics ; *Microsatellite Instability ; *Neoplasms/genetics/microbiology/immunology/pathology ; *Inflammation/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; Dysbiosis ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {BACKGROUND: Microsatellite instability (MSI) is a hallmark of DNA mismatch repair (MMR) deficiency that leads to genomic instability and increased cancer risk. The tumor microenvironment (TME) significantly influences MSI-driven tumorigenesis, and emerging evidence points to a critical role of the microbiome in shaping this complex interplay.

METHODS: This review comprehensively examines the existing literature on the intricate relationship between MSI, microbiome, and cancer development, with a particular focus on the impact of microbial dysbiosis on the TME.

RESULTS: MSI-high tumors exhibited increased immune cell infiltration owing to the generation of neoantigens. However, immune evasion mechanisms such as PD-1/CTLA-4 upregulation limit the efficacy of immune checkpoint inhibitors (ICIs) in a subset of patients. Pathobionts, such as Fusobacterium nucleatum and Bacteroides fragilis, contribute to MSI through the production of genotoxins, further promoting inflammation and oxidative stress within the TME.

CONCLUSIONS: The microbiome profoundly affects MSI-driven tumorigenesis. Modulation of the gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and dietary changes holds promise for improving ICI response rates. Further research into cancer pharmacomicrobiomics, investigating the interplay between microbial metabolites and anticancer therapies, is crucial for developing personalized treatment strategies.}, } @article {pmid40230225, year = {2025}, author = {Fang, X and Zhang, Y and Huang, X and Miao, R and Zhang, Y and Tian, J}, title = {Gut microbiome research: Revealing the pathological mechanisms and treatment strategies of type 2 diabetes.}, journal = {Diabetes, obesity & metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.16387}, pmid = {40230225}, issn = {1463-1326}, support = {CI2021A01601//Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences/ ; HLCMHPP20230CZ40907//High Level Chinese Medical Hospital Promotion Project/ ; ZZ13-YQ-026//CACMS Outstanding Young Scientific and Technological Talents Program/ ; CI2021B008//Innovation Team Project of Science and Technology Innovation Engineering of China Academy of Chinese Medical Sciences/ ; 82474323//National Natural Science Foundation of China/ ; }, abstract = {The high prevalence and disability rate of type 2 diabetes (T2D) caused a huge social burden to the world. Currently, new mechanisms and therapeutic approaches that may affect this disease are being sought. With in-depth research on the pathogenesis of T2D and growing advances in microbiome sequencing technology, the association between T2D and gut microbiota has been confirmed. The gut microbiota participates in the regulation of inflammation, intestinal permeability, short-chain fatty acid metabolism, branched-chain amino acid metabolism and bile acid metabolism, thereby affecting host glucose and lipid metabolism. Interventions focusing on the gut microbiota are gaining traction as a promising approach to T2D management. For example, dietary intervention, prebiotics and probiotics, faecal microbiota transplant and phage therapy. Meticulous experimental design and choice of analytical methods are crucial for obtaining accurate and meaningful results from microbiome studies. How to design gut microbiome research in T2D and choose different machine learning methods for data analysis are extremely critical to achieve personalized precision medicine.}, } @article {pmid40229514, year = {2025}, author = {Du, J and Guan, Y and Zhang, E}, title = {Regulatory role of gut microbiota in immunotherapy of hepatocellular carcinoma.}, journal = {Hepatology international}, volume = {}, number = {}, pages = {}, pmid = {40229514}, issn = {1936-0541}, abstract = {BACKGROUND: The gut microbiota plays a role in triggering innate immunity and regulating the immune microenvironment (IME) of hepatocellular carcinoma (HCC) by acting on various signaling receptors and transcription factors through its metabolites and related molecules. Furthermore, there is an increasing recognition of the gut microbiota as a potential therapeutic target for HCC, given its ability to modulate the efficacy of immune checkpoint inhibitors (ICIs).

OBJECTIVE: This review will discuss the mechanisms of gut microbiota in modulating immunotherapy of HCC, the predictive value of efficacy, and the therapeutic strategies for modulating the gut microbiota in detail.

METHODS: We conducted a systematic literature search in PubMed, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Chinese databases for articles involving the influence of gut microbiota on HCC immunotherapy.

RESULTS: The mechanisms underlying the effect of gut microbiota on HCC immunotherapy include gut-liver axis, tumor immune microenvironment (TIME), and antibodies. Patients who benefit from ICIs exhibit a higher abundance of gut microbiota. Antibiotics, fecal microbiota transplantation (FMT), probiotics, and prebiotics are effective methods to regulate gut microbiota.

CONCLUSION: The strong connection between the liver and gut will provide numerous opportunities for the development of microbiome-based diagnostics, treatments, or prevention strategies for HCC patients.}, } @article {pmid40229213, year = {2025}, author = {Hoops, SL and Moutsoglou, D and Vaughn, BP and Khoruts, A and Knights, D}, title = {Metagenomic source tracking after microbiota transplant therapy.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2487840}, doi = {10.1080/19490976.2025.2487840}, pmid = {40229213}, issn = {1949-0984}, mesh = {Humans ; *Metagenomics/methods ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Colitis, Ulcerative/therapy/microbiology ; *Bacteria/genetics/classification/isolation & purification ; RNA, Ribosomal, 16S/genetics ; *Metagenome ; Bayes Theorem ; Feces/microbiology ; }, abstract = {Reliable engraftment assessment of donor microbial communities and individual strains is an essential component of characterizing the pharmacokinetics of microbiota transplant therapies (MTTs). Recent methods for measuring donor engraftment use whole-genome sequencing and reference databases or metagenome-assembled genomes (MAGs) to track individual bacterial strains but lack the ability to disambiguate DNA that matches both donor and patient microbiota. Here, we describe a new, cost-efficient analytic pipeline, MAGEnTa, which compares post-MTT samples to a database comprised MAGs derived directly from donor and pre-treatment metagenomic data, without relying on an external database. The pipeline uses Bayesian statistics to determine the likely sources of ambiguous reads that align with both the donor and pre-treatment samples. MAGEnTa recovers engrafted strains with minimal type II error in a simulated dataset and is robust to shallow sequencing depths in a downsampled dataset. Applying MAGEnTa to a dataset from a recent MTT clinical trial for ulcerative colitis, we found the results to be consistent with 16S rRNA gene SourceTracker analysis but with added MAG-level specificity. MAGEnTa is a powerful tool to study community and strain engraftment dynamics in the development of MTT-based treatments that can be integrated into frameworks for functional and taxonomic analysis.}, } @article {pmid40227949, year = {2025}, author = {He, Y and Cai, J and Xie, X and Zhang, X and Qu, L and Liu, J and Cao, Y}, title = {Dimethyl Itaconate Alleviates Escherichia coli-Induced Endometritis Through the Guanosine-CXCL14 Axis via Increasing the Abundance of norank_f_Muribaculaceae.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2414792}, doi = {10.1002/advs.202414792}, pmid = {40227949}, issn = {2198-3844}, support = {2023YFD1801100//Key Technologies Research and Development Program of Anhui Province/ ; }, abstract = {Endometritis, a prevalent reproductive system disease with high incidence, leads to reproductive dysfunction in humans and animals, causing huge economic losses. Dimethyl itaconate (DI) has been demonstrated to exert protective effects in multiple inflammatory diseases. Nevertheless, the efficacy of DI in preventing endometritis and the role played by the gut microbiota remain unknown. In this study, it is found that DI ameliorated Escherichia coli (E. coli) induced endometritis in mice. The protective effect is abolished by antibiotic-induced depletion of the gut microbiota, and fecal microbiota transplantation (FMT) from DI-treated mice to recipient mice ameliorated E. coli-induced endometritis. Integrative multiomics reveals that DI promotes the multiplication of norank_f_Muribaculaceae in vivo, and supplementation of Muribaculum intestinale (DSM 28989), which belongs to the norank_f_Muribaculaceae genus, upregulates the level of guanosine in the uterus. Mechanistically, the protective effect of guanosine in endometritis is mediated by activating the expression of CXCL14 in uterine epithelial cells. Moreover, the antibody-neutralizing experiment of CXCL14 eliminated this protective effect. In conclusion, this study elucidates the significant role of the gut microbiota and its metabolites in the protection of DI against endometritis, and provides new evidence for the regulation of distal organ by the gut microbiota.}, } @article {pmid40223320, year = {2025}, author = {Yaghmaei, H and Taromiha, A and Nojoumi, SA and Soltanipur, M and Shahshenas, S and Rezaei, M and Mirhosseini, SM and Hosseini, SM and Siadat, SD}, title = {Role of Gut-Liver Axis in Non-Alcoholic Fatty Liver Disease.}, journal = {Iranian biomedical journal}, volume = {29}, number = {1 & 2}, pages = {1-8}, doi = {10.61186/ibj.4212}, pmid = {40223320}, issn = {2008-823X}, mesh = {*Non-alcoholic Fatty Liver Disease/microbiology ; Humans ; *Gastrointestinal Microbiome ; Animals ; *Liver/pathology/microbiology/metabolism ; Dysbiosis ; }, abstract = {Non-alcoholic fatty liver disease has emerged as a significant global health problem, mainly due to the increasing prevalence of obesity and metabolic syndrome. The gut microbiota plays an essential role in the development of NAFLD through the gut-liver axis. Dysbiosis of the GM is associated with the pathogenesis of NAFLD. Dietary choices and other lifestyle factors influence the composition of the GM and contribute to the development of NAFLD. At the phylum level, individuals with NAFLD show an increased level in Actinobacteria and Firmicutes, while Verrucomicrobia, Thermus, Proteobacteria, Lentiphaerae, and Fusobacteria are found to be decreased. Several genera, including Faecalibacterium and Akkermansia, exhibit alterations in NAFLD and are linked to disease progression. Modulating the GM through prebiotics, probiotics, or fecal microbiota transplantation represents a promising therapeutic strategy for NAFLD. This review summarizes the current understanding of GM changes in NAFLD, focusing on findings from both human and animal studies.}, } @article {pmid40221450, year = {2025}, author = {Kim, KS and Noh, J and Kim, BS and Koh, H and Lee, DW}, title = {Refining microbiome diversity analysis by concatenating and integrating dual 16S rRNA amplicon reads.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {57}, pmid = {40221450}, issn = {2055-5008}, support = {RS-2021-NR056579//National Research Foundation of Korea (NRF)/ ; RS-2023-KH141436//Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs)/ ; 200118770//Ministry of Trade, Industry and Energy (Ministry of Trade, Industry and Energy, Korea)/ ; }, mesh = {*RNA, Ribosomal, 16S/genetics ; Humans ; *Gastrointestinal Microbiome/genetics ; *Bacteria/classification/genetics/isolation & purification ; *Metagenomics/methods ; Sequence Analysis, DNA/methods ; Metagenome ; Colitis, Ulcerative/microbiology ; DNA, Bacterial/genetics ; Republic of Korea ; Phylogeny ; Feces/microbiology ; Biodiversity ; High-Throughput Nucleotide Sequencing ; }, abstract = {Understanding the role of human gut microbiota in health and disease requires insights into its taxonomic composition and functional capabilities. This study evaluates whether concatenating paired-end reads enhances data output for gut microbiome analysis compared to the merging approach across various regions of the 16S rRNA gene. We assessed this approach in both mock communities and Korean cohorts with or without ulcerative colitis. Our results indicate that using the direct joining method for the V1-V3 or V6-V8 regions improves taxonomic resolution compared to merging paired-end reads (ME) in post-sequencing data. While predicting microbial function based on 16S rRNA sequencing has inherent limitations, integrating sequencing reads from both the V1-V3 and V6-V8 regions enhanced functional predictions. This was confirmed by whole metagenome sequencing (WMS) of Korean cohorts, where our approach improved taxa detection that was lost using the ME method. Thus, we propose that the integrated dual 16S rRNA sequencing technique serves as a valuable tool for microbiome research by bridging the gap between amplicon sequencing and WMS.}, } @article {pmid40220715, year = {2025}, author = {Chen, Y and Chen, Z and Liang, L and Li, J and Meng, L and Yuan, W and Xie, B and Zhang, X and Feng, L and Jia, Y and Fu, Z and Su, P and Tong, Z and Zhong, J and Liu, X}, title = {Multi-kingdom gut microbiota dysbiosis is associated with the development of pulmonary arterial hypertension.}, journal = {EBioMedicine}, volume = {115}, number = {}, pages = {105686}, doi = {10.1016/j.ebiom.2025.105686}, pmid = {40220715}, issn = {2352-3964}, abstract = {BACKGROUND: Gut microbiota dysbiosis has been implicated in pulmonary arterial hypertension (PAH). However, the exact roles and underlying mechanisms of multi-kingdom gut microbiota, including bacteria, archaea, and fungi, in PAH remain largely unclear.

METHODS: The shotgun metagenomics was used to analyse multi-kingdom gut microbial communities in patients with idiopathic PAH (IPAH) and healthy controls. Furthermore, fecal microbiota transplantation (FMT) was performed to transfer gut microbiota from IPAH patients or monocrotaline (MCT)-PAH rats to normal rats and from normal rats to MCT-PAH rats.

FINDINGS: Gut microbiota analysis revealed substantial alterations in the bacterial, archaeal, and fungal communities in patients with IPAH compared with healthy controls. Notably, FMT from IPAH patients or MCT-PAH rats induced PAH phenotypes in recipient rats. More intriguingly, FMT from normal rats to MCT-PAH rats significantly ameliorated PAH symptoms; restored gut bacteria, archaea, and fungi composition; and shifted the plasma metabolite profiles of MCT-PAH rats toward those of normal rats. In parallel, RNA-sequencing analysis demonstrated the expression of genes involved in key signalling pathways related to PAH. A panel of multi-kingdom markers exhibited superior diagnostic accuracy compared with single-kingdom panels for IPAH.

INTERPRETATION: Our findings established an association between multi-kingdom gut microbiota dysbiosis and PAH, thereby indicating the therapeutic potential of FMT in PAH. More importantly, apart from gut bacteria, gut archaea and fungi were also significantly associated with PAH pathogenesis, highlighting their indispensable role in PAH.

FUNDING: This work was supported by Noncommunicable Chronic Diseases-National Science and Technology Major Projects No. 2024ZD0531200, No. 2024ZD0531201 (Research on Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases, and Metabolic Diseases), the National Natural Science Foundation of China of China (No. 82170302, 82370432), Financial Budgeting Project of Beijing Institute of Respiratory Medicine (Ysbz2025004, Ysbz2025007), National clinical key speciality construction project Cardiovascular Surgery, Reform and Development Program of Beijing Institute of Respiratory Medicine (Ggyfz202417, Ggyfz202501), Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (CYFH202209).}, } @article {pmid40220396, year = {2025}, author = {Kou, G and Yao, S and Ullah, A and Fang, S and Guo, E and Bo, Y}, title = {Polystyrene microplastics impair brown and beige adipocyte function via the gut microbiota-adipose tissue crosstalk in high-fat diet mice.}, journal = {Journal of hazardous materials}, volume = {492}, number = {}, pages = {138225}, doi = {10.1016/j.jhazmat.2025.138225}, pmid = {40220396}, issn = {1873-3336}, abstract = {BACKGROUND: Microplastics (MPs) are pervasive in the environment and food. The potential health hazards of this emerging pollutant have raised significant concerns in recent years. However, the underlying mechanism by which MPs have any impact on brown and beige adipocytes in the context of obesity is yet to be investigated.

METHODS: The C57BL/6 J mice were randomly assigned to the HFD and HFD+MPs group for 12 weeks of exposure to explore the differences in brown and beige adipocyte function. The gut microbiota analysis, fecal microbiota transplantation and metabolomic profiling were carried out to further determine its potential mechanism.

RESULTS: The present work demonstrated that high-fat diet mice accumulate lipids and have reduced energy expenditure after three months of oral administration of MPs. In addition to escalating intestinal dysbiosis, exposing HFD mice to MPs induces thermogenic dysfunction in inguinal white adipose tissue and brown adipose tissue. Following the fecal microbiota transplantation, the accumulation of lipids and dysfunction in energy expenditure within the microbiota of recipient mice further elucidated the inhibitory effect of MPs.

CONCLUSIONS: Our results suggest that MPs induced the thermogenic dysfunction of BAT and iWAT by affecting gut microbiota composition. The present study highlights the mechanisms by which MPs produce thermogenic dysfunction in BAT and iWAT and disruption in the gastrointestinal microbiota.}, } @article {pmid40220293, year = {2025}, author = {Damiani, F and Giuliano, MG and Cornuti, S and Putignano, E and Tognozzi, A and Suckow, V and Kalscheuer, VM and Pizzorusso, T and Tognini, P}, title = {Multi-site investigation of gut microbiota in CDKL5 deficiency disorder mouse models: Targeting dysbiosis to improve neurological outcomes.}, journal = {Cell reports}, volume = {44}, number = {4}, pages = {115546}, doi = {10.1016/j.celrep.2025.115546}, pmid = {40220293}, issn = {2211-1247}, abstract = {Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a rare neurodevelopmental disorder often associated with gastrointestinal (GI) issues and subclinical immune dysregulation, suggesting a link to the gut microbiota. We analyze the fecal microbiota composition in two CDKL5 knockout (KO) mouse models at postnatal days (P) 25, 32 (youth), and 70 (adulthood), revealing significant microbial imbalances, particularly during juvenile stages. To investigate the role of the intestinal microbiota in CDD and assess causality, we administer antibiotics, which lead to improved visual cortical responses and reduce hyperactivity. Additionally, microglia morphology changes, indicative of altered surveillance and activation states, are reversed. Strikingly, fecal transplantation from CDKL5 KO to wild-type (WT) recipient mice successfully transfers both visual response deficits and hyperactive behavior. These findings show that gut microbiota alterations contribute to the severity of neurological symptoms in CDD, shedding light on the interplay between microbiota, microglia, and neurodevelopmental outcomes.}, } @article {pmid40219707, year = {2025}, author = {Li, M and Bao, Y and Ren, J and Wei, W and Yu, X and He, X and Gulisima, M and Sheng, L and Zheng, N and Wan, J and Zhou, H and Zhao, L and Li, H}, title = {Aged Gut Microbiota Contributes to Cognitive Impairment and Hippocampal Synapse Loss in Mice.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e70064}, doi = {10.1111/acel.70064}, pmid = {40219707}, issn = {1474-9726}, support = {21XD1403500//Shanghai Excellent Academic Leaders Program/ ; //"Youth Qi Huang Scholar" by State Administration of TCM/ ; 2021YFE0111800//2021 UK-China Health and Ageing Flagship Challenge/ ; 81871098//National Natural Science Foundation of China/ ; }, abstract = {Gut microbiota alteration during the aging process serves as a causative factor for aging-related cognitive decline, which is characterized by the early hallmark, hippocampal synaptic loss. However, the impact and mechanistic role of gut microbiota in hippocampal synapse loss during aging remains unclear. Here, we observed that the fecal microbiota of naturally aged mice successfully transferred cognitive impairment and hippocampal synapse loss to young recipients. Multi-omics analysis revealed that aged gut microbiota was characterized with obvious change in Bifidobacterium pseudolongum (B.p) and metabolite of tryptophan, indoleacetic acid (IAA) in the periphery and brain. These features were also reproduced in young recipients that were transplanted with aged gut microbiota. Fecal B.p abundance was reduced in patients with cognitive impairment compared to healthy subjects and showed a positive correlation with cognitive scores. Microbiota transplantation from patients who had fewer B.p abundances yielded worse cognitive behavior in mice than those with higher B.p abundances. Meanwhile, supplementation of B.p was capable of producing IAA and enhancing peripheral and brain IAA bioavailability, as well as improving cognitive behaviors and microglia-mediated synapse loss in 5 × FAD transgenic mice. IAA produced from B.p was shown to prevent microglia engulfment of synapses in an aryl hydrocarbon receptor-dependent manner. This study reveals that aged gut microbiota -induced cognitive decline and microglia-mediated synapse loss that is, at least partially, due to the deficiency in B.p and its metabolite, IAA. It provides a proof-of-concept strategy for preventing neurodegenerative diseases by modulating gut probionts and their tryptophan metabolites.}, } @article {pmid40219669, year = {2025}, author = {Murray, J and Kefayat, A and Finlayson, M and Seenan, JP and Hsu, R and Din, S}, title = {RCPE in association with the American College of Gastroenterology and the Scottish Society of Gastroenterology - Gastroenterology: A global perspective.}, journal = {The journal of the Royal College of Physicians of Edinburgh}, volume = {}, number = {}, pages = {14782715251332318}, doi = {10.1177/14782715251332318}, pmid = {40219669}, issn = {2042-8189}, abstract = {On 6 November 2024, the Royal College of Physicians of Edinburgh (RCPE) hosted its annual gastroenterology symposium, marking the first collaboration with the American College of Gastroenterology (ACG) and the Scottish Society of Gastroenterology (SSG). The event addressed key global challenges in gastroenterology, including obesity, liver disease, inflammatory bowel disease (IBD), the gut microbiome, endoscopy quality and artificial intelligence (AI) applications. Discussions emphasised the growing burden of metabolic dysfunction-associated steatotic liver disease (MASLD), with promising pharmacologic and endoscopic interventions emerging. Advances in microbiome-targeted therapies, including faecal microbiota transplantation (FMT), were explored for recurrent Clostridium difficile infection and IBD. Professor David Rubin delivered the esteemed Sir Stanley Davidson lecture, highlighting the era of disease modification in IBD, emphasising early intervention and personalised treatment strategies. The symposium also addressed the role of AI in improving endoscopic detection rates and optimising resource allocation. This international collaboration underscored the importance of a multidisciplinary approach to tackling global digestive diseases, integrating clinical innovation, policy interventions and technological advancements. The event fostered knowledge exchange among global experts, aiming to advance patient care and improve long-term outcomes in gastroenterology.}, } @article {pmid40218893, year = {2025}, author = {Młynarska, E and Barszcz, E and Budny, E and Gajewska, A and Kopeć, K and Wasiak, J and Rysz, J and Franczyk, B}, title = {The Gut-Brain-Microbiota Connection and Its Role in Autism Spectrum Disorders.}, journal = {Nutrients}, volume = {17}, number = {7}, pages = {}, pmid = {40218893}, issn = {2072-6643}, mesh = {Humans ; *Autism Spectrum Disorder/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/complications/microbiology ; *Brain/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; *Brain-Gut Axis ; }, abstract = {Autism spectrum disorder (ASD) is a group of complex neurodevelopmental conditions with a heterogeneous and multifactorial etiology that is not yet fully understood. Among the various factors that may contribute to ASD development, alterations in the gut microbiota have been increasingly recognized. Microorganisms in the gastrointestinal tract play a crucial role in the gut-brain axis (GBA), affecting nervous system development and behavior. Dysbiosis, or an imbalance in the microbiota, has been linked to both behavioral and gastrointestinal (GI) symptoms in individuals with ASD. The microbiota interacts with the central nervous system through mechanisms such as the production of short-chain fatty acids (SCFAs), the regulation of neurotransmitters, and immune system modulation. Alterations in its composition, including reduced diversity or an overabundance of specific bacterial taxa, have been associated with the severity of ASD symptoms. Dietary modifications, such as gluten-free or antioxidant-rich diets, have shown potential for improving gut health and alleviating behavioral symptoms. Probiotics, with their anti-inflammatory properties, may support neural health and reduce neuroinflammation. Fecal microbiota transplantation (FMT) is being considered, particularly for individuals with persistent GI symptoms. It has shown promising outcomes in enhancing microbial diversity and mitigating GI and behavioral symptoms. However, its limitations should be considered, as discussed in this narrative review. Further research is essential to better understand the long-term effects and safety of these therapies. Emphasizing the importance of patient stratification and phenotype characterization is crucial for developing personalized treatment strategies that account for individual microbiota profiles, genetic predispositions, and coexisting conditions. This approach could lead to more effective interventions for individuals with ASD. Recent findings suggest that gut microbiota may play a key role in innovative therapeutic approaches to ASD management.}, } @article {pmid40216789, year = {2025}, author = {Shekarriz, S and Szamosi, JC and Whelan, FJ and Lau, JT and Libertucci, J and Rossi, L and Fontes, ME and Wolfe, M and Lee, CH and Moayyedi, P and Surette, MG}, title = {Detecting microbial engraftment after FMT using placebo sequencing and culture enriched metagenomics to sort signals from noise.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3469}, pmid = {40216789}, issn = {2041-1723}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Metagenomics/methods ; *Colitis, Ulcerative/therapy/microbiology ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; Male ; Female ; Placebos ; Adult ; Middle Aged ; }, abstract = {Fecal microbiota transplantation (FMT) has shown efficacy for the treatment of ulcerative colitis but with variable response between patients and trials. The mechanisms underlying FMT's therapeutic effects remains poorly understood but is generally assumed to involve engraftment of donor microbiota into the recipient's microbiome. Reports of microbial engraftment following FMT have been inconsistent between studies. Here, we investigate microbial engraftment in a previous randomized controlled trial (NCT01545908), in which FMT was sourced from a single donor, using amplicon-based profiling, shotgun metagenomics, and culture-enriched metagenomics. Placebo samples were included to estimate engraftment noise, and a significant level of false-positive engraftment was observed which confounds the prediction of true engraftment. We show that analyzing engraftment across multiple patients from a single donor enhances the accuracy of detection. We identified a unique set of genes engrafted in responders to FMT which supports strain displacement as the primary mechanism of engraftment in our cohort.}, } @article {pmid40216297, year = {2025}, author = {Tanabe, M and Kunisawa, K and Saito, I and Ojika, H and Saito, K and Nabeshima, T and Mouri, A}, title = {High-cellulose diet ameliorates cognitive impairment by modulating gut microbiota and metabolic pathways in mice.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tjnut.2025.04.004}, pmid = {40216297}, issn = {1541-6100}, abstract = {BACKGROUND: Nutrition is a key factor in cognitive function, and safe dietary interventions are promising to prevent cognitive impairment in pediatric psychiatric disorders. We previously demonstrated that childhood social isolation (SI) stress affects colonic function, leading to cognitive impairment. Cellulose, an insoluble dietary fiber, shows benefits to intestinal health, but its potential impact on cognitive impairment has not been explored.

OBJECTIVES: This study investigated whether a high-cellulose diet ameliorates cognitive impairment induced by SI through modulation of gut microbiota and metabolic pathways.

METHODS: C57BL/6J male mice (3 weeks old; n=10-15/group) were randomly divided into two groups: individually housed (SI) group and housed five mice per cage (GH) group. Each group received either a normal diet (5% cellulose) or a high-cellulose diet (30% cellulose) for 5 weeks daily until the end of the behavioral testing. We evaluated behavior abnormalities, gut microbiota composition, and metabolites, and performed two-way ANOVA.

RESULTS: Intake of a high-cellulose diet ameliorated cognitive impairment, including decreased time spent in a novel location of SI mice in novel object location test (NOLT; +30%; p < 0.01) with reduction of Iba-1 positive cells, microglia, in the hippocampus (-33%; p < 0.05). The high-cellulose diet indicated significant difference in gut microbiota clustering plots (p < 0.01) and enhanced the variation in malate-aspartate shuttle pathways in SI mice (p < 0.01). Notably, fecal microbiota transplantation (FMT) from SI mice fed a high-cellulose diet after antibiotic treatment, replicated amelioration of cognitive impairment in NOLT (+46%; p < 0.01). Additionally, the FMT replicated a decrease of Iba-1 positive cells indicating suppressed hippocampal microglial activation (-52%; p < 0.01), and enhanced the variation in malate-aspartate shuttle pathways (p < 0.01).

CONCLUSIONS: These findings suggest that a high-cellulose diet may ameliorate pediatric-specific cognitive impairment through modulation of the gut microbiota and metabolic pathways.}, } @article {pmid40211390, year = {2025}, author = {Wang, Z and Gao, X and Ji, H and Shao, M and Ni, B and Fei, S and Sun, L and Chen, H and Tan, R and Du, M and Gu, M}, title = {Characterization of gut microbiota and metabolites in renal transplant recipients during COVID-19 and prediction of one-year allograft function.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {420}, pmid = {40211390}, issn = {1479-5876}, support = {82170769//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Kidney Transplantation ; *COVID-19/metabolism/microbiology/complications ; *Gastrointestinal Microbiome/physiology ; Female ; Male ; Middle Aged ; Adult ; *Metabolome ; SARS-CoV-2 ; Allografts ; Transplant Recipients ; Feces/microbiology ; Aged ; }, abstract = {BACKGROUND: The gut-lung-kidney axis is pivotal in immune-related kidney diseases, with gut dysbiosis potentially exacerbating the severity of Coronavirus disease 2019 (COVID-19) in recipients of kidney transplant. This study aimed to characterize the gut microbiome and metabolome in renal transplant recipients with COVID-19 pneumonia over a one-year follow-up period.

METHODS: A total of 30 renal transplant recipients were enrolled, comprising 17 with COVID-19 pneumonia, six with mild COVID-19, and seven without COVID-19. Fecal samples were collected at the onset of infection for gut microbiome and metabolome analysis. Generalized Estimating Equations (GEE) model and Latent Class Growth Mixed Model (LCGMM) were employed to dissect the relationships among clinical characteristics, laboratory tests, and gut microbiota and metabolites.

RESULTS: Four microbial phyla (Deferribacteres, TM7, Fusobacteria, and Gemmatimonadetes) and 13 genera were significantly enriched across three recipients groups, correlating with baseline inflammatory response and allograft function. Additionally, 52 differentially expressed metabolites were identified, with seven significantly correlating with eight altered microbiota genera. LCGMM revealed two distinct classes of recipients, with those suffering from COVID-19 pneumonia exhibiting significantly elevated serum creatinine (Scr) trajectories over the one-year period. GEE further identified 12 genera and 181 metabolites closely associated with these trajectories; a multivariable model incorporating gut metabolites of 1-Caffeoylquinic Acid and PMK was found to effectively predict one-year allograft function.

CONCLUSIONS: Our study indicates a possible interaction between the composition of the gut microbiota and metabolites community and COVID-19 in renal transplant recipients, particularly in relation to disease severity and the prediction of one-year allograft function.}, } @article {pmid40211191, year = {2025}, author = {Li, A and Costello, SP and Bryant, RV and Haylock-Jacobs, S and Haifer, C and Lee, C and Yeung, D and Giri, P and Blunt, D and Bowen, JB and Ryan, FJ and Yong, A and Wardill, HR}, title = {A study protocol for a double-blinded, randomised, placebo-controlled trial on the use of encapsulated FMT for reducing the side effects of HSCT: the HSCT-BIOME study.}, journal = {BMC cancer}, volume = {25}, number = {1}, pages = {656}, pmid = {40211191}, issn = {1471-2407}, support = {#2021/81-QA25313//Hospital Research Foundation/ ; 2033529//National Health and Medical Research Council/ ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods/adverse effects ; Gastrointestinal Microbiome ; Adult ; Female ; Male ; *Hematologic Neoplasms/therapy ; Randomized Controlled Trials as Topic ; Middle Aged ; Diarrhea/etiology/prevention & control ; Transplantation, Autologous ; Young Adult ; }, abstract = {BACKGROUND: The composition of the gut microbiota both prior to and after haematopoietic stem cell transplantation (HSCT) is increasingly implicated in the outcomes of HSCT, including infections, poor immune reconstitution and disease relapse. Faecal microbiota transplantation (FMT) offers a potential strategy of supporting the gut microbiota and improve HSCT outcomes. Although FMT has been investigated in HSCT recipients, it has largely been evaluated therapeutically for indications such as infection, or once immunocompetency is regained.

METHODS: Peri-HSCT FMT (i.e. before and after HSCT) will be administered to eligible participants (adults undergoing autologous HSCT for a haematological malignancy) over two courses, with the first delivered immediately prior to conditioning and the second starting when ANC > 0.8. Following an open-label, safety run in (N = 5), peri-HSCT FMT will be evaluated for its efficacy in 51 participants, randomised 2:1 to FMT or placebo. The primary outcome is the proportion of participants who develop severe gastrointestinal toxicity defined by 3 consecutive days of severe diarrhoea (Bristol Stool Chart 6+), at a frequency of 4 + bowel movements/day within 3 weeks of HSCT. Safety is defined as the incidence of treatment-emergent adverse events (TE-AEs). Tolerability is defined as the incidence of TE-AEs and adherence to FMT.

DISCUSSION: The HSCT-BIOME study is a multi-centre, double-blind, randomised placebo-controlled trial designed to determine the tolerability, safety and efficacy of orally-administered encapsulated FMT to promote the stability of the gastrointestinal microenvironment for HSCT recipients. Peri-HSCT delivered FMT is hypothesised to promote microbial composition both before and following HSCT. Thus, the study will determine if administration of FMT post-HSCT during the neutropenic phase will enhance efficacy.

TRIAL REGISTRATION: ACTRN12624001104549. Date of registration: September 19, 2024 (prospectively registered).}, } @article {pmid40210439, year = {2025}, author = {Smith, BJ and Zhao, C and Dubinkina, V and Jin, X and Zahavi, L and Shoer, S and Moltzau-Anderson, J and Segal, E and Pollard, KS}, title = {Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC.}, journal = {Genome research}, volume = {}, number = {}, pages = {}, doi = {10.1101/gr.279543.124}, pmid = {40210439}, issn = {1549-5469}, abstract = {Metagenomics has greatly expanded our understanding of the human gut microbiome by revealing a vast diversity of bacterial species within and across individuals. Even within a single species, different strains can have highly divergent gene content, affecting traits such as antibiotic resistance, metabolism, and virulence. Methods that harness metagenomic data to resolve strain-level differences in functional potential are crucial for understanding the causes and consequences of this intraspecific diversity. The enormous size of pangenome references, strain mixing within samples, and inconsistent sequencing depth present challenges for existing tools that analyze samples one at a time. To address this gap, we updated the MIDAS pangenome profiler, now released as version 3, and developed StrainPGC, an approach to strain-specific gene content estimation that combines strain tracking and correlations across multiple samples. We validate our integrated analysis using a complex synthetic community of strains from the human gut and find that StrainPGC outperforms existing approaches. Analyzing a large, publicly available metagenome collection from inflammatory bowel disease patients and healthy controls, we catalog the functional repertoires of thousands of strains across hundreds of species, capturing extensive diversity missing from reference databases. Finally, we apply StrainPGC to metagenomes from a clinical trial of fecal microbiota transplantation for the treatment of ulcerative colitis. We identify two Escherichia coli strains, from two different donors, that are both frequently transmitted to patients but have notable differences in functional potential. StrainPGC and MIDAS v3 together enable precise, intraspecific pangenomic investigations using large collections of metagenomic data without microbial isolation or de novo assembly.}, } @article {pmid40210198, year = {2025}, author = {Fu, M and Wang, QW and Liu, YR and Chen, SJ}, title = {The role of the three major intestinal barriers in ulcerative colitis in the elderly.}, journal = {Ageing research reviews}, volume = {108}, number = {}, pages = {102752}, doi = {10.1016/j.arr.2025.102752}, pmid = {40210198}, issn = {1872-9649}, abstract = {With the unprecedented pace of global population aging, there has been a parallel epidemiological shift marked by increasing incidence rates of ulcerative colitis (UC) in geriatric populations, imposing a substantial disease burden on healthcare systems globally. The etiopathogenesis of UC in the elderly remains poorly delineated, while current therapeutic strategies require further optimization to accommodate the unique pathophysiological characteristics of elderly patients. This review systematically elucidates the three barrier dysfunction - encompassing the gut microbiota ecosystem, mucosal epithelial integrity, and immunoregulatory network - that collectively drives UC pathogenesis during biological senescence. We emphasize the therapeutic potential of barrier-targeted interventions, particularly highlighting emerging modalities including fecal microbiota transplantation, intestinal organoid regeneration techniques, mesenchymal stem cell-mediated immunomodulation, and precision-engineered Chimeric Antigen Receptor T-cell therapies. Through this multidimensional analysis, we propose a paradigm-shifting approach to UC management in the elderly, advocating for the development of tailored and evidence-based therapeutic interventions that address the complex interplay between age-related biological changes and intestinal barrier homeostasis in elderly patients.}, } @article {pmid40210031, year = {2025}, author = {Zhao, M and Liu, Z and Geng, Y and Lv, X and Xu, J and Zhao, X and Yu, Z and Zhu, R and Li, M and Han, F and Ma, X and Gu, N}, title = {Role of a low-molecular-weight polysaccharide from Boletus edulis Bull: Fr. in modulating gut microbiota and metabolic disorders.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {142789}, doi = {10.1016/j.ijbiomac.2025.142789}, pmid = {40210031}, issn = {1879-0003}, abstract = {This study aimed to investigate the effects of Boletus edulis Bull: Fr. polysaccharide (BEP), extracted using a deep eutectic solvent based on l-lactic acid and glycine, on glucose and lipid metabolism in high-fat diet (HFD)-fed mice. The primary mechanism by which BEP improves symptoms of glucose and lipid imbalances involves the modulation of gut microbiota. Key beneficial bacteria, including S24-7, Lachnospiraceae, [Prevotella], and Lactobacillus, were significantly enriched in the intestines of BEP-treated mice, with abundances 2.48-, 1.62-, 6.33- and 2.60-fold higher, respectively, compared to the HFD group. In contrast, the abundance of harmful bacteria, particularly Desulfovibrio, was reduced by 1.81-fold. These microbial shifts contributed to the alleviation of intestinal mucus layer damage and a 50 % reduction in serum lipopolysaccharide (LPS) levels, a key driver of systemic inflammation, compared to the HFD group. As a result, BEP effectively inhibited LPS-induced activation of the hepatic TLR4/Myd88/MAPK signaling pathway, thereby normalizing the expression of proteins related to glucose and lipid metabolism. A fecal microbiota transplantation study further demonstrated that the gut microbiota changes induced by BEP were central to its anti-metabolic syndrome effects. Overall, BEP may serve as a dietary supplement for preventing and treating diet-induced metabolism disorders by targeting the gut microbiota.}, } @article {pmid40209695, year = {2025}, author = {Yamane, T and Masaoka, T and Ishii, C and Masuoka, H and Suda, W and Kurokawa, S and Kishimoto, T and Mikami, Y and Fukuda, S and Kanai, T}, title = {Factors contributing to the efficacy of fecal microbiota transplantation for diarrhea-dominant functional bowel disorders.}, journal = {Digestion}, volume = {}, number = {}, pages = {1-22}, doi = {10.1159/000545183}, pmid = {40209695}, issn = {1421-9867}, abstract = {INTRODUCTION: In cases of effective fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), donor feces have been observed to be enriched in Bifidobacterium spp., and FMT for functional bowel disease improved psychiatric symptoms. Although intestinal dysbiosis has received attention as one of the pathophysiologies of IBS, the efficacy of FMT for IBS has not yet been established. In this study, we performed a post-hoc analysis of the efficacy of FMT, focusing on metabolites in donor feces.

METHODS: FMT was performed in 12 patients, 8 with refractory diarrhea-predominant IBS and 4 with functional diarrhea (FDr), who were refractory to medical therapy. The donors were family members within the second degree of kinship and were different for each transplant. Fecal characteristics were evaluated before and 12 weeks after transplantation using the Bristol stool scale (BS). BS scores of 3-5 at 12 weeks after transplantation were considered indicative of responders, while BS scores of 6 and 7 were indicative of non-responders. Metagenomic and metabolomic analyses of all 12 donor fecal samples were performed to compare the responder and non-responder groups.

RESULTS: Before transplantation, all 12 patients had BS scores of 6-7, but 12 weeks after transplantation, 6 were in the responder group and 6 were in the non-responder group. Metagenomic analysis showed that effective donor feces contained significantly higher levels of Prevotella than ineffective donor feces. Metabolomic analysis showed that effective donor feces contained significantly higher levels of propionate and butyrate and significantly lower lactate levels than ineffective donor feces.

CONCLUSION: Propionate-, butyrate-, or Prevotella-rich donor feces may contribute to successful FMT in patients with diarrhea-dominant functional gastrointestinal disorders.}, } @article {pmid40208412, year = {2025}, author = {Sandu, AM and Chifiriuc, MC and Vrancianu, CO and Cristian, RE and Alistar, CF and Constantin, M and Paun, M and Alistar, A and Popa, LG and Popa, MI and Tantu, AC and Sidoroff, ME and Mihai, MM and Marcu, A and Popescu, G and Tantu, MM}, title = {Healthcare-Associated Infections: The Role of Microbial and Environmental Factors in Infection Control-A Narrative Review.}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, pmid = {40208412}, issn = {2193-8229}, support = {CNFIS-FDI-2024-F-0484 INOVEX//University of Bucharest/ ; Pillar III//Ministry of Research, Innovation and Digitalization through the National Recovery and Resilience Plan (PNRR) of Romania/ ; Component C9/Investment no. 8 (I8) - contract CF 68//Ministry of Research, Innovation and Digitalization through the National Recovery and Resilience Plan (PNRR) of Romania/ ; Project No. RO1567-IBB05/2023//Institute of Biology Bucharest of the Romanian Academy/ ; project no. 23020101//The core program within the National Research Development and Innovation Plan, 2022-2027', carried out with the support of the Ministry of Research, Innovation and Digitalization (MCID),/ ; Contract no. 7N from 3 January 2023//The core program within the National Research Development and Innovation Plan, 2022-2027', carried out with the support of the Ministry of Research, Innovation and Digitalization (MCID),/ ; Dezvoltarea cercetării genomice în România - ROGEN" (Development of genomic research in Romania -ROGEN).//ROGEN/ ; }, abstract = {Healthcare-associated infections (HAIs), previously known as nosocomial infections, represent a significant threat to healthcare systems worldwide, prolonging patient hospital stays and the duration of antimicrobial therapy. One of the most serious consequences of HAIs is the increase in the rate of antibiotic resistance (AR) generated by the prolonged, frequent, and sometimes incorrect use of antibiotics, which leads to the selection of resistant bacteria, making treatment difficult and expensive, with direct consequences for the safety of patients and healthcare personnel. Therefore, timely and accurate diagnosis of HAIs is mandatory to develop appropriate infection prevention and control practices (IPC) and new therapeutic strategies. This review aimed to present the prevalence, risk factors, current diagnosis, including artificial intelligence (AI) and machine learning approaches, future perspectives in combating HAIs causative bacteria (phage therapy, microbiome-based interventions, and vaccination), and HAIs surveillance strategies. Also, we discussed the latest findings regarding the relationships of AR with climate change and environmental pollution in the context of the One Health approach. Phage therapy is an emerging option that can offer an alternative to ineffective antibiotic treatments for antibiotic-resistant bacteria causing HAIs. Clinical trials dealing with vaccine development for resistant bacteria have yielded conflicting results. Two promising strategies, fecal microbiota transplantation and probiotic therapy, proved highly effective against recurrent Clostridium difficile infections and have been shown to reduce HAI incidence in hospitalized patients undergoing antibiotic therapy. Artificial intelligence and machine learning systems offer promising predictive capabilities in processing large volumes of clinical, microbiological, and patient data but require robust data integration. Our paper argues that HAIs are still a global challenge, requiring stringent IPC policies, computer vision, and AI-powered tools. Despite promising avenues like integrated One Health approaches, optimized phage therapy, microbiome-based interventions, and targeted vaccine development, several knowledge gaps in clinical efficacy, standardization, and pathogen complexity remain to be answered.}, } @article {pmid40208053, year = {2025}, author = {Xu, K and Motiwala, Z and Corona-Avila, I and Makhanasa, D and Alkahalifeh, L and Khan, MW}, title = {The Gut Microbiome and Its Multifaceted Role in Cancer Metabolism, Initiation, and Progression: Insights and Therapeutic Implications.}, journal = {Technology in cancer research & treatment}, volume = {24}, number = {}, pages = {15330338251331960}, doi = {10.1177/15330338251331960}, pmid = {40208053}, issn = {1533-0338}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Neoplasms/metabolism/therapy/etiology/pathology/microbiology ; Disease Progression ; Animals ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {This review summarizes the intricate relationship between the microbiome and cancer initiation and development. Microbiome alterations impact metabolic pathways, immune responses, and gene expression, which can accelerate or mitigate cancer progression. We examine how dysbiosis affects tumor growth, metastasis, and treatment resistance. Additionally, we discuss the potential of microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, to modulate cancer metabolism. These interventions offer the possibility of reversing or controlling cancer progression, enhancing the efficacy of traditional treatments like chemotherapy and immunotherapy. Despite promising developments, challenges remain in identifying key microbial species and pathways and validating microbiome-targeted therapies through large-scale clinical trials. Nonetheless, the intersection of microbiome research and cancer initiation and development presents an exciting frontier for innovative therapies. This review offers a fresh perspective on cancer initiation and development by integrating microbiome insights, highlighting the potential for interdisciplinary research to enhance our understanding of cancer progression and treatment strategies.}, } @article {pmid40207935, year = {2025}, author = {Karra, DA and Suchodolski, JS and Newman, SJ and Flouraki, E and Lidbury, JA and Steiner, JM and Xenoulis, PG}, title = {Single Enema Fecal Microbiota Transplantation in Cats With Chronic Enteropathy.}, journal = {Journal of veterinary internal medicine}, volume = {39}, number = {3}, pages = {e70054}, pmid = {40207935}, issn = {1939-1676}, mesh = {Animals ; Cats ; *Cat Diseases/therapy ; *Fecal Microbiota Transplantation/veterinary ; Female ; Male ; *Enema/veterinary ; Chronic Disease ; Prospective Studies ; Dysbiosis/veterinary/therapy ; *Intestinal Diseases/veterinary/therapy ; }, abstract = {BACKGROUND: Chronic enteropathies (CE) are common in cats, and alterations of the intestinal microbiota might be involved in the pathogenesis.

HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of a single enema fecal microbiota transplantation (FMT) in improving intestinal dysbiosis and clinical scores in cats with CE.

ANIMALS: Twenty-eight cats with either chronic inflammatory enteropathy (CIE; n = 19) or small cell gastrointestinal lymphoma (SCGL; n = 9) were prospectively enrolled.

METHODS: Eleven cats were randomly selected to receive a single enema FMT (FMT-group), and 17 cats were used as controls. Clinical activity was determined using the Feline Chronic Enteropathy Activity Index (FCEAI), and intestinal dysbiosis was determined using the feline dysbiosis index (DI) on the day of FMT (T0) and 30 days after FMT (T1).

RESULTS: At T0, 14/28 cats had an abnormal DI > 0. No significant difference was found in the DI from T0 to T1 in the FMT group (mean[SD]: 0.01[2.5] vs. 0.7[2.1]; p = 0.47). No significant difference was found in the DI between the FMT group and the control group at T1 (mean[SD]: -0.7[2.1] vs. 0.8[1.8]; p = 0.92). FCEAI significantly decreased at T1 compared to T0 in the FMT group (median[IQR] 10.0[7.7-11.3] vs. 4.5[4-5]; p = 0.002). No significant difference was found in the FCEAI between the FMT group and the control group at T1 (median[IQR] 4.5[4-5] vs. 4[3-5.75]; p = 0.64).

CONCLUSIONS: In this study, single enema FMT did not lead to a significant improvement in DI or FCEAI in cats with CE compared to controls.}, } @article {pmid40207915, year = {2025}, author = {Moya Uribe, IA and Terauchi, H and Bell, JA and Zanetti, A and Jantre, S and Huebner, M and Arshad, SH and Ewart, SL and Mansfield, LS}, title = {Fecal microbiota transplants (FMT) of three distinct human communities to germ-free mice exacerbated inflammation and decreased lung function in their offspring.}, journal = {mBio}, volume = {}, number = {}, pages = {e0376424}, doi = {10.1128/mbio.03764-24}, pmid = {40207915}, issn = {2150-7511}, abstract = {UNLABELLED: Despite explosive rise in allergies, little is known about early life gut microbiota effects on postnatal respiratory function. We hypothesized that Enterobacteriaceae-dominant gut microbiota from eczemic infants increases Type 2 inflammation and decreases lung function in transplanted mice, while Bacteroidaceae-dominant gut microbiota from non-eczemic infants is protective. Fecal microbiota transplants (FMT) from eczemic infants "Infant A" and non-eczemic infants "Infant B" were successfully transplanted into germ-free C57BL/6 mice, passing to offspring unchanged. Infant A and B, Adult C-human-derived (positive control), and Mouse (negative control) microbiotas all in C57BL/6 mice were tested for effects on airway function in nonallergic (phosphate-buffered saline [PBS]) and allergic (house dust mite [HDM]) conditions. Baseline lung mechanics in mice with human microbiotas ([HU]microbiota) were significantly impaired compared to Mouse microbiota controls ([MO]microbiota) with or without HDM; respiratory system resistance (Rrs) was increased (P < 0.05-P < 0.01), and respiratory system compliance (Crs) was decreased (P < 0.05-P < 0.01). [HU]Microbiota mice showed a statistically significant impairment compared to [MO]microbiota mice in lung parameters Rrs, Ers, Rn, and G at baseline, and at multiple methacholine (MCh) doses with baseline removed. Impairment manifested as increased small airway resistance and tissue resistance. HDM significantly elevated IL-4, eosinophils, lung inflammation, and mucus cell metaplasia, and decreased macrophages and lung function (P < 0.05) in mice of all microbiotas, yet each [HU]microbiota produced distinct features. Infant B and Adult C mice had elevated basal levels of total IgE compared to [MO]microbiota and Infant A mice (P < 0.05). In [HU]microbiota mice given HDM, only Adult C had elevated IL-5 and IL-13 (P < 0.05), only Adult C and Infant B mice had elevated neutrophils (P < 0.05), and only Infant A had elevated lymphocytes (P < 0.01).

IMPORTANCE: Fecal microbiota transplants (FMT) of three distinct human communities to germ-free mice exacerbated inflammation and decreased lung function in their offspring. Taxa formerly described to induce an allergic response (agonists) and pro-inflammatory taxa were abundant in [HU]microbiotas compared to [MO]microbiota controls, while taxa formerly described to reduce allergic responses (antagonists) and anti-inflammatory taxa were numerous in [MO]microbiotas and low in [HU]microbiotas. Thus, we largely rejected our hypotheses because data supported multiple pro-inflammatory allergy agonists functioning in a community-wide fashion to impair lung function in the absence of antagonistic anti-inflammatory taxa. Structure of [HU]microbiotas played a key role in determining varied allergic responses and resulting lung impairment, yet, strikingly, all mice with [HU]microbiotas had impaired lung function even in the absence of allergens. Using a comparative approach, we showed that composition of gut microbiota can alter innate/immune regulation in the gut-lung axis to increase baseline lung function responses and the risk of allergic sensitization.}, } @article {pmid40207909, year = {2025}, author = {Spiegelhauer, MR and Offersen, SM and Mao, X and Gambino, M and Sandris Nielsen, D and Nguyen, DN and Brunse, A}, title = {Protection against experimental necrotizing enterocolitis by fecal filtrate transfer requires an active donor virome.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2486517}, pmid = {40207909}, issn = {1949-0984}, mesh = {Animals ; *Enterocolitis, Necrotizing/prevention & control/therapy/microbiology/pathology ; Swine ; Gastrointestinal Microbiome ; *Feces/virology ; *Virome/radiation effects ; *Fecal Microbiota Transplantation/methods ; Disease Models, Animal ; Animals, Newborn ; Virus Inactivation/radiation effects ; Ultraviolet Rays ; Clostridium perfringens ; Humans ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {Necrotizing enterocolitis (NEC) remains a frequent catastrophic disease in preterm infants, and fecal filtrate transfer (FFT) has emerged as a promising prophylactic therapy. This study explored the role of virome viability for the protective effect of FFT. Using ultraviolet (UV) irradiation, we established a viral inactivation protocol and administered FFT, UV-inactivated FFT (iFFT) or sterile saline orally to preterm piglets at risk for experimental NEC. The gut pathology and barrier properties were assessed, while the microbiome was explored by 16S rRNA amplicon and metavirome sequencing. Like in prior studies, FFT reduced NEC severity and intestinal inflammation, while these effects were absent in the iFFT group. Unexpectedly, piglets receiving FFT exhibited mild side effects in the form of early-onset diarrhea. The FFT also converged the gut colonization by increased viral heterogeneity and a reduced abundance of pathobionts like Clostridium perfringens and Escherichia. In contrast, the gut microbiome of iFFT recipients diverged from both FFT and the controls. These findings highlight the clear distinction between the ability of active and inactivate viromes to modulate gut microbiota and decrease pathology. The efficacy of FFT may be driven by active bacteriophages, and loss of virome activity could have consequences for the treatment efficacy.}, } @article {pmid40207766, year = {2025}, author = {Kumar, M and Mehan, S and Sharma, T and Kumar, A and Khan, Z and Sharma, AK and Kumar, N and Gupta, GD}, title = {Integrating Gut-Brain Axis: Exploring the Neurogastrointestinal Interactions and Therapeutic Potentials in Autism Spectrum Disorder.}, journal = {Endocrine, metabolic & immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303369166250325110016}, pmid = {40207766}, issn = {2212-3873}, abstract = {This comprehensive review critically examines the gut-brain axis (GBA) and its implications in autism spectrum disorder (ASD). The GBA is a complex, bidirectional communication network that integrates the gastrointestinal tract, the central nervous system, and the gut microbiota. This axis is mediated through various physiological pathways, including the enteric nervous system (ENS), the vagus nerve, immune responses, and metabolic activities of gut microorganisms. ASD, a developmental disorder marked by social impairments and repetitive behaviors, presents with notable neurological irregularities. The review highlights the increased prevalence of gastrointestinal (GI) disturbances in individuals with ASD, suggesting a potential link between GI symptoms and the severity of ASD-related behaviors. This correlation is supported by evidence of altered gut microbiota composition in ASD, indicating significant interactions between the gut environment and neurological health. Moreover, the pathophysiology of ASD is explored with an emphasis on genetic and environmental contributions to neurodevelopmental impairments. Key topics include synaptic dysfunction, the roles of neurotransmitters like GABA and serotonin, and the impact of gut-brain interactions on ASD progression. Specifically, this review addresses how gut microbiota may influence metabolic alterations, immune dysregulation, oxidative stress, mitochondrial function, and neurotransmitter production in ASD. Emerging research on microbiome-based therapies for ASD is discussed, focusing on the potential of probiotics, prebiotics, and faecal microbiota transplantation (FMT) as novel interventions. Ethical considerations in this burgeoning field are also considered, highlighting the necessity for rigorous scientific inquiry and ethical oversight. The review advocates for a multidisciplinary approach to understanding and addressing the complexities of ASD. By integrating insights from genetics, neuroscience, psychology, and gastroenterology, a more comprehensive understanding of the role of GBA in ASD can be achieved. This interdisciplinary perspective is crucial for developing effective, individualized treatments and improving the quality of life for individuals with ASD.}, } @article {pmid40207754, year = {2025}, author = {V S, S and Prasad, C and Panicker, SP}, title = {Exploring the Role of Non-Coding RNAs in the Gut and Skin Microbiome: Implications for Colorectal Cancer and Healthy Longevity.}, journal = {MicroRNA (Shariqah, United Arab Emirates)}, volume = {}, number = {}, pages = {}, doi = {10.2174/0122115366342509250401043719}, pmid = {40207754}, issn = {2211-5374}, abstract = {In the last forty years, cancer mortality rates have risen by more than 40%, with colo-rectal cancer (CRC) ranking as the third most common kind worldwide, significantly affected by dietary factors. Restricted access to sophisticated medical treatment and insufficient comprehen-sion of colorectal cancer's biology contribute to its elevated occurrence. Researchers have recog-nized dysbiosis of the gut microbiome as a critical contributor to the development of colorectal cancer, as it influences the expression of non-coding RNAs (ncRNAs) and subsequent molecular pathways essential for tumor proliferation. Moreover, interactions between gut and skin microbi-ota can impact systemic health and ncRNA regulation, influencing CRC advancement. This study shows how important the gut-skin microbiome axis is in developing colorectal cancer. It suggests that targeting this axis may lead to new treatments, such as changing the microbiome through probiotics, prebiotics, or fecal microbiota transplantation. Nonetheless, we must address obstacles such as population heterogeneity and intricate microbiome-host interactions to facilitate the tran-sition of these medicines into clinical practice. This study seeks to elucidate the roles of dietary treatments, microbiomes, and ncRNAs in the etiology and prevention of colorectal cancer (CRC).}, } @article {pmid40207229, year = {2025}, author = {Chen, S and Yi, M and Yi, X and Zhou, Y and Song, H and Zeng, M}, title = {Unveiling the fungal frontier: mycological insights into inflammatory bowel disease.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1551289}, pmid = {40207229}, issn = {1664-3224}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/immunology/etiology/metabolism ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology/microbiology ; *Fungi/immunology ; Animals ; *Mycoses/immunology/microbiology ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal disease that seriously affects the quality of life of patients around the world. It is characterized by recurrent abdominal pain, diarrhea, and mucous bloody stools. There is an urgent need for more accurate diagnosis and effective treatment of IBD. Accumulated evidence suggests that gut microbiota plays an important role in the occurrence and development of gut inflammation. However, most studies on the role of gut microbiota in IBD have focused on bacteria, while fungal microorganisms have been neglected. Fungal dysbiosis can activate the host protective immune pathway related to the integrity of the epithelial barrier and release a variety of pro-inflammatory cytokines to trigger the inflammatory response. Dectin-1, CARD9, and IL-17 signaling pathways may be immune drivers of fungal dysbacteriosis in the development of IBD. In addition, fungal-bacterial interactions and fungal-derived metabolites also play an important role. Based on this information, we explored new strategies for IBD treatment targeting the intestinal fungal group and its metabolites, such as fungal probiotics, antifungal drugs, diet therapy, and fecal microbiota transplantation (FMT). This review aims to summarize the fungal dysbiosis and pathogenesis of IBD, and provide new insights and directions for further research in this emerging field.}, } @article {pmid40206278, year = {2025}, author = {Cresci, GAM and Liu, Q and Sangwan, N and Liu, D and Grove, D and Shapiro, D and Ali, K and Cazzaniga, B and Prete, LD and Miller, C and Hashimoto, K and Quintini, C}, title = {The Impact of Liver Graft Preservation Method on Longitudinal Gut Microbiome Changes Following Liver Transplant: A Proof-of-concept Study.}, journal = {Journal of clinical and translational hepatology}, volume = {13}, number = {4}, pages = {284-294}, pmid = {40206278}, issn = {2310-8819}, abstract = {BACKGROUND AND AIMS: End-stage liver disease is associated with disruptions in gut microbiota composition and function, which may facilitate gut-to-liver bacterial translocation, impacting liver graft integrity and clinical outcomes following liver transplantation. This study aimed to assess the impact of two liver graft preservation methods on fecal microbiota and changes in fecal and breath organic acids following liver transplantation.

METHODS: This single-center, non-randomized prospective pilot study enrolled liver transplant patients whose grafts were preserved using either static cold storage or ex situ normothermic machine perfusion (NMP). Fresh stool and breath samples were collected immediately before surgery and at postoperative months 3, 6, and 12. Stool microbiota was profiled via 16S rRNA gene sequencing, stool short-chain fatty acids were measured using gas chromatography/-mass spectrometry, and breath volatile organic compounds (VOCs) were analyzed with selected-ion flow-tube mass spectrometry.

RESULTS: Both cohorts experienced a loss of microbiota diversity and dominance by single taxa. The NMP cohort demonstrated enrichment of several beneficial gut taxa, while the static cold storage cohort showed depletion of such taxa. Various gut bacteria were found to correlate with stool short-chain fatty acids (e.g., lactic acid, butyric acid) and several VOCs.

CONCLUSIONS: Fecal microbiota alterations associated with end-stage liver disease do not fully normalize to a healthy control profile following liver transplantation. However, notable differences in microbiota composition and function were observed between liver graft preservation methods. Future research with larger randomized cohorts is needed to explore whether the NMP-associated shift in gut microbiota impacts clinical outcomes and if breath VOCs could serve as biomarkers of the clinical trajectory in liver transplant patients.}, } @article {pmid40204291, year = {2025}, author = {Li, S and Li, J and Chen, K and Wang, J and Wang, L and Feng, C and Wang, K and Xu, Y and Gao, Y and Yan, X and Zhao, Q and Li, B and Qiu, Y}, title = {Chronic Arsenic Exposure Causes Alzheimer's Disease Characteristic Effects and the Intervention of Fecal Microbiota Transplantation in Rats.}, journal = {Journal of applied toxicology : JAT}, volume = {}, number = {}, pages = {}, doi = {10.1002/jat.4782}, pmid = {40204291}, issn = {1099-1263}, support = {202203021211246//Shanxi Natural Science Foundation of China/ ; 20240017//Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province/ ; }, abstract = {Arsenic exposure and intestinal microbiota disorders may be related with Alzheimer's disease (AD), but the mechanism has not been elucidated. This study conducted chronic arsenic exposure from rat's maternal body to adult offspring to investigate the mechanisms of the characteristic effects of chronic arsenic exposure on AD, and further explored the intervention effect of fecal microbiota transplantation (FMT) on arsenic-mediated neurotoxicity. Transmission electron microscopy, HE staining, and related indicators were measured in the control group, the exposed group, and the FMT intervention group. Western blot was used to determine microtubule-associated proteins Tau and p-Tau396, intestinal-brain barrier-related proteins Claudin-1 and Occludin, ELISA was used to detect the content of Aβ1-42, and 16S rRNA sequencing was used to detect the intestinal flora of feces. Results showed that chronic arsenic exposure could lead to neurobehavioral defects in rats, increase the expression levels of Tau, p-Tau396, and Aβ1-42 in hippocampus (p < 0.05), increase the abundance of Clostridium _ UCG-014, decrease the abundance of Roseburia, and decrease the expression levels of Claudin-1 and Occludin in colon and hippocampus (p < 0.05). After FMT intervention, the expression levels of Tau and p-Tau396 were decreased (p < 0.05), and the abundance of Roseburia was increased. In summary, chronic arsenic exposure caused intestinal flora disorder by changing the abundance of inflammation-related flora, thereby destroying the gut-brain barrier and causing AD characteristic effects in rats. Although the bacterial specific genus was improved and the expression of AD-related proteins was reduced after transplantation, it could not alleviate the neurobehavioral defects and neurotoxicity caused by arsenic exposure.}, } @article {pmid40203217, year = {2025}, author = {Randolph, NK and Salerno, M and Klein, H and Diaz-Campos, D and van Balen, JC and Winston, JA}, title = {Preparation of Fecal Microbiota Transplantation Products for Companion Animals.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0319161}, pmid = {40203217}, issn = {1932-6203}, support = {T35 OD010977/OD/NIH HHS/United States ; }, mesh = {Animals ; Dogs ; Cats ; *Fecal Microbiota Transplantation/methods/veterinary ; *Feces/microbiology ; *Pets/microbiology ; Microbial Viability ; }, abstract = {Fecal microbiota transplantation (FMT) is increasingly utilized in small animal medicine for the treatment of a variety of gastrointestinal and non-gastrointestinal disorders. Despite proven clinical efficacy, there is no detailed protocol available for the preparation and storage of FMT products for veterinarians in a variety of clinical settings. Herein, the effect of processing technique on the microbial community structure was assessed with amplicon sequence analysis. Microbial viability was assessed with standard culture techniques using selective media. Given the fastidious nature of many intestinal microbes, colony forming units are considered surrogate viable microbes, representing a portion of potentially viable microbes. FMT products from four screened canine fecal donors and six screened feline fecal donors were processed aerobically according to a double centrifugation protocol adapted from the human medical literature. Fresh feces from an additional three screened canine fecal donors were used to evaluate the effect of cryopreservative, centrifugation, and short-term storage on microbial community structure and in vitro surrogate bacterial viability. Finally, fresh feces from a third group of three screened canine and three screened feline fecal donors were used to evaluate the long-term in vitro surrogate bacterial viability of three frozen and lyophilized FMT products. Microbiota analysis revealed that each canine fecal donor has a unique microbial profile. Processing of canine and feline feces for FMT does not significantly alter the overall microbial community structure. The addition of cryopreservatives and lyopreservatives significantly improved long-term viability, up to 6 months, for frozen and lyophilized FMT products compared to unprocessed raw feces with no cryopreservative. These results prove the practicality of this approach for FMT preparation in veterinary medicine and provide a detailed protocol for researchers and companion animal practitioners. Future in vivo research is needed to evaluate how the preparation and microbial viability of FMT impacts the recipient's microbial community and clinical outcomes across multiple disease phenotypes.}, } @article {pmid40202719, year = {2025}, author = {Huang, Z and Liu, C and Zhao, X and Guo, Y}, title = {The effect of elevated levels of the gut metabolite TMAO on glucose metabolism after sleeve gastrectomy.}, journal = {Archives of physiology and biochemistry}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/13813455.2025.2489721}, pmid = {40202719}, issn = {1744-4160}, abstract = {Purpose：Bariatric surgery can effectively alleviate obesity and diabetes by regulation of the gut microbiota. This study aimed to investigate the change in the gut microbiota metabolite TMAO and to explore its effect on glucose metabolism after sleeve gastrectomy (SG). Materials and methods：Diet-induced obesity mouse models were established, and the mice were randomly divided into four groups: an SG group, a sham-operated group pair-fed with the SG group (PF), a sham-operated group fed ad libitum (AL), and a lean control group (C). At 10 weeks post-surgery, the changes in glycogen content of liver, gut microbiota and the level of FMO3 in the liver were evaluated, and their correlation with TMAO production was analysed. The expression levels of the TMAO/PERK/FOXO1 pathway and the gluconeogenic genes G6PC and PCK1 were measured. Results：At 10 weeks post-surgery, hepatocyte glycogen levels were restored, and serum TMA and TMAO levels were significantly increased. Faecal metagenomic sequencing results showed that the abundances of Ruminococcaceae and Lachnospiraceae, which were positively correlated with TMAO production, were significantly increased after surgery. While the changes in FMO3, the key enzyme producing TMAO in the liver was found decreased significantly after SG. The expression levels of the TMAO/PERK/FOXO1 pathway and the gluconeogenic genes G6PC and PCK1 were measured. Inconsistent with the changing trend of TMAO, the expression of PERK, FOXO1, PCK, and G6PC significantly decreased after SG. Conclusions：SG can significantly reduce obesity and restore glucose metabolism. After surgery, TMAO metabolites increased in a microbiota-dependent manner.}, } @article {pmid40202676, year = {2025}, author = {Sharma, S and Tiwari, N and Tanwar, SS}, title = {The current findings on the gut-liver axis and the molecular basis of NAFLD/NASH associated with gut microbiome dysbiosis.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {40202676}, issn = {1432-1912}, abstract = {Recent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcoholic fatty liver disease (NAFLD). The gut-liver axis plays a crucial role in NAFLD pathophysiology, with dysbiosis contributing to disease progression. Various therapeutic approaches aimed at modulating gut microbiota have shown promise, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Probiotics have demonstrated efficacy in human randomized controlled trials, while other interventions require further investigation in clinical settings. These microbiota-targeted therapies may improve NAFLD outcomes through multiple mechanisms, such as reducing inflammation and enhancing metabolic function. Although lifestyle modifications remain the primary recommendation for NAFLD management, microbiota-focused interventions offer a promising alternative for patients struggling to achieve weight loss targets.}, } @article {pmid39851236, year = {2025}, author = {Golob, JL and Hou, G and Swanson, BJ and Berinstein, JA and Bishu, S and Grasberger, H and Zataari, ME and Lee, A and Kao, JY and Kamada, N and Bishu, S}, title = {Inflammation-Induced Th17 Cells Synergize with the Inflammation-Trained Microbiota to Mediate Host Resiliency Against Intestinal Injury.}, journal = {Inflammatory bowel diseases}, volume = {31}, number = {4}, pages = {1082-1094}, doi = {10.1093/ibd/izae293}, pmid = {39851236}, issn = {1536-4844}, support = {K08DK123403//the NIDDK/ ; }, mesh = {Animals ; *Th17 Cells/immunology ; Mice ; Mice, Inbred C57BL ; Citrobacter rodentium ; *Colitis/immunology/chemically induced/microbiology/pathology ; *Inflammation/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Dextran Sulfate/toxicity ; *Intestinal Mucosa/immunology/pathology/microbiology ; Disease Models, Animal ; Mice, Knockout ; Fecal Microbiota Transplantation ; *Enterobacteriaceae Infections/immunology ; *Dysbiosis/immunology/microbiology ; }, abstract = {BACKGROUND AND AIMS: Inflammation can generate pathogenic Th17 cells and cause an inflammatory dysbiosis. In the context of inflammatory bowel disease (IBD), these inflammatory Th17 cells and dysbiotic microbiota may perpetuate injury to intestinal epithelial cells. However, many models of IBD like T-cell transfer colitis and IL-10-/- mice rely on the absence of regulatory pathways, so it is difficult to tell if inflammation can also induce protective Th17 cells.

METHODS: We subjected C57BL6, RAG1-/-, or JH-/- mice to systemic or gastrointestinal (GI) Citrobacter rodentium (Cr). Mice were then subjected to 2.5% dextran sodium sulfate (DSS) to cause epithelial injury. Fecal microbiota transfer was performed by bedding transfer and co-housing. Flow cytometry, qPCR, and histology were used to assess mucosal and systemic immune responses, cytokines, and tissue inflammation. 16s sequencing was used to assess gut bacterial taxonomy.

RESULTS: Transient inflammation with GI but not systemic Cr was protective against subsequent intestinal injury. This was replicated with sequential DSS collectively indicating that transient inflammation provides tissue-specific protection. Inflammatory Th17 cells that have a tissue-resident memory (TRM) signature expanded in the intestine. Experiments with reconstituted RAG1-/-, JH-/- mice, and cell trafficking inhibitors showed that inflammation-induced Th17 cells were required for protection. Fecal microbiota transfer showed that the inflammation-trained microbiota was necessary for protection, likely by maintaining protective Th17 cells in situ.

CONCLUSION: Inflammation can generate protective Th17 cells that synergize with the inflammation-trained microbiota to provide host resiliency against subsequent injury, indicating that inflammation-induced Th17 TRM T cells are heterogenous and contain protective subsets.}, } @article {pmid40201970, year = {2025}, author = {Chen, Y and Zeng, Y and Zhang, Y and Chen, J and Qian, Y and Huang, J and Chen, G and Xia, G and Wang, C and Feng, A and Nie, X}, title = {Differential gut microbiota and inflammatory cytokines contribute to IgA vasculitis.}, journal = {Clinical and experimental rheumatology}, volume = {43}, number = {4}, pages = {563-574}, doi = {10.55563/clinexprheumatol/ff61t7}, pmid = {40201970}, issn = {0392-856X}, mesh = {*Gastrointestinal Microbiome/immunology ; Humans ; Animals ; Male ; Female ; Child ; *Immunoglobulin A/immunology/blood ; *Cytokines/blood/immunology ; *Dysbiosis/immunology ; *IgA Vasculitis/microbiology/immunology/blood/diagnosis ; Case-Control Studies ; Mice ; *Inflammation Mediators/blood ; Disease Models, Animal ; *Bacteria/immunology/genetics ; Adolescent ; Child, Preschool ; Fecal Microbiota Transplantation ; }, abstract = {OBJECTIVES: Immunoglobulin A vasculitis (IgAV) is the most common form of vasculitis in childhood. Emerging evidence indicates that gut microbiota plays a key role in the pathogenesis of IgAV. However, the factors linking gut microbiota to the onset and progression of IgAV are poorly understood. We aimed to demonstrate that the presence of a specific dysbiosis in patients with IgAV contributes to the onset of IgAV.

METHODS: We transplanted gut microbiota from human donors with IgAV or healthy controls (HCs). The changes in gut microbiota and serum indexes of the recipient mice were detected, and the IgAV-associated bacteria were determined by integrating the results from the mouse sequence data analysis with the human sequence results.

RESULTS: 55 amplicon sequence variants (ASVs) specific to IgAV children were detected in the recipient IgAV microbiota (rIMb) mice, and 35 ASVs specific to healthy children were detected in the recipient healthy microbiota (rHMb) mice. Gut microbiota in rIMb mice differs from that in rHMb mice. Alcaligenaceae could discriminate rIMb from rHMb mice, while its abundance was decreased in rIMb compared to rHMb (p<0.05). In children with IgAV, the abundance of Burkholderiaceae (Alcaligenaceae accounted for 99.7%) at the family level was significantly lower compared to HCs, which can be used to distinguish children with IgAV from HCs, and the constructed receiver operating characteristic (ROC) curve had an area under the curve (AUC) value of 0.766. In addition, the rIMb group had a markedly higher interleukin (IL)-17A and IL-21 level than those in the rHMb group. The Spearman correlation analysis indicated significant correlations between the relative levels of these pro-inflammatory cytokines, IgA and alterations of gut microbiota.

CONCLUSIONS: IgAV is characterised by disturbances of gut microbiota composition and an imbalance in inflammatory cytokines. The manipulation of gut microbiota could be a possible way to prevent and manage IgAV.}, } @article {pmid40201831, year = {2025}, author = {Dewey, CW}, title = {Poop for thought: Can fecal microbiome transplantation improve cognitive function in aging dogs?.}, journal = {Open veterinary journal}, volume = {15}, number = {2}, pages = {556-564}, pmid = {40201831}, issn = {2218-6050}, mesh = {Dogs ; Animals ; *Fecal Microbiota Transplantation/veterinary ; *Dog Diseases/therapy/microbiology ; Dysbiosis/therapy/veterinary ; Gastrointestinal Microbiome ; *Aging ; *Cognitive Dysfunction/therapy ; Cognition ; *Alzheimer Disease/therapy/veterinary ; Humans ; }, abstract = {Canine cognitive dysfunction (CCD) is the dog version of human Alzheimer's disease (AD), and it has strikingly similar pathological features to those of this neurodegenerative disorder. The gastrointestinal system is in constant communication with the brain via several conduits collectively termed the gut-brain axis. The microbial population of the gut, referred to as the microbiota, has a profound effect on the interactions that occur along this communication route. Recent evidence suggests that dysbiosis, an abnormal gastrointestinal microbial population, is linked to cognitive impairment in rodent AD models and human AD. There is also evidence from rodent AD models that correcting dysbiosis by transferring fecal material from healthy donors to the gastrointestinal tracts of cognitively impaired recipients [fecal microbiome transplantation (FMT)] reverses AD-associated brain pathology and improves cognitive function. Although limited, some clinical reports have described the improvement of cognitive function with FMT in human AD. The goals of this review article are to provide an overview of the mechanisms involved in dysbiosis- associated cognitive decline and the role of FMT in therapy for such decline. The potential role of FMT in CCD is also discussed.}, } @article {pmid40201444, year = {2025}, author = {Liu, Y and Li, X and Chen, Y and Yao, Q and Zhou, J and Wang, X and Meng, Q and Ji, J and Yu, Z and Chen, X}, title = {Fecal microbiota transplantation: application scenarios, efficacy prediction, and factors impacting donor-recipient interplay.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1556827}, pmid = {40201444}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) represents a therapeutic approach that directly regulates the gut microbiota of recipients, normalizes its composition and reaping therapeutic rewards. Currently, in addition to its general application in treating Clostridium difficile (C. difficile) infection (CDI), FMT treatment has also been extended to the fields of other gastrointestinal diseases, infections, gut-liver or gut-brain axis disorders, metabolic diseases and cancer, etc. Prior to FMT, rigorous donor screening is essential to reduce the occurrence of adverse events. In addition, it is imperative to evaluate whether the recipient can safely and effectively undergo FMT treatment. However, the efficacy of FMT is influenced by the complex interactions between the gut microbiota of donor and recipient, the degree of donor microbiota engraftment is not necessarily positively related with the success rate of FMT. Furthermore, an increasing number of novel factors affecting FMT outcomes are being identified in recent clinical trials and animal experiments, broadening our understanding of FMT treatment. This article provides a comprehensive review of the application scenarios of FMT, the factors influencing the safety and efficacy of FMT from the aspects of both the donors and the recipients, and summarizes how these emerging novel regulatory factors can be combined to predict the clinical outcomes of patients undergoing FMT.}, } @article {pmid40200137, year = {2025}, author = {Wang, X and Geng, Q and Jiang, H and Yue, J and Qi, C and Qin, L}, title = {Fecal microbiota transplantation enhanced the effect of chemoimmunotherapy by restoring intestinal microbiota in LLC tumor-bearing mice.}, journal = {BMC immunology}, volume = {26}, number = {1}, pages = {30}, pmid = {40200137}, issn = {1471-2172}, support = {CJ20220086//Changzhou 8th Batch of Science and Technology Project (Applied Basic Research)/ ; CMCC202201//Clinical Research Project of Changzhou Medical Center, Nanjing Medical University/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Fecal Microbiota Transplantation/methods ; Mice ; *Carcinoma, Lewis Lung/therapy/immunology/microbiology ; Mice, Inbred C57BL ; *Immunotherapy/methods ; RNA, Ribosomal, 16S/genetics ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; }, abstract = {OBJECTIVE: To assess the effect of half-dose chemotherapy (HDC) and standard-dose chemotherapy (SDC) on the intestinal microbiota and to investigate whether fecal microbiota transplantation (FMT) can restore the intestinal microecology to enhance the efficacy of chemoimmunotherapy containing an anti-PD- 1 antibody (PD1).

METHODS: Lewis lung cancer (LLC) tumor-bearing mice were divided into six groups, including Control, HDC, SDC, SDC + FMT, SDC + PD1, and SDC + PD1 + FMT. After the treatment, analyses were conducted on intestinal microbiota using 16S rRNA sequencing, immune cells through flow cytometry, cytokines and chemokines via polymerase chain reaction (PCR), and programmed death-ligand 1 (PD-L1) expression in tumor tissues by immunohistochemistry.

RESULTS: Alpha and beta diversity of intestinal flora were not significantly different between HDC and SDC groups, nor was there a significant difference in the abundance of the top 10 species at the phylum, class, order, family, genus, or species levels. FMT increased both alpha and beta diversity and led to an increase in the abundance of Ruminococcus_callidus and Alistipes_finegoldii at the species level in mice receiving SDC + FMT. Besides, tumor growth was significantly slowed in SDC + PD1 + FMT compared to SDC + PD1 group, accompanied by an up-regulated Bacteroidetes/Firmicutes ratio, down-regulated abundance of Proteobacteria species (including Pseudolabrys, Comamonas, Alcaligenaceae, Xanthobacteraceae and Comamonadaceae), as well as Faecalicoccus of Firmicutes, the increased number of cDC1 cells, cDC2 cells, CD4[+] T cells and CD8[+] T cells in the peripheral blood, and IFN-γ[+]CD8[+] T cells, IFN-γ, granzyme B, TNF-α, CXCL9 and CXCL10 in intestinal tissues.

CONCLUSIONS: There were no significant differences between HDC and SDC in their effects on the intestinal microbiota. FMT exhibited a beneficial impact on gut microbiota and improved the efficacy of chemoimmunotherapy, possibly associated with the increase of immune cells and the modulation of related cytokines and chemokines.}, } @article {pmid40199985, year = {2025}, author = {Vecchiato, CG and Sabetti, MC and Sung, CH and Sportelli, F and Delsante, C and Pinna, C and Alonzo, M and Erba, D and Suchodolski, JS and Pilla, R and Pietra, M and Biagi, G and Procoli, F}, title = {Effect of faecal microbial transplantation on clinical outcome, faecal microbiota and metabolome in dogs with chronic enteropathy refractory to diet.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {11957}, pmid = {40199985}, issn = {2045-2322}, mesh = {Animals ; Dogs ; *Fecal Microbiota Transplantation/methods ; *Metabolome ; Male ; Female ; *Feces/microbiology ; *Dog Diseases/therapy/microbiology/metabolism ; Treatment Outcome ; Gastrointestinal Microbiome ; *Intestinal Diseases/therapy/veterinary/microbiology ; Chronic Disease ; Diet ; Bile Acids and Salts/metabolism ; Dysbiosis/therapy ; }, abstract = {Chronic enteropathy (CE) is a common complaint in canine gastroenterology. Recently, faecal microbiota transplantation (FMT) gained attention as a treatment strategy. However, the efficacy and long-term impact of FMT is still unclear. Clinical index (CIBDAI), faecal microbiota and metabolome were monitored in 20 CE dogs refractory to diet before (T0) and 3 months (T3) after FMT. Further data were retrospectively collected up to 1-year after FMT. Significant improvements were observed in CIBDAI, Dysbiosis Index (DI), and primary (PBAs) and secondary (SBAs) faecal bile acids and propionate one month (T1) after FMT (CIBDAI (median and range): T0 5 (1-9) vs. T1 1 (0-5), p < 0.0001; DI (median and range): T0 -0.1 (-5.6 to 3.8) vs. T1 -2.1 (-5.7 to 4.7), p < 0.05; PBAs decreased by 57%, SBAa increased by 41%; propionate increased by 20%). According to CIBDAI, 17 dogs clinically improved up to T3, and 10 dogs remained clinically stable up to one year after FMT. Alpha- and beta-diversity of the faecal microbiota of CE dogs did not differ, neither before nor after FMT, from that of 17 healthy controls. The results highlight that CE dogs refractory to diet with mild clinical signs and dysbiosis may benefit long-term from treatment with FMT.}, } @article {pmid40199868, year = {2025}, author = {Liu, C and Zheng, X and Ji, J and Zhu, X and Liu, X and Liu, H and Guo, L and Ye, K and Zhang, S and Xu, YJ and Sun, X and Zhou, W and Wong, HLX and Tian, Y and Qian, H}, title = {The carotenoid torularhodin alleviates NAFLD by promoting Akkermanisa muniniphila-mediated adenosylcobalamin metabolism.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3338}, pmid = {40199868}, issn = {2041-1723}, mesh = {Animals ; *Carotenoids/pharmacology ; Male ; *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism/microbiology ; Mice ; Humans ; Gastrointestinal Microbiome/drug effects ; Mice, Inbred C57BL ; *Akkermansia/metabolism/drug effects ; Liver/metabolism/drug effects/pathology ; Disease Models, Animal ; *Vitamin B 12/metabolism/analogs & derivatives ; Colon/metabolism/drug effects ; }, abstract = {Torularhodin, a unique carotenoid, confers beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the precise mechanism underlying its therapeutic effects remains unknown. Here, we report that torularhodin alleviates NAFLD in male mice by modulating the gut microbiota. Additionally, transplanting fecal microbiota from torularhodin-treated mice to germ-free mice also improves NAFLD. Mechanistically, torularhodin specifically enriches the abundance of Akkermansia muciniphila, which alleviates NAFLD by promoting the synthesis of adenosylcobalamin. Utilizing a human gastrointestinal system and a colonic organoid model, we further demonstrate that adenosylcobalamin confers protective effects against NAFLD through reducing ceramides, a well-known liver damaging compound, and this effect is mediated by inhibition of the hypoxia-inducible factor 2α pathway. Notably, we construct electrospun microsphere-encapsulated torularhodin, which facilitates the slow release of torularhodin in the colon. Together, our findings indicate the therapeutic potential of microbial utilization of carotenoids, such as torularhodin, for treating NAFLD.}, } @article {pmid40198451, year = {2025}, author = {Duo, R and Wang, Y and Ma, Q and Wang, X and Zhang, Y and Shen, H}, title = {MTX-induced gastrointestinal reactions in RA: Prevotella enrichment, gut dysbiosis, and PI3K/Akt/Ras/AMPK pathways.}, journal = {Clinical rheumatology}, volume = {}, number = {}, pages = {}, pmid = {40198451}, issn = {1434-9949}, support = {No. CY2023-MS-A13//CuiYing Technology Project of Lanzhou University/ ; No. 2023-4-27//Science and Technology Planning Project of Lanzhou/ ; No. 2018-3-49//Science and Technology Planning Project of Lanzhou/ ; No. CYXZ2022-13//Cuiying Scientific Training Program for Undergraduates of The Second Hospital & Clinical Medical School/ ; 25JRRA617//Natural Science Foundation of Gansu Province/ ; 2025B-020//Gansu Province Higher Education Institution Teachers' Innovation Fund Project/ ; }, abstract = {OBJECTIVES: To investigate the role of gut microbiota in methotrexate (MTX)-induced gastrointestinal reactions (MRGR) in patients with rheumatoid arthritis (RA).

METHODS: As a prospective, single-center, convenience sampling study, stool samples were obtained from 28 RA patients (male: female = 10:18) at Lanzhou University Second Hospital who were undergoing MTX treatment for analysis of their gut microbiota using 16S rRNA gene sequencing. Clinical disease activity (CDAI) and MRGR were assessed after two months of MTX therapy. All data collection periods exceeded one year. Intestinal germ-free mice, generated through antibiotic treatment, received fecal microbiota transplantation (FMT) from the patients, followed by varying doses of MTX to observe MRGR. Intestinal transcriptomics and markers related to intestinal barrier function were subsequently examined.

RESULTS: Females (84.6%) and high disease activity (CDAI scores, 39.6 ± 11.2 vs 26.3 ± 9.2) were prone to have MRGR in RA patients. Patients with MRGR (PT-GR) showed lower gut microbial diversity versus non-MRGR (PT-noGR). Prevotella abundance, positively correlated with CDAI and MRGR (p < 0.05), was elevated in PT-GR. Administering 10 mg/kg MTX to mice caused intestinal damage. FMT-GR-MTX mice exhibited weight loss (95.2%), morphological deterioration (86.4%), and reduced tight junction proteins (Claudin-1:72.4%; ZO-1:81.2%). Transcriptomics linked upregulated Gβγ/CREB/Atp4b to PI3K/Akt/Ras pathways and downregulated PFK2/PP2 to AMPK signaling in MRGR.

CONCLUSION: Our study identified notable gut microbiota alterations in RA patients prone to MRGR, with changes in intestinal gene expression and reduced intestinal barrier function potentially contributing to MRGR. These findings suggest potential strategies to mitigate MRGR in RA patients undergoing MTX treatment. Key Points • The RA-related MRGR is correlated with the intestinal microbiota. • Females, low gut diversity, and Prevotella enrichment are MRGR risks in RA. • Upregulated DEGs in MRGR linked to PI3K/Akt, Ras pathways. • Downregulated DEGs in MRGR focus on the AMPK pathway.}, } @article {pmid40198007, year = {2025}, author = {Attauabi, M and Madsen, GR and Holm, JP and Bendtsen, F and Møller, S and Seidelin, JB and Burisch, J}, title = {Incidence of Osteoporosis and Osteopenia in Newly Diagnosed Inflammatory Bowel Disease: A Population-Based Cohort Study.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf063}, pmid = {40198007}, issn = {1536-4844}, support = {//Novo Nordisk Fonden/ ; 101095470//EU Horizon Europe Program/ ; }, abstract = {BACKGROUND: Individuals with Crohn's disease (CD) and ulcerative colitis (UC) are at risk of developing osteoporosis. In Denmark, osteoporosis has been observed in 12.0% of postmenopausal women and 2.6% in men aged ≥ 50 years in the general population. We aimed to conduct a population-based analysis determining bone mineral density (BMD) at diagnosis of UC and CD.

METHODS: All adult patients diagnosed with UC or CD between May 2021 and May 2023 in an area covering 20% (1.2 million inhabitants) of the Danish population were invited for dual-energy X-ray absorptiometry at inflammatory bowel disease (IBD) diagnosis.

RESULTS: In total, 209 and 141 patients with UC and CD, respectively, were included. Among postmenopausal women (age ≥ 52 years) with UC, 15/42 (35.7%) had osteoporosis and 17/42 (40.5%) had osteopenia, while rates among patients with CD were 6/21 (28.6%, P = .57) and 8/21 (38.1%, P = .86), respectively. Among males aged ≥ 50 years, the rates were 5/38 (13.2%) and 17/38 (44.7%) in UC, respectively, and 3/24 (12.5%, P = 1.00) and 12/24 (50.0%, P = .69) in CD, respectively. Among younger patients, BMD below the expected range for age was observed in 3/69 (4.3%) and 3/60 (5.0%) of females and males with UC, and in 1/42 (2.4%) and 8/54 (14.8%) with CD, respectively. No nutritional or inflammatory marker, including C-reactive protein, fecal calprotectin, Mayo Endoscopic Score, or Simple Endoscopic Score for CD correlated with the T-score.

CONCLUSIONS: This population-based study demonstrated high rates of osteoporosis among postmenopausal women and males aged ≥ 50 years at IBD diagnosis, highlighting the need for systematic evaluation in these patients.}, } @article {pmid40197991, year = {2025}, author = {Malard, F and Thepot, S and Cluzeau, T and Carre, M and Lebon, D and Bories, P and Legrand, O and Schwarz, M and Loschi, M and Meunier, M and Joris, M and Gasc, C and Jouve, J and Levast, B and Plantamura, E and Prestat, E and Sabourin, A and Gaugler, B and Dore, J and Récher, C and Mohty, M}, title = {Gut microbiota restoration with oral pooled fecal microbiotherapy after intensive chemotherapy: the phase Ib CIMON trial.}, journal = {Blood advances}, volume = {}, number = {}, pages = {}, doi = {10.1182/bloodadvances.2024015571}, pmid = {40197991}, issn = {2473-9537}, abstract = {Intensive chemotherapy (IC) combined with broad-spectrum antibiotics for acute myeloid leukemia (AML) leads to gut microbiota dysbiosis, promoting pathological conditions and an increased incidence of complications, possibly limiting eligibility to allogenic hematopoietic cell transplantation (alloHCT). The purpose of this dose-ranging phase I study (CIMON) was to evaluate the first-in-man use of MaaT033, a pooled, allogeneic, lyophilized, and standardized fecal microbiotherapeutic product, formulated as a delayed-release capsule for oral administration. Primary objectives of the study were to evaluate the maximum tolerable dose of MaaT033 in 21 AML patients having undergone IC and antibiotics. Secondary objectives were to assess MaaT033 safety, its efficacy in restoring the patients' gut microbiome using shotgun sequencing in order to evaluate the recommended dose regimen, and patient compliance (ClinicalTrials.gov number: NCT04150393). MaaT033 was shown to be safe and effective for gut microbiota restoration in AML patients receiving IC and antibiotics, with an excellent gut microbiota reconstruction based on diversity indices at the species level, and restoration of microbial communities close to the composition of the drug product. Moreover, inflammatory markers (C-reactive protein, interleukin-6) decrease with treatment, while short-chain fatty acids increase over time. A randomized, placebo-controlled phase IIb trial, in recipients of alloHCT patients in ongoing.}, } @article {pmid40196486, year = {2025}, author = {Shealy, NG and Baltagulov, M and de Brito, C and McGovern, A and Castro, P and Schrimpe-Rutledge, AC and Malekshahi, C and Condreanu, SG and Sherrod, SD and Jana, S and Jones, K and Machado Ribeiro, T and McLean, JA and Beiting, DP and Byndloss, MX}, title = {Short-term alterations in dietary amino acids override host genetic susceptibility and reveal mechanisms of Salmonella Typhimurium small intestine colonization.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.03.25.645332}, pmid = {40196486}, issn = {2692-8205}, abstract = {In addition to individual genetics, environmental factors (e.g., dietary changes) may influence host susceptibility to gastrointestinal infection through unknown mechanisms. Herein, we developed a model in which CBA/J mice, a genetically resistant strain that tolerates intestinal colonization by the enteric pathogen Salmonella Typhimurium (S. Tm), rapidly succumb to infection after exposure to a diet rich in L-amino acids (AA). In mice, S. Tm-gastroenteritis is restricted to the large intestine (cecum), limiting their use to understand S . Tm small intestine (ileum) colonization, a feature of human Salmonellosis. Surprisingly, CBA mice fed AA diet developed ileitis with enhanced S . Tm ileal colonization. Using germ-free mice and ileal-fecal slurry transplant, we found diet-mediated S . Tm ileal expansion to be microbiota-dependent. Mechanistically, S . Tm relied on Fructosyl-asparagine utilization to expand in the ileum during infection. We demonstrate how AA diet overrides host genetics by altering the gut microbiota's ability to prevent S. Tm ileal colonization.}, } @article {pmid40195995, year = {2025}, author = {Larsen, T and Ayayee, P and Cluster, G and Clayton, J and Price, J and Ramer-Tait, A}, title = {Assessing gut microbial provisioning of essential amino acids to host in a murine model with reconstituted gut microbiomes.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-6255159/v1}, pmid = {40195995}, issn = {2693-5015}, abstract = {Gut microbial essential amino acid (EAA) provisioning to mammalian hosts remains a critical yet poorly understood aspect of host-microbe nutritional interactions, with significant implications for human and animal health. To investigate microbial EAA contributions in mice with reconstituted gut microbiomes, we analyzed stable carbon isotopes ([13]C) of six EAAs across multiple organs. Germ-free (GF) mice fed a high-protein diet (18%) were compared to conventionalized (CVZ) mice fed a low-protein diet (10%) following fecal microbiota transplantation 30 days prior and a 20-day dietary intervention. We found no evidence for microbial EAA contributions to host tissues, with [13]C-EAA fingerprinting revealing nearly identical patterns between GF and CVZ organs. Both groups maintained their expected microbiome statuses, with CVZ gut microbiota dominated by Firmicutes and Bacteroidetes phyla. These findings raise important questions about the functional capacities of reconstituted gut microbiomes. Future studies should investigate longer adaptation periods, varied dietary protein levels, and complementary analytical techniques to better understand the context-dependent nature of microbial EAA provisioning in mammalian hosts.}, } @article {pmid40195644, year = {2025}, author = {Barrios Steed, D and Koundakjian, D and Harris, AD and Rosato, AE and Konstantinidis, KT and Woodworth, MH}, title = {Leveraging strain competition to address antimicrobial resistance with microbiota therapies.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2488046}, doi = {10.1080/19490976.2025.2488046}, pmid = {40195644}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Anti-Bacterial Agents/pharmacology ; *Bacteria/drug effects/genetics/growth & development ; Fecal Microbiota Transplantation ; *Drug Resistance, Bacterial ; Animals ; Probiotics ; }, abstract = {The enteric microbiota is an established reservoir for multidrug-resistant organisms that present urgent clinical and public health threats. Observational data and small interventional studies suggest that microbiome interventions, such as fecal microbiota products and characterized live biotherapeutic bacterial strains, could be an effective antibiotic-sparing prevention approach to address these threats. However, bacterial colonization is a complex ecological phenomenon that remains understudied in the context of the human gut. Antibiotic resistance is one among many adaptative strategies that impact long-term colonization. Here we review and synthesize evidence of how bacterial competition and differential fitness in the context of the gut present opportunities to improve mechanistic understanding of colonization resistance, therapeutic development, patient care, and ultimately public health.}, } @article {pmid40192235, year = {2025}, author = {Jiao, Y and Ren, J and Xie, S and Yuan, N and Shen, J and Yin, H and Wang, J and Guo, H and Cao, J and Wang, X and Wu, D and Zhou, Z and Qi, X}, title = {Raffinose-metabolizing bacteria impair radiation-associated hematopoietic recovery via the bile acid/FXR/NF-κB signaling pathway.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2488105}, doi = {10.1080/19490976.2025.2488105}, pmid = {40192235}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/radiation effects ; *Bile Acids and Salts/metabolism ; Mice ; *NF-kappa B/metabolism/genetics ; Signal Transduction/radiation effects ; *Raffinose/metabolism ; Mice, Inbred C57BL ; Whole-Body Irradiation/adverse effects ; *Receptors, Cytoplasmic and Nuclear/metabolism/genetics ; Fecal Microbiota Transplantation ; Male ; *Acute Radiation Syndrome/microbiology/metabolism ; *Hematopoiesis/radiation effects ; *Bacteria/metabolism/genetics/classification/isolation & purification ; Dysbiosis/microbiology ; }, abstract = {Radiation-associated hematopoietic recovery (RAHR) is critical for mitigating lethal complications of acute radiation syndrome (ARS), yet therapeutic strategies remain limited. Through integrated multi-omics analysis of a total body irradiation (TBI) mouse model, we identify Bacteroides acidifaciens-dominated gut microbiota as key mediators of RAHR impairment. 16S ribosomal rRNA sequencing revealed TBI-induced dysbiosis characterized by Bacteroidaceae enrichment, while functional metagenomics identified raffinose metabolism as the most significantly perturbed pathway. Notably, raffinose supplementation (10% w/v) recapitulated radiation-induced microbiota shifts and delayed bone marrow recovery. Fecal microbiota transplantation (FMT) revealed a causative role for raffinose-metabolizing microbiota, particularly Bacteroides acidifaciens, in delaying RAHR progression. Mechanistically, B. acidifaciens-mediated bile acid deconjugation activated FXR, subsequently suppressing NF-κB-dependent hematopoietic recovery. Therapeutic FXR inhibition via ursodeoxycholic acid (UDCA) had been shown to be a viable method for rescuing RAHR. Our results delineated a microbiome-bile acid-FXR axis as a master regulator of post-irradiation hematopoiesis. Targeting B. acidifaciens or its metabolic derivatives could represent a translatable strategy to mitigate radiation-induced hematopoietic injury.}, } @article {pmid40192143, year = {2025}, author = {Feuerstadt, P and Allegretti, J and Khanna, S}, title = {Treatment of Clostridioides difficile: The Times They are a Changing.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000003445}, pmid = {40192143}, issn = {1572-0241}, } @article {pmid40192074, year = {2025}, author = {Geng, L and Yang, X and Sun, J and Ran, X and Zhou, D and Ye, M and Wen, L and Wang, R and Chen, M}, title = {Gut Microbiota Modulation by Inulin Improves Metabolism and Ovarian Function in Polycystic Ovary Syndrome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2412558}, doi = {10.1002/advs.202412558}, pmid = {40192074}, issn = {2198-3844}, support = {23Y11909600//Science and Technology Commission of Shanghai Municipality/ ; 1365//Talent reservoir program of Shanghai First Maternity and Infant Hospital/ ; 81871213//National Natural Science Foundation of China/ ; 81671468//National Natural Science Foundation of China/ ; SHDC2020CR4080//Shanghai Municipal Hospital Development Center/ ; 2021ScienceandTechnology02-37//Shanghai Collaborative Innovation Center for Chronic Disease Prevention and Health Services/ ; }, abstract = {The management of metabolic disorder associated with polycystic ovary syndrome (PCOS) has been suggested as an effective approach to improve PCOS which is highly involved with gut microbiota, while the underlying mechanism is unclear. Here, we investigated the role of inulin, a gut microbiota regulator, in the alleviation of PCOS. Our findings showed that inulin treatment significantly improved hyperandrogenism and glucolipid metabolism in both PCOS cohort and mice. Consistent with the cohort, inulin increased the abundance of microbial co-abundance group (CAG) 12 in PCOS mice, including Bifidobacterium species and other short-chain fatty acids (SCFAs)-producers. We further verified the enhancement of SCFAs biosynthesis capacity and fecal SCFAs content by inulin. Moreover, inulin decreased lipopolysaccharide-binding protein (LBP) and ameliorated ovarian inflammation in PCOS mice, whereas intraperitoneal lipopolysaccharide (LPS) administration reversed the protective effects of inulin. Furthermore, fecal microbiota transplantation (FMT) from inulin-treated patients with PCOS enhanced insulin sensitivity, improved lipid accumulation and thermogenesis, reduced hyperandrogenism and ovarian inflammatory response in antibiotic-treated mice. Collectively, these findings revealed that gut microbiota mediates the beneficial effects of inulin on metabolic disorder and ovarian dysfunction in PCOS. Therefore, modulating gut microbiota represents a promising therapeutic strategy for PCOS.}, } @article {pmid40191185, year = {2025}, author = {Chen, L and Ruan, G and Zhao, X and Yi, A and Xiao, Z and Tian, Y and Cheng, Y and Chen, D and Wei, Y}, title = {Pseudomonas aeruginosa enhances anti-PD-1 efficacy in colorectal cancer by activating cytotoxic CD8[+] T cells.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1553757}, pmid = {40191185}, issn = {1664-3224}, mesh = {Animals ; *Colorectal Neoplasms/immunology/therapy/microbiology ; *Pseudomonas aeruginosa/immunology ; Mice ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; *Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Gastrointestinal Microbiome/immunology ; Humans ; *CD8-Positive T-Lymphocytes/immunology ; Fecal Microbiota Transplantation ; Female ; Lymphocyte Activation/immunology ; *T-Lymphocytes, Cytotoxic/immunology ; Cell Line, Tumor ; Male ; }, abstract = {BACKGROUND: Immune checkpoint therapy for colorectal cancer (CRC) has been found to be unsatisfactory for clinical treatment. Fecal microbiota transplantation (FMT) has been shown to remodel the intestinal flora, which may improve the therapeutic effect of αPD-1. Further exploration of key genera that can sensitize cells to αPD-1 for CRC treatment and preliminary exploration of immunological mechanisms may provide effective guidance for the clinical treatment of CRC.

METHODS: In this study, 16S rRNA gene sequencing was analyzed in the fecal flora of both responders and no-responders to αPD-1 treatment, and the therapeutic effect was experimentally verified.

RESULTS: Pseudomonas aeruginosa was found to be highly abundant in the fecal flora of treated mice, and Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) in combination with αPD-1 was effective in the treatment of CRC through the induction of CD8[+] T-cell immunological effects.

CONCLUSION: The clinical drug PA-MSHA can be used in combination with αPD-1 for the treatment of CRC as a potential clinical therapeutic option.}, } @article {pmid40190259, year = {2025}, author = {Nagayama, M and Gogokhia, L and Longman, RS}, title = {Precision microbiota therapy for IBD: premise and promise.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2489067}, doi = {10.1080/19490976.2025.2489067}, pmid = {40190259}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; *Inflammatory Bowel Diseases/therapy/microbiology ; Animals ; *Precision Medicine/methods ; }, abstract = {Inflammatory Bowel Disease (IBD) is a spectrum of chronic inflammatory diseases of the intestine that includes subtypes of ulcerative colitis (UC) and Crohn's Disease (CD) and currently has no cure. While IBD results from a complex interplay between genetic, environmental, and immunological factors, sequencing advances over the last 10-15 years revealed signature changes in gut microbiota that contribute to the pathogenesis of IBD. These findings highlight IBD as a disease target for microbiome-based therapies, with the potential to treat the underlying microbial pathogenesis and provide adjuvant therapy to the emerging spectrum of advanced therapies for IBD. Building on the success of fecal microbiota transplantation (FMT) for Clostridioides difficile infection, therapies targeting gut microbiota have emerged as promising approaches for treating IBD; however, unique aspects of IBD pathogenesis highlight the need for more precision in the approach to microbiome therapeutics that leverage aspects of recipient and donor selection, diet and xenobiotics, and strain-specific interactions to enhance the efficacy and safety of IBD therapy. This review focuses on both pre-clinical and clinical studies that support the premise for microbial therapeutics for IBD and aims to provide a framework for the development of precision microbiome therapeutics to optimize clinical outcomes for patients with IBD.}, } @article {pmid40189556, year = {2025}, author = {Zhang, Y and Si, L and Shu, X and Qiu, C and Wan, X and Li, H and Ma, S and Jin, X and Wei, Z and Hu, H}, title = {Gut microbiota contributes to protection against porcine deltacoronavirus infection in piglets by modulating intestinal barrier and microbiome.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {93}, pmid = {40189556}, issn = {2049-2618}, mesh = {Animals ; Swine ; *Gastrointestinal Microbiome ; *Deltacoronavirus/physiology ; *Swine Diseases/microbiology/virology/prevention & control ; *Coronavirus Infections/veterinary/microbiology/virology ; Fecal Microbiota Transplantation ; *Intestinal Mucosa/microbiology ; Feces/microbiology ; Diarrhea ; Intestines/microbiology/virology ; }, abstract = {BACKGROUND: Gut microbiota plays a critical role in counteracting enteric viral infection. Our previous study demonstrated that infection of porcine deltacoronavirus (PDCoV) disturbs gut microbiota and causes intestinal damage and inflammation in piglets. However, the influence of gut microbiota on PDCoV infection remains unclear.

RESULTS: Firstly, the relationship between gut microbiota and disease severity of PDCoV infection was evaluated using 8-day-old and 90-day-old pigs. The composition of gut microbiota was significantly altered in 8-day-old piglets after PDCoV infection, leading to severe diarrhea and intestinal damage. In contrast, PDCoV infection barely affected the 90-day-old pigs. Moreover, the diversity (richness and evenness) of microbiota in 90-day-old pigs was much higher compared to the 8-day-old piglets, suggesting the gut microbiota is possibly associated with the severity of PDCoV infection. Subsequently, transplanting the fecal microbiota from the 90-day-old pigs to the 3-day-old piglets alleviated clinical signs of PDCoV infection, modulated the diversity and composition of gut microbiota, and maintained the physical and chemical barrier of intestines. Additionally, metabolomic analysis revealed that the fecal microbiota transplantation (FMT) treatment upregulated the swine intestinal arginine biosynthesis, FMT significantly inhibited the inflammatory response in piglet intestine by modulating the TLR4/MyD88/NF-κB signaling pathway.

CONCLUSIONS: PDCoV infection altered the structure and composition of the gut microbiota in neonatal pigs. FMT treatment mitigated the clinical signs of PDCoV infection in the piglets by modulating the gut microbiota composition and intestinal barrier, downregulating the inflammatory response. The preventive effect of FMT provides novel targets for the development of therapeutics against enteropathogenic coronaviruses. Video Abstract.}, } @article {pmid40189555, year = {2025}, author = {Zhou, J and Lu, P and He, H and Zhang, R and Yang, D and Liu, Q and Liu, Q and Liu, M and Zhang, G}, title = {The metabolites of gut microbiota: their role in ferroptosis in inflammatory bowel disease.}, journal = {European journal of medical research}, volume = {30}, number = {1}, pages = {248}, pmid = {40189555}, issn = {2047-783X}, support = {No.82474662//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Ferroptosis ; *Gastrointestinal Microbiome/physiology ; *Inflammatory Bowel Diseases/microbiology/metabolism/therapy/pathology ; Oxidative Stress ; Animals ; Fatty Acids, Volatile/metabolism ; Bile Acids and Salts/metabolism ; }, abstract = {Inflammatory bowel disease (IBD) includes chronic inflammatory conditions, such as Crohn's disease and ulcerative colitis, characterized by impaired function of the intestinal mucosal epithelial barrier. In recent years, ferroptosis, a novel form of cell death, has been confirmed to be involved in the pathological process of IBD and is related to various pathological changes, such as oxidative stress and inflammation. Recent studies have further revealed the complex interactions between the microbiome and ferroptosis, indicating that ferroptosis is an important target for the regulation of IBD by the gut microbiota and its metabolites. This article reviews the significant roles of gut microbial metabolites, such as short-chain fatty acids, tryptophan, and bile acids, in ferroptosis in IBD. These metabolites participate in the regulation of ferroptosis by influencing the intestinal microenvironment, modulating immune responses, and altering oxidative stress levels, thereby exerting an impact on the pathological development of IBD. Treatments based on the gut microbiota for IBD are gradually becoming a research hotspot. Finally, we discuss the potential of current therapeutic approaches, including antibiotics, probiotics, prebiotics, and fecal microbiota transplantation, in modulating the gut microbiota, affecting ferroptosis, and improving IBD symptoms. With a deeper understanding of the interaction mechanisms between the gut microbiota and ferroptosis, it is expected that more precise and effective treatment strategies for IBD will be developed in the future.}, } @article {pmid40189523, year = {2025}, author = {Yu, X and Chen, Y and Lei, L and Li, P and Lin, D and Shen, Y and Hou, C and Chen, J and Fan, Y and Jin, Y and Lu, H and Wu, D and Xu, Y}, title = {Mendelian randomization analysis of blood metabolites and immune cell mediators in relation to GVHD and relapse.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {201}, pmid = {40189523}, issn = {1741-7015}, support = {QNXM2024010//Suzhou Science and Education Strengthening Health Youth ProjectSuzhou Science and Education Strengthening Health Youth Project/ ; MQ2024022//Medical research project of Jiangsu Provincial Health Commission/ ; BXQN2023032//Boxi cultivation program project of the First Affiliated Hospital of Suzhou University/ ; KYCX23_3270//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; SKJY2021049//Suzhou Science and Technology Program Project/ ; SKY2022043//Suzhou Science and Technology Program Project/ ; SLT201911//Suzhou Science and Technology Program Project/ ; 82100231//National Natural Science Foundation of China/ ; 82020108003//National Natural Science Foundation of China/ ; 82070187//National Natural Science Foundation of China/ ; CXZX202201//Jiangsu Provincial Medical Innovation Center/ ; 2022YFC2502700//National Key Research and Development Program/ ; }, mesh = {*Graft vs Host Disease/genetics/blood/immunology ; Humans ; *Mendelian Randomization Analysis ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Recurrence ; Genome-Wide Association Study ; Male ; Female ; }, abstract = {BACKGROUND: Graft-versus-host disease (GVHD) and relapse are major complications following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Metabolites play crucial roles in immune regulation, but their causal relationships with GVHD and relapse remain unclear.

METHODS: We utilized genetic variants from genome-wide association studies (GWAS) of 309 known metabolites as instrumental variables to evaluate their causal effects on acute GVHD (aGVHD), gut GVHD, chronic GVHD (cGVHD), and relapse in different populations. Multiple causal inference methods, heterogeneity assessments, and pleiotropy tests were conducted to ensure result robustness. Multivariable MR analysis was performed to adjust for potential confounders, and validation MR analysis further confirmed key findings. Mediation MR analysis was employed to explore indirect causal pathways.

RESULTS: After correction for multiple testing, we identified elevated pyridoxate and proline levels as protective factors against grade 3-4 aGVHD (aGVHD3) and relapse, respectively. Conversely, glycochenodeoxycholate increased the risk of aGVHD3, whereas 1-stearoylglycerophosphoethanolamine had a protective effect. The robustness and stability of these findings were confirmed by multiple causal inference approaches, heterogeneity, and horizontal pleiotropy analyses. Multivariable MR analysis further excluded potential confounding pleiotropic effects. Validation MR analyses supported the causal roles of pyridoxate and 1-stearoylglycerophosphoethanolamine, while mediation MR revealed that pyridoxate influences GVHD directly and indirectly via CD39[ +] Tregs. Pathway analyses highlighted critical biochemical alterations, including disruptions in bile acid metabolism and the regulatory roles of vitamin B6 derivatives. Finally, clinical metabolic analyses, including direct fecal metabolite measurements, confirmed the protective role of pyridoxate against aGVHD.

CONCLUSIONS: Our findings provide novel insights into the metabolic mechanisms underlying GVHD and relapse after allo-HSCT. Identified metabolites, particularly pyridoxate, may serve as potential therapeutic targets for GVHD prevention and management.}, } @article {pmid40189067, year = {2025}, author = {Jiang, ST and Wang, MQ and Gao, L and Zhang, QC and Tang, C and Dong, YF}, title = {Adjusting the composition of gut microbiota prevents the development of post-stroke depression by regulating the gut-brain axis in mice.}, journal = {Journal of affective disorders}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jad.2025.03.195}, pmid = {40189067}, issn = {1573-2517}, abstract = {Disturbances in gut microbiota contribute to an imbalanced gut-brain axis, which is critical for post-stroke depression (PSD), while the underlying mechanisms remain unclear. The objective of this study was to examine the effects of modifying gut microbiota through antibiotic treatment (ABX) and fecal microbiota transplantation (FMT) on the progression of PSD. The PSD model was established by occluding the middle cerebral artery (MCAO), followed by a four-week isolated housing and restraint stress initiated three days after MCAO. For ABX, the PSD mice received antibiotic water for four weeks. While another group of PSD mice underwent FMT or fluoxetine (FLX) for four weeks. At day 35 post-MCAO, behavioral tests were conducted. Results indicated ABX and FMT significantly altered the composition of intestinal flora caused by PSD, all the treatments markedly attenuated anxiety- and depressive-like behaviors and inflammation in the gut and brain. ABX obviously alleviated PSD-induced disorder of intestinal barrier, decreased mRNA levels of TNF-α, IL-1β and IL-6, and decreased CD4[+] cells in the colon. While FMT significantly decreased CD8[+] cells and increased the goblet cells in colon. Furthermore, both ABX and FMT could reduce activated microglia and pro-inflammatory cytokines in the brain, alleviate decreased Nissl's bodies in the hippocampus, and reverse the decreases in 5-HT, Glu and DA in the striatum caused by PSD. Unlike ABX, FMT was similar to FLX. These findings suggest homeostasis of gut microbiota is indispensable for the development of PSD; adjusting the gut microbiota significantly improves PSD with enhanced functions of gut-brain axis.}, } @article {pmid40188410, year = {2025}, author = {Oyovwi, MO and Ben-Azu, B and Babawale, KH}, title = {Therapeutic potential of microbiome modulation in reproductive cancers.}, journal = {Medical oncology (Northwood, London, England)}, volume = {42}, number = {5}, pages = {152}, pmid = {40188410}, issn = {1559-131X}, mesh = {Humans ; *Microbiota ; Probiotics/therapeutic use ; Female ; Dysbiosis/microbiology/therapy ; *Genital Neoplasms, Female/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Animals ; Gastrointestinal Microbiome ; }, abstract = {The human microbiome, a complex ecosystem of microbial communities, plays a crucial role in physiological processes, and emerging research indicates a potential link between it and reproductive cancers. This connection highlights the significance of understanding the microbiome's influence on cancer development and treatment. A comprehensive review of current literature was conducted, focusing on studies that investigate the relationship between microbiome composition, reproductive cancer progression, and potential therapeutic approaches to modulate the microbiome. Evidence suggests that imbalances in the microbiome, known as dysbiosis, may contribute to the development and progression of reproductive cancers. Specific microbial populations have been associated with inflammatory responses, immune modulation, and even resistance to conventional therapies. Interventions such as probiotics, dietary modifications, and fecal microbiota transplantation have shown promise in restoring healthy microbiome function and improving cancer outcomes in pre-clinical models, with pilot studies in humans indicating potential benefits. This review explores the therapeutic potential of microbiome modulation in the management of reproductive cancers, discussing the mechanisms involved and the evidence supporting microbiome-targeted therapies. Future research is warranted to unravel the complex interactions between the microbiome and reproductive cancer pathophysiology, paving the way for innovative approaches.}, } @article {pmid40187666, year = {2025}, author = {Moreno-Sabater, A and Sintes, R and Truong, S and Lemoine, K and Camou, O and Kapel, N and Magne, D and Joly, AC and Quelven-Bertin, I and Alric, L and Hennequin, C and Sokol, H and , }, title = {Assessment of Dientamoeba fragilis interhuman transmission by fecal microbiota transplantation.}, journal = {International journal of antimicrobial agents}, volume = {}, number = {}, pages = {107504}, doi = {10.1016/j.ijantimicag.2025.107504}, pmid = {40187666}, issn = {1872-7913}, abstract = {Fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) requires careful selection of stool donors to avoid transmitting pathogens. Dientamoeba fragilis detection remains an exclusion criterion based on its uncertain pathogenicity. The aim of this study was to assess D. fragilis interhuman transmission by FMT and its impact on the clinical success of rCDI. A retrospective study was conducted in rCDI patients from the COSMIC cohort undergoing FMT to investigate the potential transfer of D. fragilis from donor to recipient. The impact of FMT involving D. fragilis was also evaluated on the clinical outcomes of rCDI and adverse effects. This protist was found to be present in 15 out of 86 healthy donors screened (18.7%) who voluntarily took part in an FMT program. Examination of D. fragilis presence in stool samples from 17 patients both before and after FMT with D. fragilis-positive donations revealed no evidence of interhuman transmission through this process. Analysis of clinical outcomes and adverse events in 124 rCDI patients who underwent FMT (with 45 receiving D. fragilis-positive donations) showed no significant differences in success rates between patients receiving positive or negative D. fragilis transplants, 95.5% and 93.6%, respectively. No significant variances were observed in other side effects analyzed. These findings underscore the safety of using fecal transplant from D. fragilis positive donors in the FMT process. D. fragilis should be removed from the donor screening, which will represent a major improvement in the donor selection process from financial and practical standpoints.}, } @article {pmid40187461, year = {2025}, author = {Yang, J and Ren, H and Cao, J and Fu, J and Wang, J and Su, Z and Lu, S and Sheng, K and Wang, Y}, title = {Gut commensal Lachnospiraceae bacteria contribute to anti-colitis effects of Lactiplantibacillus plantarum exopolysaccharides.}, journal = {International journal of biological macromolecules}, volume = {309}, number = {Pt 1}, pages = {142815}, doi = {10.1016/j.ijbiomac.2025.142815}, pmid = {40187461}, issn = {1879-0003}, abstract = {The probiotic Lactiplantibacillus plantarum (L. plantarum) could ameliorate colitis. Alterations in the composition of gut microbiota (GM) have been proved in cases of colitis. The exopolysaccharides from L. plantarum HMPM2111 (LPE) could be effective in colitis through altering the composition of the GM. These effects were linked to inhibiting intestinal inflammation, regulating the TXNIP/NLRP3 inflammasome axis, and attenuating colonic barrier dysfunction. The combination of fecal microbiota transplantation (FMT) and antibiotic inducement showed that gut bacteria susceptible to vancomycin were inversely associated with colitis features and were necessary for the anti-inflammatory effects of LPE. The elevated abundances of gut commensal Lachnospiraceae bacteria were associated with the restoration of colitis treated by LPE. Metabolomics analysis showed that colitis mice treated with LPE had higher levels of propionate and tryptophan metabolites generated from gut bacteria. The administration of these metabolites protected colitis and resulted in a reduction in inflammatory responses. The outcomes of our investigation emerge the significance of the GM in controlling the protective implications of LPE against colitis. Lachnospiraceae bacteria, together with downstream metabolites, contribute substantially to protection. This work elucidates the essential function of the GM-metabolite axis in producing comprehensive protection versus colitis and identifies prospective treatment targets.}, } @article {pmid40187430, year = {2025}, author = {Cai, M and Xue, SS and Zhou, CH and Feng, YC and Liu, JZ and Liu, R and Wang, P and Wang, HN and Peng, ZW}, title = {Effects of fecal microbiota transplantation from patients with generalized anxiety on anxiety-like behaviors: The role of the gut-microbiota-endocannabinoid-brain Axis.}, journal = {Journal of affective disorders}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jad.2025.04.018}, pmid = {40187430}, issn = {1573-2517}, abstract = {BACKGROUND: Intestinal dysbacteriosis is frequently implicated in generalized anxiety disorder (GAD). However, the molecular mechanisms and functional changes of the gut-brain axis in GAD remain largely unexplored.

METHODS: We investigated anxiety-like behaviors, gut microbiota changes, brain region-specific endocannabinoid (eCB) system alterations, including the expression of cannabinoid type 1 (CB1R), monoacylglycerol lipase (MAGL), and fatty acid amide hydrolase (FAAH) in the hippocampus (Hip), prefrontal cortex (PFC), and amygdala (Amy), as well as plasma medium- and long-chain fatty acids (MLCFAs) in a mouse model of chronic restraint stress (CRS) and antibiotic-treated mice receiving fecal microbiota transplantation from GAD patients (FMT-GAD). Additionally, we assessed the impact of FMT-GAD on anxiety-like behavior in systemic CB1R/FAAH/MAGL knockout mice.

RESULTS: CRS induced anxiety-like behaviors, suppressed eCB signaling in the brain, and altered the gut microbiota and plasma MLCFA composition in mice. FMT-GAD-treated mice exhibited anxiety-like behaviors, increased FAAH expression in the Hip and Amy, and MAGL expression in the Hip, while reducing CB1R expression in the Hip. FMT-GAD was associated with decreased plasma polyunsaturated fatty acids (PUFAs) and reduced microbiome function for fatty acid biosynthesis. Notably, FMT-GAD intensified anxiety-like behaviors in CB1R-KO mice but failed to induce anxiety-like behaviors in MAGL-KO and FAAH-KO mice.

CONCLUSIONS: This study demonstrates that the interplay between the gut microbiota and the eCB system modulates GAD-related anxiety-like behaviors.}, } @article {pmid40185558, year = {2025}, author = {Shin, JH and Jackson-Akers, JY and Hoang, SC and Behm, BW and Warren, CA}, title = {Fulminant Clostridioides difficile Infection: A Journey into the Unknown!.}, journal = {The Medical clinics of North America}, volume = {109}, number = {3}, pages = {721-734}, doi = {10.1016/j.mcna.2025.01.001}, pmid = {40185558}, issn = {1557-9859}, support = {R01 AI145322/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile/isolation & purification ; Colectomy ; Fecal Microbiota Transplantation ; Ileostomy ; Immunoglobulins, Intravenous/therapeutic use ; }, abstract = {Clostridioides difficile is 1 of the 5 urgent antibiotic resistance threats in the United States as reported by the Centers for Disease Control and Prevention. Fulminant C difficile infection (CDI), characterized by hallmarks of critical illness such as hypotension, shock, or megacolon, has been difficult to define and treat. In this article, we describe the diagnostic criteria for fulminant CDI, clinical factors and inflammatory markers. We review the currently recommended treatment modalities including antibiotics and surgical interventions, colectomy, and diverting loop ileostomy. We also included treatment approaches that are still investigational such as intestinal microbiota transplant, tigecycline, and intravenous immunoglobulin.}, } @article {pmid40185194, year = {2025}, author = {Docherty, J}, title = {Therapeutic potential of faecal microbiota transplantation for alcohol use disorder, a narrative synthesis.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {}, number = {}, pages = {111354}, doi = {10.1016/j.pnpbp.2025.111354}, pmid = {40185194}, issn = {1878-4216}, abstract = {BACKGROUND: Faecal microbiota transplantation is proposed as an alternative therapy to treat alcohol use disorder and has completed a Phase 1 clinical trial, with a Phase 2 clinical trial underway. Alcohol, a modifiable risk factor for noncommunicable diseases, resulted in approximately 3 million global deaths (5 %) in 2016 according to the World Health Organization.

AIMS: A narrative synthesis examines the effects of alcohol and faecal microbiota transplantation on gut microbiota and how gut microbiota impacts the gut-brain axis, leading to certain behavioural symptoms of alcohol use disorder. These behavioural symptoms are alcohol craving and relapse in humans; and preference for alcohol, anxiety and depression in rodents.

SEARCH METHODS AND RESULTS: Electronic databases PubMed, Embase, and Scopus were searched in January 2024 using the terms: faecal microbiota trans* AND alcohol AND microbio*. Ten studies out of 964 met the inclusion criteria of published primary studies with faecal microbiota transplantation as an intervention to study the gut-brain axis in alcohol use disorder.

RESULTS: The gut microbiota is altered in alcohol use disorder, which can be modified with faecal microbiota transplantation. Behavioural symptoms such as alcohol craving and relapse are associated with inflammation due to a loss of intestinal barrier function. Beneficial microbiota produce short-chain fatty acids that maintain intestinal barrier function and reduce inflammation. Studies also reported anxiety and depression-like behaviours, in addition to a preference for alcohol in alcohol-naïve rodents after faecal microbiota transplantation from patients with alcohol use disorder.

CONCLUSIONS: Faecal microbiota transplantation may moderate the behavioural symptoms of alcohol use disorder by altering gut microbiota, affecting intestinal permeability and inflammation, however, specific gut microbiota composition and long-term treatment outcomes require further clinical studies.}, } @article {pmid40185172, year = {2025}, author = {Liu, C and Fan, P and Dai, J and Ding, Z and Yi, Y and Zhan, X and Wang, CC and Liang, R}, title = {Integrated microbiome and metabolome analysis reveals that Zishen Qingre Lishi Huayu recipe regulates gut microbiota and butyrate metabolism to ameliorate polycystic ovary syndrome.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {107533}, doi = {10.1016/j.micpath.2025.107533}, pmid = {40185172}, issn = {1096-1208}, abstract = {BACKGROUND: s: Polycystic ovary syndrome (PCOS) is a metabolic disorder disease strongly associated with gut microbiota (GM). Zishen Qingre Lishi Huayu recipe (ZQLHR), a traditional Chinese medicinal compound, has patented and shown therapeutic effects in treating PCOS in clinical trials without clear pharmacological mechanisms. This study aimed to disclose the potential therapeutic mechanism of ZQLHR on PCOS.

METHODS: We firstly confirmed the therapeutic effects of ZQLHR treatment in PCOS patients. 16S rRNA sequencing, untargeted metabolomics, fecal microbiota transplantation (FMT), high performance liquid chromatography (HPLC) and Person's correlation analysis were conducted to elucidate the potential therapeutic mechanism.

RESULTS: These results showed that PCOS symptoms in ZQLHR patients were significantly ameliorated. ZQLHR could increase the levels of butyrate-producing Lachnospira and Faecalibacterium and decrease the abundance of Escherichia-Shigella. Untargeted metabolomics showed that ZQLHR significantly improved host metabolic function, particularly butyrate metabolism and citrate cycle (TCA cycle) metabolism. The combined Faecalibacterium and butyrate metabolism datasets were correlated. Stool samples from ZQLHR patients could ameliorate ovarian architecture, significantly reduce testosterone (T), estradiol (E2) and luteinizing hormone (LH) levels and increased follicle-stimulating hormone (FSH) levels and increase the content of butyric acid in PCOS mice (P < 0.01). Moreover, the correlation analysis showed that some biochemical parameters (T, E2, LH levels and FSH) and butyric acid were correlated.

CONCLUSION: We firstly depicted that ZQLHR could alleviate the series of symptom in women with PCOS by regulating gut microbiota and butyrate metabolism. This study provides a scientific basis and new ideas for the therapy of PCOS.}, } @article {pmid40184763, year = {2025}, author = {Huang, M and Zhang, Y and Chen, Z and Yu, X and Luo, S and Peng, X and Li, X}, title = {Gut microbiota reshapes the TNBC immune microenvironment: Emerging immunotherapeutic strategies.}, journal = {Pharmacological research}, volume = {215}, number = {}, pages = {107726}, doi = {10.1016/j.phrs.2025.107726}, pmid = {40184763}, issn = {1096-1186}, abstract = {Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and poor prognosis. The gut microbiota, a diverse community of microorganisms in the gastrointestinal tract, plays a crucial role in regulating immune responses through the gut-immune axis. Recent studies have highlighted its significant impact on TNBC progression and the efficacy of immunotherapies. This review examines the interactions between gut microbiota and the immune system in TNBC, focusing on key immune cells and pathways involved in tumor immunity. It also explores microbiota modulation strategies, including probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation, as potential methods to enhance immunotherapeutic outcomes. Understanding these mechanisms offers promising avenues for improving treatment efficacy and patient prognosis in TNBC.}, } @article {pmid40184501, year = {2025}, author = {de Schrijver, S and Vanhulle, E and Ingenbleek, A and Alexakis, L and Johannesen, CK and Broberg, EK and Harvala, H and Fischer, TK and Benschop, KSM and , }, title = {Epidemiological and clinical insights into enterovirus circulation in Europe, 2018 - 2023: a multi-center retrospective surveillance study.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiaf179}, pmid = {40184501}, issn = {1537-6613}, abstract = {BACKGROUND: Enteroviruses (EV) cause yearly outbreaks with severe infections, particularly in young children. This study investigates EV circulation, age-distribution, and clinical presentations in Europe from 2018-2023.

METHODS: Aggregated data were requested from ECDC National Focal Points for Surveillance and European Non-Polio Enterovirus Network. Data included detection month, specimen type, age-group, and clinical presentation for the ten most commonly reported EV types per year.

FINDINGS: Twenty-eight institutions from 16 countries reported 563,654 EV-tests during the study-period with 33,265 (5.9%) EV-positive. Forty-two types were identified (n=11,605 cases) with echovirus (E)30, coxsackievirus (CV)A6, EV-D68, E9, E11, CVB5, E18, CVB4, EV-A71, and E6 most frequently reported. E30 detection declined after 2018/2019, while CVA6, CVB5, E9, E11, and EV-D68 were prevalent both before and after the COVID-19 pandemic, and CVB4 and E18 were prevalent after the pandemic. Over the study period, a shift in seasons (summer to fall) and specimen positivity (feces to respiratory) was observed. Neurological signs predominated among EV-A71, CVB4, CVB5, E6, E9, E11, E18, and E30 (30-72%). CVB4, CVB5, E9, E11, and E18 were also frequently reported among neonates (18-32%). CVA6 was frequently associated with HFMD, and EV-D68 with respiratory infections. Paralysis was reported among 22 infections, associated with ten non-polio types.

CONCLUSION: This study emphasizes the widespread circulation and severe nature of EV infections in Europe, particularly among neonates, as well as the (re-)emergence of specific types post-pandemic. Our findings highlight the need for continuous EV-surveillance to monitor variation in circulation, age, and clinical presentations, including paralysis among non-polio EV infections.}, } @article {pmid40183701, year = {2025}, author = {Peng, W and Jin, Z and Liu, J and Zhang, Q and Liu, W}, title = {Tangeretin modulates gut microbiota metabolism and macrophage immunity following fecal microbiota transplantation in obesity.}, journal = {Journal of food science}, volume = {90}, number = {4}, pages = {e70171}, doi = {10.1111/1750-3841.70171}, pmid = {40183701}, issn = {1750-3841}, support = {//National Natural Science Foundation of China (81670481)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Obesity/therapy/immunology/microbiology/metabolism/drug therapy ; Male ; Mice, Inbred C57BL ; Mice ; *Fecal Microbiota Transplantation ; *Macrophages/immunology/drug effects ; *Flavones/pharmacology ; Diet, High-Fat/adverse effects ; Adipose Tissue/metabolism ; }, abstract = {Obesity, characterized by excessive body fat, is a leading preventable cause of death globally and represents one of the most critical public health challenges of the 21st century. This study aimed to investigate the action of tangeretin on gut microbiota metabolism and inflammation in high-fat diet (HFD)-induced obese mice. A model of obesity was established using 6-week-old male C57BL/6J mice fed with HFD, which were then used for the treatment with tangeretin (20 mg/kg/mice/day) or antibiotic (Abx). The results showed that the tangeretin intervention alleviated fat deposition and disorder of cellular structural integrity in the model group. The obese mice showed a significant increase in the levels of lipid (glycerol, triglyceride, and total cholesterol), inflammatory factors (IL-6 and TNF-α), and F4/80 expression in both serum and adipose tissues. Following tangeretin treatment, the levels of lipid, inflammatory factors, and the ratio of F4/80 + CD206 + macrophages were decreased in both serum and adipose tissue. 16S rRNA sequencing and LC-MS/MS analysis revealed that tangeretin decreased obesity in HFD-induced obese mice by interacting with gut microbiota, particularly influencing Parabacteroides, Blautia, and Parasutterella, and amino acids such as threonine, isoleucine, leucine, phenylalanine, arginine, glutamine, L-tryptophan, and tyrosine. Abx-mediated clearance of gut microbiota blocked the HFD-induced obesity and abrogated the therapeutic effects of tangeretin in obese mice. Fecal microbiota transplantation (FMT) proved that clearing gut microbiota with Abx blocked the beneficial effects of FMT[HFD+Tangeretin] intervention. These findings suggested that tangeretin improved HFD-induced obesity by regulating lipid metabolism and modulating F4/80 macrophage activation via gut microbiota.}, } @article {pmid40182777, year = {2025}, author = {Zhou, S and Zhou, X and Zhang, P and Zhang, W and Huang, J and Jia, X and He, X and Sun, X and Su, H}, title = {The gut microbiota-inflammation-HFpEF axis: deciphering the role of gut microbiota dysregulation in the pathogenesis and management of HFpEF.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1537576}, pmid = {40182777}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Heart Failure/microbiology/therapy/physiopathology/etiology ; *Inflammation/microbiology ; *Dysbiosis ; Animals ; Stroke Volume ; }, abstract = {Heart failure with preserved left ventricular ejection fraction (HFpEF) is a disease that affects multiple organs throughout the body, accounting for over 50% of heart failure cases. HFpEF has a significant impact on individuals' life expectancy and quality of life, but the exact pathogenesis remains unclear. Emerging evidence implicates low-grade systemic inflammation as a crucial role in the onset and progression of HFpEF. Gut microbiota dysregulation and associated metabolites alteration, including short-chain fatty acids, trimethylamine N-oxides, amino acids, and bile acids can exacerbate chronic systemic inflammatory responses and potentially contribute to HFpEF. In light of these findings, we propose the hypothesis of a "gut microbiota-inflammation-HFpEF axis", positing that the interplay within this axis could be a crucial factor in the development and progression of HFpEF. This review focuses on the role of gut microbiota dysregulation-induced inflammation in HFpEF's etiology. It explores the potential mechanisms linking dysregulation of the gut microbiota to cardiac dysfunction and evaluates the therapeutic potential of restoring gut microbiota balance in mitigating HFpEF severity. The objective is to offer novel insights and strategies for the management of HFpEF.}, } @article {pmid40182189, year = {2025}, author = {Burdette, RA and Whitt, CC and Behm, BW and Warren, CA}, title = {Avoiding Premature Antibiotic Use in Recurrent Clostridioides difficile Infection After Fecal Microbiota Transplant.}, journal = {ACG case reports journal}, volume = {12}, number = {4}, pages = {e01660}, pmid = {40182189}, issn = {2326-3253}, abstract = {Recurrent Clostridioides difficile infection (rCDI) remains a major clinical challenge, often requiring fecal microbiota transplantation (FMT) after conventional treatment fails. An 86-year-old woman with rCDI underwent FMT after failing multiple antibiotic therapies. Shortly after FMT, she experienced diarrhea and abdominal pain, alongside positive C. difficile stool tests. Antibiotics were withheld because of clinical improvement, and she achieved complete resolution of symptoms without further treatment. This case demonstrates the potential benefit of withholding antibiotics in rCDI patients soon after FMT to allow sufficient time for donor microbiota engraftment and underscores the need for further research to optimize post-FMT management.}, } @article {pmid40180421, year = {2025}, author = {Clavijo-Salomon, MA and Trinchieri, G}, title = {Unlocking the power of the microbiome for successful cancer immunotherapy.}, journal = {Journal for immunotherapy of cancer}, volume = {13}, number = {4}, pages = {}, pmid = {40180421}, issn = {2051-1426}, mesh = {Humans ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Fecal Microbiota Transplantation/methods ; *Microbiota ; }, abstract = {In recent years, evidence has shown that the gut microbiome significantly influences responses to immunotherapy. This has sparked interest in targeting it to improve therapy outcomes and predictions of response and toxicity. Research has demonstrated that dysbiosis, often resulting from antibiotic use, can diminish the effectiveness of immune checkpoint inhibitors, and this lack of efficacy could be linked to systemic inflammation. Certain bacterial species have been identified as having beneficial and harmful effects on immunotherapy in the clinic. While a clear consensus has yet to emerge on the optimal species for therapeutic use, introducing a new microbiome into immunotherapy-refractory patients may boost their chances of responding to further treatment attempts. State-of-the-art interventions targeting the microbiome-such as fecal microbiota transplantation-are being assessed clinically for their safety and potential to enhance treatment outcomes, with promising results. Additionally, the microbiome has been leveraged for its power to predict clinical outcomes using machine learning, and surprisingly, its predictive capability is comparable to that of other described multi-biomarker clinical scores. Here, we discuss developing knowledge concerning the microbiome's significance in cancer immunotherapy and outline future strategies for maximizing its potential in immuno-oncology.}, } @article {pmid40177494, year = {2025}, author = {Liu, J and Li, F and Yang, L and Luo, S and Deng, Y}, title = {Gut microbiota and its metabolites regulate insulin resistance: traditional Chinese medicine insights for T2DM.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1554189}, pmid = {40177494}, issn = {1664-302X}, abstract = {The gut microbiota is closely associated with the onset and development of type 2 diabetes mellitus (T2DM), characterized by insulin resistance (IR) and chronic low-grade inflammation. However, despite the widespread use of first-line antidiabetic drugs, IR in diabetes and its complications continue to rise. The gut microbiota and its metabolic products may promote the development of T2DM by exacerbating IR. Therefore, regulating the gut microbiota has become a promising therapeutic strategy, with particular attention given to probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. This review first examines the relationship between gut microbiota and IR in T2DM, summarizing the research progress of microbiota-based therapies in modulating IR. We then delve into how gut microbiota-related metabolic products contribute to IR. Finally, we summarize the research findings on the role of traditional Chinese medicine in regulating the gut microbiota and its metabolic products to improve IR. In conclusion, the gut microbiota and its metabolic products play a crucial role in the pathophysiological process of T2DM by modulating IR, offering new insights into potential therapeutic strategies for T2DM.}, } @article {pmid40177417, year = {2025}, author = {Wu, Y and Chen, X and Wu, Q and Wang, Q}, title = {Research progress on fecal microbiota transplantation in tumor prevention and treatment.}, journal = {Open life sciences}, volume = {20}, number = {1}, pages = {20220954}, pmid = {40177417}, issn = {2391-5412}, abstract = {The application of fecal microbiota transplantation (FMT) as a therapeutic strategy to directly modify the makeup of the gut microbiota has made significant progress in the last few decades. The gut microbiota, a sizable microbial community present in the human gut, is essential for digestion, immunomodulation, and nutrition absorption. Alternatively, a growing body of research indicates that gut microbiota is a key contributor to cancer, and intratumoral bacteria are considered to be crucial "accomplices" in the development and metastasis of malignancies. The exceptional clinical effectiveness of FMT in treating melanoma patients has been adequately established in earlier research, which has created new avenues for the diagnosis and treatment of cancer and sparked an increasing interest in the treatment and prevention of other cancers. However, further research on the function and mechanisms of the gut microbiota is required to properly comprehend the impact and role of these organisms in tumor regulation. In this article, we present a detailed account of the influence of FMT on the entire course of cancer patients' illness and treatment, from tumor development, metastasis, and invasion, to the impact and application of treatment and prognosis, as well as address the associated mechanisms.}, } @article {pmid40176987, year = {2025}, author = {Yarahmadi, A and Najafiyan, H and Yousefi, MH and Khosravi, E and Shabani, E and Afkhami, H and Aghaei, SS}, title = {Beyond antibiotics: exploring multifaceted approaches to combat bacterial resistance in the modern era: a comprehensive review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1493915}, pmid = {40176987}, issn = {2235-2988}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use/pharmacology ; *Drug Resistance, Bacterial ; *Bacterial Infections/therapy/microbiology/drug therapy ; Animals ; *Bacteria/drug effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Antimicrobial Peptides/therapeutic use ; }, abstract = {Antibiotics represent one of the most significant medical breakthroughs of the twentieth century, playing a critical role in combating bacterial infections. However, the rapid emergence of antibiotic resistance has become a major global health crisis, significantly complicating treatment protocols. This paper provides a narrative review of the current state of antibiotic resistance, synthesizing findings from primary research and comprehensive review articles to examine the various mechanisms bacteria employ to counteract antibiotics. One of the primary sources of antibiotic resistance is the improper use of antibiotics in the livestock industry. The emergence of drug-resistant microorganisms from human activities and industrial livestock production has presented significant environmental and public health concerns. Today, resistant nosocomial infections occur following long-term hospitalization of patients, causing the death of many people, so there is an urgent need for alternative treatments. In response to this crisis, non-antibiotic therapeutic strategies have been proposed, including bacteriophages, probiotics, postbiotics, synbiotics, fecal microbiota transplantation (FMT), nanoparticles (NPs), antimicrobial peptides (AMPs), antibodies, traditional medicines, and the toxin-antitoxin (TA) system. While these approaches offer innovative solutions for addressing bacterial infections and preserving the efficacy of antimicrobial therapies, challenges such as safety, cost-effectiveness, regulatory hurdles, and large-scale implementation remain. This review examines the potential and limitations of these strategies, offering a balanced perspective on their role in managing bacterial infections and mitigating the broader impact of antibiotic resistance.}, } @article {pmid40176137, year = {2025}, author = {Sommer, F and Bernardes, JP and Best, L and Sommer, N and Hamm, J and Messner, B and López-Agudelo, VA and Fazio, A and Marinos, G and Kadibalban, AS and Ito, G and Falk-Paulsen, M and Kaleta, C and Rosenstiel, P}, title = {Life-long microbiome rejuvenation improves intestinal barrier function and inflammaging in mice.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {91}, pmid = {40176137}, issn = {2049-2618}, support = {SO1141/10-1//Deutsche Forschungsgemeinschaft/ ; CRC1182//Deutsche Forschungsgemeinschaft/ ; miTARGET//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; RNA, Ribosomal, 16S/genetics ; *Fecal Microbiota Transplantation ; *Aging/physiology ; Feces/microbiology ; *Bacteria/classification/genetics/isolation & purification ; Male ; *Intestinal Mucosa/microbiology/metabolism ; *Inflammation/microbiology ; Mice, Inbred C57BL ; *Rejuvenation ; Permeability ; *Intestines/microbiology ; Metagenomics ; Intestinal Barrier Function ; }, abstract = {BACKGROUND: Alterations in the composition and function of the intestinal microbiota have been observed in organismal aging across a broad spectrum of animal phyla. Recent findings, which have been derived mostly in simple animal models, have even established a causal relationship between age-related microbial shifts and lifespan, suggesting microbiota-directed interventions as a potential tool to decelerate aging processes. To test whether a life-long microbiome rejuvenation strategy could delay or even prevent aging in non-ruminant mammals, we performed recurrent fecal microbial transfer (FMT) in mice throughout life. Transfer material was either derived from 8-week-old mice (young microbiome, yMB) or from animals of the same age as the recipients (isochronic microbiome, iMB) as control. Motor coordination and strength were analyzed by rotarod and grip strength tests, intestinal barrier function by serum LAL assay, transcriptional responses by single-cell RNA sequencing, and fecal microbial community properties by 16S rRNA gene profiling and metagenomics.

RESULTS: Colonization with yMB improved coordination and intestinal permeability compared to iMB. yMB encoded fewer pro-inflammatory factors and altered metabolic pathways favoring oxidative phosphorylation. Ecological interactions among bacteria in yMB were more antagonistic than in iMB implying more stable microbiome communities. Single-cell RNA sequencing analysis of intestinal mucosa revealed a salient shift of cellular phenotypes in the yMB group with markedly increased ATP synthesis and mitochondrial pathways as well as a decrease of age-dependent mesenchymal hallmark transcripts in enterocytes and TA cells, but reduced inflammatory signaling in macrophages.

CONCLUSIONS: Taken together, we demonstrate that life-long and repeated transfer of microbiota material from young mice improved age-related processes including coordinative ability (rotarod), intestinal permeability, and both metabolic and inflammatory profiles mainly of macrophages but also of other immune cells. Video Abstract.}, } @article {pmid40175647, year = {2025}, author = {Ahn, JS and Kim, S and Han, EJ and Hong, ST and Chung, HJ}, title = {Increasing spatial working memory in mice with Akkermansia muciniphila.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {546}, pmid = {40175647}, issn = {2399-3642}, support = {C512230//Korea Basic Science Institute (KBSI)/ ; RS-2023-00224099//National Research Foundation of Korea (NRF)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; *Memory, Short-Term/physiology ; Male ; *Spatial Memory/physiology ; Akkermansia ; Humans ; Verrucomicrobia ; Feces/microbiology ; Brain-Derived Neurotrophic Factor/metabolism ; }, abstract = {Recent research has shown the gut microbiome's impact on memory, yet limitations hinder the identification of specific microbes linked to cognitive function. We measured spatial working memory in individual mice before and after fecal microbiota transplantation (FMT) to develop a targeted analysis that identifies memory-associated strains while minimizing host genetic effects. Transplantation of human fecal into C57BL/6 mice yielded varied outcomes: some mice showed significant improvements while others had negligible changes, indicating that these changes are due to differences in FMT colonization. Metagenomic analysis, stratified by memory performance, revealed a positive correlation between the abundance of Akkermansia muciniphila and improved memory. Moreover, administering two A. muciniphila strains, GMB 0476 and GMB 2066, to wild-type mice elevated spatial working memory via BDNF activation. Our findings indicate that specific gut microbes, particularly A. muciniphila, may modulate memory and represent potential targets for therapeutic intervention in cognitive enhancement.}, } @article {pmid40175389, year = {2025}, author = {Braga, JD and Yang, Y and Nagao, T and Kato, N and Yanaka, N and Nishio, K and Okada, M and Kuroda, M and Yamaguchi, S and Kumrungsee, T}, title = {Fructooligosaccharides and Aspergillus enzymes increase brain GABA and homocarnosine by modulating microbiota in adolescent mice.}, journal = {NPJ science of food}, volume = {9}, number = {1}, pages = {48}, pmid = {40175389}, issn = {2396-8370}, abstract = {Recent research suggests that dietary prebiotics, probiotics, or healthy fecal-microbiota transplantation attenuate gut microbiota dysbiosis and ameliorate neurological disorders, in which gut-microbiota-derived γ-aminobutyric acid (GABA) has gained much attention as one of key mediators in the gut-brain axis. Although it is widely accepted that prebiotics and probiotics induce gut and brain GABA production via modulating gut microbiota, only evidence of probiotics has been solidly demonstrated while this evidence of prebiotics is scarce. Here, we demonstrated that prebiotic fructo-oligosaccharides and Aspergillus-derived enzymes elevated gut and brain GABA concentrations by modulating gut microbiota. Interestingly, we found that the prebiotic and enzymes increased a brain-specific dipeptide, homocarnosine. Gut GABA levels were found correlated with brain GABA/homocarnosine levels. Parabateroides, Akkermansia, Muribaculum, Hungatella, Marvinbryantia, Flavonifractor, and Incertae_sedis exhibited a positive correlation with gut GABA and brain GABA/homocarnosine levels, while Blautia, Unclassified_Lachnospiraceae, Colidextribacter, Acetatifactor, Roseburia, Unclassified_Oscillospiraceae, Romboutsia, and Eubacterium_coprostanoligenes exhibited a negative correlation with those levels.}, } @article {pmid40174272, year = {2025}, author = {Abavisani, M and Tafti, P and Khoshroo, N and Ebadpour, N and Khoshrou, A and Kesharwani, P and Sahebkar, A}, title = {The heart of the matter: How gut microbiota-targeted interventions influence cardiovascular diseases.}, journal = {Pathology, research and practice}, volume = {269}, number = {}, pages = {155931}, doi = {10.1016/j.prp.2025.155931}, pmid = {40174272}, issn = {1618-0631}, abstract = {The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.}, } @article {pmid40171188, year = {2025}, author = {Li, C and Cheng, D and Ren, H and Zhang, T}, title = {Unraveling the gut microbiota's role in PCOS: a new frontier in metabolic health.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1529703}, pmid = {40171188}, issn = {1664-2392}, mesh = {Humans ; *Polycystic Ovary Syndrome/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; Female ; *Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Animals ; Prebiotics ; }, abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting reproductive-age women, characterized primarily by hyperandrogenism, ovulatory dysfunction, and metabolic abnormalities. In recent years, the gut microbiota has garnered widespread attention for its potential role as a key regulator of host metabolism in the pathogenesis of PCOS. Studies have shown that PCOS patients exhibit dysbiosis in their gut microbiota, characterized by reduced microbial diversity, an imbalance in the ratio of Firmicutes to Bacteroidetes, changes in the abundance of specific taxa, and abnormal levels of metabolic products. These alterations may exacerbate metabolic dysfunction in PCOS through multiple mechanisms, including influencing host energy metabolism, disrupting lipid and bile acid metabolism, and inducing chronic inflammation. Addressing gut dysbiosis through the modulation of patients' microbiomes-such the use of, prebiotics, fecal microbiota transplantation, and optimizing diet lifestyle-may offer strategies for improving metabolic abnormalities and alleviating clinical symptoms in PCOS. Additionally, the gut microbiome promises as a potential marker, aiding in the precise diagnosis and personalization of PCOS. Although our current understanding of how the gut microbiota influences PCOS is still limited, research is needed to explore the causal relationships and mechanisms involved, providing a more reliable theoretical basis for clinical. This review aims summarize the research progress on the relationship between gut microbiota and PCOS, and to suggest future directions to promote the development of prevention and treatment strategies for PCOS.}, } @article {pmid40171160, year = {2025}, author = {Chen, F and Zhang, H and Wei, Q and Tang, J and Yin, L and Ban, Y and Zhou, Q}, title = {Disrupted gut microbiota promotes the progression of chronic kidney disease in 5/6 nephrectomy mice by Bacillus pumilus gavage.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1548767}, pmid = {40171160}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Renal Insufficiency, Chronic/microbiology/metabolism ; Mice ; *Probiotics/administration & dosage ; *Nephrectomy ; *Disease Models, Animal ; *RNA, Ribosomal, 16S/genetics ; *Disease Progression ; *Bacillus pumilus ; Feces/microbiology ; Kidney/pathology ; Male ; Dysbiosis/microbiology ; Bacteria/classification/isolation & purification/genetics ; Mice, Inbred C57BL ; Metabolomics ; }, abstract = {BACKGROUND: Our previous study identified differences in the gut microbiota between patients with chronic kidney disease (CKD) and healthy individuals. We observed that antibiotic-treated mice exhibited symptoms similar to those of patients with CKD after receiving a gut microbiota transplant from patients with CKD. Bacillus pumilus (B. pumilus), an alien microorganism to both human and mouse gut microbiota, possesses antibiotic properties that can alter the microbial community structure. Therefore, this study aimed to explore how changes in the gut microbiota structure induced by the oral gavage of B. pumilus affect the progression of CKD. We sought to identify the gut microbes and metabolic pathways associated with CKD to lay the groundwork for future clinical probiotic applications in patients with CKD.

METHODS: We constructed sham-operated and 5/6 nephrectomy mice as the sham control (SC) and CKD models, respectively. CKD models were divided into a control group (CG) and an intervention group (IG). After 16 weeks of normal feeding, the IG were treated with B. pumilus by oral gavage, while SC and CG were treated with PBS once daily, 5 days per week, for 7 weeks. Fecal samples were collected for 16s rRNA sequencing and metabolomic analysis, kidneys were harvested for histological examination, and the colon was used for RT-PCR analysis.

RESULTS: B. pumilus intervention exacerbated gut microbial homeostasis in CKD mice and increased serum creatinine and urea nitrogen levels, further aggravating kidney damage. 16s rRNA and metabolomic analysis revealed that Parvibacter and Enterorhabdus were probiotics related to kidney function, while Odoribacter was associated with kidney injury. Metabolomic analysis showed that glycerophospholipid and lysine metabolism were upregulated in CKD model mice, correlating with kidney damage.

CONCLUSION: This study shows that changes in the gut microbiota can affect the kidneys through gut metabolism, confirming that the lack of probiotics and the proliferation of harmful bacteria leading to gut microbiota dysbiosis are drivers of CKD progression. Our findings provide a basis for clinical interventions using gut microbes and offer a reference for targeted probiotic therapy.}, } @article {pmid40170570, year = {2025}, author = {Yao, N and Liu, Y and Zhang, ZY and Tian, M and Xie, WJ and Zhao, H and Yang, H and Rodewald, LE and Wen, N and Yin, ZD and Wang, FZ and Wang, Q and Xu, JW}, title = {Excretion and clearance of Sabin-like type 3 poliovirus in a child diagnosed with severe combined immunodeficiency.}, journal = {Human vaccines & immunotherapeutics}, volume = {21}, number = {1}, pages = {2484882}, pmid = {40170570}, issn = {2164-554X}, mesh = {Humans ; *Severe Combined Immunodeficiency/complications ; *Poliovirus/genetics/immunology ; *Virus Shedding ; *Poliomyelitis ; *Feces/virology ; Infant ; Female ; Child, Preschool ; Pilot Projects ; Male ; Child ; Poliovirus Vaccine, Oral/adverse effects/immunology ; Homeodomain Proteins/genetics ; Hematopoietic Stem Cell Transplantation/adverse effects ; }, abstract = {Children with primary immunodeficiency disorder (PID) are at higher risk of developing vaccine-associated paralytic poliomyelitis (VAPP) or vaccine-derived polioviruses (VDPV) infection when inadvertently expose to poliovirus vaccine, oral (OPV). A pilot study was initiated to describe the epidemiology of immunodeficiency-associated VDPV (iVDPV) and to estimate the risk of iVDPV shedding among individuals with PID. Children under 18 years of age newly diagnosed with PID were recruited for investigation and tested for poliovirus excretion. Children with poliovirus-positive stool samples had regular follow-up testing for poliovirus excretion and determination of clinical prognosis. A patient with severe combined immunodeficiency (SCID) with compound heterozygous mutations in the RAG1 gene was found to be excreting Sabin-like type 3 (SL3) poliovirus. Excretion stopped six weeks after hematopoietic stem-cell transplantation (HSCT). Graft versus host disease (GVHD) and poor graft function (PGF) occurred after HSCT, resulting in failure of hematopoiesis and immune system reconstitution. Given deficient innate and adaptive immunity, immune-mediated destruction of gastrointestinal (GI) tract caused by GVHD and inflammatory diarrheal illness of the girl may have contributed to her clearance of SL3 poliovirus. Intermittent surveillance of immune system parameters for iVDPV excreters receiving HSCT should be included in the PID surveillance program for further understanding poliovirus clearance mechanisms.}, } @article {pmid40170504, year = {2025}, author = {Zheng, Y and Chen, J and Zhang, Y and Guan, H and Deng, S and Chang, D and Wang, Y and Lu, J and Zhou, X and Xie, Q and Song, J and Huang, M}, title = {Gut Microbiota and Bile Acid Metabolism in the Mechanism of Ginsenoside Re Against Nonalcoholic Fatty Liver Disease.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8474}, pmid = {40170504}, issn = {1099-1573}, support = {2022YFC3501205//National Key Research and Development Program of China Stem Cell and Translational Research/ ; 2021FX02//Collaborative Innovation Platform Project of Fuxiaquan National Innovation Demonstration Zone/ ; 82274080//National Natural Science Foundation of China Projects/ ; //Research Support Program Fellowship, Western Sydney University/ ; }, abstract = {Gut microbiota and bile acid metabolism play crucial roles in the progression of nonalcoholic fatty liver disease (NAFLD). Early evidence demonstrates that Ginsenoside Re (Re) possesses pharmacological effects on NAFLD, but its mechanisms of action are not well understood. This study aimed to investigate the hepatic protective effects of Re in NAFLD and elucidate relevant mechanisms. The effects of Re treatments (10, 20, or 40 mg/kg) against high-fat diet-induced NAFLD were initially tested on male C57BL/6 mice. Then, a separate mouse group received Re with or without antibiotics to confirm the regulatory role of microbiota in the effect of Re. Finally, another group of mice received fecal microbiota transplantation (FMT) from the initial experiment of NAFLD mice to further investigate the mechanistic role of gut microbiota. Re significantly improved liver function by reducing hepatic lipid accumulation, injury and hepatocyte steatosis, and inflammation. The liver protection was mediated by the regulation of gut microbiota as evidenced by restored intestinal barrier integrity, normalized Firmicutes/Bacteroidota ratio, enhanced abundances of Adlercreutzia equolifaciens, and reduced Faecalibaculum rodentium. Following that, Re reduced total and primary bile acids and downregulated bile acid synthesis genes and proteins such as farnesoid X receptor and cytochrome P450 family 7 subfamily A member 1. The co-administration of antibiotic cocktail counteracted the effect of Re against NAFLD. Further, the results obtained from the FMT animal study confirmed that Re's liver protective effects were at least partly driven by the regulation of gut microbiota. Re modulated bile salt hydrolase-related microbial genera to alter bile acid synthesis pathways, thereby inhibiting NAFLD progression.}, } @article {pmid40168721, year = {2025}, author = {Shi, Y and Jiang, M and Zhu, W and Chang, K and Cheng, X and Bao, H and Peng, Z and Hu, Y and Li, C and Fang, F and Song, J and Jian, C and Chen, J and Shu, X}, title = {Cyclosporine combined with dexamethasone regulates hepatic Abca1 and PPARα expression and lipid metabolism via butyrate derived from the gut microbiota.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {186}, number = {}, pages = {118017}, doi = {10.1016/j.biopha.2025.118017}, pmid = {40168721}, issn = {1950-6007}, abstract = {Immunosuppression often leads to drastic metabolic, hormonal, and physiological disorders. Changes in the gut microbiota are believed to be one of the factors contributing to these disorders, but the association remains uncertain. Clinical studies can be complicated by confounding variables, such as diet and other drivers of heterogeneity in human microbiomes. In this study, we identified pronounced gut microbiome signatures in rhesus macaques (RMs) with immunosuppression-induced lipid metabolism disorders following cyclosporine combined with dexamethasone. Furthermore, we observed similar changes in the gut microbiota of mice with immunosuppression-induced lipid metabolism disorders, which were associated with short-chain fatty acid metabolism. ELISA showed that immunosuppression significantly reduced the levels of butyric acid in both feces and serum of mice. Spearman correlation analysis identified a significant correlation between serum butyric acid levels and gut microbial dysbiosis induced by immunosuppression, particularly in relation to f_Lachnospiraceae, g_unidentified_Ruminococcaceae, and s_Clostridium leptum. Additionally, mice transplanted with gut microbiota from immunosuppressed mice exhibited hepatic lipid metabolism disorders, and RNA sequencing revealed significant downregulation of ABC transporters and PPARα in the liver, which was closely associated with lipid transport and metabolism, particularly Abca1. Moreover, butyric acid supplementation alleviated hepatic lipid metabolism disorders and upregulated the expression of Abca1 and PPARα in mice transplanted with immunosuppression-induced gut microbiota. Thus, we propose that the combination of cyclosporine and dexamethasone regulates the expression of hepatic Abca1 and PPARα by modulating the gut microbiota and its derived butyrate, particularly Lachnospiraceae and Clostridium leptum, further regulating hepatic lipid metabolism.}, } @article {pmid40168084, year = {2025}, author = {Ishikawa, D and Watanabe, H and Nomura, K and Zhang, X and Maruyama, T and Odakura, R and Koma, M and Shibuya, T and Osada, T and Fukuda, S and Nakahara, T and Terauchi, J and Nagahara, A and Yamada, T}, title = {Patient-donor similarity and donor-derived species contribute to the outcome of faecal microbiota transplantation for ulcerative colitis.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjaf054}, pmid = {40168084}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: Clinical applications of faecal microbiota transplantation (FMT) for treating ulcerative colitis (UC) have shown promising results. However, whether the beneficial effects of FMT are due to the transfer and colonisation of donor-derived species in patients remains unclear. Here, we investigated the factors affecting the efficacy of administration of triple antibiotics (A-FMT) and the criteria for appropriate donor and patient-donor matching.

METHODS: Ninety-seven patients with active UC who were enrolled between March 2014 and October 2019 underwent FMT. The clinical features were assessed based on a reduction in Lichtiger's clinical activity index 4 weeks after A-FMT, with long-term responders (LTR) defined as those with no increase or intensification within 12 months after A-FMT. Microbiome analysis was performed on 147 faecal samples (pre-A-FMT, post-A-FMT, and donor) from 49 patient-donor combinations that were assigned using the one patient-to-one donor strategy.

RESULTS: Of the 97 patients, 61 achieved a clinical response, and of those, 35 were classified as having clinical remission. The efficacy of A-FMT was affected by UC severity and previous administration of steroids (p = 0.027), immunosuppressants (p = 0.049), and biologics (p = 0.029). Effective donors were rich in taxa such as Bacteroidota, which are lost in UC, and the abundances of "patient-origin" and "new-amplicon sequence variant" taxa were significantly lower in Responders compared to Nonresponders (Remission; p = 0.03, LTR; p = 0.05). "Donor-derived" amplicon sequence variant sequences, Oscillospiraceae UCG-002 and Alistipes, were significantly enriched in Responders (p < 0.05). Our results showed that the taxonomic composition of patients and the similarity of Bacteroides and butyric acid-producing bacteria in the patient-donor microbiota significantly influenced A-FMT efficacy (p < 0.05).

CONCLUSIONS: This study provides important insights for developing patient-tailored FMT-based therapies for UC.}, } @article {pmid40167852, year = {2025}, author = {Xiang, M and Wu, S and Liu, M and Zhang, B and Xia, X and Tan, W and Xiang, S}, title = {Iota-carrageenan oligosaccharide ameliorates DSS-induced colitis in mice by mediating gut microbiota dysbiosis and modulating SCFAs-PI3K-AKT pathway.}, journal = {Inflammopharmacology}, volume = {}, number = {}, pages = {}, pmid = {40167852}, issn = {1568-5608}, support = {NO.2024AFD252//the Natural Science Foundation of Hubei Province/ ; }, abstract = {Iota-carrageenan oligosaccharides (iCOs), derived from marine red algae, are traditionally used as antithrombotic and anti-inflammatory agents in folk medicinal practice. Despite the prevailing emphasis on these aspects in their applications, the potential of iCOs as a prebiotic agent for gut health and its subsequent impact on intestinal disorders such as colitis remains largely unexplored. A DSS-induced colitis model was employed in C57BL/6 male mice to analyze the gut microbiota via 16S rRNA sequencing. Fecal microbiota transplantation (FMT) was used to assess the therapeutic effects of iCOs on colitis. RNA sequencing (RNA-Seq) identified pathways and genes affected by iCOs. ELISA measured inflammatory cytokines, while western blot and RT-qPCR evaluated protein and gene expressions, respectively. The iCOs increased beneficial bacteria, such as Lactobacillus, Bifidobacterium, and Akkermansia. They enhanced short-chain fatty acid production and upregulated GPR41, GPR43, and GPR109A mRNA, influencing cytokine secretion. The iCOs reduced mRNA of SPHK1, BDKRB1, LCN2, and so on, potentially through PI3K-Akt pathway inhibition, and promoted tight junction protein expression. Our findings highlight the novel therapeutic potential of iCOs in colitis, indicating a multifaceted approach to treatment that includes gut microbiota modulation, intestinal barrier restoration, and the suppression of inflammatory responses.}, } @article {pmid40166981, year = {2025}, author = {Huang, M and Ji, Q and Huang, H and Wang, X and Wang, L}, title = {Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2486519}, doi = {10.1080/19490976.2025.2486519}, pmid = {40166981}, issn = {1949-0984}, mesh = {Humans ; *Carcinoma, Hepatocellular/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; *Liver Neoplasms/immunology/therapy/microbiology ; *Immunotherapy ; *Tumor Microenvironment/immunology ; *Probiotics/therapeutic use/administration & dosage ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited treatment options at advanced stages. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, plays a pivotal role in regulating immune responses through the gut-liver axis. Emerging evidence underscores its impact on HCC progression and the efficacy of immunotherapy. This review explores the intricate interactions between gut microbiota and the immune system in HCC, with a focus on key immune cells and pathways involved in tumor immunity. Additionally, it highlights strategies for modulating the gut microbiota - such as fecal microbiota transplantation, dietary interventions, and probiotics - as potential approaches to enhancing immunotherapy outcomes. A deeper understanding of these mechanisms could pave the way for novel therapeutic strategies aimed at improving patient prognosis.}, } @article {pmid40166958, year = {2025}, author = {Zhang, Z and Zhu, T and Li, Y and Yu, B and Tao, H and Zhao, H and Cui, B}, title = {Butyrate Regulates Intestinal DNA Virome and Lipopolysaccharide Levels to Prevent High-Fat Diet-Related Liver Damage in Rats.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c07966}, pmid = {40166958}, issn = {1520-5118}, abstract = {As the adsorption receptor of bacteriophage tail protein, bacterial lipopolysaccharide (LPS) is a main culprit responsible for nonalcoholic fatty liver disease (NAFLD) caused by high-fat diets. However, few studies have focused on how the interaction between intestinal bacteriophages and bacterial LPS affects the development and progression of NAFLD. Herein, we determined that excessive fat intake significantly increases the levels of endogenous LPS, while the administration of beneficial metabolites of the intestinal microbiota (specifically butyrate) alleviated hepatic injury in rats. The beneficial mechanism of butyrate was attributed to the reprogramming of the structure of the intestinal DNA virome (primarily, phageome). Butyrate possesses the potential to augment bacteriophagic microbial diversity, thereby potentially facilitating interactions between intestinal bacteriophages and bacterial LPS (in the case of homologous phage), further improving mitochondrial dysfunction and reactive oxygen species production, which, in turn, lowered HepG2 cell damage. Likewise, fecal phage transplantation further confirmed that intestinal phages from rats that received butyrate could effectively interact with bacterial LPS to reduce liver damage in rats. Taken together, modifying the intestinal phageome is a promising treatment option for high-fat diet-related NAFLD.}, } @article {pmid40166696, year = {2025}, author = {Halvorsen, N and Hassan, C and Correale, L and Pilonis, N and Helsingen, LM and Spadaccini, M and Repici, A and Foroutan, F and Olav Vandvik, P and Sultan, S and Løberg, M and Kalager, M and Mori, Y and Bretthauer, M}, title = {Benefits, burden, and harms of computer aided polyp detection with artificial intelligence in colorectal cancer screening: microsimulation modelling study.}, journal = {BMJ medicine}, volume = {4}, number = {1}, pages = {e001446}, pmid = {40166696}, issn = {2754-0413}, abstract = {OBJECTIVE: To estimate the benefits, burden, and harms of implementing computer aided detection (CADe) of polyps in colonoscopy of population based screening programmes for colorectal cancer.

DESIGN: Microsimulation modelling study.

SETTING: Cost effectiveness working package in the OperA (optimising colorectal cancer prevention through personalised treatment with artificial intelligence) project. A parallel guideline committee panel (BMJ Rapid recommendation) was consulted in defining the screening interventions and selection of outcome measures.

POPULATION: Four cohorts of 100 000 European individuals aged 60-69 years.

INTERVENTION: The intervention was one screening of colonoscopy and a screening of colonoscopy after faecal immunochemical test every other year with CADe. The comparison group had the same screening every other year without CADe.

MAIN OUTCOME MEASURES: Benefits (colorectal cancer incidence and death), burden (surveillance colonoscopies), and harms (colonoscopy related adverse events) over 10 years were measured. The certainty in each outcome was assessed by use of the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

RESULTS: For 100 000 individuals participating in colonoscopy screening, 824 (0.82%) were diagnosed with colorectal cancer within 10 years without CADe versus 713 (0.71%) with CADe (risk difference -0.11% (95% CI -0.43% to 0.21%)). For faecal immunochemical test screening colonoscopy, the risk was 5.82% (n=5820) without CADe versus 5.77% (n=5770) with CADe (difference -0.05% (-0.33% to 0.15%)). The risk of surveillance colonoscopy increased from 26.45% (n=26 453) to 32.82% (n=32 819) (difference 6.37% (5.8% to 6.9%)) for colonoscopy screening and from 52.26% (n=52 263) to 53.08% (n=53 082) (difference 0.82% (0.38% to 1.26%)) for faecal immunochemical test screening colonoscopy. No significant differences were noted in adverse events related to the colonoscopy between CADe and no CADe. The model estimates were sensitive to the assumed effects of screening on colorectal cancer risk and of CADe on adenoma detection rates. All outcomes were graded as low certainty.

CONCLUSION: With low certainty of evidence, adoption of CADe in population based screening provides small and uncertain clinical meaningful benefit, no incremental harms, and increased surveillance burden after screening.}, } @article {pmid40165964, year = {2025}, author = {Ding, W and Cheng, Y and Liu, X and Zhu, Z and Wu, L and Gao, J and Lei, W and Li, Y and Zhou, X and Wu, J and Gao, Y and Ling, Z and Jiang, R}, title = {Harnessing the human gut microbiota: an emerging frontier in combatting multidrug-resistant bacteria.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1563450}, pmid = {40165964}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Drug Resistance, Multiple, Bacterial ; *Fecal Microbiota Transplantation ; *Dysbiosis/microbiology ; *Anti-Bacterial Agents/therapeutic use/pharmacology ; Bacterial Infections/microbiology/immunology/drug therapy ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; Bacteria/drug effects ; Animals ; }, abstract = {Antimicrobial resistance (AMR) has become a major and escalating global health threat, undermining the effectiveness of current antibiotic and antimicrobial therapies. The rise of multidrug-resistant bacteria has led to increasingly difficult-to-treat infections, resulting in higher morbidity, mortality, and healthcare costs. Tackling this crisis requires the development of novel antimicrobial agents, optimization of current therapeutic strategies, and global initiatives in infection surveillance and control. Recent studies highlight the crucial role of the human gut microbiota in defending against AMR pathogens. A balanced microbiota protects the body through mechanisms such as colonization resistance, positioning it as a key ally in the fight against AMR. In contrast, gut dysbiosis disrupts this defense, thereby facilitating the persistence, colonization, and dissemination of resistant pathogens. This review will explore how gut microbiota influence drug-resistant bacterial infections, its involvement in various types of AMR-related infections, and the potential for novel microbiota-targeted therapies, such as fecal microbiota transplantation, prebiotics, probiotics, phage therapy. Elucidating the interactions between gut microbiota and AMR pathogens will provide critical insights for developing novel therapeutic strategies to prevent and treat AMR infections. While previous reviews have focused on the general impact of the microbiota on human health, this review will specifically look at the latest research on the interactions between the gut microbiota and the evolution and spread of AMR, highlighting potential therapeutic strategies.}, } @article {pmid40165428, year = {2025}, author = {Wang, L and Shao, L and Gao, YC and Liu, J and Li, XD and Zhou, J and Li, SF and Song, YL and Liu, B and Zhang, W and Huang, WH}, title = {Panax notoginseng Saponins Alleviate Inflammatory Bowel Disease via Alteration of Gut Microbiota-Bile Acid Metabolism.}, journal = {The American journal of Chinese medicine}, volume = {}, number = {}, pages = {1-30}, doi = {10.1142/S0192415X25500223}, pmid = {40165428}, issn = {1793-6853}, abstract = {Bile acid metabolism mediated by gut microbiota is significantly related to immunity regulation that plays an important role in the development and treatment of inflammatory bowel disease (IBD). Our previous study has demonstrated that Panax notoginseng saponins (PNS) alleviate colitis due to the regulation of T helper 17/Regulatory T cells (Th17/Treg) balance via gut microbiota. However, the effects and mechanism of PNS on colitis pertinent to bile acid metabolism mediated by gut microbiota remain elusive. This study aims to investigate the anti-colitis mechanism of PNS by regulating the Th17/Treg balance pertinent to gut microbiota-bile acid metabolism. Results showed that PNS significantly decreased the relative abundance of Allobaculum, Dubosiella, Muribaculum, and Alistipes, and up-regulated the relative contents of conjugated bile acids, such as TCA and TCDCA. Fecal microbiota transplantation (FMT) showed that the gut microbiota remodeled by PNS had a regulatory effect on bile acid metabolism, and up-regulated the relative contents of TCA and TCDCA, which alleviated IBD and promoted Treg cell expression in vivo and in vitro. Taken together, PNS could reshape the profiling of gut microbiota to generate more TCA and TCDCA, which improve the balance of Th17/Treg to exert anti-IBD effects.}, } @article {pmid40164697, year = {2025}, author = {Jia, L and Ke, Y and Zhao, S and Liu, J and Luo, X and Cao, J and Liu, Y and Guo, Q and Chen, WH and Chen, F and , and Wang, J and Wu, H and Ding, J and Zhao, XM}, title = {Metagenomic analysis characterizes stage-specific gut microbiota in Alzheimer's disease.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {40164697}, issn = {1476-5578}, abstract = {Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a decade-long preclinical pathological period that can be divided into several stages. Emerging evidence has revealed that the microbiota-gut-brain axis plays an important role in AD pathology. However, the role of gut microbiota in different AD stages has not been well characterized. In this study, we performed fecal shotgun metagenomic analysis on a Chinese cohort with 476 participants across five stages of AD pathology to characterize stage-specific alterations in gut microbiota and evaluate their diagnostic potential. We discovered extensive gut dysbiosis that is associated with neuroinflammation and neurotransmitter dysregulation, with over 10% of microbial species and gene families showing significant alterations during AD progression. Furthermore, we demonstrated that microbial gene families exhibited strong diagnostic capabilities, evidenced by an average AUC of 0.80 in cross-validation and 0.75 in independent external validation. In the optimal model, the most discriminant gene families are primarily involved in the metabolism of carbohydrates, amino acids, energy, glycan and vitamins. We found that stage-specific microbial gene families in AD pathology could be validated by an in vitro gut simulator and were associated with specific genera. We also observed that the gut microbiota could affect the progression of cognitive decline in 5xFAD mice through fecal microbiota transplantation, which could be used for early intervention of AD. Our multi-stage large cohort metagenomic analysis demonstrates that alterations in gut microbiota occur from the very early stages of AD pathology, offering important etiological and diagnostic insights.}, } @article {pmid40163879, year = {2025}, author = {Cintosun, A and Jamal, I and Samnani, S and Song, YN and Bretthauer, M}, title = {Gastroenterology/Hepatology: What You May Have Missed in 2024.}, journal = {Annals of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.7326/ANNALS-25-00959}, pmid = {40163879}, issn = {1539-3704}, abstract = {This article highlights selected major advances in gastroenterology and hepatology from 2024 that are relevant for internal medicine specialists. In colorectal cancer (CRC) screening, new developments include a head-to-head comparison of different fecal immunochemical tests and a new blood-based DNA screening test, benefits and harms of artificial intelligence-assisted colonoscopy, and adenoma detection rate improvement and risk for cancer. Treatment options for metabolic dysfunction-associated steatotic liver disease now include resmetirom, a recently approved drug for treatment of patients with moderate-to-severe fibrosis, and liver transplantation may now be an option in patients with unresectable colorectal liver metastases. Also featured are new data on the efficacy of indomethacin and pancreatic stent placement for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography and news on the efficacy and safety of zastaprazan, a new potassium-competitive acid blocker for reflux esophagitis. Finally, a recent randomized trial is highlighted that has dispelled concerns about potential harms of proton-pump inhibitors for stress ulcer prophylaxis in patients receiving invasive mechanical ventilation.}, } @article {pmid40162905, year = {2025}, author = {Sigtryggsson, AT and Helgason, KO and Bjarnason, A and Gottfredsson, M}, title = {[Clostridioides difficile infections at Landspítali University Hospital 2017-2022].}, journal = {Laeknabladid}, volume = {111}, number = {4}, pages = {158-165}, doi = {10.17992/lbl.2025.04.834}, pmid = {40162905}, issn = {1670-4959}, mesh = {Humans ; *Hospitals, University ; Female ; Male ; Iceland/epidemiology ; Incidence ; *Anti-Bacterial Agents/therapeutic use ; Risk Factors ; Time Factors ; Aged ; Middle Aged ; *Clostridium Infections/epidemiology/diagnosis/microbiology/therapy/mortality/drug therapy ; *Recurrence ; Treatment Outcome ; *Clostridioides difficile/pathogenicity/isolation & purification/drug effects ; Cross Infection/epidemiology/diagnosis/microbiology/mortality/drug therapy ; Aged, 80 and over ; Adult ; Community-Acquired Infections/epidemiology/diagnosis/microbiology/therapy/mortality/drug therapy ; }, abstract = {OBJECTIVE: To investigate the epidemiology, severity, treatment, and prognosis of patients with C. difficile infections (CDI) diagnosed at Landspítali University Hospital from 2017-2022.

MATERIALS AND METHODS: The study population consisted of adult patients at Landspítali with double-positive (PCR + ELISA) diagnostic tests. If the same patient had two or more positive samples within a 28-day period, they were considered to reflect the same infection, and the latter samples were excluded.

RESULTS: Overall, 358 CDI were identified in 301 patients. The majority of cases were diagnosed in women (59.5%). The incidence of healthcare-associated CDI was 3.23 infections/10.000 in-hospital days (range 2.65 - 3.26). Incidence of community-associated CDI was 0.57 infections/10.000 inhabitants of the Reykjavik metropolitan area. Incidence was positively correlated with increasing age and remained similar throughout the study period. The recurrence rate during the study period was 15.3% with a mean follow-up period of 1.6 person-years. At least 85.5% of patients had taken antibiotics within a month before diagnosis, most commonly from the penicillin class (57.8%), followed by cephalosporins (51.5%). More than half (54.7%) of patients had taken proton pump inhibitors preceding diagnosis. Metronidazole was the most common initial treatment (63.0%). Of these, 29.4% of cases required further treatment within 28 days of treatment start. Fecal microbiota transplantation was performed in 13 cases. The 30-day all-cause mortality rate was 7.3%.

CONCLUSIONS: The incidence of CDI at Landspítali has remained stable and comparable to what has been reported in Europe during the same period. Most patients had one or more risk factors present. Most received antibiotics as treatment, most commonly metronidazole. The results of this study indicate that incidence and clinical presentation of CDI in Iceland are stable, whilst novel treatment options look promising.}, } @article {pmid40161578, year = {2025}, author = {Zhong, XS and Lopez, KM and Krishnachaitanya, SS and Liu, M and Xiao, Y and Ou, R and Nagy, HI and Kochkarian, T and Powell, DW and Fujise, K and Li, Q}, title = {Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.03.13.643179}, pmid = {40161578}, issn = {2692-8205}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with significant extraintestinal manifestations, including cardiovascular derangements. However, the molecular mechanisms underlying the cardiac remodeling and dysfunction remain unclear.

METHODS: We investigated the effects of chronic colitis on the heart using two mouse models: DSS-induced colitis and Il10 [-/-] spontaneous colitis. Echocardiography was employed to assess heart function and molecular characterization was performed using bulk RNA-sequencing, RT-qPCR, and western blot.

RESULTS: Both models exhibited significant cardiac impairment, including reduced ejection fraction and fractional shortening as well as increased collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed upregulation of fibrosis markers (i.e. COL1A1, COL3A1, Fibronectin) and β-catenin reactivation, indicating a pro-fibrotic cardiac environment. Each model yielded common upregulation of eicosanoid-associated and inflammatory genes (Cyp2e1 , Map3k6 , Pck1 , Cfd), and model-specific alterations in pathways regulating cAMP- and cGMP-signaling, arachidonic and linoleic acid metabolism, Cushing syndrome-related genes, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, while Il10 [-/-] colitis yielded 105 dysregulated genes, revealing distinct molecular pathways driving cardiac dysfunction. Importantly, therapeutic fecal microbiota transplantation (FMT) restored heart function in both models, characterized by reduced fibrosis markers and downregulated pro-inflammatory genes (Lbp and Cdkn1a in Il10 [-/-] mice and Fos in DSS mice), while also mitigating intestinal inflammation. Post-FMT cardiac RNA-sequencing revealed significant gene expression changes, with three altered genes in DSS mice and 67 genes in Il10 [-/-] mice. Notably, Il10 [-/-] mice showed relatively less cardiac recovery following FMT, highlighting IL-10's cardioprotective and anti-inflammatory contribution.

CONCLUSIONS: Our findings elucidate novel insights into colitis-induced cardiac remodeling and dysfunction and suggest that FMT mitigates cardiac dysfunction by attenuating systemic inflammation and correcting gut dysbiosis. This study underscores the need for further evaluation of gut-heart interactions and microbiome-based therapies to improve cardiovascular health in IBD patients.}, } @article {pmid40161500, year = {2025}, author = {Dai, W and Chen, X and Zhou, H and Liu, N and Jin, M and Guo, Z}, title = {Microbiota modulation for infectious complications following allogeneic hematopoietic stem cell transplantation in pediatric hematological malignancies.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1509612}, pmid = {40161500}, issn = {2296-2360}, abstract = {The intervention of microbiota modulation in the treatment of infection complications after allogeneic hematopoietic stem cell transplantation in pediatric patients with hematological malignancies has shown potential benefits. Through the use of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), these interventions modulate the gut microbiota and enhance immune function to prevent and treat infections. They have been shown to reduce the incidence of diarrhea and intestinal infections, mitigate the issue of antibiotic resistance, and promote the recovery of gut microbiota. Future research is needed to further assess the safety and efficacy of these interventions and to establish standardized treatment protocols.}, } @article {pmid40160347, year = {2025}, author = {Tucker, EC and Angelica, B and Mathias, RM and Edwards, L and Bryant, RV and Costello, SP}, title = {Outcomes of Fecal Microbiota Transplantation for Clostridioides difficile Infection in South Australia.}, journal = {Open forum infectious diseases}, volume = {12}, number = {4}, pages = {ofaf149}, pmid = {40160347}, issn = {2328-8957}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) sourced from a bank of prescreened anaerobically processed frozen donor stool has been available in South Australia since 2013. This study aimed to evaluate the real-world clinical and safety outcomes of FMT for recurrent, refractory, and/or severe or fulminant Clostridioides difficile infection (CDI) facilitated via this centralized facility.

METHODS: Donor screening test data were prospectively collected on all donors who passed prescreening evaluations between April 2013 and August 2023. The South Australian FMT for CDI database prospectively recorded outcomes for consecutive patients who underwent FMT for CDI from August 2013 to May 2023 in South Australia.

RESULTS: An overall 98 potential donors passed prescreening assessments and underwent laboratory screening tests: 32 (33%) had tests that failed, 5 (5%) had incomplete screening, and 61 (62%) passed. Detection of an extended-spectrum β-lactamase-producing organism (9/65, 14%) was the common reason for ineligibility following completion of screening tests. In total 220 cases of CDI were recorded, and follow-up data were available in 216. Primary cure occurred in 84% of cases (182/216): 88% (132/150) for recurrent CDI, 76% (50/66) for refractory CDI, 85% (51/60) for severe disease, and 65% (17/26) for fulminant disease. Repeat FMT was delivered in 23 of 34 cases (68%), with secondary cure in 74% (17/23 cases). Serious adverse events were observed in 6 patients overall (3%). No deaths were directly attributable to FMT.

CONCLUSIONS: FMT was safe and efficacious for management of recurrent and refractory CDI over a 10-year period in a real-world prospective Australian cohort. Further studies to optimize the use of FMT for severe and fulminant CDI are warranted.}, } @article {pmid40160324, year = {2025}, author = {Cao, Z and Gao, T and Bajinka, O and Zhang, Y and Yuan, X}, title = {Fecal microbiota transplantation-current perspective on human health.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1523870}, pmid = {40160324}, issn = {2296-858X}, abstract = {Recently, microbiome medicine has attracted the attention of researchers. While this rapidly growing medical approach for various diseases and disorders is changing the paradigm, it is imperative to weigh both its benefits and the associated risk factors. For instance, manipulation of the gut microbiota (GM) has positive effects on metabolic and neurodegenerative diseases. Notably, fecal microbiota transplantation (FMT), a complex method, has shown promise; however, many doubt its feasibility without adverse effects on human health. Given the number of human clinical trials investigating FMT for the treatment of various disorders, this review summarizes recent findings on its impact on human health. This review summarizes the metabolic responses associated with FMT and their reversal effects on gastrointestinal infections, behavioral changes, and immune responses. Additionally, this review discusses the role of FMT in antimicrobial resistance and its co-supplementation effects on human health, safety, potential risks, limitations, prospects, and recommendations. Although this review does not cover all the studies in the database, the searched terms for FMT and human health in clinical trials are sufficient to provide a summary of the current perspective.}, } @article {pmid40158522, year = {2025}, author = {Bretthauer, M and Kalager, M}, title = {First head-to-head trial of colonoscopy versus faecal testing for colorectal cancer screening.}, journal = {Lancet (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1016/S0140-6736(25)00288-0}, pmid = {40158522}, issn = {1474-547X}, } @article {pmid40157463, year = {2025}, author = {Han, Y and Zhang, Y and Chen, J and Jiang, S and Zheng, Y and Xu, Y and Li, Y and Kong, J and Yu, X and Du, H}, title = {Iron overload exacerbates metabolic dysfunction-associated steatohepatitis via the microbiota-gut-liver axis through lipopolysaccharide-mediated Akr1b8 activation.}, journal = {Free radical biology & medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.freeradbiomed.2025.03.039}, pmid = {40157463}, issn = {1873-4596}, abstract = {Iron homeostatic is closely linked to the development of metabolic dysfunction-associated steatohepatitis (MASH). However, the underlying mechanisms remain poorly understood. HFE knockout (KO) mice were used to generate mild iron-overload models. MASH was induced by feeding mice a methionine- and choline-deficient (MCD) diet for 4 weeks. Iron overload significantly exacerbated the pathologies of MCD-induced MASH, including liver injury, hepatic lipid accumulation, inflammation, and fibrosis. Additionally, iron overload reshaped the composition of gut microbiota, and fecal microbiota transplantation assay proved that gut microbiota from iron-overload mice contributed to hepatic lipid accumulation in control mice. Furthermore, iron overload-induced dysbacteriosis altered the metabolite profiles, reducing short-chain fatty acid levels and increasing lipopolysaccharide (LPS) levels. Notably, elevated LPS levels upregulated the expression of aldo-keto reductase family 1 member B8 (Akr1b8), which accelerated lipid accumulation and inflammation in hepatocytes. Above results indicated that iron overload promoted MASH progression through the microbiota-gut-liver axis, mediated by LPS-induced activation of Akr1b8. These findings highlight the critical role of iron homeostasis and gut microbiota in MASH pathogenesis.}, } @article {pmid40157004, year = {2025}, author = {Rahimi, A and Baghernejadan, Z and Hazrati, A and Malekpour, K and Samimi, LN and Najafi, A and Falak, R and Khorramdelazad, H}, title = {Combination therapy with immune checkpoint inhibitors in colorectal cancer: Challenges, resistance mechanisms, and the role of microbiota.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {186}, number = {}, pages = {118014}, doi = {10.1016/j.biopha.2025.118014}, pmid = {40157004}, issn = {1950-6007}, abstract = {Colorectal cancer (CRC) is still one of the leading causes of cancer deaths worldwide. Even though there has been progress in cancer immunotherapy, the results of applying immune checkpoint inhibitors (ICIs) have been unsatisfactory, especially in microsatellite stable (MSS) CRC. Single-agent ICIs that target programmed cell death-1 (PD-1)/ PD-L1, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell Ig- and mucin-domain-containing molecule-3 (TIM-3), and lymphocyte activation gene (LAG)-3 have emerged as having specific benefits. However, many primary and secondary resistance mechanisms are available in the tumor microenvironment (TME) that prevent it from happening. Combination strategies, such as the use of anti-PD-1 and anti-CTLA-4, can be effective in overcoming these resistance pathways, but toxicities remain a significant concern. Moreover, ICIs have been integrated with various treatment modalities, including chemotherapy, radiotherapy, antibiotics, virotherapy, polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, and heat shock protein 90 (HSP90) inhibitors. The outcomes observed in both preclinical and clinical settings have been encouraging. Interestingly, manipulating gut microbiota via fecal microbiota transplantation (FMT) has been identified as a new strategy to increase the efficacy of immunotherapy in CRC patients. Therefore, integrating ICIs with other treatment approaches holds promise in enhancing the prognosis of CRC patients. This review focuses on the unmet need for new biomarkers to select patients for combination therapies and the ongoing work to overcome resistance and immune checkpoint blockade.}, } @article {pmid40156349, year = {2025}, author = {Karataş, M and Bloemen, M and Cuypers, L and Wollants, E and Van Ranst, M and Matthijnssens, J}, title = {14 years of rotavirus A surveillance: unusual dominance of equine-like G3P[8] genotype with DS-1-like genotype constellation after the pandemic, Belgium, 2009 to 2023.}, journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin}, volume = {30}, number = {12}, pages = {}, pmid = {40156349}, issn = {1560-7917}, mesh = {*Rotavirus/genetics/isolation & purification ; Humans ; *Rotavirus Infections/epidemiology/virology ; *Genotype ; Belgium/epidemiology ; Child, Preschool ; *Gastroenteritis/virology/epidemiology ; Infant ; *COVID-19/epidemiology/virology ; *Feces/virology ; *SARS-CoV-2/genetics ; Child ; Capsid Proteins/genetics ; Pandemics ; Male ; Female ; Antigens, Viral/genetics ; Animals ; Adolescent ; Infant, Newborn ; Rotavirus Vaccines/administration & dosage ; Adult ; }, abstract = {IntroductionDespite vaccine availability, rotavirus persists as a leading cause of gastroenteritis in children younger than 5 years.AimWe aimed to evaluate temporal changes in rotavirus epidemiology in Belgium between 2009 and 2023, including the period of the COVID-19 pandemic.MethodsWe collected 8,024 rotavirus-positive stool samples throughout Belgium. For 6,352 samples, we determined the G and/or P genotypes through sequencing of the genes encoding the outer capsid proteins VP7 and VP4.ResultsBefore the COVID-19pandemic, we received on average 622 samples per rotavirus epidemiological year, which decreased to 114 and 111 samples during the two pandemic rotavirus epidemiological years, followed by a peak of 1,048 samples in the first post-pandemic year. Notably, the proportion of cases in the age group 2-5-years increased from 20.3% before to 33% after the pandemic (p < 0.001). Over the 14-year study period, the most common genotypes were G2P[4], G3P[8] and G9P[8]. Post-pandemic data show an unusually strong dominance of the equine-like G3P[8] genotype which carried a DS-1-like genotype constellation in the period 2021 to 2023. Additionally, vaccinated individuals were significantly overrepresented among patients infected with the equine-like VP7 carrying G3P[8] rotavirus compared with other genotypes, including typical human VP7 G3P[8].ConclusionDespite the presence of typical yearly genotype fluctuations, several epidemiological changes were associated with the COVID-19 pandemic, including the unusual dominance of an emerging rotavirus strain against which current vaccines may be less effective. It is essential to closely monitor this strain to determine if the phenomenon is temporary.}, } @article {pmid40154780, year = {2025}, author = {Lin, SM and Le, PH and Chen, CL and Yeh, YM and Liao, HL and Chiu, CH}, title = {Fecal microbiota transplantation to decolonize vancomycin-resistant Enterococcus: A pilot study to evaluate safety and clinical outcome.}, journal = {Journal of global antimicrobial resistance}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgar.2025.03.011}, pmid = {40154780}, issn = {2213-7173}, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) has shown promise as a treatment for recurrent or refractory Clostridioides difficile infections. This study aimed to evaluate the decolonization effects of FMT on vancomycin-resistant Enterococcus (VRE).

METHODS: This feasibility trial prospectively recruited patients with more than three recurrent VRE infections. FMT was performed by infusing fecal microbiota solutions from healthy, unrelated donors into the participants' guts via colonoscopy. Fecal microbiota profiles before and after FMT were analyzed.

RESULTS: Three of the six patients (50%) experienced VRE decolonization after FMT, lasting over six months. Baseline analysis revealed that patients who achieved decolonization had greater microbial diversity compared to those with persistent VRE colonization. Throughout the study, there were no adverse events observed in the patients after FMT. Elevated alpha diversity persisted in responders, while non-responders showed no significant changes. In responders, the abundance of genera within the phylum Firmicutes (Bacillota), including Anaerostipes, Blautia, Faecalibacterium, and Ruminococcus, and the genus Collinsella within the phylum Actinobacteriota increased steadily through 180 days post-FMT.

CONCLUSIONS: FMT may leverage bacterial strain competition to facilitate decolonization of drug-resistant organisms, with successful VRE decolonization potentially linked to increased abundance of phyla Firmicutes and Actinobacteriota over 6 months.}, } @article {pmid40154488, year = {2025}, author = {Martin, D and Bonneau, M and Orfila, L and Horeau, M and Hazon, M and Demay, R and Lecommandeur, E and Boumpoutou, R and Guillotel, A and Guillemot, P and Croyal, M and Cressard, P and Cressard, C and Cuzol, A and Monbet, V and Derbré, F}, title = {Atypical gut microbial ecosystem from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen store in mice.}, journal = {Cell reports}, volume = {}, number = {}, pages = {115448}, doi = {10.1016/j.celrep.2025.115448}, pmid = {40154488}, issn = {2211-1247}, abstract = {Although the gut microbiota is known to act as a bridge between dietary nutrients and the body's energy needs, the interactions between the gut microbiota, host energy metabolism, and exercise capacity remain uncertain. Here, we characterized the gut microbiota ecosystem in a cohort of healthy normo-weight humans with highly heterogeneous aerobic exercise capacities and closely related body composition and food habits. While our data support the idea that the bacterial ecosystem appears to be modestly altered between individuals with low-to-high exercise capacities and close food habits, we report that gut bacterial α diversity, density, and functional richness are significantly reduced in athletes with very high exercise capacity. By using fecal microbiota transplantation, we report that the engraftment of gut microbiota from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen stores into transplanted mice, which highlights promising therapeutic perspectives in fecal transplantation from human donors selected based on exercise capacity traits.}, } @article {pmid40153399, year = {2025}, author = {Gabarre, P and Palacios, R and Perez, K and Seksik, P and Bonnard, B and Loens, C and Lefranc, C and de Barros, JP and Anjou, L and Tamzali, Y and Zahr, N and Jaisser, F and Tourret, J}, title = {Immunosuppressive drugs and diet interact to modify the gut microbiota and cardiovascular risk factors, and to trigger diabetes.}, journal = {PloS one}, volume = {20}, number = {3}, pages = {e0320438}, pmid = {40153399}, issn = {1932-6203}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; Male ; Mice ; *Diet, High-Fat/adverse effects ; *Immunosuppressive Agents/pharmacology/adverse effects ; Mice, Inbred C57BL ; Diabetes Mellitus/microbiology ; Insulin Resistance ; Cardiometabolic Risk Factors ; Cardiovascular Diseases/etiology ; Feces/microbiology ; }, abstract = {BACKGROUND: Kidney transplant recipients are prescribed an immunosuppressive therapy (IST) and some of them follow a high fat diet (HFD) despite medical recommendations. Both are frequently associated with gut microbiota changes and metabolic disorders. We aimed at precisely identifying the effect of the IST and the HFD on metabolic parameters and the gut microbiota in mice, and at establishing correlations between the latters.

METHODS: 8-week-old male mice were treated with IST (a combination of prednisone, mycophenolate mofetil and tacrolimus) or not and were fed HFD or standard chow. Metabolic parameters were measured, and the gut microbiota was explored by the quantification of specific bacterial groups by qPCR and by 16S rDNA sequencing.

RESULTS: The HFD increased insulinemia and decreased the fecal proportion of Bacteroidetes and of Bacteroides. The IST increased systolic blood pressure and the fecal proportion of Escherichia coli. The HFD and the IST administered together resulted in an additive effect on glucose intolerance, high fasting blood glucose, homeostasis model assessment of insulin resistance (HOMA-IR), percentage of fat mass, blood triglyceride, blood cholesterol, and endotoxemia. On the opposite, the HFD and the IST had antagonistic effects on body weight, the proportion of Firmicutes, the Firmicutes/Bacteroidetes ratio, and the proportion of Clostridium leptum, Bifidobacterium, and Lactobacillus in the feces. Finally, we found that the correlations between gut bacterial communities and metabolic consequences of the HFD were altered by the IST.

CONCLUSION: The IST and the HFD have specific consequences on the gut microbiota and metabolism. We hypothesize that the metabolic consequences are at least partially mediated by IST/HFD-induced dysbiosis.}, } @article {pmid40151642, year = {2025}, author = {Cai, X and Cho, JY and Chen, L and Liu, Y and Ji, F and Salgado, K and Ge, S and Yang, D and Yu, H and Shao, J and Futreal, PA and Sepesi, B and Gibbons, D and Chen, Y and Wang, G and Cheng, C and Wu, M and Zhang, J and Hsiao, A and Xia, T}, title = {Enriched pathways in gut microbiome predict response to immune checkpoint inhibitor treatment across demographic regions and various cancer types.}, journal = {iScience}, volume = {28}, number = {4}, pages = {112162}, pmid = {40151642}, issn = {2589-0042}, abstract = {Understanding the effect of gut microbiota function on immune checkpoint inhibitor (ICI) responses is urgently needed. Here, we integrated 821 fecal metagenomes from 12 datasets to identify differentially abundant genes and construct random forest models to predict ICI response. Gene markers demonstrated excellent predictive performance, with an average area under the curve (AUC) of 0.810. Pathway analyses revealed that quorum sensing (QS), ABC transporters, flagellar assembly, and amino acid biosynthesis pathways were enriched between responders (R) and non-responders (NRs) across 12 datasets. Furthermore, luxS, manA, fliC, and trpB exhibited consistent changes between R and NR across 12 datasets. Follow-up microbiota transplant experiments showed that inter-species signaling by different QS autoinducer-2 (AI-2) molecules (synthesized by luxS) can act on overall community function to promote the colonization of Akkermansia muciniphila, which is associated with superior ICI responses. Together, our data highlight the role of gut microbiota function in modulating the microbiome and antitumor immunity.}, } @article {pmid40150325, year = {2025}, author = {Wang, K and Suo, Y and Shen, D and Shi, Y and Jin, X and Li, Y and Li, C}, title = {Improvement in Heat Stress-Induced Damage to Sperm Quality Following Fecal Microbiota Transplantation from L-Arginine-Treated Mice.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {6}, pages = {}, pmid = {40150325}, issn = {2076-2615}, support = {32372935//National Natural Science Foundation of China/ ; }, abstract = {Heat stress has become a significant concern in animal husbandry, as it adversely affects reproductive performance, particularly sperm quality, through mechanisms that are not fully understood. This study aimed to investigate the protective effects of L-arginine against heat stress-induced sperm damage and explore its potential mechanisms through the modulation of the intestinal microbiota. This study consisted of two experiments. First, in a heat-stressed mouse model, L-arginine was administered to evaluate its effects on the reproductive health of heat-stressed mice. In the second experiment, by transplanting L-arginine-induced changes in the gut microbiota into heat-stressed mice, the protective effects of the microbiota on the sperm of heat-stressed mice were assessed. The findings revealed a significant amelioration of decreased sperm quality and testicular injury induced by heat stress. Post heat stress, mice supplemented with L-arginine presented an increase in seminal vesicle gland weight and index, partial alleviation of testicular tissue morphology, and a substantial increase in testosterone concentration (p < 0.05). Additionally, L-arginine upregulated the expression of testosterone synthesis genes and the mRNA levels of sperm generation-related genes, including 3β-HSD, Stra8, WT1, and Gdnf (p < 0.05). Concurrently, L-arginine-induced microbial communities mitigated heat stress-induced decreases in sperm quality and testicular injury, coupled with increases in the mRNA expression levels of Cyp17a1, 17β-HSD, Plzf, and Gdnf (p < 0.05). Furthermore, there was a reduction in the expression of proinflammatory factors, namely, NFκB, MyD88, TNF-α, and TGF-β3 (p < 0.05). In conclusion, L-arginine may influence the ratio of beneficial bacteria to harmful bacteria in the intestinal microbiota, thereby reducing inflammation caused by heat stress, maintaining intestinal health, and influencing the microenvironment for spermatogenesis.}, } @article {pmid40149692, year = {2025}, author = {Sivakumar, N and Krishnamoorthy, A and Ryali, H and Arasaradnam, RP}, title = {Gut Microbial Targets in Inflammatory Bowel Disease: Current Position and Future Developments.}, journal = {Biomedicines}, volume = {13}, number = {3}, pages = {}, pmid = {40149692}, issn = {2227-9059}, abstract = {Inflammatory bowel disease (IBD) is a debilitating condition in which surgery is often seen as a last resort. However, this is associated with morbidity and, in some cases, mortality. There are emerging therapies that seek to better modulate the immune response of hosts with IBD. Aims: The main aim of this study is to focus on novel therapies and techniques studied in the last year that are non-surgical treatments of IBD. Methods: We looked at all the research between March 2024 and February 2025 detailing treatment in IBD and focused on the gut microbiome and gene therapy. Results: Novel therapies are gaining traction in safety and popularity. The results from some animal studies show promise and, with FDA approval, some probiotic therapies show optimistic research potential for future human trials. Conclusions: The research into the diagnostics and novel therapies available on the horizon for humans is very promising. Animal studies have shown potentially transferrable and safe therapies that can target specific sites of inflammation. Modulating the inflammatory response is a powerful therapy with what is shown to be a reasonably safe profile to build further research on.}, } @article {pmid40149377, year = {2025}, author = {Zhang, B and Mohd Sahardi, NFN and Di, W and Long, X and Shafiee, MN}, title = {The Gut-Endometrium Axis: Exploring the Role of Microbiome in the Pathogenesis and Treatment of Endometrial Cancer-A Narrative Review.}, journal = {Cancers}, volume = {17}, number = {6}, pages = {}, pmid = {40149377}, issn = {2072-6694}, abstract = {Background/Objectives: Endometrial cancer (EC) is a prevalent gynecological malignancy with an increasing incidence, particularly in developed countries. Recent research has demonstrated the significant involvement of gut and endometrial microbiomes in the pathogenesis and progression of EC. This review provides a comprehensive overview of the existing knowledge on the interactions between these microbial communities and their influence on EC. Methodology: A literature review was conducted using electronic databases including Google Scholar, Scopus, and PUBMED, covering the period from 2017 to 2024. The following keywords were used for the literature search: (1) gut microbiome and endometrial cancer, (2) endometrium microbiome and endometrial cancer, and (3) endometrial cancer and microbial dysbiosis. The selected articles were chosen based on inclusion and exclusion criteria. Scale for Assessment of Narrative Review Articles (SANRA) was used for evaluating and assessing the quality of articles. Results: The gut microbiome modulates systemic inflammation, immune responses, and estrogen metabolism, all of which are crucial factors in EC development. Dysbiosis is an imbalance in the composition of microbes that can cause chronic inflammation and hormonal imbalances, which can contribute to the EC. Similarly, the endometrial microbiome, while less extensively studied, has been implicated in EC through mechanisms involving local immune modulation and the production of harmful metabolites. Probiotics, prebiotics, fecal microbiota transplantation (FMT), and personalized microbiota-based therapies can be used as clinical interventions for EC management. This review emphasizes the need for further research to explore the gut-endometrium axis and its potential for innovative therapeutic approaches. Understanding these complex interactions will become a novel strategy to prevent and treat EC, ultimately enhancing patient outcomes.}, } @article {pmid40149075, year = {2025}, author = {Kenneth, MJ and Wu, CC and Fang, CY and Hsu, TK and Lin, IC and Huang, SW and Chiu, YC and Hsu, BM}, title = {Exploring the Impact of Chemotherapy on the Emergence of Antibiotic Resistance in the Gut Microbiota of Colorectal Cancer Patients.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, pmid = {40149075}, issn = {2079-6382}, support = {R0010//This research was supported by Cheng Hsin General Hospital, Dalin Tzu Chi Hospital, Asia University Hospital, and Ditmanson Medical Foundation Chiayi Christian Hospital-National Chung Cheng University Joint Research Program/ ; }, abstract = {With nearly half of colorectal cancer (CRC) patients diagnosed at advanced stages where surgery alone is insufficient, chemotherapy remains a cornerstone for this cancer treatment. To prevent infections and improve outcomes, antibiotics are often co-administered. However, chemotherapeutic interactions with the gut microbiota cause significant non-selective toxicity, affecting not only tumor and normal epithelial cells but also the gut microbiota. This toxicity triggers the bacterial SOS response and loss of microbial diversity, leading to bacterial mutations and dysbiosis. Consequently, pathogenic overgrowth and systemic infections increase, necessitating broad-spectrum antibiotics intervention. This review underscores how prolonged antibiotic use during chemotherapy, combined with chemotherapy-induced bacterial mutations, creates selective pressures that drive de novo antimicrobial resistance (AMR), allowing resistant bacteria to dominate the gut. This compromises the treatment efficacy and elevates the mortality risk. Restoring gut microbial diversity may mitigate chemotherapy-induced toxicity and improve therapeutic outcomes, and emerging strategies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, show considerable promise. Given the global threat posed by antibiotic resistance to cancer treatment, prioritizing antimicrobial stewardship is essential for optimizing antibiotic use and preventing resistance in CRC patients undergoing chemotherapy. Future research should aim to minimize chemotherapy's impact on the gut microbiota and develop targeted interventions to restore microbial diversity affected during chemotherapy.}, } @article {pmid40147837, year = {2025}, author = {Foroutan, F and Vandvik, PO and Helsingen, LM and Kalager, M and Rutter, M and Selby, K and Pilonis, ND and Anderson, JC and McKinnon, A and Fuchs, JM and Quinlan, C and Buskermolen, M and Senore, C and Wang, P and Sung, JJY and Haug, U and Bjerkelund, S and Triantafyllou, K and Shung, DL and Halvorsen, N and McGinn, T and Hafver, TL and Reinthaler, V and Guyatt, G and Agoritsas, T and Sultan, S}, title = {Computer aided detection and diagnosis of polyps in adult patients undergoing colonoscopy: a living clinical practice guideline.}, journal = {BMJ (Clinical research ed.)}, volume = {388}, number = {}, pages = {e082656}, doi = {10.1136/bmj-2024-082656}, pmid = {40147837}, issn = {1756-1833}, mesh = {Humans ; *Colonoscopy/adverse effects/standards/methods ; *Colorectal Neoplasms/diagnosis ; *Colonic Polyps/diagnosis ; *Diagnosis, Computer-Assisted/methods ; Middle Aged ; Aged ; Adult ; Early Detection of Cancer/methods ; Artificial Intelligence ; }, abstract = {CLINICAL QUESTION: In adult patients undergoing colonoscopy for any indication (screening, surveillance, follow-up of positive faecal immunochemical testing, or gastrointestinal symptoms such as blood in the stools) what are the benefits and harms of computer-aided detection (CADe)?

CONTEXT AND CURRENT PRACTICE: Colorectal cancer (CRC), the third most common cancer and the second leading cause of cancer-related death globally, typically arises from adenomatous polyps. Detection and removal of polyps during colonoscopy can reduce the risk of cancer. CADe systems use artificial intelligence (AI) to assist endoscopists by analysing real-time colonoscopy images to detect potential polyps. Despite their increasing use in clinical practice, guideline recommendations that carefully balance all patient-important outcomes remain unavailable. In this first iteration of a living guideline, we address the use of CADe at the level of an individual patient.

EVIDENCE: Evidence for this recommendation is drawn from a living systematic review of 44 randomised controlled trials (RCTs) involving more than 30 000 participants and a companion microsimulation study simulating 10 year follow-up for 100 000 individuals aged 60-69 years to assess the impact of CADe on patient-important outcomes. While no direct evidence was found for critical outcomes of colorectal cancer incidence and post-colonoscopy cancer incidence, low certainty data from the trials indicate that CADe may increase positive endoscopy findings. The microsimulation modelling, however, suggests little to no effect on CRC incidence, CRC-related mortality, or colonoscopy-related complications (perforation and bleeding) over the 10 year follow-up period, although low certainty evidence indicates CADe may increase the number of colonoscopies performed per patient. A review of values and preferences identified that patients value mortality reduction and quality of care but worry about increased anxiety, overdiagnosis, and more frequent surveillance.

RECOMMENDATION: For adults who have agreed to undergo colonoscopy, we suggest against the routine use of CADe (weak recommendation).

An international panel, including three patient partners, 11 healthcare providers, and seven methodologists, deemed by MAGIC and The BMJ to have no relevant competing interests, developed this recommendation. For this guideline the panel took an individual patient approach. The panel started by defining the clinical question in PICO format, and prioritised outcomes including CRC incidence and mortality. Based on the linked systematic review and microsimulation study, the panel sought to balance the benefits, harms, and burdens of CADe and assumed patient preferences when making this recommendation UNDERSTANDING THE RECOMMENDATION: The guideline panel found the benefits of CADe on critical outcomes, such as CRC incidence and post-colonoscopy cancer incidence, over a 10 year follow up period to be highly uncertain. Low certainty evidence suggests little to no impact on CRC-related mortality, while the potential burdens-including more frequent surveillance colonoscopies-are likely to affect many patients. Given the small and uncertain benefits and the likelihood of burdens, the panel issued a weak recommendation against routine CADe use.The panel acknowledges the anticipated variability in values and preferences among patients and clinicians when considering these uncertain benefits and potential burdens. In healthcare settings where CADe is available, individual decision making may be appropriate.

UPDATES: This is the first iteration of a living practice guideline. The panel will update this living guideline if ongoing evidence surveillance identifies new CADe trial data that substantially alters our conclusions about CRC incidence, mortality, or burdens, or studies that increase our certainty in values and preferences of individual patients. Updates will provide recommendations on the use of CADe from a healthcare systems perspective (including resource use, acceptability, feasibility, and equity), as well as the combined use of CADe and computer aided diagnosis (CADx). Users can access the latest guideline version and supporting evidence on MAGICapp, with updates periodically published in The BMJ.}, } @article {pmid40147790, year = {2025}, author = {Shawcross, DL and Patel, VC}, title = {FMT for Hepatic Encephalopathy? The THEMATIC Trial aims to make is a 'no brainer'.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2025.03.009}, pmid = {40147790}, issn = {1600-0641}, } @article {pmid40147263, year = {2025}, author = {Ye, X and An, X and Zhang, T and Kong, Y and Jia, S and Wu, J}, title = {CGA protects against experimental colitis by modulating host purine metabolism through the gut microbiota.}, journal = {International immunopharmacology}, volume = {153}, number = {}, pages = {114547}, doi = {10.1016/j.intimp.2025.114547}, pmid = {40147263}, issn = {1878-1705}, abstract = {OBJECTIVE: Alterations in the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Chlorogenic acid (CGA), a product of the esterification of caffeic acid and quinic acid, is one of the most abundant polyphenols in the human diet and has potential beneficial effects on gut function. However, the underlying mechanisms remain unclear. In this study, the pharmacological effects of CGA on colitis and the potential underlying mechanisms were investigated.

METHODS: A mouse model of colitis was induced via the use of 4 % dextran sulfate sodium (DSS), and the mice were treated with 200 mg/kg CGA. Body weight, colon length, colon tissue pathology, and plasma and colon inflammatory cytokine levels were assessed. RNA sequencing was used to detect changes in gene expression in mouse colon tissues, and 16S rRNA sequencing was used to analyze the composition and structure of the gut microbiota. Fecal metabolomic analysis was performed, and fecal microbiota transplantation (FMT) was used to evaluate the contribution of the gut microbiota.

RESULTS: CGA significantly alleviated DSS-induced colitis, alleviating intestinal mucosal barrier damage and gut microbiota dysbiosis. It significantly enriched bacteria that produce short-chain fatty acids (SCFAs). CGA inhibited the accumulation of purine metabolites derived from the microbiota and suppressed immune-related signaling cascades, exerting immunomodulatory effects. Furthermore, the gut microbiota of CGA-treated mice alleviated DSS-induced colitis through FMT.

CONCLUSION: CGA alleviates colitis in a gut microbiota-dependent manner, potentially providing a new strategy for the treatment of IBD.}, } @article {pmid40143866, year = {2025}, author = {Zhou, M and Niu, B and Ma, J and Ge, Y and Han, Y and Wu, W and Yue, C}, title = {Intervention and research progress of gut microbiota-immune-nervous system in autism spectrum disorders among students.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1535455}, pmid = {40143866}, issn = {1664-302X}, abstract = {Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by difficulties in social interaction and communication, repetitive and stereotyped behaviors, restricted interests, and sensory abnormalities. Its etiology is influenced by both genetic and environmental factors, with no definitive cause identified and no specific pharmacological treatments available, posing a significant burden on patients' families and society. In recent years, research has discovered that gut microbiota dysbiosis plays a crucial role in the pathogenesis of ASD. The gut microbiota can influence brain function and behavior through the gut-brain axis via the nervous system, immune system, and metabolic pathways. On the one hand, specific gut microbes such as Clostridium and Prevotella species are found to be abnormal in ASD patients, and their metabolic products, like short-chain fatty acids, serotonin, and GABA, are also involved in the pathological process of ASD. On the other hand, ASD patients exhibit immune system dysfunction, with gut immune cells and related cytokines affecting neural activities in the brain. Currently, intervention methods targeting the gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, have shown some potential in improving ASD symptoms. However, more studies are needed to explore their long-term effects and optimal treatment protocols. This paper reviews the mechanisms and interrelationships among gut microbiota, immune system, and nervous system in ASD and discusses the challenges and future directions of existing research, aiming to provide new insights for the prevention and treatment of ASD.}, } @article {pmid40143713, year = {2025}, author = {Zhang, F and Kamm, MA and Wu, X and Kao, D and Borody, TJ and Chen, LA and He, X and Fischer, M and Wong, SH and Ng, SC and Cui, B and Chan, FK and Nie, Y and Sood, A and Li, J and Sun, Y and Dai, I and Chen, Q and Lv, M and Zhang, Z and Ianiro, G and Yang, Y and Kelly, CR}, title = {Preferred Reporting Items for Microbiotherapy (PRIM) Guidelines Across Medical Disciplines: An International Delphi Consensus.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16947}, pmid = {40143713}, issn = {1440-1746}, support = {2021YFA0717004//Ministry of Science and Technology of China, National Key Program/ ; 82170563//National Natural Science Fundation of China/ ; 2020-3HIM//Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; }, abstract = {Microbiotherapy has opened new avenues for managing dysbiosis-related diseases. However, many studies did not cover all the necessary reporting items for microbiotherapy making the interpretation of results, safety assessment, technology extension, and even the transparency of legitimacy difficult. This project consisted of 2 phases. First, we proposed an initial preferred reporting items for microbiotherapy (PRIM) checklist and applied it to oncology studies from 2011 to 2023 according to Meta-Analyses guideline. Only 39.3% (n = 64) of these studies (n = 163) met all PRIM checklist items. The culture-based microbiotherapy (CMT) studies had higher score than non-culture-based (NMT) ones (p = 0.018). In the second phase, the expert panel consisting of 22 specialists from eight countries across Asia, Australia, Europe, and North America refined and finalized the PRIM guidelines (named as PRIM 2024) through Delphi consensus. The PRIM 2024 guidelines conclude 10 statements and 18 points on diagnosis, delivery route, source, classification, preparation, dosage, state, concomitant treatment, efficacy, and safety. The panel defined less than 80% of all PRIM points (14 points) as low-quality reports. These guidelines are recommended for reporting on microbiotherapy in clinical studies and reports on compassionate use, including but not limited to fecal microbiota transplantation, phage therapy, probiotics, and synbiotics. These consistent and transparent reporting items can help researchers and practitioners better evaluate, compare, implement research findings in microbiotherapy.}, } @article {pmid40142532, year = {2025}, author = {Niu, Q and Yang, K and Zhou, Z and Huang, Q and Wang, J}, title = {Intergenerational Transmission of Gut Microbiome from Infected and Non-Infected Salmonella pullorum Hens.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, pmid = {40142532}, issn = {2076-2607}, support = {2022-02-08-00-12-F01184//Shanghai Agriculture Applied Technology Development Program,China/ ; }, abstract = {Pullorum disease (PD) is one of the common infectious diseases in the poultry industry in the world. Our previous study showed that gut bacterial structure has a significant difference between positive and negative hens. However, the gut bacterial basis of intergenerational transmission of PD continues to elude a scientific explanation. The present study carried out fecal microbiota transplantation (FMT) in chicks of a negative group, then fecal samples of the chicks in the control team (CT), Salmonella pullorum (S. pullorum)-negative transplantation team (PN) and S. pullorum-positive transplantation team (PP) were separately collected to be analyzed for microbial structure and prediction functions. Microbial diversity results revealed that there was a large difference in the gut microbiota of these three groups. Prevotella and Parasutterella with higher abundance in PN (p < 0.05) were transplanted from gut bacteria of S. pullorum-negative hens. Furthermore, the differences of the most major microbial functions (top 100) were similar in hens and chicks, including a pentose phosphate pathway and oxidative phosphorylation. The data provided a reference for exploring the intergenerational transmission and genetic mechanisms of gut microbiota associated with S. pullorum in poultry, as well as a theoretical basis for improving intestinal health through the rational regulation of microbiota-host interactions.}, } @article {pmid40142480, year = {2025}, author = {Shaheen, M and McDougall, C and Chan, L and Franz, R and Wong, K and Giebelhaus, RT and Nguyen, G and Nam, SL and de la Mata, AP and Yeo, S and Harynuk, JJ and Pakpour, S and Xu, H and Kao, D}, title = {Impact of Fecal Microbiota Transplant Formulations, Storage Conditions, and Duration on Bacterial Viability, Functionality, and Clinical Outcomes in Patients with Recurrent Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, pmid = {40142480}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is the most effective therapy for preventing recurrent Clostridioides difficile infection (rCDI). However, the impact of FMT formulations and storage conditions on bacterial viability, community structure, functionality, and clinical efficacy remains under-investigated. We studied the effect of different storage conditions on the bacterial viability (live/dead staining and cell sorting), community structure (16S rDNA analysis), and metabolic functionality (fermentation) of frozen and lyophilized FMT formulations. The clinical success rates of rCDI patients were correlated retrospectively with FMT formulations, storage durations, and host factors using the Edmonton FMT program database. Bacterial viability remained at 10-20% across various storage conditions and formulations and was comparable to that of fresh FMT. Live and dead bacterial fractions in both frozen and lyophilized FMT preparations exhibited distinct community structures. Storage durations, but not temperatures, negatively affected bacterial diversity. More short-chain fatty acids were found in the metabolomic profiling of in vitro fermentation products using lyophilized than frozen FMT. Clinical success rates in 537 rCDI patients receiving a single dose of FMT were not significantly different among the three formulations. However, longer storage durations and advanced recipient age negatively impacted clinical efficacy. Together, our findings suggest that FMT formulations and storage durations should be considered when establishing guidelines for product shelf life for optimal treatment outcomes.}, } @article {pmid40142449, year = {2025}, author = {Kume, M and Din, J and Zegarra-Ruiz, DF}, title = {Dysregulated Intestinal Host-Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, pmid = {40142449}, issn = {2076-2607}, abstract = {Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.}, } @article {pmid40141109, year = {2025}, author = {Ye, Y and Abulizi, A and Zhang, Y and Lu, F and An, Y and Ren, C and Zhang, H and Wang, Y and Lin, D and Lu, D and Li, M and Yang, B}, title = {Ganoderic Acid Ameliorates Ulcerative Colitis by Improving Intestinal Barrier Function via Gut Microbiota Modulation.}, journal = {International journal of molecular sciences}, volume = {26}, number = {6}, pages = {}, pmid = {40141109}, issn = {1422-0067}, support = {82273999//National Natural Science Foundation of China grants/ ; 81974083//National Natural Science Foundation of China grants/ ; 7212151//Beijing Natural Science Foundation grant/ ; 2022-JKCS-15//The grant from the non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/drug therapy/microbiology/chemically induced/metabolism ; Mice ; *Triterpenes/pharmacology ; *Intestinal Mucosa/metabolism/drug effects/microbiology/pathology ; *Dextran Sulfate/adverse effects ; Male ; Disease Models, Animal ; Humans ; Zonula Occludens-1 Protein/metabolism/genetics ; Colon/drug effects/metabolism/pathology/microbiology ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Intestinal Barrier Function ; }, abstract = {Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal disease that affects millions of humans worldwide and imposes a huge social and economic burden. It is necessary to find safe and efficient drugs for preventing and treating UC. The aim of this study was to determine whether ganoderic acid (GA), the main bioactive components of Ganoderma lucidum, has preventive and therapeutic effect on UC in a dextran sulfate sodium (DSS)-induced UC mouse model. Our experimental results showed that GA significantly ameliorated the body weight loss and disease activity index (DAI) of UC mice. GA significantly restored 11% of the colon length and 69% of the spleen index compared to UC mice. GA significantly decreased the intestinal inflammatory response and improved the barrier function of the intestine by upregulating the tight junction proteins Zonula occludens-1 (ZO-1), occludin and claudin-1. A co-housing experiment showed that gut microbiota accounted for the therapeutic activity of GA on UC, which was confirmed by fecal microbiota transplantation from GA-treated mice to the UC mice. Furthermore, 16S rDNA high-throughput sequencing of fecal bacteria showed that GA significantly enriched the abundance of Lactobacillus, Oscillospira, Odoribacter and Ruminococcus, which were positively correlated with colon length. Furthermore, this study found the functional metabolites, including Indole-3-acetaldehyde (IAAld), Glutamine (Gln) and Glutathione (GSH), reduced barrier damage in the Caco-2 cell model. In conclusion, this study suggests that GA could ameliorate UC by improving intestinal barrier function via modulating gut microbiota and associated metabolites.}, } @article {pmid40141007, year = {2025}, author = {Wang, Y and Chen, Y and Xiao, Z and Shi, Y and Fu, C and Cao, Y}, title = {Fecal microbiota transplantation modulates myeloid-derived suppressor cells and attenuates renal fibrosis in a murine model.}, journal = {Renal failure}, volume = {47}, number = {1}, pages = {2480749}, pmid = {40141007}, issn = {1525-6049}, mesh = {Animals ; *Myeloid-Derived Suppressor Cells/metabolism/immunology ; *Fecal Microbiota Transplantation ; *Mice, Inbred C57BL ; Mice ; *Disease Models, Animal ; *Fibrosis ; *Kidney/pathology ; *Renal Insufficiency, Chronic/therapy/microbiology ; Male ; Cytokines/metabolism ; Gastrointestinal Microbiome ; Ureteral Obstruction/complications/therapy ; Dysbiosis/therapy/complications ; }, abstract = {BACKGROUND: Renal fibrosis is a hallmark of progressive chronic kidney disease (CKD), with emerging evidence linking gut microbiota dysbiosis to disease progression. Myeloid-derived suppressor cells (MDSCs) have demonstrated renoprotective effects, yet the impact of fecal microbiota transplantation (FMT) on MDSC-mediated modulation of renal fibrosis remains unclear.

METHODS: C57BL/6J mice underwent unilateral ureteral obstruction (UUO) to induce renal fibrosis, followed by FMT administration via gavage. Flow cytometry was used to quantify granulocytic (G-MDSCs) and monocytic (M-MDSCs) MDSC populations in peripheral blood, kidney, and spleen. To elucidate the role of MDSCs in FMT-mediated effects, MDSCs were depleted or adoptively transferred in vivo. Renal fibrosis severity and inflammatory cytokine expression were subsequently analyzed.

RESULTS: FMT altered MDSC distribution, increasing M-MDSC accumulation in the blood and kidney. This was associated with downregulation of proinflammatory cytokines and attenuation of renal fibrosis. Adoptive MDSC transfer similarly produced anti-inflammatory and antifibrotic effects, reinforcing their therapeutic role in FMT-mediated renal protection.

CONCLUSIONS: FMT enhances M-MDSC-mediated immunomodulation, reducing inflammation and renal fibrosis in UUO-induced CKD. These findings suggest a potential therapeutic strategy targeting the gut-kidney axis in CKD management.}, } @article {pmid40140901, year = {2025}, author = {Wu, Y and Cheng, R and Lin, H and Li, L and Jia, Y and Philips, A and Zuo, T and Zhang, H}, title = {Gut virome and its implications in the pathogenesis and therapeutics of inflammatory bowel disease.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {183}, pmid = {40140901}, issn = {1741-7015}, support = {2023YFS0279//Sichuan Science and Technology Program/ ; }, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/microbiology/virology ; *Virome ; *Gastrointestinal Microbiome ; }, abstract = {Inflammatory bowel disease (IBD) refers to chronic, recurrent inflammatory intestinal disorders, primarily including Crohn's disease (CD) and Ulcerative colitis (UC). Numerous studies have elucidated the importance of the gut microbiome in IBD. Recently, numerous studies have focused on the gut virome, an intriguing and enigmatic aspect of the gut microbiome. Alterations in the composition of phages, eukaryotic viruses, and human endogenous retroviruses that occur in IBD suggest potential involvement of the gut virome in IBD. Nevertheless, the mechanisms by which it maintains intestinal homeostasis and interacts with diseases are only beginning to be understood. Here, we thoroughly reviewed the composition of the gut virome in both healthy individuals and IBD patients, emphasizing the key viruses implicated in the onset and progression of IBD. Furthermore, the complex connections between the gut virome and the intestinal barrier, immunity, and gut microbiome were dissected to advance the interpretation of IBD pathogenesis. The updated discussion of the evidence regarding the gut virome will advance our knowledge in gut virome and chronic gastrointestinal diseases. Targeting the gut virome is a promising avenue for IBD treatment in future.}, } @article {pmid40138872, year = {2025}, author = {Liang, T and Jiang, T and Liang, Z and Li, L and Chen, Y and Chen, T and Yang, L and Zhang, N and Dong, B and Xie, X and Gu, B and Wu, Q}, title = {Gut microbiota-driven BCAA biosynthesis via Staphylococcus aureus -expressed acetolactate synthase impairs glycemic control in type 2 diabetes in South China.}, journal = {Microbiological research}, volume = {296}, number = {}, pages = {128145}, doi = {10.1016/j.micres.2025.128145}, pmid = {40138872}, issn = {1618-0623}, abstract = {An increase in branched-chain amino acid (BCAA) levels can result in insulin resistance at different stages of type 2 diabetes (T2D), however, the causes of this increase are unclear. We performed metagenomics and metabolomics profiling in patients with prediabetes (PDM), newly diagnosed diabetes (NDDM), and post-medication type 2 diabetes (P2DM) to investigate whether altered gut microbes and metabolites could explain the specific clinical characteristics of different disease stages of T2D. Here we identify acetolactate synthase (ALS) a BCAA biosynthesis enzyme in Staphylococcus aureus as a cause of T2D insulin resistance. Compared with healthy peoples, patients with PDM, NDDM, and P2DM groups, especially in P2DM group, have increased faecal numbers of S. aureus. We also demonstrated that insulin administration may be a risk factor for S. aureus infection in T2D. The presence of ALS-positive S. aureus correlated with the levels of BCAAs and was associated with an increased fasting blood glucose (FBG) and insulin resistance. Humanized microbiota transplantation experiment indicated that ALS contributes to disordered insulin resistance mediated by S. aureus. We also found that S. aureus phage can reduced the FBG levels and insulin resistance in db/db mice. The ALS-positive S. aureus are associated with insulin resistance in T2D, opening a new therapeutic avenue for the prevention or treatment of diabetes.}, } @article {pmid40137411, year = {2025}, author = {Mougiou, D and Gioula, G and Skoura, L and Anastassopoulou, C and Kachrimanidou, M}, title = {Insights into the Interaction Between Clostridioides difficile and the Gut Microbiome.}, journal = {Journal of personalized medicine}, volume = {15}, number = {3}, pages = {}, pmid = {40137411}, issn = {2075-4426}, abstract = {Clostridioides difficile (C. difficile) is a significant healthcare-associated pathogen that is predominantly caused by antibiotic-induced microbiota disturbance. Antibiotics decrease microbial diversity, resulting in C. difficile colonization and infection. Clostridium difficile infection (CDI) manifests through toxins A and B, causing diarrhea and colitis. Antibiotic usage, old age, and hospitalization are significant risk factors. A healthy gut microbiota, which is dominated by Firmicutes and Bacteroidetes, provides colonization resistance to C. difficile due to competition for nutrients, creating inhibitory substances and stimulating the immune response. Antibiotic-induced dysbiosis decreases resistance, allowing C. difficile spores to transform into vegetative forms. Patients with CDI have decreased gut microbiota diversity, with a decrease in beneficial bacteria, including Bacteroidetes, Prevotella, and Bifidobacterium, and a rise in harmful bacteria like Clostridioides and Lactobacillus. This disparity worsens the infection's symptoms and complicates therapy. Fecal Microbiota Transplantation (FMT) has emerged as a potential therapy for recurrent CDI by restoring gut microbiota diversity and function. Comprehending the connection between gut microbiota and CDI pathogenesis is critical for establishing effective preventive and treatment plans. Maintaining a healthy gut microbiota through careful antibiotic use and therapeutic options such as FMT can help in the management and prevention of CDI.}, } @article {pmid40136508, year = {2025}, author = {Zalila-Kolsi, I and Dhieb, D and Osman, HA and Mekideche, H}, title = {The Gut Microbiota and Colorectal Cancer: Understanding the Link and Exploring Therapeutic Interventions.}, journal = {Biology}, volume = {14}, number = {3}, pages = {}, pmid = {40136508}, issn = {2079-7737}, abstract = {CRC remains a significant public health challenge due to its high prevalence and mortality rates. Emerging evidence highlights the critical role of the gut microbiota in both the pathogenesis of CRC and the efficacy of treatment strategies, including chemotherapy and immunotherapy. Dysbiosis, characterized by imbalances in microbial communities, has been implicated in CRC progression and therapeutic outcomes. This review examines the intricate relationship between gut microbiota composition and CRC, emphasizing the potential for microbial profiles to serve as biomarkers for early detection and prognosis. Various interventions, such as prebiotics, probiotics, postbiotics, fecal microbiota transplantation, and dietary modifications, aim to restore microbiota balance and shift dysbiosis toward eubiosis, thereby improving health outcomes. Additionally, the integration of microbial profiling into clinical practice could enhance diagnostic capabilities and personalize treatment strategies, advancing the field of oncology. The study of intratumoral microbiota offers new diagnostic and prognostic tools that, combined with artificial intelligence algorithms, could predict treatment responses and assess the risk of adverse effects. Given the growing understanding of the gut microbiome-cancer axis, developing microbiota-oriented strategies for CRC prevention and treatment holds promise for improving patient care and clinical outcomes.}, } @article {pmid40134274, year = {2025}, author = {Flores-Treviño, S and Bocanegra-Ibarias, P and Salas-Treviño, D and Ramírez-Elizondo, MT and Pérez-Alba, E and Camacho-Ortiz, A}, title = {Microbiota transplantation and administration of live biotherapeutic products for the treatment of dysbiosis-associated diseases.}, journal = {Expert opinion on biological therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14712598.2025.2484303}, pmid = {40134274}, issn = {1744-7682}, abstract = {INTRODUCTION: The microbiota composition in humans varies according to the anatomical site and is crucial for maintaining homeostasis and an overall healthy state. Several gastrointestinal, vaginal, respiratory, and skin diseases are associated with dysbiosis. Alternative therapies such as microbiota transplantation can help restore microbiota normal composition and can be implemented to treat clinically relevant diseases.

AREAS COVERED: Current microbiota transplantation therapies conducted in clinical trials were included in this review (after searching on MEDLINE database from years 2017 to 2025) such as fecal microbiota transplantation (FMT) against recurrent Clostridiodes difficile infection (rCDI) and vaginal microbiota transplantation (VMT) against bacterial vaginosis. Washed microbiota transplantation (WMT) and live biotherapeutic products (LBPs) were also reviewed.

EXPERT OPINION: In microbiota-based transplantation therapy, selecting optimal donors is a limitation. A stool or a vaginal microbiota bank should be implemented to overcome the time-consuming and expensive process of donor recruitment. Microbiota-based LBPs are also promising treatment alternatives for rCDI and other dysbiosis-associated diseases. Specific LBPs could be engineered out of donor fluids-derived strains to achieve the selection of specific beneficial microorganisms for the treatment of specific dysbiosis-associated diseases. Personalized microbiota-based treatments are promising solutions for dysbiosis-associated diseases, which remains an important necessity in clinical practice.}, } @article {pmid40134246, year = {2025}, author = {Gao, Q and Bai, M and Qi, T and Zhai, J and Song, Y and Zhang, W and Liang, G}, title = {Changes in Vitamin D and Gut Microbiota in Pediatric Hematopoietic Stem Cell Transplantation Patients with Bloodstream Infections.}, journal = {International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition}, volume = {95}, number = {1}, pages = {26126}, doi = {10.31083/IJVNR26126}, pmid = {40134246}, issn = {0300-9831}, support = {2022QN07//Aerospace Center Hospital Youth Innovation Fund/ ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; Female ; *Vitamin D/blood/analogs & derivatives ; Child ; Case-Control Studies ; Prospective Studies ; Child, Preschool ; Adolescent ; Feces/microbiology ; Infant ; Bacteremia/microbiology/epidemiology/etiology ; }, abstract = {BACKGROUND: Vitamin D (VD) and gut microbiota (GM) are important variables in pediatric hematopoietic stem cell transplantation (HSCT) recipients with bloodstream infections (BSI). Both VD and GM play significant roles in immune regulation and in maintaining intestinal barrier function.

METHODS: This prospective case-control study included 48 consecutive pediatric patients who underwent HSCT, as well as 20 healthy children from the community. Plasma samples were collected pre- and post-HSCT, together with post-HSCT fecal samples. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were measured using chemiluminescence and enzyme linked immunosorbent assay, respectively. GM was analyzed by 16S rDNA next generation sequencing.

RESULTS: The incidence of BSI in pediatric HSCT recipients was 33.3% (16/48). No significant differences in serum 25(OH)D or 1,25(OH)2D3 levels were observed between the BSI and non-BSI groups either before or after transplantation, or with the healthy control group. The α-diversity of GM in BSI and non-BSI patients was significantly lower than in healthy subjects. Proteobacteria were significantly more abundant in BSI patients than in non-BSI patients (p = 0.0434) or healthy controls (p = 0.0193). Pediatric HSCT patients showed significantly higher levels of Staphylococcus (p < 0.001), Pseudomonas (p < 0.001), Enterococcus (p < 0.001), Clostridium innocuum (p = 0.0175) and Enterobacter (p = 0.0394) compared to the controls, whereas the levels of Firmicutes (p = 0.009), Actinobacteria (p < 0.001), Bifidobacterium (p < 0.001) and Faecalibacterium (p < 0.001) were significantly lower. β-diversity analysis revealed significant population differences between the three groups.

CONCLUSIONS: These results indicate there is no practical value in monitoring VD in HSCT patients. During HSCT and BSI, the GM experiences a loss of probiotics and an increase in potential pathogens.}, } @article {pmid40133348, year = {2025}, author = {Jing, Y and Wang, Q and Bai, F and Li, Z and Li, Y and Liu, W and Yan, Y and Zhang, S and Gao, C and Yu, Y}, title = {Age-related alterations in gut homeostasis are microbiota dependent.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {51}, pmid = {40133348}, issn = {2055-5008}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Homeostasis ; Mice ; *Aging ; *Fecal Microbiota Transplantation ; Gene Expression Profiling ; Mice, Inbred C57BL ; Transcriptome ; Colon/microbiology ; Intestinal Mucosa/microbiology/metabolism ; Male ; Computational Biology/methods ; }, abstract = {Accumulating data suggest that remodeling aged gut microbiota improves aging-related imbalance in intestinal homeostasis. However, evidence in favor of the beneficial effect of remodeling gut microbiota on intestinal stress and immune responses during aging is scarce. The current study revealed that old mice presented impaired gut barrier integrity. Transcriptome sequencing coupled with bioinformatics analysis revealed that aging altered gene expression profiles of the colon and mesenteric lymph nodes, which are involved mainly in stress and immune responses, respectively. Notably, gut microbiota was closely related to the differentially expressed genes. Microbiota depletion in old mice ameliorated gut barrier integrity and partially reversed the inflammatory factors upregulated in aging mice. Furthermore, fecal microbiota transplantation from young mice to old mice resulted in a significant improvement in intestinal barrier integrity and immune homeostasis. These findings highlight the potential of microbiota-targeted interventions on aging-related physiological processes and call for further investigation.}, } @article {pmid40133336, year = {2025}, author = {Tillett, BJ and Dwiyanto, J and Secombe, KR and George, T and Zhang, V and Anderson, D and Duggan, E and Giri, R and Loo, D and Stoll, T and Morrison, M and Begun, J and Hill, MM and Gurzov, EN and Bell, KJ and Saad, S and Barlow, CK and Creek, DJ and Chong, CW and Mariño, E and Hamilton-Williams, EE}, title = {SCFA biotherapy delays diabetes in humanized gnotobiotic mice by remodeling mucosal homeostasis and metabolome.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2893}, pmid = {40133336}, issn = {2041-1723}, support = {2-SRA-2019-703-M-B, 201308399//Juvenile Diabetes Research Foundation Australia (JDRF Australia)/ ; 2002917, 2028813//Department of Health | National Health and Medical Research Council (NHMRC)/ ; }, mesh = {Animals ; *Fatty Acids, Volatile/metabolism ; Humans ; *Germ-Free Life ; *Diabetes Mellitus, Type 1/immunology/therapy/metabolism ; *Gastrointestinal Microbiome ; *Metabolome ; Mice ; *Homeostasis ; Intestinal Mucosa/metabolism/immunology/microbiology ; Male ; Female ; Fecal Microbiota Transplantation ; Mice, Inbred NOD ; Adult ; Biological Therapy/methods ; Immunity, Mucosal/drug effects ; }, abstract = {Type 1 diabetes (T1D) is linked to an altered gut microbiota characterized by reduced short-chain fatty acid (SCFA) production. Oral delivery of a SCFA-yielding biotherapy in adults with T1D was followed by increased SCFAs, altered gut microbiota and immunoregulation, as well as delaying diabetes in preclinical models. Here, we show that SCFA-biotherapy in humans is accompanied by remodeling of the gut proteome and mucosal immune homeostasis. Metabolomics showed arginine, glutamate, nucleotide and tryptophan metabolism were enriched following the SCFA-biotherapy, and found metabolites that correlated with glycemic control. Fecal microbiota transfer demonstrated that the microbiota of SCFA-responders delayed diabetes progression in humanized gnotobiotic mice. The protected mice increased similar metabolite pathways to the humans including producing aryl-hydrocarbon receptor ligands and reducing inflammatory mucosal immunity and increasing IgA production in the gut. These data demonstrate that a potent SCFA immunomodulator promotes multiple beneficial pathways and supports targeting the microbiota as an approach against T1D. Trial registration: Australia New Zealand Clinical Trials Registry ACTRN12618001391268.}, } @article {pmid40131972, year = {2025}, author = {Duan, JQ and Sun, YF and Wang, X and Liu, HY and Chang, ZP and Shao, YY and Liu, JJ and Hou, RG}, title = {Shaoyao-Gancao decoction improves dyslipidemia in rats with polycystic ovary syndrome by reshaping the gut microbiota and regulating the bile acid/FXR pathway.}, journal = {Journal of Asian natural products research}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/10286020.2025.2482072}, pmid = {40131972}, issn = {1477-2213}, abstract = {This study aims to investigate the potential mechanism of Shaoyao-Gancao Decoction (SGD) in treating polycystic ovary syndrome (PCOS). Our results suggested that SGD effectively regulated estrous cycles, reduced body weight and serum lipid levels in PCOS rats. Additionally, SGD administration significantly remodeled the structure of gut microbiota, especially the BA-related bacteria. The mRNA expressions of BAs metabolism pathway-related genes were significantly changed by SGD treatment. Furthermore, transplantation of fecal microbiota from SGD rats verified these results. In conclusion, SGD could ameliorate dyslipidemia in PCOS rats by remodeling the structure of the gut microbiome and regulating the bile acid/FXR pathway.}, } @article {pmid40131871, year = {2025}, author = {Kellingray, L and Savva, GM and Garcia-Gutierrez, E and Snell, J and Romano, S and Yara, DA and Altera, A and de Oliveira Martins, L and Hutchins, C and Baker, D and Hayhoe, A and Hacon, C and Elumogo, N and Narbad, A and Sayavedra, L}, title = {Temporal dynamics of SARS-CoV-2 shedding in feces and saliva: a longitudinal study in Norfolk, United Kingdom during the 2021-2022 COVID-19 waves.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0319524}, doi = {10.1128/spectrum.03195-24}, pmid = {40131871}, issn = {2165-0497}, abstract = {UNLABELLED: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was originally described as a respiratory illness; however, it is now known that the infection can spread to the gastrointestinal tract, leading to shedding in feces potentially being a source of infection through wastewater. We aimed to assess the prevalence and persistence of SARS-CoV-2 in fecal and saliva samples for up to 7 weeks post-detection in a cohort of 98 participants from Norfolk, United Kingdom using RT-qPCR. Secondary goals included sequencing the viral isolates present in fecal samples and comparing the genetic sequence with isolates in the saliva of the same participant. Furthermore, we sought to identify factors associated with the presence of detectable virus in feces or saliva after a positive SARS-CoV-2 test. Saliva remained SARS-CoV-2-positive for longer periods compared to fecal samples, with all positive fecal samples occurring within 4 weeks of the initial positive test. Detectable virus in fecal samples was positively associated with the number of symptoms experienced by the individuals. Based on the genome sequencing and taxonomic classification of the virus, one donor had a distinct strain in feces compared to saliva on the same collection date, which suggests that different isolates could dominate different tissues. Our results underscore the importance of considering multiple biological samples, such as feces, in the detection and characterization of SARS-CoV-2, particularly in clinical procedures involving patient fecal material transplant. Such insights could contribute to enhancing the safety protocols surrounding the handling of patient samples and aid in devising effective strategies for mitigating the spread of coronavirus disease.

IMPORTANCE: This study provides critical insights into the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding in fecal and saliva samples, demonstrating that while viral RNA is detectable shortly after diagnosis, its prevalence declines rapidly over the course of infection. Detection was more common among individuals with more concurrent symptoms, emphasizing the potential influence of symptom burden on viral persistence. By analyzing a United Kingdom-based cohort, this study fills a significant gap in the literature, which has largely focused on Asian and North American populations, offering a geographically unique perspective on viral shedding dynamics. Our findings contribute to a globally relevant understanding of SARS-CoV-2 shedding by revealing differences in shedding durations compared to studies from other regions. These differences highlight the need for geographically diverse research to account for variations in genetic background, immune response, and healthcare practices.}, } @article {pmid40130013, year = {2024}, author = {Wang, IC and Buffington, SA and Salas, R}, title = {Microbiota-Gut-Brain Axis in Psychiatry: Focus on Depressive Disorders.}, journal = {Current epidemiology reports}, volume = {11}, number = {4}, pages = {222-232}, pmid = {40130013}, issn = {2196-2995}, support = {I01 CX001937/CX/CSRD VA/United States ; R01 HD109095/HD/NICHD NIH HHS/United States ; R01 HD109780/HD/NICHD NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: Gut microbiota contribute to several physiological processes in the host. The composition of the gut microbiome is associated with different neurological and neurodevelopmental diseases. In psychiatric disease, stress may be a major factor leading to gut microbiota alterations. Depressive disorders are the most prevalent mental health issues worldwide and patients often report gastrointestinal symptoms. Accordingly, evidence of gut microbial alterations in depressive disorders has been growing. Here we review current literature revealing links between the gut microbiome and brain function in the context of depression.

RECENT FINDINGS: The gut-brain axis could impact the behavioral manifestation of depression and the underlying neuropathology via multiple routes: the HPA axis, immune function, the enteric nervous system, and the vagus nerve. Furthermore, we explore possible therapeutic interventions including fecal microbiota transplant or probiotic supplementation in alleviating depressive symptoms.

SUMMARY: Understanding the mechanisms by which bidirectional communication along the gut-brain axis can be dysregulated in patients with depression could lead to the development of personalized, microbiome-targeted therapies for the treatment of this disorder.}, } @article {pmid40128912, year = {2025}, author = {Feng, Y and Chen, W and Chen, J and Sun, F and Kong, F and Li, L and Zhao, Y and Wu, S and Li, Z and Du, Y and Kong, X}, title = {Dietary emulsifier carboxymethylcellulose-induced gut dysbiosis and SCFA reduction aggravate acute pancreatitis through classical monocyte activation.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {83}, pmid = {40128912}, issn = {2049-2618}, support = {82172572//National Natural Science Foundation of China/ ; 82170659//National Natural Science Foundation of China/ ; 82072760//National Natural Science Foundation of China/ ; 2019YFC1315900//National Key R&D Program of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dysbiosis/microbiology ; Mice ; *Mice, Inbred C57BL ; *Carboxymethylcellulose Sodium ; *Monocytes/metabolism ; Humans ; *Fatty Acids, Volatile/metabolism ; *Pancreatitis ; Male ; Fecal Microbiota Transplantation ; Emulsifying Agents/adverse effects ; Akkermansia ; Feces/microbiology ; Verrucomicrobia ; Disease Models, Animal ; Butyrates/metabolism ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVE: Carboxymethylcellulose (CMC), one of the most common emulsifiers used in the food industry, has been reported to promote chronic inflammatory diseases, but its impact on acute inflammatory diseases, e.g., acute pancreatitis (AP), remains unclear. This study investigates the detrimental effects of CMC on AP and the potential for mitigation through Akkermansia muciniphila or butyrate supplementation.

DESIGN: C57BL/6 mice were given pure water or CMC solution (1%) for 4 weeks and then subjected to caerulein-induced AP. The pancreas, colon, and blood were sampled for molecular and immune parameters associated with AP severity. Gut microbiota composition was assessed using 16S rRNA gene amplicon sequencing. Fecal microbiota transplantation (FMT) was used to illustrate gut microbiota's role in mediating the effects of CMC on host mice. Additional investigations included single-cell RNA sequencing, monocytes-specific C/EBPδ knockdown, LPS blocking, fecal short-chain fatty acids (SCFAs) quantification, and Akkermansia muciniphila or butyrate supplementation. Finally, the gut microbiota of AP patients with different severity was analyzed.

RESULTS: CMC exacerbated AP with gut dysbiosis. FMT from CMC-fed mice transferred such adverse effects to recipient mice, while single-cell analysis showed an increase in classical monocytes in blood. LPS-stimulated C/EBPδ, caused by an impaired gut barrier, drives monocytes towards classical phenotype. LPS antagonist (eritoran), Akkermansia muciniphila or butyrate supplementation ameliorates CMC-induced AP exacerbation. Fecal Akkermansia muciniphila abundance was negatively correlated with AP severity in patients.

CONCLUSIONS: This study reveals the detrimental impact of CMC on AP due to gut dysbiosis, with Akkermansia muciniphila or butyrate offering potential therapeutic avenues for counteracting CMC-induced AP exacerbation. Video Abstract.}, } @article {pmid40127764, year = {2025}, author = {Verbiest, A and Møller Andersen, JH and Hvistendahl, MK and Tóth, J and Vandermeulen, G and De Meyere, L and Joly, F and Verbeke, K and Jeppesen, PB and Vanuytsel, T}, title = {TRANSFERABILITY OF METABOLIC BALANCE STUDIES IN SHORT BOWEL SYNDROME.}, journal = {Clinical nutrition ESPEN}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clnesp.2025.03.029}, pmid = {40127764}, issn = {2405-4577}, abstract = {BACKGROUND: Metabolic balance studies (MBS) are the gold standard method to assess the intestinal absorptive function in patients with short bowel syndrome (SBS). During a full MBS, patients are admitted to the hospital to collect duplicates of all ingested foods and drinks, as well as their fecal and urinary output, typically over a 72-hour period. These collections are further processed to assess absorption of energy, macronutrients (nitrogen, fat and carbohydrate) and electrolytes (sodium, potassium, calcium and magnesium). Full MBS require dedicated laboratory personnel, equipment, knowledge and experience, which explains why they are currently only performed in one center.

AIM: We aimed to explore the transferability of full MBS in patients with SBS from the reference center to a clinical center that was new to and unexperienced in MBS.

METHODS: A collaboration between the centers was initiated to transfer knowledge on how to perform MBS collections, how to process and how to analyze energy, macronutrient and electrolyte content in the collected samples. At practical level, transferability included successful MBS collecting and processing. At analytical level, transferability included the lyophilization of homogenized samples at both centers. The powder that was created at the reference center was measured at both centers to assess the transferability of the analytical methods; while the site-specific powder was measured at the corresponding center to determine full process transferability. The intraclass correlation coefficient (ICC) was calculated to define the absolute agreement between both centers.

RESULTS: A total of 21 MBS were performed in 7 patients with SBS at the new center. A total of 189 samples were collected, equally distributed among combined meals and drinks (n=63), fecal output (n=63) and urinary output (n=63). Meals and drinks samples and fecal output samples were processed in the new center and lyophilized at both centers, with a perfect reliability for dry matter between the centers (ICC = 1). At the level of method transferability, there was an excellent absolute agreement between centers for energy and nitrogen analyses (ICC>0.9). For fat, the mean coefficients of variation (cv) between centers for fecal output (6.3%) and meals and drinks (12.0%) were higher, but ICC showed excellent (0.957) to good (0.787) agreement, respectively. Carbohydrate results differed more between the centers (mean cv of 17.5% for fecal output and 16.4% for meals and drinks), translating into a moderate (meals and drinks, ICC = 0.654) to good (fecal output, ICC = 0.812) reliability. Similar results and degrees of agreement as obtained for the method transferability were observed with the site-specific powder.

CONCLUSION: Our study showed the feasibility of a full MBS transferability to a new unexperienced center with promising agreement of the results obtained between both centers. Our findings aim to inspire other specialized intestinal failure centers to adopt the full MBS methodology for both clinical practice and research purposes.}, } @article {pmid40123400, year = {2025}, author = {Tian, HL and Wang, L and Ma, CL and Yang, B and Li, L and Ye, C and Zhao, D and Lin, ZL and Cui, JQ and Liu, YK and Zhu, WY and Zhou, SL and Li, N and Chen, QY}, title = {[Fecal microbiota transplantation for the treatment of intestinal disorders: An analysis of treatment of 15 000 patients].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {296-303}, doi = {10.3760/cma.j.cn441530-20250114-00025}, pmid = {40123400}, issn = {1671-0274}, support = {82100698//National Natural Science Foundation of China/ ; 2021SYPDRC045//the Climb Plan of Tenth People's Hospital of Tongji University/ ; 202240177//Shanghai Health Commission's Surface Project/ ; }, mesh = {Humans ; Female ; Male ; Middle Aged ; *Fecal Microbiota Transplantation/methods ; Retrospective Studies ; Adult ; *Constipation/therapy ; Treatment Outcome ; Irritable Bowel Syndrome/therapy ; Diarrhea/therapy ; Intestinal Diseases/therapy/microbiology ; Inflammatory Bowel Diseases/therapy ; Clostridium Infections/therapy ; Dysbiosis/therapy ; Autistic Disorder/therapy ; }, abstract = {Objective: To examine the long-term efficacy and complications of fecal microbiota transplantation (FMT) for the treatment of diseases related to intestinal dysbiosis. Methods: This was a retrospective descriptive study. Relevant data were collected from the records of 15 000 patients who had undergone FMT and been followed up for more than 3 months during the period from May 2017 to September 2024. The patient cohort comprised 3746 male and 11 254 female patients aged (45.3±12.2) years. The inclusion criterion was meeting the indications for FMT. Application of this criterion yielded 8258 patients with constipation, 684 with Clostridium difficile infection, 1730 with chronic diarrhea, 510 with inflammatory bowel disease, 432 with radiation enteritis, 1940 with irritable bowel syndrome, 365 with autism, 870 with postoperative gastrointestinal dysfunction, and 211 with neurodegenerative diseases. The three routes of delivering FMT comprised infusion of an enterobacterial solution through a nasoenteric tube into the jejunum for 6 consecutive days (upper gastrointestinal FMT group, 11 125 patients), oral intake of enterobacterial capsules for 6 consecutive days (oral capsule FMT, 3597 patients), and a single injection of a bacterial solution into the colon via colonoscopy (lower gastrointestinal FMT group, 278 patients). Other treatments were discontinued during the treatment and follow-up period and administration of other medications was not recommended unless absolutely necessary. The primary outcomes were the efficacy of FMT after 3, 12 and 36 months of treatment, and improvement in chronic constipation, C. difficile infection, chronic diarrhea, inflammatory bowel disease, radiation enteritis, irritable bowel syndrome, post-surgery gastrointestinal dysfunction, and autism. Other outcomes included the occurrence of short-term (within 2 weeks after treatment) and long-term (within 36 months after treatment) adverse reactions. Results: At 3, 12 and 36 months after treatment, the overall rates of effectiveness of treatment were 71.8% (10 763/15 000), 64.4% (7600/11 808) and 58.8% (3659/6218), respectively. Specifically, the rates of clinical improvement were 70.3% (5805/8258), 62.6% (3970/6345), and 56.5% (1894/3352), respectively, for constipation; 85.8% (587/684), 72.3% (408/564), and 67.3% (218/324), respectively, for C.difficile infection; 81.0% (1401/1730), 78.1% (1198/1534), and 72.3% (633/876), respectively, for chronic diarrhea; 64.3% (328/510), 52.3% (249/476), and 46.6 % (97/208), respectively, for inflammatory bowel disease; 77.3% (334/432), 65.4% (212/324), and 53.6% (82/153), respectively, for radiculitis; 70.6% (1370/1940), 64.5% (939/1456), and 60.4% (475/786), respectively, for irritable bowel syndrome; 75.3% (275/365), 70.0% (201/287), and 63.6% (112/176), respectively, for autism; 65.3% (568/870), 54.3% (355/654), and 46.5% (114/245), respectively, for post-surgical gastrointestinal dysfunction; and 45.0% (95/211), 40.5% (68/168), and 34.7% (34/98), respectively, for neurodegenerative diseases. At 3, 12, and 36 months post-treatment, clinical improvement rates were 77.1% (8580/11 125), 67.1% (6437/9595), and 62.1% (3196/5145), respectively, in the upper gastrointestinal route group; and 57.3% (2062/3597), 53.6% (1115/2081), and 45.0% (453/1006), respectively, in the oral capsule group; and 43.5% (121/278) , 36.4% (48/132) and 14.9% (10/67), respectively, in the lower gastrointestinal route group. No serious adverse reactions occurred during treatment or follow-up. The most common adverse reactions in the upper gastrointestinal route group, oral capsule group, and lower gastrointestinal route group were respiratory discomfort (20.4%, 2269/11 125), nausea and vomiting on swallowing the capsule (7.6%, 273/3597), and diarrhea (47.5%, 132/278), respectively; these symptoms resolved at the end of treatment. At 36 months of follow-up, 19 patients reported exacerbation of symptoms of pre-existing diseases and there had been 16 deaths that were not directly related to FMT. Additionally, no systemic diseases had developed after FMT. Conclusion: FMT for the treatment of intestinal dysfunction associated with disorders of the intestinal flora and related extraintestinal diseases is effective and not associated with serious adverse events.}, } @article {pmid40123399, year = {2025}, author = {Li, L and Wang, L and Guo, GG and Fan, YH and Shi, JG and Yuan, XG and Dong, XS and Liu, L and Li, N and Chen, QY}, title = {[Evaluation of the efficacy and safety of multi-center fecal microbiota transplantation for treatment of functional constipation: A retrospective real-world study].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {288-295}, doi = {10.3760/cma.j.cn441530-20250102-00001}, pmid = {40123399}, issn = {1671-0274}, support = {82470701//National Natural Science Foundation of China/ ; YJXYS-C-003//Research Physician Training Program of Shanghai 10th People's Hospital/ ; 20234Y0079//Scientific Research Project of Shanghai Municipal Health Commission/ ; }, mesh = {Humans ; *Constipation/therapy ; Male ; Female ; Retrospective Studies ; Middle Aged ; *Fecal Microbiota Transplantation/methods ; Adult ; Treatment Outcome ; Aged ; Quality of Life ; }, abstract = {Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for treating functional constipation, analyze the incidence of, and factors that influence, adverse events, and provide scientific evidence for optimizing FMT treatment. Methods: This retrospective, multicenter, single-arm, pre-post real-world study included 1529 patients with functional constipation from four clinical centers. Eligibility criteria comprised meeting the diagnostic criteria for functional constipation, having undergone at least one FMT treatment, complete pre- and post-treatment data available, and age ≥18 years. Patients who had received other interventions affecting gut function within 1 month before treatment and those with severe organic diseases or immune deficiencies were excluded. Applying the above criteria yielded 1529 eligible patients with functional constipation from four medical centers (1405 from the Shanghai Tenth People's Hospital Affiliated to Tongji University, 20 from the Central Hospital of Wuhan, 67 from the Shanxi Bethune Hospital and 37 from the Longgang District People's Hospital of Shenzhen). The study cohort comprised 746 male (48.8%) and 783 female patients (51.2%) of mean age (51.4 ± 17.4) years, mean body mass index (26.4 ± 4.9) kg/m[2], and mean duration of disease (15.0 ± 8.3) years. The primary outcomes were the incidence, types, and severity of adverse reactions during treatment, and their impact on patients' quality of life. Secondary outcomes included: (1) the efficacy of FMT in treating constipation. This was assessed based on changes in Patient Assessment of Constipation Symptoms (PAC-SYM) scores, where higher score indicates worse symptom. (2) Subjective satisfaction, evaluated through questionnaires or rating scales, reflecting patients' acceptance of and satisfaction with the treatment, with scores ranging from 1 to 5, where higher scores indicated greater satisfaction. Paired t-tests and Wilcoxon signed-rank tests were used to evaluate changes in symptom scores and biochemical indicators before and after treatment. Logistic regression was performed to analyze factors influencing adverse events, and subgroup analyses to explored differences in efficacy between patient groups. Results: In this cohort of 1529 patients with functional constipation, adverse reactions were primarily mild to moderate (1048/1529,68.5%). They comprised fever in 54 patients (3.5%), dizziness or fatigue in 218 (14.3%), throat discomfort in 806 (52.7%), nausea and vomiting in 166 (10.9%), and abdominal distension or pain in 415 (27.1%). According to multivariate logistic regression analysis, PAC-SYM scores were associated with the rate of adverse reactions, higher scores indicating a lower risk (OR = 0.958, 95% CI: 0.923-0.993, P=0.021). Among the 1529 patients, 274 (17.9%) underwent two or more treatment courses. After one treatment course, the patients' PAC-SYM scores decreased from (37.7 ± 3.2) pre-treatment to (23.7 ± 8.6) (mean difference 14.0 ± 9.1). PAC-SYM scores decreased by (20.7 ± 7.7) after two courses of FMT, and by (19.4 ± 6.3) after three courses. After treatment, 50.7%(775/1529) of patients reported satisfaction scores of ≥4. Adverse reactions impacted satisfaction; specifically, dizziness/fatigue, throat discomfort, and abdominal distension/pain were significantly associated with satisfaction (all P < 0.05). Conclusions: FMT achieved good relief of symptoms of functional constipation and multiple treatment courses have a cumulative effect. Adverse reactions, mainly dizziness/fatigue, throat discomfort, and abdominal distension/pain, had significant negative impacts on patient satisfaction.}, } @article {pmid40123398, year = {2025}, author = {Xu, Y and Ye, C and Li, N and Chen, QY}, title = {[Challenges and progress in in the clinical application of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {266-273}, doi = {10.3760/cma.j.cn441530-20241224-00420}, pmid = {40123398}, issn = {1671-0274}, support = {82470701, 82401727//National Natural Science Foundation of China/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Feces/microbiology ; Clostridium Infections/therapy ; Inflammatory Bowel Diseases/therapy/microbiology ; Irritable Bowel Syndrome/therapy/microbiology ; Gastrointestinal Diseases/therapy/microbiology ; Diarrhea/therapy/microbiology ; Clostridioides difficile ; }, abstract = {With the deepening understanding of the role of gut microbiota in human health and disease, fecal microbiota transplantation has gained widespread attention as an emerging therapeutic approach in recent years. This technique involves the transplantation of microbial communities from the feces of healthy donors into patients to reconstruct or improve the gut microbiota structure, thereby achieving therapeutic goals. Fecal microbiota transplantation has become an effective method for treating recurrent or refractory Clostridium difficile infections and has shown good therapeutic effects and safety in clinical trials for various gastrointestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, slow transit constipation, and chronic diarrhea. Moreover, its application has been extended to research in metabolic diseases and neurological disorders, which are not directly related to the gut. However, the clinical efficacy of fecal microbiota transplantation still needs improvement, and there are many challenges regarding specific application strategies that remain to be addressed. This article discusses the current progress and challenges of fecal microbiota transplantation strategies and reviews cutting-edge interventional methods such as small intestine microbiota intervention and bacteriophage therapy, aiming to provide reference for further research in fecal microbiota transplantation.}, } @article {pmid40123397, year = {2025}, author = {Jin, YF and Wen, WJ and Zuo, T}, title = {[Phages in human health and gut microbiota transplantation therapy].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {261-265}, doi = {10.3760/cma.j.cn441530-20241130-00387}, pmid = {40123397}, issn = {1671-0274}, support = {82172323, 32100134//National Natural Science Foundation of China/ ; 2024A1515010533//Guangdong Provincial Natural Science Foundation/ ; 202206010014//Guangzhou Key R&D program/ ; 2022JBGS03//Seed Fund from the Sixth Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Bacteriophages/physiology ; Phage Therapy/methods ; Bacteria ; }, abstract = {Phages, prokaryotic viruses widely present in the human, are a crucial component of the gut microbiome. They play a significant role in human health and the development of diseases. Emerging evidence indicates that phages can interact with bacteria to affect their abundance, metabolism, and antibiotic resistance, thereby influencing the balance of the gut microbiota. In addition, phages also contribute to the gut immune response, and can become dysregulated in a range of immune-related diseases. Gut phages also carry important roles in fecal microbiota transplantation (FMT) for disease treatment. Phages can target specific bacterial members and communities, thereby reduce the risk of bacterial infections or the presence of bacteria, and maintain the stability of the gut microbiome. However, gut phageome research is still in its infancy and additional basic and clinical researches are required to evaluate its species composition, mechanisms of pathogenicity or protection, as well as its efficacy and safety.}, } @article {pmid40123396, year = {2025}, author = {Wang, XJ and Zhao, D and Qin, YH and Yu, LT and Cao, Z and Liu, WH and Yang, B and Li, N and Chen, QY and Qin, HL}, title = {[How close is fecal microbiota transplantation to moving to precision medicine?].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {254-260}, doi = {10.3760/cma.j.cn441530-20241220-00415}, pmid = {40123396}, issn = {1671-0274}, support = {82300753, 82330093, 82470701//National Natural Science Foundation of China/ ; 2024YFA1307101//National Key R&D Program/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Precision Medicine/methods ; Gastrointestinal Microbiome ; Feces/microbiology ; China ; }, abstract = {Fecal microbiota transplantation (FMT) has the potential to rebuild the intestinal microbiome of patients, which can influence the disease course, alleviate symptoms, or even cure the disease. It is seen as a promising breakthrough for treating major chronic diseases that are difficult to manage. Currently, FMT therapy has been clinically studied for over 80 diseases and has led to significant breakthroughs. However, there are still four main challenges: (1) identifying the effective characteristics of donor microbiota and ensuring precise matching between donors and recipients; (2) understanding the pathways and molecular mechanisms by which key FMT bacteria and metabolites improve disease outcomes; (3) studying strain interactions and colonization mechanisms to restore intestinal microbiota balance; and (4) refining the precision of microbiome and functional microbiota transplantation. To address these clinical challenges, this article reviews the latest research both domestically and internationally, outlines the response patterns of FMT therapy, examines the reasons behind FMT failure, and explores future directions for the development of FMT. The aim is to accelerate the scientific and precise advancement of FMT technology in China.}, } @article {pmid40123393, year = {2025}, author = {, and , and , }, title = {[Consensus of Chinese experts on gut microbiota and fecal microbiota transplantation in inflammatory bowel disease (2025 edition)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {3}, pages = {225-235}, doi = {10.3760/cma.j.cn441530-20241224-00422}, pmid = {40123393}, issn = {1671-0274}, support = {2022YFC2010101//Ministry of Science and Technology Major Research and Development Program/ ; 2022YFA1304100//Ministry of Science and Technology Major Research and Development Program Subproject/ ; 82470701, 81700480, 82300753//National Natural Science Foundation of China/ ; 076478684Q/2023-00154//Shanghai Municipal Health Commission Key Project/ ; ZJ2022-ZD-005//Shanghai Zhangjiang National Independent Innovation Demonstration Zone Special Development Fund Major Project/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Gastrointestinal Microbiome ; China ; *Consensus ; Feces/microbiology ; Donor Selection ; }, abstract = {In recent years, significant progress has been made in the clinical and basic research on fecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease (IBD). With the continuous application of new microbiota-based diagnostic and therapeutic concepts in clinical practice, it is imperative to standardize the diagnostic and therapeutic processes of FMT for IBD and provide consensus recommendations based on the latest evidence from evidence-based medicine for clinical practitioners. Organized by the Chinese Society for Parenteral and Enteral Nutrition of the Chinese Medical Association, the Gut Microbiota and FMT Committee of the Chinese Society for Human Health Sciences, and the Gut Microbiota Committee of the Shanghai Preventive Medicine Association, and with reference to the latest international consensus and relevant research advancements, this consensus integrates the clinical practice experience of domestic experts to establish the "Consensus of Chinese experts on gut microbiota and fecal microbiota transplantation in inflammatory bowel disease (2025 edition)". This consensus provides 29 recommendations focusing on the selection of FMT indications, gut microbiota analysis, donor selection and quality control for IBD transplantation, considerations during the transplantation period, selection of transplantation routes and dosages, management of FMT-related complications, and future research directions, aiming to offer standardized guidance for the clinical application of FMT in the treatment of IBD.}, } @article {pmid40122676, year = {2025}, author = {González-Correa, C and Moleón, J and Miñano, S and Robles-Vera, I and de la Visitación, N and Guerra-Hernández, E and Toral, M and Jiménez, R and Duarte, J and Romero, M}, title = {Protective Effect of Dietary Fiber on Blood Pressure and Vascular Dysfunction Through Regulation of Sympathetic Tone and Immune Response in Genetic Hypertension.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8484}, pmid = {40122676}, issn = {1099-1573}, support = {B-CTS-046-UGR18//Junta de Andalucía and European Regional Development Fund (ERDF)/ ; CTS 164//Junta de Andalucía and European Regional Development Fund (ERDF)/ ; P20_00193//Junta de Andalucía and European Regional Development Fund (ERDF)/ ; MCIN/AEI/10.13039/501100011033//Ministry of Science and Innovation- State Research Agency of Spain (MSI-SRA)/ ; PID2020-116347RB-I00//Ministry of Science and Innovation- State Research Agency of Spain (MSI-SRA)/ ; FJC2021-048099-I//Ministerio de Economia y Competitividad (MINECO)/ ; FPU18/02561//Ministerio de Economia y Competitividad (MINECO)/ ; FPU22/00397//Ministerio de Economia y Competitividad (MINECO)/ ; }, abstract = {The mechanisms underlying the antihypertensive effect of dietary fibers remain poorly understood. This study investigates whether dietary fiber supplementation can prevent cardiovascular damage and high blood pressure in a genetic model of neurogenic hypertension. Six-week-old male spontaneously hypertensive rats (SHR) and their respective normotensive control, Wistar Kyoto rats (WKY), were divided into four groups: Untreated WKY, untreated SHR, SHR treated with resistant starch (SHR + RS), and SHR treated with inulin-type fructans (SHR + ITF) for 12 weeks. Additionally, a faecal microbiota transplantation (FMT) experiment was conducted, transferring faecal content from treated SHR donors to recipient SHRs. A diet rich in RS fiber reduced vascular oxidative stress, inflammation, and high blood pressure. These protective effects were associated with a reshaped gut microbiota, leading to increased short-chain fatty acid production, reduced endotoxemia, decreased sympathetic activity, and a restored balance between Th17 and Treg lymphocytes in mesenteric lymph nodes and aorta. Elevated plasma levels of acetate and butyrate in the SHR + RS group correlated with increased expression of aortic GPR41, GRP43 and PPARδ. Conversely, ITF treatment failed to prevent hypertension or endothelial dysfunction in SHR. FMT from the SHR + RS group to recipient SHR partially replicated these beneficial effects. This study highlights the antihypertensive benefits of dietary insoluble RS fiber, which are attributed to enhanced short-chain fatty acids production in the gut. This leads to improved gut permeability, reduced sympathetic tone, and diminished vascular T-cell accumulation. Therefore, dietary interventions with RS fiber may offer promising therapeutic strategies for preventing hypertension.}, } @article {pmid40122597, year = {2025}, author = {Su, R and Wen, W and Jin, Y and Cao, Z and Feng, Z and Chen, J and Lu, Y and Zhou, G and Dong, C and Gao, S and Li, X and Zhang, H and Chao, K and Lan, P and Wu, X and Philips, A and Li, K and Gao, X and Zhang, F and Zuo, T}, title = {Dietary whey protein protects against Crohn's disease by orchestrating cross-kingdom interaction between the gut phageome and bacteriome.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-334516}, pmid = {40122597}, issn = {1468-3288}, abstract = {BACKGROUND: The gut microbiome and diet are important factors in the pathogenesis and management of Crohn's disease (CD). However, the role of the gut phageome under dietary influences is unknown.

OBJECTIVE: We aim to explore the effect of diet on the gut phageome-bacteriome interaction linking to CD protection.

DESIGN: We recruited CD patients and healthy subjects (n=140) and conducted a multiomics investigation, including paired ileal mucosa phageome and bacteriome profiling, dietary survey and phenome interrogation. We screened for the effect of diet on the gut phageome and bacteriome, as well as its epidemiological association with CD risks. The underlying mechanisms were explored in target phage-bacteria monocultures and cocultures in vitro and in two mouse models in vivo.

RESULTS: On dietary screening in humans, whey protein (WP) consumption was found to profoundly impact the gut phageome and bacteriome (more pronounced on the phageome) and was associated with a lower CD risk. Indeed, the WP reshaped gut phageome can causally attenuate intestinal inflammation, as shown by faecal phageome versus bacteriome transplantation from WP-consuming versus WP-non-consuming mice to recipient mice. Mechanistically, WP induced phage (a newly isolated phage AkkZT003P herein) lysis of the mucin-foraging bacterium Akkermansia muciniphila, which unleashed the symbiotic bacterium Streptococcus thermophilus to counteract intestinal inflammation.

CONCLUSION: Our study charted the importance of cross-kingdom interaction between gut phage and bacteria in mediating the dietary effect on CD protection. Importantly, we uncovered a beneficial dietary WP, a keystone phage AkkZT003P, and a probiotic S. thermophilus that can be used in CD management in the future.}, } @article {pmid40120791, year = {2025}, author = {Xu, DQ and Geng, JX and Gao, ZK and Fan, CY and Zhang, BW and Han, X and He, LQ and Dai, L and Gao, S and Yang, Z and Zhang, Y and Arshad, M and Fu, Y and Mu, XQ}, title = {To explore the potential combined treatment strategy for colorectal cancer: inhibition of cancer stem cells and enhancement of intestinal immune microenvironment.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {177533}, doi = {10.1016/j.ejphar.2025.177533}, pmid = {40120791}, issn = {1879-0712}, abstract = {BACKGROUND: The antibiotic salinomycin, a well-known cancer stem cell inhibitor, may impact the diversity of the intestinal microbiota in colorectal cancer (CRC) mice, which plays a pivotal role in shaping the immune system. This study explores the anti-cancer effects and mechanisms of combining salinomycin and fecal microbiota transplantation (FMT) in treating CRC.

METHODS: FMT was given via enema, while salinomycin was injected intraperitoneally into the CRC mouse model induced by azoxymethane/dextran sodium sulfate.

RESULTS: In CRC mice, a large number of LGR5-labeled cancer stem cells and severe disturbances in the intestinal microbiota were observed. Interestingly, salinomycin inhibited the proliferation of cancer stem cells without exacerbating the microbial disorder as expected. In comparison to salinomycin treatment, the combination of salinomycin and FMT significantly improved pathological damage and restored intestinal microbial diversity, which is responsible for shaping the anti-cancer immune microenvironment. The supplementation of FMT significantly increased the levels of propionic acid and butyric acid while also promoting the infiltration of CD8[+] T cells and Ly6G[+] neutrophils, as well as reducing F4/80[+] macrophage recruitment. Notably, cytokines that were not impacted by salinomycin exhibited robust reactions to alterations in the gut microbiota. These included pro-inflammatory factors (IL6, IL12b, IL17, and IL22), chemokine-like protein OPN, and immunosuppressive factor PD-L1.

CONCLUSIONS: Salinomycin plays the role of "eliminating pathogenic qi," targeting cancer stem cells; FMT plays the role of "strengthening vital qi," reversing the intestinal microbiota disorder and enhancing anti-cancer immunity. They have a synergistic effect on the development of CRC.}, } @article {pmid40120542, year = {2025}, author = {Luo, F and Yang, J and Song, Z and Zhao, Y and Wang, P and Liu, K and Mou, X and Liu, W and Li, W}, title = {Renshen Zhuye decoction ameliorates high-fat diet-induced obesity and insulin resistance by modulating gut microbiota and metabolic homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {141}, number = {}, pages = {156655}, doi = {10.1016/j.phymed.2025.156655}, pmid = {40120542}, issn = {1618-095X}, abstract = {BACKGROUND: Obesity, characterized by excessive adipose tissue accumulation, has become a global health challenge with rapidly increasing prevalence. It contributes significantly to metabolic disorders including insulin resistance (IR). Renshen-zhuye decoction (RZD), a traditional Chinese medicine formula historically used for diabetes, shows potential for improving metabolic parameters, but its effects and mechanisms in obesity and insulin resistance remain unclear.

PURPOSE: This study aimed to evaluate the therapeutic benefits of RZD on obesity and insulin resistance, and to elucidate the underlying mechanisms through which it improves glucose and lipid metabolism.

METHODS: The role of RZD was evaluated in a high-fat diet (HFD) mouse model. The formula was characterized using UPLC-MS. Comprehensive analyses including histopathological staining, immunofluorescence, biochemical assays, 16S rRNA gene sequencing of gut microbiota, and non-targeted metabolomic analysis were performed. To validate the role of gut microbiota, we employed antibiotic treatment (ABX) to deplete intestinal flora and conducted fecal microbiota transplantation (FMT) experiments.

RESULTS: RZD treatment dose-dependently alleviated HFD-induced dyslipidemia and insulin resistance, improving glucose tolerance, insulin sensitivity, and energy expenditure. Gut microbiota analysis revealed that RZD significantly modulated the composition of intestinal flora and their metabolic profiles. Additionally, RZD reduced intestinal and systemic inflammation by enhancing intestinal barrier integrity, particularly through increased expression of tight junction proteins such as Occludin. Importantly, the beneficial effects of RZD on weight management and glucose homeostasis were antagonized by antibiotic intervention, while FMT experiments confirmed that these improvements were mediated through gut microbiota modulation.

CONCLUSION: This study provides new insights into RZD's modulatory effects on gut microbiota and subsequent improvements in obesity-related metabolic parameters. RZD alleviates HFD-induced obesity and insulin resistance in mice by modulating gut microbiota composition and function, which subsequently improves intestinal barrier integrity, reduces inflammation, and enhances metabolic homeostasis.}, } @article {pmid40120240, year = {2025}, author = {Gao, C and Chen, Y and Zhang, Z and Xu, D and Liu, X and Wang, D and Shi, L and Wang, X and Chen, H and Hao, E}, title = {LAYING RATE WAS CORRELATED WITH MICROBIAL Fecal microbiota transplantation improves the laying performance by changing the gut microbiota composition in late laying period.}, journal = {Poultry science}, volume = {104}, number = {5}, pages = {105064}, doi = {10.1016/j.psj.2025.105064}, pmid = {40120240}, issn = {1525-3171}, abstract = {This research investigated the differences and succession patterns of microbes in different ages, the performance of laying hens, and the effect of Fecal Microbiota Transplantation (FMT) on aged laying hens. First, based on the different laying rates and age, we divided the laying hens into four groups: 75-week-old high-yield (OH, laying rate (LR) > 90%), 75-week-old low-yield (OL, LR < 60%), 75-week-old non-laying hens (OZ, LR = 0%) and 35-week-old high-yield (YH, LR > 90%) with 5 replicates in each group and 6 chickens in each replicate. The microbial metabolic patterns between different ages and laying rates were determined using 16S rDNA technology. Then, to verify the results of microbiome research, we utilized FMT technology to transplant the gut microbiota from OH to OZ (OZFMT-OH), thereby revealing the connection between gut microbes and production performance. The results showed that high-yielding hens (YH and OH groups) had higher levels of Superoxide dismutase (SOD) and Immunoglobulin A (IgA) compared to OL and OZ groups. The Villus height to Crypt depth ratio(V/C) was significantly higher in the YH group than in 75-week-old hens (P < 0.05). Alpha diversity indicated higher microbial diversity in the YH group compared to older hens (P < 0.05), with YH hens harboring more Megamonas, OH hens more Bacteroides, and OL and OZ groups showing higher levels of harmful bacteria. The villus height, V/C, mucosal layer thickness, cup cell number acetic acid level, and LR in the OZFMT-OH group were significantly higher than those in the OZ group (P < 0.05), while the IL-2 level, crypt depth and cecal intestinal wall thickness were significantly lower than those in OZ group (P < 0.05). FMT also changed the morphological structure of grade follicles and small yellow follicles, improved the microbe composition of cecum and increased Bacteroides abundance. In the late laying period, if the intestinal flora cannot maintain the dynamic balance and carry out timely replacement, the production performance may be decreased, and the increase of Bacteroides abundance in the intestinal tract can improve the intestinal health and production performance of laying hens in the late laying period.}, } @article {pmid40118401, year = {2025}, author = {Zhang, J and Zhou, J and He, Z and Xia, Z and Liu, H and Wu, Y and Chen, S and Wu, B and Li, H}, title = {Salidroside attenuates NASH through regulating bile acid-FXR/TGR5 signaling pathway via targeting gut microbiota.}, journal = {International journal of biological macromolecules}, volume = {307}, number = {Pt 4}, pages = {142276}, doi = {10.1016/j.ijbiomac.2025.142276}, pmid = {40118401}, issn = {1879-0003}, abstract = {Nonalcoholic steatohepatitis (NASH) is a significant threat to human health. Our previous study revealed that salidroside attenuated NASH and regulated the gut microbiota. However, whether the therapeutic effect of salidroside depends on gut microbiota remains to be determined. Therefore, we conducted further experiments to elucidate the essential functions of gut microbiota-associated metabolic pathways in the anti-NASH effects of salidroside. Our results showed that salidroside effectively alleviated lipid accumulation and inflammatory injury in NASH mice. 16S rRNA sequencing revealed that salidroside increased the abundance of Bacteroides. Mice receiving fecal microbiota transplantation (FMT) from salidroside-treated also presented less hepatic steatosis and higher abundance of Bacteroides. Antibiotics eliminated the effects of salidroside on hepatic steatosis and the gut microbiota. Mechanistically, salidroside and FMT from salidroside-treated altered the bile acid (BA) profile by decreasing the levels of conjugated BAs and tauro-α/β-muricholic acid and activated downstream farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Furthermore, we found that inhibitors of bile salt hydrolase (BSH) and FXR/TGR5 abolished the effects of salidroside and reduced downstream carnitine palmitoyltransferase 1α and lipoprotein lipase expression. These data demonstrate that salidroside attenuated NASH via gut microbiota-BA-FXR/TGR5 signaling pathway and reveal the underlying mechanism of salidroside on NASH.}, } @article {pmid40118127, year = {2025}, author = {Wu, S and Qiao, L and Liu, H and Li, YL and Wang, R and Yin, Y and Li, E and Wang, L and Guan, X and Yin, L and Liu, Q and Peng, X and Zhang, Y and Yang, Z and Zuo, L and Zhang, C}, title = {Age related gut microbiota regulates energy-related metabolism to influence natural aging phenotypes in the heart.}, journal = {Experimental gerontology}, volume = {203}, number = {}, pages = {112734}, doi = {10.1016/j.exger.2025.112734}, pmid = {40118127}, issn = {1873-6815}, abstract = {As the population ages, problems pertaining to health and life expectancy due to the aging heart have become increasingly prominent. The gut microbiota has become a potential therapeutic target in several diseases, including cardiovascular diseases. Current studies on the roles of the gut microbiota in the cardiovascular system have focused mainly on cardiovascular diseases; therefore, the effects of the gut microbiota on the natural aging of myocardial tissue remain unclear. The present study aimed to explore the roles and mechanisms of the gut microbiota and related metabolites in the natural aging of the heart. Animal models of fecal microbiota transplantation (FMT) were established in elderly and young rats. 16S rRNA sequencing revealed that the gut microbiota of the recipients shifted toward the profile of the donors, with concomitant cardiac structure and diastolic function changes detected via ultrasound and positron emission tomography-computed tomography (PET-CT). A group of significantly enriched myocardial metabolites detected by LC/MS were involved in the fatty acid β-oxidation process. Together with altered glucose uptake, as revealed by PET-CT, changes in ATP content and mitochondrial structure further verified a metabolic difference related to energy among rats transplanted with the gut microbiota from donors of different ages. This study demonstrated that gut microbes may participate in the physiological aging process of the rat heart by regulating oxidative stress and autophagy. The gut microbiota has been shown to be involved in the natural aging of the heart at multiple levels, from the organ level to the metabolically plastic myocardiocytes and associated molecules.}, } @article {pmid40116713, year = {2025}, author = {Chinna Meyyappan, A and Sgarbossa, C and Bromley, H and Forth, E and Müller, DJ and Vazquez, G and Cabrera, C and Milev, R}, title = {The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression - A Phase 2, Double-Blind, Placebo-Controlled Study: Clinical Results: Innocuité et efficacité du traitement de l'écosystème microbien (met-2) dans la dépression majeure - une étude de phase 2 à double insu contrölée par placebo : résultats cliniques.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437251328270}, pmid = {40116713}, issn = {1497-0015}, abstract = {ObjectivesThis study examines the safety and efficacy of a fecal transplant alternative, Microbial Ecosystem Therapeutic-2 (MET-2), in improving symptoms of depression. The primary objective of this study is to assess changes in depressive symptoms before, during, and after administration of MET-2 in comparison to placebo. Mood-related symptoms such as anxiety and anhedonia, gastrointestinal symptoms, and safety of the therapeutic were also assessed using both self-report and clinician-rated measures.MethodsTwenty-nine participants (n = 29) experiencing a major depressive episode were recruited from the Kingston and Toronto areas. Participants orally consumed MET-2, an encapsulated microbial therapeutic containing 40 different strains of bacteria, or placebo alternative, once daily for 6 weeks with a 2-week follow-up. Participants underwent a series of clinical assessments used to measure mood, anxiety, and gastrointestinal symptoms.ResultsThere was a significant improvement in depressive symptomology over time as determined by Montgomery-Åsberg Depression Rating Scale scores (p < 0.0001); however there was no significant difference between placebo and MET-2 groups (p = 0.338). No serious adverse events were reported. The findings of this study are the first to provide evidence for the role of oral microbial therapeutics, such as MET-2, as treatment for symptoms of depression.ConclusionsThough there are positive trends suggesting a greater improvement in depressive symptomology among the MET-2 group compared to the placebo group, a larger sample size is needed for more conclusive results. Clinicaltrials.gov NCT04602715.}, } @article {pmid40116683, year = {2025}, author = {Prati, D and Caprioli, F and Stea, L and Berzuini, A and Pizzotti, D and Petrillo, E and Coluccio, E and Erba, E and Lamorte, G and Ferrari, F and Cariani, L and Amoroso, C and Preti, AC and Bandera, A and Callegaro, A and Castaldi, S and Cardillo, M and Vecchi, M and Valenti, L and De Angelis, V}, title = {A "movement" worth making: why and how Transfusion Services can play a role in Fecal Microbiota Transplant programs.}, journal = {Blood transfusion = Trasfusione del sangue}, volume = {}, number = {}, pages = {}, doi = {10.2450/BloodTransfus.929}, pmid = {40116683}, issn = {2385-2070}, abstract = {Fecal Microbiota Transplantation (FMT) is an innovative therapy with growing applications, particularly for recurrent Clostridioides difficile infections (rCDI). However, the broader use of FMT is challenged by the complexities of donor recruitment, the necessity of stringent screening protocols, and the need for maintaining high-quality stool biobanks. This paper explores the integration of FMT programs within transfusion medicine departments, taking advantage of their expertise in donor management and biological material processing. Despite the complexities of donor screening, including a low eligibility rate, the collaboration between transfusion services and other hospital departments demonstrates a viable model for expanding FMT access. Additionally, the recent EU regulations on substances of human origin (SoHO) offer a framework for standardizing and scaling stool banking, enhancing the safety and efficacy of FMT procedures.}, } @article {pmid40116376, year = {2025}, author = {Yang, Y and Zhang, Y and Zhang, W and Lu, K and Wang, L and Liu, Y and Du, L and Yang, J and Guan, L and Ma, H}, title = {Flammulina velutipes residue Polysaccharide Alleviates Immunosuppression and Intestinal Injury by Modulating Gut Microbiota and Associated Metabolites.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c12105}, pmid = {40116376}, issn = {1520-5118}, abstract = {This study elucidated the mechanisms underlying the immunoregulatory and gut-microbiota-modulating effects of Flammulina velutipes residue polysaccharide (FVRP) using cyclophosphamide (CTX)-induced mouse models. FVRP supplementation alleviated CTX-induced intestinal damage and boosted antioxidant enzyme activity and cytokine secretion. Additionally, FVRP enhanced the diversity and total species richness of the gut microbiota, promoting the proliferation of beneficial bacteria (e.g., Prevotellaceae), while reducing the abundance of CTX-derived bacteria (Lachnospiraceae and Rikenellaceae). FVRP facilitates the accumulation of short-chain fatty acids. Untargeted metabolomic analyses of cecal content revealed that FVRP treatment notably restored the levels of 32 endogenous metabolites altered by CTX. Based on a pseudosterility mice model, fecal microbiota transplantation (FMT), and fecal filtrate transplantation (FFT), gut microbiota and associated metabolites were demonstrated to play a crucial role in the immunomodulatory and protective effects of FVRP against intestinal injury. In conclusion, FVRP exhibits significant potential as an immune enhancer and natural therapeutic agent for alleviating intestinal inflammatory conditions.}, } @article {pmid40115610, year = {2025}, author = {Waterman, A and Doumas, SA and Fischer, M and Mattar, M and Charbel, S and Jennings, J and Doman, DB}, title = {Uncovering the Hidden Link Between the Aberrant Intestinal Microbiome and Fibromyalgia.}, journal = {Gastroenterology & hepatology}, volume = {21}, number = {2}, pages = {111-121}, pmid = {40115610}, issn = {1554-7914}, abstract = {Fibromyalgia is a multifaceted syndrome primarily characterized by chronic widespread pain and fatigue. Despite its significant prevalence and incidence, the mechanisms mediating the disease pathogenesis have remained poorly understood; however, increasing evidence suggests a potentially central role of intestinal dysbiosis. Researchers have been examining possible diagnostic biomarkers, such as Helicobacter pylori infection, urine metabolite profiles, and cytokine levels, which reflect these microbiome changes. Additionally, evaluation of therapeutic interventions targeting the gut microbiome, including probiotics, fecal microbiota transplantation, and antibiotics for specific infections, has highlighted their potential in alleviating fibromyalgia symptoms. This article delves into the emerging role of the gut microbiome in fibromyalgia pathogenesis, illustrating how alterations in gut bacterial composition and diversity are implicated in the pathophysiology of the disease through the gut-brain axis, and sets a direction for future research to enhance diagnostic accuracy and therapeutic efficacy of this complex condition.}, } @article {pmid40111698, year = {2025}, author = {Vernon, JJ}, title = {Modulation of the Human Microbiome: Probiotics, Prebiotics, and Microbial Transplants.}, journal = {Advances in experimental medicine and biology}, volume = {1472}, number = {}, pages = {277-294}, pmid = {40111698}, issn = {0065-2598}, mesh = {Humans ; *Prebiotics/administration & dosage ; *Probiotics/therapeutic use ; *Microbiota/physiology ; Mouth/microbiology ; Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation/methods ; }, abstract = {The balance between health and disease is intrinsically linked to the interactions between microbial communities and the host. This complex environment of antagonism and synergy involves both prokaryotic and eukaryotic cells, whose collaborative metabolic pathways and immunomodulatory elements influence system homeostasis. As with the gut and other niches, the oral microbiome has the capacity to affect distal host sites. The ability to manipulate this environment holds the potential to impact local and systemic disease.With the increasing threat of antimicrobial resistance, novel approaches to reduce the burden of disease are essential. The use of probiotics and prebiotics is one such strategy. Probiotics introduce non-pathogenic bacteria into the environment to compete with pathogens for nutrients and attachment sites, or to produce metabolites that counteract disease aetiologies. Prebiotic compounds enhance the growth of health-associated organisms, offering additional benefits, whilst a conjunctive approach with probiotics potentially holds even greater promise. Though widely studied in the gastrointestinal context, their potential for treating oral diseases, such as dental caries and periodontitis, is less understood. Additionally, the use of microbial transplantations has demonstrated efficacy in other areas, reducing systemic inflammation and recolonising with commensal bacteria. Here we evaluate their use in the oral context and their modulatory impact on overall health.In this chapter, we discuss how pro- and prebiotic strategies seek to modulate both the oral and gut environments to promote oral health and prevent disease. We assess novel approaches for utilising health-associated microorganisms to combat oral disorders, either administered locally in the mouth or imparting influence through immune modulation via the oral-gut axis. By examining available clinical trial data, we aim to further understand the intricacies involved in this discipline. Furthermore, we consider the challenges facing the research community, including optimal candidate organism/compound selection and colonisation retention, as well as considerations for future research.}, } @article {pmid40110391, year = {2025}, author = {Zhu, B and Gu, Z and Hu, H and Huang, J and Zeng, Z and Liang, H and Yuan, Z and Huang, S and Qiu, Y and Sun, XD and Liu, Y}, title = {Altered Gut Microbiota Contributes to Acute-Respiratory-Distress-Syndrome-Related Depression through Microglial Neuroinflammation.}, journal = {Research (Washington, D.C.)}, volume = {8}, number = {}, pages = {0636}, pmid = {40110391}, issn = {2639-5274}, abstract = {Acute respiratory distress syndrome (ARDS) survivors often suffer from long-term psychiatric disorders such as depression, but the underlying mechanisms remain unclear. Here, we found marked alterations in the composition of gut microbiota in both ARDS patients and mouse models. We investigated the role of one of the dramatically changed bacteria-Akkermansia muciniphila (AKK), whose abundance was negatively correlated with depression phenotypes in both ARDS patients and ARDS mouse models. Specifically, while fecal transplantation from ARDS patients into naive mice led to depressive-like behaviors, microglial activation, and intestinal barrier destruction, colonization of AKK or oral administration of its metabolite-propionic acid-alleviated these deficits in ARDS mice. Mechanistically, AKK and propionic acid decreased microglial activation and neuronal inflammation through inhibiting the Toll-like receptor 4/nuclear factor κB signaling pathway. Together, these results reveal a microbiota-dependent mechanism for ARDS-related depression and provide insight for developing a novel preventative strategy for ARDS-related psychiatric symptoms.}, } @article {pmid40110192, year = {2025}, author = {Zhang, C and Wang, Y and Cheng, L and Cao, X and Liu, C}, title = {Gut microbiota in colorectal cancer: a review of its influence on tumor immune surveillance and therapeutic response.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1557959}, pmid = {40110192}, issn = {2234-943X}, abstract = {Colorectal cancer (CRC) poses a significant global health burden, with gut microbiota emerging as a crucial modulator of CRC pathogenesis and therapeutic outcomes. This review synthesizes current evidence on the influence of gut microbiota on tumor immune surveillance and responses to immunotherapies and chemotherapy in CRC. We highlight the role of specific microbial taxa in promoting or inhibiting tumor growth and the potential of microbiota-based biomarkers for predicting treatment efficacy. The review also discusses the implications of microbiota modulation strategies, including diet, probiotics, and fecal microbiota transplantation, for personalized CRC management. By critically evaluating the literature, we aim to provide a comprehensive understanding of the gut microbiota's dual role in CRC and to inform future research directions in this field.}, } @article {pmid40110027, year = {2025}, author = {Cai, S and Li, Z and Bai, J and Ding, Y and Liu, R and Fang, L and Hou, D and Zhang, S and Wang, X and Wang, Y and Jiang, Y and Xiang, Y and Wu, W and He, Y and Zhang, Y and Ren, X}, title = {Optimized oxygen therapy improves sleep deprivation-induced cardiac dysfunction through gut microbiota.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1522431}, pmid = {40110027}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Sleep Deprivation ; Mice ; *Fecal Microbiota Transplantation ; *RNA, Ribosomal, 16S/genetics ; *Disease Models, Animal ; Male ; Fibrosis ; Mice, Inbred C57BL ; Heart Diseases/therapy/microbiology ; Oxygen Inhalation Therapy/methods ; Oxygen/metabolism ; }, abstract = {Adequate sleep is of paramount importance for relieving stress and restoring mental vigor. However, the adverse physiological and pathological responses resulting from sleep insufficiency or sleep deprivation (SD) are becoming increasingly prevalent. Currently, the impact of sleep deficiency on gut microbiota and microbiota-associated human diseases, especially cardiac diseases, remains controversial. Here, we employed the following methods: constructed an experimental sleep-deprivation model in mice; conducted 16S rRNA sequencing to investigate the changes in gut microbiota; through fecal microbiota transplantation (FMT) experiments, transplanted fecal microbiota from sleep-deprived mice to other mice; established an environment with a 30% oxygen concentration to explore the therapeutic effects of oxygen therapy on gut microbiota-associated cardiac fibrosis and dysfunction; and utilized transcriptome data to study the underlying mechanisms of oxygen therapy. The results revealed that: sleep-deprived mice exhibited weakness, depression-like behaviors, and dysfunction in multiple organs. Pathogenic cardiac hypertrophy and fibrosis occurred in sleep-deprived mice, accompanied by poor ejection fraction and fractional shortening. 16S rRNA sequencing indicated that sleep deprivation induced pathogenic effects on gut microbiota, and similar phenomena were also observed in mice that received fecal microbiota from sleep-deprived mice in the FMT experiments. The environment with a 30% oxygen concentration effectively alleviated the pathological impacts on cardiac function. Transcriptome data showed that oxygen therapy targeted several hypoxia-dependent pathways and inhibited the production of cardiac collagen. In conclusion, these results demonstrate the significance of sufficient sleep for gut microbiota and may represent a potential therapeutic strategy, where the oxygen environment exerts a protective effect on insomniacs through gut microbiota.}, } @article {pmid39979777, year = {2025}, author = {Nagy, M and Wychera, C and Schemm, J and Brewster, R and Duncan, CN}, title = {Bacterial and Parasitic Stool Studies Have Limited Utility in Pediatric Hematopoietic Stem Cell Transplant Patients.}, journal = {Pediatric blood & cancer}, volume = {72}, number = {5}, pages = {e31617}, doi = {10.1002/pbc.31617}, pmid = {39979777}, issn = {1545-5017}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Child ; Female ; *Feces/microbiology/parasitology ; Child, Preschool ; Adolescent ; Infant ; Retrospective Studies ; Diarrhea/etiology/microbiology/parasitology ; Follow-Up Studies ; Graft vs Host Disease/etiology/microbiology ; Prognosis ; Bacteria/isolation & purification ; Bacterial Infections/etiology/epidemiology ; Parasites/isolation & purification ; }, abstract = {BACKGROUND: Diarrhea is a common complication among pediatric hematopoietic stem cell transplantation (HCT) recipients. Although many of the cases are secondary to graft-versus-host disease (GVHD), stool microbiological studies are often performed to evaluate an underlying infectious etiology. The aim of this study was to assess the frequency and utility of stool studies in children who have undergone HCT.

METHODS: Demographics, clinical characteristics, and stool study results (viral, parasitic, and bacterial) of all patients who underwent HCT at a large, academic, freestanding children's hospital between January 2006 and December 2023 were obtained. Statistical analysis conducted included t tests, chi-square, and linear regression.

RESULTS: Overall, 1381 HCT recipients (9.2 ± 6.6 years) were included. Altogether, 6509 stool studies were obtained among 741 (54%) patients. Salmonella, Shigella, Yersinia, Campylobacter, and Escherichia coli (SSYCE) studies were sent on 363 (26%, 2252 studies) patients with 1 (0.04%) positive result. Clostridium difficile was sent on 706 (51%, 2055 studies) patients, with 156 positive studies (7.6%). Stool ova and parasite testing was sent on 143 (10%, 242 studies) patients, with two positive results (0.8%). Viral studies were sent on 638 (46%, 1960 studies) patients, with 107 positive studies (5.5%).

CONCLUSIONS: While testing for Clostridium difficile and enteric viruses may have value in the work-up of pediatric HCT patients, SSYCE and O&P studies hold little to no value. Clinical practices surrounding routine stool microbiological studies should be reconsidered.}, } @article {pmid40107339, year = {2025}, author = {Xue, M and Deng, Q and Deng, L and Xun, T and Huang, T and Zhao, J and Wei, S and Zhao, C and Chen, X and Zhou, Y and Liang, Y and Yang, X}, title = {Alterations of gut microbiota for the onset and treatment of psoriasis: A systematic review.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {177521}, doi = {10.1016/j.ejphar.2025.177521}, pmid = {40107339}, issn = {1879-0712}, abstract = {Psoriasis is a chronic, recurrent and systemic inflammatory skin disease which is mediated by immunoreaction. Its pathogenesis is multifactorial, and the exact driving factor remains unclear. Recent studies showed that gut microbiota, which maintain immune homeostasis of our bodies, is closely related with occurrence, development and prognosis of psoriasis. The intestinal microbial abundance and diversity in patients with psoriasis have changed significantly, including intestinal microbiota disorders and reduced production of short chain fatty acids (SCFAs), abnormalities in Firmicutes/Bacteroidetes (F/B), etc. Besides, the intestinal microbiota of psoriasis patients has also changed after treatment of systemic drugs, biologics and small molecule chemical drugs, suggesting that the intestinal microbiota may be a potential response-to-treatment biomarker for evaluating treatment effectiveness. Oral probiotics and prebiotics administration as well as fecal microbial transplantation were also reported to benefit well in psoriasis patients. Additionally, we also discussed the microbial changes from the skin and other organs, which regulated both the onset and treatment of psoriasis together with gut microbiota. Herein, we reviewed recent studies on the psoriasis-related microbiota in an attempt to confidently identify the "core" microbiota of psoriatic patients, understand how microbiota influence psoriasis through the gut-skin axis, and explore potential therapeutic strategies for psoriasis.}, } @article {pmid40104324, year = {2025}, author = {Gu, C and Sha, G and Zeng, B and Cao, H and Cao, Y and Tang, D}, title = {Therapeutic potential of fecal microbiota transplantation in colorectal cancer based on gut microbiota regulation: from pathogenesis to efficacy.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251327167}, pmid = {40104324}, issn = {1756-283X}, abstract = {Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with its progression intricately linked to gut microbiota dysbiosis. Disruptions in microbial homeostasis contribute to tumor initiation, immune suppression, and inflammation, establishing the microbiota as a key therapeutic target. Fecal microbiota transplantation (FMT) has emerged as a transformative approach to restore microbial balance, enhance immune responses, and reshape the tumor microenvironment. This review explores the mechanisms underlying FMT's therapeutic potential, evaluates its advantages over other microbiota-based interventions, and addresses challenges such as donor selection, safety concerns, and treatment standardization. Looking forward, the integration of FMT into personalized CRC therapies requires robust clinical trials and the identification of predictive biomarkers to optimize its efficacy and safety.}, } @article {pmid40104059, year = {2025}, author = {Sharma, P and Jain, T and Sorgen, A and Iyer, S and Tarique, M and Roy, P and Kurtom, S and Sethi, V and Bava, EP and Gutierrez-Garcia, AK and Vaish, U and Suresh, DS and Sahay, P and Edwards, D and Afghani, J and Putluri, S and Reddy, KRK and Amara, CS and Kamal, AHM and Fodor, A and Dudeja, V}, title = {Smoking-induced gut microbial dysbiosis mediates cancer progression through modulation of anti-tumor immune response.}, journal = {iScience}, volume = {28}, number = {3}, pages = {112002}, pmid = {40104059}, issn = {2589-0042}, abstract = {Cigarette smoke exposure (CSE) increases the risk for a plethora of cancers. Recent evidence indicates that the gut microbiome can influence cancer progression by immune system modulation. Since CSE alters the gut microbiome, we hypothesized that the gut microbiome serves as a causative link between smoking and cancer growth. Through a combination of syngeneic animal models and fecal microbiota transplantation studies, we established an essential role for smoke-induced dysbiosis in cancer growth. 16s rRNA sequencing and liquid chromatography-mass spectrometry indicated a unique CSE-associated microbial and metabolomic signature. Immunophenotyping of tumor specimens and experiments in Rag1-KO and CD8-KO demonstrated that smoke-induced tumor growth requires functional adaptive immunity. Finally, utilizing gut microbial ablation strategies with broad- and narrow-spectrum antibiotics, we demonstrated the reversal of phenotypic effects of CSE. Our study provides evidence for gut microbiome as an actionable target to mitigate CSE-induced tumor promotion.}, } @article {pmid40103733, year = {2025}, author = {Hirsch, W and Fischer, M and Khoruts, A and Allegretti, JR and Kelly, CR and Vaughn, B}, title = {Risk Factors for Antibiotic Exposure Post-Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection: A Prospective Multicenter Observational Study.}, journal = {Open forum infectious diseases}, volume = {12}, number = {3}, pages = {ofaf130}, pmid = {40103733}, issn = {2328-8957}, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) is primarily driven by antibiotic-induced disruption of the indigenous intestinal microbiota. Restoration of microbiota through fecal microbiota transplantation (FMT) is effective in preventing subsequent CDI, although this effect is attenuated with additional antibiotic exposure. The aim of this study was to identify the risk factors for recurrent antibiotic administration after FMT.

METHODS: This is a prospective cohort of patients who were administered FMT for recurrent CDI from 1 July 2019 through 23 November 2023 across 6 institutions in the United States. Providers collected de-identified data at the time of FMT administration and in the months post-FMT administration.

RESULTS: The analysis included 448 patients. Risk factors for non-CDI antibiotic administration within 2 months of FMT included immunocompromised status (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.1-4.4]; P = .02), >3 non-CDI antibiotic courses pre-FMT (OR, 3.1 [95% CI, 1.4-6.8]; P = .006), and prior hospitalization for CDI (OR, 2.0 [95% CI, 1.1-3.8]; P = .02). The most common indications for non-CDI antibiotic administration post-FMT were urinary tract infections, respiratory infections, and procedure prophylaxis.

CONCLUSIONS: Non-CDI antibiotic exposure significantly increases the risk of CDI recurrence post-FMT. Risk factors for non-CDI antibiotic administration within 2 months of FMT include immunocompromised status, multiple prior non-CDI antibiotics, and prior hospitalization for CDI. These individuals may benefit from additional or modified recurrent CDI prevention strategies.}, } @article {pmid40099491, year = {2025}, author = {Deng, Z and Mei, S and Ouyang, Z and Wang, R and Wang, L and Zou, B and Dai, J and Mao, K and Li, Q and Guo, Q and Yi, C and Meng, F and Xie, M and Zhang, X and Wang, R and Deng, T and Wang, Z and Li, X and Wang, Q and Liu, B and Tian, X}, title = {Dysregulation of gut microbiota stimulates NETs-driven HCC intrahepatic metastasis: therapeutic implications of healthy faecal microbiota transplantation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2476561}, pmid = {40099491}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; Animals ; *Gastrointestinal Microbiome ; *Carcinoma, Hepatocellular/therapy/microbiology/pathology ; Humans ; *Liver Neoplasms/therapy/microbiology/pathology ; Mice ; *Extracellular Traps/metabolism ; Male ; Bacteria/classification/genetics/isolation & purification ; Female ; Middle Aged ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Disease Models, Animal ; }, abstract = {The stringent regulation of intrahepatic metastases is essential for improving survival outcomes in patients with hepatocellular carcinoma (HCC). This study investigated the impact of gut microbiota on intrahepatic metastasis of HCC and evaluated the therapeutic potential of healthy fecal microbiota transplantation (FMT). Dysregulation of the gut microbiota, characterized by a significant reduction in the abundance of beneficial bacteria, such as Anaerotruncus colihominis and Dysosmobacter welbionis, was observed in patients with intrahepatic metastatic HCC. A human flora-associated (HFA) intrahepatic metastatic HCC mouse model was successfully established through consecutive 4 weeks of human-mouse FMT. Dysregulation of gut microbiota promoted intrahepatic metastasis in the mouse model, primarily by enhancing neutrophil-mediated inflammatory responses and lead to excessive formation of neutrophil extracellular traps (NETs). Consequently, it promoted tumor vascular growth and tissue necrosis, resulting in intrahepatic metastasis of HCC. Notably, FMT from healthy donors mitigated these pathological processes. This study elucidated the role and mechanism of dysregulated gut microbiota in promoting intrahepatic metastasis of HCC. Healthy FMT emerges as a promising novel therapeutic strategy for preventing and treating intrahepatic metastasis of HCC.}, } @article {pmid40098090, year = {2025}, author = {Xiao, P and Li, Y and Li, X and Ge, T and Li, D and Xu, Q and Ruan, Y and Xiao, F and Xiao, Y and Zhang, T}, title = {Long-term safety of fecal microbiota transplantation in Chinese children from 2013 to 2023: a single-center retrospective study.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {152}, pmid = {40098090}, issn = {1471-2180}, mesh = {Humans ; Retrospective Studies ; Male ; Female ; *Fecal Microbiota Transplantation/methods/adverse effects ; Child ; Child, Preschool ; China ; Adolescent ; Infant ; *Gastrointestinal Microbiome ; Treatment Outcome ; Feces/microbiology ; East Asian People ; }, abstract = {BACKGROUND: The gut microbiome plays a vital role in influencing various health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a rapid, safe, and effective method for modifying the microbiome. However, there is a lack of long-term safety data regarding FMT in children. This study presents the largest single-center analysis of the long-term safety outcomes of FMT in pediatric patients in China, featuring a substantial sample size and an extended follow-up period to thoroughly examine its safety in children.

METHODS: A retrospective study was conducted on 813 patients who underwent FMT treatments at our hospital from December 2013 to December 2023. All FMT procedures adhered to standardized protocols. The safety of these treatments was retrospectively assessed, focusing on adverse events (AEs) and serious adverse events (SAEs). AEs associated with FMT were categorized as short-term (within 48 h post-FMT) and long-term (within 3 months). Various potential influencing factors for AEs, including sex, age, route of administration, disease type, and consanguineous donor, were examined as independent variables. Significant independent factors and their associated risk ratios with 95% confidence intervals (CI) were determined through multivariate logistic regression analysis. A p-value of less than 0.05 was considered statistically significant.

RESULTS: A total of 813 patients underwent FMT, with a median age of 93 months (range 4-215) and 68.0% being males. The average follow-up time was 32.3 months (range 1-122). All short-term AEs resolved within 48 h, with an overall occurrence rate of 5.8% (47/813). The most common short-term AEs included vomiting (2.0%), abdominal pain (1.6%), diarrhea (0.9%), fever (0.7%), dysphoria (0.4%), and nausea (0.4%). Multivariable analysis revealed that patients with inflammatory bowel disease (IBD) (OR: 3.98, 95% CI: 1.78-8.92, P = 0.001) and those who received FMT via capsules (OR: 0.09, 95% CI: 0.03-0.27, P = 0.000) were independent risk factors for FMT-related AEs. All 813 patients were followed up for at least 1 month, with 78.8% followed for more than 12 months. No long-term AEs occurred during the longest follow-up period of 122 months.

CONCLUSIONS: FMT is a promising treatment option that appears to be safe and well tolerated. This study stands out for its substantial sample size, making it's the largest reported series in pediatrics, as well as for having the longest follow-up period for FMT in this population.

CLINICAL TRIAL NUMBER: Not applicable.}, } @article {pmid40098052, year = {2025}, author = {Oami, T and Shimazui, T and Yumoto, T and Otani, S and Hayashi, Y and Coopersmith, CM}, title = {Gut integrity in intensive care: alterations in host permeability and the microbiome as potential therapeutic targets.}, journal = {Journal of intensive care}, volume = {13}, number = {1}, pages = {16}, pmid = {40098052}, issn = {2052-0492}, support = {R35 GM148217/GM/NIGMS NIH HHS/United States ; GM148217//Foundation for the National Institutes of Health/ ; }, abstract = {BACKGROUND: The gut has long been hypothesized to be the "motor" of critical illness, propagating inflammation and playing a key role in multiple organ dysfunction. However, the exact mechanisms through which impaired gut integrity potentially contribute to worsened clinical outcome remain to be elucidated. Critical elements of gut dysregulation including intestinal hyperpermeability and a perturbed microbiome are now recognized as potential therapeutic targets in critical care.

MAIN BODY: The gut is a finely tuned ecosystem comprising ~ 40 trillion microorganisms, a single cell layer intestinal epithelia that separates the host from the microbiome and its products, and the mucosal immune system that actively communicates in a bidirectional manner. Under basal conditions, these elements cooperate to maintain a finely balanced homeostasis benefitting both the host and its internal microbial community. Tight junctions between adjacent epithelial cells selectively transport essential molecules while preventing translocation of pathogens. However, critical illness disrupts gut barrier function leading to increased gut permeability, epithelial apoptosis, and immune activation. This disruption is further exacerbated by a shift in the microbiome toward a "pathobiome" dominated by pathogenic microbes with increased expression of virulence factors, which intensifies systemic inflammation and accelerates organ dysfunction. Research has highlighted several potential therapeutic targets to restore gut integrity in the host, including the regulation of epithelial cell function, modulation of tight junction proteins, and inhibition of epithelial apoptosis. Additionally, microbiome-targeted therapies, such as prebiotics, probiotics, fecal microbiota transplantation, and selective decontamination of the digestive tract have also been extensively investigated to promote restoration of gut homeostasis in critically ill patients. Future research is needed to validate the potential efficacy of these interventions in clinical settings and to determine if the gut can be targeted in an individualized fashion.

CONCLUSION: Increased gut permeability and a disrupted microbiome are common in critical illness, potentially driving dysregulated systemic inflammation and organ dysfunction. Therapeutic strategies to modulate gut permeability and restore the composition of microbiome hold promise as novel treatments for critically ill patients.}, } @article {pmid40097405, year = {2025}, author = {Li, L and Li, T and Liang, X and Zhu, L and Fang, Y and Dong, L and Zheng, Y and Xu, X and Li, M and Cai, T and Zhao, F and Xin, M and Shao, M and Guan, Y and Liu, M and Li, F and Zhang, C and Wang, Q and Sun, W and Zheng, Y}, title = {A decrease in Flavonifractor plautii and its product, phytosphingosine, predisposes individuals with phlegm-dampness constitution to metabolic disorders.}, journal = {Cell discovery}, volume = {11}, number = {1}, pages = {25}, pmid = {40097405}, issn = {2056-5968}, support = {2023T160729//China Postdoctoral Science Foundation/ ; }, abstract = {According to traditional Chinese medicine (TCM) constitutional theory, individuals with phlegm-dampness constitution (PDC) are at increased risk for metabolic disorders. Previous studies have indicated that PDC individuals exhibit gene expression changes associated with metabolic disorders, even individuals with normal metabolic indices. However, the biological mechanisms underlying these changes remain unclear. The gut microbiota has recently emerged as a promising avenue for elucidating TCM principles. Here, we revealed that individuals with PDC have distinct gut microbiota and serum metabolite profiles. A decrease in phytosphingosine was associated with increased PDC scores and metabolic disorder severity. Subsequent experiments demonstrated that Flavonifractor plautii can biosynthesize phytosphingosine, which was also negatively correlated with the PDC score. Interestingly, both F. plautii and phytosphingosine levels decreased in PDC subjects with normal metabolic indices. Fecal transplantation from these individuals accelerated the development of metabolic disorders in mice. However, supplementation with F. plautii and phytosphingosine ameliorated metabolic disorders by increasing phytosphingosine levels in the gut‒hepatic axis. Mechanistic investigations confirmed that phytosphingosine can directly bind to hepatic peroxisome proliferator-activated receptor α (PPARα) and activate its nuclear transcription activity, thereby regulating downstream gene expression related to glucose‒lipid metabolism. Our research indicates that the decrease in F. plautii and its product, phytosphingosine, contributes to gene expression changes related to metabolic disorders in PDC individuals and increases their susceptibility to metabolic disorders. These findings suggest that diagnosing PDC may be beneficial for identifying at-risk populations among apparently healthy individuals, thereby advancing the broader field of metabolic disorder prevention and TCM integration.}, } @article {pmid40096354, year = {2025}, author = {Dongre, DS and Saha, UB and Saroj, SD}, title = {Exploring the role of gut microbiota in antibiotic resistance and prevention.}, journal = {Annals of medicine}, volume = {57}, number = {1}, pages = {2478317}, pmid = {40096354}, issn = {1365-2060}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; *Dysbiosis/microbiology ; Drug Resistance, Multiple, Bacterial/genetics ; Fecal Microbiota Transplantation ; Drug Resistance, Microbial/genetics ; Bacteria/drug effects/genetics ; Probiotics/administration & dosage/therapeutic use ; }, abstract = {BACKGROUND/INTRODUCTION: Antimicrobial resistance (AMR) and the evolution of multiple drug-resistant (MDR) bacteria is of grave public health concern. To combat the pandemic of AMR, it is necessary to focus on novel alternatives for drug development. Within the host, the interaction of the pathogen with the microbiome plays a pivotal role in determining the outcome of pathogenesis. Therefore, microbiome-pathogen interaction is one of the potential targets to be explored for novel antimicrobials.

MAIN BODY: This review focuses on how the gut microbiome has evolved as a significant component of the resistome as a source of antibiotic resistance genes (ARGs). Antibiotics alter the composition of the native microbiota of the host by favouring resistant bacteria that can manifest as opportunistic infections. Furthermore, gut dysbiosis has also been linked to low-dosage antibiotic ingestion or subtherapeutic antibiotic treatment (STAT) from food and the environment.

DISCUSSION: Colonization by MDR bacteria is potentially acquired and maintained in the gut microbiota. Therefore, it is pivotal to understand microbial diversity and its role in adapting pathogens to AMR. Implementing several strategies to prevent or treat dysbiosis is necessary, including faecal microbiota transplantation, probiotics and prebiotics, phage therapy, drug delivery models, and antimicrobial stewardship regulation.}, } @article {pmid40095949, year = {2025}, author = {Newsome, RC and McGriff, C and Gharaibeh, RZ and Jobin, C}, title = {Preparation and Maintenance of Bioexclusion IsoPositive Cage Experiment for Human Fecal Transplantation into Germ-Free Mice.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {216}, pages = {}, doi = {10.3791/68029}, pmid = {40095949}, issn = {1940-087X}, mesh = {Animals ; Mice ; Humans ; *Fecal Microbiota Transplantation/methods ; *Germ-Free Life ; Feces/microbiology ; Housing, Animal ; Animal Husbandry/methods ; }, abstract = {Germ-free mice are an important investigation tool for understanding the contribution of microorganisms in host health and disease, enabling assessment of the specific role of individuals, defined or complex groups of microorganisms in host response. Traditionally bred and reared in flexible-film or semi-rigid isolators, germ-free mouse husbandry and experimental manipulation are costly and require numerous trained staff and a large space footprint in animal housing facilities. The IsoPositive caging system allows for experimental manipulation of germ-free mice in individual, hermetically-sealed, positive-pressure isolator cages (isocages), reducing cost and enabling greater flexibility in experimental manipulations. Here, a protocol is described for transferring germ-free mice from breeding isolators to isocages and subsequent fecal transfer from human donor stool into mice to create stable long-term gut "humanized" mice for future studies. The materials and preparation needed for the utilization of the isocage system are described, including the use of chlorine-dioxide sterilant chemical sterilant to clean cages, supplies, equipment, and personal protective equipment. The methods for confirming the germ-free status of transferred mice and how to determine contamination in the caging system are discussed. The procedure for husbandry, including bedding, food, and water supply, is further discussed. The protocol for human fecal slurry preparation and gavage into germ-free mice to create gut "humanized" mice, along with stool collection to monitor the microbial community composition of these mice, are described. An experiment illustrates that two weeks post-human fecal transplant allows for stable colonization of donor microbiota in the murine hosts, enabling subsequent experimental usage. Furthermore, the collection of humanized mouse feces in viability preservation media, enabling use in further functional experiments, is described. Overall, these methods allow for the safe and effective establishment of humanized mouse communities in experimental gnotobiotic cages for further manipulation.}, } @article {pmid40094148, year = {2025}, author = {Wang, X and Wang, WY and Yu, XL and Chen, JW and Yang, JS and Wang, MK}, title = {Comprehensive review of Clostridium difficile infection: Epidemiology, diagnosis, prevention, and treatment.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {16}, number = {1}, pages = {100560}, pmid = {40094148}, issn = {2150-5349}, abstract = {In recent years, nosocomial infections caused by Clostridium difficile (C. difficile) have risen, becoming a leading cause of hospital-acquired diarrhea. The global prevalence of C. difficile infection (CDI) varies across regions and populations. The diagnosis relies primarily on laboratory testing, including toxin, glutamate dehydrogenase, and nucleic acid amplification tests. Treatment strategies for CDI include antimicrobial therapy (e.g., metronidazole, vancomycin, and fidamycin), fecal transplantation, and immunotherapy (e.g., belotozumab), depending on the patient's specificity and severity. This paper reviews recent research on CDI's epidemiological characteristics, risk factors, diagnosis, treatment, and prevention, aiming to support hospitals and public health initiatives in implementing effective detection, prevention, and treatment strategies.}, } @article {pmid40091757, year = {2025}, author = {Le, PH and Chen, CL and Kuo, CJ and Yeh, PJ and Chen, CC and Chen, YC and Chiu, CT and Cheng, HT and Tsou, YK and Pan, YB and Chiu, CH}, title = {Impact of Clostridioides difficile Infection on Clinical Outcomes in Hospitalized IBD Patients and the Role of Fecal Microbiota Transplantation: A Retrospective Cohort Study.}, journal = {The Kaohsiung journal of medical sciences}, volume = {}, number = {}, pages = {e70002}, doi = {10.1002/kjm2.70002}, pmid = {40091757}, issn = {2410-8650}, support = {MOHW113-TDU-B-212-114010//Ministry of Health and Welfare (Taiwan)/ ; }, abstract = {Clostridioides difficile infection (CDI) worsens the prognosis of patients with inflammatory bowel disease (IBD). This retrospective cohort study aimed to evaluate the risk factors, clinical manifestations, and outcomes of CDI in hospitalized patients with IBD, including those with toxin A/B results between April 2007 and April 2021. Patients were classified into the CDI and control groups. Patients with IBD and recurrent or refractory CDI underwent fecal microbiota transplantation (FMT). A total of 144 inpatients with IBD-45 in the CDI group and 99 in the control group-were analyzed. The incidence of CDI in inpatients with IBD was 31%. The Risk factors for CDI included longer IBD duration, biological therapy failure, and biological use. More patients in the CDI group presented with abdominal pain (77.8% vs. 55.6%, p = 0.011). In the antibiotic treatment-only group, the symptom improvement rate was 60.7% (17/28), the microbiological cure rate was 89.3% (25/28), and the overall success rate was 71.4% (20/28). After antibiotic treatment and FMT, 71.4% (10/14) of the patients tested negative for CDI, and 64.3% (9/14) had improved clinical symptoms. CDI led to more hospitalizations (median two times [range 0-12] vs. median one time [range 0-19], p = 0.008), a lower steroid-free remission rate (46.7% vs. 67.7%, p = 0.017), and higher Mayo scores (median 5 points [range 2-12] vs. median 3 points [range 0-12]). Patients who received FMT had fewer hospitalizations and fewer IBD-related complications during follow-up than those who received antibiotics alone. FMT should be considered in patients with IBD with refractory or recurrent CDI to improve clinical outcomes.}, } @article {pmid40091072, year = {2025}, author = {Liu, Y and Liu, J and Ren, R and Xin, Z and Luo, Y and Chen, Y and Huang, C and Liu, Y and Yang, T and Wang, X}, title = {Short-term and long-term high-fat diet promote metabolic disorder through reprogramming mRNA m[6]A in white adipose tissue by gut microbiota.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {75}, pmid = {40091072}, issn = {2049-2618}, support = {32330098//National Natural Science Foundation of China/ ; 2022R52023//Science and technology innovation leading talent project of Zhejiang Province/ ; 2023YFD1301303//National Key Research and Development Program of China/ ; }, mesh = {*Gastrointestinal Microbiome ; *Diet, High-Fat/adverse effects ; Animals ; *Adipose Tissue, White/metabolism ; Mice ; Male ; *Metabolic Diseases/metabolism/microbiology/genetics ; *RNA, Messenger/genetics/metabolism ; *Mice, Inbred C57BL ; Endogenous Retroviruses/genetics ; Fecal Microbiota Transplantation ; Long Interspersed Nucleotide Elements/genetics ; Epigenesis, Genetic ; Adenosine/analogs & derivatives ; }, abstract = {BACKGROUND: Although short-term high-fat diet (S-HFD) and long-term high-fat diet (L-HFD) induce metabolic disorder, the underlying epigenetic mechanism is still unclear.

RESULTS: Here, we found that both 4 days of S-HFD and 10 weeks of L-HFD increased mRNA m[6]A level in epididymal white adipose tissue (eWAT) and impaired metabolic health. Interestingly, S-HFD activated transposable elements (TEs), especially endogenous retroviruses (ERVs) in eWAT, while L-HFD activated long interspersed elements (LINEs). Subsequently, we demonstrated that both S-HFD and L-HFD increased m[6]A level of Ehmt2 and decreased EHMT2 protein expression and H3K9me2 level, accounting for activation of ERVs and LINEs. Overexpression of EHMT2 in eWAT or inhibition of ERVs and LINEs by antiviral therapy improved metabolic health under HFD feeding. Notably, we found that both short-term and long-term HFD feeding increased Fimicutes/Bacteroidota ratio and decreased the gut microbiome health index. Fecal microbiota transplantation (FMT) experiments demonstrated that gut microbiota from S-HFD and L-HFD was responsible for increased m[6]A level in eWAT, resulting in glucose intolerance and insulin insensitivity. Furthermore, we identified that both S-HFD and L-HFD increased the abundance of the gut microbial metabolite homogentisic acid (HGA), and HGA level was positively correlated with unclassified_f__Lachnospiraceae which was both increased in S-HFD and L-HFD feeding mice. Administration of HGA increased the m[6]A level of Ehmt2 and decreased the EHMT2 protein expression and H3K9me2 level in eWAT, leading to metabolic disorder in mice.

CONCLUSIONS: Together, this study reveals a novel mechanism that S-HFD and L-HFD induce metabolism disorder through gut microbiota-HGA-m[6]A-Ehmt2-ERV/LINE signaling. These findings may provide a novel insight for prevention and treatment of metabolism disorder upon short-term or long-term dietary fat intake. Video Abstract.}, } @article {pmid40089059, year = {2025}, author = {Fan, J and Wu, Y and Wang, X and Ullah, H and Ling, Z and Liu, P and Wang, Y and Feng, P and Ji, J and Li, X}, title = {The probiotic enhances donor microbiota stability and improves the efficacy of fecal microbiota transplantation for treating colitis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.03.017}, pmid = {40089059}, issn = {2090-1224}, abstract = {INTRODUCTION: The stability and metabolic functionality of donor microbiota are critical determinants of fecal microbiota transplantation (FMT) efficacy in inflammatory bowel disease (IBD). While probiotics show potential to enhance microbiota resilience, their role in optimizing donor microbiota for FMT remains underexplored.

OBJECTIVES: This study investigated whether pretreatment of donor microbiota with L. plantarum GR-4 could improve FMT outcomes in a DSS-induced colitis model by modulating microbial stability, metabolic activity, and host-microbiome interactions.

METHODS: Donor mice received L. plantarum GR-4 for 3 weeks to generate modified FMT (MFMT). DSS-colitis mice were treated with MFMT, conventional FMT, or 5-aminosalicylic acid (5-ASA). Multi-omics analyses and functional assays (stress resistance, engraftment efficiency) were used to evaluate therapeutic mechanisms.

RESULTS: GR-4 pretreatment conferred three key advantages to donor microbiota: Ecological stabilization: 1. GR-4-driven acidification (pH 3.97 vs. 4.59 for LGG, p < 0.0001) enriched butyrogenic Butyricicoccus (73 % butyrate increase, p < 0.05) and improved stress resistance to bile acids/gastric conditions (1.25 × survival vs. FMT). 2. Metabolic reprogramming: GR-4 metabolized 25.3 % of tryptophan (vs. 10.3 % for LGG) to generate immunomodulatory indoles (ILA, IAA), activating aryl hydrocarbon receptor (AHR) signaling and upregulating anti-inflammatory IL-10/IL-22. 3. Bile acid remodeling: MFMT restored sulfolithocholic acid and β-MCA levels, outperforming FMT in resolving DSS-induced dysregulation. MFMT achieved an 83 % remission rate (vs. 50 % for FMT), enhanced gut barrier integrity, and reversed colitis-associated metabolic dysregulation (e.g., elevated spermidine, 7-sulfocholic acid). Probiotic preconditioning improved donor engraftment by 1.25 × and enriched success-associated taxa (Sporobacter, Butyricimonas), while suppressing pathogens (Clostridium papyrosolvens).

CONCLUSIONS: L. plantarum GR-4 optimizes donor microbiota via pH-driven niche engineering, immunometabolic reprogramming, and bile acid modulation, addressing key limitations of conventional FMT. The multi-targeted efficacy of MFMT, evidenced by superior remission rates and metabolic restoration, establishes this approach as a translatable strategy for IBD therapy. This study establishes probiotic-enhanced FMT as a paradigm for precision microbiome interventions.}, } @article {pmid40088964, year = {2025}, author = {Hajjeh, O and Rajab, I and Bdair, M and Saife, S and Zahran, A and Nazzal, I and AbuZahra, MI and Jallad, H and Abukhalil, MM and Hallak, M and Al-Said, OS and Al-Braik, R and Sawaftah, Z and Milhem, F and Almur, O and Saife, S and Aburemaileh, M and Abuhilal, A}, title = {Enteric nervous system dysfunction as a driver of central nervous system disorders: The Forgotten brain in neurological disease.}, journal = {Neuroscience}, volume = {572}, number = {}, pages = {232-247}, doi = {10.1016/j.neuroscience.2025.03.015}, pmid = {40088964}, issn = {1873-7544}, abstract = {The Enteric Nervous System (ENS), often called the "second brain," is a complex network of neurons and glial cells within the gastrointestinal (GI) tract. It functions autonomously while maintaining close communication with the central nervous system (CNS) via the gut-brain axis (GBA). ENS dysfunction plays a crucial role in neurodegenerative and neurodevelopmental disorders, including Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Disruptions such as altered neurotransmission, gut microbiota imbalance, and neuroinflammation contribute to disease pathogenesis. The GBA enables bidirectional communication through the vagus nerve, gut hormones, immune signaling, and microbial metabolites, linking gut health to neurological function. ENS dysregulation is implicated in conditions like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), influencing systemic and CNS pathology through neuroinflammation and impaired barrier integrity. This review highlights emerging therapeutic strategies targeting ENS dysfunction, including prebiotics, probiotics, fecal microbiota transplantation (FMT), and vagus nerve stimulation, which offer novel ways to modulate gut-brain interactions. Unlike previous perspectives that view the ENS as a passive disease marker, this review repositions it as an active driver of neurological disorders. By integrating advances in ENS biomarkers, therapeutic targets, and GBA modulation, this article presents a paradigm shift-emphasizing ENS dysfunction as a fundamental mechanism in neurodegeneration and neurodevelopmental disorders. This perspective paves the way for innovative diagnostics, personalized gut-targeted therapies, and a deeper understanding of the ENS's role in brain health and disease.}, } @article {pmid40087204, year = {2025}, author = {Lin, D and Howard, A and Raihane, AS and Di Napoli, M and Cáceres, E and Ortiz, M and Davis, J and Abdelrahman, AN and Divani, AA}, title = {Traumatic Brain Injury and Gut Microbiome: The Role of the Gut-Brain Axis in Neurodegenerative Processes.}, journal = {Current neurology and neuroscience reports}, volume = {25}, number = {1}, pages = {23}, pmid = {40087204}, issn = {1534-6293}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neurodegenerative Diseases/microbiology/physiopathology ; *Brain Injuries, Traumatic/microbiology/physiopathology/complications ; *Brain-Gut Axis/physiology ; Animals ; Dysbiosis ; Brain/physiopathology ; }, abstract = {PURPOSE OF REVIEW: A deeper understanding of the communication network between the gut microbiome and the central nervous system, termed the gut-brain axis (GBA), has revealed new potential targets for intervention to prevent the development of neurodegenerative disease associated with tramatic brain injury (TBI). This review aims to comprehensively examine the role of GBA post-traumatic brain injury (TBI).

RECENT FINDINGS: The GBA functions through neural, metabolic, immune, and endocrine systems, creating bidirectional signaling pathways that modulate brain and gastrointestinal (GI) tract physiology. TBI perturbs these signaling pathways, producing pathophysiological feedback loops in the GBA leading to dysbiosis (i.e., a perturbed gut microbiome, impaired brain-blood barrier, impaired intestinal epithelial barrier (i.e., "leaky gut"), and a maladaptive, systemic inflammatory response. Damage to the CNS associated with TBI leads to GI dysmotility, which promotes small intestinal bacterial overgrowth (SIBO). SIBO has been associated with the early stages of neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Many of the bacteria associated with this overgrowth promote inflammation and, in rodent models, have been shown to compromise the structural integrity of the intestinal mucosal barrier, causing malabsorption of essential nutrients and further exacerbating dysbiosis. TBI-induced pathophysiology is strongly associated with an increased risk of neurodegenerative diseases, including Parkinson's and Alzheimer's diseases, which represents a significant public health burden and challenge for patients and their families. A healthy gut microbiome has been shown to promote improved recovery from TBI and prevent the development of neurodegenerative disease, as well as other chronic complications. The role of the gut microbiome in brain health post-TBI demonstrates the potential for microbiome-targeted interventions to mitigate TBI-associated comorbidities. Promising new evidence on prebiotics, probiotics, diet, and fecal microbiota transplantation may lead to new therapeutic options for improving the quality of life for patients with TBI. Still, many of these preliminary findings must be explored further in clinical settings. This review covers the current understanding of the GBA in the setting of TBI and how the gut microbiome may provide a novel therapeutic target for treatment in this patient population.}, } @article {pmid40084003, year = {2025}, author = {Oliwa-Libumska, K and Jaworska-Czerwinska, A and Mallek-Grabowska, M and Wlodarski, R and Zuratynski, P and Kozlowski, B}, title = {Fecal microbiota transplantation in a patient hospitalized in the intensive care unit - Case report.}, journal = {Heliyon}, volume = {11}, number = {4}, pages = {e42793}, pmid = {40084003}, issn = {2405-8440}, abstract = {Clostridioides difficile infections are difficult and serious problem occurring in patients staying in intensive care units. In recent years, the number and severity of these infections, as well as the mortality rate, have been increasing, posing a serious epidemiological problem. This is caused, among other factors, by stressors, artificial nutrition, and sepsis, which lead to disturbances in the patients' microbiome. Basic method of treatment is antibiotic therapy, however some patients experience recurrences of the infection. Fecal Microbiota Transplantation (FMT) is one of the alternative methods used in treating recurring infections of Clostridioides difficile etiology (Clostridioides Difficile Infection, CDI). The presented case refers to a patient with severe pseudomembranous enterocolitis who underwent FMT twice. This report highlights the role of FMT in the treatment of severe Clostridioides difficile infections in critically ill patients.}, } @article {pmid40083791, year = {2025}, author = {, }, title = {Erratum: Integrative analysis of intestinal flora and untargeted metabolomics in attention-deficit/hyperactivity disorder.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1576969}, doi = {10.3389/fmicb.2025.1576969}, pmid = {40083791}, issn = {1664-302X}, abstract = {[This corrects the article DOI: 10.3389/fmicb.2025.1452423.].}, } @article {pmid40083245, year = {2025}, author = {Özdirik, B and Berger, H and Tonetti, FR and Cabré, N and Treichel, N and Clavel, T and Tacke, F and Sigal, M and Schnabl, B}, title = {Faecal Cytolysin is Associated With Worse Survival in Patients With Primary Sclerosing Cholangitis.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {45}, number = {4}, pages = {e16181}, doi = {10.1111/liv.16181}, pmid = {40083245}, issn = {1478-3231}, support = {OE821/1-1;Ta434/8-1;CRC1382Project-ID403224013//Deutsche Forschungsgemeinschaft/ ; R01AA24726;R37AA020703;U01AA026939;P30DK120515//National Institutes of Healthy (NIH)/ ; BX004594//Biomedical Laboratory Research & Development Service of the VA Office of Research and Development/ ; }, mesh = {Humans ; *Cholangitis, Sclerosing/mortality/microbiology ; *Feces/microbiology/chemistry ; Male ; Female ; Adult ; Middle Aged ; *Perforin/genetics/metabolism ; *RNA, Ribosomal, 16S/genetics ; Case-Control Studies ; Enterococcus faecalis/isolation & purification ; Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/microbiology/mortality ; Aged ; Liver Transplantation ; Virulence Factors/genetics ; }, abstract = {BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy without treatment options beyond liver transplantation. The gut-liver axis, especially the role of gut microbes, has emerged as a crucial pathway contributing to PSC pathogenesis. Recent research has revealed Enterococcus (E.) faecalis and its virulence factor cytolysin to increase mortality risk in patients with alcohol-associated hepatitis. Thus, we studied the role of enterococci, particularly E. faecalis and its virulence factor genes cytolysin and gelatinase, in faecal samples from patients with PSC.

METHODS: To assess the relevance of Enterococcus species, we performed 16S rRNA gene amplicon analysis in faecal samples from 60 patients with PSC. We validated our findings by qPCR of faecal microbial DNA in an extended cohort of 105 patients with PSC, 104 patients with inflammatory bowel disease (IBD) and 68 healthy subjects.

RESULTS: High-throughput 16S rRNA amplicon analysis revealed an increased relative abundance of enterococci in PSC patients compared with healthy controls and IBD patients, respectively, (p < 0.0001). PSC patients with high enterococci abundance had a decreased probability of transplant-free survival (p = 0.028). E. faecalis and its virulence factors cytolysin and gelatinase were more abundant in patients with PSC. Higher faecal cytolysin was associated with lower overall survival (p = 0.04), while survival was independent of gelatinase levels.

CONCLUSION: Our data highlight the association of E. faecalis and faecal cytolysin with lower survival in patients with PSC. These data should prompt further research into the pathogenic role of cytolysin-positive E. faecalis, and to explore its role as a potential therapeutic target.}, } @article {pmid40082770, year = {2025}, author = {Jahn, B and Bundo, M and Arvandi, M and Schaffner, M and Todorovic, J and Sroczynski, G and Knudsen, A and Fischer, T and Schiller-Fruehwirth, I and Öfner, D and Renner, F and Jonas, M and Kuchin, I and Kruse, J and Santamaria, J and Ferlitsch, M and Siebert, U}, title = {One in three adenomas could be missed by white-light colonoscopy - findings from a systematic review and meta-analysis.}, journal = {BMC gastroenterology}, volume = {25}, number = {1}, pages = {170}, pmid = {40082770}, issn = {1471-230X}, mesh = {Humans ; *Colonoscopy/methods ; *Adenoma/diagnostic imaging/diagnosis/pathology ; *Colorectal Neoplasms/diagnosis/pathology/diagnostic imaging ; Early Detection of Cancer/methods ; Missed Diagnosis/statistics & numerical data ; Diagnostic Errors/statistics & numerical data ; Light ; }, abstract = {BACKGROUND: White light (conventional) colonoscopy (WLC) is widely used for colorectal cancer screening, diagnosis and surveillance but endoscopists may fail to detect adenomas. Our goal was to assess and synthesize overall and subgroup-specific adenoma miss rates (AMR) of WLC in daily practice.

METHODS: We conducted a systematic review in MEDLINE, EMBASE, Cochrane Library, and grey literature on studies evaluating diagnostic WLC accuracy in tandem studies with novel-colonoscopic technologies (NCT) in subjects undergoing screening, diagnostic or surveillance colonoscopy. Information on study design, AMR overall and specific for adenoma size, histology, location, morphology and further outcomes were extracted and reported in standardized evidence tables. Study quality was assessed using the QUADAS-2 tool. Random-effects meta-analyses and meta-regression were performed to estimate pooled estimates for AMR with 95% confidence intervals (95% CI) and to explain heterogeneity.

RESULTS: Out of 5,963 identified studies, we included sixteen studies with 4,101 individuals in our meta-analysis. One in three adenomas (34%; 95% CI: 30-38%) was missed by WLC in daily practice individuals. Subgroup analyses showed significant AMR differences by size (36%, adenomas 1-5 mm; 27%, adenomas 6-9 mm; 12%, adenomas ≥ 10 mm), histology (non-advanced: 42%, advanced: 21%), morphology (flat: 50%, polypoid: 27%), but not by location (distal: 36%, proximal: 36%).

CONCLUSIONS: Based on our meta-analysis, one in three adenomas could be missed by WLC. This may significantly contribute to interval cancers. Our results should be considered in health technology assessment when interpreting sensitivity of fecal occult blood or other screening tests derived from studies using WLC as "gold standard".}, } @article {pmid40082445, year = {2025}, author = {Manns, MP and Bergquist, A and Karlsen, TH and Levy, C and Muir, AJ and Ponsioen, C and Trauner, M and Wong, G and Younossi, ZM}, title = {Primary sclerosing cholangitis.}, journal = {Nature reviews. Disease primers}, volume = {11}, number = {1}, pages = {17}, pmid = {40082445}, issn = {2056-676X}, mesh = {Humans ; *Cholangitis, Sclerosing/physiopathology/therapy/epidemiology/diagnosis/complications ; Liver Transplantation/methods ; Ursodeoxycholic Acid/therapeutic use ; }, abstract = {Primary sclerosing cholangitis (PSC) is a chronic biliary inflammation associated with periductular fibrosis of the intrahepatic and extrahepatic bile ducts leading to strictures, bacterial cholangitis, decompensated liver disease and need for liver transplantation. This rare focal liver disease affects all races and ages, with a predominance of young males. There is an up to 88% association with inflammatory bowel disease. Although the aetiology is unknown and the pathophysiology is poorly understood, PSC is regarded as an autoimmune liver disease based on a strong immunogenetic background. Further, the associated risk for various malignancies, particularly cholangiocellular carcinoma, is also poorly understood. No medical therapy has been approved so far nor has been shown to improve transplant-free survival. However, ursodeoxycholic acid is widely used since it improves the biochemical parameters of cholestasis and is safe at low doses. MRI of the biliary tract is the primary imaging technology for diagnosis. Endoscopic interventions of the bile ducts should be limited to clinically relevant strictures for balloon dilatation, biopsy and brush cytology. End-stage liver disease with decompensation is an indication for liver transplantation with recurrent PSC in up to 38% of patients. Several novel therapeutic strategies are in various stages of development, including apical sodium-dependent bile acid transporter and ileal bile acid transporter inhibitors, integrin inhibitors, peroxisome proliferator-activated receptor agonists, CCL24 blockers, recombinant FGF19, CCR2/CCR5 inhibitors, farnesoid X receptor bile acid receptor agonists, and nor-ursodeoxycholic acid. Manipulation of the gut microbiome includes faecal microbiota transplantation. This article summarizes present knowledge and defines unmet medical needs to improve quality of life and survival.}, } @article {pmid40081233, year = {2025}, author = {Yang, S and Pan, H and Wang, T and Zhou, X and Fan, L and Xiao, H and Zhou, Z and Xiao, Y and Shi, D}, title = {Bacillus paralicheniformis-mediated gut microbiota promotes M2 macrophage polarization by inhibiting P38 MAPK signaling to alleviate necrotizing enterocolitis and apoptosis in mice.}, journal = {Microbiological research}, volume = {296}, number = {}, pages = {128136}, doi = {10.1016/j.micres.2025.128136}, pmid = {40081233}, issn = {1618-0623}, abstract = {Clostridial necrotizing enterocolitis is a severe gastrointestinal disease induced by Clostridium, strongly associated with intestinal dysbiosis. Fecal microbiota transplantation (FMT) has proven effective in treating gastrointestinal diseases by remodeling intestinal microbial homeostasis. However, it remains unclear whether FMT from donors with beneficial microbiota can improve the recipient's intestinal function more efficiently. This study found that probiotic Bacillus paralicheniformis SN-6-mediated gut microbiota effectively prevent Clostridial necrotizing enteritis and explored the underlying molecular mechanisms. Data demonstrated that SN-6 altered gut microbiota composition, ameliorated Clostridium perfringens-induced intestinal microbiota dysbiosis and metabolic reprogramming, particularly enhancing tryptophan metabolism. This led to a marked reduction in intestinal barrier damage and inflammation. FMT from SN-6-treated mice reduced jejunal inflammation in Clostridium perfringens-infected mice, strengthened jejunal barrier and enriched beneficial bacteria, such as Lactobacillus, Blautia, Akkermansia. Furthermore, 3-indoleacetic acid (IAA), a metabolite enriched by SN-6, activated aryl hydrocarbon receptor (AhR), suppressed the P38 mitogen-activated protein kinase (P38 MAPK) signaling, and drove macrophage polarization from M0 to M2-type, thereby reducing apoptosis and excessive inflammation. This study highlights Bacillus paralicheniformis SN-6 as a key modulator of intestinal immunomodulation via the gut microbiota-IAA-AhR-P38 MAPK axis, offering a potential therapeutic target for preventing and controlling clostridial necrotizing enteritis.}, } @article {pmid40079755, year = {2025}, author = {Menozzi, E and Schapira, AHV and Borghammer, P}, title = {The Gut-Brain Axis in Parkinson disease: Emerging Concepts and Therapeutic Implications.}, journal = {Movement disorders clinical practice}, volume = {}, number = {}, pages = {}, doi = {10.1002/mdc3.70029}, pmid = {40079755}, issn = {2330-1619}, support = {ASAP-000420//Aligning Science Across Parkinson's/ ; MR/T046007/1//EU Joint Programme - Neurodegenerative Disease Research/ ; }, abstract = {BACKGROUND: The gut-brain axis, i.e. the bidirectional communication system between the gut and the brain, has become of central importance in Parkinson disease (PD) research over the past 20 years.

AIMS: We aimed to describe the milestones of the gut-brain axis research in PD and the development of theories proposing the involvement of the gastrointestinal tract in PD pathogenesis.

METHODS: We searched PubMed using the terms 'gut-brain axis' AND 'Parkinson disease', and selected relevant articles to provide the foundation for reconstructing an historical overview of the gut-brain axis research in PD.

RESULTS: Mounting evidence from preclinical, clinical and post-mortem studies suggests that a subgroup of PD patients present with a range of prodromal symptoms (e.g., autonomic dysfunction, rapid eye movement sleep behaviour disorder) which reflect initial accumulation and later spread of pathological α-synuclein rostrally from the gastrointestinal tract ("body-first" PD). Through neural connections along the gut-brain axis, pathological α-synuclein may spread to the brain, producing clinically manifest disease. Recently, two mechanisms involving the gut-brain axis have attracted increasing attention for their role in PD pathogenesis and progression, namely the perturbation of the composition of the microorganisms living in the gut (the gut microbiome), and the dysfunction of enteroendocrine cells.

CONCLUSION: Treatments targeting the gut-brain axis, especially the gut microbiome and the enteroendocrine cells pathway, could potentially slow disease progression or even prevent disease onset. Among these, pre/probiotics, faecal microbiota transplantation, and glucagon-like peptide-1 receptor agonists, have entered advanced stages of clinical trials in humans and shown potential symptomatic and disease-modifying effects.}, } @article {pmid40078367, year = {2025}, author = {Ullah, H and Arbab, S and Chang, C and Bibi, S and Muhammad, N and Rehman, SU and Suleman, and Ullah, I and Hassan, IU and Tian, Y and Li, K}, title = {Gut microbiota therapy in gastrointestinal diseases.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1514636}, pmid = {40078367}, issn = {2296-634X}, abstract = {The human gut microbiota, consisting of trillions of microorganisms, plays a crucial role in gastrointestinal (GI) health and disease. Dysbiosis, an imbalance in microbial composition, has been linked to a range of GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and colorectal cancer. These conditions are influenced by the interactions between the gut microbiota, the host immune system, and the gut-brain axis. Recent research has highlighted the potential for microbiome-based therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications, to restore microbial balance and alleviate disease symptoms. This review examines the role of gut microbiota in the pathogenesis of common gastrointestinal diseases and explores emerging therapeutic approaches aimed at modulating the microbiome. We discuss the scientific foundations of these interventions, their clinical effectiveness, and the challenges in their implementation. The review underscores the therapeutic potential of microbiome-targeted treatments as a novel approach to managing GI disorders, offering personalized and alternative options to conventional therapies. As research in this field continues to evolve, microbiome-based interventions hold promise for improving the treatment and prevention of gastrointestinal diseases.}, } @article {pmid40077957, year = {2025}, author = {Ma, Z and Wen, X and Zhang, Y and Ai, Z and Zhao, X and Dong, N and Dou, X and Shan, A}, title = {Thymol Alleviates Colitis by Modulating Intestinal Barrier Damage, Gut Microbiota, and Amino Acid Metabolic Pathways.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c10406}, pmid = {40077957}, issn = {1520-5118}, abstract = {Thymol (THY) is a phenolic monoterpene compound that has garnered attention due to its various biological properties, including antioxidant, anti-inflammatory, and immune-regulatory effects. The purpose of this study was to determine the therapeutic and protective effects of THY in colitic mice, with a particular focus on the mechanisms involving gut microbiota. The results showed that early intervention with THY (40 and 80 mg/kg) not only alleviated the clinical symptoms and colonic damage in mice with dextran sodium sulfate (DSS)-induced colitis but also suppressed the colonic production of inflammatory cytokines (IL-1β, IL-6, and IL-18) and enhanced the expression of mucins (MUC1 and MUC2) and trefoil factor family 3 (TFF3), thereby improving the integrity of the intestinal epithelial barrier. In addition, THY altered the composition of the gut microbiota in colitis mice by increasing the abundance of Bacteroides and reducing the abundance of Proteobacteria. Fecal microbial transplantation (FMT) results demonstrated that FM from THY donor mice significantly improved symptoms of inflammatory bowel disease (IBD), confirming the crucial role of the gut microbiota. Metagenomic and untargeted metabolomic studies found that the characteristic microbiota of THY is Prevotellaceae, and THY significantly upregulated the amino acid metabolic pathways related to arginine and proline metabolism, arginine biosynthesis, and glycerophospholipid metabolism. In summary, THY holds significant potential as a functional additive to enhance host intestinal activity.}, } @article {pmid40077671, year = {2025}, author = {Gao, Y and Borjihan, Q and Zhang, W and Li, L and Wang, D and Bai, L and Zhu, S and Chen, Y}, title = {Complex Probiotics Ameliorate Fecal Microbiota Transplantation-Induced IBS in Mice via Gut Microbiota and Metabolite Modulation.}, journal = {Nutrients}, volume = {17}, number = {5}, pages = {}, pmid = {40077671}, issn = {2072-6643}, support = {2022-Science and Technology Xing Meng-Quality improvement-02//the Science and Technology Xing Meng action focus project of Inner Mongolia Autonomous Region/ ; 2022-Science and Technology Xing Meng-Quality improvement-02//the Science and Technology Xing Meng action focus project of Inner Mongolia Autonomous Region/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Irritable Bowel Syndrome/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Probiotics/pharmacology ; Mice ; *Feces/microbiology ; *Disease Models, Animal ; Mice, Inbred C57BL ; Male ; Dysbiosis/therapy ; Serotonin/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism ; Acetic Acid ; Constipation/therapy/microbiology/metabolism ; Butyric Acid/metabolism ; Tryptophan/metabolism ; }, abstract = {Background/Objectives: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Emerging evidence implicates gut microbiota dysbiosis in IBS pathogenesis, and probiotic interventions targeting microbial modulation hold therapeutic promise. Methods: this study used fecal microbiota transplantation to establish a mouse model of IBS before evaluating the effects of the complex probiotic by using metagenomics and targeted metabolomics to explore the potential mechanism. Results: After 14 days, the probiotic relieved constipation, reduced inflammation and intestinal permeability, lowered 5-HT levels and increased serotonin transporter (SERT) expression in tissues. Metagenomic analysis showed a reduced inflammation-related species abundance. It also decreased fecal butyric acid, acetic acid and tryptophan levels in IBS mice. Conclusions: The probiotic complex effectively alleviated IBS symptoms in mice by modulating gut microbiota and fecal metabolites, providing insights for future IBS research and treatment.}, } @article {pmid40076864, year = {2025}, author = {Hatamnejad, MR and Medzikovic, L and Dehghanitafti, A and Rahman, B and Vadgama, A and Eghbali, M}, title = {Role of Gut Microbial Metabolites in Ischemic and Non-Ischemic Heart Failure.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, pmid = {40076864}, issn = {1422-0067}, support = {R01 HL174472/HL/NHLBI NIH HHS/United States ; R01HL147586/NH/NIH HHS/United States ; R01HL159865/NH/NIH HHS/United States ; 24CDA1263497//American Heart Association/ ; R01 HL162124/HL/NHLBI NIH HHS/United States ; R01HL162124/NH/NIH HHS/United States ; R01 HL147586/HL/NHLBI NIH HHS/United States ; R01 HL159865/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Heart Failure/metabolism ; Animals ; Hydrogen Sulfide/metabolism ; Fatty Acids, Volatile/metabolism ; Myocardial Ischemia/metabolism/microbiology ; Methylamines/metabolism ; }, abstract = {The effect of the gut microbiota extends beyond their habitant place from the gastrointestinal tract to distant organs, including the cardiovascular system. Research interest in the relationship between the heart and the gut microbiota has recently been emerging. The gut microbiota secretes metabolites, including Trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids (BAs), indole propionic acid (IPA), hydrogen sulfide (H2S), and phenylacetylglutamine (PAGln). In this review, we explore the accumulating evidence on the role of these secreted microbiota metabolites in the pathophysiology of ischemic and non-ischemic heart failure (HF) by summarizing current knowledge from clinical studies and experimental models. Elevated TMAO contributes to non-ischemic HF through TGF-ß/Smad signaling-mediated myocardial hypertrophy and fibrosis, impairments of mitochondrial energy production, DNA methylation pattern change, and intracellular calcium transport. Also, high-level TMAO can promote ischemic HF via inflammation, histone methylation-mediated vascular fibrosis, platelet hyperactivity, and thrombosis, as well as cholesterol accumulation and the activation of MAPK signaling. Reduced SCFAs upregulate Egr-1 protein, T-cell myocardial infiltration, and HDAC 5 and 6 activities, leading to non-ischemic HF, while reactive oxygen species production and the hyperactivation of caveolin-ACE axis result in ischemic HF. An altered BAs level worsens contractility, opens mitochondrial permeability transition pores inducing apoptosis, and enhances cholesterol accumulation, eventually exacerbating ischemic and non-ischemic HF. IPA, through the inhibition of nicotinamide N-methyl transferase expression and increased nicotinamide, NAD+/NADH, and SIRT3 levels, can ameliorate non-ischemic HF; meanwhile, H2S by suppressing Nox4 expression and mitochondrial ROS production by stimulating the PI3K/AKT pathway can also protect against non-ischemic HF. Furthermore, PAGln can affect sarcomere shortening ability and myocyte contraction. This emerging field of research opens new avenues for HF therapies by restoring gut microbiota through dietary interventions, prebiotics, probiotics, or fecal microbiota transplantation and as such normalizing circulating levels of TMAO, SCFA, BAs, IPA, H2S, and PAGln.}, } @article {pmid40076603, year = {2025}, author = {Wang, K and Hu, Y and Wu, Y and Xu, J and Zhao, Y and Yang, J and Li, X}, title = {The Therapeutic Potential of Gut-Microbiota-Derived Metabolite 4-Phenylbutyric Acid in Escherichia coli-Induced Colitis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, pmid = {40076603}, issn = {1422-0067}, support = {32360904//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis/microbiology/drug therapy/metabolism/chemically induced ; Mice ; *Escherichia coli ; *Phenylbutyrates/pharmacology/therapeutic use ; *Escherichia coli Infections/microbiology/drug therapy ; *Fecal Microbiota Transplantation ; *Toll-Like Receptor 4/metabolism ; *Myeloid Differentiation Factor 88/metabolism/genetics ; Disease Models, Animal ; Cytokines/metabolism ; NF-kappa B/metabolism ; Cattle ; Signal Transduction/drug effects ; Female ; }, abstract = {Pathogenic Escherichia coli (E. coli) is a widely distributed pathogen that can cause varying degrees of zoonotic diseases, and infected animals often experience intestinal inflammation accompanied by diarrhea and dysbiosis. Previously, for the first time, we isolated Escherichia coli primarily of type B2 from a large-scale dairy farm in Yunnan, China. The 16s rRNA sequencing showed significant differences in the gut microbiota of calves infected with B2 E. coli, with higher abundance of harmful bacteria and lower abundance of beneficial bacteria compared with healthy calves. The metabolomics indicated that the concentrations of oxoadipic acid, 16-oxopalmitate, oerillyl alcohol, palmitoleic acid, and 4-phenylbutyrate (4-PBA) were significantly higher in the healthy group than in the infected group. The mouse model was established to assess the regulatory effect of 4-PBA on E. coli-induced colitis. Both oral administration of 4-PBA and fecal microbiota transplantation (FMT) had strong resistance to E. coli infection, improved survival rate and body weight, reduced intestinal tissue damage, decreased the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and restrained TLR4/MyD88/NF-κB pathway. Our study demonstrated that 4-PBA could relieve E. coli-induced colitis by improving gut microbiota structure and inhibiting the expression of pro-inflammatory cytokines through the TLR4/MyD88/NF-κB pathway. The present finding reveals the therapeutic potential of the gut-microbiota-derived metabolite 4-PBA for the treatment of colitis caused by E. coli.}, } @article {pmid39140311, year = {2025}, author = {Durkee-Shock, J and Cohen, A and Maghzian, N and Pezzella, G and Jensen-Wachspress, M and Hostal, A and Barton, K and Gangler, K and Dávila Saldaña, BJ and Chaimongkol, N and Bollard, CM and Sosnovtsev, SV and Cohen, J and Nagata, BM and Alves, DA and Ghosh, R and Seifert, BA and Freeman, A and Gonzalez, C and Notarangelo, LD and Green, KY and Keller, MD}, title = {Reconstitution of Norovirus-Specific T-Cell Responses Following Hematopoietic Stem Cell Transplantation in Patients With Inborn Errors of Immunity and Chronic Norovirus Infection.}, journal = {The Journal of infectious diseases}, volume = {231}, number = {3}, pages = {773-783}, doi = {10.1093/infdis/jiae398}, pmid = {39140311}, issn = {1537-6613}, support = {R01HL152161/HL/NHLBI NIH HHS/United States ; //Jeffrey Modell Foundation/ ; }, mesh = {Humans ; *Norovirus/immunology/genetics ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Caliciviridae Infections/immunology ; Male ; *Guanine Nucleotide Exchange Factors/genetics/deficiency/immunology ; T-Lymphocytes/immunology ; X-Linked Combined Immunodeficiency Diseases/immunology/genetics ; Infant ; Viral Load ; Chronic Disease ; Feces/virology ; Antibodies, Viral/blood ; B-Lymphocytes/immunology ; Persistent Infection/immunology ; Child, Preschool ; }, abstract = {BACKGROUND: Chronic norovirus infection (CNI) causes significant morbidity in immunocompromised patients. No effective prevention or treatment currently exists.

METHODS: Two patients with inborn errors of immunity, X-linked severe combined immunodeficiency (X-SCID) and DOCK8 deficiency, were followed longitudinally for clinical course, immune reconstitution, norovirus-specific T-cell (NST) response, B-cell reconstitution, and norovirus-specific antibody production. Samples were obtained in the peri-hematopoietic stem cell transplant (HSCT) setting before and after CNI clearance. The norovirus strain causing CNI was followed longitudinally for norovirus stool viral loads and sequencing.

RESULTS: The noroviruses were identified as GII.4 Sydney[P4 New Orleans] in 1 patient and GII.17[P17] in the other. An exacerbation of diarrhea post-HSCT in the patient with X-SCID was consistent with norovirus infection but not with graft-versus-host disease on pathologic samples. Both patients recovered polyfunctional NSTs in the CD4 and CD8 T-cell compartments that recognized multiple norovirus structural and nonstructural viral antigens. T-cell responses were minimal during active CNI but detectable after resolution. Mapping of NST responses between the patient with DOCK8 deficiency and his matched sibling donor were nearly identical. B-cell reconstitution or new endogenous antibody production for immunoglobulin A or immunoglobulin G was not observed.

CONCLUSIONS: This report is the first to demonstrate reconstitution of NST immunity after HSCT closely temporally aligned with clearance of CNI, suggesting that cellular immunity is sufficient for norovirus clearance.}, } @article {pmid40075967, year = {2025}, author = {Luo, S and Huang, X and Chen, S and Li, J and Wu, H and He, Y and Zhou, L and Liu, B and Feng, J}, title = {The Gut Microbiota of the Greater Horseshoe Bat Confers Rapidly Corresponding Immune Cells in Mice.}, journal = {Animals : an open access journal from MDPI}, volume = {15}, number = {5}, pages = {}, pmid = {40075967}, issn = {2076-2615}, support = {202311439011//College Students' Innovative Entrepreneurial Training Plan Program/ ; }, abstract = {BACKGROUND: Emerging infectious diseases threaten human and animal health, with most pathogens originating from wildlife. Bats are natural hosts for many infectious agents. Previous studies have demonstrated that changes in some specific genes in bats may contribute to resistance to viral infections, but they have mostly overlooked the immune function of the bat gut microbiota.

AIMS: In this study, we used fecal transplants to transfer the gut microbiota from the Greater Horseshoe Bat (Rhinolophus ferrumequinum) into mice treated with antibiotics. The gut microbiota changes in mice were detected using 16S rRNA high-throughput sequencing technology. Flow cytometry was used to detect changes in associated immune cells in the spleen and mesenteric lymph nodes of the mice.

RESULTS: The results showed that the gut microbiota of mice showed characteristics of some bat gut microbiota. The Greater Horseshoe Bat's gut microbiota changed some immune cells' composition in the spleen and mesenteric lymph nodes of mice and also conferred a faster and higher proportion of natural killer cell activation.

CONCLUSION: This result provides new evidence for the regulatory immune function of bat gut microbiota and contributes to a deeper insight into the unique immune system of bats.}, } @article {pmid40075266, year = {2025}, author = {Cao, H and Xu, J and Wang, H and Yi, W and Yang, D and Yang, J and Sun, J and Wang, Y and Zhang, F and Yan, J and Li, D}, title = {Fecal microbiota transplantation mitigates postdieting weight regain in mice by modulating the gut-liver axis.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {135}, pmid = {40075266}, issn = {1471-2180}, support = {2023YFF1104305//National Key Research and Development Program of China/ ; 2022YFF1100601//National Key Research and Development Program of China/ ; K2023004//Key Research project of Health Commission of Jiangsu Province/ ; M2021055//Key Research project of Health Commission of Jiangsu Province/ ; Y2021001//Wuxi Science and Technology Bureau, "Taihu Light" Science and Technology Research program/ ; K20221026//Wuxi Science and Technology Bureau, "Taihu Light" Science and Technology Research program/ ; CXTD2021003//Key discipline construction program of Wuxi Commission of Health/ ; KX-23-B050//Soft Science Project of Wuxi Science and Technology Association/ ; KX-23-C196//Soft Science Project of Wuxi Science and Technology Association/ ; YJZ202305//Medical research projects in research-oriented hospitals of Affiliated Hospital of Jiangnan University/ ; HB2023062//"Shuangbai Talents" research program of Wuxi Commission of Health/ ; HB2023063//"Shuangbai Talents" research program of Wuxi Commission of Health/ ; HB2023061//"Shuangbai Talents" research program of Wuxi Commission of Health/ ; LCYJ202347//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; LCYJ202310//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; LCYJ202322//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; LCYJ202303//Clinical Research and translational medicine research program of Affiliated Hospital of Jiangnan University/ ; BK20210468//Natural Science Foundation of Jiangsu Province/ ; BK20210060//Natural Science Foundation of Jiangsu Province/ ; 82370809//National Natural Science Foundation of China/ ; 32101033//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Mice ; *Weight Gain ; *Liver/metabolism ; Male ; Bacteria/classification/isolation & purification/genetics/metabolism ; Mice, Inbred C57BL ; Feces/microbiology ; Dysbiosis/therapy/microbiology ; Fatty Acids, Volatile/metabolism ; Lipid Metabolism ; }, abstract = {BACKGROUND: Dysbiosis of the microbiome is strongly associated with weight rebound after dieting. However, the interactions between the host and microbiome and their relevance to the pathogenesis of post-diet weight rebound remain unclear.

PURPOSE: This study aimed to evaluate the effects of fecal microbiota transplantation (FMT) on post-diet weight regain and to investigate the underlying mechanisms by which FMT inhibits weight regain.

METHODS: FMT was administered once daily to mice for 5 weeks. Gas chromatography tandem mass spectrometry was employed to analyze short-chain fatty acid levels in serum, ultrahigh-performance liquid chromatography tandem mass spectrometry was utilized for analyzing hepatic lipid metabolites, and shotgun metagenomic sequencing was applied to examine the intestinal microbiome.

RESULTS: FMT reduced weight regain and prevented lipid accumulation in both liver and adipose tissue while also improving glucose intolerance in mice. Furthermore, FMT increased the abundance of Enterorhabdus caecimuris and decreased the abundances of Burkholderiales, Sutterellaceae, Turicimonas muris, Bacteroides stercorirosoris, and Acetivibrio ethanolgignens within the gut microbiota. Additionally, elevated propionic acid levels and significant alterations in hepatic lipid metabolites were observed following FMT administration.

CONCLUSIONS: Our findings demonstrate that FMT effectively mitigates post-diet weight regain and associated complications. These effects are mediated through interactions between the gut microbiota and the liver via the gut-propionic acid-liver axis.

CLINICAL TRIAL NUMBER: Not applicable.}, } @article {pmid40074992, year = {2025}, author = {Bakhshandi, AK and Minasazi, A and Yeganeh, O and Behi, M}, title = {Therapeutic potential of microbiota modulation in psoriasis: current evidence and future directions.}, journal = {Archives of dermatological research}, volume = {317}, number = {1}, pages = {561}, pmid = {40074992}, issn = {1432-069X}, mesh = {*Psoriasis/immunology/therapy/microbiology ; Humans ; *Probiotics/therapeutic use ; *Dysbiosis/immunology/therapy/microbiology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; Skin/microbiology/immunology/pathology ; Quality of Life ; }, abstract = {The human microbiota plays a significant role in health and the development of autoimmune diseases by maintaining gut-skin homeostasis through diverse microbial communities. Dysbiosis, or imbalance in these communities, is increasingly recognized as a contributing factor in the pathogenesis of autoimmune and inflammatory diseases, including psoriasis. Psoriasis is characterized by immune dysregulation, leading to red and scaly plaques that significantly reduce patients' quality of life. Current evidence highlights the gut microbiota's critical role in driving immune responses and chronic inflammation associated with psoriasis. Therapeutic strategies aimed at restoring microbial balance, such as probiotics, have demonstrated promise in reducing disease severity. Additionally, fecal microbiota transplantation (FMT) has emerged as a novel intervention, with early studies suggesting its potential to alleviate symptoms by correcting gut dysbiosis. These approaches underscore the importance of microbiota-targeted therapies in addressing the systemic nature of psoriasis and pave the way for advancements in personalized treatment strategies.}, } @article {pmid39461459, year = {2024}, author = {Attauabi, M and Madsen, GR and Bendtsen, F and Seidelin, JB and Burisch, J}, title = {Multidimensional Patient-Reported Outcomes and Quality of Life at Diagnosis of IBD: A Population-Based Inception Cohort Study.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.08.047}, pmid = {39461459}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Patient-reported outcomes (PROs) are pivotal in assessing treatment efficacy and estimating the burden of inflammatory bowel diseases (IBDs). We investigated PROs at the time of IBD diagnosis.

METHODS: The Short Inflammatory Bowel Disease Questionnaire (SIBDQ), IBD Disability Index (IBD-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and disease activity-related PROs were assessed in the Copenhagen IBD Inception Cohort, a prospective, population-based cohort of patients newly diagnosed with IBD between May 2021 and May 2023.

RESULTS: A total of 203 ulcerative colitis (UC) and 116 Crohn's disease (CD) patients were recruited. At diagnosis, 160 (78.8%) and 99 (85.3%) patients with UC and CD, respectively, reported moderate-to-severe impairment in at least 1 PRO (P = .18), with 89 (43.8%) and 74 (63.8%), respectively, reporting moderate-to-severe impairment in at least 2 PROs (P < .01). Being female, the disease extent of UC, and extraintestinal manifestations were associated with impaired PROs. There were no differences found according to CD phenotype. FACIT-F, IBD-DI, and SIBDQ scores showed weak, but significant, correlations with the Mayo endoscopic score in UC, and the FACIT-F score with C-reactive protein. In CD, SIBDQ, IBD-DI, and FACIT-F correlated moderately with C-reactive protein and fecal calprotectin but not with the endoscopic severity of CD. None of the PROs correlated with iron, ferritin, or vitamin D levels. Among the most prevalent symptoms reported were fatigue, abdominal pain, urgency, and passing of blood in both CD and UC.

CONCLUSIONS: We found a substantial patient-reported disease burden in newly diagnosed IBD, underscoring the importance of vigilant PRO monitoring in clinical practice.}, } @article {pmid40074633, year = {2025}, author = {Le, PH and Yeh, YM and Chen, YC and Chen, CL and Tsou, YK and Chen, CC and Chiu, CT and Chiu, CH}, title = {Fecal microbiota transplantation for vancomycin-resistant Clostridium innocuum infection in inflammatory bowel disease: A pilot study evaluating safety and clinical and microbiota outcome.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jmii.2025.03.004}, pmid = {40074633}, issn = {1995-9133}, abstract = {BACKGROUND: Clostridium innocuum is a vancomycin-resistant pathobiome associated with poor clinical outcomes in inflammatory bowel disease (IBD). In ulcerative colitis (UC), it correlates with reduced remission rates, while in Crohn's disease (CD), it is linked to creeping fat formation and intestinal strictures. Notably, some patients experience refractory or recurrent C. innocuemailum infections despite metronidazole treatment. This study evaluates the safety and efficacy of single-dose fecal microbiota transplantation (FMT) in IBD patients with refractory or recurrent C. innocuum infections.

METHODS: We conducted a feasibility pilot study involving seven IBD patients (3 CD, 4 UC) with refractory (n = 5) or recurrent (n = 2) C. innocuum infections following metronidazole treatment. Patients underwent single-dose FMT and were monitored for six months.

RESULTS: No adverse events were recorded. All participants demonstrated improved disease activity post-FMT, as assessed by the Crohn's Disease Activity Index and Mayo Score. However, a mild increase in symptom severity was noted at six months. Follow-up cultures showed persistent C. innocuum infection in one patient and asymptomatic recurrence in another at three months. Alpha diversity of the gut microbiome increased post-FMT, and Bray-Curtis dissimilarity analysis revealed a microbiota composition more similar to that of the donor.

CONCLUSION: Single-dose FMT appears to be a safe and feasible therapeutic approach for refractory or recurrent C. innocuum infections in IBD patients, with potential benefits in disease activity and microbiome restoration. Further studies are warranted to optimize long-term outcomes.}, } @article {pmid40072575, year = {2025}, author = {Habeeb, TAAM and Chiaretti, M and Kryvoruchko, IA and Pesce, A and Kechagias, A and Elias, AA and Adam, AAM and Gadallah, MA and Ali Ahmed, SM and Khyrallh, A and Alsayed, MH and Tharwat Kamel Awad, E and Elshafey, MH and Abo Alsaad, MI and Ali, AK and Elbelkasi, H and Abou Zaid, MA and Youssef, HAA and Al-Zamek, MMF and Fiad, A and Elshahidy, TM and Elballat, MR and El Taher, AK and Mohamed, MMM and AboZeid, AK and Mansour, MI and Yassin, MA and Arafa, AS and Lotfy, M and Mousa, B and Atef, B and Naguib, SM and Heggy, IA and Elnemr, M and Zaitoun, MA and AbdAllah, ES and Moussa, MS and Hamed, AEM and Elsayed, RS}, title = {Mucosal advancement flap versus ligation of the inter-sphincteric fistula tract for management of trans-sphincteric perianal fistulas in the elderly: a retrospective study.}, journal = {International journal of colorectal disease}, volume = {40}, number = {1}, pages = {61}, pmid = {40072575}, issn = {1432-1262}, mesh = {Humans ; Aged ; Retrospective Studies ; Male ; *Rectal Fistula/surgery ; Female ; *Surgical Flaps ; *Anal Canal/surgery/physiopathology ; *Recurrence ; Ligation ; *Fecal Incontinence/etiology ; Middle Aged ; Risk Factors ; Treatment Outcome ; Postoperative Complications/etiology ; Intestinal Mucosa/surgery ; }, abstract = {PURPOSE: There is no consensus on the standard approach for trans-sphincteric perianal fistulas (TPAF) in the elderly population. The most commonly used sphincter-saving procedures are ligation of the inter-sphincteric fistula tract (LIFT) and mucosal advancement flap (MAF). We aimed to evaluate the incidence and risk factors for recurrence and incontinence in elderly patients with TPAF using both approaches.

METHODS: This retrospective study included 257 patients who underwent LIFT (136 patients) or MAF (121 patients) for de novo and cryptoglandular TPAF between July 2018 and July 2021. Recurrent fistulas were clinically and radiologically detected using MRI. Postoperative incontinence was evaluated using the Wexner score and anorectal manometry. Logistic regression analysis was used to detect the risks of recurrence and incontinence.

RESULTS: The median ages of the patients were 68 (64, 74) and 68 (65, 74) years in the LIFT and MAF groups, respectively. Higher recurrence rates were observed after LIFT (17 (12.5%)) than after MAF (13 (10.7%)), but the difference was not statistically significant (P = 0.662). Postoperative incontinence was observed in 18 patients (13.2%) and seven patients (5.8%) in the LIFT and MAF groups, respectively (P = 0.044). The predictors for fistula recurrence were smoking (OR, 75.52; 95% CI, 1.02 to 5611.35; P = 0.049), length of tract (OR, 17.3; 95% CI, 1.49 to 201.13; P = 0.023), and CD classification (OR, 7.08; 95% CI, 1.51 to 33.14; P = 0.013). A low Charlson comorbidity index score (≤ 5) (OR, 0.68; 95% CI, 0.47 to 0.99; P = 0.046) and high postoperative mean squeeze anal pressure (OR, 0.97; 95% CI, 0.95 to 0.99; P = 0.001) were significant factors associated with reduced risk of incontinence. In particular, LIFT was associated with a significantly higher risk of incontinence than MAF (OR, 2.089; 95% CI, 1.006 to 4.33; P = 0.04).

CONCLUSIONS: The healing rates of MAF and LIFT procedures did not differ significantly; however, continence was significantly better after MAF. MAF should be added to the guidelines as a good option for the treatment of TPAF in elderly patients.

TRIAL REGISTRATION: The study was registered as a clinical trial www.

CLINICALTRIALS: gov (NCT06616662).}, } @article {pmid40072345, year = {2025}, author = {Chen, M and Song, Y and Pan, J and Liu, S and Zheng, X}, title = {Effects of faecal microbiota transplantation supplemented with inulin on early immunity and immune organ histomorphology in chickens.}, journal = {British poultry science}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/00071668.2025.2458581}, pmid = {40072345}, issn = {1466-1799}, abstract = {1. Faecal microbiota transplantation (FMT) is a technique that promotes gut microbiota diversity and abundance by transplantation of faeces into a recipient's gastrointestinal tract via multiple routes.2. Inulin, a plant polysaccharide, is a natural functional dietary fibre found in a variety of plants, including vegetables and fruits. Inulin can inhibit pathogenic bacterial growth by lowering pH, promote mineral absorption and improve intestinal barrier integrity.3. In this study 90 one-day-old chicks were randomly into three groups; control (CON) group was fed a basic diet; FMT group fed two diets containing 40 ml faecal microbial suspension; and INU group fed a diet containing 1.5% inulin and 40 ml faecal microbial suspension.4. Administering the FMT mixed with inulin effectively reduced blood levels of IL-1β, IL-4 and IL-6, promoted the growth of thymus, bursa of Fabricius and spleen. In addition, it enhanced intestinal barrier function, increased intestinal goblet cells and Paneth cells production, promoted probiotic colonisation and butyrate formation and reduced intestinal inflammation.5. In summary, inulin mixed with FMT promoted the growth of the bursa of Fabricius, thymus and spleen as well as facilitated early growth of chick by promoting intestinal health, reducing inflammation and boosting chick immunity.}, } @article {pmid40072088, year = {2025}, author = {Świdnicka-Siergiejko, A and Daniluk, J and Miniewska, K and Daniluk, U and Guzińska-Ustymowicz, K and Pryczynicz, A and Dąbrowska, M and Rusak, M and Ciborowski, M and Dąbrowski, A}, title = {Inflammatory Stimuli and Fecal Microbiota Transplantation Accelerate Pancreatic Carcinogenesis in Transgenic Mice, Accompanied by Changes in the Microbiota Composition.}, journal = {Cells}, volume = {14}, number = {5}, pages = {}, pmid = {40072088}, issn = {2073-4409}, support = {No NCN 2017/27/B/NZ5/02904//National Science Center/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Mice, Transgenic ; *Pancreatic Neoplasms/microbiology/genetics/pathology ; Mice ; *Inflammation/pathology/microbiology ; *Gastrointestinal Microbiome/genetics ; *Carcinoma, Pancreatic Ductal/microbiology/genetics/pathology ; Carcinogenesis/genetics/pathology ; Feces/microbiology ; Proto-Oncogene Proteins p21(ras)/genetics ; Pancreas/pathology ; }, abstract = {An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes. Stool Actinobacteriota abundance and pancreatic Actinobacteriota and Bifidobacterium abundances increased. In contrast, stool abundance of Firmicutes, Verrucomicrobiota, Spirochaetota, Desulfobacterota, Butyricicoccus, Roseburia, Lachnospiraceae A2, Lachnospiraceae unclassified, and Oscillospiraceae unclassified decreased, and pancreatic detection of Alloprevotella and Oscillospiraceae uncultured was not observed. Furthermore, FMT accelerated tumorigenesis, gradually decreased the stool alpha diversity, and changed the pancreatic and stool microbial composition in mice with a Kras mutation. Specifically, the abundance of Actinobacteriota, Bifidobacterium and Faecalibaculum increased, while the abundance of genera such as Lachnospiraceace A2 and ASF356, Desulfovibrionaceace uncultured, and Roseburia has decreased. In conclusion, pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota. In particular, a decrease in stool microbiota diversity and abundance of bacteria known to be involved in short-fatty acids production were observed. PDAC mouse model can be used for further research on microbiota-PDAC interactions and towards more personalized and effective cancer therapies.}, } @article {pmid40071861, year = {2025}, author = {Organski, AC and Rajwa, B and Reddivari, A and Jorgensen, JS and Cross, TL}, title = {Gut microbiome-driven regulation of sex hormone homeostasis: a potential neuroendocrine connection.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2476562}, doi = {10.1080/19490976.2025.2476562}, pmid = {40071861}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Male ; Female ; Mice ; *Homeostasis ; *Fecal Microbiota Transplantation ; Gonadal Steroid Hormones/metabolism/blood ; Mice, Inbred C57BL ; Germ-Free Life ; Bacteria/classification/metabolism/isolation & purification/genetics ; Testosterone/blood/metabolism ; Testis/metabolism/microbiology ; Hypothalamo-Hypophyseal System/metabolism ; Feces/microbiology ; Neurosecretory Systems/metabolism ; }, abstract = {The gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.}, } @article {pmid40070843, year = {2025}, author = {Ren, S and Zhang, Y and Wang, X and Su, J and Wang, X and Yuan, Z and He, X and Guo, S and Chen, Y and Deng, S and Wu, X and Li, M and Du, F and Zhao, Y and Shen, J and Hu, W and Li, X and Xiao, Z}, title = {Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1526967}, pmid = {40070843}, issn = {1664-3224}, mesh = {Humans ; *Carcinoma, Hepatocellular/immunology/therapy/microbiology ; *Liver Neoplasms/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Tumor Microenvironment/immunology ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progression, particularly its effects on immune cells within the HCC tumor microenvironment (TME). Furthermore, we explore the potential of gut microbiota-targeted interventions, such as antibiotics, probiotics, prebiotics, and fecal microbiota transplantation (FMT), to modulate the immune response and improve outcomes of immunotherapy in HCC. By synthesizing insights from recent studies, this review aims to highlight microbiota-based strategies that may enhance immunotherapy outcomes, advancing personalized approaches in HCC treatment.}, } @article {pmid40068791, year = {2025}, author = {Huang, H and Zhao, T and Ma, W}, title = {Omega-3 polyunsaturated fatty acids attenuates cognitive impairment via the gut-brain axis in diabetes-associated cognitive dysfunction rats.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2025.03.015}, pmid = {40068791}, issn = {1090-2139}, abstract = {Diabetes-related cognitive dysfunction (DACD) is a comorbidity of type 2 diabetes that has a negative effect on patients' quality of life. Research has indicated that disruption of the gut microbiota (GM) may be linked to dementia with altered cognitive performance. Conversely, omega-3 polyunsaturated fatty acids (n-3 PUFAs) may reverse DACD. The present study aimed to assess the effects of an n-3 PUFA intervention and fecal microbiota transplantation (FMT) on high-fat and streptozotocin-induced DACD model rats. In DACD rats, n-3 PUFA treatment restored fasting blood glucose (FBG) levels and cognitive function, increased the expression of anti-inflammatory cytokines and downregulated the expression of proinflammatory cytokines in the cortex and colon. Additionally, the expression of the postsynaptic density protein-95 mRNA and protein varied with n-3 PUFA treatment. Treatment with n-3 PUFAs also increased the expression of tight junction proteins. Beneficial and short-chain fatty acid-producing bacteria were more abundant when rats were exposed to n-3 PUFAs. After FMT from the rats with DACD symptoms that were improved by the n-3 PUFA dietary intervention into another batch of DACD rats, we observed recovery in recipient DACD rats. These results indicated that the alleviation of DACD symptoms by n-3 PUFAs was attributed to gut microbiota remodeling.}, } @article {pmid40066068, year = {2025}, author = {Ganesan, R and Thirumurugan, D and Vinayagam, S and Kim, DJ and Suk, KT and Iyer, M and Yadav, MK and HariKrishnaReddy, D and Parkash, J and Wander, A and Vellingiri, B}, title = {A critical review of microbiome-derived metabolic functions and translational research in liver diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1488874}, pmid = {40066068}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Diseases/microbiology/metabolism ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; Animals ; *Translational Research, Biomedical ; *Probiotics/therapeutic use ; Liver/metabolism/microbiology ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Significant changes in gut microbial composition are associated with chronic liver disease. Using preclinical models, it has been demonstrated that ethanol/alcohol-induced liver disease is transmissible through fecal microbiota transplantation (FMT). So, the survival rate of people with severe alcoholic hepatitis got better, which suggests that changes in the makeup and function of gut microbiota play a role in metabolic liver disease. The leaky intestinal barrier plays a major role in influencing metabolic-related liver disease development through the gut microbiota. As a result, viable bacteria and microbial products can be transported to the liver, causing inflammation, contributing to hepatocyte death, and causing the fibrotic response. As metabolic-related liver disease starts and gets worse, gut dysbiosis is linked to changes in the immune system, the bile acid composition, and the metabolic function of the microbiota in the gut. Metabolic-related liver disease, as well as its self-perpetuation, will be demonstrated using data from preclinical and human studies. Further, we summarize how untargeted treatment approaches affect the gut microbiota in metabolic-related liver disease, including dietary changes, probiotics, antibiotics, and FMT. It discusses how targeted therapies can improve liver disease in various areas. These approaches may improve metabolic-related liver disease treatment options.}, } @article {pmid40064933, year = {2025}, author = {Madill-Thomsen, KS and Venner, JM and Parsons, DE and Famulski, KS and Thiesen, AL and Hoque, S and Kroeker, KI and Wong, K and Peerani, F and Dieleman, LA and Hoentjen, F and Baumgart, DC and Halloran, PF and Halloran, BP}, title = {Relating the molecular phenotype of ulcerative colitis to the clinical course.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {8342}, pmid = {40064933}, issn = {2045-2322}, mesh = {Humans ; *Colitis, Ulcerative/genetics/metabolism/pathology ; Male ; Female ; Adult ; Middle Aged ; *Leukocyte L1 Antigen Complex/metabolism ; Prospective Studies ; Phenotype ; Disease Progression ; Biopsy ; Aged ; Immunity, Innate ; Colon/pathology/metabolism ; }, abstract = {The expanding portfolio of targeted therapies for ulcerative colitis (UC) suggests that a more precise approach to defining disease activity will aid clinical decision-making. This prospective study used genome-wide microarrays to characterize gene expression in biopsies from the most inflamed colon segments from patients with UC and analyzed associations between molecular changes and short-term outcomes while on standard-of-care treatment. We analyzed 141 biopsies-128 biopsies from 112 UC patients and 13 biopsies from eight inflammatory bowel disease unclassified (IBDU) patients. Endoscopic disease was associated with expression of innate immunity transcripts, e.g. complement factor B (CFB); inflammasome genes (ZBP1 and PIM2); calprotectin (S100A8 and S100A9); and inflammation-, injury-, and innate immunity-associated pathway analysis terms. A cross-validated molecular machine learning classifier trained on the endoscopic Mayo subscore predicted the endoscopic Mayo subscore with area-under-the-curve of 0.85. A molecular calprotectin transcript score showed strong associations with fecal calprotectin and the endoscopic Mayo subscore. Logistic regression models showed that molecular features (e.g. molecular classifier and molecular calprotectin scores) improved the prediction of disease progression over conventional, clinical features alone (e.g. total Mayo score, fecal calprotectin, physician global assessment). The molecular features of UC showed strong correlations with disease activity and permitted development of machine-learning predictive disease classifiers that can be applied to expanded testing in diverse cohorts.}, } @article {pmid40063530, year = {2025}, author = {Serbanescu, M and Lee, S and Li, F and Boppana, SH and Elebasy, M and White, JR and Mintz, CD}, title = {Effects of Perioperative Exposure on the Microbiome and Outcomes From an Immune Challenge in C57Bl/6 Adult Mice.}, journal = {Anesthesia and analgesia}, volume = {}, number = {}, pages = {}, doi = {10.1213/ANE.0000000000007467}, pmid = {40063530}, issn = {1526-7598}, abstract = {BACKGROUND: Previous work suggests that the gut microbiome can be disrupted by antibiotics, anesthetics, opiates, supplemental oxygen, or nutritional deprivation-all of which are common and potentially modifiable perioperative interventions that nearly all patients are exposed to in the setting of surgery. Gut microbial dysbiosis has been postulated to be a risk factor for poor surgical outcomes, but how perioperative care-independent of the surgical intervention-impacts the gut microbiome, and the potential consequences of this impact have not been directly investigated.

METHODS: We developed a perioperative exposure model (PEM) in C57Bl/6 mice to emulate the most common elements of perioperative medicine other than surgery, which included 12 hours of nutritional deprivation, 4 hours of volatile general anesthetic, 7 hours of supplemental oxygen, surgical antibiotics (cefazolin), and opioid pain medication (buprenorphine). Gut microbial dynamics and inferred metabolic changes were longitudinally assessed before-and at 3 time points after-PEM by 16S rRNA amplicon sequencing. We then used fecal microbial transplant in secondary abiotic mice to test if, compared to preexposure microbiota, day 3 post-PEM microbial communities affect the clinical response to immune challenge in an endotoxemia model.

RESULTS: We observed transient changes in microbiota structure and function after the PEM, including reduced biodiversity, loss of diverse commensals associated with health (including Lactobacillus, Roseburia, and Ruminococcus), and changes in microbiota-mediated amino acid metabolic pathways. Mice engrafted with day 3 post-PEM microbial communities demonstrated markedly reduced survival after endotoxemia compared to those bearing preexposure communities (7-day survival of ~20% vs ~70%, P = .0002).

CONCLUSIONS: These findings provide the first clear evidence that the combined effects of common perioperative factors, independent of surgery, cause gut microbial dysbiosis and alter the host response to inflammation in the postoperative period.}, } @article {pmid40062406, year = {2025}, author = {Moutsoglou, D and Ramakrishnan, P and Vaughn, BP}, title = {Microbiota transplant therapy in inflammatory bowel disease: advances and mechanistic insights.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2477255}, pmid = {40062406}, issn = {1949-0984}, mesh = {Humans ; *Inflammatory Bowel Diseases/therapy/microbiology/immunology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {Microbiota transplant therapy is an emerging therapy for inflammatory bowel disease, but factors influencing its efficacy and mechanism remain poorly understood. In this narrative review, we outline key elements affecting therapeutic outcomes, including donor factors (such as age and patient relationship), recipient factors, control selection, and elements impacting engraftment and its correlation with clinical response. We also examine potential mechanisms through inflammatory bowel disease trials, focusing on the interplay between the microbiota, host, and immune system. Finally, we briefly explore potential future directions for microbiota transplant therapy and promising emerging treatments.}, } @article {pmid40061173, year = {2025}, author = {Borah, P and Gautam, V and Kumar, V and Saikia, B and Naithani, R}, title = {Fecal Microbiota Transplantation for Refractory Clostridioides difficile Infection Post Haploidentical Transplant for Pediatric Acute Myeloid Leukemia.}, journal = {Blood cell therapy}, volume = {8}, number = {1}, pages = {170-172}, pmid = {40061173}, issn = {2432-7026}, abstract = {BACKGROUND: Clostridioides difficile (C. difficile) infections are common in immunosuppressed patients. Sometimes these are difficult to treat in post-bone marrow transplant situations.

METHODS: A 2-year-old child with relapsed acute myeloid leukemia underwent a haploidentical bone marrow transplant. He developed 30-40 episodes/day of loose watery stools on day +19. The stool was positive for C. difficile infection. He failed oral vancomycin and metronidazole therapy. He received a fecal microbiota transplant (FMT) on day +43. The donor was the same sister who donated hematopoietic stem cells.

RESULTS: Three days later (day +46), stool frequency reduced from 22-24/day to 12-14/day. Color normalized to yellow and consistency improved from watery to semisolid without blood. He was discharged from the hospital 10 days after FMT on oral vancomycin and nasogastric feeding. Stool tested for C. difficile 16 days after FMT was negative and oral vancomycin was stopped.

CONCLUSION: Fecal microbiota transplant could be a useful modality in children with severe C. difficile infection post-bone marrow transplant.}, } @article {pmid40060755, year = {2025}, author = {Yi, D and Li, T and Xiao, Y and Zhang, X and Hao, Q and Zhang, F and Qiu, T and Yang, G and Sun, X and Dong, Y and Wang, N}, title = {Fecal microbiota transplantation for the treatment of intestinal and extra-intestinal diseases: Mechanism basis, clinical application, and potential prospect.}, journal = {Bioengineering & translational medicine}, volume = {10}, number = {2}, pages = {e10728}, pmid = {40060755}, issn = {2380-6761}, abstract = {To review the theoretical basis and therapeutic effects of fecal microbiota transplantation (FMT) in various diseases in animal experiments and clinical studies, as well as the limitations and current standards of FMT application. PubMed and Web of Science databases were searched for articles published only in English between 1975 and 2023 on reliable results of animal experiments and clinical treatment of FMT. The properties of the gut microbiota and its interactions with the host metabolism are critical to human health, and microbiome disturbance is closely associated with human intestinal and extra-intestinal diseases. Therefore, therapeutic tools targeting on the modulation of gut microbiota have attracted increasing attention, among which FMT represents the most widely studied intervention strategy. This review gathered and summarized application of FMT in intestinal diseases, metabolic diseases, hypertension, cancer, nervous system diseases and arthritis, and elaborated the beneficial effects that can be achieved by altering the microbiota with FMT and the mechanisms of action. In addition, the potential risks and side effects of FMT approach are discussed, as well as current efforts to standardize the development of FMT. Through a systemic review of the outcome and mechanism of FMT in the treatment of intestinal diseases and extra-intestinal diseases, we aimed to provide a theoretical basis for the construction of an optimized FMT framework, so as to better exert its application prospects.}, } @article {pmid40060387, year = {2025}, author = {Kim, M and Wang, J and Pilley, SE and Lu, RJ and Xu, A and Kim, Y and Liu, M and Fu, X and Booth, SL and Mullen, PJ and Benayoun, BA}, title = {Estropausal gut microbiota transplant improves measures of ovarian function in adult mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.05.03.592475}, pmid = {40060387}, issn = {2692-8205}, abstract = {Decline in ovarian function with age not only affects fertility but is also linked to a higher risk of age-related diseases in women (e.g . osteoporosis, dementia). Intriguingly, earlier menopause is linked to shorter lifespan; however, the underlying molecular mechanisms of ovarian aging are not well understood. Recent evidence suggests the gut microbiota may influence ovarian health. In this study, we characterized ovarian aging associated microbial profiles in mice and investigated the effect of the gut microbiome from young and estropausal female mice on ovarian health through fecal microbiota transplantation. We demonstrate that the ovarian transcriptome can be broadly remodeled after heterochronic microbiota transplantation, with a reduction in inflammation-related gene expression and trends consistent with transcriptional rejuvenation. Consistently, these mice exhibited enhanced ovarian health and increased fertility. Using metagenomics-based causal mediation analyses and serum untargeted metabolomics, we identified candidate microbial species and metabolites that may contribute to the observed effects of fecal microbiota transplantation. Our findings reveal a direct link between the gut microbiota and ovarian health.}, } @article {pmid40058319, year = {2025}, author = {Zhang, W and Yi, C and Song, Z and Yu, B and Jiang, X and Guo, L and Huang, S and Xia, T and Huang, F and Yan, Y and Li, H and Dai, Y}, title = {Reshaping the gut microbiota: Tangliping decoction and its core blood-absorbed component quercetin improve diabetic cognitive impairment.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {140}, number = {}, pages = {156560}, doi = {10.1016/j.phymed.2025.156560}, pmid = {40058319}, issn = {1618-095X}, abstract = {BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive decline, which can result in diabetic cognitive impairment (DCI). Recent studies have indicated that gut microbiota plays a significant role in the development of DCI. Tangliping Decoction (TLP), a traditional Chinese medicine compound, contains various active ingredients that have been shown to regulate the microecology of gut microbiota and potentially improve DCI. However, it remains unclear whether TLP can improve DCI by modulating gut microbiota, as well as which specific component is primarily responsible for these effects.

PURPOSE: Assess the impact of TLP on alleviating DCI and investigate the contribution of quercetin (QR), the core blood-absorbed component of TLP, in this process. and investigate the underlying mechanisms through which TLP and QR enhance DCI by modulating gut microbiota composition.

STUDY DESIGN AND METHODS: Initially, experiments such as morris water maze (MWM), morphological analysis, and 16S ribosomal RNA (16S rRNA) gene amplicon sequencing from DCI mice, were performed to validate the pharmacological efficacy of TLP in mitigating DCI. The results indicated that TLP possesses the capacity to modulate the composition and quantity of gut microbiota and safeguard the integrity of the gut barrier and brain barrier. Secondly, high performance liquid chromatography coupled with high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) combined with network pharmacology methods were used to screen for blood-absorbed components, suggesting that QR may be a potential core blood-absorbed component of TLP in the treatment of DCI. Subsequently, the pharmacological efficacy of QR in ameliorating DCI was confirmed, and the characteristics of gut microbiota as well as the permeability of the gut and brain barrier, were assessed. Finally, fecal microbiota transplantation (FMT) experiments were conducted, wherein fecal matter from TLP and QR-treated mice (donor mice) was transplanted into pseudo-sterile DCI mice with antibiotic-induced depletion of gut microbiota. This approach aimed to elucidate the specific mechanisms by which TLP and QR improve DCI through the modulation of the structure, composition, and abundance of gut microbiota.

RESULTS: TLP and QR have the potential to enhance learning and memory capabilities in DCI mice, as well as reduce homeostasis model assessment insulin resistance (HOMA-IR) and restore homeostasis model assessment-β function (HOMA- β), leading to increased fasting insulin (FIN) levels and decreased fasting blood glucose (FBG) levels. Simultaneously, the administration of FMT from donor mice to pseudo-sterile DCI mice has been shown to alter the composition and abundance of gut microbiota, leading to amelioration of pathological damage in the colon and hippocampal tissues. Ultimately, FMT utilizing fecal suspensions from donor mice treated with TLP and QR improved cognitive function in pseudo-sterile DCI mice, restore gut microbiota dysbiosis, and maintained the integrity of the gut and brain barriers.

CONCLUSION: The results of this study indicate that TLP and its core component, QR, which is absorbed into the bloodstream, improve DCI through a gut microbiota-dependent mechanism, providing further evidence for gut microbiota as a therapeutic target for DCI treatment.}, } @article {pmid40058316, year = {2025}, author = {Tang, X and Huang, L and Ma, W and Huang, M and Zeng, Z and Yu, Y and Qin, N and Zhou, F and Li, F and Gong, S and Yang, H}, title = {Intestinal 8 gingerol attenuates TBI-induced neuroinflammation by inhibiting microglia NLRP3 inflammasome activation in a PINK1/Parkin-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {140}, number = {}, pages = {156580}, doi = {10.1016/j.phymed.2025.156580}, pmid = {40058316}, issn = {1618-095X}, abstract = {BACKGROUND: traumatic brain injury (TBI) is irreversible brain damage, leading to inflammation and cognitive dysfunction. Microglia involved in the inflammatory response after TBI. The gut microbiota, known as the body's "second brain," regulates neurogenesis and immune responses, but its precise role in regulating TBI remains unclear.

PURPOSE: to investigate the effect of gut microbiota and metabolites disorder on TBI injury.

STUDY DESIGN: 16SrRNA and metabolomics compared gut microbiota and metabolites in sham group and TBI group, then proved that the differential metabolite 8-gingerol (8G) alleviated the microglia neuroinflammatory response after TBI.

METHODS: fecal microbiota transplantation explored the role of dysbiosis in TBI. LC/MS detected the content of 8-gingerol in cecum, blood, and brain. HE, Nissl, Tunel staining and mNSS score evaluated brain injury. Western blot and immunofluorescence detected the expression of inflammasome-related proteins and mitophagy-related proteins in brain tissue and BV2 cells. RNA sequencing analyzed the molecular mechanism of 8-gingerol.

RESULT: rats transplanted with TBI feces had worse brain injury and neurological deficits than those with normal feces. 16SrRNA and metabolomics found that TBI caused dysbiosis and decreased 8-gingerol level, leading to severe neuroinflammation. Mechanistically, 8-gingerol inhibited NLRP3 inflammasome by promoting PINK1-Parkin mediated mitophagy in microglia. Inhibition of Parkin, through either small interfering RNA or the inhibitor 3MA reversed the inhibitory effect of 8-gingerol on NLRP3 by blocking mitophagy. BV2 cells transcriptome showed that 8-gingerol significantly increased the expression of autophagy factor Wipi1, and small interfering RNA of Wipi1 abolished the effect of 8-gingerol on promoting mitophagy and the inhibitory effect on NLRP3.

CONCLUSION: our findings shed light on the pivotal role of gut microbes in TBI, and identify 8 gingerol as an important anti-inflammatory compound during TBI.}, } @article {pmid40058066, year = {2025}, author = {Mu, X and Feng, L and Wang, Q and Li, H and Zhou, H and Yi, W and Sun, Y}, title = {Decreased gut microbiome-derived indole-3-propionic acid mediates the exacerbation of myocardial ischemia/reperfusion injury following depression via the brain-gut-heart axis.}, journal = {Redox biology}, volume = {81}, number = {}, pages = {103580}, doi = {10.1016/j.redox.2025.103580}, pmid = {40058066}, issn = {2213-2317}, abstract = {Despite the increasing recognition of the interplay between depression and cardiovascular disease (CVD), the precise mechanisms by which depression contributes to the pathogenesis of cardiovascular disease remain inadequately understood. The involvement of gut microbiota and their metabolites to health and disease susceptibility has been gaining increasing attention. In this study, it was found that depression exacerbated cardiac injury, impaired cardiac function (EF%: P < 0.01; FS%: P < 0.05), hindered long-term survival (P < 0.01), and intensified adverse cardiac remodeling (WGA: P < 0.01; MASSON: P < 0.0001) after myocardial ischemia/reperfusion (MI/R) in mice. Then we found that mice receiving microbiota transplants from chronic social defeat stress (CSDS) mice exhibited worse cardiac function (EF%: P < 0.01; FS%: P < 0.01) than those receiving microbiota transplants from non-CSDS mice after MI/R injury. Moreover, impaired tryptophan metabolism due to alterations in gut microbiota composition and structure was observed in the CSDS mice. Mechanistically, we analyzed the metabolomics of fecal and serum samples from CSDS mice and identified indole-3-propionic acid (IPA) as a protective agent for cardiomyocytes against ferroptosis after MI/R via NRF2/System xc-/GPX4 axis, played a role in mediating the detrimental influence of depression on MI/R. Our findings provide new insights into the role of the gut microbiota and IPA in depression and CVD, forming the basis of intervention strategies aimed at mitigating the deterioration of cardiac function following MI/R in patients experiencing depression.}, } @article {pmid40055837, year = {2025}, author = {Alexandra, P and Noémie, P and Solène, SB and Jean-Benoit, H and Riche, VP and Odile, C and Michel, G and Guy, V and Hamy, A and Mehdi, O and Yannick, T and Jeremie H, L and Amar, A and Emeric, A and Jean-Michel, B and Bridoux, V and Dumont, F and June, F and Alexandra, J and Meurette, G and Duchalais, E}, title = {Evaluation of pelvic floor rehabilitation in the prevention of low anterior resection syndrome: Study protocol of the CONTICARE trial.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {27}, number = {3}, pages = {e70045}, doi = {10.1111/codi.70045}, pmid = {40055837}, issn = {1463-1318}, support = {//French Ministry of Health (PHRCI 2016 - API16/N/055)/ ; }, mesh = {Humans ; *Pelvic Floor/physiopathology ; *Rectal Neoplasms/surgery/rehabilitation ; *Postoperative Complications/prevention & control/rehabilitation ; Syndrome ; Female ; *Quality of Life ; *Proctectomy/adverse effects/methods/rehabilitation ; *Fecal Incontinence/etiology/prevention & control/rehabilitation ; Biofeedback, Psychology/methods ; Randomized Controlled Trials as Topic ; Male ; Anal Canal/surgery ; Middle Aged ; Adult ; Multicenter Studies as Topic ; Treatment Outcome ; Aged ; Exercise Therapy/methods ; Low Anterior Resection Syndrome ; }, abstract = {AIM: Bowel dysfunction following sphincter-preserving rectal resection for cancer, commonly referred to as low anterior resection syndrome (LARS), significantly impacts patients' quality of life. Preventing this condition is essential for healthcare teams. Postoperative pelvic floor rehabilitation, including anal biofeedback therapy, has shown potential in alleviating established LARS symptoms. This trial aims to evaluate the effectiveness of pelvic floor rehabilitation prior to bowel continuity restoration in preventing LARS in patients undergoing sphincter-preserving rectal resection for cancer.

METHODS: CONTICARE is a national multicentre randomized trial. Patients who have undergone total mesorectal excision with sphincter preservation and a defunctioning stoma (n = 174; 87 per arm) will be randomly assigned to either the rehabilitation or control group before stoma closure. The rehabilitation group will receive systematic pelvic floor rehabilitation, comprising four sessions before and six sessions after stoma closure, following a standardized approach. The control group will receive standard follow-up care, which includes symptom-based therapy after ileostomy closure. The primary outcome measure will be the severity of LARS, assessed using the dedicated LARS score at 6 months. Comparisons of faecal incontinence symptoms, quality of life and complications related to biofeedback therapy will also be evaluated at 6 weeks, 6 months and 1 year between the two groups.

CONCLUSION: Pelvic floor rehabilitation has the potential to enhance symptom management and quality of life for patients following rectal resection by preventing LARS. The combination of anal exercises and biofeedback therapy, which has been extensively studied without reported adverse effects, suggests that the anticipated benefits outweigh any potential risks.

CLINICAL TRIAL REGISTRATION: Registration number NCT03876561, first published on 15 March 2019.

CLINICALTRIALS: gov.}, } @article {pmid40054499, year = {2025}, author = {Luan, WW and Gu, HW and Qiu, D and Ding, X and Liu, PM and Hashimoto, K and Yang, JJ and Wang, XM}, title = {Repeated administration of esketamine ameliorates mechanical allodynia in mice with chemotherapy-induced peripheral neuropathy: A role of gut microbiota and metabolites.}, journal = {Neurochemistry international}, volume = {185}, number = {}, pages = {105961}, doi = {10.1016/j.neuint.2025.105961}, pmid = {40054499}, issn = {1872-9754}, abstract = {Chemotherapy-induced peripheral neuropathy (CIPN) severely diminishes the quality of life for cancer survivors, yet effective treatments remain scarce. Esketamine, a commonly used anesthetic, has demonstrated neuroprotective effects by restoring gut microbiome dysbiosis. In this study, we investigated the impact of esketamine on nociceptive sensitivity in a mouse model of CIPN and explored the potential involvement of the gut microbiome. In mice treated with oxaliplatin, repeated esketamine doses (in contrast to a single dose) significantly improved the paw withdrawal threshold (PWT). Western blot and qPCR analyses further revealed that repeated esketamine administration markedly reduced microglial activation and neuroinflammation in the dorsal root ganglion (DRG), underscoring its potent anti-inflammatory properties. Moreover, fecal 16S rRNA analysis indicated that esketamine partially restored the abnormal gut microbiota composition (β-diversity). Plasma metabolome analysis showed that repeated esketamine treatment significantly lowered the elevated levels of 6H-indolo[2,3-b]quinoline and restored the reduced levels of (3-exo)-3-[3-methyl-5-(1-methylethyl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]octane observed in oxaliplatin-treated mice. In addition, fecal microbiota transplantation from esketamine-treated CIPN mice notably improved both the diminished PWT and DRG neuroinflammation in oxaliplatin-treated mice. Collectively, these findings suggest that repeated esketamine administration may alleviate mechanical allodynia in CIPN mice by modulating neuroinflammation, gut microbiota, and associated metabolites.}, } @article {pmid40053245, year = {2025}, author = {Lukic, I and Ivkovic, S and Glavonic, E and Adzic, M and Mitic, M}, title = {Long-lasting Depressive Behavior of Adolescent Chronically Stressed Mice is Mediated by Gut Microbiota Dysbiosis.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {40053245}, issn = {1559-1182}, abstract = {Depression is one of the most common mental disorders worldwide, and its prevalence sharply rises during adolescence. Adolescence is a particularly sensitive period to the effects of environmental stressors, which can cause persistent depressive behavior extending into adulthood. However, the studies assessing if changes in gut microbiota could be one of the mediators of long-term effects of adolescent stress are scarce. In the present study, we examined enduring effects of adolescent chronic unpredictable stress (CUS) on mice behavior along with alterations in their gut microbiome, by using 16 s rRNA gene sequencing and fecal microbiota transplantation (FMT). CUS mice, as well as naïve mice receiving FMT from stressed animals, showed long-lasting anxiety and depressive-like behavior extending into adulthood. The microbiota dysbiosis in adolescence was characterized by higher abundance of Alloprevotella and lower abundance of Paraprevotella, Parasutterella, Parabacteroides, and undefined genus Rikenellaceae_RC9_gut_group. On the contrary, microbiota dysbiosis in adulthood was characterized by higher abundance of Bacteroides, Enterorhabdus, Marvinbriantia, and Parabacteroides and lower abundance of Akkermansia, Odoribacter, and Rikenella. In particular, depressive-like behavior in adolescence was negatively correlated with Paraprevotella, while depressive-like behavior in adulthood was negatively correlated with Rikenella abundance, in both CUS and FMT mice. Therefore, the transfer of microbiota from mice stressed in adolescence is able to induce long-lasting depressive-like behavior in naïve mice, clearly showing the importance of gut microbiota dysbiosis in adolescence in shaping enduring depressive behavior. Moreover, our results indicate that changes in specific but different bacteria are related to depressive behavior in adolescence and in adulthood.}, } @article {pmid40051947, year = {2025}, author = {Bhalla, A and Shahi, A and Maity, M and Safa, F and Srividya, V and Clementina, R and Anugu, GR and Younas, S}, title = {Inflammatory Bowel Disease in Children: Current Diagnosis and Treatment Strategies.}, journal = {Cureus}, volume = {17}, number = {2}, pages = {e78462}, pmid = {40051947}, issn = {2168-8184}, abstract = {Pediatric inflammatory bowel disease (PIBD), including Crohn's disease and ulcerative colitis, has emerged as a significant global health challenge with rising incidence rates. Unlike adult inflammatory bowel disease, PIBD presents complexities, including growth impairment, nutritional deficiencies, and psychosocial challenges that necessitate tailored management strategies. This article reviews current diagnostic and emerging treatment strategies to highlight the evolution from traditional therapies such as aminosalicylates, corticosteroids, and immunomodulators to advanced biologic agents like infliximab and adalimumab. Emerging biological therapies, including vedolizumab and ustekinumab, show promise, while novel small molecule therapies such as Janus kinase (JAK) inhibitors are under investigation for potential use in the pediatric population. Supportive treatments, including exclusive enteral nutrition, modified diets, and probiotics, play a critical role in comprehensive disease management. Stem cell therapy and fecal microbiota transplant represent innovative approaches still under clinical evaluation. The review underscores the significance of holistic care, incorporating mind-body interventions and psychosocial support to improve patient quality of life. Key challenges persist, such as infection risks associated with long-term biological therapy use, gaps in pediatric-specific guidelines, and the limited inclusion of children in clinical trials. Future recommendations emphasize the importance of structured transition programs bridging pediatric and adult care, regular updates to clinical guidelines, and the integration of precision medicine to personalize treatment plans. Continued research and collaboration are essential for advancing the understanding and management of PIBD, ensuring that pediatric patients benefit from the most effective, evidence-based care available.}, } @article {pmid40050917, year = {2025}, author = {Zou, B and Liu, S and Dong, C and Shen, H and Lv, Y and He, J and Li, X and Ruan, M and Huang, Z and Shu, S}, title = {Fecal microbiota transplantation restores gut microbiota diversity in children with active Crohn's disease: a prospective trial.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {288}, pmid = {40050917}, issn = {1479-5876}, mesh = {Humans ; *Crohn Disease/therapy/microbiology ; Child ; Female ; Male ; Prospective Studies ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Adolescent ; Biodiversity ; Feces/microbiology ; Biomarkers/metabolism ; Treatment Outcome ; }, abstract = {BACKGROUND: Clinical data on oral fecal microbiota transplantation (FMT), a promising therapy for Crohn's disease (CD), are limited. Herein, we determined the short-term safety and feasibility of FMT for pediatric patients with active CD.

METHODS: In this open-label, parallel-group, single-center prospective trial, patients with active CD were treated with oral FMT capsules combined with partial enteral nutrition (PEN) (80%). The control group comprised pediatric patients with active CD treated with PEN (80%) and immunosuppressants. Thirty-three patients (11.6 ± 1.82 years)-17 in the capsule and 16 in the control groups-were analyzed. Data regarding the adverse events, clinical reactions, intestinal microbiome composition, and biomarker parameters were collected and compared post-treatment.

RESULTS: At week 10, the clinical and endoscopic remission rates did not differ between the two groups. By week 10, the mean fecal calprotectin level, C-reactive protein level, erythrocyte sedimentation rate, simple endoscopic score for CD, and pediatric CD activity index decreased significantly in the capsule group (all P < 0.05). The main adverse event was mild-to-moderate constipation. Core functional genera, Agathobacter, Akkermansia, Roseburia, Blautia, Subdoligranulum, and Faecalibacterium, were lacking pre-treatment. Post-treatment, the implantation rates of these core functional genera increased significantly, which positively correlated with the anti-inflammatory factor, interleukin (IL)-10, and negatively correlated with the pro-inflammatory factor, IL-6. The combination of these six functional genera distinguished healthy children from those with CD (area under the curve = 0.96).

CONCLUSIONS: Oral FMT capsules combined with PEN (80%) could be an effective therapy for children with active CD. The six core functional genera identified here may be candidate biomarkers for identifying children with CD.

TRIAL REGISTRATION: ClinicalTrials.gov, retrospectively registered, ID# NCT05321758, NCT05321745, date of registration: 2022-04-04.}, } @article {pmid40050761, year = {2025}, author = {Salazar-Arenas, JA and Hurtado-Bermúdez, LJ and Salazar-Cardona, ED and Rojas-Rojas, NE and Cubides-Martinez, JF and Toro-Palma, JD and Zúñiga-Restrepo, V and Rojas-Rodríguez, CA}, title = {Clinical and microbiological profile of patients with diarrhea evaluated using the gastrointestinal panel in a high-complexity center.}, journal = {BMC gastroenterology}, volume = {25}, number = {1}, pages = {147}, pmid = {40050761}, issn = {1471-230X}, mesh = {Humans ; *Diarrhea/microbiology/epidemiology ; Male ; Female ; Cross-Sectional Studies ; Middle Aged ; Colombia/epidemiology ; *Immunocompromised Host ; Adult ; Aged ; Feces/microbiology/parasitology ; Young Adult ; }, abstract = {INTRODUCTION: Gastrointestinal infections represent a worldwide public health problem. In Colombia, the incidence reaches 21.4 cases per 1,000 inhabitants. Given the limitations of traditional diagnostic methods in terms of sensitivity and specificity, the gastrointestinal panel (GIP) has emerged as a promising tool, allowing rapid detection of 22 pathogens. This study aimed to describe the clinical and microbiological characteristics of immunosuppressed and immunocompetent adult patients with diarrhea and the influence of the gastrointestinal panel in their treatment in a high-complexity hospital in Colombia.

MATERIALS AND METHODS: A cross-sectional observational study was carried out including 350 adult patients treated at the Fundación Valle del Lili hospital between 2021 and 2022. Demographic and clinical variables, GIP findings and treatment were analyzed by univariate and bivariate analysis. We compare immunocompromised and immunocompetent adult patients using Chi-square tests, Fisher's F test for qualitative variables, Student's t-test, and the Mann-Whitney U test for quantitative variables. A significance level of 5% was applied to demonstrate the significance of the variables in all the tests used.

RESULTS: The results showed that 52% were men, with an average age of 52 years. 72.0% presented acute diarrhea, being inflammatory in 60.1%. 39.1% of the patients were immunosuppressed, mainly transplant recipients (31.3%). 53% of the GIPs were positive, with up to 5 pathogens per sample. Bacteria were detected in 80%, viruses in 14.4%, and parasites in 5.5%. The most frequent bacteria were enteropathogenic E. coli (43.0%), enteroaggregative E. coli (18.6%), and C. difficile (17.4%). Norovirus was the predominant virus (67.7%) and Cryptosporidium the most common parasite (41.7%). A higher frequency of Vibrio spp. was observed in non-immunosuppressed patients (p = 0.004) and of enterotoxigenic E. coli in immunosuppressed patients. 41.0% of patients received antibiotic/antiviral therapy, 83% empirically. GIP influenced the treatment of 56.7% of patients, with a 90.0% recovery rate.

CONCLUSION: This study confirms that GIP is a valuable diagnostic tool in the management of adult patients with diarrheal disease, particularly in immunocompromised patients. In our setting it is still a costly and difficult to access test, which makes it necessary to standardize the indications for its application. Future studies could evaluate its cost-effectiveness in our context.}, } @article {pmid40049043, year = {2025}, author = {Huang, JN and Gao, CC and Ren, HY and Wen, B and Wang, ZN and Gao, JZ and Chen, ZZ}, title = {Multi-omics association pattern between gut microbiota and host metabolism of a filter-feeding fish in situ exposed to microplastics.}, journal = {Environment international}, volume = {197}, number = {}, pages = {109360}, doi = {10.1016/j.envint.2025.109360}, pmid = {40049043}, issn = {1873-6750}, abstract = {Microplastics (MPs) are widespread in water environments and can affect gut microbiota and host metabolism of fish, but whether changes in host metabolism under MPs are mediated by gut microbiota remains unclear. Here, silver carp, a filter-feeding fish with important ecological functions, was in-situ exposure to environmentally relevant MPs. Multi-omics analysis and fecal microbiota transplantation were used to reveal the metabolic responses of carp along gut-liver-muscle axis. After three months of in situ exposure to MPs, community structure of gut microbiota of carp was reshaped, and five dominate phyla were significantly changed, including increased Cyanobacteria, Chloroflexi and Planctomycetota but decreased Firmicutes and Fusobacteriota. Weighted gene co-expression network analysis was further performed between these phyla and liver transcription spectrum, showing that the hub gene module contained up-regulated hppD, maiA and plg and activated ubiquinone and other terpenoid-quinone biosynthesis and phenylalanine metabolism. By fecal microbiota transplantation, the key gene module associated with core microbiota phyla of carp was verified in germ-free zebrafish. Interestingly, up-regulated hppD, maiA and plg and enriched phenylalanine metabolism were also observed in this module. Subsequently, metabolome performed in carp liver also shared activated phenylalanine metabolism, including increased trans-cinnamic acid and L-tyrosine. Furthermore, high-associated mapping showed that the differentially expressed metabolites (gamma-aminobutyric acid, ornithine and L-serine) related to amino acid metabolism in carp muscle were significantly accompanied with increased L-tyrosine in its liver. Overall, MPs exposure could change gut microbiome of silver carp and alter host metabolism especially amino acid metabolism along the gut-liver-muscle axis.}, } @article {pmid40047909, year = {2025}, author = {Heinze, T and Heimke, M and Stelzner, S and Wedel, T}, title = {[Surgical anatomy of the anorectum].}, journal = {Chirurgie (Heidelberg, Germany)}, volume = {}, number = {}, pages = {}, pmid = {40047909}, issn = {2731-698X}, abstract = {The anorectum corresponds to the last segment of the gastrointestinal tract and is responsible for mediating fecal continence and controlled defecation. An understanding of the complex topographic anatomy is an indispensable prerequisite for the surgical treatment of benign and malignant diseases in the anorectal region. The detailed description of perirectal fascia, anorectal blood supply and lymph vessel drainage, pelvic autonomic nerves and components of the anal canal and anal sphincter complex has significantly contributed to improvement of the oncological and functional surgical outcome. In this article the state of knowledge relating to the anorectal anatomy is outlined providing a practical basis for rectal and proctological surgical procedures.}, } @article {pmid40046764, year = {2025}, author = {Hou, PF and Yao, Y and Wu, Y and Yu, HT and Qin, Y and Yi, L and Mi, MT}, title = {Fecal microbiota transplantation improves hepatic steatosis induced by HFD in a mouse model associated with liver ILC1 regulation and indole-3-carbinol level.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1500293}, pmid = {40046764}, issn = {2296-861X}, abstract = {BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased worldwide. In recent years, fecal microbiota transplantation (FMT) has become an important promising method for the treatment of MASLD. However, the mechanism remains unclear.

METHODS: The animal model with C57BL/6 male mice induced by high-fat diet (HFD) for 12 weeks has been introduced. Fecal microbiota and indole-3-carbinol (I3C) was given by oral gavage.

RESULTS: Our study demonstrated that a 6-week healthy gut microbiota transplantation tended to ameliorate hepatic steatosis and reverse the decreased liver ILC1 induced by HFD. Interestingly, there was also a negative correlation between liver ILC1 and liver TG, TC level. Furthermore, the protective effect was associated with the elevated levels of serum indole-3-carbinol (I3C). Also, a I3C administration for 6 weeks improved liver steatosis and increased the frequency of liver ILC1 induced by HFD through aryl hydrocarbon receptor (AhR) activation. Moreover, I3C binds to the residues of ALA349, PHE348, LEU309, TYR316, PHE318 on AhR through hydrogen bonds, Π bonds, hydrophobic bonds which was proved by molecular docking.

CONCLUSION: To conclude, our data demonstrated that FMT improved liver steatosis induced by HFD associated with liver ILC1 regulation and indole-3-carbinol level. The study highlighted the potential treatment value of FMT and microbiota-derived I3C in the MASLD treatment and regulation of liver ILC1 function.}, } @article {pmid40046008, year = {2024}, author = {Zeng, Z and Feng, M and He, F and Zhang, E and Li, X and Cao, Z}, title = {Gut microbiota mediates the pro-pyroptosis effect of xierezhuyubuxu decoction in hepatocellular carcinoma.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1481111}, pmid = {40046008}, issn = {1664-302X}, abstract = {INTRODUCTION: Xierezhuyubuxu decoction (XRZYBXD) is prepared by adding and reducing the Dahuang Zhechong Pill, which is a traditional Chinese medicinal formula in "The Synopsis of Prescriptions of the Golden Chamber". XRZYBXD has previously been reported to have good efficacy in treating Hepatocellular carcinoma (HCC) in clinical and basic research. However, its underlying mechanism in treating HCC has not been fully elucidated. The aim of the study is to investigate the pro-pyroptosis effect of XRZYBXD in HCC and the role of gut microbiota in this process.

METHODS: Firstly, we executed comprehensive analyses of XRZYBXD on pyroptosis, intestinal flora, microbial metabolites and intestinal barrier function using TUNEL, IHC, ELISA, WB, Q-PCR, 16S rRNA sequencing, and untargeted metabolomics in a H22 tumor-bearing mice model. Further, through rescue experiment of antibiotics-induced microbiota depletion and fecal microbial transplantation (FMT) experiment, the mechanism of XRZYBXD promoting pyroptosis of HCC by improving intestinal flora was verified.

RESULTS: We found that XRZYBXD medium and high dose significantly inhibited the growth of tumor and induced pyroptosis of hepatoma cells. They also modified intestinal ecological disorders by expansion of the abundance of beneficial bacteria (such as Akkermansia muciniphila and Parabacteroides distasonis) and reduction of the abundance of harmful bacteria (such as Barnesiella intestinihominis). Accordingly, microbiota metabolites and intestinal barrier function were also significantly improved by XRZYBXD.

DISCUSSION: Further, elimination of gut microbiota by antibiotics weakened the efficacy of XRZYBXD, and FMT with feces from the XRZYBXD high dose group achieved similar therapeutic efficacy as XRZYBXD. In brief, XRZYBXD promote pyroptosis of hepatoma cells via adjusting intestinal dysbiosis.}, } @article {pmid40045660, year = {2025}, author = {Hu, J and Xu, F and Zhu, L and Cui, Y and Au, R and Li, Y and Tong, Y and Shen, H}, title = {Angelica dahurica Polysaccharides Ameliorate Colitis by Reducing the Restriction of Gut Microbiota-Derived Imidazole Propionate on PPAR-γ Signaling Activation.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8466}, pmid = {40045660}, issn = {1099-1573}, support = {82205023//National Natural Science Foundation of China/ ; 82274483//National Natural Science Foundation of China/ ; }, abstract = {Angelica dahurica radix (ADR), the root of the botanical family Apiaceae (genus Angelica, species Angelica dahurica (Hoffm.)), has been used to treat colitis in clinical practice. The immunomodulatory effects of ADR are attributed to its polysaccharides (RP). However, its mechanism of action has not been elucidated. In this study, RP's structure was determined through nuclear magnetic resonance analysis. Dextran sulfate sodium-induced colitis in mice was utilized to assess the therapeutic efficacy of RP, while experiments involving fecal microbiota transplantation (FMT) and antibiotic treatment were performed to investigate the contribution of gut microbiota to RP's protective function. Non-targeted metabolomics was utilized to identify potential targets for elucidating the underlying mechanisms. RP is likely composed of (→4)-α-D-Glcp-(1→ and →4)-α-D-Galp-(1→). It effectively alleviated DSS-induced colitis by restoring the balance of the gut microbial community, a finding validated through FMT and antibiotic intervention experiments. Imidazole propionate (ImP) emerged as a potential target for RP's efficacy in treating colitis, which inhibits the activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). Our findings suggest that RP may confer protection against colitis by activating the PPAR-γ signaling pathway through alleviating the constraint imposed by ImP.}, } @article {pmid40044736, year = {2025}, author = {Song, Y and Li, N and Jiang, S and Wang, K and Lv, G and Fan, Z and Du, X and Gao, W and Lei, L and Wang, Z and Liu, G and Li, X}, title = {Microbiota-derived H2S induces c-kit[+] cDC1 autophagic cell death and liver inflammation in metabolic dysfunction-associated steatohepatitis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2222}, pmid = {40044736}, issn = {2041-1723}, support = {U24A20454//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32473104//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Liver/pathology/metabolism ; Humans ; *Autophagy ; Male ; *Proto-Oncogene Proteins c-kit/metabolism/genetics ; *Hydrogen Sulfide/metabolism ; *Fatty Liver/metabolism/pathology/microbiology ; *Mice, Inbred C57BL ; Disease Models, Animal ; Dysbiosis/microbiology/metabolism ; Mice, Knockout ; Inflammation/metabolism/pathology ; Dendritic Cells/metabolism/immunology ; Diet, Western/adverse effects ; Female ; }, abstract = {Immune dysregulation-induced inflammation serves as a driving force in the progression of metabolic dysfunction-associated steatohepatitis (MASH), while the underlying cellular and molecular mechanisms remain largely uncharted. A Western diet (WD) is employed to construct mouse models of metabolic dysfunction associated steatotic liver disease (MASLD) or MASH. Mass cytometry identifies a c-kit[+] cDC1 subset whose frequency is reduced in the livers of mice and patients with MASH compared with healthy controls. Adoptive cell transfer of c-kit[+] cDC1 protects the progression of MASH. Moreover, analysis of gut microbe sequence shows that WD-fed mice and MASLD/MASH patients exhibit gut microbiota dysbiosis, with an elevated abundance of H2S-producing Desulfovibrio_sp. Transplanting of MASH-derived fecal flora, Desulfovibrio_sp., or injecting H2S intraperitoneally into MASLD mice decreases the c-kit[+]cDC1 population and exacerbates liver inflammation. Mechanistically, H2S induces autophagic cell death of cDC1 in a c-kit-dependent manner in cDC-specific c-kit[-/-] and Atg5[-/-] mice. We thus uncover that microbiota-derived H2S triggers the autophagic cell death of c-kit[+] cDC1 and ignites the liver inflammatory cascade in MASH.}, } @article {pmid40042965, year = {2025}, author = {Sun, W and Jia, J and Liu, G and Liang, S and Huang, Y and Xin, M and Chang, Z and Liu, X and Ma, C and Song, X and He, F and Song, Y and Wu, M}, title = {Polysaccharides Extracted from Old Stalks of Asparagus officinalis L. Improve Nonalcoholic Fatty Liver by Increasing the Gut Butyric Acid Content and Improving Gut Barrier Function.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c07078}, pmid = {40042965}, issn = {1520-5118}, abstract = {Nonalcoholic fatty liver disease (NAFLD) ranks among the most prevalent chronic liver diseases worldwide, yet effective treatments remain scarce. Old stalks of Asparagus officinalis L. are rich in polysaccharides. The anti-NAFLD mechanism of polysaccharides from old stalks of A. officinalis (AP) requires further study. Here, we studied the effects of AP on NAFLD mice and its impact on the gut microbiota. AP intervention reduces blood lipids and liver lipids and reduces liver injury and inflammation in mice with NAFLD. Moreover, AP intervention changed gut microbiota composition and increased the abundances of butyric acid-producing bacteria, thereby increasing plasma concentration of butyric acid. Furthermore, AP intervention regulated the AMPK/SREBPs signaling pathway, thereby affecting hepatic lipid synthesis. Additionally, AP intervention improved gut barrier function and reduced plasma LPS levels, which subsequently inhibited the LPS/TLR4/NF-κB signaling pathway, thereby alleviating inflammation in NAFLD model mice. Importantly, fecal microbiota transplant (FMT) outcomes demonstrated that AP-induced changes in the gut microbiota impact the AMPK/SREBPs and LPS/TLR4/NF-κB pathways. These data suggest that AP intervention ameliorates NAFLD by regulating the gut microbiota. These research provides a scientific foundation for the use of the stalks of A. officinalis in the treatment of NAFLD.}, } @article {pmid40041456, year = {2025}, author = {Farah, A and Paul, P and Khan, AS and Sarkar, A and Laws, S and Chaari, A}, title = {Targeting gut microbiota dysbiosis in inflammatory bowel disease: a systematic review of current evidence.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1435030}, pmid = {40041456}, issn = {2296-858X}, abstract = {INTRODUCTION: The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies.

METHODS: Through a comprehensive systematic review spanning key scientific databases-PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar-we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse.

RESULTS: From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT.

CONCLUSION: Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments' clinical efficacy and safety before widespread recommendations for clinical application.}, } @article {pmid40040709, year = {2025}, author = {Liu, X and Yang, K and Jia, Y and Yeertai, Y and Wu, C and Wang, X and Jia, Q and Gu, Z and Cong, J and Ling, J}, title = {Chaihushugan powder regulates the gut microbiota to alleviate mitochondrial oxidative stress in the gastric tissues of rats with functional dyspepsia.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1549554}, pmid = {40040709}, issn = {1664-3224}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dyspepsia/drug therapy/metabolism/therapy ; *Oxidative Stress/drug effects ; Rats ; Male ; *Mitochondria/metabolism/drug effects ; Rats, Sprague-Dawley ; Disease Models, Animal ; Powders ; Gastric Mucosa/metabolism/microbiology/drug effects ; Fecal Microbiota Transplantation ; Drugs, Chinese Herbal/pharmacology/therapeutic use ; Gastrointestinal Motility/drug effects ; Antioxidants/pharmacology ; }, abstract = {INTRODUCTION: Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder associated with oxidative stress (OS) and dysbiosis. Chaihushugan powder (CHSGP) demonstrates efficacy in treating FD; however, the underlying therapeutic mechanism is not yet elucidated. This study aims to investigate the effects of CHSGP on OS and gut microbiota (GM) in FD rats, with a particular emphasis on the role of GM as a potential target for the antioxidant properties of CHSGP.

METHODS: The FD rat model was established with a modified tail-clamp stimulation and the administration of the CHSGP decoction at a dosage of 9.6 g/kg via gavage for a duration of 4 weeks. The GM was depleted by the administration of a cocktail of metronidazole (200 mg/kg), ampicillin (200 mg/kg), neomycin sulfate (200 mg/kg), and vancomycin (100 mg/kg). Fecal microbiota transplantation (FMT) was performed with CHSGP-treated fecal supernatant at a dosage of 10 mL/kg. The gastrointestinal motility was measured using the rates of gastric emptying and small intestine propulsion. Hematoxylin and eosin staining was employed to elucidate the pathological changes, while the transmission electron microscope was used to examine the microstructures of the interstitial cells of Cajal (ICC). Chemiluminescence, colorimetric assay, immunofluorescence co-staining, and western blot assay were employed to identify the OS-related markers (ROS, SOD, NOX4, PRDX1, and TRX2). Sequencing of fecal microbiota was performed utilizing 16S rDNA.

RESULTS: The CHSGP decoction promoted gastrointestinal motility, protected the microstructure of ICC, and reduced OS in FD rats. The GM composition was also regulated by CHSGP. However, these effects disappeared after microbiota depletion. Fortunately, the FMT therapy reinstated them.

CONCLUSION: Chaihushugan powder decoction might regulate the GM to alleviate mitochondrial OS in the gastric tissues of FD rats.}, } @article {pmid40040609, year = {2025}, author = {Liu, FQ and An, ZY and Cui, LJ and Xiao, MY and Wu, YJ and Li, W and Zhang, BS and Yu, L and Feng, J and Liu, ZG and Feng, R and Jiang, ZX and Huang, RB and Jing, HM and Ren, JH and Zhu, XY and Cheng, YF and Li, YH and Zhou, HB and Gao, D and Liu, Y and Yu, F and Wang, X and Qiao, JL and Hu, DH and Wang, LL and Zang, MT and Chen, Q and Qu, QY and Zhou, JY and Li, ML and Chen, YX and Huang, QS and Fu, HX and Li, YY and Wang, QF and Huang, XJ and Zhang, XH and , }, title = {Correlation Between Fecal Microbiota and Corticosteroid Responsiveness in Primary Immune Thrombocytopenia: an Exploratory Study.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2410417}, doi = {10.1002/advs.202410417}, pmid = {40040609}, issn = {2198-3844}, support = {2023YFC2507803//Key Technologies Research and Development Program/ ; 82300149//National Natural Science Foundation of China/ ; 82130008//National Natural Science Foundation of China/ ; 82230004//National Natural Science Foundation of China/ ; 82350004//National Natural Science Foundation of China/ ; 82430006//National Natural Science Foundation of China/ ; 2024M761208//China Postdoctoral Science Foundation/ ; 2023ZB182//Department of Human Resources and Social Security of Jiangsu Province/ ; 2022-1-4082//Capital Health Research and Development of Special Fund/ ; 7242154//Natural Science Foundation of Beijing Municipality/ ; 7232188//Natural Science Foundation of Beijing Municipality/ ; 71003Y3035//Peking University Medicine/ ; }, abstract = {Corticosteroids (CSs) are the initial therapy for immune thrombocytopenia (ITP); however, their efficacy is not adequately predicted. As a novel biomarker, the composition of the gut microbiota is non-invasively tested and altered in patients with ITP. This study aims to develop a predictive model that leverages gut microbiome data to predict the CS response in patients with ITP within the initial four weeks of treatment. Metagenomic sequencing is performed on fecal samples from 212 patients with ITP, 152 of whom underwent CS treatment and follow-up. Predictive models are trained using six machine-learning algorithms, integrating clinical indices and gut microbiome data. The support vector machine (SVM) algorithm-based model has the highest accuracy (AUC = 0.80). This model utilized a comprehensive feature set that combined clinical data (including sex, age, duration, platelet count, and bleeding scales) with selected microbial species (including Bacteroides ovatus, Bacteroides xylanisolvens, and Parabacteroides gordonii), alpha diversities, KEGG pathways, and microbial modules. This study will provide new ideas for the prediction of clinical CS efficacy, enabling informed decision-making regarding the initiation of CS or personalized treatment in patients with ITP.}, } @article {pmid40038211, year = {2025}, author = {Malik, S and Naqvi, SAA and Shadali, AH and Khan, H and Christof, M and Niu, C and Schwartz, DA and Adler, DG}, title = {Fecal Microbiota Transplantation (FMT) and Clinical Outcomes Among Inflammatory Bowel Disease (IBD) Patients: An Umbrella Review.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {40038211}, issn = {1573-2568}, abstract = {BACKGROUND AND AIMS: Recent systematic reviews and meta-analyses (SRMAs) have shown inconsistent effectiveness of FMT among patients with IBD. This study aimed to appraise the evidence for clinically relevant outcomes with FMT in patients with IBD using published SRMAs.

METHODS: We searched major databases from inception through Nov 2023 to identify SRMAs assessing the effectiveness of FMT in patients with IBD. Primary outcomes included clinical remission, clinical response, endoscopic remission/response, a composite endpoint, and adverse effects. We included SRMAs investigating FMT's effect in patients with IBD using RCTs and observational studies data. Methodological quality and evidence certainty were assessed using AMSTAR 2 and GRADE.

RESULTS: Out of 106 citations, 16 SRMAs were included with varying study sizes (2 to 60 primary studies) and participants (112 to 1169 per SRMA). Five SRMAs assessed FMT in IBD, while 11 focused on Ulcerative Colitis (UC). Seven SRMAs included RCTs only, and nine included both RCTs and observational studies. Methodological quality was critically low in 9 SRMAs (56%) and low in 7 studies (44%). FMT showed clinical remission benefit in all 16 SRMAs, with varying certainty: 3 high, 4 moderate, 4 low, and 5 very low. Endoscopic remission/response was reported in 5 meta-analyses on UC, with 1 high, 3 moderate, and 1 very low certainty. Combined clinical remission and endoscopic response were reported in 3 SRMAs on UC, with 1 low and 2 moderate certainty. Adverse events were reported in 6 SRMAs, with 1 high, 3 moderate, 1 low, and 1 very low certainty.

CONCLUSION: Current evidence shows potential benefits of FMT in IBD, particularly UC, supported by significant associations in 16 meta-analyses. However, poor methodological quality and variability in evidence certainty call for high-quality RCTs to strengthen the evidence.}, } @article {pmid40037667, year = {2025}, author = {Wei, Y and Qin, L and Wu, X and Li, D and Qian, D and Jiang, H and Geng, Q}, title = {Faecal microbiota transplantation combined with platinum-based doublet chemotherapy and tislelizumab as first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC): study protocol for a prospective, multicentre, single-arm exploratory trial.}, journal = {BMJ open}, volume = {15}, number = {3}, pages = {e094366}, pmid = {40037667}, issn = {2044-6055}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung/therapy/drug therapy ; *Lung Neoplasms/therapy/drug therapy ; *Fecal Microbiota Transplantation/methods ; Prospective Studies ; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Adult ; Female ; Multicenter Studies as Topic ; Male ; Middle Aged ; Combined Modality Therapy ; Aged ; }, abstract = {INTRODUCTION: The standard first-line treatment for driver-gene negative advanced non-small cell lung cancer (NSCLC) is chemotherapy combined with immunotherapy. However, owing to the immune microenvironment imbalance and immune status impairment caused by repeated chemotherapy, as well as the primary or secondary resistance to immune checkpoint inhibitors, the efficacy of immunotherapy combined with chemotherapy remains unsatisfactory. Recent studies have shown that faecal microbiota transplantation (FMT) can modulate the intestinal microflora, influence the tumour immune microenvironment and even enhance the efficacy of immunotherapy. Hence, we conduct such a prospective, exploratory study to evaluate the efficacy and safety of integrating FMT with standard first-line treatment in patients with driver-gene negative advanced NSCLC.

METHODS AND ANALYSIS: FMT-JSNO-02 (NCT06403111) is a prospective, multicentre, single-arm exploratory study. It is planned to include 62 cases of previously untreated driver-gene negative, Eastern Cooperative Oncology Group Performance Status 0-1, programmed death ligand 1<50% advanced NSCLC patients, who will be given FMT by orally ingested stool capsules on the basis of standard first-line treatment of chemotherapy combined with immunotherapy. The primary endpoint of this study is the 12-month progression-free survival rate.

ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Second People's Hospital of Changzhou (number [2024] YLJSA005) and is being conducted in accordance with the principles of the Declaration of Helsinki. The results of this study will be disseminated through publication in a peer-reviewed journal and presentation at scientific conferences.

TRIAL REGISTRATION NUMBER: NCT06403111. Date of registration: 7 May 2024, the first version protocol.}, } @article {pmid40037430, year = {2025}, author = {Gao, J and He, Y and Shi, F and Hou, F and Wu, X and Yi, Y and Zhang, Y and Gong, Q}, title = {Activation of Sirt6 by icariside Ⅱ alleviates depressive behaviors in mice with poststroke depression by modulating microbiota-gut-brain axis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.03.002}, pmid = {40037430}, issn = {2090-1224}, abstract = {BACKGROUND: Sirt6-mediated gut microbiota plays a vital role in poststroke depression (PSD). Icariside Ⅱ (ICS Ⅱ) is a naturally-occurring neuroprotectant with Sirt6 induction potency. However, it is unknown whether ICS Ⅱ protects against PSD through modulation of gut microbiota.

OBJECTIVE: This study aimed to reveal the effect and potential mechanisms of ICS Ⅱ on PSD, and the role of the microbiota-gut-brain axis was investigated.

METHODS: Using middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) to establish post-stroke depression (PSD) mice, we assessed anti-depressant effects of ICS Ⅱ via behavioral tests, immunohistochemistry, and western blot. Transcriptome profiling, molecular docking, and surface plasmon resonance were used to identify key targets. 16S rDNA genomic-derived taxonomic profiling and fecal microbiota transplantation (FMT) were conducted to figure out the mechanistic role of the gut microbiota and short-chain fatty acids (SCFAs).

RESULTS: ICS Ⅱ ameliorated depressive-like behaviors in PSD mice as evidenced by sucrose preference test, forced swimming test and tail suspension test. ICS Ⅱ restored mitochondrial function, reduced oxidative damage and pro-inflammatory cytokines both in brain and intestine through regulation of Sirt6/NF-κB pathway. ICS Ⅱ significantly increased the abundance of gut microbiota (such asAkkermansia and Ligilactobacillus), enhanced SCFAs concentrations, repaired intestinal barrier integrity and upreglated the tight junction protein expression. FMT from ICS II-treated mice replicated these benefits, confirming gut microbiota's role. Mechanistically, ICS Ⅱ directly bound to Sirt6 and enhanced its activity. However, ICS Ⅱ-mediated neuroprotection was neutralized in PSD mice or hydrogen peroxide-induced enteric glial cells when Sirt6 was absent.

CONCLUSION: Our findings expand the pharmacological properties of ICS II by demonstrating its ability to ameliorate PSD through modulation of the microbiota-gut-brain axis. ICS Ⅱ, as a novel Sirt6 activator, could be translated into an alternative microbiota-targeted avenue for coping with PSD.}, } @article {pmid40037353, year = {2025}, author = {Tian, S and Kim, MS and Zhao, J and Heber, K and Hao, F and Koslicki, D and Tian, S and Singh, V and Patterson, AD and Bisanz, JE}, title = {A designed synthetic microbiota provides insight to community function in Clostridioides difficile resistance.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2025.02.007}, pmid = {40037353}, issn = {1934-6069}, abstract = {Clostridioides difficile, a major cause of antibiotic-associated diarrhea, is suppressed by the gut microbiome, but the precise mechanisms are not fully described. Through a meta-analysis of 12 human studies, we designed a synthetic fecal microbiota transplant (sFMT1) by reconstructing microbial networks negatively associated with C. difficile colonization. This lab-built 37-strain consortium formed a functional community suppressing C. difficile in vitro and in animal models. Using sFMT1 as a tractable model system, we find that bile acid 7α-dehydroxylation is not a determinant of sFMT1 efficacy while one strain performing Stickland fermentation-a pathway of competitive nutrient utilization-is both necessary and sufficient for the suppression of C. difficile, replicating the efficacy of a human fecal transplant in a gnotobiotic mouse model. Our data illustrate the significance of nutrient competition in suppression of C. difficile and a generalizable approach to interrogating complex community function through robust methods to leverage publicly available sequencing data.}, } @article {pmid40036939, year = {2025}, author = {Mallick, K and Khodve, G and Ruwatia, R and Banerjee, S}, title = {Gut microbes: Therapeutic Target for neuropsychiatric disorders.}, journal = {Journal of psychiatric research}, volume = {184}, number = {}, pages = {27-38}, doi = {10.1016/j.jpsychires.2025.02.031}, pmid = {40036939}, issn = {1879-1379}, abstract = {Neuropsychiatric diseases encompass a range of mental and neurological disorders that have a significant and far-reaching effect on an individual's quality of life. These conditions affect not only the mental status but also the physical well-being of individuals, which leads to weakened immune systems and other diseases. Emerging research underscores a significant connection between the gut microbiome and neuropsychiatric diseases, suggesting that microbial communities within the gastrointestinal tract may influence brain function and mental health. Gut dysbiosis is caused by various factors, including stress, diet, inappropriate usage of antibiotics, infections, and so on, all of which can disrupt numerous pathways, resulting in abnormal neurotransmitter signaling, inflammation, and impaired brain function. Similarly, various neuropsychiatric diseases can disrupt the specific microbiome in the gut, leading to gut dysbiosis, often impairing memory and cognitive function. The growing evidence supporting the role of gut dysbiosis in neuropsychiatric disorders has opened up new avenues for therapeutic interventions. Modulating the gut microbiome through strategies such as probiotics, prebiotics, or fecal microbiota transplantation has shown promising results in various studies of neuropsychiatric disorders. However, further research is needed to fully elucidate the mechanisms involved in gut dysbiosis-associated brain changes to develop effective and personalized treatment strategies for neuropsychiatric diseases.}, } @article {pmid40035163, year = {2025}, author = {Longhitano, A and Roder, C and Blackmore, T and Campbell, A and May, M and Athan, E}, title = {Australasian Society of Infectious Diseases updated guidelines for the management of Clostridioides difficile infection in adults and children in Australia and New Zealand.}, journal = {Internal medicine journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/imj.16638}, pmid = {40035163}, issn = {1445-5994}, abstract = {Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality within the Australian population. Treatment recommendations for CDI pose challenges at both community and hospital-based levels due to the recurrent, refractory and potentially severe nature of the disease. Since the last published Australasian guidelines in 2016, new therapeutic options are available, prompting a necessary update to management recommendations. On behalf of the Australasian Society of Infectious Diseases, we present the updated guidelines for the management of CDI in adults and children exploring the changes to treatment recommendations - including the replacement of oral metronidazole with vancomycin for initial CDI and the emerging role for fidaxomicin and faecal-microbiota transplant.}, } @article {pmid40033229, year = {2025}, author = {Sóti, Á and Nagy, G and Győri, Z and Vass, T and Hetzman, L and Fenyves, BG and Varga, C}, title = {Tension pneumothorax from large bowel herniation and perforation as a late presentation of traumatic diaphragmatic hernia during pregnancy: a case report.}, journal = {International journal of emergency medicine}, volume = {18}, number = {1}, pages = {40}, pmid = {40033229}, issn = {1865-1372}, abstract = {BACKGROUND: Diaphragmatic hernias can be congenital or acquired, with trauma being the primary cause of the latter. Both types may have delayed presentations, with abdominal organs protruding into the thoracic cavity, causing symptoms of varying severity. Pregnancy can sometimes precipitate the condition. Tension pneumothorax resulting from bowel perforation into the thorax is exceptionally rare, with only a few cases reported. To the best of the authors knowledge, this is the third documented case of a late-presenting trauma-related diaphragmatic hernia during pregnancy, complicated by tension pneumothorax.

CASE PRESENTATION: A 30-year-old woman, 29 weeks pregnant, was referred to Semmelweis University emergency department with moderate dyspnea. Initial investigation revealed tension pneumothorax. Chest tube placement released air, pus, and feces. Computer tomography identified a diaphragmatic hernia with bowel incarceration and perforation as the underlying cause. The patient underwent a delayed cesarean section and surgical repair, with a good outcome. A history of thoracic trauma eight years prior was later revealed.

CONCLUSION: Evaluating pregnant patients with shortness of breath in the emergency department is challenging. Identifying a history of thoracic or abdominal trauma is crucial, as this can raise the suspicion of diaphragmatic hernia, which can present with a wide range of symptoms. Spontaneous tension pneumothorax in pregnant women is extremely rare and requires cautious management. A multidisciplinary approach is crucial for the successful treatment of maternal diaphragmatic hernia.}, } @article {pmid40027572, year = {2025}, author = {Zhang, JG and Wang, YW and Wang, QY and Wen, B}, title = {Clinical features and risk factors for combined Klebsiella pneumoniae infection in patients with liver cirrhosis.}, journal = {World journal of hepatology}, volume = {17}, number = {2}, pages = {103648}, pmid = {40027572}, issn = {1948-5182}, abstract = {This article discusses the findings presented by Zhang et al. They analyzed the risk factors and clinical characteristics associated with Klebsiella pneumoniae infection in patients with liver cirrhosis treated at a hospital in Beijing. In this article, we focus on the connection between chronic kidney disease and the intestinal microbiota, and propose microbiota transplantation as a potential treatment for this patient group. We also examine an intriguing phenomenon related to hepatic encephalopathy, and provide insights into the future research.}, } @article {pmid40027490, year = {2025}, author = {Xie, C and Cheng, J and Chen, P and Yan, X and Luo, C and Qu, H and Shu, D and Ji, J}, title = {Integrating gut and IgA-coated microbiota to identify Blautia as a probiotic for enhancing feed efficiency in chickens.}, journal = {iMeta}, volume = {4}, number = {1}, pages = {e264}, pmid = {40027490}, issn = {2770-596X}, abstract = {This study explores the role of IgA-coated bacteria in improving feed efficiency in chickens, offering a novel perspective for probiotic screening. Chickens with high feed efficiency were found to have a greater abundance of Gram-positive bacteria, while low feed efficiency chickens exhibited higher levels of Gram-negative bacteria and potential pathogens. Through fecal microbiota transplantation (FMT) and integrating analysis of cecal and IgA-coated microbiota, we precisely identified Blautia as a key genus linked to improved feed efficiency. Further validation demonstrated that Blautia coccoides, a representative species of this genus, enhances feed efficiency and activates B cells to produce Immunoglobulin A (IgA), both in vivo and in vitro. Our findings provide new insights into the potential of IgA-coated bacteria as functional probiotics, offering a promising strategy for enhancing feed efficiency in animal production.}, } @article {pmid40027485, year = {2025}, author = {Liu, Y and Li, H and Sun, T and Sun, G and Jiang, B and Liu, M and Wang, Q and Li, T and Cao, J and Zhao, L and Xiao, F and Zhao, F and Cui, H}, title = {Gut microbiome and metabolome characteristics of patients with cholesterol gallstones suggest the preventive potential of prebiotics.}, journal = {iMeta}, volume = {4}, number = {1}, pages = {e70000}, pmid = {40027485}, issn = {2770-596X}, abstract = {Cholesterol gallstones (CGS) still lack effective noninvasive treatment. The etiology of experimentally proven cholesterol stones remains underexplored. This cross-sectional study aims to comprehensively evaluate potential biomarkers in patients with gallstones and assess the effects of microbiome-targeted interventions in mice. Microbiome taxonomic profiling was conducted on 191 samples via V3-V4 16S rRNA sequencing. Next, 60 samples (30 age- and sex-matched CGS patients and 30 controls) were selected for metagenomic sequencing and fecal metabolite profiling via liquid chromatography-mass spectrometry. Microbiome and metabolite characterizations were performed to identify potential biomarkers for CGS. Eight-week-old male C57BL/6J mice were given a lithogenic diet for 8 weeks to promote gallstone development. The causal relationship was examined through monocolonization in antibiotics-treated mice. The effects of short-chain fatty acids such as sodium butyrate, sodium acetate (NaA), sodium propionate, and fructooligosaccharides (FOS) on lithogenic diet-induced gallstones were investigated in mice. Gut microbiota and metabolites exhibited distinct characteristics, and selected biomarkers demonstrated good diagnostic performance in distinguishing CGS patients from healthy controls. Multi-omics data indicated associations between CGS and pathways involving butanoate and propanoate metabolism, fatty acid biosynthesis and degradation pathways, taurine and hypotaurine metabolism, and glyoxylate and dicarboxylate metabolism. The incidence of gallstones was significantly higher in the Clostridium glycyrrhizinilyticum group compared to the control group in mice. The grade of experimental gallstones in control mice was significantly higher than in mice treated with NaA and FOS. FOS could completely inhibit the formation of gallstones in mice. This study characterized gut microbiome and metabolome alterations in CGS. C. glycyrrhizinilyticum contributed to gallstone formation in mice. Supplementing with FOS could serve as a potential approach for managing CGS by altering the composition and functionality of gut microbiota.}, } @article {pmid40027479, year = {2025}, author = {Shi, Y and Chen, Z and Fang, T and Chen, X and Deng, Y and Qin, H and Lian, M and Shen, J and Zong, Y and Chu, H and Hoebinger, C and Guo, H and Yuan, Z and Zheng, J and Zhou, Y and Pan, Y and Mendes, BG and Lang, S and Hendrikx, T and Zeng, S and Cao, H and Yang, L and Chen, L and Chen, P and Dai, L and Wang, H and Yin, S and Zhu, S and Ma, X and Schnabl, B and Chen, H and Duan, Y}, title = {Gut microbiota in treating inflammatory digestive diseases: Current challenges and therapeutic opportunities.}, journal = {iMeta}, volume = {4}, number = {1}, pages = {e265}, pmid = {40027479}, issn = {2770-596X}, support = {P30 DK120515/DK/NIDDK NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; }, abstract = {Accumulating evidence indicates that the gut microbiota is intricately involved in the initiation and progression of human diseases, forming a multidirectional regulatory axis centered on intestinal microbiota. This article illustrates the challenges in exploring the role of the gut microbiota in inflammatory digestive diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD) and inflammatory bowel disease (IBD), and summarizes the existing microbiome-focused treatment strategies (probiotics, prebiotics, symbiotics, fecal microbiota transplantation, and bacteriophages therapy), emerging technologies (gut microbiome-on-a-chip and artificial intelligence), as well as possible future research directions. Taken together, these therapeutic strategies and technologies present both opportunities and challenges, which require researchers and clinicians to test the rationality and feasibility of various therapeutic modalities in continuous practice.}, } @article {pmid39805029, year = {2025}, author = {Xiong, Y and Lu, X and Li, B and Xu, S and Fu, B and Sha, Z and Tian, R and Yao, R and Li, Q and Yan, J and Guo, D and Cong, Z and Du, Y and Lin, X and Wu, H}, title = {Bacteroides Fragilis Transplantation Reverses Reproductive Senescence by Transporting Extracellular Vesicles Through the Gut-Ovary Axis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {12}, number = {9}, pages = {e2409740}, pmid = {39805029}, issn = {2198-3844}, support = {92369115,92469110,82422048//National Natural Science Foundation of China/ ; 2024CDJXY-016//Fundamental Research Funds for the Central Universities/ ; CSTB2023NSCQMSX0402//Natural Science Foundation of Chongqing, China/ ; cstc2021ycjh-bgzxm0099//Chongqing Talents: Exceptional Young Talents Project/ ; }, mesh = {*Extracellular Vesicles/metabolism ; Female ; *Bacteroides fragilis/metabolism ; Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Ovary/metabolism/microbiology ; Reproduction/physiology ; Fecal Microbiota Transplantation/methods ; Models, Animal ; Aging/metabolism/physiology ; }, abstract = {The diverse and dynamic population of microorganisms present in the gut microbiota may affect host health. There are evidences to support the role of gut microbiota as a key player in reproductive development. Unfortunately, the relationship between reproductive disorders caused by aging and gut microbiota remains largely unknown. Here, it is shown for the first time that gut microorganism Bacteroides fragilis (BF) transplantation ameliorates ovarian aging by transporting extracellular vesicles (EVs) through the gut-ovary axis. Mechanistically, miR-1246 is enriched in EVs derived from BF-treated intestinal cells, and these miR-1246-enriched EVs are transferred to ovaries, thereby effectively improving reproductive senescence by reducing oxidative stress in the ovaries. Specifically, miR-1246 reduces the ubiquitination of p62 and stabilizes the protein level of p62 by targeting E3 ligase SKP2. Then Keap1-Nrf2 complex is dissociated and Keap1 is recruited to form the p62-Keap1 complex. With the dissociation of Keap1-Nrf2 complex, Nrf2 is released and activated, thus promoting the transcription of antioxidant enzymes and relieving reproductive senescence. Collectively, the data indicates that intestinal cell-derived EVs serve as natural information carriers in the crosstalk between the gut and the ovary, and intestinal microorganism transplantation is a promising approach for the treatment of ovarian dysfunction diseases.}, } @article {pmid38579985, year = {2025}, author = {Tao, W and Zhang, Y and Wang, B and Nie, S and Fang, L and Xiao, J and Wu, Y}, title = {Advances in molecular mechanisms and therapeutic strategies for central nervous system diseases based on gut microbiota imbalance.}, journal = {Journal of advanced research}, volume = {69}, number = {}, pages = {261-278}, doi = {10.1016/j.jare.2024.03.023}, pmid = {38579985}, issn = {2090-1224}, mesh = {*Gastrointestinal Microbiome ; Humans ; Animals ; *Central Nervous System Diseases/microbiology/therapy/metabolism ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; Fecal Microbiota Transplantation/methods ; Mice ; Dysbiosis/microbiology/therapy ; }, abstract = {BACKGROUD: Central nervous system (CNS) diseases pose a serious threat to human health, but the regulatory mechanisms and therapeutic strategies of CNS diseases need to be further explored. It has been demonstrated that the gut microbiota (GM) is closely related to CNS disease. GM structure disorders, abnormal microbial metabolites, intestinal barrier destruction and elevated inflammation exist in patients with CNS diseases and promote the development of CNS diseases. More importantly, GM remodeling alleviates CNS pathology to some extent.

AIM OF REVIEW: Here, we have summarized the regulatory mechanism of the GM in CNS diseases and the potential treatment strategies for CNS repair based on GM regulation, aiming to provide safer and more effective strategies for CNS repair from the perspective of GM regulation.

The abundance and composition of GM is closely associated with the CNS diseases. On the basis of in-depth analysis of GM changes in mice with CNS disease, as well as the changes in its metabolites, therapeutic strategies, such as probiotics, prebiotics, and FMT, may be used to regulate GM balance and affect its microbial metabolites, thereby promoting the recovery of CNS diseases.}, } @article {pmid40026419, year = {2025}, author = {Marizzoni, M and Tournier, BB and Chevalier, C and Saleri, S and Lathuilière, A and Ceyzériat, K and Paquis, A and Park, R and Troesch, E and Cattaneo, A and Millet, P and Frisoni, GB}, title = {Stools from a human APOEe2 donor reduces amyloid and tau pathology and increases neuroinflammation in a 3xTg AD mouse model.}, journal = {Frontiers in aging neuroscience}, volume = {17}, number = {}, pages = {1539067}, pmid = {40026419}, issn = {1663-4365}, abstract = {BACKGROUND: The mechanisms underlying the protective effect of the e2 variant of the APOE gene (APOEe2) against Alzheimer's disease (AD) have not been elucidated. We altered the microbiota of 3xTgAD mice by fecal microbiota transplantation from a human APOEe2 donor (e2-FMT) and tested the effect of microbiota perturbations on brain AD pathology.

METHODS: FMT of bacteria isolated from stools of untreated 3xTgAD mice (M-FMT) or e2-FMT were transplanted in 15-month-old 3xTgAD mice. FMT was done alone or in combination with antibiotic and proton-pump inhibitor following the Microbiota Transfer Therapy protocol (MTT). The effect of donor (M or e2) and transplantation protocol (FMT or MTT) on hippocampal amyloid, tau pathology and neuroinflammation were assessed at the end of the treatment.

RESULTS: e2-FMT reduced amyloid, and tau pathology as well as increased neuroinflammation as compared with M-FMT. MTT was associated with reduced number of Aβ40+ plaques and tau pathology. Low levels of amyloid were associated with high levels of pro-inflammatory molecules in e2-FMT mice. These associations were partially attenuated by MTT.

CONCLUSION: Bacteria from a human APOEe2 donor reduced AD pathology and increased neuroinflammation in mice suggesting that the gut microbiota may be a mediator of the protective effect of APOEe2.}, } @article {pmid40025650, year = {2025}, author = {Qi, C and Li, Z and Tu, H and Sun, F and Guo, W and Di, C and He, R and Ze, X and Zhang, L and Gao, R and Hu, P and Yang, W and Li, K and Liu, J and Pan, X and Jin, Z and Sun, J}, title = {2'-FL and cross-feeding bifidobacteria reshaped the gut microbiota of infants with atopic dermatitis ex vivo and prevented dermatitis in mice post-microbiota transplantation through retinol metabolism activation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2474148}, doi = {10.1080/19490976.2025.2474148}, pmid = {40025650}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Humans ; *Dermatitis, Atopic/microbiology/therapy/metabolism ; *Bifidobacterium/metabolism ; Infant ; *Trisaccharides/metabolism ; *Vitamin A/metabolism ; *Fatty Acids, Volatile/metabolism ; Milk, Human/metabolism ; Fecal Microbiota Transplantation ; Probiotics/administration & dosage ; Female ; Male ; Bifidobacterium bifidum/physiology/metabolism ; Mice, Inbred BALB C ; }, abstract = {2'-Fucosyllactose (2'-FL), a predominant human milk oligosaccharide, plays a crucial role in the development of the infant gut microbiota and immune system. However, the microbiota of infants with atopic dermatitis (AD) often has difficulty utilizing 2'-FL. Here, we found that strains from human milk, Bifidobacterium bifidum FN120 and Bifidobacterium longum subsp. longum FN103, utilized 2'-FL for growth by cross-feeding. Through an ex vivo continuous fermentation system, we found that 2'-FL and cross-feeding bifidobacteria synergistically enhanced the production of short-chain fatty acids (SCFAs), particularly acetate and propionate, while reshaping the gut microbiota in infants with AD. The reshaped microbiota was then transplanted into oxazolone-induced mice. We observed that AD symptoms in mice were effectively prevented, with significant changes in the ileum microbiota and increased intestinal SCFA levels. RNA sequencing analysis of Peyer's patches in the small intestine revealed activation of the retinol metabolic pathway. Nontargeted metabolomics analysis revealed a significant increase in plasma retinoate levels, which correlated markedly with AD-related markers. Collectively, our study demonstrated that supplementation with cross-feeding bifidobacteria and 2'-FL reshaped the gut microbiota, activated retinol metabolic pathways, promoted immune tolerance, and thereby prevented AD. Our findings provide novel insights into the therapeutic potential of combining prebiotics and probiotics to modulate the gut - skin axis and support immune tolerance in early life, offering a promising strategy for infantile AD management and prevention.}, } @article {pmid40025585, year = {2025}, author = {Guo, H and Jiang, H and Liu, H}, title = {Case report of clostridium difficile infection after rectal resection with ileostomy.}, journal = {World journal of surgical oncology}, volume = {23}, number = {1}, pages = {70}, pmid = {40025585}, issn = {1477-7819}, mesh = {Humans ; *Ileostomy/adverse effects ; *Clostridioides difficile/isolation & purification ; *Rectal Neoplasms/surgery/pathology ; *Clostridium Infections/etiology/diagnosis/microbiology/therapy ; *Postoperative Complications/microbiology/diagnosis/etiology ; Male ; Prognosis ; Fecal Microbiota Transplantation/adverse effects ; Proctectomy/adverse effects ; Aged ; Middle Aged ; }, abstract = {Colorectal cancer is the third most common cancer worldwide, with high incidence and mortality rates. Surgical resection is the primary treatment for rectal cancer. To reduce the occurrence and severity of postoperative complications such as anastomotic leakage, prophylactic ileostomy is often performed concurrently. However, following ileostomy creation, there is a disruption in intestinal ecology, making patients susceptible to clostridium difficile infection. clostridium difficile is a Gram-positive anaerobic spore-forming bacterium that is resistant to most antibiotics due to spore formation, leading to high recurrence rates and treatment failure. Additionally, in the early stages of clostridium difficile infection, increased ileostomy output can be challenging to differentiate from normal postoperative conditions, potentially resulting in missed diagnosis, delayed treatment, and increased healthcare burden.This case report describes a case of high out-put ileostomy caused by clostridium difficile infection following rectal resection with ileostomy, which was successfully treated by fecal microbiota transplantation, providing evidence-based medicine for clinical practice.}, } @article {pmid40024791, year = {2025}, author = {Kushima, H and Ishii, H}, title = {Cryptococcosis.}, journal = {Medical mycology journal}, volume = {66}, number = {1}, pages = {27-31}, doi = {10.3314/mmj.25.001}, pmid = {40024791}, issn = {2186-165X}, mesh = {Humans ; *Cryptococcosis/immunology/drug therapy/diagnosis ; *Cryptococcus neoformans/isolation & purification/immunology/pathogenicity ; *Immunocompromised Host ; Animals ; Antifungal Agents/therapeutic use ; Organ Transplantation/adverse effects ; }, abstract = {Approximately one million new cases of cryptococcosis develop each year worldwide, resulting in approximately 600,000 deaths. Most cases occurred in HIV patients from African countries south of the Sahara Desert. In light of this situation, in 2022, the World Health Organization presented a list of priority fungal pathogens to guide research, development, and public health action, with Cryptococcus neoformans as the most important critical fungus. In contrast, a recent retrospective study in developed countries showed that 90% of cases with cryptococcosis were non-HIV patients, including immunocompetent individuals. Underlying diseases of non-HIV immunocompromised patients include cancer and solid organ transplantation. High serum titers cryptococcal antigens independently predicted the risk of central nervous system involvement. Even if the patient is asymptomatic, high antigen levels are considered a possibility of cryptococcal meningitis, and a spinal fluid examination may be recommended. The absence of a history of contact with pigeons should not be used as a basis for denying cryptococcosis because C. neoformans is often detected in old and dried feces of chickens other than pigeons. Donor-derived cryptococcosis is a unique feature of cryptococcosis in solid organ transplant recipients. Pre-transplant screening tests for cryptococcosis, pre-transplant treatment for the donor, and prophylactic antifungal therapy for the recipient may be useful. Defense against cryptococcal infection is regulated by various mechanisms, including Th1, Th2, and Th17 immune responses. Molecularly targeted medicines that target specific cytokines or surface antigen molecules have been widely used with excellent clinical efficacy for the treatment of various diseases. Since cryptococcosis has been recently reported to develop during the use of certain medicines, such as ibrutinib and eculizumab, clinicians need to be mindful that the number of similar cases may increase in the future.}, } @article {pmid40024538, year = {2025}, author = {Sliti, A and Kim, RH and Lee, D and Shin, JH}, title = {Whole Genome Sequencing and In Silico Analysis of the Safety and Probiotic Features of Lacticaseibacillus paracasei FMT2 Isolated from Fecal Microbiota Transplantation (FMT) Capsules.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {107405}, doi = {10.1016/j.micpath.2025.107405}, pmid = {40024538}, issn = {1096-1208}, abstract = {Lacticaseibacillus paracasei is widely used as a probiotic supplement and food additive in the medicinal and food industries. However, its application requires careful evaluation of safety traits associated with probiotic pathogenesis, including the transfer of antibiotic-resistance genes, the presence of virulence and pathogenicity factors, and the potential disruptions of the gut microbiome and immune system. In this study, we conducted whole genome sequencing (WGS) of L. paracasei FMT2 isolated from fecal microbiota transplantation (FMT) capsules and performed genome annotation to assess its probiotic and safety attributes. Our comparative genomic analysis assessed this novel strain's genetic attributes and functional diversity and unraveled its evolutionary relationships with other L. paracasei strains. The assembly yielded three contigs: one corresponding to the chromosome and two corresponding to plasmids. Genome annotation revealed the presence of 2,838 DNA-coding sequences (CDS), 78 ribosomal RNAs (rRNAs), 60 transfer RNAs (tRNAs), three non-coding RNAs (ncRNAs), and 126 pseudogenes. The strain lacked antibiotic resistance genes and pathogenicity factors. Two intact prophages, one Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) region, and three antimicrobial peptide gene clusters were identified, highlighting the genomic stability and antimicrobial potential of the strain. Furthermore, genes linked to probiotic functions, such as mucosal colonization, stress resistance, and biofilm formation, were characterized. The pan-genome analysis identified 3,358 orthologous clusters, including 1,775 single-copy clusters, across all L. paracasei strains. Notably, L. paracasei FMT2 contained many unique singleton genes, potentially contributing to its distinctive probiotic properties. Our findings confirm the potential of L. paracasei FMT2 for food and therapeutic applications based on its probiotic profile and safety.}, } @article {pmid40024260, year = {2025}, author = {Karmisholt Grosen, A and Mikkelsen, S and Aas Hindhede, L and Ellegaard Paaske, S and Dahl Baunwall, SM and Mejlby Hansen, M and Frederik Dahlerup, J and Steen Mortensen, M and Rask Licht, T and Kjærgaard Boldsen, J and Tornvig Erikstrup, L and Lodberg Hvas, C and Erikstrup, C}, title = {Effects of clinical donor characteristics on the success of faecal microbiota transplantation for patients in Denmark with Clostridioides difficile infection: a single-centre, prospective cohort study.}, journal = {The Lancet. Microbe}, volume = {}, number = {}, pages = {101034}, doi = {10.1016/j.lanmic.2024.101034}, pmid = {40024260}, issn = {2666-5247}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment for patients with recurrent Clostridioides difficile infection, but donor selection can influence its clinical success. We aimed to investigate the effect of clinical donor characteristics on FMT outcomes in patients with C difficile infection.

METHODS: In this single-centre, prospective cohort study, we included all donors who fulfilled the national criteria for faeces donation and delivered donations to the Centre for Faecal Microbiota Transplantation, Aarhus University Hospital, Denmark, between May 2, 2016, and Oct 31, 2023, and corresponding recipients treated with one-dose FMT for primary or recurrent C difficile infection. In mixed-effects models, we evaluated the effect of donor sex, age, BMI, smoking status, donation stool consistency, total donation weight, antibiotic use, Helicobacter pylori carriage, birth mode, donor-recipient sex concordance, and the alpha diversity of faeces donations on FMT outcomes in recipients. The primary outcome was the resolution of diarrhoea associated with C difficile infection in patients 8 weeks after FMT.

FINDINGS: Among 145 blood donors who also donated faeces, 115 (79·3%) were men and 30 (20·7%) were women. 90 (62·1%) provided faeces for 1351 evaluable FMTs in 952 patients with C difficile infection. 1037 (76·8%) FMTs were administered through oral capsules, 151 (11·2%) via colonoscopy, and 163 FMTs (12·1%) via nasojejunal tube. Antibiotic use 3-12 months before donation decreased the effectiveness of FMT (odds ratio 0·55 [95% CI 0·33-0·91]; p=0·019). Compared with donations with a Bristol Stool Form Scale (BSFS) score of 3, donations with a score of 4 (odds ratio 1·38 [95% CI 1·04-1·83]; p=0·024) and 5 or above (2·89 [1·33-6·26]; p=0·0072) showed improved FMT effectiveness. Donor sex, BMI, smoking status, H pylori carriage, birth mode, total donation weight, and donor-recipient sex concordance did not affect FMT outcomes.

INTERPRETATION: Expanding current donor selection criteria to avoid antibiotic use in the 12 months preceding donation and including donations with a BSFS score of 5 might improve FMT outcomes for patients with C difficile infection. Our findings call for the revision of current clinical donor screening practices, and future studies could further optimise the criteria for selecting optimal faeces donors.

FUNDING: Innovation Fund Denmark.}, } @article {pmid40023843, year = {2025}, author = {Golomb, SM and Guldner, IH and Aleksandrovic, E and Fross, SR and Liu, X and Diao, L and Liang, K and Wu, J and Wang, Q and Lopez, JA and Zhang, S}, title = {Temporal dynamics of immune cell transcriptomics in brain metastasis progression influenced by gut microbiome dysbiosis.}, journal = {Cell reports}, volume = {44}, number = {3}, pages = {115356}, doi = {10.1016/j.celrep.2025.115356}, pmid = {40023843}, issn = {2211-1247}, abstract = {Interactions between metastatic cancer cells and the brain microenvironment regulate brain metastasis (BrMet) progression. Central nervous system (CNS)-native and peripheral immune cells influence the BrMet immune landscape, but the dynamics and factors modulating this microenvironment remain unclear. As the gut microbiome impacts CNS and peripheral immune activity, we investigated its role in regulating immune response dynamics throughout BrMet stages. Antibiotic-induced (ABX) gut dysbiosis significantly increased BrMet burden versus controls but was equalized with fecal matter transplantation, highlighting microbiome diversity as a regulator of BrMet. Single-cell sequencing revealed a highly dynamic immune landscape during BrMet progression in both conditions. However, the timing of the monocyte inflammatory response was altered. Microglia displayed an elevated activation signature in late-stage metastasis in ABX-treated mice. T cell and microglia perturbation revealed involvement of these cell types in modulating BrMet under gut dysbiosis. These data indicate profound effects on immune response dynamics imposed by gut dysbiosis across BrMet progression.}, } @article {pmid40023320, year = {2025}, author = {Petracco, G and Faimann, I and Reichmann, F}, title = {Inflammatory bowel disease and neuropsychiatric disorders: Mechanisms and emerging therapeutics targeting the microbiota-gut-brain axis.}, journal = {Pharmacology & therapeutics}, volume = {}, number = {}, pages = {108831}, doi = {10.1016/j.pharmthera.2025.108831}, pmid = {40023320}, issn = {1879-016X}, abstract = {Crohn's disease (CD) and ulcerative colitis (UC) are the two major entities of inflammatory bowel disease (IBD). These disorders are known for their relapsing disease course and severe gastrointestinal symptoms including pain, diarrhoea and bloody stool. Accumulating evidence suggests that IBD is not only restricted to the gastrointestinal tract and that disease processes are able to reach distant organs including the brain. In fact, up to 35 % of IBD patients also suffer from neuropsychiatric disorders such as generalized anxiety disorder and major depressive disorder. Emerging research in this area indicates that in many cases these neuropsychiatric disorders are a secondary condition as a consequence of the disturbed communication between the gut and the brain via the microbiota-gut-brain axis. In this review, we summarise the current knowledge on IBD-associated neuropsychiatric disorders. We examine the role of different pathways of the microbiota-gut-brain axis in the development of CNS disorders highlighting altered neural, immunological, humoral and microbial communication. Finally, we discuss emerging therapies targeting the microbiota-gut-brain axis to alleviate IBD and neuropsychiatric symptoms including faecal microbiota transplantation, psychobiotics, microbial metabolites and vagus nerve stimulation.}, } @article {pmid40022204, year = {2025}, author = {Debray, R and Dickson, CC and Webb, SE and Archie, EA and Tung, J}, title = {Shared environments complicate the use of strain-resolved metagenomics to infer microbiome transmission.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {59}, pmid = {40022204}, issn = {2049-2618}, support = {R01AG071684/NH/NIH HHS/United States ; R01AG071684/NH/NIH HHS/United States ; R61AG078470//National Science Foundation/ ; R61AG078470//National Science Foundation/ ; }, mesh = {Animals ; *Metagenomics/methods ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Humans ; Papio/microbiology ; Feces/microbiology ; Bacteria/classification/genetics/isolation & purification ; Metagenome ; }, abstract = {BACKGROUND: In humans and other social animals, social partners have more similar microbiomes than expected by chance, suggesting that social contact transfers microorganisms. Yet, social microbiome transmission can be difficult to identify based on compositional data alone. To overcome this challenge, recent studies have used information about microbial strain sharing (i.e., the shared presence of highly similar microbial sequences) to infer transmission. However, the degree to which strain sharing is influenced by shared traits and environments among social partners, rather than transmission per se, is not well understood.

RESULTS: Here, we first use a fecal microbiota transplant dataset to show that strain sharing can recapitulate true transmission networks under ideal settings when donor-recipient pairs are unambiguous and recipients are sampled shortly after transmission. In contrast, in gut metagenomes from a wild baboon population, we find that demographic and environmental factors can override signals of strain sharing among social partners.

CONCLUSIONS: We conclude that strain-level analyses provide useful information about microbiome similarity, but other facets of study design, especially longitudinal sampling and careful consideration of host characteristics, are essential for inferring the underlying mechanisms of strain sharing and resolving true social transmission network. Video Abstract.}, } @article {pmid40020386, year = {2025}, author = {Zhang, W and Qi, X and Han, M and Jia, Q and Li, X and Yin, W and Wang, Y and Wu, H and Shao, H and Peng, C and Su, C and Sai, L}, title = {Activation of Sirt1 by acetate alleviates silicofibrosis: Contribution of the gut microbiota.}, journal = {Ecotoxicology and environmental safety}, volume = {292}, number = {}, pages = {117969}, doi = {10.1016/j.ecoenv.2025.117969}, pmid = {40020386}, issn = {1090-2414}, abstract = {Silicosis is a prevalent occupational disease marked by progressive pulmonary fibrosis. Despite its significant health burden, the pathogenesis of silicosis remains unclear, and no specific therapeutic drugs are available. In this study, we developed a novel intervention strategy targeting gut microbiota and investigated its underlying mechanisms. Using 16S rRNA gene sequencing, we observed significant gut microbiota dysbiosis in silicosis rats at different times (1-8 weeks), notably characterized by altered relative abundance of Ruminococcus and Lactobacillus. Fecal microbiota transplantation altered the gut microbiota structure of silicosis rats, alleviated silica-induced lung histopathological injury, with LEfSe analysis identifying Bifidobacterium as a potential biomarker. Treatment with Bifidobacterium reduced the level of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and fibrosis markers (collagen III, α-SMA and vimentin) in the lungs of silicosis rats, accompanied with increased serum acetic acid levels. Acetate, a major metabolite of Bifidobacterium, demonstrated similar protective effects against silicosis in this study, suggesting its role as a key mediator of Bifidobacterium action in the lungs. Both Bifidobacterium and acetate significantly upregulated Sirt1 in intestinal and lung tissues, while Sirt1 inhibition diminished their benefits to silicosis. As a widely studied histone deacetylase, Sirt1 was proven to be markedly reduced in the lungs of silicosis rats in this study. EX-527, a potent Sirt1 inhibitor, could worsen silicosis damage by upregulating the level of TGF-β1 and the degree of Smad2/3 acetylation. Our study highlights the efficacy of postbiotics, such as Bifidobacterium and acetate, and identifies Sirt1 as a promising target for silicosis treatment.}, } @article {pmid40019272, year = {2025}, author = {Peng, C and Lei, P and Qi, H and Zhu, Q and Huang, C and Fu, J and Zhao, C}, title = {Effect of fecal microbiota transplantation on diabetic wound healing through the IL-17A-mTOR-HIF1α signaling axis.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0201924}, doi = {10.1128/aem.02019-24}, pmid = {40019272}, issn = {1098-5336}, abstract = {UNLABELLED: Diabetes is the third most common chronic disorder worldwide. Diabetic wounds are a severe complication that is costly and often results in non-traumatic lower limb amputation. Recent investigations have demonstrated that the gut microbiota as a "virtual organ" can regulate metabolic diseases like diabetes. Fecal microbiota transplantation (FMT) is an innovative therapeutic approach for promoting wound healing, but its function remains incompletely defined. A diabetes model was established by supplying mice with a high-fat diet and performing an intraperitoneal injection of streptozotocin. Diabetic wounds were then created, followed by bacterial transplantation. The relevant indexes of wound healing were evaluated to verify the promoting effect of FMT on the diabetic wounds. Human skin keratinocytes were also cultured, and cell scratch experiments were conducted to further investigate the underlying mechanism. The FMT regulated the levels of specific bacteria in the diabetic mice and helped restore the balance of intestinal microbes. This transplantation also enhanced wound healing in the diabetic mice by augmenting the closure rate, accelerating re-epithelialization, and boosting collagen deposition in skin wounds. Furthermore, FMT promoted the production of IL-17A, which significantly enhanced the growth and movement of human keratinocytes. Inhibiting molecules related to the IL-17A-mTOR-HIF1α signaling axis were shown to hinder wound re-epithelialization.This study clarifies the function of the IL-17A-mTOR-HIF1α signaling axis in the utilization of FMT in diabetic wound healing, providing a new therapeutic method and target for promoting the healing of diabetic wounds.

IMPORTANCE: The Intestinal microbiota, as the organ with the largest number of microorganisms in the body, plays a crucial role in the physiological functions of the human body. Normal microbiota can be involved in various functions such as energy absorption, metabolism, and immunity of the body, and microbiota imbalance is related to many diseases such as obesity and diabetes. Diabetes, as one of the world's three major chronic diseases, is a significant health issue that troubles more than a billion people globally. Diabetic wounds are a problem that all diabetic patients must confront when undergoing surgery, and it is an important cause of non-traumatic amputations. Exploring the role of intestinal microorganisms in the wound-healing process of diabetic mice can offer the possibility of using microorganisms as a therapeutic means to intervene in clinically related diseases.}, } @article {pmid40015179, year = {2025}, author = {Patra, D and Dev, G and Hand, TW and Overacre-Delgoffe, A}, title = {Friends close, enemies closer: the complex role of the microbiome in antitumor immunity.}, journal = {Current opinion in immunology}, volume = {93}, number = {}, pages = {102537}, doi = {10.1016/j.coi.2025.102537}, pmid = {40015179}, issn = {1879-0372}, abstract = {Immunotherapy has achieved remarkable advances in cancer treatment by harnessing the immune system to combat tumors, yet its effectiveness remains inconsistent across patients and tumor types. The microbiota, a diverse assemblage of microorganisms residing at host barrier surfaces, is pivotal in shaping immune responses. This review explores the direct and indirect mechanisms via which the microbiota modulates antitumor immune responses both locally within the tumor microenvironment and systemically by affecting distant tumors. We discuss recent findings linking microbiota-derived metabolites and microbiota-derived antigens with antitumor immunity and immunotherapy response. Additionally, we discuss recent advances in microbiome-based therapies, including fecal microbiota transplantation. We propose the use and development of new analytical techniques to further characterize the complex functions and interactions between the microbiome and immune system. To conclude, we outline recommendations for future research and therapeutic approaches to leverage the microbiome to improve current immunotherapies.}, } @article {pmid40015156, year = {2025}, author = {Tang, L and Li, J and Luan, M and Qin, M and Zhong, C and Zhang, Y and Xie, Y and Shi, M and Qiu, L and Yu, J}, title = {Edgeworthia gardneri (Wall.) Meisn protects against HFD-induced murine atherosclerosis through improving gut microbiota-mediated intestinal barrier integrity.}, journal = {Atherosclerosis}, volume = {403}, number = {}, pages = {119132}, doi = {10.1016/j.atherosclerosis.2025.119132}, pmid = {40015156}, issn = {1879-1484}, abstract = {BACKGROUND: Gut microbiota plays a crucial role in the development and progression of atherosclerosis. Edgeworthia gardneri (Wall.) Meisn, a member of the Thymelaeaceae family and the Edgeworthia genus, has been previously shown in our studies to attenuate atherogenesis when administered orally as an ethanolic extract (EEEG). However, the interaction between EEEG and gut microbiota, and the mechanism by which gut microbiota exerts anti-atherosclerotic effects, remains unclear.

AIMS: This study aims to determine whether the anti-atherosclerotic properties of EEEG are associated with gut microbiota remodeling.

METHOD: Atherosclerosis was induced in ApoE[-/-] mice using a high-fat diet (HFD). The mice were treated with EEEG or Lactobacillus plantarum for 16 weeks. The composition of gut microbiota was analyzed through 16S rDNA sequencing. To assess whether the anti-atherosclerotic effects of EEEG depend on the gut microbiota, HFD-fed mice were treated with a cocktail of antibiotics or underwent fecal microbiota transplantation (FMT). Simultaneously, plaque areas in the aortic roots and whole aortas of apolipoprotein E deficient (ApoE[-/-]) mice were evaluated using oil red O staining and hematoxylin-eosin staining. Serum levels of LPS, fluorescein isothiocyanate-dextran, and expression levels of tight junction proteins were measured to identify the effects of EEEG on gut barrier dysfunction in HFD-fed ApoE[-/-] mice.

RESULTS: The results revealed that EEEG treatment significantly reduced atherosclerotic lesions by ameliorating lipid accumulation and preserving gut barrier integrity. The protective effects were abrogated by antibiotics administration, concomitant with an increase in gut barrier permeability by decreasing expression of tight junction proteins. The microbial analysis indicated an augmented abundance of Lactobacillus, Turicibacter, Faecalibacterium, Akkermansia, and Desulfovibrio following EEEG treatment. Meanwhile, transplantation of fecal microbiota from EEEG-treated mice exerted the anti-atherosclerotic effect in the high-fat diet (HFD)-fed ApoE[-/-] recipient mice, accompanied by improvement of gut barrier integrity through upregulation of tight junction protein expression. Furthermore, exogenous supplementation of Lactobacillus plantarum mitigated AS in ApoE[-/-] mice and improved the gut epithelial barrier function by increasing the expression level of Zo-1.

CONCLUSION: These results suggest that the anti-atherosclerotic efficacy of EEEG is attributed to the preservation of gut barrier integrity mediated by gut microbiota. EEEG and its enriched Lactobacillus plantarum may be promising adjuncts for AS management.

IMPORTANCE: Atherosclerosis (AS) is the primary pathological basis of cardiovascular disease (CVD). The gut microbiota is known to play an important role in the development and progression of atherosclerosis. In the clinical management of AS, pharmacological classes such as antioxidants, lipid-lowering drugs, and antiplatelet agents are commonly utilized. Despite their ability to decelerate the progression of AS, complications and adverse reactions still limit their application. Edgeworthia gardneri (Wall.) Meisn, a member of the Thymelaeaceae family and Edgeworthia Meisn genus, has been shown in previous studies to attenuate atherogenesis when orally administered as an ethanolic extract (EEEG). However, the interaction between EEEG and the gut microbiota, as well as the mechanism by which the gut microbiota exerts its anti-atherosclerotic effects, remain unclear. The significance of our research lies in identifying the mechanism behind the anti-atherosclerotic effect of Edgeworthia gardneri. The expected results will provide an important scientific basis for the clinical development and application of Edgeworthia gardneri in the prevention and treatment of AS.}, } @article {pmid40013938, year = {2025}, author = {Hou, S and Yu, J and Li, Y and Zhao, D and Zhang, Z}, title = {Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2413197}, doi = {10.1002/advs.202413197}, pmid = {40013938}, issn = {2198-3844}, abstract = {This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.}, } @article {pmid40012737, year = {2025}, author = {Yassin, LK and Nakhal, MM and Alderei, A and Almehairbi, A and Mydeen, AB and Akour, A and Hamad, MIK}, title = {Exploring the microbiota-gut-brain axis: impact on brain structure and function.}, journal = {Frontiers in neuroanatomy}, volume = {19}, number = {}, pages = {1504065}, pmid = {40012737}, issn = {1662-5129}, abstract = {The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. The MGBA serves as a conduit between the CNS and the ENS, facilitating communication between the emotional and cognitive centers of the brain via diverse pathways. In the initial stages of this review, we will examine the way how MGBA affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, brain blood barrier (BBB) structure and permeability, and synaptic structure. Furthermore, we will review the potential mechanistic pathways of neuroplasticity through MGBA influence. The short-chain fatty acids (SCFAs) play a pivotal role in the MGBA, where they can modify the BBB. We will therefore discuss how SCFAs can influence microglia, neuronal, and astrocyte function, as well as their role in brain disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). Subsequently, we will examine the technical strategies employed to study MGBA interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), and antibiotics-induced dysbiosis. Finally, we will examine how particular bacterial strains can affect brain structure and function. By gaining a deeper understanding of the MGBA, it may be possible to facilitate research into microbial-based pharmacological interventions and therapeutic strategies for neurological diseases.}, } @article {pmid40011318, year = {2025}, author = {Sedeek, SA and Farowski, F and Youssafi, S and Tsakmaklis, A and Brodesser, S and El-Attar, MM and Abdelmalek, MO and Vehreschild, MJGT}, title = {In vitro validation concept for lyophilized fecal microbiota products with a focus on bacterial viability.}, journal = {World journal of microbiology & biotechnology}, volume = {41}, number = {3}, pages = {83}, pmid = {40011318}, issn = {1573-0972}, mesh = {Humans ; *Feces/microbiology ; *Freeze Drying ; *RNA, Ribosomal, 16S/genetics ; *Microbial Viability ; *Fecal Microbiota Transplantation/methods ; *Bile Acids and Salts ; Clostridium Infections/microbiology ; Bacteria/classification/genetics/isolation & purification/growth & development ; Gastrointestinal Microbiome ; Clostridioides difficile ; Germany ; }, abstract = {Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), typically administered as a fresh or frozen stool suspension through colonoscopy, nasojejunal tube, or oral capsules. Lyophilized fecal microbiota (LFM) are an alternative to frozen FM products. We aimed to assess whether lyophilization affects bacterial viability and metabolite levels and to develop LFM capsules for clinical use in Germany. Fecal donations from pre-screened volunteers were aliquoted and analyzed through microbial cell counting, bacterial culture, 16S rRNA gene amplicon sequencing, and bile acid assays. Results showed higher counts of viable bacterial cells and cultured anaerobes in unprocessed stool compared to freshly processed stool (p = 0.012 and p < 0.001, respectively). No significant difference in viable bacterial counts was found between freshly processed (day 0), lyophilized (day 3) and frozen FM (day 3) (p = 0.15), nor between freshly processed (day 0), lyophilized (days 30 and 90) and frozen FM (day 30) (p = 0.07). lyophilization did not significantly impact bile acid and 16S rRNA profiling. Encapsulation of lyophilized powder required fewer capsules (10-14) than frozen capsules (30). LFM products are a practical, viable alternative to frozen and fresh FM products, potentially improving storage and patient acceptance.}, } @article {pmid40011195, year = {2025}, author = {Li, T and Chen, J and Xu, Y and Ji, W and Yang, S and Wang, X}, title = {Hawthorn Pectin Alleviates DSS-Induced Colitis in Mice by Ameliorating Intestinal Barrier Function and Modulating Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c07965}, pmid = {40011195}, issn = {1520-5118}, abstract = {Pectin, as a kind of soluble dietary fiber in hawthorns, exhibits a wide range of biological activities. Nevertheless, its role and mechanism in ulcerative colitis (UC) remain unclear. In this study, the effect of hawthorn pectin (HP) against dextran sulfate sodium (DSS)-induced UC in mice and its underlying mechanism were evaluated. HP dramatically alleviated the pathological symptoms related to colitis in mice, displaying an increase in body weight and colon length and inhibition in colon damage. Importantly, HP inhibited the serum levels of inflammation-related factors including tumor necrosis factor-α, IL-1β, and IL-6 as well as decreased the number of F4/80-positive macrophages in the colon. Moreover, the expression levels of ZO-1 and occludin proteins related to intestinal permeability were increased. A significant decrease in a dose-dependent manner at the gut bacterial genus level (such as Alistipes, Colidextribacter, and Blautia) was observed after HP treatment. HP improved the metabolic pathways of gut microbiota and increased the concentrations of short-chain fatty acids in cecal contents of UC mice. Intriguingly, fecal microbiota transplantation intervention with an HP-derived microbiome notably increased the length and relieved histopathological changes of colon in UC mice. Conclusively, our study provided valuable insights into the potential of HP as a prebiotic for maintaining intestinal health and confirmed that HP could ameliorate UC in a gut microbiota-dependent manner.}, } @article {pmid40010549, year = {2025}, author = {Wei, J and Chen, A and Huang, D and Teng, C and Cai, D and Wu, X and Wang, T and Hu, W and Huang, Z and Wang, P and Guan, X and Zheng, X and Chen, X}, title = {Gut microbiome-derived lipopolysaccharides aggravate cognitive impairment via TLR4-mediated inflammatory signaling in neonatal rats following hypoxic-ischemic brain damage.}, journal = {Brain, behavior, and immunity}, volume = {127}, number = {}, pages = {4-24}, doi = {10.1016/j.bbi.2025.02.029}, pmid = {40010549}, issn = {1090-2139}, abstract = {Hypoxic-ischemic brain damage (HIBD) is a leading cause of infant mortality and neurological disabilities in children. Recent evidence indicates that gut microbiota significantly contributes to the development of inflammation and cognitive impairments following brain injury. However, the mechanisms by which gut microbiota influence inflammation and cognitive function in the neonates after HIBD are not well understood. This study established a neonatal rat model of HIBD by the classic Rice-Vannucci technique to investigate gut dysbiosis following hypoxic-ischemic (HI) insult and to elucidate the causal relationship between gut dysbiosis and cognitive impairments. Our results demonstrated that HI insult resulted in significant gut microbial dysbiosis, characterized by an expansion of Enterobacteriaceae. This dysbiosis was associated with intestinal barrier damage, lipopolysaccharides (LPS) leakage, and systemic inflammation. Conversely, administration of aminoguanidine (AG) to inhibit Enterobacteriaceae overgrowth restored intestinal barrier integrity and reduced systemic inflammation. Importantly, AG treatment effectively suppressed microglial activation, neuronal damage, and cognitive impairments in the neonatal rats subjected to HI insult. Additionally, RNA sequencing analysis revealed that differentially expressed genes in both colonic and hippocampal tissues were primarily associated with inflammation and neuronal apoptosis after HI insult. Further mechanistic exploration revealed that AG treatment mitigated intestinal LPS leakage, thereby reducing the activation of the TLR4/MyD88/NF-κB signaling pathway and production of the downstream inflammatory cytokines in both the colon and hippocampus. Notably, fecal microbiota transplantation (FMT) from the HIBD rats to the antibiotic cocktail-treated recipient rats resulted in microglial activation, neuronal damage, and cognitive impairments in the recipients. However, these adverse effects were effectively mitigated in the recipient rats that received FMT from the AG-treated donors, as well as in those undergoing hippocampal TLR4 knockdown. In conclusion, our findings indicate that LPS derived from gut Enterobacteriaceae overgrowth plays a critical role in the TLR4-mediated inflammatory signaling, providing a novel microbiota-based therapeutic approach for cognitive impairments following neonatal HIBD.}, } @article {pmid40009694, year = {2025}, author = {Wang, LL and Shen, X and Xie, Y and Ge, A and Lu, H and Gu, S and Kong, L and Narayana, JK and Mattner, J and Chotirmall, SH and Xu, JF}, title = {A gut Eggerthella lenta-derived metabolite impairs neutrophil function to aggravate bacterial lung infection.}, journal = {Science translational medicine}, volume = {17}, number = {787}, pages = {eadq4409}, doi = {10.1126/scitranslmed.adq4409}, pmid = {40009694}, issn = {1946-6242}, mesh = {Animals ; *Neutrophils/metabolism ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Pseudomonas aeruginosa ; Lung/microbiology/pathology ; Mice ; Pseudomonas Infections/drug therapy/microbiology/metabolism ; AMP-Activated Protein Kinases/metabolism ; Mice, Inbred C57BL ; Bronchiectasis/microbiology/drug therapy ; Female ; Male ; Disease Models, Animal ; Metformin/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {The composition of the gut microbiota in patients with bronchiectasis has been proven to be distinct from that of healthy individuals, and this disrupted gut microbiota can exacerbate lung infections. However, the responsible microbes and mechanisms in the "gut-lung" axis in bronchiectasis remain unknown. Here, we report that Eggerthella lenta was enriched in the gut, and taurine ursodeoxycholic acid (TUDCA) was enriched in both the guts and sera of patients with bronchiectasis, with both being associated with disease severity. Fecal microbiota transfer from patients with bronchiectasis as well as administration of E. lenta independently exacerbated pulmonary Pseudomonas aeruginosa infections in murine models. E. lenta-associated TUDCA bound adenosine monophosphate-activated protein kinase (AMPK) within neutrophils and interfered with the interaction between liver kinase B1 and AMPK, with a consequential decrease in AMPK phosphorylation. This ultimately reduced ATP production in neutrophils, inhibited their function, and compromised P. aeruginosa elimination from the lung, aggravating tissue injury. Metformin treatment improved disease severity and outcome in the mouse models. In sum, the gut bacterium E. lenta raises the stakes of bacterial lung infection because it causes dysfunction of neutrophils circulated from serum to lung via the metabolite TUDCA. Interventions targeting E. lenta or AMPK phosphorylation may serve as adjunctive strategies to complement existing approaches for managing chronic pulmonary infection in bronchiectasis and other chronic respiratory disease states.}, } @article {pmid39675817, year = {2025}, author = {Ang, TL and Koo, SH and Ang, D and Tan, CK and Wang, LM and Wong, SH and Chow, PKH}, title = {Postcholecystectomy Gut Microbiome Changes and the Clinical Impact: A Systematic Review With Narrative Synthesis.}, journal = {Journal of gastroenterology and hepatology}, volume = {40}, number = {3}, pages = {574-583}, doi = {10.1111/jgh.16846}, pmid = {39675817}, issn = {1440-1746}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Cholecystectomy/adverse effects ; *Dysbiosis ; Diarrhea/microbiology/etiology ; Feces/microbiology ; Bile Acids and Salts/metabolism ; Female ; Prevotella/isolation & purification ; Male ; Bacteroides/isolation & purification ; Firmicutes/isolation & purification ; }, abstract = {BACKGROUND: Cholecystectomy (CCE) can affect the enterohepatic circulation of bile acids and result in gut microbiome changes. This systematic review aimed to clarify the effect of CCE on gut microbiome composition and its clinical impact.

METHOD: A systematic search was conducted in PubMed, Web of Science, and Scopus, combining keywords such as "cholecystectomy" or "post-cholecystectomy" with "gut microbiome," "stool microbiome," or "gut dysbiosis." Data were extracted and synthesized using narrative review. Study quality was assessed using the Newcastle-Ottawa scale.

RESULTS: A total of 1373 articles were screened and 14 studies were selected. Significant but inconsistent microbiome changes were reported. Changes were observed in alpha and beta diversity. At phylum level, an increase in Bacteroides and Ascomycota, decrease in Firmicutes, Actinomycetes, and Basidiomycota, and both increase and decrease in Fusobacteria were reported. At genus level, an increase in Prevotella and a decrease in Faecalibacterium were reported. In post-CCE diarrhea, decreased beta diversity, a decreased F/B ratio, an increase in Prevotella, an increase in Phocaeicola vulgatus, and a decrease in Prevotella copri were noted. For post-CCE syndrome, a higher abundance of Proteobacteria and decreased Firmicutes/Bacteroides (F/B) ratio were reported. A decreased relative abundance of Bifidobacterium longum subsp. longum from controls to CCE without colonic neoplasia to CCE with colonic neoplasia, and an increased abundance of Candida glabrata from controls, to CCE without colonic neoplasia and CCE with colonic neoplasia, were reported.

CONCLUSION: Patients who underwent CCE had significant gut dysbiosis. However, current studies could not clarify the detailed gut microbial structural and functional changes associated with CCE.}, } @article {pmid38535607, year = {2024}, author = {George, UE and Faleye, TOC and De Coninck, L and Agbaje, ST and Ifeorah, IM and Onoja, BA and Oni, EI and Olayinka, AO and Ajileye, TG and Oragwa, AO and Akinleye, TE and Popoola, BO and Osasona, OG and Olayinka, OT and George, OA and Muhammad, AI and Komolafe, I and Adeniji, AJ and Matthijnssens, J and Adewumi, MO}, title = {Metagenomic Detection and Genetic Characterization of Human Sapoviruses among Children with Acute Flaccid Paralysis in Nigeria.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {38535607}, issn = {2076-0817}, mesh = {Humans ; Nigeria/epidemiology ; *Sapovirus/genetics/isolation & purification ; *Phylogeny ; *Genotype ; *Genome, Viral/genetics ; *Caliciviridae Infections/virology/epidemiology/diagnosis ; *Metagenomics ; Child ; Child, Preschool ; *Feces/virology ; Gastroenteritis/virology/epidemiology ; Genetic Variation/genetics ; Infant ; Male ; Female ; Paralysis/virology/epidemiology ; }, abstract = {Using a metagenomic sequencing approach on stool samples from children with Acute Flaccid Paralysis (AFP), we describe the genetic diversity of Sapoviruses (SaVs) in children in Nigeria. We identified six complete genome sequences and two partial genome sequences. Several SaV genogroups and genotypes were detected, including GII (GII.4 and GII.8), GIV (GIV.1), and GI (GI.2 and GI.7). To our knowledge, this is the first description of SaV infections and complete genomes from Nigeria. Pairwise identity and phylogenetic analysis showed that the Nigerian SaVs were related to previously documented gastroenteritis outbreaks with associated strains from China and Japan. Minor variations in the functional motifs of the nonstructural proteins NS3 and NS5 were seen in the Nigerian strains. To adequately understand the effect of such amino acid changes, a better understanding of the biological function of these proteins is vital. The identification of distinct SaVs reinforces the need for robust surveillance in acute gastroenteritis (AGE) and non-AGE cohorts to better understand SaVs genotype diversity, evolution, and its role in disease burden in Nigeria. Future studies in different populations are, therefore, recommended.}, } @article {pmid40008452, year = {2025}, author = {Chen, A and Teng, C and Wei, J and Wu, X and Zhang, H and Chen, P and Cai, D and Qian, H and Zhu, H and Zheng, X and Chen, X}, title = {Gut microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2471015}, pmid = {40008452}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology ; *Cognitive Dysfunction/etiology/physiopathology ; Rats ; *Animals, Newborn ; *Hypoxia-Ischemia, Brain/microbiology ; *Rats, Sprague-Dawley ; *Toll-Like Receptor 4/metabolism/genetics ; Male ; Neuroinflammatory Diseases ; Fecal Microbiota Transplantation ; Intestines/microbiology/pathology ; Lipopolysaccharides ; Hippocampus/metabolism ; Dexamethasone/pharmacology ; Brain-Gut Axis/physiology ; Bacteria/classification/isolation & purification ; Disease Models, Animal ; }, abstract = {Neonatal hypoxic-ischemic brain damage (HIBD) is considered as a major cause of long-term cognitive impairments in newborns. It has been demonstrated that gut microbiota is closely associated with the prognosis of various neurological disorders. However, the role of microbiota-gut-brain axis on cognitive function following neonatal HIBD remains elusive. In this experiment, the correlation analysis supported the involvement of gut microbial changes following hypoxic-ischemic (HI) insult in the development of long-term cognitive impairments. Subsequent experiment revealed the involvement of the intestinal dysfunction in the hippocampal neuroinflammation and synaptic injury. In causal relationship validation experiments, fecal microbiota transplantation (FMT) from cognitively normal rats could restore gut microbial composition, improve intestinal dysfunction, reduce the serum levels of lipopolysaccharides (LPS) and inflammatory mediators, and alleviate neuroinflammation, synaptic damage and cognitive impairments in neonatal HIBD recipient rats. Conversely, the FMT from neonatal HIBD rats could induce above adverse pathological changes in the normal recipient rats. Moreover, oral administration of anti-inflammatory agent dexamethasone (DEX) exhibited the potential to alleviate these detrimental effects in neonatal HIBD rats, with the efficacy being partly reliant on gut microbiota. Further experiment on the potential molecular mechanisms using RNA sequencing indicated a significant increase in the toll-like receptor 4 (TLR4) gene in the intestinal tissues of neonatal HIBD rats. Additionally, the interventions such as TLR4 inhibitor TLR4-IN-C34 administration, FMT, and oral DEX were demonstrated to modulate intestinal function by inhibiting the LPS/TLR4 signaling pathway, thereby exerting neuroprotective effects. Collectively, these findings underscore the contribution of gut microbial dysbiosis post HI insult in activating the LPS/TLR4 signaling pathway, triggering intestinal inflammation and dysfunction, exacerbating systemic inflammation, and consequently worsening synaptic and cognitive impairments in neonatal HIBD rats. Hence, rectifying gut microbial dysbiosis or regulating intestinal function may represent a promising strategy for alleviating long-term cognitive impairments in neonates affected by HIBD.}, } @article {pmid40008084, year = {2025}, author = {Zheng, J and Huang, Y and Zhang, L and Liu, T and Zou, Y and He, L and Guo, S}, title = {Role of the Gut-Lung Microbiome Axis in Airway Inflammation in OVA-Challenged Mice and the Effect of Azithromycin.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {2661-2676}, pmid = {40008084}, issn = {1178-7031}, abstract = {OBJECTIVE: This study aimed to investigate the role of the gut-lung microbiome axis in airway inflammation in asthma and to evaluate the effect of azithromycin on this axis, with a focus on the potential mechanism by which azithromycin reduces allergic airway inflammation.

METHODS: Haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were used to assess pathological changes in the lung tissues of asthmatic mice. Leukocyte cell types in bronchoalveolar lavage fluid (BALF) samples were quantified following Wright-Giemsa staining. Total IgE, OVA-specific IgE, IL-4, IL-6, and IL-17A levels in BALF and total IgE in serum were measured by ELISA. The respiratory and gut microbiota were analysed using 16S rRNA gene sequencing and subsequent taxonomic analysis.

RESULTS: OVA-challenged asthmatic mice with gut microbiota dysbiosis exhibited alterations in the respiratory microbiota, resulting in further aggravation of airway inflammation. Following faecal microbiota transplantation (FMT) to restore gut microbiota, respiratory microbiota dysbiosis was partially improved, and airway inflammation was significantly alleviated. Furthermore, azithromycin reduced airway inflammation in asthmatic mice, particularly non-eosinophilic inflammation, for which low-dose azithromycin combined with budesonide proved more effective. Azithromycin significantly enhanced the diversity and microbial composition of the gut microbiota and also affected the respiratory microbiota. At the phylum level, azithromycin decreased the abundance of Proteobacteria in the gut microbiota. At the genus level, azithromycin reduced the abundance of Pseudomonas in the respiratory microbiota.

CONCLUSION: The gut-lung microbiome axis plays a crucial role in airway inflammation in asthma. Azithromycin may reduce airway inflammation in asthma through modulation of the gut-lung microbiome axis.}, } @article {pmid40007342, year = {2025}, author = {Wang, L and Zhang, Z and Chen, X and Wang, Z and Song, X and Geng, Z and Zhang, X and Wang, Y and Li, J and Hu, J and Zuo, L}, title = {Sakuranetin ameliorates experimental colitis in a gut microbiota-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {139}, number = {}, pages = {156540}, doi = {10.1016/j.phymed.2025.156540}, pmid = {40007342}, issn = {1618-095X}, abstract = {BACKGROUND: The progression of inflammatory bowel disease (IBD) is closely connected with intestinal flora dysbiosis. Sakuranetin (SAK) is a natural compound with anti-inflammatory and antibiosis activities. We investigated the properties and mechanisms of SAK on IBD-like colitis.

METHODS: Mice with dextran sulfate sodium (DSS)-induced colitis were accomplished to assess the effects of SAK on colitis, as well as intestinal mucosal immune imbalance and intestinal barrier dysfunction. 16S rDNA was used to characterize the intestinal flora, and the short-chain fatty acid (SCFA) content in faeces was calculated using GS‒MS. Faecal microbiota transplantation (FMT) and a pseudosterile model (antibiotic cocktail, ABX) were used to evaluate whether the effects of SAK on colitis were dependent on the gut flora. Pathohistological and biochemical tests were used to estimate the safety of SAK.

RESULTS: SAK significantly ameliorated DSS-induced colitis in mice, verified by decreased weight loss, less colon shortening, and lower disease activity, histology and colonoscopy scores. Moreover, SAK alleviated gut dysbiosis and elevated the abundance of SCFA-producing bacteria in DSS-treated mice. Meanwhile, SAK increased faecal SCFA levels and activated GPR41/43 signalling. SAK also improved Treg/Th17 homeostasis and intestinal barrier function. In addition, ABX and FMT experiments confirmed that the ability of SAK to alleviate colitis was mediated through the gut flora. Finally, a safety experiment revealed that SAK had no significant adverse effects on major organ or liver/kidney function.

CONCLUSIONS: SAK may improve the intestinal immune balance and barrier function by regulating intestinal flora dysbiosis and increasing SCFA production, thereby protecting against colitis.}, } @article {pmid40007058, year = {2025}, author = {Ge, P and Guo, Y and Che, B and Jin, H and Chen, L and Chen, Z and Tang, K}, title = {Modulation of NLRP3 Inflammasome Activation by QYHT Decoction: Implications for the Treatment of Erectile Dysfunction in Hyperuricemia.}, journal = {American journal of men's health}, volume = {19}, number = {1}, pages = {15579883251318307}, pmid = {40007058}, issn = {1557-9891}, mesh = {Male ; *Erectile Dysfunction/drug therapy ; Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Rats ; *Hyperuricemia/drug therapy ; *Inflammasomes/metabolism ; *Drugs, Chinese Herbal/pharmacology ; Humans ; Disease Models, Animal ; Oxidative Stress/drug effects ; Rats, Sprague-Dawley ; Gastrointestinal Microbiome/drug effects ; Fecal Microbiota Transplantation ; Middle Aged ; }, abstract = {Hyperuricemia (HUA) causes vascular endothelial dysfunction and oxidative stress, and simultaneously activates the NLRP3 inflammasome, leading to inflammatory reactions and erectile dysfunction (ED). This study aimed to investigate the effects of QYHT (Quyuhuatanerxian decoction) decoction on the NLRP3 inflammasome and explore its potential in treating HUA-induced ED. This study employed four treatment methods: (a) treating HUA-induced ED patients with QYHT and analyzing changes in gut microbiota abundance and fecal metabolites through 16S sequencing; (b) establishing an HUA-induced ED rat model, treating with different doses of QYHT, and examining changes in serum metabolites; (c) conducting fecal microbiota transplantation (FMT) therapy; evaluating erectile function, oxidative stress, inflammatory response, and NLRP3 inflammasome activation levels; and (d) exploring key monomeric compounds and potential targets in QYHT through network pharmacology and molecular docking. The treatment with QYHT and FMT increased testosterone levels, reduced oxidative stress and inflammatory marker levels, and inhibited the expressions of NLRP3-related factors. QYHT affected the gut microbiota structure and metabolite levels. The key components were linoleoyl acetate and mandanol, and the target was JAK2. QYHT decoction regulates the distribution of gut microbiota, improves amino acid metabolism, and effectively inhibits the activation of NLRP3 inflammasomes. This, in turn, enhances erectile function and reduces oxidative stress and inflammatory response levels, leading to successful treatment of HUA-induced ED.}, } @article {pmid40005809, year = {2025}, author = {Parodi, E and Novi, M and Bottino, P and La Porta, E and Merlotti, G and Castello, LM and Gotta, F and Rocchetti, A and Quaglia, M}, title = {The Complex Role of Gut Microbiota in Systemic Lupus Erythematosus and Lupus Nephritis: From Pathogenetic Factor to Therapeutic Target.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005809}, issn = {2076-2607}, abstract = {The role of gut microbiota (GM) and intestinal dysbiosis in triggering the onset and/or modulating the severity and progression of lupus nephritis (LN) has been the object of intense research over the last few years. Some alterations at the phyla level, such as the abundance of Proteobacteria and reduction in Firmicutes/Bacteroidetes (F/B) ratio and in α-diversity have been consistently reported in systemic lupus erythematosus (SLE), whereas a more specific role has been ascribed to some species (Bacteroides thetaiotaomicron and Ruminococcus gnavus) in LN. Underlying mechanisms include microbial translocation through a "leaky gut" and subsequent molecular mimicry, immune dysregulation (alteration of IFNγ levels and of balance between Treg and Th17 subsets), and epigenetic interactions. Levels of bacterial metabolites, such as butyrate and other short-chain fatty acids (SCFAs), appear to play a key role in modulating LN. Beyond bacterial components of GM, virome and mycobiome are also increasingly recognized as important players in the modulation of an immune response. On the other hand, microbiota-based therapy appears promising and includes diet, prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). The modulation of microbiota could correct critical alterations, such as F/B ratio and Treg/Th17 imbalance, and blunt production of autoantibodies and renal damage. Despite current limits, GM is emerging as a powerful environmental factor that could be harnessed to interfere with key mechanisms leading to SLE, preventing flares and organ damage, including LN. The aim of this review is to provide a state-of-the-art analysis of the role of GM in triggering and modulating SLE and LN on the one hand, while exploring possible therapeutic manipulation of GM to control the disease on the other hand.}, } @article {pmid40005733, year = {2025}, author = {Romano, FS and Lallo, MA and Romano, RS and Isidoro, LPS and Cardoso, MR and Sodré, LC and Melchert, A and Guimarães-Okamoto, PTC and Pappalardo, MCF and Amaral, AR and Vendramini, THA}, title = {Fecal Microbiota Transplantation as a Treatment for Granulomatous Colitis in a French Bulldog: A Case Report.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005733}, issn = {2076-2607}, abstract = {Granulomatous colitis, or ulcerative colitis, is an infectious and inflammatory disease that primarily affects the colon and occasionally extends to the ileum, particularly in young Boxer and French Bulldogs. Unlike typical chronic colitis in small animals, the early onset of the disease suggests a genetic predisposition. The condition is characterized by the overgrowth of Escherichia coli, specifically the enteroinvasive variant, which displaces beneficial gut bacteria, contributing to its infectious nature. Secondary dysbiosis and chronic-active inflammation involving histiocytes and other leukocytic infiltrates are prominent features. Clinical manifestations include chronic diarrhea with blood and mucus, frequent tenesmus, and pain, with variable degrees of weight loss depending on disease severity. The final diagnosis is based on clinical history (chronic diarrhea with hematochezia), macroscopic findings from colonoscopy (edema, ulcers, and wall hyperplasia), histopathology (presence of histiocytes), and Escherichia coli growth in culture from a colon fragment. Treatment is guided by colon antibiograms, which often require prolonged antibiotic therapy. Fecal microbiota transplantation (FMT) has emerged as a potential treatment, either as a primary intervention or adjunctive therapy, for conditions such as acute enteritis (e.g., canine parvovirus), dysbiosis, and chronic enteropathies. However, its application to modulate the microbiota and reduce inflammation in granulomatous colitis, potentially leading to longer intervals between relapses, remains an area of ongoing investigation. This is a case report of a French Bulldog diagnosed with ulcerative colitis accompanied by dysbiosis and refractory to standard treatments but sensitive and partially responsive to amikacin. The patient achieved control and sustained improvement in fecal scoring following fecal transplantation. This approach prevented the need for additional antibiotic therapy, ensuring clinical amelioration alongside microbiome restoration.}, } @article {pmid40005617, year = {2025}, author = {Kaltsas, A and Giannakodimos, I and Markou, E and Adamos, K and Stavropoulos, M and Kratiras, Z and Zachariou, A and Dimitriadis, F and Sofikitis, N and Chrisofos, M}, title = {The Role of Gut Microbiota Dysbiosis in Erectile Dysfunction: From Pathophysiology to Treatment Strategies.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005617}, issn = {2076-2607}, abstract = {Erectile dysfunction (ED) is a prevalent male sexual disorder characterized by the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance. While its etiology is multifactorial, encompassing vascular, neurological, hormonal, and psychological components, emerging evidence suggests a significant role for gut microbiota dysbiosis in its development. The gut microbiota influences various metabolic, inflammatory, and neuropsychological processes critical to erectile function. Dysbiosis can lead to systemic inflammation, endothelial dysfunction, hormonal imbalances, and altered neurotransmitter production, all of which are key factors in ED pathogenesis. This narrative review synthesizes current research on the association between gut microbiota alterations and ED, highlighting specific bacterial taxa implicated in ED through mechanisms involving inflammation, metabolic disturbances, and hormonal regulation. This review explores potential mechanisms linking gut microbiota and ED, including pro-inflammatory cytokines, gut barrier integrity disruption, metabolic disorders, psychological factors via the gut-brain axis, and hormonal regulation. Furthermore, the gut microbiota offers promising avenues for developing non-invasive biomarkers and therapeutic interventions such as probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation. Future research should focus on longitudinal studies, mechanistic explorations, and clinical trials to validate these findings and translate them into clinical practice. Understanding the interplay between the gut microbiota and erectile function could unveil novel diagnostic biomarkers and pave the way for innovative treatments targeting the microbiota, ultimately improving men's sexual and overall health.}, } @article {pmid40005608, year = {2025}, author = {Pasta, A and Formisano, E and Calabrese, F and Marabotto, E and Furnari, M and Bodini, G and Torres, MCP and Pisciotta, L and Giannini, EG and Zentilin, P}, title = {From Dysbiosis to Hepatic Inflammation: A Narrative Review on the Diet-Microbiota-Liver Axis in Steatotic Liver Disease.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005608}, issn = {2076-2607}, abstract = {The gut microbiota has emerged as a critical player in metabolic and liver health, with its influence extending to the pathogenesis and progression of steatotic liver diseases. This review delves into the gut-liver axis, a dynamic communication network linking the gut microbiome and liver through metabolic, immunological, and inflammatory pathways. Dysbiosis, characterized by altered microbial composition, contributes significantly to the development of hepatic steatosis, inflammation, and fibrosis via mechanisms such as gut barrier dysfunction, microbial metabolite production, and systemic inflammation. Dietary patterns, including the Mediterranean diet, are highlighted for their role in modulating the gut microbiota, improving gut-liver axis integrity, and attenuating liver injury. Additionally, emerging microbiota-based interventions, such as fecal microbiota transplantation and bacteriophage therapy, show promise as therapeutic strategies for steatotic liver disease. However, challenges such as population heterogeneity, methodological variability, and knowledge gaps hinder the translational application of current findings. Addressing these barriers through standardized approaches and integrative research will pave the way for microbiota-targeted therapies to mitigate the global burden of steatotic liver disease.}, } @article {pmid40005065, year = {2025}, author = {Noureldein, MH and Rumora, AE and Teener, SJ and Rigan, DM and Hayes, JM and Mendelson, FE and Carter, AD and Rubin, WG and Savelieff, MG and Feldman, EL}, title = {Dietary Fatty Acid Composition Alters Gut Microbiome in Mice with Obesity-Induced Peripheral Neuropathy.}, journal = {Nutrients}, volume = {17}, number = {4}, pages = {}, pmid = {40005065}, issn = {2072-6643}, support = {1R01DK076169-00A1/NH/NIH HHS/United States ; 1R01DK115255-00A1/NH/NIH HHS/United States ; 1K99AG081390-00A1/NH/NIH HHS/United States ; 1R00DK119366-00A1/NH/NIH HHS/United States ; 1P30DK063608-00A20/NH/NIH HHS/United States ; 1R01DK130913-00A1/NH/NIH HHS/United States ; P30DK020572//Michigan Diabetes Research Center/ ; not applicable//Dr. John H. Doran Neuropathy Research Initiative/ ; not applicable//Richard and Jane Manoogian Foundation/ ; not applicable//Nathan and Rose Milstein Research Fund/ ; not applicable//Sinai Medical Staff Foundation/ ; not applicable//Taubman Foundation/ ; not applicable//NeuroNetwork for Emerging Therapies/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Obesity/microbiology ; Mice ; *Peripheral Nervous System Diseases/etiology ; *Mice, Inbred C57BL ; *Fatty Acids/metabolism ; *Diet, High-Fat/adverse effects ; Male ; Fecal Microbiota Transplantation ; Dietary Fats ; Disease Models, Animal ; Fatty Acids, Monounsaturated/metabolism ; }, abstract = {BACKGROUND: Peripheral neuropathy (PN), a complication of diabetes and obesity, progresses through a complex pathophysiology. Lifestyle interventions to manage systemic metabolism are recommended to prevent or slow PN, given the multifactorial risks of diabetes and obesity. A high-fat diet rich in saturated fatty acids (SFAs) induces PN, which a diet rich in monounsaturated fatty acids (MUFAs) rescues, independent of weight loss, suggesting factors beyond systemic metabolism impact nerve health. Interest has grown in gut microbiome mechanisms in PN, which is characterized by a distinct microbiota signature that correlates with sciatic nerve lipidome.

METHODS: Herein, we postulated that SFA- versus MUFA-rich diet would impact gut microbiome composition and correlate with PN development. To assess causality, we performed fecal microbiota transplantation (FMT) from donor mice fed SFA- versus MUFA-rich diet to lean recipient mice and assessed metabolic and PN phenotypes.

RESULTS: We found that the SFA-rich diet altered the microbiome community structure, which the MUFA-rich diet partially reversed. PN metrics correlated with several microbial families, some containing genera with feasible mechanisms of action for microbiome-mediated effects on PN. SFA and MUFA FMT did not impact metabolic phenotypes in recipient mice although SFA FMT marginally induced motor PN.

CONCLUSIONS: The involvement of diet-mediated changes in the microbiome on PN and gut-nerve axis may warrant further study.}, } @article {pmid40004205, year = {2025}, author = {Blanquet, L and Serra, D and Marrinhas, C and Almeida, A}, title = {Exploring Gut Microbiota-Targeted Therapies for Canine Idiopathic Epilepsy.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004205}, issn = {1422-0067}, mesh = {Dogs ; Animals ; *Gastrointestinal Microbiome ; *Epilepsy/microbiology/therapy ; *Dog Diseases/microbiology/therapy ; *Dysbiosis/microbiology ; Brain-Gut Axis ; }, abstract = {Epilepsy stands out as one of the most prevalent chronic neurological conditions affecting companion animals. Recent research has increasingly focused on exploring the role of gut microbiota in influencing neurological conditions, like epilepsy. This influence stems from the bidirectional communication pathways between gut bacteria and the brain, which involve metabolic, neural, immunological, and endocrine mechanisms. In fact, a balanced and stable gut microbiota is essential to maintaining normal gut physiology and ensuring appropriate signaling along the gut-brain axis. Conversely, dysbiosis can have detrimental effects on gut physiology and may contribute to the development or exacerbation of neurological conditions, including epilepsy. Considering these findings, this review article aims to deepen the understanding of the mechanisms underlying the microbiota-gut-brain connection in the context of canine idiopathic epilepsy. Moreover, this review presents recent data on innovative gut-related therapeutic strategies for canine idiopathic epilepsy treatment.}, } @article {pmid40004161, year = {2025}, author = {Wang, Z and Ma, X and Shi, W and Zhu, W and Feng, X and Xin, H and Zhang, Y and Cong, B and Li, Y}, title = {The Gut Microbiota Metabolite Butyrate Modulates Acute Stress-Induced Ferroptosis in the Prefrontal Cortex via the Gut-Brain Axis.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004161}, issn = {1422-0067}, support = {82072109//National Natural Science Foundation of China/ ; 82130055//National Natural Science Foundation of China/ ; 82293651//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Prefrontal Cortex/metabolism ; *Ferroptosis/drug effects ; Mice ; Male ; *Stress, Psychological/microbiology/metabolism ; *Brain-Gut Axis/drug effects ; Butyrates/metabolism/pharmacology ; Depression/metabolism/drug therapy/microbiology ; Neurons/metabolism/drug effects ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Stress has been implicated in the onset of mental disorders such as depression, with the prefrontal cortex (PFC) playing a crucial role. However, the underlying mechanisms remain to be fully elucidated. Metabolites secreted by intestinal flora can enter the bloodstream and exert regulatory effects on the body. Consequently, this study aims to investigate the molecular mechanisms by which gut flora influences ferroptosis in PFC neurons, thereby affecting depression-like behavioral changes in mice subjected to acute stress. Initially, we established a mouse model of acute restraint stress (3-day duration) and verified that stress-induced ferroptosis of PFC neurons contributed to depression-like behavioral alterations in mice, as evidenced by morphological, behavioral, and molecular biology assessments. Subsequently, through fecal microbiota transplantation (FMT) experiments, we established a significant correlation between gut microbiota and ferroptosis of PFC neurons in acute stress-exposed mice. 16S rDNA sequencing identified butyric acid-producing bacteria, specifically g_Butyricimonas and its primary metabolite, butyric acid, as critical regulators of ferroptosis in PFC neurons in acutely stressed mice. Furthermore, the intervention of butyrate demonstrated its potential to ameliorate damage to the intestinal and blood-brain barriers in these mice. This intervention also mitigated depression-like behaviors induced by ferroptosis of PFC neurons by alleviating systemic inflammatory responses. The findings of this study indicate that acute stress-induced ferroptosis of PFC neurons plays a critical role in depression-like behavioral changes in mice. Additionally, the gut microbiota metabolite butyrate can modulate ferroptosis and depression-like behavioral changes through the gut-brain axis.}, } @article {pmid40004115, year = {2025}, author = {Zhang, J and Wei, J and Lai, W and Sun, J and Bai, Y and Cao, H and Guo, J and Su, Z}, title = {Focus on Glucagon-like Peptide-1 Target: Drugs Approved or Designed to Treat Obesity.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40004115}, issn = {1422-0067}, mesh = {Humans ; *Obesity/drug therapy/metabolism ; *Glucagon-Like Peptide 1/metabolism ; Animals ; Anti-Obesity Agents/therapeutic use/pharmacology ; Glucagon-Like Peptide-1 Receptor/metabolism ; Gastrointestinal Microbiome/drug effects ; }, abstract = {Obesity is closely related to metabolic diseases, which brings a heavy burden to the health care system. It is urgent to formulate and implement effective treatment strategies. Glucagon-like peptide-1 (GLP-1) is a protein with seven transmembrane domains connected by type B and G proteins, which is widely distributed and expressed in many organs and tissues. GLP-1 analogues can reduce weight, lower blood pressure, and improve blood lipids. Obesity, diabetes, cardiovascular diseases, and other diseases have caused scientists' research and development boom. Among them, GLP-1R agonist drugs have developed rapidly in weight-loss drugs. In this paper, based on the target of GLP-1, the mechanism of action of GLP-1 in obesity treatment was deeply studied, and the drugs approved and designed for obesity treatment based on GLP-1 target were elaborated in detail. Innovatively put forward and summarized the double and triple GLP-1 targeted drugs in the treatment of obesity with better effects and less toxic and side effects, and this can make full use of multi-target methods to treat other diseases in the future. Finally, it is pointed out that intestinal flora and microorganisms have many benefits in the treatment of obesity, and fecal bacteria transplantation may be a potential treatment for obesity with less harm to the body. This article provides some promising methods to treat obesity, which have strong practical value.}, } @article {pmid40003979, year = {2025}, author = {Flynn, CK and Adams, JB and Krajmalnik-Brown, R and Khoruts, A and Sadowsky, MJ and Nirmalkar, K and Takyi, E and Whiteley, P}, title = {Review of Elevated Para-Cresol in Autism and Possible Impact on Symptoms.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40003979}, issn = {1422-0067}, support = {N/A//Zoowalk for Autism Research/ ; }, mesh = {*Cresols/metabolism/urine ; Humans ; Animals ; *Gastrointestinal Microbiome ; Autism Spectrum Disorder/metabolism/microbiology ; Autistic Disorder/metabolism ; Mice ; Sulfuric Acid Esters/metabolism/urine ; Child ; }, abstract = {Para-cresol (p-cresol), and its primary human metabolite p-cresol sulfate (pCS), are among the most studied gut-derived metabolites relevant to autism spectrum disorder (ASD). P-cresol is produced by bacterial modification of phenylalanine or tyrosine and is one of many potentially deleterious metabolites produced by the gut microbiota. Seventeen studies have observed p-cresol and/or p-cresol sulfate as being higher in the urine of children with autism spectrum disorder (ASD) vs. controls. P-cresol has harmful effects on the body, including within the gut, brain, kidneys, liver, immune system, and mitochondria. Some of these effects may contribute to autism and comorbid symptoms. In the gut, p-cresol acts as an antibiotic, altering the gut microbiome to favor the bacteria that produce it. In the mitochondria, p-cresol disrupts ATP production and increases oxidative stress, which is also common in autism. In the brain, p-cresol impairs neuronal development. P-cresol inactivates dopamine beta-hydroxylase, which converts dopamine to noradrenaline. P-cresol sulfate impairs kidney function and is linked to chronic kidney disease (CKD), which is more common in ASD adults. P-cresol also interferes with immune function. Three animal studies have demonstrated that p-cresol causes autism-related symptoms in mice, and that mice can be recovered by the administration of fecal microbiota transplant from healthy mice. Similarly, it was found that microbiota transplant therapy treatment in children with ASD significantly reduced p-cresol sulfate levels to normal and led to significant improvements in gastrointestinal (GI) and ASD symptoms. In summary, p-cresol and pCS likely contribute to ASD core symptoms in a substantial subset of children with ASD.}, } @article {pmid40003971, year = {2025}, author = {Yu, F and Zhu, C and Wu, W}, title = {Senile Osteoarthritis Regulated by the Gut Microbiota: From Mechanisms to Treatments.}, journal = {International journal of molecular sciences}, volume = {26}, number = {4}, pages = {}, pmid = {40003971}, issn = {1422-0067}, support = {11DZ2261100//Shanghai Key Laboratory of Human Performance/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Osteoarthritis/microbiology/therapy ; *Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Prebiotics/administration & dosage ; Animals ; Aging ; Medicine, Chinese Traditional/methods ; }, abstract = {Osteoarthritis (OA) is a chronic, progressive degenerative joint disease that affects the entire synovial joint, leading to the progressive degeneration of articular cartilage. It seriously affects the quality of life and global disability of patients. OA is affected by a variety of factors; the most significant risk factor for OA is age. As individuals age, the risk and severity of OA increase due to the exacerbation of cartilage degeneration and wear and tear. In recent years, research has indicated that the gut microbiota may play a significant role in the aging and OA processes. It is anticipated that regulating the gut microbiota may offer novel approaches to the treatment of OA. The objective of this paper is to examine the relationship between the gut microbiota and senile OA, to investigate the potential mechanisms involved. This review also summarizes the therapeutic strategies related to gut flora in OA management, such as prebiotics and probiotics, diet, exercise, traditional Chinese medicine (TCM) modification, and fecal microbiota transplantation (FMT), highlighting the potential clinical value of gut flora and elucidating the current challenges. The foundation for future research directions is established through the summarization of current research progress.}, } @article {pmid40003268, year = {2025}, author = {Todor, SB and Ichim, C}, title = {Microbiome Modulation in Pediatric Leukemia: Impact on Graft-Versus-Host Disease and Treatment Outcomes: A Narrative Review.}, journal = {Children (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, doi = {10.3390/children12020166}, pmid = {40003268}, issn = {2227-9067}, abstract = {The gut microbiome significantly influences the outcomes of pediatric leukemia, particularly in patients undergoing hematopoietic stem cell transplantation (HSCT). Dysbiosis, caused by chemotherapy, antibiotics, and immune system changes, contributes to complications such as graft-versus-host disease (GVHD), gastrointestinal issues, and infections. Various microbiome-related interventions, including prebiotics, probiotics, postbiotics, and fecal microbiota transplantation (FMT), have shown potential in mitigating these complications. Specific microbial signatures have been linked to GVHD risk, and interventions like inulin, Lactobacillus, and SCFAs (short-chain fatty acids), particularly butyrate, may help modulate the immune system and improve outcomes. FMT, while showing promising results in restoring microbial balance and alleviating GVHD, still requires careful monitoring due to potential risks in immunocompromised patients. Despite positive findings, more research is needed to optimize microbiome-based therapies and ensure their safety and efficacy in pediatric leukemia care.}, } @article {pmid40002939, year = {2025}, author = {Vučinić, D and Redžović, A and Hauser, G and Mikolašević, I}, title = {Microbiota and Radiotherapy: Unlocking the Potential for Improved Gastrointestinal Cancer Treatment.}, journal = {Biomedicines}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/biomedicines13020526}, pmid = {40002939}, issn = {2227-9059}, abstract = {Radiotherapy (RT) is one of the major cornerstones in managing gastrointestinal (GI) cancers. However, several side effects, such as intestinal inflammation, mucosal injury, and dysbiosis, often compromise this. The gut microbiota increasingly attracts much interest as an essential modulator of RT effects influencing immune responses and tissue repair. Through short-chain fatty acids such as butyrate, representatives of certain bacterial species play a crucial role under normal conditions, keeping the mucosal integrity intact and reducing oxidative stress-mediated damage. Dysbiosis, a state where diminished microbial diversity and increased pathogenic species in the microbiota are seen, amplifies RT-induced toxicity in patients. Clinical investigations highlight that microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, hold the means to augment RT efficacy and lessen toxicity. Increased microflora diversity and specific microbial profiles have yielded serious patient improvements. Advanced RT methods use stereotactic body radiotherapy combined with microbiota modulation as a promising technique to shield healthy tissue and maximize immune-mediated antitumor effects. Additionally, there is an implication in tumor behavior regulated by the intratumoral microbiota regarding the response to radiotherapy. Notably, the modulation of gut and tumor microbiota provides an avenue to optimize RT benefits in GI cancers, underscoring the importance of personalized therapy.}, } @article {pmid40002835, year = {2025}, author = {Mafe, AN and Büsselberg, D}, title = {Microbiome Integrity Enhances the Efficacy and Safety of Anticancer Drug.}, journal = {Biomedicines}, volume = {13}, number = {2}, pages = {}, doi = {10.3390/biomedicines13020422}, pmid = {40002835}, issn = {2227-9059}, support = {NPRP 14S0311-210033//QNRF/ ; }, abstract = {The intricate relationship between anticancer drugs and the gut microbiome influences cancer treatment outcomes. This review paper focuses on the role of microbiome integrity in enhancing the efficacy and safety of anticancer drug therapy, emphasizing the pharmacokinetic interactions between anticancer drugs and the gut microbiota. It explores how disruptions to microbiome composition, or dysbiosis, can alter drug metabolism, immune responses, and treatment side effects. By examining the mechanisms of microbiome disruption caused by anticancer drugs, this paper highlights specific case studies of drugs like cyclophosphamide, 5-fluorouracil, and irinotecan, and their impact on microbial diversity and clinical outcomes. The review also discusses microbiome-targeted strategies, including prebiotics, probiotics, postbiotics, and fecal microbiota transplantation (FMT), as promising interventions to enhance cancer treatment. Furthermore, the potential of microbiome profiling in personalizing therapy and integrating these interventions into clinical practice is explored. Finally, this paper proposes future research directions, including developing novel biomarkers and a deeper comprehension of drug-microbiome interactions, to respond to current gaps in knowledge and improve patient outcomes in cancer care.}, } @article {pmid40002529, year = {2025}, author = {Kalaga, P and Ray, SK}, title = {Mental Health Disorders Due to Gut Microbiome Alteration and NLRP3 Inflammasome Activation After Spinal Cord Injury: Molecular Mechanisms, Promising Treatments, and Aids from Artificial Intelligence.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/brainsci15020197}, pmid = {40002529}, issn = {2076-3425}, abstract = {Aside from its immediate traumatic effects, spinal cord injury (SCI) presents multiple secondary complications that can be harmful to those who have been affected by SCI. Among these secondary effects, gut dysbiosis (GD) and the activation of the NOD (nucleotide-binding oligomerization domain) like receptor-family pyrin-domain-containing three (NLRP3) inflammasome are of special interest for their roles in impacting mental health. Studies have found that the state of the gut microbiome is thrown into disarray after SCI, providing a chance for GD to occur. Metabolites such as short-chain fatty acids (SCFAs) and a variety of neurotransmitters produced by the gut microbiome are hampered by GD. This disrupts healthy cognitive processes and opens the door for SCI patients to be impacted by mental health disorders. Additionally, some studies have found an increased presence and activation of the NLRP3 inflammasome and its respective parts in SCI patients. Preclinical and clinical studies have shown that NLRP3 inflammasome plays a key role in the maturation of pro-inflammatory cytokines that can initiate and eventually aggravate mental health disorders after SCI. In addition to the mechanisms of GD and the NLRP3 inflammasome in intensifying mental health disorders after SCI, this review article further focuses on three promising treatments: fecal microbiome transplants, phytochemicals, and melatonin. Studies have found these treatments to be effective in combating the pathogenic mechanisms of GD and NLRP3 inflammasome, as well as alleviating the symptoms these complications may have on mental health. Another area of focus of this review article is exploring how artificial intelligence (AI) can be used to support treatments. AI models have already been developed to track changes in the gut microbiome, simulate drug-gut interactions, and design novel anti-NLRP3 inflammasome peptides. While these are promising, further research into the applications of AI for the treatment of mental health disorders in SCI is needed.}, } @article {pmid40002492, year = {2025}, author = {Gao, A and Lv, J and Su, Y}, title = {The Inflammatory Mechanism of Parkinson's Disease: Gut Microbiota Metabolites Affect the Development of the Disease Through the Gut-Brain Axis.}, journal = {Brain sciences}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/brainsci15020159}, pmid = {40002492}, issn = {2076-3425}, support = {Grant No. 81601330-YS//National Natural Science Foundation of China/ ; Grant No. 2022CFB178-YS//Natural Science Foundation of Hubei Province/ ; }, abstract = {Parkinson's disease is recognized as the second most prevalent neurodegenerative disorder globally, with its incidence rate projected to increase alongside ongoing population growth. However, the precise etiology of Parkinson's disease remains elusive. This article explores the inflammatory mechanisms linking gut microbiota to Parkinson's disease, emphasizing alterations in gut microbiota and their metabolites that influence the disease's progression through the bidirectional transmission of inflammatory signals along the gut-brain axis. Building on this mechanistic framework, this article further discusses research methodologies and treatment strategies focused on gut microbiota metabolites, including metabolomics detection techniques, animal model investigations, and therapeutic approaches such as dietary interventions, probiotic treatments, and fecal transplantation. Ultimately, this article aims to elucidate the relationship between gut microbiota metabolites and the inflammatory mechanisms underlying Parkinson's disease, thereby paving the way for novel avenues in the research and treatment of this condition.}, } @article {pmid40001573, year = {2025}, author = {Mafe, AN and Büsselberg, D}, title = {Modulation of the Neuro-Cancer Connection by Metabolites of Gut Microbiota.}, journal = {Biomolecules}, volume = {15}, number = {2}, pages = {}, doi = {10.3390/biom15020270}, pmid = {40001573}, issn = {2218-273X}, support = {NPRP 14S0311-210033//QNRF/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Brain Neoplasms/metabolism/microbiology ; Animals ; Brain-Gut Axis ; Fatty Acids, Volatile/metabolism ; Bile Acids and Salts/metabolism ; Dysbiosis/metabolism/microbiology ; Tryptophan/metabolism ; Fecal Microbiota Transplantation ; Lipopolysaccharides/metabolism ; }, abstract = {The gut-brain-cancer axis represents a novel and intricate connection between the gut microbiota, neurobiology, and cancer progression. Recent advances have accentuated the significant role of gut microbiota metabolites in modulating systemic processes that influence both brain health and tumorigenesis. This paper explores the emerging concept of metabolite-mediated modulation within the gut-brain-cancer connection, focusing on key metabolites such as short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, and lipopolysaccharides (LPS). While the gut microbiota's impact on immune regulation, neuroinflammation, and tumor development is well established, gaps remain in grasping how specific metabolites contribute to neuro-cancer interactions. We discuss novel metabolites with potential implications for neurobiology and cancer, such as indoles and polyamines, which have yet to be extensively studied. Furthermore, we review preclinical and clinical evidence linking gut dysbiosis, altered metabolite profiles, and brain tumors, showcasing limitations and research gaps, particularly in human longitudinal studies. Case studies investigating microbiota-based interventions, including dietary changes, fecal microbiota transplantation, and probiotics, demonstrate promise but also indicate hurdles in translating these findings to clinical cancer therapies. This paper concludes with a call for standardized multi-omics approaches and bi-directional research frameworks integrating microbiome, neuroscience, and oncology to develop personalized therapeutic strategies for neuro-cancer patients.}, } @article {pmid40001396, year = {2025}, author = {Sher, AA and Whitehead-Tillery, CE and Peer, AM and Bell, JA and Vocelle, DB and Dippel, JT and Zhang, L and Mansfield, LS}, title = {Dynamic Spread of Antibiotic Resistance Determinants by Conjugation to a Human-Derived Gut Microbiota in a Transplanted Mouse Model.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {2}, pages = {}, doi = {10.3390/antibiotics14020152}, pmid = {40001396}, issn = {2079-6382}, support = {RN031097-DEHN//Albert C. and Lois E. Dehn Chair Endowment/ ; NC1202//United States Department of Agriculture/ ; GS100019//University Distinguished Professor Endowment, Michigan State University/ ; U19AI090872//National Institutes of Health, Enterics Research Investigational Network, Cooperative Research Center/ ; Stipend to Azam A. Sher//College of Veterinary Medicine/ ; }, abstract = {BACKGROUND: Antibiotic-resistant (AR) bacteria pose an increasing threat to public health, but the dynamics of antibiotic resistance gene (ARG) spread in complex microbial communities are poorly understood. Conjugation is a predominant direct cell-to-cell mechanism for the horizontal gene transfer (HGT) of ARGs. We hypothesized that commensal Escherichia coli donor strains would mediate the conjugative transfer of ARGs to phylogenetically distinct bacteria without antibiotic selection pressure in gastrointestinal tracts of mice carrying a human-derived microbiota with undetectable levels of E. coli. Our objective was to identify a mouse model to study the factors regulating AR transfer by conjugation in the gut.

METHODS: Two donor E. coli strains were engineered to carry chromosomally encoded red fluorescent protein, and an ARG- and green fluorescent protein (GFP)-encoding broad host range RP4 conjugative plasmid. Mice were orally gavaged with two donor strains (1) E. coli MG1655 or (2) human-derived mouse-adapted E. coli LM715-1 and their colonization assessed by culture over time. Fluorescence-activated cell sorting (FACS) and 16S rDNA sequencing were performed to trace plasmid spread to the microbiota.

RESULTS: E. coli LM715-1 colonized mice for ten days, while E. coli MG1655 was not recovered after 72 h. Bacterial cells from fecal samples on days 1 and 3 post inoculation were sorted by FACS. Samples from mice given donor E. coli LM715-1 showed an increase in cells expressing green but not red fluorescence compared to pre-inoculation samples. 16S rRNA gene sequencing analysis of FACS GFP positive cells showed that bacterial families Lachnospiraceae, Clostridiaceae, Pseudomonadaceae, Rhodanobacteraceae, Erysipelotrichaceae, Oscillospiraceae, and Butyricicoccaceae were the primary recipients of the RP4 plasmid.

CONCLUSIONS: Results show this ARG-bearing conjugative RP4 plasmid spread to diverse human gut bacterial taxa within a live animal where they persisted. These fluorescent marker strategies and human-derived microbiota transplanted mice provided a tractable model for investigating the dynamic spread of ARGs within gut microbiota and could be applied rigorously to varied microbiotas to understand conditions facilitating their spread.}, } @article {pmid40000989, year = {2025}, author = {Zhao, M and Zhang, Y and Liu, S and Wang, F and Zhang, P}, title = {Eradication of Helicobacter pylori reshapes gut microbiota and facilitates the evolution of antimicrobial resistance through gene transfer and genomic mutations in the gut.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {90}, pmid = {40000989}, issn = {1471-2180}, support = {32201393//National Natural Science Foundation of China/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects/genetics ; Humans ; *Helicobacter pylori/genetics/drug effects ; *Drug Resistance, Bacterial/genetics ; *Anti-Bacterial Agents/pharmacology ; *Helicobacter Infections/microbiology/drug therapy ; *Gene Transfer, Horizontal ; *Feces/microbiology ; Mutation ; Metagenomics ; Klebsiella/genetics/drug effects ; Female ; Male ; Genome, Bacterial/genetics ; Adult ; Escherichia/genetics/drug effects ; Middle Aged ; Genes, Bacterial/genetics ; }, abstract = {Treating Helicobacter pylori (H. pylori) infection requires large quantities of antibiotics, thus dramatically promoting the enrichment and dissemination of antimicrobial resistance (AMR) in feces. However, the influence of H. pylori eradication on the AMR mobility and the gut microbiota evolution has yet to be thoroughly investigated. Here, a study involving 12 H. pylori-positive participants was conducted, and the pre- and post- eradication fecal samples were sequenced. Metagenomic analysis revealed that the eradication treatment drastically altered the gut microbiome, with the Escherichia and Klebsiella genera emerging as the predominant bacteria. Interestingly, the eradication treatment significantly increased the relative abundance and diversity of resistome and mobilome in gut microbiota. Eradication of H. pylori also enriched AMR genes (ARGs) conferring resistance to antibiotics not administered because of the co-location with other ARGs or mobile genetic elements (MGEs). Additionally, the Escherichia and Klebsiella genera were identified as the primary bacterial hosts of these highly transferable ARGs. Furthermore, the genomic variations associated with ARGs in Escherichia coli (E. coli) caused by the eradication treatment were profiled, including the parC, parE, and gyrA genes. These findings revealed that H. pylori eradication promoted the enrichment of ARGs and MGEs in the Escherichia and Klebsiella genera, and further facilitated bacterial evolution through the horizontal transfer of ARGs and genomic variations.}, } @article {pmid39999537, year = {2025}, author = {Dhanasekaran, D and Venkatesan, M and Sabarathinam, S}, title = {Efficacy of microbiome-targeted interventions in obesity management- A comprehensive systematic review.}, journal = {Diabetes & metabolic syndrome}, volume = {19}, number = {2}, pages = {103208}, doi = {10.1016/j.dsx.2025.103208}, pmid = {39999537}, issn = {1878-0334}, abstract = {BACKGROUND: Obesity is a global health crisis linked to numerous chronic diseases. The gut microbiome plays a crucial role in human metabolism, and emerging evidence suggests that modulating the microbiome may offer novel therapeutic avenues for obesity management.

OBJECTIVE: This systematic review aimed to assess the efficacy and safety of microbiome-targeted interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, in improving body composition, metabolic parameters, and inflammatory markers in overweight and obese adults.

METHODS: A comprehensive search of PubMed, Scopus, and ScienceDirect was conducted to identify relevant studies published between 2005 and 2023. Included studies were assessed for methodological quality and risk of bias using the Cochrane Collaboration tool.

RESULTS: Body composition: Most studies demonstrated significant reductions in body weight, Body mass index, and body fat percentage.

METABOLIC PARAMETERS: Improvements were observed in lipid profiles (reduced cholesterol, triglycerides) and glucose metabolism (improved insulin sensitivity).

INFLAMMATORY MARKERS: Significant reductions were observed in inflammatory markers such as Interleukins (IL-6, IL-8) and C-reactive protein.

MICROBIAL COMPOSITION: Interventions generally led to shifts in microbial composition, with increases in beneficial bacteria such as Bifidobacterium and Lactobacillus.

ADVERSE EVENTS: Adverse events were generally minimal and limited.

CONCLUSION: This review provides strong evidence that microbiome-targeted interventions can effectively improve body composition, metabolic parameters, and inflammatory markers in individuals with obesity. Further research is needed to optimize intervention strategies, identify specific microbial targets, and translate these findings into effective clinical applications.}, } @article {pmid39999013, year = {2025}, author = {Tashkent, Y and Choo, JM and Richard, A and Wang, Z and Calzadilla-Bertot, L and Vasil, E and Miller, S and Taylor, SL and Ivey, KL and Woodman, R and Adler, B and Ayonrinde, OT and Olynyk, JK and Beilin, LJ and Mori, TA and Wigg, AJ and Muller, KR and Adams, LA and Rogers, GB}, title = {Steatotic Liver Disease in Younger Adults is Associated With Altered Gut Microbiology.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {45}, number = {3}, pages = {e70032}, pmid = {39999013}, issn = {1478-3231}, support = {//Gastroenterological Society of Australia/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Male ; Adult ; Female ; Cross-Sectional Studies ; *Feces/microbiology ; Magnetic Resonance Imaging ; Fatty Liver/microbiology/diagnostic imaging ; }, abstract = {BACKGROUND AND AIMS: Steatotic liver disease (SLD) is a leading cause of chronic liver disease worldwide. As SLD pathogenesis has been linked to gut microbiome alterations, we aimed to identify SLD-associated gut microbiome features early in SLD development by utilising a highly characterised cohort of community-dwelling younger adults.

METHODS AND RESULTS: At age 27 years, 588 participants of the Raine Study Generation 2 underwent cross-sectional assessment. Hepatic steatosis was quantified using a validated magnetic resonance imaging (MRI) volumetric liver fat fraction (VLFF) equation (HepaFat). Of the 588 participants, 488 (83%) were classified as having 'no SLD' (VLFF ≤ 3.55%), 76 (12.9%) with 'mild-moderate' SLD (VLFF: 3.56%-13.4%) and 24 (4.10%) with 'severe' SLD (VLFF > 13.4%). Stool microbiome profiling identified an association between severe SLD and lower microbiota alpha diversity (observed features [p = 0.015], Pielou evenness [p = 0.001] and Shannon diversity [p = 0.002]) compared to no SLD. Faecal microbiota composition differed significantly between no SLD and both mild-moderate (p = 0.004) and severe SLD groups (p = 0.001). There was no significant difference in microbiota dispersion between SLD groups. Reduced relative abundance of short-chain fatty acid producing bacteria, and higher levels of proinflammatory bacterial taxa, were both significantly associated with severe SLD (q < 0.05).

CONCLUSIONS: SLD in younger adults is associated with reduced intestinal microbial diversity and a pattern of bacterial taxa depletion that is consistent with other chronic inflammatory conditions. Our characterisation of gut microbiome characteristics in early SLD development provides a potential basis for risk identification and reduction.

TRIAL REGISTRATION: The Raine Study is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617001599369).}, } @article {pmid39998920, year = {2025}, author = {Lundgrin, EL and Hatipoglu, B}, title = {Trending Modalities in Type 2 Diabetes Prevention.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {110}, number = {Supplement_2}, pages = {S187-S192}, doi = {10.1210/clinem/dgaf040}, pmid = {39998920}, issn = {1945-7197}, support = {//This work was supported by the Deborah and Ronald Ratner Fund/ ; //Mary B. Lee Chair/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/prevention & control ; *Prediabetic State/therapy ; Hypoglycemic Agents/therapeutic use ; Fecal Microbiota Transplantation ; Incretins/therapeutic use ; Gastrointestinal Microbiome ; Life Style ; }, abstract = {CONTEXT: Prediabetes now affects a substantial proportion of the population, marking a growing group of individuals at increased risk for the development of type 2 diabetes (T2D). Given the profound effect of T2D on an individual's morbidity and mortality, T2D prevention is of critical importance.

EVIDENCE ACQUISITION: We searched PubMed and Ovid MEDLINE databases for recent systematic reviews, meta-analyses, and original research articles pertaining to prediabetes and the prevention of T2D.

EVIDENCE SYNTHESIS: T2D prevention strategies have focused on intensive lifestyle modification as well as numerous medications that ultimately improve insulin resistance. Recently, a better understanding of the gut microbiome's role in diabetes progression has suggested a possible preventive role for fecal transplant. Finally, multiple incretin pharmaceutical agents have been developed that show promise in the prevention and treatment of T2D.

CONCLUSION: The number of novel ways to prevent T2D is rapidly growing. A thorough understanding of the indications, outcomes, and limitations of these new therapies is critical for all who care for individuals with diabetes.}, } @article {pmid39998294, year = {2025}, author = {Wolfe, TM and Jo, J and Pinkham, NV and Garey, KW and Walk, ST}, title = {The impact of ibezapolstat and other Clostridioides difficile infection-relevant antibiotics on the microbiome of humanized mice.}, journal = {Antimicrobial agents and chemotherapy}, volume = {}, number = {}, pages = {e0160424}, doi = {10.1128/aac.01604-24}, pmid = {39998294}, issn = {1098-6596}, abstract = {Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for the treatment of Clostridioides difficile infection (CDI). Previous studies demonstrated that IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics. Groups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare the gut microbiome perturbations between treatment and no-drug control groups. Among the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversities following FDX- and IBZ-treated groups were less pronounced than those observed in VAN- or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of Bacteroidota (phylum), with IBZ additionally increasing the relative abundance of Actinomycetota (phylum). In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity than VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.}, } @article {pmid39996827, year = {2025}, author = {Lu, D and Ma, X and Tao, K and Lei, H}, title = {Advancements in the Pathogenesis, Diagnosis, and Therapeutic Implications of Intestinal Bacteria.}, journal = {Current issues in molecular biology}, volume = {47}, number = {2}, pages = {}, pmid = {39996827}, issn = {1467-3045}, support = {2024AFB070//Hubei Natural Science Foundation/ ; 2023XHYN043//Science Foundation of Union Hospital/ ; 82403220//National Natural Science Foundation of China/ ; }, abstract = {Intestinal bacteria form one of the most complex microbial communities in the human body, playing a crucial role in maintaining host health and contributing to the development of various diseases. Here, we provide a comprehensive overview of the composition and function of intestinal bacteria, the factors affecting their homeostasis, and their association and mechanisms with a range of diseases (e.g., inflammatory bowel diseases, colorectal cancer, metabolic diseases). Additionally, their advanced potential in disease diagnosis and treatment is highlighted. Therapies, such as chemotherapy, radiotherapy, and immunotherapy, are significantly impacted by intestinal bacteria, with research indicating that bacteria can enhance chemoimmunotherapy efficiency by affecting T cell recruitment and immune cell infiltration. Fecal microbiota transplantation has emerged as a promising option for treating recurrent Clostridium difficile infections and certain metabolic and neurological disorders. Gut bacteria-related serum metabolites serve as non-invasive indicators for diagnosing CRC, while fecal immunochemical tests offer promising applications in CRC screening. Future research is needed to better understand the causal relationships between intestinal bacteria and diseases, develop more precise diagnostic tools, and evaluate the effectiveness and safety of microbiome-targeted therapies in clinical treatment. This study provides deeper insights into the role of intestinal bacteria in human health and disease, providing a scientific basis for innovative therapeutic strategies that have the potential to transform the landscape of healthcare.}, } @article {pmid39996549, year = {2025}, author = {Yu, YS and Weng, YT and Wu, CW and Tzeng, YS}, title = {Successful Perianal Wound Treatment Using the Fecal Management System: A Report of 2 Cases.}, journal = {Annals of plastic surgery}, volume = {94}, number = {3S Suppl 1}, pages = {S87-S89}, doi = {10.1097/SAP.0000000000004197}, pmid = {39996549}, issn = {1536-3708}, mesh = {Humans ; Female ; Aged ; Young Adult ; *Wound Healing/physiology ; Negative-Pressure Wound Therapy/methods ; Debridement/methods ; Anal Canal/injuries/surgery ; Skin Transplantation/methods ; Burns/therapy ; Treatment Outcome ; Colostomy/methods ; }, abstract = {BACKGROUND: Fecal diversion is important for healing of perianal wounds. However, traditional fecal diversion with colostomy is associated with risks of general anesthesia and requires healthy abdominal skin for stoma creation. Alternative methods of fecal diversion are needed.

AIM AND OBJECTIVES: We aimed to illustrate an effective alternate method of fecal diversion in patients with perianal wounds by reporting 2 patients with perianal wounds who were successfully treated using the fecal management system.

MATERIALS AND METHODS: The first patient was a 79-year-old female with a grade IV sacral pressure injury who underwent operative debridements and vacuum-assisted wound closure. The second patient was a 21-year-old female with extensive perianal burn wounds who underwent a series of debridements, wound dressing changes, and split-thickness skin grafts. The fecal management system was utilized for fecal diversion in both patients.

RESULTS: Satisfactory wound healing was achieved in each patient using the fecal management system for fecal diversion.

CONCLUSIONS: Based on our 2 patients and previous studies that have reported successful treatment of perianal wounds using the fecal management system, this system is feasible to use and effective. We suggest its use in patients with perianal wounds, particularly those in whom colostomy is not preferable or contraindicated.}, } @article {pmid39996473, year = {2025}, author = {Wang, X and Hu, M and Wu, W and Lou, X and Gao, R and Ma, T and Dheen, ST and Cheng, J and Xiong, J and Chen, X and Wang, J}, title = {Indole derivatives ameliorated the methamphetamine-induced depression and anxiety via aryl hydrocarbon receptor along "microbiota-brain" axis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2470386}, doi = {10.1080/19490976.2025.2470386}, pmid = {39996473}, issn = {1949-0984}, mesh = {Animals ; Mice ; *Receptors, Aryl Hydrocarbon/metabolism/genetics ; *Methamphetamine/adverse effects ; *Depression/chemically induced/metabolism/drug therapy ; *Indoles/pharmacology/metabolism ; *Anxiety/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Brain-Gut Axis/drug effects ; Male ; Humans ; *Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Bacteria/classification/genetics/metabolism/isolation & purification ; Tryptophan/metabolism ; Brain/metabolism ; Mice, Knockout ; Adult ; Substance Withdrawal Syndrome/drug therapy/metabolism ; }, abstract = {In addition to the high neurotoxicity, depression, and anxiety are the most prominent characteristics of methamphetamine (Meth) withdrawal. Studies to date on the issue of Meth-associated depression and anxiety are focused on the brain, however, whether peripheral homeostasis, especially the "microbiota-gut" axis participates in these adverse outcomes, remains poorly understood. In the current study, with the fecal microbiota transplantation (FMT) assay, the mice received microbiota from Meth withdrawal mice displayed marked depression and anxiety behaviors. The 16S rRNA sequencing results showed that Meth withdrawal contributed to a striking reduction of Akkermansia, Bacteroides, Faecalibaculum, Desulfovibrio, and Anaerostipes, which are known to be associated with tryptophan (TRP) metabolism. Noteworthily, the substantial decreases of the indole derivatives from the TRP metabolic pathway, including IAA, IPA, ILA, IET, IArA, IAld, and TRM were observed in the serum of both Meth abusing humans and mice during Meth withdrawal with the UHPLC-MS/MS analysis. Combining the high and low TRP diet mouse model, the mice with high TRP diet obviously impeded Meth-associated depression and anxiety behaviors, and these results were further strengthened by the evidence that administration of IPA, IAA, and indole dramatically ameliorated the Meth induced aberrant behaviors. Importantly, these protective effects were remarkably counteracted in aryl hydrocarbon receptor knockout (AhR KO) mice, underlining the key roles of microbiota-indoles-AhR signaling in Meth-associated depression and anxiety. Collectively, the important contribution of the present work is that we provide the first evidence that peripheral gut homeostasis disturbance but not limited to the brain, plays a key role in driving the Meth-induced depression and anxiety in the periods of withdrawal, especially the microbiota and the indole metabolic disturbance. Therefore, targeting AhR may provide novel insight into the therapeutic strategies for Meth-associated psychological disorders.}, } @article {pmid39996135, year = {2025}, author = {Sehgal, K and Berry, P and Cho, J and Saffouri, G and Dierkhising, RA and Battaglioli, E and Kashyap, PC and Pardi, D and Khanna, S}, title = {Body mass index changes after fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251321121}, pmid = {39996135}, issn = {1756-283X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a successful therapy for Clostridioides difficile infection (CDI). FMT from overweight donors is speculated to influence the recipient's body mass index (BMI) after administration for CDI.

OBJECTIVES: We investigated changes in the recipient's BMI after FMT in relation to the donor's BMI.

DESIGN: We conducted a retrospective cohort study involving patients who underwent FMT for recurrent CDI at Mayo Clinic between 2012 and 2019.

METHODS: We analyzed demographic and donor data for patients undergoing FMT at Mayo Clinic (2012-2019). Recipient BMI (pre- and post-FMT) and donor BMI were extracted from medical records. Mixed-effects linear regression was used to evaluate the impact of donor BMI, donor BMI category, recipient baseline BMI, time before and after FMT, and interactions between these variables on overall BMI change and BMI change per month. Kaplan-Meier curves were used to assess BMI changes (⩾5 units) based on the last recorded post-FMT BMI.

RESULTS: We analyzed data from 401 patients with recorded BMI measurements before and after FMT. The median age of the recipients at the time of FMT was 59.1 years (interquartile range (IQR): 40.5-70.1 years), with 61.6% being female. The median BMI for recipients prior to FMT was 26.7 kg/m² (IQR: 22.7-31.6 kg/m²), while the median BMI of the donors was 24.5 kg/m[2] (IQR: 23.9-27.5 kg/m[2]). Stool from donors with a normal BMI was used for 58.2% of recipients, while 41.8% received stool from pre-obese donors. Donor BMI data were missing for 3.2% of recipients. Donor BMI was not significantly associated with changes in recipient BMI; for each 1-unit increase in donor BMI, a 0.01-unit monthly increase was observed (95% confidence interval: -0.0003, 0.02; p = 0.11). The log-rank test for BMI increases (⩾+5) and decreases (⩽-5) revealed no significant differences among the donor BMI groups (Chi-squared = 4.4, p = 0.1 for increases, Chi-squared = 2, p = 0.4 for decreases).

CONCLUSION: The lack of impact of donor BMI on BMI changes post-FMT suggests that these changes are more dependent on the recipient's metabolic profile. Prospective, controlled trials are required to analyze these results more comprehensively.}, } @article {pmid39996003, year = {2025}, author = {Ren, K and Yong, C and Jin, Y and Rong, S and Xue, K and Cao, B and Wei, H}, title = {Unraveling the microbial mysteries: gut microbiota's role in ulcerative colitis.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1519974}, pmid = {39996003}, issn = {2296-861X}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. Recent research has highlighted the significant role of gut microbiota in the pathogenesis and treatment of UC. This review aims to provide a comprehensive overview of the current understanding of the relationship between gut microbiota and UC. We discuss the involvement of gut microbiota in the onset of UC, including the dysbiosis observed in patients and its potential mechanisms. Additionally, the role of extra-intestinal microbiota in UC pathogenesis is explored, which has been less studied but is gaining attention. The influence of gut microbiota on the efficacy of biological immunotherapy for UC is also examined, highlighting how microbial composition can influence treatment outcomes. Furthermore, we review microbiota transplantation, and their potential benefits in UC management. Finally, we consider the combined use of antibiotics and biological agents in UC treatment, discussing their synergistic effects and potential drawbacks. This review underscores the importance of gut microbiota in UC and suggests that targeting microbial communities could offer new avenues for effective treatment.}, } @article {pmid39995913, year = {2025}, author = {Morshedbak, M and Rahimi, K and Tabandeh, MR}, title = {Effect of fecal microbiota transplantation on ulcerative colitis model in rats: The gut-brain axis.}, journal = {Heliyon}, volume = {11}, number = {3}, pages = {e42430}, pmid = {39995913}, issn = {2405-8440}, abstract = {STUDY OBJECTIVES: The impact of fecal microbiota transplantation (FMT) on the TLR4/MYD88/NF-kB signaling pathway in the colon in the ulcerative colitis model, as well as the incidence of anxiety behaviors caused by the colitis model was investigated.

METHODS: Twenthy four ats were induced with ulcerative colitis using a 4 % acetic acid solution administered intrarectally and were subsequently treated with prednisolone and FMT. The study examined several indicators, such as TLR4, MYD88, and NF-κB mRNA expression, along with oxidative stress factors. Additionally, it examined the relationship between anxiety-related behaviors and colitis and assessed the pro-inflammatory cytokines in the hippocampus.

RESULTS: FMT led to lower disease score index and improved colon tissue pathology findings. This was associated with reduced mRNA expression of TLR4, MYD88, and NF-κB, as well as lower levels of TOS, and higher levels of TAC, GSH, and GSSG in colon tissues. FMT was found to reduce anxiety in both the open field and elevated plus maze tests. Additionally, levels of IL-6 and TNF-a were decreased in the hippocampus.

CONCLUSIONS: FMT suppressed acetic acid-induced colitis by inhibiting the TLR4/MYD88/NF-kB signaling pathway. FMT reduced anxiety in open field and plus maze tests, and resulted in decreased levels of IL-6 and TNF-a in the hippocampus.}, } @article {pmid39994836, year = {2025}, author = {Wan, J and Zhou, J and Wang, Z and Liu, D and Zhang, H and Xie, S and Wu, K}, title = {Recent advances in epidemiology, pathogenesis, diagnosis, and treatment of inflammatory bowel disease: Insights from the past two years.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, pmid = {39994836}, issn = {2542-5641}, abstract = {Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic inflammation of the gastrointestinal tract with unknown etiology. The cause of IBD is widely considered multifactorial, with prevailing hypotheses suggesting that the microbiome and various environmental factors contribute to inappropriate activation of the mucosal immune system in genetically susceptible individuals. Although the incidence of IBD has stabilized in Western countries, it is rapidly increasing in newly industrialized countries, particularly China, making IBD a global disease. Significant changes in multiple biomarkers before IBD diagnosis during the preclinical phase provide opportunities for earlier diagnosis and intervention. Advances in technology have driven the development of telemonitoring tools, such as home-testing kits for fecal calprotectin, serum cytokines, and therapeutic drug concentrations, as well as wearable devices for testing sweat cytokines and heart rate variability. These tools enable real-time disease activity assessment and timely treatment strategy adjustments. A wide range of novel drugs for IBD, including interleukin-23 inhibitors (mirikizumab, risankizumab, and guselkumab) and small-molecule drugs (etrasimod and upadacitinib), have been introduced in the past few years. Despite these advancements, approximately one-third of patients remain primary non-responders to the initial treatment, and half eventually lose response over time. Precision medicine integrating multi-omics data, advanced combination therapy, and complementary approaches, including stem cell transplantation, psychological therapies, neuromodulation, and gut microbiome modulation therapy, may offer solutions to break through the therapeutic ceiling.}, } @article {pmid39994634, year = {2025}, author = {Almheiri, RT and Hajjar, B and Alkhaaldi, SMI and Rabeh, N and Aljoudi, S and Abd-Elrahman, KS and Hamdan, H}, title = {Beyond weight loss: exploring the neurological ramifications of altered gut microbiota post-bariatric surgery.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {223}, pmid = {39994634}, issn = {1479-5876}, mesh = {Humans ; *Bariatric Surgery ; *Gastrointestinal Microbiome ; *Weight Loss ; *Nervous System Diseases/microbiology ; Animals ; }, abstract = {This review discusses findings related to neurological disorders, gut microbiota, and bariatric surgery, focusing on neurotransmitters, neuroendocrine, the pathophysiology of bacteria contributing to disorders, and possible therapeutic interventions. Research on neurotransmitters suggests that their levels are heavily influenced by gut microbiota, which may link them to neurological disorders such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Depression, and Autism spectrum disorder. The pathophysiology of bacteria that reach and influence the central nervous system has been documented. Trends in microbiota are often observed in specific neurological disorders, with a prominence of pro-inflammatory bacteria and a reduction in anti-inflammatory types. Furthermore, bariatric surgery has been shown to alter microbiota profiles similar to those observed in neurological disorders. Therapeutic interventions, including fecal microbiota transplants and probiotics, have shown potential to alleviate neurological symptoms. We suggest a framework for future studies that integrates knowledge from diverse research areas, employs rigorous methodologies, and includes long-trial clinical control groups.}, } @article {pmid39991465, year = {2025}, author = {Ahmadi, A and Kouhsari, E and Razavi, S and Mohamadzadeh, N and Besharat, S and Vakili, MA and Amiriani, T}, title = {Comparative analysis of dominant gut microbiota in Inflammatory Bowel Disease patients and healthy individuals: A case-control study.}, journal = {New microbes and new infections}, volume = {64}, number = {}, pages = {101567}, pmid = {39991465}, issn = {2052-2975}, abstract = {BACKGROUND: Chronic inflammation in the gut might be linked to microbiota dysbiosis.

OBJECTIVE: This study aimed to investigate alterations in the gut microbiota composition of adult IBD patients compared to healthy controls.

METHODS: This case-control study investigated the relationship between faecal microbiota composition and IBD in adults. Real-time qPCR analysis using bacterial 16S rRNA gene quantified the abundance of six key bacterial groups (Firmicutes, Lactobacillus spp., Bifidobacterium spp., Fusobacterium spp., Bacteroides fragilis, and Faecalibacterium prausnitzii) in faecal samples from 30 IBD patients (13 Crohn's disease, 17 ulcerative colitis) and 30 healthy controls. A correlation matrix was employed to assess relationships between these bacteria.

RESULTS: Real-time qPCR revealed significant differences (p-value <0.05) in the abundance of several bacterial groups between IBD patients and healthy controls. Firmicutes, Fusobacterium spp., and B. fragilis were significantly more abundant (p-value <0.05) in IBD patients compared to controls. Conversely, Lactobacillus spp. and F. prausnitzii were both significantly less abundant (p-value <0.05) in IBD patients. While some bacterial groups exhibited trends toward higher abundance in either CD or UC patients, these differences were not statistically significant (p-value >0.111). The correlation matrix analysis revealed specific co-occurrence patterns: Bacteroides showed a strong negative correlation with Prevotella, more abundant in healthy controls, suggesting a shift in dominance in IBD patients. Lactobacillus spp. and F. prausnitzii exhibited a positive correlation in healthy individuals, indicating their potential cooperative role in maintaining gut homeostasis.

CONCLUSION: This study identified significant alterations in gut microbiota composition in adult IBD patients compared to healthy controls, with notable differences in the abundance of specific bacterial groups. These findings suggest that gut microbiota dysbiosis may play a critical role in IBD pathogenesis. The identification of specific bacterial imbalances provides a foundation for developing microbiota-based therapies, such as probiotics, prebiotics, and fecal microbiota transplantation, as potential interventions for restoring microbial balance and mitigating disease progression. Further research is needed to translate these insights into targeted therapeutic strategies and to explore their effectiveness in clinical settings.}, } @article {pmid39989875, year = {2025}, author = {Bednárik, DS and Földvári-Nagy, KC and Simon, V and Rancz, A and Gede, N and Veres, DS and Paraskevopoulos, P and Schnabel, T and Erőss, B and Hegyi, P and Lenti, K and Földvári-Nagy, L}, title = {Comparative effectiveness of different therapies for Clostridioides difficile infection in adults: a systematic review and network meta-analysis of randomized controlled trials.}, journal = {The Lancet regional health. Europe}, volume = {49}, number = {}, pages = {101151}, pmid = {39989875}, issn = {2666-7762}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated diarrhea, with substantial morbidity and mortality. CDI is a severe and growing problem with numerous treatment options. We evaluated the effectiveness of all therapies in recurrent and non-recurrent infections and their prevention.

METHODS: This network meta-analysis and systematic review of randomized controlled trials (RCTs) compared all CDI therapies and preventions. We included RCTs published until 19 August 2024 and focused on adult population. We performed a systematic search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Inclusion criteria were patients: adults (>16) treated against CDI; study type: randomized controlled trial; outcome: cure rate, recurrence or effectiveness of prevention. Any publication not meeting all criteria was considered to be ineligible and excluded. We applied random-effects meta-analysis using frequentist methods. We reported our main results as odds ratios (as a symmetric effect size measure, OR) with 95% confidence interval (95% CI). We used the Cochrane risk-of-bias tool to assess the risk of bias. Our study protocol was preregistered in PROSPERO (CRD42022371210).

FINDINGS: We assessed 73 RCTs with 28 interventions, involving 27,959 patients (49.2% female) in five networks. Fecal microbiota transplantation (FMT) was the most effective treatment in terms of the cure rate overall (P-score: 0.9952) and in recurrent cases (P-score: 0.9836). In recurrent cases, fidaxomicin (P-score: 0.6734) showed significantly greater effectiveness than vancomycin (P-score: 0.3677) and tolevamer (P-score: 0.0365). For non-recurrent CDI treatments ridinilazole, fidaxomicin, FMT and nitazoxanide were equally effective. Ridinilazole (P-score: 0.7671) and fidaxomicin (P-score: 0.7627) emerged as the most effective in preventing recurrence. Probiotics were not effective in preventing CDI, since network meta-analyses did not show significant differences between probiotics and placebo. In probiotics' subgroups pairwise meta-analyses Lactobacillaceae proved to be significantly more effective in prevention than placebo. Oral and colonoscopic FMT administration methods were equally effective. The study-level aggregated risk of bias of the publications included ranged from low to high. We observed relevant heterogeneity among studies in therapeutic doses, treatment durations, and follow-up times.

INTERPRETATION: The superiority of FMT in the treatment of CDI highlights the potential for increased use of FMT in clinical settings. Further research on optimizing FMT protocols and exploring its long-term safety and efficacy in larger samples is needed. Our findings suggest that the preventive use of probiotics might be questioned.

FUNDING: None.}, } @article {pmid39989768, year = {2025}, author = {Reddi Sree, R and Kalyan, M and Anand, N and Mani, S and Gorantla, VR and Sakharkar, MK and Song, BJ and Chidambaram, SB}, title = {Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review.}, journal = {ACS omega}, volume = {10}, number = {6}, pages = {5148-5171}, pmid = {39989768}, issn = {2470-1343}, abstract = {Alzheimer's disease (AD) is an aging-related irreversible neurodegenerative disease affecting mostly the elderly population. The main pathological features of AD are the extracellular Aβ plaques generated by APP cleavage through the amyloidogenic pathway, the intracellular neurofibrillary tangles (NFT) resulting from the hyperphosphorylated tau proteins, and cholinergic neurodegeneration. However, the actual causes of AD are unknown, but several studies suggest hereditary mutations in PSEN1 and -2, APOE4, APP, and the TAU genes are the major perpetrators. In order to understand the etiology and pathogenesis of AD, various hypotheses are proposed. These include the following hypotheses: amyloid accumulation, tauopathy, inflammation, oxidative stress, mitochondrial dysfunction, glutamate/excitotoxicity, cholinergic deficiency, and gut dysbiosis. Currently approved therapeutic interventions are donepezil, galantamine, and rivastigmine, which are cholinesterase inhibitors (ChEIs), and memantine, which is an N-methyl-d-aspartate (NMDA) antagonist. These treatment strategies focus on only symptomatic management of AD by attenuating symptoms but not regeneration of neurons or clearance of Aβ plaques and hyperphosphorylated Tau. This review focuses on the pathophysiology, novel therapeutic targets, and disease-altering treatments such as α-secretase modulators, active immunotherapy, passive immunotherapy, natural antioxidant products, nanomaterials, antiamyloid therapy, tau aggregation inhibitors, transplantation of fecal microbiota or stem cells, and microtubule stabilizers that are in clinical trials or still under investigation.}, } @article {pmid39989751, year = {2025}, author = {Arantes, JA and Di Pietro, R and Ratté, M and Arroyo, LG and Leclère, M and Costa, MC}, title = {Changes in bacterial viability after preparation and storage of fecal microbiota transplantation solution using equine feces.}, journal = {PeerJ}, volume = {13}, number = {}, pages = {e18860}, pmid = {39989751}, issn = {2167-8359}, mesh = {Animals ; Horses/microbiology ; *Feces/microbiology ; *Fecal Microbiota Transplantation/methods ; *Microbial Viability/drug effects ; Cryoprotective Agents/pharmacology ; Freezing ; Glycerol/pharmacology ; Cryopreservation/methods ; Bacteria/drug effects ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been used as a treatment option for horses (Equus caballus) with gastrointestinal diseases. Several preparation and conservation protocols to improve bacterial survival have been studied in other species.

METHODS: This study aimed to evaluate the impact of oxygen exposure and different protectant solutions on bacterial viability before and after freezing using horse feces. Fecal samples from 10 healthy horses were aliquoted and diluted in cryoprotectant solutions containing antioxidants (n = 40) or 10% glycerol (n = 40). Half of the aliquots from each dilution condition were prepared inside an anaerobic chamber, while the other half were prepared under ambient air conditions. Each sample was also analyzed fresh and after freezing at -20 °C for 90 days. Bacterial viability was assessed using flow cytometry. A mixed linear model and the Friedman and Wilcoxon tests were used depending on data distribution.

RESULTS: Freeze-thawing decreased bacterial viability by 47% (mean ± SD: 51 ± 27% before, 27 ± 8% after; p < 0.001). Glycerol was superior to the cryoprotectant after freezing (32 ± 8% glycerol, 24 ± 8% cryoprotectant; p < 0.001). Oxygen exposure did not affect viability (p = 0.13). There was no statistical difference between protectant solutions in fresh samples (p = 0.16).

CONCLUSIONS: Fresh FMT solutions may be better for treating horses with dysbiosis, but if freezing cannot be avoided, glycerol should be used to dilute feces.}, } @article {pmid39988618, year = {2025}, author = {Liang, Y and Du, M and Li, X and Gao, J and Li, Q and Li, H and Li, J and Gao, X and Cong, H and Huang, Y and Li, X and Wang, L and Cui, J and Gan, Y and Tu, H}, title = {Upregulation of Lactobacillus spp. in gut microbiota as a novel mechanism for environmental eustress-induced anti-pancreatic cancer effects.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2470372}, doi = {10.1080/19490976.2025.2470372}, pmid = {39988618}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Animals ; Mice ; Humans ; *Pancreatic Neoplasms/microbiology/immunology/therapy/pathology ; *Lactobacillus/physiology ; *Killer Cells, Natural/immunology ; *Carcinoma, Pancreatic Ductal/microbiology/immunology/therapy/pathology ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Tumor Microenvironment/immunology ; Up-Regulation ; Male ; Female ; Feces/microbiology ; Probiotics/administration & dosage/pharmacology ; Limosilactobacillus reuteri/physiology ; Cell Line, Tumor ; }, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited effective treatment options. Emerging evidence links enriched environment (EE)-induced eustress to PDAC inhibition. However, the underlying mechanisms remain unclear. In this study, we explored the role of gut microbiota in PDAC-suppressive effects of EE. We demonstrated that depletion of gut microbiota with antibiotics abolished EE-induced tumor suppression, while fecal microbiota transplantation (FMT) from EE mice significantly inhibited tumor growth in both subcutaneous and orthotopic PDAC models housed in standard environment. 16S rRNA sequencing revealed that EE enhanced gut microbiota diversity and selectively enriched probiotic Lactobacillus, particularly L. reuteri. Treatment with L. reuteri significantly suppressed PDAC tumor growth and increased natural killer (NK) cell infiltration into the tumor microenvironment. Depletion of NK cells alleviated the anti-tumor effects of L. reuteri, underscoring the essential role of NK cell-mediated immunity in anti-tumor response. Clinical analysis of PDAC patients showed that higher fecal Lactobacillus abundance correlated with improved progression-free and overall survival, further supporting the therapeutic potential of L. reuteri in PDAC. Overall, this study identifies gut microbiota as a systemic regulator of PDAC under psychological stress. Supplementation of psychobiotic Lactobacillus may offer a novel therapeutic strategy for PDAC.}, } @article {pmid39984137, year = {2025}, author = {Dai, J and Yang, J and Han, S and Li, N and Wang, S and Xia, S and Kim, HH and Jun, Y and Lee, S and Kitagawa, Y and Xie, F and Yang, L and Shen, S and Chen, L and Turner, DP and Hodin, RA and Martyn, JAJ and Mao, J and You, Z}, title = {Deficiency of intestinal alkaline phosphatase affects behavior and microglia activity in mice.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2025.02.006}, pmid = {39984137}, issn = {1090-2139}, abstract = {The gut microbiota plays crucial roles in the development and functions of the central nervous system (CNS) as well as in modulation of neurobehavior in heath and disease. The gut brush border enzyme intestinal alkaline phosphatase (IAP) is an important positive regulator of gut microbial homeostasis. In mice, IAP is encoded by Akp3 gene, which is specifically expressed in the duodenum of the small intestine. IAP deficiency alters gut bacterial composition and gut barrier function. Decreased IAP activity has been observed in aging, gut inflammatory diseases, and metabolic disorders. We hypothesized that this enzyme could also play an important role in modulating neurobehavior. We performed deep sequencing of gut bacterial 16S rRNA and found that IAP deficiency changed gut microbiota composition at various taxonomic levels. Using targeted metabolomic analysis, we also found that IAP deficiency resulted in changes of gut bacteria-derived metabolites in serum and brain metabolism. Neurobehavioral analyses revealed that Akp3[-/-] (IAP knockout) mice had decreased basal nociception thresholds, increased anxiety-like behavior, and reduced locomotor activity. Furthermore, Akp3[-/-] mice had more pronounced brain microglial phagocytic activity, together with an increase in the activated microglia population. Fecal microbiota transplantation from wildtype to Akp3[-/-] mice partially improved neurobehavior and reduced brain microglial phagocytic activity in Akp3[-/-] mice. This study demonstrates that deficiency of the endogenous gut-derived host factor IAP induces behavioral phenotype changes (nociception; motor activity, and anxiety) and affects brain microglia activity. Changes in the gut microbiota induced by knocking down Akp3 contribute to behavioral changes, which is probably mediated by microglia activity modulated by the gut bacteria-derived metabolites.}, } @article {pmid39983749, year = {2025}, author = {Davido, B and Merrick, B and Kuijper, E and Benech, N and Biehl, LM and Corcione, S and , }, title = {How can the gut microbiome be targeted to fight multidrug-resistant organisms?.}, journal = {The Lancet. Microbe}, volume = {}, number = {}, pages = {101063}, doi = {10.1016/j.lanmic.2024.101063}, pmid = {39983749}, issn = {2666-5247}, abstract = {The rise of antimicrobial resistance presents a challenge to public health, undermines the efficacy of antibiotics, and compromises the management of infectious diseases. Gut colonisation by multidrug-resistant organisms, such as multidrug-resistant Enterobacterales and vancomycin-resistant enterococci, is associated with increased morbidity and mortality rates, as well as health-care costs. Of late, the role of the gut microbiome in combating colonisation by multidrug-resistant organisms, which could precede invasive infection, has garnered interest. Innovative interventions, including faecal microbiota transplantation, probiotics, phage therapy, and bacterial consortia, represent potential preventive or therapeutic options to counteract colonisation by multidrug-resistant organisms. In this Personal View, we have synthesised the current findings on these interventions and elucidated their potential as solutions to the crisis of antimicrobial resistance.}, } @article {pmid39981255, year = {2025}, author = {Yao, K and Zheng, L and Chen, W and Xie, Y and Liao, C and Zhou, T}, title = {Characteristics, pathogenic and therapeutic role of gut microbiota in immunoglobulin A nephropathy.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1438683}, pmid = {39981255}, issn = {1664-3224}, mesh = {*Glomerulonephritis, IGA/microbiology/therapy/immunology/drug therapy ; Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Dysbiosis ; Immunity, Mucosal ; Immunoglobulin A/immunology ; }, abstract = {Immunoglobulin A nephropathy (IgAN) is the most prevalent glomerulonephritis in the world, and it is one of the leading causes of end-stage kidney disease. It is now believed that the pathogenesis of IgAN is the mesangial deposition of immune complex containing galactose-deficient IgA1, resulting in glomerular injury. Current treatments for IgAN include supportive care and immunosuppressive therapy. A growing number of studies found that the gut microbiota in IgAN was dysregulated. Gut microbiota may be involved in the development and progression of IgAN through three main aspects: destruction of intestinal barrier, changes in metabolites and abnormal mucosal immunity. Interestingly, therapies by modulating the gut microbiota, such as fecal microbiota transplantation, antibiotic treatment, probiotic treatment, Chinese herbal medicine Zhen Wu Tang treatment, gluten-free diet, and hydroxychloroquine treatment, can improve IgAN. In this review, the alteration of gut microbiota in IgAN, potential pathogenic roles of gut microbiota on IgAN and potential approaches to treat IgAN by modulating the gut microbiota are summarized.}, } @article {pmid39979990, year = {2025}, author = {Xie, H and Zhang, H and Zhou, L and Chen, J and Yao, S and He, Q and Li, Z and Zhou, Z}, title = {Fecal microbiota transplantation promotes functional recovery in mice with spinal cord injury by modulating the spinal cord microenvironment.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {210}, pmid = {39979990}, issn = {1479-5876}, support = {202201010803//Science and Technology Project Foundation of Guangzhou City/ ; 2024A03J1068//Science and Technology Project Foundation of Guangzhou City/ ; }, mesh = {Animals ; *Spinal Cord Injuries/therapy/physiopathology/microbiology ; *Recovery of Function ; *Spinal Cord/pathology/physiopathology ; *Fecal Microbiota Transplantation ; *Mice, Inbred C57BL ; Gastrointestinal Microbiome ; Cellular Microenvironment ; Female ; Mice ; Axons ; RNA, Ribosomal, 16S/genetics ; Inflammation/pathology ; }, abstract = {BACKGROUND: spinal cord injury (SCI) disrupts the gut microbiota, worsening the injury's impact. Fecal microbiota transplantation (FMT) is increasingly recognized as a promising strategy to improve neural function post-SCI, yet its precise mechanisms are still far from clear. The present study aims to elucidate how FMT influences motor function recovery and its underlying mechanisms utilizing a SCI mouse model.

METHODS: Mice with SCI received FMT from healthy donors. We used 16 S rRNA amplicon sequencing to analyze the alterations of gut microbes. Pathological alterations in the spinal cord tissue, including neuronal survival, axonal regeneration, cell proliferation, and neuroinflammation, were assessed among experimental groups. Additionally, RNA sequencing (RNA-seq) was used to explore alterations in relevant signaling pathways.

RESULTS: Significant shifts in gut microbiota composition following SCI were observed through 16 S rRNA analysis. On day 7 post-SCI, the FMT group exhibited a significantly higher diversity of gut microbiota compared to the ABX group, with the composition in the FMT group more closely resembling that of healthy mice. FMT promoted neuronal survival and axonal regeneration, leading to notable improvements in motor function compared to control mice. Immunofluorescence staining showed increased neuronal survival, alleviated extracellular matrix (ECM) deposition, diminished glial scar formation, and reduced inflammation in FMT-treated mice. RNA-seq analysis indicated that FMT induced transcriptomic changes associated with material metabolism, ECM remodeling, and anti-inflammatory responses.

CONCLUSIONS: FMT restored gut microbiota balance in SCI mice, mitigated inflammation, and promoted ECM remodeling, establishing an optimal environment for neural recovery. These findings demonstrated that FMT may represent a valuable approach to enhance functional recovery following SCI.}, } @article {pmid39978693, year = {2025}, author = {Jiang, Y and Shi, L and Qu, Y and Ou, M and Du, Z and Zhou, Z and Zhou, H and Zhu, H}, title = {Multi-omics analysis reveals mechanisms of FMT in Enhancing antidepressant effects of SSRIs.}, journal = {Brain, behavior, and immunity}, volume = {126}, number = {}, pages = {176-188}, doi = {10.1016/j.bbi.2025.02.011}, pmid = {39978693}, issn = {1090-2139}, abstract = {OBJECTIVE: This study explores the behavioral and molecular biological impacts of Fecal Microbiota Transplantation (FMT) on depressive mice unresponsive to treatment with Selective Serotonin Reuptake Inhibitors (SSRIs).

METHODS: Healthy male C57BL/6 mice were used to establish a depression model through chronic restraint stress, treated with fluoxetine, and categorized into Response and Non-response groups. An FMT treatment was added to the Non-response group. Behavioral tests were conducted to assess symptoms of depression. The gut microbiome, plasma metabolites, and hippocampal tissue gene expression and function changes were analyzed using 16S rRNA gene sequencing, LC-MS, and RNA sequencing.

RESULTS: FMT significantly improved the depressive symptoms in SSRIs-resistant mice. There was a partial restoration in the diversity and structure of the gut microbiota in the FMT group. Compared to the Non-response group, significant changes were noted in the metabolomic profiles of the FMT group, identifying various differential metabolites. Functional annotations indicated that these metabolites are involved in multiple metabolic pathways. In the Non-response group, certain gene expression levels were significantly restored. GO and KEGG enrichment analyses revealed that these differential genes mainly involve cytokine activity, receptor signaling regulation, and NOD-like receptor signaling pathways. Joint analysis suggested that FMT may exert its effects through an increase in the abundance of g__Paraprevotella, leading to decreased baicalin content and increased Tal2 expression.

CONCLUSION: FMT has potential in improving depressive symptoms unresponsive to SSRIs treatment. Its mechanism may be related to the modulation of the gut microbiota and its metabolites, subsequently affecting gene expression.}, } @article {pmid39978276, year = {2025}, author = {Luo, X and Cheng, P and Fang, Y and Wang, F and Mao, T and Shan, Y and Lu, Y and Wei, Z}, title = {Yinzhihuang formula modulates the microbe‒gut‒liver axis and bile acid excretion to attenuate cholestatic liver injury.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {139}, number = {}, pages = {156495}, doi = {10.1016/j.phymed.2025.156495}, pmid = {39978276}, issn = {1618-095X}, abstract = {BACKGROUND: Cholestatic liver injury is a hepatobiliary disorder primarily characterized by cholestasis, which significantly contributes to liver damage. The Yinzhihuang (YZH) oral preparation is an effective clinical treatment for cholestatic liver injury; however, the specific mechanism of action has not been clarified.

PURPOSE: This study investigated YZH's pharmacological mechanisms associated with the microbe‒gut‒liver axis in cholestatic mice, offering new perspectives for the treatment of cholestasis.

METHODS: YZH's protective effects were evaluated by evaluating serum liver injury indices and liver staining in an alpha-nephthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis mouse model. Colon hematoxylin‒eosin (H&E) and alcian blue staining and FITC‒dextran leakage assays were performed to assess intestinal barrier integrity. Fluorescence in situ hybridization was employed to analyze bacterial translocation. Additionally, 16S rRNA sequencing, fecal microbiota transplantation, and bile acid metabolomics analysis were conducted to examine the relationships among the microbiome, bile acid metabolism, and YZH formula.

RESULTS: We found that YZH administration alleviated symptoms of ANIT-induced hepatic pathological injury and fibrosis. In addition, YZH reduced the transfer of gut bacteria to liver tissue by maintaining an intact intestinal barrier. Notably, YZH influenced the intestinal microbiota composition, upregulated the abundance of bile acid metabolism-associated probiotic bacteria, including Clostridiales, Lachnospiraceae and Bifidobacterium pseudolongum; and downregulated the abundance of Escherichia-Shigella and Serratia, thereby promoting bile acid excretion.

CONCLUSION: YZH protects against cholestatic liver damage by promoting bile excretion and maintaining intestinal mucosal barrier integrity. Furthermore, YZH alleviates cholestasis in a gut microbiota-dependent manner, and upregulation of probiotics may be crucial for YZH's influence on bile acid metabolism.}, } @article {pmid39975140, year = {2025}, author = {Oppenheimer, M and Tao, J and Moidunny, S and Roy, S}, title = {Anxiety-like behavior during protracted morphine withdrawal is driven by gut microbial dysbiosis and attenuated with probiotic treatment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.29.633224}, pmid = {39975140}, issn = {2692-8205}, abstract = {The development of anxiety during protracted opioid withdrawal heightens the risk of relapse into the cycle of addiction. Understanding the mechanisms driving anxiety during opioid withdrawal could facilitate the development of therapeutics to prevent negative affect and promote continued abstinence. Our lab has previously established the gut microbiome as a driver of various side effects of opioid use, including analgesic tolerance and somatic withdrawal symptoms. We therefore hypothesized that the gut microbiome contributes to the development of anxiety-like behavior during protracted opioid withdrawal. In this study, we first established a mouse model of protracted morphine withdrawal, characterized by anxiety-like behavior and gut microbial dysbiosis. Next, we used fecal microbiota transplantation (FMT) to show that gut dysbiosis alone is sufficient to induce anxiety-like behavior. We further demonstrate that probiotic therapy during morphine withdrawal attenuates the onset of anxiety-like behavior, highlighting its therapeutic potential. Lastly, we examined transcriptional changes in the amygdala of morphine-withdrawn mice treated with probiotics to explore mechanisms by which the gut-brain axis mediates anxiety-like behavior. Our results support the use of probiotics as a promising therapeutic strategy to prevent gut dysbiosis and associated anxiety during opioid withdrawal, with potential implications for improving treatment outcomes in opioid recovery programs.}, } @article {pmid39975029, year = {2025}, author = {Zhang, XS and Wang, Y and Sun, H and Zerbe, C and Falcone, E and Bhattacharya, S and Zhang, M and Gao, Z and Diaz-Rubio, ME and Bharj, D and Patel, D and Pan, S and Ro, G and Grenard, J and Armstrong, A and Yin, YS and Dominguez-Bello, MG and Holland, S and Su, X and Blaser, MJ}, title = {Gut microbiota phospholipids regulate intestinal gene expression and can counteract the effects of antibiotic treatment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39975029}, issn = {2692-8205}, abstract = {The gut microbiome influences immune and metabolic homeostasis. Our research using non-obese diabetic (NOD) mice revealed that early-life antibiotic exposure remodels the gut microbiome affecting metabolism and accelerating type 1 diabetes (T1D) incidence, with cecal material transplant (CMT) mitigating the damage. Now examining murine intestinal lipidomic profiles, we identified 747 compounds. Comparing the lipidomic profiles of cecal contents of conventional and germ-free mice and their diets, we identified 87 microbially-produced lipids reduced by antibiotic exposure but CMT-restored. Parallel analysis of human fecal lipid profiles after azithromycin-exposure showed significant alterations with substantial overlap with mice. In vitro co-culture with mouse macrophages or small intestinal epithelial cells and human colonic epithelial cells identified phospholipids that repress inflammation through the NFκB pathway. Oral administration of these phospholipids to antibiotic-treated NOD mice reduced expression of ileal genes involved in early stages of T1D pathogenesis. These findings indicate potential therapeutic anti-inflammatory roles of microbially-produced lipids.}, } @article {pmid39974080, year = {2025}, author = {McCann, JR and Yang, C and Bihlmeyer, N and Tang, R and Truong, T and An, J and Jawahar, J and Ilkayeva, O and Muehlbauer, M and Hu, ZZ and Dressman, H and Poppe, L and Granek, J and David, LA and Shi, P and Balikcioglu, PG and Shah, S and Armstrong, SC and Newgard, CB and Seed, PC and Rawls, JF}, title = {Branched chain amino acid metabolism and microbiome in adolescents with obesity during weight loss therapy.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.02.03.25321363}, pmid = {39974080}, abstract = {BACKGROUND: Towards improving outcomes for adolescents with obesity, we aimed to define metabolic and microbiome phenotypes at baseline and post-weight loss intervention.

METHODS: The Pediatric Obesity Microbiome and Metabolism Study enrolled 220 adolescents aged 10-18 with severe obesity (OB) and 67 healthy weight controls (HWC). Blood, stool, and clinical measures were collected at baseline and after a 6-month intervention for the OB group. Serum metabolomic and fecal microbiome data were analyzed for associations with BMI, insulin resistance, and inflammation. Fecal microbiome transplants were performed on germ-free mice using samples from both groups to assess weight gain and metabolomic changes.

RESULTS: Adolescents with OB exhibited elevated serum branched-chain amino acids (BCAA) but reduced ketoacid metabolites (BCKA) compared to HWC. This pattern was sex- and age-dependent, unlike adults with OB, who showed elevated levels of both. The fecal microbiomes of adolescents with OB and HWC had similar diversity but differed in membership and functional potential. FMT from OB and HWC donors had similar effects on mouse body weight, with specific taxa linked to weight gain in FMT recipients. Longitudinal analysis identified metabolic and microbial features correlated with changes in health measures during the intervention.

CONCLUSION: Adolescents with OB have unique metabolomic adaptations and microbiome signatures compared to their HWC counterparts and adults with OB.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03139877 (Observational Study) and NCT02959034 (Repository).

FUNDING SOURCES: American Heart Association Grants: 17SFRN33670990, 20PRE35180195National Institute of Diabetes and Digestive and Kidney Diseases Grant: R24-DK110492.}, } @article {pmid39973149, year = {2025}, author = {Zhang, T and Liu, S and Liu, S and Zhao, P and Zhang, C and Wang, X and Meng, Y and Lu, Y}, title = {Oleanolic Acid Alleviates Hyperuricemia via Gut Microbiota Control the Integrity of Gut Barrier and the Expressions of Urate Transporter in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c09270}, pmid = {39973149}, issn = {1520-5118}, abstract = {Hyperuricemia (HUA) is a globally prevalent metabolic disorder characterized by an imbalance in uric acid (UA) production and excretion. In this study, we found that oleanolic acid (OA), a natural pentacyclic triterpene, effectively reduced HUA and associated kidney injury in C57BL/6J mice. A 12-week OA treatment significantly and dose-dependently reduced UA and creatinine levels in serum and urine while suppressing hepatic xanthine oxidase activity in HUA mice. Mechanistic analysis revealed that OA modulates the expression of urate transporters including ABCG2, GLUT9, and URAT1 in the kidney and small intestine. Furthermore, OA restored gut microbiota imbalances, increased short-chain fatty acid production, and enhanced the expressions of intestinal tight junction proteins in HUA mice, thereby improving gut barrier integrity in HUA mice. Consequently, fecal microbiota transplantation (FMT) was employed to illustrate the major mediating role of gut microbiota in OA's alleviation of HUA in mice. Recipient HUA mice transplanted with feces from OA-treated HUA mice exhibited significantly lower blood and urinary UA levels, reduced kidney inflammation, and improved gut microbiota balance compared to those receiving feces from untreated HUA mice (p < 0.05). Additionally, FMT normalized urate transporter expression and reinforced intestinal tight junctions in recipient mice. These findings underscore that OA mitigates HUA primarily by modulating gut microbiota, regulating urate transporter expression, and reinforcing gut barrier integrity, offering novel insights into its preventive potential for managing HUA and related complications.}, } @article {pmid39971913, year = {2025}, author = {Cune, D and Pitasi, CL and Rubiola, A and Jamma, T and Simula, L and Boucher, C and Fortun, A and Adoux, L and Letourneur, F and Saintpierre, B and Donnadieu, E and Terris, B and Bossard, P and Chassaing, B and Romagnolo, B}, title = {Inhibition of Atg7 in intestinal epithelial cells drives resistance against Citrobacter rodentium.}, journal = {Cell death & disease}, volume = {16}, number = {1}, pages = {112}, pmid = {39971913}, issn = {2041-4889}, mesh = {*Citrobacter rodentium ; Animals ; *Autophagy-Related Protein 7/metabolism/genetics ; Mice ; *Enterobacteriaceae Infections/immunology/microbiology/pathology ; *Gastrointestinal Microbiome ; *Intestinal Mucosa/microbiology/immunology/metabolism/pathology ; *Autophagy ; Epithelial Cells/metabolism/microbiology/immunology ; Mice, Inbred C57BL ; Colitis/microbiology/immunology/pathology ; }, abstract = {Autophagy, a cytoprotective mechanism in intestinal epithelial cells, plays a crucial role in maintaining intestinal homeostasis. Beyond its cell-autonomous effects, the significance of autophagy in these cells is increasingly acknowledged in the dynamic interplay between the microbiota and the immune response. In the context of colon cancer, intestinal epithelium disruption of autophagy has been identified as a critical factor influencing tumor development. This disruption modulates the composition of the gut microbiota, eliciting an anti-tumoral immune response. Here, we report that Atg7 deficiency in intestinal epithelial cells shapes the intestinal microbiota leading to an associated limitation of colitis induced by Citrobacter rodentium infection. Mice with an inducible, intestinal epithelial-cell-specific deletion of the autophagy gene, Atg7, exhibited enhanced clearance of C. rodentium, mitigated hyperplasia, and reduced pathogen-induced goblet cell loss. This protective effect is linked to a higher proportion of neutrophils and phagocytic cells in the early phase of infection. At later stages, it is associated with the downregulation of pro-inflammatory pathways and an increase in Th17 and Treg responses-immune responses known for their protective roles against C. rodentium infection, modulated by specific gut microbiota. Fecal microbiota transplantation and antibiotic treatment approaches revealed that the Atg7-deficiency-shapped microbiota, especially Gram-positive bacteria, playing a central role in driving resistance to C. rodentium infection. In summary, our findings highlight that inhibiting autophagy in intestinal epithelial cells contributes to maintaining homeostasis and preventing detrimental intestinal inflammation through microbiota-mediated colonization resistance against C. rodentium. This underscores the central role played by autophagy in shaping the microbiota in promoting immune-mediated resistance against enteropathogens.}, } @article {pmid39971742, year = {2025}, author = {Akagbosu, CO and McCauley, KE and Namasivayam, S and Romero-Soto, HN and O'Brien, W and Bacorn, M and Bohrnsen, E and Schwarz, B and Mistry, S and Burns, AS and Perez-Chaparro, PJ and Chen, Q and LaPoint, P and Patel, A and Krausfeldt, LE and Subramanian, P and Sellers, BA and Cheung, F and Apps, R and Douagi, I and Levy, S and Nadler, EP and Hourigan, SK}, title = {Gut microbiome shifts in adolescents after sleeve gastrectomy with increased oral-associated taxa and pro-inflammatory potential.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2467833}, pmid = {39971742}, issn = {1949-0984}, support = {R25 DK096944/DK/NIDDK NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome ; Adolescent ; Humans ; *Gastrectomy/adverse effects ; Animals ; Female ; Male ; *Feces/microbiology ; Mice ; Inflammation/microbiology ; Bacteria/classification/isolation & purification/genetics/metabolism ; Th17 Cells/immunology ; T-Lymphocytes, Regulatory/immunology ; Bariatric Surgery ; Metabolome ; Obesity, Morbid/surgery/microbiology ; Child ; Leukocyte L1 Antigen Complex/analysis/metabolism ; }, abstract = {Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown. Here, we show that adolescents exhibit significant gut microbiome and metabolome shifts several months after laparoscopic vertical sleeve gastrectomy (VSG), with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited a potentially inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG. We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG.}, } @article {pmid39969373, year = {2024}, author = {Li, Q and Obi, E and Marciniak, A and Newman, R and Whittle, I and Kufakwaro, J}, title = {Clinical and economic outcomes associated with fidaxomicin in comparison to vancomycin, metronidazole, and FMT: A systematic literature review.}, journal = {Medicine}, volume = {103}, number = {52}, pages = {e39219}, pmid = {39969373}, issn = {1536-5964}, mesh = {Humans ; *Vancomycin/therapeutic use/economics ; *Fidaxomicin/therapeutic use ; *Metronidazole/therapeutic use/economics ; *Clostridium Infections/economics/drug therapy/therapy ; *Anti-Bacterial Agents/therapeutic use/economics ; *Fecal Microbiota Transplantation/economics ; Cost-Benefit Analysis ; Treatment Outcome ; }, abstract = {BACKGROUND: There are an estimated half a million cases of Clostridioides difficile infection (CDI), in the United States annually. Fidaxomicin, vancomycin, and metronidazole are commonly used for CDI treatment, with fidaxomicin recommended by clinical guidelines as the preferred treatment for initial and recurrent CDI. This systematic literature review aimed to explore clinical and economic outcomes associated with fidaxomicin use with or without comparison to vancomycin, metronidazole, or fecal microbiota transplantation (FMT).

METHODS: The EMBASE, Medline, EconLit, and Evidence Based Medicine Reviews databases were searched from January 1st, 2012 to December 6th, 2022, as fidaxomicin was first approved for adult use in 2011. Identified publications were assessed and extracted by 2 independent reviewers.

RESULTS: Seventy-nine publications were included. Articles reporting at least 50 patients with follow-up ≤90 days were selected to obtain comparable outcome definitions (N = 14). Sustained clinical cure rate at 30- and 60-days follow-up was higher among fidaxomicin-treated patients (70.0-75.1% and 63.2-78.9%; N = 3) than vancomycin (45.1-58.2% and 38.9-50.0%; N = 3). Lower recurrence rates were reported post-fidaxomicin treatment compared to vancomycin, however the ranges overlapped at 30-, 60-, and 90-days follow-up. Limited outcomes for comparators metronidazole and FMT were identified. Healthcare resource use data were limited, with 2 studies reporting direct costs finding that fidaxomicin use-associated savings were driven by reduced hospital admission-related costs. Fidaxomicin was cost-effective in 14 of 21 economic analyses (11 vs vancomycin). Three studies reported vancomycin or FMT as more cost-effective than fidaxomicin. Fidaxomicin was consistently cost-effective or cost-saving among patients receiving concomitant antibiotics, and patients with cancer or renal impairment. Ten publications reported that the higher acquisition cost of fidaxomicin was offset by reduced recurrence and hospital readmission costs.

CONCLUSIONS: Fidaxomicin was clinically effective compared to vancomycin. Fidaxomicin is often reported as cost-effective, consistently within high-risk subpopulations.}, } @article {pmid39968682, year = {2025}, author = {Yu, RL and Weber, HC}, title = {Irritable bowel syndrome, the gut microbiome, and diet.}, journal = {Current opinion in endocrinology, diabetes, and obesity}, volume = {}, number = {}, pages = {}, doi = {10.1097/MED.0000000000000905}, pmid = {39968682}, issn = {1752-2978}, abstract = {PURPOSE OF REVIEW: To provide an update of recent studies exploring the role of the gut microbiota and diet in the pathogenesis and treatment of irritable bowel syndrome (IBS).

RECENT FINDINGS: The human gut microbiome has been recognized as an important, active source of signaling molecules that explain in part the disorder of the gut brain interaction (DGBI) in IBS. Subsequent changes in the metabolome such as the production of short-chain fatty acids (SCFA) and serotonin are associated with IBS symptoms. Dietary components are recognized as important triggers of IBS symptoms and a diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) has been shown effective and safe, even when used long-term. Fecal microbiota transplantation (FMT) in IBS has not shown sustained and effective IBS symptom reduction in controlled clinical trials.

SUMMARY: This update elucidates recent developments in IBS as it relates to clinical trial results targeting dietary and gut microbiota interventions. The gut microbiome is metabolically active and affects the bi-directional signaling of the gut-brain axis.}, } @article {pmid39773539, year = {2025}, author = {Zeng, J and Zhao, D and Way, G and Fagan, A and Fuchs, M and Puri, P and Davis, BC and Wang, X and Gurley, EC and Hylemon, PB and Fan, JG and Sikaroodi, M and Gillevet, PM and Zhou, H and Bajaj, JS}, title = {Intestinal mucosal mitochondrial oxidative phosphorylation worsens with cirrhosis progression and is ameliorated with fecal microbiota transplantation.}, journal = {JCI insight}, volume = {10}, number = {4}, pages = {}, doi = {10.1172/jci.insight.186649}, pmid = {39773539}, issn = {2379-3708}, mesh = {*Fecal Microbiota Transplantation/methods ; *Intestinal Mucosa/microbiology/metabolism/pathology ; *Oxidative Phosphorylation ; *Liver Cirrhosis/therapy/metabolism/microbiology/pathology ; *Disease Progression ; *Mitochondria/metabolism ; Humans ; Male ; *Gastrointestinal Microbiome ; Animals ; Mice ; Middle Aged ; Female ; }, abstract = {Cirrhosis, the end-stage of liver disease, progresses through altered gut-liver axis and microbial change. Here we show that intestinal mucosal mitochondrial oxidative phosphorylation, which affects intestinal barrier worsens with cirrhosis progression. This is ameliorated with fecal microbiota transplantation.}, } @article {pmid39968343, year = {2025}, author = {Sun, T and Song, B and Li, B}, title = {Gut microbiota and atrial cardiomyopathy.}, journal = {Frontiers in cardiovascular medicine}, volume = {12}, number = {}, pages = {1541278}, pmid = {39968343}, issn = {2297-055X}, abstract = {Atrial cardiomyopathy is a multifaceted heart disease characterized by structural and functional abnormalities of the atria and is closely associated with atrial fibrillation and its complications. Its etiology involves a number of factors, including genetic, infectious, immunologic, and metabolic factors. Recent research has highlighted the critical role of the gut microbiota in the pathogenesis of atrial cardiomyopathy, and this is consistent with the gut-heart axis having major implications for cardiac health. The aim of this work is to bridge the knowledge gap regarding the interactions between the gut microbiota and atrial cardiomyopathy, with a particular focus on elucidating the mechanisms by which gut dysbiosis may induce atrial remodeling and dysfunction. This article provides an overview of the role of the gut microbiota in the pathogenesis of atrial cardiomyopathy, including changes in the composition of the gut microbiota and the effects of its metabolites. We also discuss how diet and exercise affect atrial cardiomyopathy by influencing the gut microbiota, as well as possible future therapeutic approaches targeting the gut-heart axis. A healthy gut microbiota can prevent disease, but ecological dysbiosis can lead to a variety of symptoms, including the induction of heart disease. We focus on the pathophysiological aspects of atrial cardiomyopathy, the impact of gut microbiota dysbiosis on atrial structure and function, and therapeutic strategies exploring modulation of the microbiota for the treatment of atrial cardiomyopathy. Finally, we discuss the role of gut microbiota in the treatment of atrial cardiomyopathy, including fecal microbiota transplantation and oral probiotics or prebiotics. Our study highlights the importance of gut microbiota homeostasis for cardiovascular health and suggests that targeted interventions on the gut microbiota may pave the way for innovative preventive and therapeutic strategies targeting atrial cardiomyopathy.}, } @article {pmid39963784, year = {2025}, author = {Li, J and Jia, J and Teng, Y and Wang, X and Xia, X and Song, S and Zhu, B and Xia, X}, title = {Sea cucumber polysaccharides overcome immunotherapy resistance in tumor-bearing mice via modulation of the gut microbiome.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo05449k}, pmid = {39963784}, issn = {2042-650X}, abstract = {Cancer immunotherapy has been successful in patients with different types of cancers, but its efficacy in treating certain types of colorectal cancer (CRC) is limited. The aim of this study was to explore whether sea cucumber polysaccharides (SCP) could impact resistance to anti-programmed cell death-1 (anti-PD1) immunotherapy of CRC and the role of microbiota in mediating their effects. Mice inoculated with immunotherapy resistant CT-26 CRC cells were pretreated with SCP, followed by treatment with/without the anti-PD1 antibody. SCP alone exhibited no inhibitory effect on tumor growth, but they drastically enhanced the efficacy of anti-PD1 treatment, which alone showed minimal effect on tumor development. Compared to anti-PD1 only treatment, a combination of SCP and anti-PD1 increased CD8[+] T cells, especially IFN-γ[+] cytotoxic CD8[+] T cells, and decreased regulatory CD4[+] T cells. SCP modulated gut microbiota and increased the relative abundance of bacteria including Bifidobacterium and Faecalibaculum. A fecal microbiota transplantation experiment showed that the sensitizing effect of SCP was at least partly mediated by microbiota. Furthermore, oral supplementation of Bifidobacterium pseudolongum or Faecalibaculum rodentium recapitulated the beneficial effect of SCP in potentiating anti-PD1 efficacy. Altogether, these findings demonstrated that SCP could be potentially developed as a dietary adjuvant to increase the efficacy of immunotherapy in CRC.}, } @article {pmid39963663, year = {2025}, author = {Lin, DJ and Hu, DX and Wu, QT and Huang, LG and Lin, ZH and Xu, JT and He, XX and Wu, L}, title = {Analysis of influencing factors of washed microbiota transplantation in treating patients with metabolic syndrome.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1508381}, pmid = {39963663}, issn = {2296-861X}, abstract = {BACKGROUND AND AIMS: Metabolic Syndrome (MS) is a cluster of metabolic abnormalities closely associated with hypertension, diabetes, hyperlipidemia, obesity, etc. Our previous research indicated that fecal microbiota transplantation (FMT) could improve MS, but the factors influencing the efficacy of washed microbiota transplantation (WMT) in treating MS patients remain unclear. The objective of this study is to analyze the influencing factors of WMT in treating MS patients.

METHODS: The clinical data and influencing factors related to MS patients were collected retrospectively. Not only the changes in body mass index [BMI = weight (kg)/height (m)[2]], blood glucose, blood lipids, and blood pressure were analyzed, but also the influencing factors of WMT in treating MS patients were carried out based on Logistic Regression. The 16S rRNA gene amplicon sequencing was performed on fecal samples before and after WMT treatment.

RESULTS: A total of 210 patients were included, including 68 patients in the WMT group and 142 patients in the drug treatment (DT) group. WMT had a significant improvement and ASCVD downregulation effect on MS patients, and 42.65% of MS patients removed the label of MS after WMT treatment. Independent influencing factors for treating MS patients through WMT include age < 60 years old, high smoking index, infection, single donor selection, single-course WMT treatment, and having hypertension, diabetes, or obesity. WMT treated MS patients by maintaining the balance of gut microbiota.

CONCLUSIONS: WMT has a significant effect in improving MS and downregulating ASCVD risk stratification. The therapeutic effect of WMT on MS patients is closely related to their age, smoking index, infection, chronic disease status, donor type, and WMT courses. Therefore, we can improve the efficacy of WMT by reducing independent influencing factors that affect gut microbiota homeostasis.}, } @article {pmid39962884, year = {2025}, author = {Marasco, G and Cannarile, DC and Cremon, C and Papalia, G and Marangoni, A and Zucchelli, A and Barone, M and Lazzarotto, T and Brigidi, P and Stanghellini, V and Barbara, G}, title = {Fecal microbiota transplantation for Clostridioides difficile infection in a peritoneal dialysis patient: A case report.}, journal = {Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis}, volume = {}, number = {}, pages = {8968608251316165}, doi = {10.1177/08968608251316165}, pmid = {39962884}, issn = {1718-4304}, abstract = {Chronic kidney disease (CKD) may be associated with dysbiosis which may increase the risk of gastrointestinal infections. Patients with kidney failure have a predominance of bacteria responsible for the exacerbation of chronic inflammation through the production of ureases, uricase, and uremic toxins and a reduction of bacteria-producing protective molecules as short-chain fatty acids. Patients with CKD have an increased risk of Clostridioides difficile infection. Currently, besides antibiotic therapy, fecal microbiota transplantation (FMT) is the only effective gut microbiota-targeted therapy for treating this infection. Scant evidence is available on FMT in those receiving peritoneal dialysis (PD). In this case, we report a successful FMT performed by colonoscopy in a patient receiving PD for polycystic kidney disease suffering from recurrent Clostridioides difficile infections. The FMT was repeated to enhance microbiota engraftment. The role of FMT in treating Clostridioides difficile in individuals receiving PD may be an important and promising therapeutic strategy but requires further prospective study.}, } @article {pmid39961405, year = {2025}, author = {Wang, Z and Liu, T and Liu, L and Xie, J and Tang, F and Pi, Y and Zhong, Y and He, Z and Zhang, W and Zheng, C}, title = {Lactobacillus vaginalis alleviates DSS induced colitis by regulating the gut microbiota and increasing the production of 3-indoleacrylic acid.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107663}, doi = {10.1016/j.phrs.2025.107663}, pmid = {39961405}, issn = {1096-1186}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory disorder, and its incidence is experiencing an upward trend worldwide. UC can result in gut microbiota dysbiosis, impaired intestinal epithelial barrier, and systemic inflammation, for all of which there is presently no definitive treatment available. Lactobacillus is known to regulate gut microbiota and related metabolites to intervene in the development of UC. The objective of this study was to explore the underlying mechanism through which a novel probiotic, Lactobacillus vaginalis, alleviates DSS-induced colitis. Specifically, L. vaginalis were found to ameliorate the DSS-induced UC phenotype, restore intestinal microbiota balance and intestinal barrier function, and elevate the levels of 3-indoleacrylic acid (IAA) in mouse feces. Furthermore, fecal microbiota transplantation and fecal filtrate transplantation provide additional evidence that L. vaginalis alleviate DSS-induced colitis through metabolic products. Additionally, IAA has been shown to alleviate DSS-induced colitis symptoms, decrease inflammatory responses, and enhance intestinal barrier function. Finally, our findings confirm that L. vaginal and metabolites possess the capability to regulate the immune microenvironment in mice with colitis. And the RNA-seq analysis suggests that L. vaginal may play a pivotal role in alleviating colitis by modulating the PPAR signaling pathway. In conclusion, our findings suggest that oral administration of L. vaginalis alleviates DSS induced colonic inflammation by increasing the levels of IAA. L. vaginalis, as an emerging probiotic, provides a potential therapeutic strategy for clinical UC.}, } @article {pmid39959619, year = {2025}, author = {Hao, J and Xu, H and Chang, B and Ren, J and Wang, H and Ji, L}, title = {Acupuncture mediates the "gut-testis axis" to improve asthenozoospermia.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1514010}, pmid = {39959619}, issn = {1664-2392}, mesh = {Male ; Animals ; *Asthenozoospermia/therapy/metabolism ; Mice ; *Testis/metabolism ; *Acupuncture Therapy ; *Sperm Motility ; Gastrointestinal Microbiome/physiology ; Spermatozoa/metabolism ; Disease Models, Animal ; Blood-Testis Barrier/metabolism ; }, abstract = {BACKGROUND: Asthenozoospermia is a common cause of male infertility. Studies have shown that sperm quality and motility are affected by the gut-testis axis that can regulate testicular metabolism and function through the gut microbiota and its metabolites. Acupuncture is an important modality of complementary and alternative medicine. It can improve sperm motility, but it remains unclear whether acupuncture can enhance sperm vitality by influencing the gut-testis axis.

METHODS: In this study, sperm quality, testicular pathology, and serum hormone levels were assessed using a cyclophosphamide-induced mouse model. Real-time PCR, a western blot analysis, and immunofluorescence techniques were used to assess the effects of acupuncture on the gut barrier and blood-testis barrier functions. In addition, gut microbiome and metabolomics were used to study the impact of acupuncture on the gut microbiota structure, serum, and testicular metabolites in asthenozoospermic mice. Further validation was obtained by performing a fecal microbiota transplantation (FMT).

RESULTS: Acupuncture improved the sperm quality; ameliorated testicular pathology; increased serum testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels; and repaired gut and blood-testis barrier damage in asthenozoospermic mice. The abundances of Bacteroidota, Firmicutes, Faecalibaculum, and Dubosiella were associated with sperm motility, as shown by a gut microbiome analysis. Serum metabolomics revealed that differentially expressed metabolites (DEMs), such as cytosine and N-oleyl-leucine, were closely related to sperm motility. Testicular metabolomics analysis revealed DEMs, such as 5-fluorouridine and 1-acetylimidazole, were also associated with sperm motility. Furthermore, reproductive function improvements in asthenozoospermic mice through acupuncture were achieved via an FMT.

CONCLUSION: Acupuncture may alleviate asthenozoospermia symptoms by modulating the gut-testis axis and repairing the gut-testis barrier.}, } @article {pmid39958442, year = {2025}, author = {Ozbey, D and Saribas, S and Kocazeybek, B}, title = {Gut microbiota in Crohn's disease pathogenesis.}, journal = {World journal of gastroenterology}, volume = {31}, number = {6}, pages = {101266}, pmid = {39958442}, issn = {2219-2840}, mesh = {Humans ; *Crohn Disease/microbiology/immunology/therapy ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Treatment Outcome ; Intestinal Mucosa/microbiology/immunology/pathology ; Feces/microbiology ; Colon/microbiology/pathology/immunology ; Dysbiosis ; Ileum/microbiology/pathology/immunology ; Animals ; Colitis, Ulcerative/microbiology/therapy/immunology ; }, abstract = {Inflammatory bowel diseases (IBDs) are classified into two distinct types based on the area and severity of inflammation: Crohn's disease (CD) and ulcerative colitis. In CD, gut bacteria can infiltrate mesenteric fat, causing expansion known as creeping fat, which may limit bacterial spread and inflammation but can promote fibrosis. The gut bacteria composition varies depending on whether the colon or ileum is affected. Fecal microbiota transplantation (FMT) transfers feces from a healthy donor to restore gut microbiota balance, often used in IBD patients to reduce inflammation and promote mucosal repair. The use of FMT for CD remains uncertain, with insufficient evidence to fully endorse it as a definitive treatment. While some studies suggest it may improve symptoms, questions about the duration of these improvements and the need for repeated treatments persist. There is a pressing need for methods that provide long-term benefits, as highlighted by Wu et al's research.}, } @article {pmid39957504, year = {2025}, author = {Jiang, X and Zheng, Y and Sun, H and Dang, Y and Yin, M and Xiao, M and Wu, T}, title = {Fecal Microbiota Transplantation Improves Cognitive Function of a Mouse Model of Alzheimer's Disease.}, journal = {CNS neuroscience & therapeutics}, volume = {31}, number = {2}, pages = {e70259}, pmid = {39957504}, issn = {1755-5949}, support = {81971237//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Alzheimer Disease/therapy ; *Fecal Microbiota Transplantation ; Mice ; *Disease Models, Animal ; *Mice, Transgenic ; *Gastrointestinal Microbiome/physiology ; Cognition/physiology ; Amyloid beta-Peptides/metabolism ; Presenilin-1/genetics ; Male ; Amyloid beta-Protein Precursor/genetics/metabolism ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: A growing body of evidence suggests a link between the gut microbiota and Alzheimer's disease (AD), although the underlying mechanisms remain elusive. This study aimed to investigate the impact of fecal microbiota transplantation (FMT) on cognitive function in a mouse model of AD.

METHODS: Four-month-old 5 × FAD (familial Alzheimer's disease) mice underwent antibiotic treatment to deplete their native gut microbiota. Subsequently, they received FMT either weekly or every other day. After 8 weeks, cognitive function and β-amyloid (Aβ) load were assessed through behavioral testing and pathological analysis, respectively. The composition of the gut microbiota was analyzed using 16S rRNA sequencing.

RESULTS: Initial weekly FMT failed to alleviate memory deficits or reduce brain Aβ pathology in 5 × FAD mice. In contrast, FMT administered every other day effectively restored gut dysbiosis in 5 × FAD mice and decreased Aβ pathology and lipopolysaccharide levels in the colon and hippocampus. Mechanistically, FMT reduced the expression of amyloid β precursor protein, β-site APP cleaving enzyme 1, and presenilin-1, potentially by inhibiting the Toll-like receptor 4/inhibitor of kappa B kinase β/nuclear factor kappa-B signaling pathway. However, the cognitive benefits of FMT on 5 × FAD mice diminished over time.

CONCLUSION: These findings demonstrate the dose- and time-dependent efficacy of FMT in mitigating AD-like pathology, underscoring the potential of targeting the gut microbiota for AD treatment.}, } @article {pmid39955611, year = {2025}, author = {Launspach, M and Mindermann, A and Schulz, J and Alasfar, L and Cyrull, S and Zirngibl, F and Oevermann, L and Künkele, A and Deubzer, HE and von Bernuth, H and Pruß, A and Lang, P and Bufler, P and Eggert, A and von Stackelberg, A and Schulte, JH}, title = {High Incidence and Impact of Suspected Exocrine Pancreatic Insufficiency in Patients Post-Hematopoietic Stem Cell Transplantation: A Single-Center Prospective Observational Study.}, journal = {United European gastroenterology journal}, volume = {}, number = {}, pages = {}, doi = {10.1002/ueg2.12769}, pmid = {39955611}, issn = {2050-6414}, support = {//Charité - Universitätsmedizin Berlin & the Berlin Institute of Health;/ ; }, abstract = {Exocrine pancreatic insufficiency (EPI) is suspected but remains understudied in immunosuppressed conditions such as post-hematopoietic stem cell transplantation (HSCT). This prospective observational study aimed to investigate the incidence, impact, and risk factors of EPI in a cohort of 83 pediatric and young adult patients who underwent allogeneic HSCT at Charité - Universitätsmedizin Berlin between 2020 and 2023. Fecal pancreatic elastase (PE) measurements and transabdominal ultrasound were utilized to evaluate pancreatic function over a one-year period. Secondary analysis explored the association of EPI with clinical complications and included a multivariable regression analysis of potential risk factors. Low PE levels significantly correlated with pathological pancreatic imaging findings, independent of concurrent diarrhea. EPI was suspected in 45% (32/71) of patients (95%CI: [34.1%, 56.6%]), with 29% (13/45) (95%CI: [17.7%, 43.4%]) showing signs of prolonged EPI (pEPI) lasting at least 8 weeks. After excluding cases with confounding factors such as missing enteral nutrition and diarrhea, the cumulative incidence of prolonged EPI was 20% (8/41) (95%CI: 10.2%-34.0%) in the overall cohort. EPI was associated with weight loss, prolonged dependence on parenteral nutrition, and extended hospitalizations. Adenovirus (ADV) infection emerged as a significant risk factor for EPI (hazard ratio 3.22 [95%CI:1.26-8.2], p = 0.014), along with additional factors such as higher BMI pre-HSCT, pre-existing pancreatic damage and early post-HSCT fasting. The persistence of pancreatic atrophy and EPI beyond two years post-HSCT in individual cases suggests a potential for permanent pancreatic damage. This study underscores that EPI is a common complication following HSCT, with ADV infection being an important risk factor. The findings support routine PE measurements and early initiation of pancreatic enzyme replacement therapy (PERT), alongside aggressive treatment of ADV infections. Further research is necessary to evaluate the effects of PERT in this population and to explore the applicability of these findings in other immunosuppressed groups.}, } @article {pmid39947548, year = {2025}, author = {Ma, X and Liu, J and Jiang, L and Gao, Z and Shi, Z and Zhang, N and Wang, Z and Li, S and Zhang, R and Xu, S}, title = {Dynamic changes in the gut microbiota play a critical role in age-associated cognitive dysfunction via SCFAs and LPS synthesis metabolic pathways during brain aging.}, journal = {International journal of biological macromolecules}, volume = {304}, number = {Pt 2}, pages = {140945}, doi = {10.1016/j.ijbiomac.2025.140945}, pmid = {39947548}, issn = {1879-0003}, abstract = {BACKGROUND: Gut microbiota plays an essential role in cognitive dysfunction during aging. The aim of this study was to investigate the dynamic alterations in the gut microbiota and screen for key gut bacterial taxa correlated with age-associated cognitive dysfunction during natural aging.

METHODS: 16S rRNA gene sequencing was performed to determine the composition of the gut microbiota in faecal samples from SAMR1 and SAMP8 mice, cognitively normal controls (NC), and patients with amnestic mild cognitive impairment (aMCI). Faecal microbiota transplantation (FMT) and GMrepo database were used to screen key gut microbiota associated with cognitive decline in aging mice and humans.

RESULTS: The composition of the gut microbiota dynamically changed during natural aging in SAMR1 and SAMP8 mice, as well as in healthy subjects of different ages extracted from the GMrepo database. FMT from SAMR1 to SAMP8 mice altered the gut microbiota composition and improved the cognitive impairment in SAMP8 mice. Key gut bacterial taxa, including Lactobacillus, Akkermansia, Clostridium, Oscillospira and Dorea, were screened and validated to correlate with aging-associated cognitive decline. The function of the key gut bacterial taxa predicted by PICRUSt2 indicated that the metabolic pathways related to short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS) synthesis were involved in age-associated cognitive dysfunction during natural aging.

CONCLUSION: These results demonstrate that the composition of the gut microbiota changes dynamically during brain aging, with some key gut bacterial taxa playing critical roles in age-associated cognitive dysfunction through SCFAs and LPS synthesis metabolic pathways.}, } @article {pmid39946793, year = {2025}, author = {Chen, C and Xiao, Q and Wen, Z and Gong, F and Zhan, H and Liu, J and Li, H and Jiao, Y}, title = {Gut microbiome-derived indole-3-carboxaldehyde regulates stress vulnerability in chronic restraint stress by activating aryl hydrocarbon receptors.}, journal = {Pharmacological research}, volume = {213}, number = {}, pages = {107654}, doi = {10.1016/j.phrs.2025.107654}, pmid = {39946793}, issn = {1096-1186}, abstract = {Chronic stress constitutes a major precipitating factor for Major Depressive Disorder (MDD), and comprehending individual differences in stress responses is crucial for the development of effective intervention strategies for MDD. Recent studies indicate that an individual's vulnerability to chronic stress is closely associated with gut microbiota composition, but the underlying mechanisms remain unclear. This study aims to investigate whether the gut microbiota and its metabolites can serve as gut-brain signaling molecules and explores how the gut microbiota affects stress sensitivity. Here, we showed that gut microbiome-derived indole-3-carboxaldehyde (I3C) can act as a gut-brain signaling molecule that links tryptophan metabolism by gut microbes to stress vulnerability in the host. First, we identified a specific reduction in gut microbiome-derived I3C levels in the hippocampus and colon through untargeted and targeted metabolomic analyses. Then, the study of gut microbiota suggested that the relative abundance of lactobacillus was reduced significantly in stress-susceptible rats, whereas fecal microbiota transplantation regulates stress vulnerability. Furthermore, supplementation with I3C and the representative I3C-producing strain, Lactobacillus reuteri, was shown to alleviate depression-like behaviors induced by chronic stress. Further research confirms that I3C can inhibit neuroinflammation and promote hippocampal neurogenesis through the aryl hydrocarbon receptors (AhR) signal pathway, thereby mitigating the host's susceptibility to stress. In conclusion, our findings elucidate that the gut microbiome-derived-I3C can help buffer the host's stress through the AhR/SOCS2/NF-κB/NLRP3 pathway, providing a gut-brain signaling basis for emotional behavior.}, } @article {pmid39946032, year = {2025}, author = {Karam, F and El Deghel, Y and Iratni, R and Dakroub, AH and Eid, AH}, title = {The Gut Microbiome and Colorectal Cancer: An Integrative Review of the Underlying Mechanisms.}, journal = {Cell biochemistry and biophysics}, volume = {}, number = {}, pages = {}, pmid = {39946032}, issn = {1559-0283}, abstract = {Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. While the incidence and mortality of CRC have decreased overall due to better screening, rates in adults under 50 have risen. CRC can manifest as inherited syndromes (10%), familial clustering (20%), or sporadic forms (70%). The gut microbiota, comprising mainly firmicutes and bacteroidetes, play a key role in CRC development and prevention. Indeed, CRC progression is influenced by the dynamic interaction between the gut microbiota, the intestinal barrier, the immune system, and the production of short-chain fatty acids. Not surprisingly, imbalance in the gut microbiota, termed dysbiosis, has been linked to CRC due to ensuing chronic inflammation, DNA damage, and oxidative stress. This may explain the notion that probiotics and fecal microbiota transplantation offer potential strategies for CRC prevention and treatment by restoring microbial balance and enhancing anti-cancer immune responses. This review appraises the roles of gut microbiota in promoting or preventing CRC. It also discusses the mechanistic interplay between microbiota composition, the intestinal barrier, and the immune system, with the hope of developing potential therapeutic strategies.}, } @article {pmid39945558, year = {2025}, author = {Zhang, L and Liu, ZX and Liu, YH and Chen, Y and Chen, J and Lu, CH}, title = {Auricularia auriculaPolysaccharides Exert Anti-inflammatory Effects in Hepatic Fibrosis by the Gut-Liver Axis and Enhancing SCFA Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c07952}, pmid = {39945558}, issn = {1520-5118}, abstract = {Auricularia auricula, esteemed in Chinese culture for their culinary and medicinal properties, exhibits notable metabolic and immunomodulatory effects. The principal active constituents are indigestible fermentable polysaccharides, which not only exhibit anti-inflammatory activities but also facilitate the proliferation of beneficial gut microbiota. However, the influence of gut-derived components on liver-regulated metabolic products remains insufficiently understood. This item offers insights into the therapeutic potential of wood ear mushrooms for treating hepatic fibrosis and the associated mechanisms. Following 8 weeks of treatment, a substantial reduction in ECM deposition was recorded, linked to modulation of the NLRP3 inflammasome activation. This study aims to reveal the potential microbiome-mediated mechanisms behind its therapeutic effects. Insights from antibiotic combination treatments indicate that the protective effects against ECM deposition rely on the presence of specific gut microbiota. This fecal microbiota intervention enhances key physiological mechanisms, underscoring the contributions of Lactobacillales, Rikenellaceae, and Bacteroidaceae in potentially mitigating fibrosis. Collectively, these findings suggest that interventions utilizing wood ear mushrooms may reduce inflammation and ECM deposition, mediated by the TLR4/NF-κB pathway.}, } @article {pmid39944648, year = {2025}, author = {Lu, J and Jiang, M and Chai, D and Sun, Y and Wu, L}, title = {Integrative analysis of intestinal flora and untargeted metabolomics in attention-deficit/hyperactivity disorder.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1452423}, pmid = {39944648}, issn = {1664-302X}, abstract = {Attention Deficit Hyperactivity Disorder (ADHD) is a clinically common neurodevelopmental disorder of the brain. In addition to genetic factors, an imbalance in gut flora may also play a role in the development of ADHD. Currently, it is critical to investigate the function of gut flora and related metabolites, which may form the fundamental basis of bidirectional cross-linking between the brain and the gut, in addition to focusing on the changed gut flora in ADHD. This study aimed to investigate the possible relationship between changes in gut flora and metabolites and ADHD by analyzing metagenome and untargeted metabolomics of fecal samples from ADHD patients. Specifically, we attempted to identify key metabolites and the metabolic pathways they are involved in, as well as analyze in detail the structure and composition of the gut flora of ADHD patients. In order to further investigate the relationship between gut flora and ADHD symptoms, some behavioral studies were conducted following the transplantation of gut flora from ADHD patients into rats. The results of the metagenome analysis revealed several distinct strains, including Bacteroides cellulosilyticus, which could be important for diagnosing ADHD. Additionally, the ADHD group showed modifications in several metabolic pathways and metabolites, including the nicotinamide and nicotinic acid metabolic pathways and the metabolite nicotinamide in this pathway. The behavioral results demonstrated that rats with ADHD gut flora transplants displayed increased locomotor activity and interest, indicating that the onset of behaviors such as ADHD could be facilitated by the flora associated with ADHD. This research verified the alterations in gut flora and metabolism observed in ADHD patients and provided a list of metabolites and flora that were significantly altered in ADHD. Simultaneously, our findings revealed that modifications to the microbiome could potentially trigger behavioral changes in animals, providing an experimental basis for comprehending the function and influence of gut flora on ADHD. These results might provide new perspectives for the development of novel treatment strategies.}, } @article {pmid39944265, year = {2024}, author = {Ye, ZN and Eslick, GD and Huang, SG and He, XX}, title = {Faecal microbiota transplantation for eradicating Helicobacter pylori infection: clinical practice and theoretical postulation.}, journal = {eGastroenterology}, volume = {2}, number = {4}, pages = {e100099}, pmid = {39944265}, issn = {2976-7296}, abstract = {The sustained increase in antibiotic resistance leads to a declining trend in the eradication rate of Helicobacter pylori (H. pylori) infection with antibiotic-based eradication regimens. Administration of a single probiotic shows limited efficacy in eradicating H. pylori infection. This review indicates that faecal microbiota transplantation (FMT), a novel therapeutic approach, either as a monotherapy or adjunctive therapy, exhibits beneficial effects in terms of the eradication of H. pylori infection and the prevention of adverse events. The role of FMT in H. pylori eradication may be associated directly or indirectly with some therapeutic constituents within the faecal suspension, including bacteria, viruses, antimicrobial peptides and metabolites. In addition, variations in donor selection, faecal suspension preparation and delivery methods are believed to be the main factors determining the effectiveness of FMT for the treatment of H. pylori infection. Future research should refine the operational procedures of FMT to achieve optimal efficacy for H. pylori infection and explore the mechanisms by which FMT acts against H. pylori.}, } @article {pmid39943805, year = {2025}, author = {Ju, H and Zhou, Y and Wei, W and Hu, Y and Fang, H and Chen, Z and Sun, X and Shi, Y and Fang, H}, title = {Ageing-associated gut dysbiosis deteriorates mouse cognition.}, journal = {Acta biochimica et biophysica Sinica}, volume = {}, number = {}, pages = {}, doi = {10.3724/abbs.2024217}, pmid = {39943805}, issn = {1745-7270}, abstract = {Ageing is an independent factor for cognitive dysfunction. Ageing-associated alterations in the gut microbiota also affect cognition. The present study is designed to investigate changes in the gut microbiota and their participation in ageing-associated cognitive impairment. Both 10-week-old and 18-month-old mice are used. Mouse cognition is examined by novel object recognition and T-maze tests. Mouse feces are collected for sequencing and transplantation. Protein expression in the mouse intestine and hippocampus is studied using immunohistochemistry and immunofluorescence staining. Senescent neurons are induced by hydrogen peroxide in vitro. The cell lysates are used for western blot analysis and adenosine triphosphate (ATP) measurement. Our results show that 18-month-old mice exhibit cognitive dysfunction compared with young mice. In aged mice, transplanting the microbiota of young mice increases the protein presence of synaptophysin in the hippocampus and partially restores cognition. The protein expressions of mucin-2 and E-cadherin in the intestine are reduced in aged mice but are increased by transplantation. Gut microbiota analyses reveal that the reduced abundance of the microbe Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus in aged mice is restored by transplantation. Fecal microbiota transplantation in young mice increases the serum level of acetic acid in aged mice. Hydrogen peroxide stimulation induces senescence and reduces the protein expression levels of synaptophysin and acetyl-coenzyme A synthetase member 2 (ACSS2) in primary neurons. Incubation with acetic acid upregulates the protein expressions of ACSS2 and synaptophysin and further increases ATP production in senescent neurons. In summary, gut microbiota transplantation increases the abundance of Lactobacillales, elevates serum acetic acid level, and improves cognitive function in aged mice. Gut microbiota transplantation has therapeutic importance for ageing-associated cognitive decline.}, } @article {pmid39941980, year = {2025}, author = {Li, J and Jia, J and Teng, Y and Wang, X and Xia, X and Song, S and Zhu, B and Xia, X}, title = {Polysaccharides from Sea Cucumber (Stichopus japonicus) Synergize with Anti-PD1 Immunotherapy to Reduce MC-38 Tumor Burden in Mice Through Shaping the Gut Microbiome.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, pmid = {39941980}, issn = {2304-8158}, support = {Dljswgj202403//Dalian Jinshiwan Laboratory Project/ ; 81972692//National Natural Science of Foundation of China/ ; 2022YFD2100104//National Key Research and Development Program of China/ ; }, abstract = {Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and significantly improved outcomes for patients with certain malignancies. However, immunotherapy with ICIs is only effective in a subset of patients and the gut microbiota have been identified as an important factor associated with response to ICI therapy. Polysaccharides from sea cucumber (Stichopus japonicus) (SCP) have been shown to modulate the gut microbiota and exhibit beneficial health functions, but whether SCP could synergize with anti-PD1 immunotherapy remains unexplored. In this study, mice with ICI-sensitive MC38 tumors were treated with anti-PD1 antibody after supplementation with or without SCP to examine the potential impact of SCP on the efficacy of immunotherapy. SCP strongly amplified the anti-tumor activity of anti-PD1 in MC38 tumor-bearing mice. Flow cytometry and immunohistological staining demonstrated that SCP treatment increased cytotoxic CD8[+] T lymphocytes while decreasing regulatory Foxp3[+] CD4[+] T lymphocytes. Gut microbiota and metabolomic analysis revealed that SCP modulated the microbiota and increased the abundance of certain metabolites such as indole-3-carboxylic acid. Furthermore, fecal microbiota transplantation experiments justified that the synergistic effect of SCP with anti-PD1 was partially mediated through the gut microbiota. Mice receiving microbiota from SCP-treated mice showed a boosted response to anti-PD1, along with enhanced anti-tumor immunity. These findings indicate that SCP could be utilized as a dietary strategy combined with anti-PD1 therapy to achieve improved outcomes in patients.}, } @article {pmid39939643, year = {2025}, author = {Tandoro, Y and Chiu, HF and Tan, CL and Hsieh, MH and Huang, YW and Yu, J and Wang, LS and Chan, CH and Wang, CK}, title = {Black raspberry supplementation on overweight and Helicobacter pylori infected mild dementia patients a pilot study.}, journal = {NPJ science of food}, volume = {9}, number = {1}, pages = {9}, pmid = {39939643}, issn = {2396-8370}, support = {R01 CA148818/CA/NCI NIH HHS/United States ; }, abstract = {Alzheimer's disease (AD) is the most common form of dementia. H. pylori infection and overweight have been implicated in AD via the gut-brain axis (GBA). This study aimed to determine whether supplementation of BRBs has a meaningful effect on H. pylori infection, overweight, and AD development in a clinical trial setting. We conducted a randomized placebo-controlled clinical trial in patients with mild clinical dementia who also had H. pylori infection and were overweight. The study was conducted over 10 weeks, consisting of an 8-week intervention period (25 g powder of black raspberries, BRBs, or placebo twice daily, morning and evening) and a 2-week follow-up. The primary outcomes were changes in Clinical Dementia Rating (CDR), Urea Breath Test (UBT), and Body Mass Index (BMI). Consumption of BRBs improved cognitive functions (p < 0.00001), compared to the placebo group (p > 0.05). Besides, BRBs ingestion decreased H. pylori infection and BMI (p < 0.00001 and p < 0.05 respectively) while the placebo group stayed statistically the same (p = 0.98 and p = 0.25 respectively). BRBs significantly decreased inflammatory markers, improved oxidative index, and adiponectin (p < 0.05) compared to the placebo group, while adenosine monophosphate-activated protein kinase (AMPK) and leptin did not significantly change. BRBs modulated the abundance of several fecal probiotics, particularly, Akkermansia muciniphila. Our results provided that BRBs suppressed H. pylori infection, decreased BMI, and rebalanced the gut microbiome, which could improve cognitive functions in mild dementia patients. Longer and larger randomized clinical trials of BRB interventions targeting H. pylori infection, overweight, or mild dementia are warranted to confirm the results from this pilot trial. Trial Registration: ClinicalTrials.gov identifier: NCT05680532.}, } @article {pmid39938959, year = {2025}, author = {Støy, S and Eriksen, LL and Lauszus, JS and Damsholt, S and Baunwall, SMD and Erikstrup, C and Vilstrup, H and Jepsen, P and Hvas, C and Thomsen, KL}, title = {Cirrhosis and Faecal microbiota Transplantation (ChiFT) protocol: a Danish multicentre, randomised, placebo-controlled trial in patients with decompensated liver cirrhosis.}, journal = {BMJ open}, volume = {15}, number = {2}, pages = {e091078}, pmid = {39938959}, issn = {2044-6055}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Liver Cirrhosis/therapy/complications/microbiology ; Denmark ; Double-Blind Method ; Randomized Controlled Trials as Topic ; Gastrointestinal Microbiome ; Multicenter Studies as Topic ; Male ; Disease Progression ; Female ; Adult ; Treatment Outcome ; }, abstract = {INTRODUCTION: Liver cirrhosis is a progressive disease with high mortality. Gut microbiota derangement, increased gut permeability, bacterial translocation and chronic inflammation all drive disease progression. This trial aims to investigate whether faecal microbiota transplantation (FMT) may improve the disease course in patients with acute decompensation of liver cirrhosis.

METHODS AND ANALYSIS: In this Danish, multicentre, randomised, double-blinded, placebo-controlled trial, 220 patients with acute decompensation of liver cirrhosis and a Child-Pugh score≤12 will be randomised (1:1) to oral, encapsulated FMT or placebo in addition to standard of care. Before the intervention, the patients will be examined and biological samples obtained, and this is repeated at 1 and 4 weeks and 3, 6 and 12 months after the intervention. The primary outcome is the time from randomisation to new decompensation or death. Secondary endpoints include mortality, number of decompensation events during follow-up and changes in disease severity and liver function.

ETHICS AND DISSEMINATION: The Central Denmark Region Research Ethics Committee approved the trial protocol (no. 1-10-72-302-20). The results will be published in an international peer-reviewed journal, and all patients will receive a summary of the results.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov study identifier NCT04932577.}, } @article {pmid39935515, year = {2024}, author = {Yao, L and Zhou, X and Jiang, X and Chen, H and Li, Y and Xiong, X and Tang, Y and Zhang, H and Qiao, P}, title = {High-fat diet promotes gestational diabetes mellitus through modulating gut microbiota and bile acid metabolism.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1480446}, pmid = {39935515}, issn = {1664-302X}, abstract = {INTRODUCTION: Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance during pregnancy, estimated to affect approximately 20% of the whole pregnancies and is increasing in prevalence globally. However, there is still a big gap in knowledge about the association between gut microbiota associated metabolism alterations and GDM development.

METHODS: All the participants accomplished the validated internet-based dietary questionnaire for Chinese and serum, fecal samples were collected. HFD, control diet or colesevelam intervention was fed to GDM mice models or Fxr-/- mice models, with or without antibiotics cocktail treatment. Fecal microbiota transplantation were used for further validation. Gut microbiota and metabolites were detected by metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Bile acids of serum, fecal samples from human and mice were analysised. Body weight, average feed intake, blood glucose, insulin levels and oral glucose tolerance test was performed among each groups. Expression levels of Fxr, Shp and Fgf15 mRNA and protein were detected by quantitative reverse transcription polymerase chain reaction and western blot, respectively.

RESULTS: Our data indicated that high fat diet (HFD) was linked with higher prevalence of GDM, and HFD was positively associated with poor prognosis in GDM patients. Moreover, compared with normal diet (ND) group, GDM patients from HFD group performed a loss of gut microbiota diversity and enrichment of Alistipes onderdonkii, Lachnospiraceae bacterium 1_7_58FAA, and Clostridium aspaaragiforme while ruduction of Akkermansiaceae, Paraprevotell xylaniphila, and Prevotella copri. Additionally, HFD aggravated GDM in mice and gut microbiota depletion by antibiotics crippled the effect of excess fat intake. BAs profile altered in HFD GDM patients and mice models. Fecal microbiota transplantation (FMT) further confirmed that gut microbiota contributed to bile acids (BAs) metabolic dysfunction during HFD-associated GDM development. Mechanically, HFD-FMT administration activated Fxr, Shp, and Fgf15 activity, disturbed the glucose metabolism and aggravated insulin resistance but not in HFD-FMT Fxr-/- mice and ND-FMT Fxr-/- mice. Furthermore, colesevelam intervention alleviated HFD-associated GDM development, improved BAs metabolism, suppressed Fxr, Shp, and Fgf15 activity only in WT mice but not in the Fxr-/- HFD + Colesevelam group and Fxr-/- HFD group. HFD induced GDM and contributed to poor prognosis in GDM parturients through inducing gut microbial dysbiosis and metabolic alteration, especially appeared in BAs profile. Moreover, Fxr pathway participated in regulating HFD-associated gut microbiota disordered BAs metabolites and aggravating GDM in mice.

DISCUSSION: Modulating gut microbiota and BAs metabolites could be a potential therapeutic strategy in the prevention and treatment of HFD-associated GDM.}, } @article {pmid39933444, year = {2025}, author = {Rob, M and Yousef, M and Lakshmanan, AP and Mahboob, A and Terranegra, A and Chaari, A}, title = {Microbial signatures and therapeutic strategies in neurodegenerative diseases.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {184}, number = {}, pages = {117905}, doi = {10.1016/j.biopha.2025.117905}, pmid = {39933444}, issn = {1950-6007}, abstract = {Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), arise from complex interactions between genetic factors, environmental exposures, and aging. Additionally, gut dysbiosis has been linked to systemic inflammation and neurodegeneration. Advances in microbiome and metabolome profiling techniques have provided deeper insights into how alterations in gut microbiota and dietary patterns affect metabolic pathways and contribute to the progression of NDs. This review explores the profiles of gut microbiome and metabolome derived biomarkers and their roles in NDs. Across phyla, families, and genera, we identified 55 microbial alterations in PD, 24 in AD, 4 in ALS, and 17 in MS. Some notable results include an increase in Akkermansia in PD, AD, and MS and a decrease in short-chain fatty acids (SCFAs) in PD and AD. We examined the effects of probiotics, prebiotics, fecal microbiota transplants (FMT), sleep, exercise, and diet on the microbiota, all of which contributed to delayed onset and alleviation of symptoms. Further, artificial intelligence (AI) and machine learning (ML) algorithms applied to omics data have been crucial in identifying novel therapeutic targets, diagnosing and predicting prognosis, and enabling personalized medicine using microbiota-modulating therapies in NDs patients.}, } @article {pmid39933221, year = {2025}, author = {Cao, Y and Fan, X and Zang, T and Li, Y and Tu, Y and Wei, Y and Bai, J and Liu, Y}, title = {Gut microbiota causes depressive phenotype by modulating glycerophospholipid and sphingolipid metabolism via the gut-brain axis.}, journal = {Psychiatry research}, volume = {346}, number = {}, pages = {116392}, doi = {10.1016/j.psychres.2025.116392}, pmid = {39933221}, issn = {1872-7123}, abstract = {Emerging evidence suggests that changes in the gut microbiota (GM) are related to prenatal depression onset, but the underlying molecular mechanisms remain obscure. This study was conducted to explore how disordered GM is involved in the onset of prenatal depression through the microbiome-gut-brain (MGB) axis. We transplanted fecal microbiota from women with and without prenatal depression into germ-free mice. Fecal metagenomic sequencing and LC-MS untargeted metabolomics analysis were performed to identify the GM composition, function, and metabolites in mice. Lipid metabolomics analysis was then used to characterize the lipid metabolism of brain tissue in mice. We found that mice transplanted with fecal microbiota from women with prenatal depression exhibited depressive-like behaviors as well as characteristic disorders of the phylum Firmicutes. Weighted Gene Correlation Network Analysis identified three microbial and one metabolic module in the gut, alongside two lipid metabolic modules in the brain, as significantly related to all depressive-like behaviors. These modules were enriched for glycerophospholipid and sphingolipid metabolism. In addition, the GM of mice with depressive-like behaviors were enriched and deficient in relevant functions and enzymes in the glycerophospholipid (mainly phosphatidylethanolamine) and sphingolipid (mainly hexosyl-ceramide) metabolic pathways, respectively. Consistently, glycerophospholipid and sphingolipid metabolites in the brains of depressive-like mice were up- and down-regulated. Increased phosphatidylethanolamine and decreased hexosyl-ceramide were significantly related to differential genera in the gut. Collectively, our findings provide a novel microbial and metabolic framework for understanding the role of the MGB axis in prenatal depression, indicating that the GM may be involved in the onset of depressive phenotypes by modulating central glycerophospholipid and sphingolipid metabolic homeostasis.}, } @article {pmid39932857, year = {2025}, author = {Lopetuso, LR and Deleu, S and Puca, P and Abreu, MT and Armuzzi, A and Barbara, G and Caprioli, F and Chieng, S and Costello, SP and Damiani, A and Danese, S and Del Chierico, F and D'Haens, G and Dotan, I and Facciotti, F and Falony, G and Fantini, MC and Fiorino, G and Gionchetti, P and Godny, L and Hart, A and Kupčinskas, J and Iqbal, T and Laterza, L and Lombardini, L and Maharshak, N and Marasco, G and Masucci, L and Papa, A and Paramsothy, S and Petito, V and Piovani, D and Pugliese, D and Putignani, L and Raes, J and Ribaldone, DG and Sanguinetti, M and Savarino, EV and Sokol, H and Vetrano, S and Ianiro, G and Cammarota, G and Cominelli, F and Pizarro, TT and Tilg, H and Gasbarrini, A and Vermeire, S and Scaldaferri, F}, title = {Guidance for Fecal Microbiota Transplantation Trials in Ulcerative Colitis: The Second ROME Consensus Conference.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf013}, pmid = {39932857}, issn = {1536-4844}, support = {//European Crohn's and Colitis Organization/ ; //Crohn's & Colitis Foundation: Clinical Research Investigator Initiated Award (CRIA)/ ; 882725//Senior Research Award (SRA)/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is emerging as a potential treatment modality for individuals living with inflammatory bowel disease (IBD). Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical investigation. Notwithstanding differences in methodologies, current studies demonstrate its potential for inducing remission in UC patients. Therefore, standardized and robust randomized clinical trials (RCTs) are needed to further support its efficacy for managing UC. The aim of the second Rome Consensus Conference was to address gaps and uncertainties identified in previous research regarding FMT and to offer a robust framework for future studies applied to the treatment of UC.

METHODS: Global experts in the field of clinical IBD, mucosal immunology, and microbiology (N = 48) gathered to address the need for standardized clinical trials in FMT investigation. The group focused on key issues, such as stool donation, donor selection, characterization of fecal biomass, potential administration routes, as well as the process of induction, maintenance, and endpoint readouts.

RESULTS AND CONCLUSIONS: The consensus achieved during this conference established standardization of methods and protocols to enhance the current quality of research, with the aim of eventual implementation of FMT in managing UC and the ultimate goal of improving patient outcomes.}, } @article {pmid39931541, year = {2025}, author = {Dong, S and Du, Y and Wang, H and Yuan, W and Ai, W and Liu, L}, title = {Research progress on the interaction between intestinal flora and microRNA in pelvic inflammatory diseases.}, journal = {Non-coding RNA research}, volume = {11}, number = {}, pages = {303-312}, pmid = {39931541}, issn = {2468-0540}, abstract = {Pelvic inflammatory disease (PID) is a common infectious disease of the female upper reproductive tract, and its pathological basis is immune inflammatory response. The imbalance of gut microflora (GM) may lead to the development of inflammatory process. A large number of studies have shown that fecal microbiota transplantation, probiotics, bacteria, prebiotics, and dietary intervention may play a potential role in remodeling GM and treating diseases. MicroRNAs (miRNAs) are involved in cell development, proliferation, apoptosis and other physiological processes. In addition, they play an important role in the inflammatory process, participating in the regulation of proinflammatory and anti-inflammatory pathways. Differences in miRNA profiles may be PID diagnostic tools and serve as prognostic markers of the disease. The relationship between miRNA and GM has not been fully elucidated. Recent studies have shown the role of miRNA in the regulation and induction of GM dysbiosis. In turn, microbiota can regulate the expression of miRNA and improve the immune status of the body. Therefore, this review aims to describe the interaction between GM and miRNA in PID, and to find potential precise targeted therapy for PID.}, } @article {pmid39931312, year = {2025}, author = {Zhu, L and Yang, X}, title = {Gut Microecological Prescription: A Novel Approach to Regulating Intestinal Micro-Ecological Balance.}, journal = {International journal of general medicine}, volume = {18}, number = {}, pages = {603-626}, pmid = {39931312}, issn = {1178-7074}, abstract = {The intestinal microecology is comprises intestinal microorganisms and other components constituting the entire ecosystem, presenting characteristics of stability and dynamic balance. Current research reveals intestinal microecological imbalances are related to various diseases. However, fundamental research and clinical applications have not been effectively integrated. Considering the importance and complexity of regulating the intestinal microecological balance, this study provides an overview of the high-risk factors affecting intestinal microecology and detection methods. Moreover, it proposes the definition of intestinal microecological imbalance and the definition, formulation, and outcomes of gut microecological prescription to facilitate its application in clinical practice, thus promoting clinical research on intestinal microecology and improving the quality of life of the population.}, } @article {pmid39931240, year = {2025}, author = {Wang, H and Li, S and Zhang, L and Zhang, N}, title = {Corrigendum: The role of fecal microbiota transplantation in type 2 diabetes mellitus treatment.}, journal = {Frontiers in endocrinology}, volume = {16}, number = {}, pages = {1555601}, doi = {10.3389/fendo.2025.1555601}, pmid = {39931240}, issn = {1664-2392}, abstract = {[This corrects the article DOI: 10.3389/fendo.2024.1469165.].}, } @article {pmid39931170, year = {2025}, author = {Wang, H and Huang, W and Pan, X and Tian, M and Chen, J and Liu, X and Li, Q and Qi, J and Ye, Y and Gao, L}, title = {Quzhou Aurantii Fructus Flavonoids Ameliorate Inflammatory Responses, Intestinal Barrier Dysfunction in DSS-Induced Colitis by Modulating PI3K/AKT Signaling Pathway and Gut Microbiome.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {1855-1874}, pmid = {39931170}, issn = {1178-7031}, abstract = {PURPOSE: To explore the protective effect and underlying mechanism of Quzhou Aurantii Fructus flavonoids (QAFF) on Ulcerative colitis (UC).

METHODS: The constituents of QAFF were accurately determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The therapeutic impacts of QAFF were assessed in dextran sulfate sodium (DSS)-induced UC mice, focusing on the changes in body weight, disease activity index (DAI), colon length, histological assessment of colonic tissues, levels of pro-inflammatory cytokines, and expression of tight junction proteins. Western blotting confirmed key regulatory proteins within the differential signaling pathways, guided by transcriptome analysis. Additionally, the influence of QAFF on the gut microbiome was explored through 16S ribosomal RNA (rRNA) sequencing. The alterations in endogenous metabolites were detected by untargeted metabolomics, and their potential correlation with intestinal flora was then examined utilizing Spearman correlation analysis. Subsequently, the regulation of gut microbiome by QAFF was validated by fecal microbiota transplantation (FMT).

RESULTS: Eleven flavonoids, including Naringin and hesperidin, were initially identified from QAFF. In vivo experiments demonstrated that QAFF effectively ameliorated colitis symptoms, reduced IL-6, IL-1β, and TNF-α levels, enhanced intestinal barrier integrity, and downregulated PI3K/AKT pathway activation. Furthermore, QAFF elevated the levels of beneficial bacteria like Lachnospiraceae_NK4A136_group and Alloprevotella and concurrently reduced the pathogenic bacteria such as Escherichia-Shigella, [Eubacterium]_siraeum_group, and Parabacteroides. Metabolomics analysis revealed that 34 endogenous metabolites exhibited significant alterations, predominantly associated with Glycerophospholipid metabolism. These metabolites were significantly correlated with those differential bacteria modulated by QAFF. Lastly, the administration of QAFF via FMT ameliorated the colitis symptoms.

CONCLUSION: QAFF could ameliorate inflammatory responses and intestinal barrier dysfunction in DSS-induced UC mice probably by modulating the PI3K/AKT signaling pathway and gut microbiome, offering promising evidence for the therapeutic potential of QAFF in UC treatment.}, } @article {pmid39930537, year = {2025}, author = {Liu, Q and Akhtar, M and Kong, N and Zhang, R and Liang, Y and Gu, Y and Yang, D and Nafady, AA and Shi, D and Ansari, AR and Abdel-Kafy, EM and Naqvi, SU and Liu, H}, title = {Early fecal microbiota transplantation continuously improves chicken growth performance by inhibiting age-related Lactobacillus decline in jejunum.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {49}, pmid = {39930537}, issn = {2049-2618}, support = {2017YFE0113700//National Key Research and Development Program of China/ ; HBZY2023B007//Supporting High Quality Development of Seed Industry Fund Project of Hubei Province/ ; }, mesh = {*Fecal Microbiota Transplantation/veterinary ; *Chickens/growth & development/microbiology ; *Jejunum/microbiology ; *Lactobacillus/physiology ; Age Factors ; Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Body Weight ; Insulin-Like Growth Factor I/genetics/metabolism ; Growth Hormone/genetics/metabolism ; Gene Expression ; Gene Expression Profiling/veterinary ; Male ; Animals ; }, abstract = {BACKGROUND: At an early age, chickens commonly exhibit a rise in the average daily gain, which declines as they age. Further studies indicated that the decrease in chicken growth performance at a later age is closely associated with an age-related decline in Lactobacillus abundance in the small intestines. Whether inhibiting the age-related decline in Lactobacillus in the small intestine by early fecal microbiota transplantation (FMT) could improve chicken growth performance is an interesting question.

RESULTS: 16S rRNA gene sequencing revealed a higher jejunal Lactobacillus abundance in high body weight chickens in both two different chicken breeds (yellow feather chickens, H vs L, 85.96% vs 55.58%; white feather chickens, H vs L, 76.21% vs 31.47%), which is significantly and positively associated with body and breast/leg muscle weights (P < 0.05). Moreover, the jejunal Lactobacillus abundance declined with age (30 days, 74.04%; 60 days, 50.80%; 120 days, 34.03%) and the average daily gain rose in early age and declined in later age (1 to 30 days, 5.78 g; 30 to 60 days, 9.86 g; 60 to 90 days, 7.70 g; 90 to 120 days, 3.20 g), indicating the age-related decline in jejunal Lactobacillus abundance is closely related to chicken growth performance. Transplanting fecal microbiota from healthy donor chickens with better growth performance and higher Lactobacillus abundance to 1-day-old chicks continuously improved chicken growth performance (Con vs FMT; 30 days, 288.45 g vs 314.15 g, P < 0.05; 60 days, 672.77 g vs 758.15 g, P < 0.01; 90 days, 1146.08 g vs 1404.43 g, P < 0.0001) even after stopping fecal microbiota transplantation at 4th week. Four-week FMT significantly inhibited age-related decline in jejunal Lactobacillus abundance (Con vs FMT, 30 days, 65.07% vs 85.68%, P < 0.01; 60 days, 38.87% vs 82.71%, P < 0.0001 and 90 days, 34.23% vs 60.86%, P < 0.01). Moreover, the numbers of goblet and Paneth cells were also found significantly higher in FMT groups at three time points (P < 0.05). Besides, FMT triggered GH/IGF-1 underlying signaling by significantly increasing the expressions of GH, GHR, and IGF-1 in the liver and IGF-1 and IGF-1R in muscles along age (P < 0.05).

CONCLUSION: These findings revealed that age-related decline in jejunal Lactobacillus abundance compromised chicken growth performance, while early fecal microbiota transplantation continuously improved chicken growth performance by inhibiting age-related jejunal Lactobacillus decline, promoting the integrity of jejunal mucosal barrier and up-regulating the expression level of genes related to growth axis. Video Abstract.}, } @article {pmid39929593, year = {2025}, author = {Harigai, W and Mikami, K and Choudhury, ME and Yamauchi, H and Yajima, C and Shimizu, S and Miyaue, N and Nagai, M and Kubo, M and Tanaka, J and Katayama, T}, title = {Effects of fecal microbiota transplantation on behavioral abnormality in attention deficit hyperactivity disorder-like model rats.}, journal = {Journal of pharmacological sciences}, volume = {157}, number = {3}, pages = {189-198}, doi = {10.1016/j.jphs.2025.01.007}, pmid = {39929593}, issn = {1347-8648}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Attention Deficit Disorder with Hyperactivity/therapy/microbiology ; *Disease Models, Animal ; *Gastrointestinal Microbiome ; Male ; *Behavior, Animal ; Rats ; Dysbiosis/therapy ; Rats, Sprague-Dawley ; }, abstract = {Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. ADHD symptoms not only impact patients and their families but also impose societal costs. Current treatments for ADHD, including environmental adjustments and medication, are symptomatic and require long-term management. Recently, the link between gut microbiota dysbiosis and various psychiatric and neurological disorders has become evident. The effectiveness of fecal microbiota transplantation (FMT) from healthy individuals in treating autism spectrum disorder, a neurodevelopmental disorder related to ADHD, has been demonstrated. However, despite suggestions of a relationship between ADHD and gut microbiota, few studies have explored the efficacy of FMT for ADHD. In the current study, we used 16S rDNA analysis to show that ADHD-like model rats possess a gut microbiota that is distinct from that of healthy rats, and we demonstrated that FMT from healthy rats improved hyperactivity in ADHD-like model rats. Our findings suggest that differences in gut microbiota underlie ADHD-like behaviors and that FMT may be an effective treatment for ADHD.}, } @article {pmid39926318, year = {2025}, author = {Rågård, N and Baumwall, SMD and Paaske, SE and Hansen, MM and Høyer, KL and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Validation methods for encapsulated faecal microbiota transplantation: a scoping review.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848251314820}, pmid = {39926318}, issn = {1756-283X}, abstract = {Faecal microbiota transplantation (FMT) is increasingly used for diseases associated with a disrupted intestinal microbiome, mainly Clostridioides difficile infection. Encapsulated FMT is a patient-friendly application method that improves accessibility and convenience. Capsule processing may be standardised, but validation protocols are warranted. This review aimed to describe published validation methods for encapsulated FMT. Original studies reporting using encapsulated faecal formulations were included, regardless of indication. Studies were excluded if they did not address processing and validation or used non-donor-derived content. We conducted a comprehensive scoping review, implementing a systematic search strategy in PubMed, Embase and Web of Science. Processing data and validation methods were registered during full-text analysis and combined to create an overview of approaches for assessing quality in encapsulated FMT processing. The searches identified 324 unique studies, of which 44 were included for data extraction and analysis. We identified eight validation covariables: donor selection, pre-processing, preservation, oxygen-sparing processing, microbial count, viability, engraftment and clinical effect outcomes, from which we constructed a model for quality assessment of encapsulated FMT that exhaustively categorised processing details and validation measures. Our model comprised three domains: (1) Processing (donor selection and processing protocol), (2) Content analysis (microbiota measures and dose measures) and (3) Clinical effect (engraftment and clinical outcomes). No studies presented a reproducible capsule protocol; their validation strategies were sparse and divergent. The validation of FMT capsules is heterogeneous, and processing requires relevant standardisation protocols, mainly focusing on capsule content. Future studies should report validation covariables to enable accurate comparative assessments of clinical effects.}, } @article {pmid39926224, year = {2025}, author = {Paul, JK and Azmal, M and Haque, ASNB and Meem, M and Talukder, OF and Ghosh, A}, title = {Unlocking the secrets of the human gut microbiota: Comprehensive review on its role in different diseases.}, journal = {World journal of gastroenterology}, volume = {31}, number = {5}, pages = {99913}, pmid = {39926224}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology/physiology ; *Dysbiosis/immunology/microbiology ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; *Fecal Microbiota Transplantation ; Neoplasms/microbiology/immunology/therapy ; Bacteria/immunology ; Autoimmune Diseases/microbiology/immunology ; Metabolic Diseases/microbiology/immunology/therapy ; }, abstract = {The human gut microbiota, a complex and diverse community of microorganisms, plays a crucial role in maintaining overall health by influencing various physiological processes, including digestion, immune function, and disease susceptibility. The balance between beneficial and harmful bacteria is essential for health, with dysbiosis - disruption of this balance - linked to numerous conditions such as metabolic disorders, autoimmune diseases, and cancers. This review highlights key genera such as Enterococcus, Ruminococcus, Bacteroides, Bifidobacterium, Escherichia coli, Akkermansia muciniphila, Firmicutes (including Clostridium and Lactobacillus), and Roseburia due to their well-established roles in immune regulation and metabolic processes, but other bacteria, including Clostridioides difficile, Salmonella, Helicobacter pylori, and Fusobacterium nucleatum, are also implicated in dysbiosis and various diseases. Pathogenic bacteria, including Escherichia coli and Bacteroides fragilis, contribute to inflammation and cancer progression by disrupting immune responses and damaging tissues. The potential for microbiota-based therapies, such as probiotics, prebiotics, fecal microbiota transplantation, and dietary interventions, to improve health outcomes is examined. Future research directions in the integration of multi-omics, the impact of diet and lifestyle on microbiota composition, and advancing microbiota engineering techniques are also discussed. Understanding the gut microbiota's role in health and disease is essential for formulating personalized, efficacious treatments and preventive strategies, thereby enhancing health outcomes and progressing microbiome research.}, } @article {pmid39924929, year = {2025}, author = {Zhong, H and Jiang, M and Yuan, K and Sheng, F and Xu, X and Cui, Y and Sun, X and Tan, W}, title = {Alterations in gut microbiota and metabolites contribute to postoperative sleep disturbances.}, journal = {Animal models and experimental medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/ame2.12557}, pmid = {39924929}, issn = {2576-2095}, support = {82171187//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The composition of the intestinal flora and the resulting metabolites affect patients' sleep after surgery.

METHODS: We intended to elucidate the mechanisms by which disordered intestinal flora modulate the pathophysiology of postoperative sleep disturbances in hosts. In this study, we explored the impacts of anesthesia, surgery, and postoperative sleep duration on the fecal microbiota and metabolites of individuals classified postprocedurally as poor sleepers (PS) and good sleepers (GS), as diagnosed by the bispectral index. We also performed fecal microbiota transplantation in pseudo-germ-free (PGF) rats and applied Western blotting, immunohistochemistry, and gut permeability analyses to identify the potential mechanism of its effect.

RESULTS: Research finding shows the PS group had significantly higher postoperative stool levels of the metabolites tryptophan and kynurenine than the GS group. PGF rats that received gut microbiota from PSs exhibited less rapid eye movement (REM) sleep than those that received GS microbiota (GS-PGF: 11.4% ± 1.6%, PS-PGF: 4.8% ± 2.0%, p < 0.001). Measurement of 5-hydroxytryptophan (5-HTP) levels in the stool, serum, and prefrontal cortex (PFC) indicated that altered 5-HTP levels, including reduced levels in the PFC, caused sleep loss in PGF rats transplanted with PS gut flora. Through the brain-gut axis, the inactivity of tryptophan hydroxylase 1 (TPH1) and TPH2 in the colon and PFC, respectively, caused a loss of REM sleep in PGF rats and decreased the 5-HTP level in the PFC.

CONCLUSIONS: These findings indicate that postoperative gut dysbiosis and defective 5-HTP metabolism may cause postoperative sleep disturbances. Clinicians and sleep researchers may gain new insights from this study.}, } @article {pmid39924893, year = {2025}, author = {Chen, Y and Fang, H and Chen, H and Liu, X and Zhao, J and Stanton, C and Ross, RP and Chen, W and Yang, B}, title = {Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2464945}, pmid = {39924893}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Colorectal Neoplasms/microbiology/metabolism/prevention & control/pathology ; Humans ; *Bifidobacterium/metabolism/physiology ; *Linoleic Acids, Conjugated/metabolism ; Male ; Probiotics/administration & dosage/pharmacology ; Female ; Carcinogenesis ; PPAR gamma/metabolism/genetics ; Fatty Acids/metabolism ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Middle Aged ; Apoptosis ; Disease Progression ; Butyric Acid/metabolism ; Disease Models, Animal ; }, abstract = {Colorectal cancer (CRC) represents the third most common cancer worldwide. Consequently, there is an urgent need to identify novel preventive and therapeutic strategies for CRC. This study aimed to screen for beneficial bacteria that have a preventive effect on CRC and to elucidate the potential mechanisms. Initially, we compared gut bacteria and bacterial metabolites of healthy volunteers and CRC patients, which demonstrated that intestinal conjugated linoleic acid (CLA), butyric acid, and Bifidobacterium in CRC patients were significantly lower than those in healthy volunteers, and these indicators were significantly negatively correlated with CRC. Next, spontaneous CRC mouse model were conducted to explore the effect of supplemental CLA-producing Bifidobacterium on CRC. Supplementation of mice with CLA-producing Bifidobacterium breve CCFM683 and B. pseudocatenulatum MY40C significantly prevented CRC. Moreover, molecular approaches demonstrated that CLA and the CLA-producing gene, bbi, were the key metabolites and genes for CCFM683 to prevent CRC. Inhibitor intervention results showed that PPAR-γ was the key receptor for preventing CRC. CCFM683 inhibited the NF-κB signaling pathway, up-regulated MUC2, Claudin-1, and ZO-1, and promoted tumor cell apoptosis via the CLA-PPAR-γ axis. Additionally, fecal microbiota transplantation (FMT) and metagenomic analysis showed that CCFM683 up-regulated Odoribacter splanchnicus through CLA production, which then prevented CRC by producing butyric acid, up-regulating TJ proteins, regulating cytokines, and regulating gut microbiota. These results will contribute to the clinical trials of Bifidobacterium and the theoretical research and development of CRC dietary products.}, } @article {pmid39924042, year = {2025}, author = {Wu, T and Song, F and Huang, J and Cui, S and Wang, L and Yang, Q and Wu, Y and Li, B and Tu, Y and Wan, X and Liu, J}, title = {Gut microbiota: The pivotal conduit in the onset of constipation and its alleviation by tea flower polysaccharides (TFP) in a mouse model.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {140808}, doi = {10.1016/j.ijbiomac.2025.140808}, pmid = {39924042}, issn = {1879-0003}, abstract = {Plant-derived bioactive components, such as polysaccharides, provide promising alleviating effects on constipation with minimal side-effects compared to pharmacological interventions. This study aimed to explore the therapeutic potential of tea flower polysaccharides (TFP) on constipation and the involved mechanisms. In a loperamide-induced constipation mouse model, TFP administration significantly increased fecal water content from 54.23-57.30 % to 63.70-79.36 %, enhanced intestinal transit rate from 30.80 % to 38.81 %, and reduced gastrointestinal (GI) transit time from 234.4 min to 186.2 min. TFP restored levels of both excitatory and inhibitory hormones related to GI motility. Transcriptomic analysis of colonic epithelial cells revealed that TFP restored expression of 544 genes involved in various pathways, including the NF-κB and JAK-STAT signaling pathways, which are associated with the improvement of constipation. Gut microbiota analysis demonstrated that TFP mitigated dysbiosis by normalizing the Firmicutes/Bacteroidota ratio, inhibiting pathogenic genera (e.g., Helicobacter), and promoting beneficial genera (e.g., Muribaculaceae, Bacteroides, Parabacteroides). The mediating role of gut microbiota in the onset of constipation and its alleviation was confirmed through fecal microbiota transplantation (FMT). Furthermore, TFP and its combination with anti-constipation drugs alleviated constipation-induced hepatorenal damage. This study highlights TFP's potential in treating constipation and underscores the essential role of gut microbiota in its therapeutic effects.}, } @article {pmid39923429, year = {2025}, author = {Yang, F and Yan, Q and Wang, Y and Li, Q and Wang, J and Zeng, X and Pi, Y and Zhang, M and Wei, L}, title = {AMP1-1 alleviates bone loss in weightless rats by reducing peripheral 5-HT content via the microbiota-gut-bone axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {139}, number = {}, pages = {156447}, doi = {10.1016/j.phymed.2025.156447}, pmid = {39923429}, issn = {1618-095X}, abstract = {BACKGROUND: Weightlessness-induced bone loss (WIBL) refers to the reduction of bone mass and the decline of bone resistance to load in a weightless environment. However, current treatment strategies aimed at increasing bone mass are associated with various limitations and side effects, highlighting the urgent need for safer and more effective therapeutic options to address WIBL.

PURPOSE: We aimed to further explore the potential mechanism of the anti-WIBL effect of Atractylodes macrocephalon polysaccharide1-1(AMP1-1). To find a better way to treat WIBL and provide new insights for the development of therapeutic drugs for this condition.

METHODS: Firstly, the anti-weightlessness bone loss of AMP1-1 was verified by micro-computed tomography (Micro-CT), three-point mechanical bending test and Western Blot (WB). Subsequently, the intestinal barrier was examined using histopathology, immunohistochemistry (IHC), and WB. Finally, validation experiments were performed using fecal microbiota transplantation (FMT). After FMT, 16S rDNA sequencing was used to analyze the gut microbiota composition in the rat feces.

RESULTS: AMP1-1 was able to inhibit WIBL by enhancing bone mass, improving toughness, and increasing osteogenic activity. Meanwhile, AMP1-1 reduced peripheral 5-HT content by restoring enterochromaffin cell function through gut microbiota regulation and tight junction repair. FMT of rat fecal microbiota after gavage of AMP1-1 into tail suspension rats still has the effects of regulating gut microbiota, repairing intestinal barrier and reducing bone loss.

CONCLUSION: Our results demonstrate that AMP1-1 exerts a protective effect against WIBL in rats, potentially by modulating 5-HT content and 5-HT-related metabolism in bone tissue through microbiota-gut-bone axis. This study is the first to elucidate the mechanism of AMP1-1 in mitigating WIBL through the perspective of the microbiota-gut-bone axis. Moreover, this research integrates plant extract research with the issue of bone loss induced by microgravity (aerospace medicine), thereby opening new avenues for natural drug research.}, } @article {pmid39922394, year = {2025}, author = {Xu, W and Liu, A and Gong, Z and Xiao, W}, title = {L-Theanine prevents ulcerative colitis by regulating the CD4+ T cell immune response through the gut microbiota and its metabolites.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109845}, doi = {10.1016/j.jnutbio.2025.109845}, pmid = {39922394}, issn = {1873-4847}, abstract = {The disturbance of gut microbiota and its metabolites are considered to be the causes of ulcerative colitis (UC), which leads to immune abnormalities. Diet is the most important regulator of gut microbiota; therefore, it has a beneficial impact on UC. A novel food ingredient, L-theanine, alters the gut microbiota, thereby regulating gut immunity. However, whether L-theanine prevents UC by altering the gut microbiota, as well as the underlying mechanisms, remains unknown. Here, L-theanine was used to optimize the gut microbiota and its metabolites. Furthermore, to explore the mechanism by which L-theanine prevents UC, an L-theanine fecal microbiota solution was used to prevent dextran sulfate sodium-induced UC via fecal microbiota transplantation. Improvements in the colonic structure, colon histology scores, immune factors (IL-10), and inflammatory factors (IL-1β) demonstrated the preventive effect of L-theanine on UC. The 16S rDNA and metabolomic results showed that tryptophan-, short chain fatty acid-, and bile acid-related microbiota, such as Muribaculaceae, Lachnospiraceae, Alloprevotella, and Prevotellaceae were the dominant. Flow cytometry results showed that L-theanine decreased helper T (Th)1 and Th17 immune responses, and increased Th2 and T-regulatory immune responses via regulation of antigen-presenting cell responses, such as dendritic cells and macrophages. Therefore, L-theanine regulated the immune response of colon CD4 + T cells to dendritic cell and macrophage antigen presentation via tryptophan-, short chain fatty acid-, and bile acid-related microbiota, thereby preventing dextran sulfate sodium-induced UC.}, } @article {pmid39921898, year = {2025}, author = {Cohen, S and Spencer, EA and Dolinger, MT and Suskind, DL and Mitrova, K and Hradsky, O and Conrad, MA and Kelsen, JR and Uhlig, HH and Tzivinikos, C and Henderson, P and Wlazlo, M and Hackl, L and Shouval, DS and Bramuzzo, M and Urlep, D and Olbjørn, C and D'Arcangelo, G and Pujol-Muncunill, G and Yogev, D and Kang, B and Gasparetto, M and Rungoe, C and Kolho, KL and Hojsak, I and Norsa, L and Rinawi, F and Sansotta, N and Rimon, RM and Granot, M and Scarallo, L and Trindade, E and Rodríguez-Belvís, MV and Turner, D and Yerushalmy-Feler, A}, title = {Upadacitinib for Induction of Remission in Paediatric Crohn's Disease: An International Multicentre Retrospective Study.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.70016}, pmid = {39921898}, issn = {1365-2036}, abstract = {BACKGROUND: There are scarce data available on upadacitinib in children with Crohn's disease (CD).

AIM: To evaluate the effectiveness and safety of upadacitinib as an induction therapy in paediatric CD.

METHODS: This was a multicentre retrospective study between 2022 and 2024 of children treated with upadacitinib for induction of remission of active CD conducted in 30 centres worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN. We recorded demographic, clinical and laboratory data and adverse events (AEs) at week 8 post-induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle.

RESULTS: We included 100 children (median age 15.8 [interquartile range 14.3-17.2]). All were previously treated with biologic therapies including 89 with ≥ 2 biologics. At the end of the 8-week induction period, we observed clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) in 75%, 56% and 52%, respectively. By the end of induction, 68% had achieved normalisation of C-reactive protein, and 58% had faecal calprotectin (FC) < 150 mcg/g. There was combined CFR and FC remission in 13/31 children with available data at 8 weeks (13% of the ITT population). AEs were recorded in 24 children; the most frequent was acne in 12. Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy.

CONCLUSION: Upadacitinib is an effective induction therapy for refractory paediatric CD. Efficacy should be weighed against the potential risks of AEs.}, } @article {pmid39920804, year = {2025}, author = {Mooyottu, S and Muyyarikkandy, MS and Yousefi, F and Li, G and Sahin, O and Burrough, E and Scaria, J and Sponseller, B and Ramirez, A}, title = {Fecal microbiota transplantation modulates jejunal host-microbiota interface in weanling piglets.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {45}, pmid = {39920804}, issn = {2049-2618}, support = {2022-67015-40720//National Institute of Food and Agriculture/ ; 2022-67015-40720//National Institute of Food and Agriculture/ ; 2022-67015-40720//National Institute of Food and Agriculture/ ; 19-216 IPPA//Iowa Pork Producers Association/ ; 19-216 IPPA//Iowa Pork Producers Association/ ; }, mesh = {Animals ; Swine ; *Weaning ; *Fecal Microbiota Transplantation ; *Jejunum/microbiology ; *Gastrointestinal Microbiome ; *Feces/microbiology ; Bacteria/classification/genetics/isolation & purification ; Diarrhea/microbiology/therapy/veterinary ; Enterotoxigenic Escherichia coli ; Escherichia coli Infections/microbiology/therapy ; Swine Diseases/microbiology/therapy ; }, abstract = {BACKGROUND: Weaning-associated enteric diseases are a major concern in the swine industry. This study investigates the effects of fecal microbiota transplantation (FMT) on the jejunum of weanling piglets, a segment of bowel less studied in terms of microbiomic changes despite its primary involvement in major post-weaning enteric diseases, including postweaning diarrhea (PWD). Thirty-two 3-week-old piglets were divided equally into two groups: Control and FMT. The FMT group received fecal microbiota preparation from 3-month-old healthy pigs on the 1st and 3rd day after weaning. Half of each group was inoculated with an enterotoxigenic E. coli (ETEC) isolate 10 days post-FMT. Piglets were euthanized in the third week (14th and 18th days post-FMT) after weaning to collect intestinal tissues and contents for microbiomic, metabolomic, and transcriptomic analyses.

RESULTS: The jejunal microbiota showed a significant increase in alpha diversity in the third week post-FMT compared with the ileum and colon. FMT significantly enriched the jejunal microbiota composition, while multiple bacterial genera were specifically lacking in control weanling piglets. FMT was strongly associated with the enrichment of the genus Pseudoscardovia of the Bifidobacteriaceae family, which was found lacking in the jejunum of weanling control piglets and inversely associated with the abundance of the genus Bifidobacterium within the same family. Other genera associated with FMT included Solobacterium, Shuttleworthia, and Pseudoraminibacter, whereas bacteria such as Erysipelotrichaceae and Acidaminococcus were identified as most abundant in the control piglets. Metabolomic analysis revealed a significant modulatory effect of FMT on carbohydrate, amino acid, nucleotide, vitamin, and xenobiotic metabolisms, suggesting improved nutrient utilization. Transcriptomic analyses further confirmed the regulatory effects of FMT on gene expression associated with immune, metabolic, barrier, and neuroendocrine functions. Prior FMT treatment in the context of ETEC infection indicated a potential protective role, as evidenced by a significant shift in microbial diversity and metabolomic compositions and decreased diarrhea severity even though no effect on pathogen shedding was evident.

CONCLUSIONS: This study underscores the promise of FMT in enhancing jejunal health. In addition, the results suggest that FMT could be considered a potential strategy to address conditions associated with small intestinal dysbiosis in swine and other monogastric species with similar gut anatomy and physiology, such as humans. Video Abstract.}, } @article {pmid39917846, year = {2025}, author = {Jeong, S and Davis, CK and Chokkalla, AK and Kim, B and Park, S and Vemuganti, R}, title = {Fecal microbiota transplantation fails to impart the benefits of circadian-dependent intermittent fasting following ischemic stroke.}, journal = {Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism}, volume = {}, number = {}, pages = {271678X251319636}, pmid = {39917846}, issn = {1559-7016}, support = {R35 NS132184/NS/NINDS NIH HHS/United States ; IK6 BX005690/BX/BLRD VA/United States ; I01 BX006062/BX/BLRD VA/United States ; R01 NS130763/NS/NINDS NIH HHS/United States ; I01 BX005127/BX/BLRD VA/United States ; }, abstract = {Intermittent fasting (IF) is known to induce significant ischemic tolerance. Diet is a major proponent of gut microbiota, and gut microbial dysbiosis plays a role in post-stroke brain damage. Hence, we currently evaluated whether IF-mediated ischemic tolerance is mediated by gut microbiota. Additionally, circadian cycle is known to modulate post-ischemic outcomes, and thus we further evaluated if gut microbiota would be influenced by prophylactic IF during the inactive phase (fasting during daytime; IIF) or active phase (fasting during nighttime; AIF). The AIF, but not IIF, cohort showed a significantly decreased fecal Firmicutes/Bacteroidetes ratio compared with the ad libitum (AL) cohort. Moreover, the levels of gut microbiota-derived metabolites butyrate and propionate decreased in AL cohort following focal ischemia, whereas they increased in AIF cohort. However, fecal microbiota transplantation (FMT) from IIF or AIF cohort had no significant effects on post-ischemic motor and cognitive function recovery, anxiety-, and depression-like behaviors compared with FMT from AL cohort. Furthermore, FMT from IIF or AIF cohort did not influence the post-ischemic infarct volume, atrophy volume or white matter damage. Overall, the current findings indicate that the beneficial effects of IF after focal ischemia are not mediated by the gut microbiota.}, } @article {pmid39916498, year = {2025}, author = {Chen, Q and Gao, Y and Li, F and Yuan, L}, title = {The role of gut-islet axis in pancreatic islet function and glucose homeostasis.}, journal = {Diabetes, obesity & metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.16225}, pmid = {39916498}, issn = {1463-1326}, support = {82170812//National Natural Science Foundation of China/ ; }, abstract = {The gastrointestinal tract plays a vital role in the occurrence and treatment of metabolic diseases. Recent studies have convincingly demonstrated a bidirectional axis of communication between the gut and islets, enabling the gut to influence glucose metabolism and energy homeostasis in animals strongly. The 'gut-islet axis' is an essential endocrine signal axis that regulates islet function through the dialogue between intestinal microecology and endocrine metabolism. The discovery of glucagon-like peptide-1 (GLP-1), gastric inhibitory peptide (GIP) and other gut hormones has initially set up a bridge between gut and islet cells. However, the influence of other factors remains largely unknown, such as the homeostasis of the gut microbiota and the integrity of the gut barrier. Although gut microbiota primarily resides and affect intestinal function, they also affect extra-intestinal organs by absorbing and transferring metabolites derived from microorganisms. As a result of this transfer, islets may be continuously exposed to gut-derived metabolites and components. Changes in the composition of gut microbiota can damage the intestinal barrier function to varying degrees, resulting in increased intestinal permeability to bacteria and their derivatives. All these changes contribute to the severe disturbance of critical metabolic pathways in peripheral tissues and organs. In this review, we have outlined the different gut-islet axis signalling mechanisms associated with metabolism and summarized the latest progress in the complex signalling molecules of the gut and gut microbiota. In addition, we will discuss the impact of the gut renin-angiotensin system (RAS) on the various components of the gut-islet axis that regulate energy and glucose homeostasis. This work also indicates that therapeutic approaches aiming to restore gut microbial homeostasis, such as probiotics and faecal microbiota transplantation (FMT), have shown great potential in improving treatment outcomes, enhancing patient prognosis and slowing down disease progression. Future research should further uncover the molecular links between the gut-islet axis and the gut microbiota and explore individualized microbial treatment strategies, which will provide an innovative perspective and approach for the diagnosis and treatment of metabolic diseases.}, } @article {pmid39915986, year = {2025}, author = {Escobar, C and Aldeguer, X and Vivas, D and Manzano Fernández, S and Gonzalez Caballero, E and Garcia Martín, A and Barrios, V and Freixa-Pamias, R}, title = {The gut microbiota and its role in the development of cardiovascular disease.}, journal = {Expert review of cardiovascular therapy}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/14779072.2025.2463366}, pmid = {39915986}, issn = {1744-8344}, abstract = {INTRODUCTION: The pathophysiology of cardiovascular diseases encompasses a complex interplay of genetic and environmental risk factors. Even if traditional risk factors are treated to target, there remains a residual risk.

AREAS COVERED: This manuscript reviews the potential role of gut microbiota in the development of cardiovascular disease, and as potential target. A systematic search was conducted until 30 October 2024 on PubMed (MEDLINE), using the MeSH terms [Gut microbiota] + [Dysbiosis] + [Cardiovascular] + [TMAO] + [bile acids] + [short-chain fatty acids].

EXPERT OPINION: The term dysbiosis implies changes in equilibrium, with modifications in the composition and functionality of microbiota and a series of additional factors: reduced diversity and uniformity of microorganisms; reduced short-chain fatty acid-producing bacteria; increased gut permeability; release of metabolites, such as trimethylamine N-oxide, betaine, phenylalanine, tryptophan-kynurenine, phenylacetylglutamine, and lipopolysaccharides; and reduced secondary bile acid excretion, leading to inflammation, oxidative stress, and endothelial dysfunction and facilitating the onset of pathological conditions, including obesity, hypertension, diabetes, atherosclerosis, and heart failure. Attempts to restore gut microbiota balance through different interventions, mainly changes in diet, have been shown to positively affect individual components and metabolites and reduce the risk of cardiovascular disease. In addition, probiotics and prebiotics are potentially useful. Fecal microbiota transplantation is a promising therapy.}, } @article {pmid39135640, year = {2024}, author = {Cao, H and Zhang, D and Wang, P and Wang, Y and Shi, C and Wu, H and Du, H and Zhang, W and Gou, Z and Zhou, H and Wang, S}, title = {Gut microbiome: a novel preventive and therapeutic target for prostatic disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1431088}, pmid = {39135640}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; *Prostatic Diseases/microbiology/prevention & control/therapy ; Humans ; Male ; Inflammation/microbiology/pathology ; Metabolome ; Diet ; Fecal Microbiota Transplantation ; Medicine, Chinese Traditional ; }, abstract = {The human gut microbiome (GM) impacts various physiological processes and can lead to pathological conditions and even carcinogenesis if homeostasis is disrupted. Recent studies have indicated a connection between the GM and prostatic disease. However, the underlying mechanisms are still unclear. This review aims to provide a summary of the existing information regarding the connection between the GM and various prostatic conditions such as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), benign prostatic hyperplasia (BPH), and prostate cancer (PCa). Furthermore, the review aims to identify possible pathogenic mechanisms and suggest potential ways of targeting GM to prevent and treat prostatic disease. Due to the complexity of the mechanism between GM and prostatic diseases, additional research is required to comprehend the association between the two. This will lead to more effective treatment options for prostatic disease.}, } @article {pmid39915243, year = {2025}, author = {Zhao, S and Lin, H and Li, W and Xu, X and Wu, Q and Wang, Z and Shi, J and Chen, Y and Ye, L and Xi, L and Chen, L and Yuan, M and Su, J and Gao, A and Jin, J and Ying, X and Wang, X and Ye, Y and Sun, Y and Zhang, Y and Deng, X and Shen, B and Gu, W and Ning, G and Wang, W and Hong, J and Wang, J and Liu, R}, title = {Post sleeve gastrectomy-enriched gut commensal Clostridia promotes secondary bile acid increase and weight loss.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2462261}, doi = {10.1080/19490976.2025.2462261}, pmid = {39915243}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Bile Acids and Salts/metabolism ; *Weight Loss ; Mice ; *Gastrectomy ; Humans ; Male ; *Clostridium/metabolism/genetics ; *Mice, Inbred C57BL ; *Obesity/microbiology/metabolism/surgery ; Receptors, G-Protein-Coupled/metabolism/genetics ; Fecal Microbiota Transplantation ; Female ; Adult ; Feces/microbiology ; Symbiosis ; Bariatric Surgery ; Adipose Tissue/metabolism ; }, abstract = {The gut microbiome is altered after bariatric surgery and is associated with weight loss. However, the commensal bacteria involved and the underlying mechanism remain to be determined. We performed shotgun metagenomic sequencing in obese subjects before and longitudinally after sleeve gastrectomy (SG), and found a significant enrichment in microbial species in Clostridia and bile acid metabolizing genes after SG treatment. Bile acid profiling further revealed decreased primary bile acids (PBAs) and increased conjugated secondary bile acids (C-SBAs) after SG. Specifically, glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) were increased at different follow-ups after SG, and were associated with the increased abundance of Clostridia and body weight reduction. Fecal microbiome transplantation with post-SG feces increased SBA levels, and alleviated body weight gain in the recipient mice. Furthermore, both Clostridia-enriched spore-forming bacteria and GDCA supplementation increased the expression of genes responsible for lipolysis and fatty acid oxidation in adipose tissue and reduced adiposity via Takeda G-protein-coupled receptor 5 (TGR5) signaling. Our findings reveal post-SG gut microbiome and C-SBAs as contributory to SG-induced weight loss, in part via TGR5 signaling, and suggest SBA-producing gut microbes as a potential therapeutic target for obesity intervention.}, } @article {pmid39912727, year = {2025}, author = {Ma, X and Li, M and Zhang, Y and Xu, T and Zhou, X and Qian, M and Yang, Z and Han, X}, title = {Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {39912727}, issn = {2050-084X}, support = {32172765//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Wnt Signaling Pathway ; *Akkermansia/physiology ; *Gastrointestinal Microbiome/physiology ; Mice ; Swine ; *Enterotoxigenic Escherichia coli/physiology ; *Fecal Microbiota Transplantation ; Intestinal Mucosa/microbiology/metabolism ; Escherichia coli Infections/microbiology/therapy ; Disease Models, Animal ; Bacteroides fragilis/physiology ; Organoids ; }, abstract = {As the largest mucosal surface, the gut has built a physical, chemical, microbial, and immune barrier to protect the body against pathogen invasion. The disturbance of gut microbiota aggravates pathogenic bacteria invasion and gut barrier injury. Fecal microbiota transplantation (FMT) is a promising treatment for microbiome-related disorders, where beneficial strain engraftment is a significant factor influencing FMT outcomes. The aim of this research was to explore the effect of FMT on antibiotic-induced microbiome-disordered (AIMD) models infected with enterotoxigenic Escherichia coli (ETEC). We used piglet, mouse, and intestinal organoid models to explore the protective effects and mechanisms of FMT on ETEC infection. The results showed that FMT regulated gut microbiota and enhanced the protection of AIMD piglets against ETEC K88 challenge, as demonstrated by reduced intestinal pathogen colonization and alleviated gut barrier injury. Akkermansia muciniphila (A. muciniphila) and Bacteroides fragilis (B. fragilis) were identified as two strains that may play key roles in FMT. We further investigated the alleviatory effects of these two strains on ETEC infection in the AIMD mice model, which revealed that A. muciniphila and B. fragilis relieved ETEC-induced intestinal inflammation by maintaining the proportion of Treg/Th17 cells and epithelial damage by moderately activating the Wnt/β-catenin signaling pathway, while the effect of A. muciniphila was better than B. fragilis. We, therefore, identified whether A. muciniphila protected against ETEC infection using basal-out and apical-out intestinal organoid models. A. muciniphila did protect the intestinal stem cells and stimulate the proliferation and differentiation of intestinal epithelium, and the protective effects of A. muciniphila were reversed by Wnt inhibitor. FMT alleviated ETEC-induced gut barrier injury and intestinal inflammation in the AIMD model. A. muciniphila was identified as a key strain in FMT to promote the proliferation and differentiation of intestinal stem cells by mediating the Wnt/β-catenin signaling pathway.}, } @article {pmid39911724, year = {2025}, author = {Dutta, SK and Firnberg, E and Verma, S and Phillips, L and Nair, PP}, title = {Detection of Human Y Chromosome and the SRY Gene in Fecal Samples of Female Patients Following Fecal Microbiota Transplantation.}, journal = {Gastro hep advances}, volume = {4}, number = {2}, pages = {100568}, pmid = {39911724}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: We have postulated that fecal microbiota transplantation (FMT) is associated with transfer of microbiota from the donor and engraftment of intestinal epithelial cells in the recipient's colonic mucosa enabling the restoration of a stable microbial environment.

METHODS: We analyzed the presence of human Y chromosome (ChrY) and sex-determining region Y (SRY) gene within total human DNA extracted from fecal samples collected from 30 donors and 22 recurrent Clostridium difficile infection (RCDI) patients before and up to 24 months after FMT. A next-generation sequencing data analysis pipeline was applied to quantify the percentage of reads aligning to human ChrY. SRY gene detection was also performed by quantitative polymerase chain reaction and droplet digital polymerase chain reaction.

RESULTS: A significantly higher percentage of ChrY reads were identified in fecal samples of male donors as compared to female donor (P < .0001). Fecal samples collected from female RCDI patients who received FMT from male donors showed a significantly (P < .05) higher percentage of ChrY reads compared to female samples without male FMT donors. Four female patients with RCDI who received FMT from male donors showed a very large percent ChrY increase post-FMT even several months after FMT. SRY gene signal was detected by droplet digital polymerase chain reaction in 7 of the 11 fecal samples collected from the male donor pool but none from the female pool.

CONCLUSION: These observations clearly demonstrate the presence of ChrY and SRY gene signal in stool samples collected from male patients. The presence of increased ChrY in the stool samples of female RCDI patients after FMT from a male donor suggests possible engraftment of exfoliated intestinal epithelial cells in a subset of these patients.}, } @article {pmid39910418, year = {2025}, author = {Li, L and Mo, Q and Wan, Y and Zhou, Y and Li, W and Li, W}, title = {Antimicrobial peptide AP2 ameliorates Salmonella Typhimurium infection by modulating gut microbiota.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {64}, pmid = {39910418}, issn = {1471-2180}, support = {No. 82003436//Young Scientists Fund of the National Natural Science Foundation of China/ ; No. 2011BAD26B02//the 'twelfth five-year-plan' in National Support Program for Science and Technology for rural development in China/ ; No. 31472128//Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Salmonella typhimurium/drug effects/pathogenicity ; Mice ; *Cecum/microbiology ; *Salmonella Infections/microbiology/drug therapy ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; Cytokines/metabolism ; Antimicrobial Peptides/pharmacology ; Feces/microbiology ; Administration, Oral ; Salmonella Infections, Animal/drug therapy/microbiology ; Antimicrobial Cationic Peptides/pharmacology ; Fecal Microbiota Transplantation ; Bacteria/drug effects/classification/genetics ; Female ; }, abstract = {BACKGROUND: Endogenous antimicrobial peptides and proteins are essential for shaping and maintaining a healthy gut microbiota, contributing to anti-inflammatory responses and resistance to pathogen colonization. Salmonella enterica subsp. enterica serovar Typhimurium (ST) infection is one of the most frequently reported bacterial diseases worldwide. Manipulation of the gut microbiota through exogenous antimicrobial peptides may protect against ST colonization and improve clinical outcomes.

RESULTS: This study demonstrated that oral administration of the antimicrobial peptide AP2 (2 µg /mouse), an optimized version of native apidaecin IB (AP IB), provided protective effects against ST infection in mice. These effects were evidenced by reduced ST-induced body weight loss and lower levels of serum inflammatory cytokines. A 16 S rRNA-based analysis of the cecal microbiota revealed that AP2 significantly modulated the gut microbiota, increasing the relative abundance of Bifidobacterium while decreasing that of Akkermansia at the genus level. Furthermore, the transplantation of fecal microbiota from AP2-treated donor mice, rather than from Control mice, significantly reduced cecal damage caused by ST and decreased the concentration of ST by one order of magnitude after infection.

CONCLUSIONS: These findings reveal a novel mechanism by which exogenous antimicrobial peptides mitigate Salmonella Typhimurium infection through the modulation of gut microbiota.}, } @article {pmid39909032, year = {2025}, author = {Zhu, X and Hu, M and Huang, X and Li, L and Lin, X and Shao, X and Li, J and Du, X and Zhang, X and Sun, R and Tong, T and Ma, Y and Ning, L and Jiang, Y and Zhang, Y and Shao, Y and Wang, Z and Zhou, Y and Ding, J and Zhao, Y and Xuan, B and Zhang, H and Zhang, Y and Hong, J and Fang, JY and Xiao, X and Shen, B and He, S and Chen, H}, title = {Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2024.12.013}, pmid = {39909032}, issn = {1932-7420}, abstract = {Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but remains effective in only a subset of patients. Emerging evidence suggests that the gut microbiome and its metabolites critically influence ICB efficacy. In this study, we performed a multi-omics analysis of fecal microbiomes and metabolomes from 165 patients undergoing anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy, identifying microbial and metabolic entities associated with treatment response. Integration of data from four public metagenomic datasets (n = 568) uncovered cross-cohort microbial and metabolic signatures, validated in an independent cohort (n = 138). An integrated predictive model incorporating these features demonstrated robust performance. Notably, we characterized five response-associated enterotypes, each linked to specific bacterial taxa and metabolites. Among these, the metabolite phenylacetylglutamine (PAGln) was negatively correlated with response and shown to attenuate anti-PD-1 efficacy in vivo. This study sheds light on the interplay among the gut microbiome, the gut metabolome, and immunotherapy response, identifying potential biomarkers to improve treatment outcomes.}, } @article {pmid39908366, year = {2025}, author = {Wu, F and Lin, S and Luo, H and Wang, C and Liu, J and Zhu, X and Pang, Y}, title = {Noncontact microbiota transplantation by core-shell microgel-enabled nonleakage envelopment.}, journal = {Science advances}, volume = {11}, number = {6}, pages = {eadr7373}, pmid = {39908366}, issn = {2375-2548}, mesh = {*Microgels/chemistry ; *Gastrointestinal Microbiome ; Humans ; Fecal Microbiota Transplantation/methods ; Animals ; Probiotics ; Gelatin/chemistry ; Bacteria/metabolism ; }, abstract = {Transplantation of beneficial bacteria to specific microbiota has been widely exploited to treat diseases by reshaping a healthy microbial structure. However, direct exposure of exogenous bacteria in vivo suffers from low bioavailability and infection risk. Here, we describe a noncontact microbiota transplantation system (NMTS) by core-shell microgel-enabled nonleakage envelopment. Bacteria are encapsulated into the core of core-shell microgels via two-step light-initiated emulsion polymerization of gelatin methacrylate. NMTS is versatile for biocontainment of diverse strains, showing near complete encapsulation and negligible influence on bacterial activity. As a proof-of-concept study on probiotic transplantation to the gut microbiota, NMTS demonstrates the shielding effect to protect sealed bacteria from intraluminal insults of low pH and bile acid, the toughness to prevent bacterial leakage during entire gastrointestinal passage and reduce infection risk, and the permeability to release beneficial metabolites and reconstruct a balanced intestinal microbial structure, proposing a contactless fashion for advanced microbiota transplantation.}, } @article {pmid39908176, year = {2025}, author = {}, title = {Correction to: A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {80}, number = {1}, pages = {242-243}, doi = {10.1093/cid/ciaf032}, pmid = {39908176}, issn = {1537-6591}, } @article {pmid39907559, year = {2025}, author = {Ding, Q and Xue, J and Li, N and Hu, Z and Song, J}, title = {Fecal microbiota transplantation alleviates radiation enteritis by modulating gut microbiota and metabolite profiles.}, journal = {Biomolecules & biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2025.11835}, pmid = {39907559}, issn = {2831-090X}, abstract = {This study investigates the safety and underlying mechanisms of fecal microbiota transplantation (FMT) in treating radiation enteritis (RE). A rat model of RE was established with six groups: NC, RT, H-FMT, modified FMT (M-FMT), L-FMT, and BTAC. The therapeutic effects of FMT were assessed using the Disease Activity Index (DAI), histological analysis, and biochemical tests, including ink-propelling, xylitol exclusion, and enzyme-linked immunosorbent assay (ELISA). Gut microbiota alterations and fecal metabolism were analyzed via 16S rDNA sequencing and targeted metabolomics. The results demonstrated that FMT, particularly in the M-FMT group, effectively alleviated RE by reducing DAI scores, histological damage, and inflammatory markers while enhancing enzyme activity, superoxide dismutase (SOD) levels, and intestinal absorption. FMT also modulated gut microbiota composition, increasing beneficial species, such as Blautia wexlerae and Romboutsia timonensis while decreasing Enterococcus ratti. Metabolomics analysis revealed that FMT influenced niacin, nicotinamide, and starch metabolism, with notable changes in pantothenic acid and fatty acid levels. Spearman correlation analysis further indicated that these microbial shifts were associated with improved metabolic profiles. Overall, FMT mitigates RE by regulating gut microbiota and metabolites, with pantothenic acid and fatty acids emerging as potential therapeutic targets. Further research is needed to explore the underlying mechanisms in greater detail.}, } @article {pmid39906503, year = {2025}, author = {Song, Q and Zhang, K and Li, S and Weng, S}, title = {Trichosanthes kirilowii Maxim. Polysaccharide attenuates diabetes through the synergistic impact of lipid metabolism and modulating gut microbiota.}, journal = {Current research in food science}, volume = {10}, number = {}, pages = {100977}, pmid = {39906503}, issn = {2665-9271}, abstract = {Polysaccharide, a chain of sugars bound by glycosidic bonds, have a wide range of physiological activities, including hypoglycemic activity. In present study, we established T2DM mice models to explore the effects and mechanism of Trichosanthes kirilowii Maxim polysaccharide (TMSP1) on high-fat diet/streptozotocin (HF-STZ) induced diabetes mice. The results showed that high-fat diet significantly increased the oral glucose tolerance test (OGTT), viscera index, oxidative stress, impaired glucose tolerance, decreased body weight, immune response and short-chain fatty acid (SCFAs) content, and disrupted the balance of intestinal flora structure. However, after 6 weeks of TMSP1 intervention decreased lipid accumulation, ameliorated gut microbiota dysbiosis by increasing SCFAs-producing bacteria and mitigated intestinal inflammation and oxidative stress. Moreover, TMSP1 significantly restored the integrity of the intestinal epithelial barrier and mucus barrier. The results of fecal microbiota transplantation confirmed that TMSP1 exerted hypoglycemic effect through regulating intestinal flora to a certain extent. Collectively, the findings revealed TMSP1 intervention inhibits hyperglycemia by improving gut microbiota disorder, lipid metabolism, and inflammation. Hence, TMSP1 may be an effective measure to ameliorate HF-STZ induced diabetes.}, } @article {pmid39905483, year = {2025}, author = {Lin, Z and Feng, Y and Wang, J and Men, Z and Ma, X}, title = {Microbiota governs host chenodeoxycholic acid glucuronidation to ameliorate bile acid disorder induced diarrhea.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {36}, pmid = {39905483}, issn = {2049-2618}, mesh = {Animals ; *Chenodeoxycholic Acid/analogs & derivatives/metabolism ; Mice ; *Diarrhea/microbiology ; *Gastrointestinal Microbiome ; Swine ; *Bile Acids and Salts/metabolism ; Limosilactobacillus reuteri/metabolism ; Fecal Microbiota Transplantation ; Intestinal Mucosa/metabolism/microbiology ; Apoptosis ; Indoles/metabolism ; Glucuronides/metabolism ; Humans ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Sirtuin 1/metabolism ; Receptors, Cytoplasmic and Nuclear ; }, abstract = {BACKGROUND: Disorder in bile acid (BA) metabolism is known to be an important factor contributing to diarrhea. However, the pathogenesis of BA disorder-induced diarrhea remains unclear.

METHODS: The colonic BA pool and microbiota between health piglets and BA disorder-induced diarrheal piglets were compared. Fecal microbiota transplantation and various cell experiments further indicated that chenodeoxycholic acid (CDCA) metabolic disorder produced CDCA-3β-glucuronide, which is the main cause of BA disorder diarrhea. Non-targeted metabolomics uncovered the inhibition of the BA glucuronidation by Lactobacillus reuteri (L. reuteri) is through deriving indole-3-carbinol (I3C). In vitro, important gene involved in the reduction of BA disorder induced-diarrhea were screened by RNA transcriptomics sequencing, and activation pathway of FXR-SIRT1-LKB1 to alleviate BA disorder diarrhea and P53-mediated apoptosis were proposed in vitro by multifarious siRNA interference, CO-IP, immunofluorescence, and so on, which mechanism was also verified in a variety of mouse models.

RESULTS: Here, we reveal for the first time that core microbiota derived I3C represses gut epithelium glucuronidation, particularly 3β-glucuronic CDCA production, which reaction is mediated by host UDP glucuronosyltransferase family 1 member A4 (UGT1A4) and necessary of BA disorder induced diarrhea. Mechanistically, L. reuteri derived I3C activates aryl hydrocarbon receptor to decrease UGT1A4 transcription and CDCA-3β-glucuronide content, thereby upregulating FXR-SIRT1-LKB1 signal. LKB1 binds with P53 based on protein interaction, ultimately resists to apoptosis and diarrhea. Moreover, I3C assists CDCA to attain the ameliorative effects of FXR activation in BA disorder diarrhea, through reversion of abnormal metabolism pathway, improving the outcomes of CDCA supplement.

CONCLUSION: These findings uncover the crucial interplay between gut epithelial cells and microbes, highlighting UGT1A4-mediated conversion of CDCA-3β-glucuronide as a key target for ameliorating BA disorder-induced diarrhea. Video Abstract.}, } @article {pmid39725357, year = {2025}, author = {Ju, C and Liu, R and Ma, Y and Dong, H and Xu, R and Hu, H and Hao, D}, title = {Targeted microbiota dysbiosis repair: An important approach to health management after spinal cord injury.}, journal = {Ageing research reviews}, volume = {104}, number = {}, pages = {102648}, doi = {10.1016/j.arr.2024.102648}, pmid = {39725357}, issn = {1872-9649}, mesh = {*Spinal Cord Injuries/microbiology/therapy ; Humans ; *Dysbiosis ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation/methods ; }, abstract = {Current research primarily focuses on the pathological mechanisms of spinal cord injury (SCI), seeking to promote spinal cord repair and restore motorial and sensory functions by elucidating mechanisms of cell death or axonal regeneration. However, SCI is almost irreversible, and patients often struggle to regain mobility or self-care abilities after injuries. Consequently, there has been significant interest in modulating systemic symptoms following SCI to improve patients' quality of life. Neuron axonal disconnection and substantial apoptotic events following SCI result in signal transmission loss, profoundly impacting various organ and systems, including the gastrointestinal tract. Dysbiosis can lead to severe bowel dysfunction in patients, substantially lowering their quality of life and significantly reducing life expectancy of them. Therefore, researches focusing on the restoration of the gut microbiota hold promise for potential therapeutic strategies aimed at rehabilitation after SCI. In this paper, we explore the regulatory roles that dietary fiber, short-chain fatty acids (SCFAs), probiotics, and microbiota transplantation play in patients with SCI, summarize the potential mechanisms of post-SCI dysbiosis, and discuss possible strategies to enhance long-term survival of SCI patients. We aim to provide potential insights for future research aimed at ameliorating dysbiosis in SCI patients.}, } @article {pmid39904968, year = {2025}, author = {Ashiqueali, SA and Hayslip, N and Chaudhari, DS and Schneider, A and Zhu, X and Rubis, B and Seavey, CE and Alam, MT and Hussein, R and Noureddine, SA and Golusinska-Kardach, E and Pazdrowski, P and Yadav, H and Masternak, MM}, title = {Fecal microbiota transplant from long-living Ames dwarf mice alters the microbial composition and biomarkers of liver health in normal mice.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {39904968}, issn = {2509-2723}, support = {R56AG074499/NH/NIH HHS/United States ; R56AG069676/NH/NIH HHS/United States ; R56AG064075/NH/NIH HHS/United States ; RF1AG071762/NH/NIH HHS/United States ; R21AG072379/NH/NIH HHS/United States ; U01AG076928/NH/NIH HHS/United States ; W81XWH-18-PRARP AZ180098//U.S. Department of Defense/ ; 22A17//Florida Department of Health/ ; 22A17//Florida Department of Health/ ; HORIZON 2020-MSCA-RISE//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; HORIZON 2020-MSCA-RISE//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; }, abstract = {Aging is associated with intestinal dysbiosis, a condition characterized by diminished microbial biodiversity and inflammation. This leads to increased vulnerability to extraintestinal manifestations such as autoimmune, metabolic, and neurodegenerative conditions thereby accelerating mortality. As such, modulation of the gut microbiome is a promising way to extend healthspan. In this study, we explore the effects of fecal microbiota transplant (FMT) from long-living Ames dwarf donors to their normal littermates, and vice versa, on the recipient gut microbiota and liver transcriptome. Importantly, our previous studies highlight differences between the microbiome of Ames dwarf mice relative to their normal siblings, potentially contributing to their extended lifespan and remarkable healthspan. Our findings demonstrate that FMT from Ames dwarf mice to normal mice significantly alters the recipient's gut microbiota, potentially reprogramming bacterial functions related to healthy aging, and changes the liver transcriptome, indicating improved metabolic health. Particularly, the microbiome of Ames dwarf mice, characterized by a higher abundance of beneficial bacterial families such as Peptococcaceae, Oscillospiraceae, and Lachnospiraceae, appears to play a crucial role in modulating these effects. Alongside, our mRNA sequencing and RT-PCR validation reveals that FMT may contribute to the significant downregulation of p21, Elovl3, and Insig2, genes involved with cellular senescence and liver metabolic pathways. Our data suggest a regulatory axis exists between the gut and liver, highlighting the potential of microbiome-targeted therapies in promoting healthy aging. Future research should focus on functional validation of altered microbial communities and explore the underlying biomolecular pathways that confer geroprotection.}, } @article {pmid39904603, year = {2025}, author = {Lou, F and Yan, L and Luo, S and Dong, Y and Xu, J and Kang, N and Wang, H and Liu, Y and Pu, J and Yang, B and Cannon, RD and Xie, P and Ji, P and Jin, X}, title = {Dysbiotic oral microbiota-derived kynurenine, induced by chronic restraint stress, promotes head and neck squamous cell carcinoma by enhancing CD8[+] T cell exhaustion.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-333479}, pmid = {39904603}, issn = {1468-3288}, abstract = {BACKGROUND: Chronic restraint stress (CRS) is a tumour-promoting factor. However, the underlying mechanism is unknown.

OBJECTIVE: We aimed to investigate whether CRS promotes head and neck squamous cell carcinoma (HNSCC) by altering the oral microbiota and related metabolites and whether kynurenine (Kyn) promotes HNSCC by modulating CD8[+] T cells.

DESIGN: 4-nitroquinoline-1-oxide (4NQO)-treated mice were exposed to CRS. Germ-free mice treated with 4NQO received oral microbiota transplants from either CRS or control mouse donors. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were performed on mouse saliva, faecal and plasma samples to investigate alterations in their microbiota and metabolites. The effects of Kyn on HNSCC were studied using the 4NQO-induced HNSCC mouse model.

RESULTS: Mice subjected to CRS demonstrated a higher incidence of HNSCC and oral microbial dysbiosis than CRS-free control mice. Pseudomonas and Veillonella species were enriched while certain oral bacteria, including Corynebacterium and Staphylococcus species, were depleted with CRS exposure. Furthermore, CRS-altered oral microbiota promoted HNSCC formation, caused oral and gut barrier dysfunction, and induced a host metabolome shift with increased plasma Kyn in germ-free mice exposed to 4NQO treatment. Under stress conditions, we also found that Kyn activated aryl hydrocarbon receptor (AhR) nuclear translocation and deubiquitination in tumour-reactive CD8[+] T cells, thereby promoting HNSCC tumourigenesis.

CONCLUSION: CRS-induced oral microbiota dysbiosis plays a protumourigenic role in HNSCC and can influence host metabolism. Mechanistically, under stress conditions, Kyn promotes CD8[+] T cell exhaustion and HNSCC tumourigenesis through stabilising AhR by its deubiquitination.}, } @article {pmid39903739, year = {2025}, author = {Men, J and Li, H and Cui, C and Ma, X and Liu, P and Yu, Z and Gong, X and Yao, Y and Ren, J and Zhao, C and Song, B and Yin, K and Wu, J and Liu, W}, title = {Fecal bacteria transplantation replicates aerobic exercise to reshape the gut microbiota in mice to inhibit high-fat diet-induced atherosclerosis.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0314698}, pmid = {39903739}, issn = {1932-6203}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Atherosclerosis/microbiology/etiology ; Male ; Mice ; *Physical Conditioning, Animal ; *Mice, Inbred C57BL ; Disease Models, Animal ; Lipids/blood ; }, abstract = {Aerobic exercise exerts a significant impact on the gut microbiota imbalance and atherosclerosis induced by a high-fat diet. However, whether fecal microbiota transplantation, based on aerobic exercise, can improve atherosclerosis progression remains unexplored. In this study, we utilized male C57 mice to establish models of aerobic exercise and atherosclerosis, followed by fecal microbiota transplantation(Fig 1a). Firstly, we analyzed the body weight, somatotype, adipocyte area, and aortic HE images of the model mice. Our findings revealed that high-fat diet -induced atherosclerosis mice exhibited elevated lipid accumulation, larger adipocyte area, and more severe atherosclerosis progression. Additionally, we assessed plasma lipid levels, inflammatory factors, and gut microbiota composition in each group of mice. high-fat diet -induced atherosclerosis mice displayed dyslipidemia along with inflammatory responses and reduced gut microbiota diversity as well as abundance of beneficial bacteria. Subsequently performing fecal microbiota transplantation demonstrated that high-fat diet -induced atherosclerosis mice experienced weight loss accompanied by reduced lipid accumulation while normalizing their gut microbiota profile; furthermore it significantly improved blood lipids and inflammation markers thereby exhibiting notable anti- atherosclerosis effects. The findings suggest that aerobic exercise can modify gut microbiota composition and improve high-fat diet-induced atherosclerosis(Fig 1b). Moreover, these beneficial effects can be effectively transmitted through fecal microbiota transplantation, offering a promising therapeutic approach for managing atherosclerosis.}, } @article {pmid39902926, year = {2025}, author = {Rahman, R and Fouhse, JM and Ju, T and Fan, Y and Bhardwaj, T and Brook, RK and Nosach, R and Harding, J and Willing, BP}, title = {The impact of wild-boar-derived microbiota transplantation on piglet microbiota, metabolite profile, and gut proinflammatory cytokine production differs from sow-derived microbiota.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0226524}, doi = {10.1128/aem.02265-24}, pmid = {39902926}, issn = {1098-5336}, abstract = {Colonization of co-evolved, species-specific microbes in early life plays a crucial role in gastrointestinal development and immune function. This study hypothesized that modern pig production practices have resulted in the loss of co-evolved species and critical symbiotic host-microbe interactions. To test this, we reintroduced microbes from wild boars (WB) into conventional piglets to explore their colonization dynamics and effects on gut microbial communities, metabolite profiles, and immune responses. At postnatal day (PND) 21, 48 piglets were assigned to four treatment groups: (i) WB-derived mixed microbial community (MMC), (ii) sow-derived MMC, (iii) a combination of WB and sow MMC (Mix), or (iv) Control (PBS). Post-transplantation analyses at PND 48 revealed distinct microbial communities in WB-inoculated piglets compared with Controls, with trends toward differentiation from Sow but not Mix groups. WB-derived microbes were more successful in colonizing piglets, particularly in the Mix group, where they competed with Sow-derived microbes. WB group cecal digesta enriched with Lactobacillus helveticus, Lactobacillus mucosae, and Lactobacillus pontis. Cecal metabolite analysis showed that WB piglets were enriched in histamine, acetyl-ornithine, ornithine, citrulline, and other metabolites, with higher histamine levels linked to Lactobacillus abundance. WB piglets exhibited lower cecal IL-1β and IL-6 levels compared with Control and Sow groups, whereas the Mix group showed reduced IFN-γ, IL-2, and IL-6 compared with the Sow group. No differences in weight gain, fecal scores, or plasma cytokines were observed, indicating no adverse effects. These findings support that missing WB microbes effectively colonize domestic piglets and may positively impact metabolite production and immune responses.IMPORTANCEThis study addresses the growing concern over losing co-evolved, species-specific microbes in modern agricultural practices, particularly in pig production. The implementation of strict biosecurity measures and widespread antibiotic use in conventional farming systems may disrupt crucial host-microbe interactions that are essential for gastrointestinal development and immune function. Our research demonstrates that by reintroducing wild boar-derived microbes into domestic piglets, these microbes can successfully colonize the gut, influence microbial community composition, and alter metabolite profiles and immune responses without causing adverse effects. These findings also suggest that these native microbes can fill an intestinal niche, positively impacting immune activation. This research lays the groundwork for future strategies to enhance livestock health and performance by restoring natural microbial populations that produce immune-modulating metabolites.}, } @article {pmid39901991, year = {2025}, author = {Hemachandra, S and Rathnayake, SN and Jayamaha, AA and Francis, BS and Welmillage, D and Kaur, DN and Zaw, HK and Zaw, LT and Chandra, HA and Abeysekera, ME}, title = {Fecal Microbiota Transplantation as an Alternative Method in the Treatment of Obesity.}, journal = {Cureus}, volume = {17}, number = {1}, pages = {e76858}, pmid = {39901991}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for various health conditions, particularly obesity and metabolic disorders. This review examines the mechanisms underlying FMT, including its role in restoring gut microbiota diversity and enhancing immunomodulatory functions, which are essential for maintaining overall health. Recent studies indicate that FMT can significantly improve body weight and metabolic parameters, suggesting its potential as an alternative or complementary treatment to current obesity therapies. However, the effectiveness of FMT depends on several factors, including the composition of the donor microbiota, recipient characteristics, and concomitant medications or dietary interventions. Despite its great promise, challenges such as standardized protocols, donor screening, and the need for a deeper understanding of gut microbiota dynamics remain key hurdles. Future research should focus on elucidating the specific microbial compositions necessary for optimal therapeutic outcomes and exploring personalized FMT approaches tailored to individual patient profiles. This evolving field presents exciting opportunities for innovative strategies in obesity treatment, warranting further investigation and clinical application.}, } @article {pmid39901521, year = {2025}, author = {Kappel, SS and Sangild, PT and Zachariassen, G and Andersen, JH and Rasmussen, KK and Jeppesen, PB and Aunsholt, L}, title = {Protein and energy digestibility in preterm infants fed fortified human milk.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.70000}, pmid = {39901521}, issn = {1536-4801}, support = {//Innovation Fund Denmark (NEOCOL grant 6150-00004B)./ ; }, abstract = {OBJECTIVES: The objective of the present study is to determine whether the apparent nutrient digestibility differs between very preterm infants fortified with bovine colostrum (BC) compared to those fortified with a conventional fortifier (CF), building on previous findings that BC was associated with looser stools and reduced need for laxatives in very preterm infants (VPI).

METHODS: We conducted a 24-h digestibility balance study in 10 VPIs to assess the retention of protein, energy, and wet-weight following the intake of fortified human milk and collection of faecal excretions. Infants (n = 5) were matched by gestational age and birthweight.

RESULTS: In the 10 infants, the mean gestational age and birthweight were 28 ± 1 weeks and 899 ± 182 g, respectively. Infants fortified with BC had a higher faecal energy loss compared with infants fortified with CF (BC: 178 [range 111-205] vs. CF: 153 [96-235] kJ/kg, p < 0.05). No differences (p > 0.05) were found for wet-weight intake (421 [360-427] vs. 494 [328-500] kJ/kg), relative absorption of protein (60 [33-75] vs. 50 [33-75]%) or absolute protein absorption (249 [159-310) vs. 281 [210-347]).

CONCLUSION: Nutrient absorption was similar between groups although higher energy loss indicates reduced overall digestibility of BC versus CF, however, with a large variation within each group. Studies on more infants are required to confirm these results. A 24-h digestibility balance study can successfully be used to assess nutrient and energy retention in preterm infants.}, } @article {pmid39900090, year = {2025}, author = {Tay, SW and Low, AHL}, title = {Is faecal microbiota transplantation ready for prime time in systemic sclerosis?.}, journal = {The Lancet. Rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2665-9913(24)00376-X}, pmid = {39900090}, issn = {2665-9913}, } @article {pmid39843757, year = {2025}, author = {Pitashny, M and Kesten, I and Shlon, D and Hur, DB and Bar-Yoseph, H}, title = {The Future of Microbiome Therapeutics.}, journal = {Drugs}, volume = {85}, number = {2}, pages = {117-125}, pmid = {39843757}, issn = {1179-1950}, mesh = {Humans ; *Microbiota ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation/methods ; Phage Therapy/methods ; Synthetic Biology/methods/trends ; }, abstract = {The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving the way for the development of novel microbiome therapeutics, across a wide range of indications. In this narrative review, we provide an overview of state-of-the-art technologies in late-stage development, examining their advantages and limitations. By covering a spectrum, from fecal-derived products to live biotherapeutics, phage therapy, and synthetic biology, we illuminate the path toward the future of microbiome therapeutics.}, } @article {pmid39900089, year = {2025}, author = {Fretheim, H and Barua, I and Bakland, G and Dhainaut, A and Halse, AK and Carstens, MN and Didriksen, H and Midtvedt, Ø and Lundin, KEA and Aabakken, L and Sarna, VK and Zaré, HK and Khanna, D and Distler, O and Midtvedt, T and Bækkevold, ES and Olsen, IC and Domanska, D and Pesonen, ME and Molberg, Ø and Hoffmann-Vold, AM}, title = {Faecal microbiota transplantation in patients with systemic sclerosis and lower gastrointestinal tract symptoms in Norway (ReSScue): a phase 2, randomised, double-blind, placebo-controlled trial.}, journal = {The Lancet. Rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2665-9913(24)00334-5}, pmid = {39900089}, issn = {2665-9913}, abstract = {BACKGROUND: Gastrointestinal tract involvement is highly prevalent in systemic sclerosis, with few treatment options. We assessed the efficacy and safety of faecal microbiota transplantation using standardised anaerobic cultivated human intestinal microbiome (ACHIM) as a novel treatment option for patients with systemic sclerosis and symptomatic lower gastrointestinal tract involvement.

METHODS: In this phase 2, randomised, double-blind, placebo-controlled trial done at four university hospitals in Norway, we enrolled adults aged 18-85 years with systemic sclerosis and moderate-to-severe lower gastrointestinal tract symptoms (bloating or diarrhoea). Participants were randomly assigned 1:1 to intestinal infusions of placebo or ACHIM at weeks 0 and 2, stratified by worst symptom (bloating or diarrhoea). The primary endpoint was change in worst lower gastrointestinal tract symptom (bloating or diarrhoea) from week 0 to week 12, measured using the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 scoring system in the intention-to-treat population. Safety was assessed at weeks 0, 2, 4, 6, and 12 in all participants who received at least one infusion. A person with lived experience of systemic sclerosis was involved in the study planning and conduct. This trial was registered at ClinicalTrials.gov, NCT04300426.

FINDINGS: Between Sept 24, 2020, and Jan 14, 2022, 67 participants were enrolled and randomly allocated to placebo (n=34) or ACHIM (n=33). Mean age was 58·91 years (SD 11·59). 62 (93%) of 67 participants were women, five (7%) were men, and 50 (75%) were anti-centromere antibody positive. Change in worst lower gastrointestinal tract symptom from week 0 to week 12 did not differ between participants who received ACHIM (-0·13, 95% CI -0·37 to 0·11) and participants who received placebo (-0·33, -0·57 to -0·09; average marginal effect 0·20, 95% CI -0·12 to 0·52; p=0·22). Adverse events, mostly mild and short-lived gastrointestinal tract symptoms, were reported by 16 (48%) of 33 participants in the ACHIM group and 19 (56%) of 34 in the placebo group. During gastroscopy, one participant had a duodenal perforation.

INTERPRETATION: Faecal microbiota transplantation with ACHIM was well tolerated in participants with systemic sclerosis but did not result in an improvement in lower gastrointestinal tract symptoms.

FUNDING: KLINBEFORSK.

TRANSLATION: For the Norwegian translation of the abstract see Supplementary Materials section.}, } @article {pmid39899452, year = {2025}, author = {Chaki, T and Horiguchi, Y and Tachibana, S and Sato, S and Hirahata, T and Nishihara, N and Kii, N and Yoshikawa, Y and Hayamizu, K and Yamakage, M}, title = {Gut Microbiota Influences Developmental Anesthetic Neurotoxicity in Neonatal Rats.}, journal = {Anesthesia and analgesia}, volume = {}, number = {}, pages = {}, doi = {10.1213/ANE.0000000000007410}, pmid = {39899452}, issn = {1526-7598}, abstract = {BACKGROUND: Anesthetic exposure during childhood is significantly associated with impairment of neurodevelopmental outcomes; however, the causal relationship and detailed mechanism of developmental anesthetic neurotoxicity remain unclear. Gut microbiota produces various metabolites and influences the brain function and development of the host. This relationship is referred to as the gut-brain axis. Gut microbiota may influence developmental anesthetic neurotoxicity caused by sevoflurane exposure. This study investigated the effect of changes in the composition of gut microbiota after fecal microbiota transplantation on spatial learning disability caused by developmental anesthetic neurotoxicity in neonatal rats.

METHODS: Neonatal rats were allocated into the Control (n = 10) and Sevo (n = 10) groups in Experiment 1 and the Sevo (n = 20) and Sevo+FMT (n = 20) groups in Experiment 2, according to the randomly allocated mothers' group. The rats in Sevo and Sevo+FMT groups were exposed to 2.1% sevoflurane for 2 hours on postnatal days 7 to 13. Neonatal rats in the Sevo+FMT group received fecal microbiota transplantation immediately after sevoflurane exposure on postnatal days 7 to 13. The samples for fecal microbiota transplantation were obtained from nonanesthetized healthy adult rats. Behavioral tests, including Open field, Y-maze, Morris water maze, and reversal Morris water maze tests, were performed to evaluate spatial learning ability on postnatal days 26 to 39.

RESULTS: Experiment 1 revealed that sevoflurane exposure significantly altered the gut microbiota composition. The relative abundance of Roseburia (effect value: 1.01) and Bacteroides genus (effect value: 1.03) increased significantly after sevoflurane exposure, whereas that of Lactobacillus (effect value: -1.20) decreased significantly. Experiment 2 revealed that fecal microbiota transplantation improved latency to target (mean ± SEM; Sevo group: 9.7 ± 8.2 seconds vs, Sevo+FMT group: 2.7 ± 2.4 seconds, d=1.16, 95% confidence interval: -12.7 to -1.3 seconds, P = .019) and target zone crossing times (Sevo group: 2.4 ± 1.6 vs, Sevo+FMT group: 5.4 ± 1.4, d=1.99, 95% confidence interval: 2.0-5.0, P < .001) in the reversal Morris water maze test. Microbiota analysis revealed that the α-diversity of gut microbiota increased after fecal microbiota transplantation. Similarly, the relative abundance of the Firmicutes phylum (effect value: 1.44), Ruminococcus genus (effect value: 1.69), and butyrate-producing bacteria increased after fecal microbiota transplantation. Furthermore, fecal microbiota transplantation increased the fecal concentration of butyrate and induced histone acetylation and the mRNA expression of brain-derived neurotrophic factor in the hippocampus, thereby suppressing neuroinflammation and neuronal apoptosis.

CONCLUSIONS: The alternation of gut microbiota after fecal microbiota transplantation influenced spatial learning ability in neonatal rats with developmental anesthetic neurotoxicity. Modulation of the gut microbiota may be an effective prophylaxis for developmental anesthetic neurotoxicity in children.}, } @article {pmid39897551, year = {2025}, author = {Yu, C and Sun, R and Yang, W and Gu, T and Ying, X and Ye, L and Zheng, Y and Fan, S and Zeng, X and Yao, S}, title = {Exercise ameliorates osteopenia in mice via intestinal microbial-mediated bile acid metabolism pathway.}, journal = {Theranostics}, volume = {15}, number = {5}, pages = {1741-1759}, pmid = {39897551}, issn = {1838-7640}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Fecal Microbiota Transplantation/methods ; *Bone Diseases, Metabolic/metabolism/therapy ; *Bile Acids and Salts/metabolism ; Female ; *Physical Conditioning, Animal/physiology ; Ovariectomy ; Mice, Inbred C57BL ; Disease Models, Animal ; Osteoporosis/metabolism/therapy ; RNA, Ribosomal, 16S/genetics ; Bone and Bones/metabolism ; Metabolomics/methods ; }, abstract = {Rationale: Physical exercise is essential for skeletal integrity and bone health. The gut microbiome, as a pivotal modulator of overall physiologic states, is closely associated with skeletal homeostasis and bone metabolism. However, the potential role of intestinal microbiota in the exercise-mediated bone gain remains unclear. Methods: We conducted microbiota depletion and fecal microbiota transplantation (FMT) in ovariectomy (OVX) mice and aged mice to investigate whether the transfer of gut ecological traits could confer the exercise-induced bone protective effects. The study analyzed the gut microbiota and metabolic profiles via 16S rRNA gene sequencing and LC-MS untargeted metabolomics to identify key microbial communities and metabolites responsible for bone protection. Transcriptome sequencing and RNA interference were employed to explore the molecular mechanisms. Results: We found that gut microbiota depletion hindered the osteogenic benefits of exercise, and FMT from exercised osteoporotic mice effectively mitigated osteopenia. Comprehensive profiling of the microbiome and metabolome revealed that the exercise-matched FMT reshaped intestinal microecology and metabolic landscape. Notably, alterations in bile acid metabolism, specifically the enrichment of taurine and ursodeoxycholic acid, mediated the protective effects on bone mass. Mechanistically, FMT from exercised mice activated the apelin signaling pathway and restored the bone-fat balance in recipient MSCs. Conclusion: Our study underscored the important role of the microbiota-metabolic axis in the exercise-mediated bone gain, heralding a potential breakthrough in the treatment of osteoporosis.}, } @article {pmid39897545, year = {2025}, author = {Hou, W and Cao, Y and Wang, J and Yin, F and Wang, J and Guo, N and Wang, Z and Lv, X and Ma, C and Chen, Q and Yang, R and Wei, H and Li, J and Wang, R and Qin, H}, title = {Single-cell nanocapsules of gut microbiota facilitate fecal microbiota transplantation.}, journal = {Theranostics}, volume = {15}, number = {5}, pages = {2069-2084}, pmid = {39897545}, issn = {1838-7640}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Nanocapsules ; *Fecal Microbiota Transplantation/methods ; Mice ; Colitis/therapy/microbiology ; Disease Models, Animal ; Phosphatidylcholines/chemistry ; Fibroins ; Mice, Inbred C57BL ; Male ; }, abstract = {Rationale: Fecal microbiota transplantation (FMT) is advantageous for treating intractable diseases via the microbiota-gut-organ axis. However, invasive administration of gut microbiota via nasal feeding tubes limits the widespread application of FMT. Here, we attempted to develop a novel strategy to deliver gut microbiota using nanocapsules. Methods: Single-cell nanocapsules were fabricated within 1 h by layer-by-layer assembly of silk fibroin and phosphatidylcholine to generate a protective nanoshell on the cell surface of complicated microbiota. The physical properties of the microbiota nanocapsules were analyzed. The protective effects of nanocapsules on the gastrointestinal tract were analyzed both in vitro and in vivo. The efficacy of FMT assisted by single-cell nanocapsules (NanoFMT) was evaluated using the inflammatory response, gut microbiota balance, and histopathological analysis in animal model. Results: The nanocapsules achieved a good coating ratio for a single type of microbe and complex microbiota, resulting in a remarkable increase in the survival rate of microbes in the gastrointestinal tract. NanoFMT improved the diversity and abundance of the gut microbiota better than common FMT in germ-free mice. Moreover, NanoFMT alleviated intestinal inflammation and positively reversed the microbiota balance in a mouse model of colitis compared with common FMT, assisted by the inherent anti-inflammatory effects of silk fibroin and phosphatidylcholine. Conclusions: Considering its rapid preparation, convenient delivery, and perfect therapeutic effect, we anticipate that NanoFMT may be a promising clinical candidate for next-generation FMT treatment.}, } @article {pmid39896755, year = {2025}, author = {Zhao, B and Zhou, H and Lin, K and Xu, J and Zhou, B and Xie, D and Ma, J and Yang, L and Su, C and Yang, L}, title = {Antimicrobial peptide DP7 alleviates dextran sulfate sodium (DSS)-induced colitis via modifying gut microbiota and regulating intestinal barrier function.}, journal = {MedComm}, volume = {6}, number = {2}, pages = {e70085}, pmid = {39896755}, issn = {2688-2663}, abstract = {Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), represent a growing global health concern. Restoring the balance of the gut microbiota, a crucial factor in intestinal health, offers potential for treating IBD. DP7, a novel antimicrobial peptide with potent antibacterial activity, was investigated for its anti-inflammatory effects in a dextran sulfate sodium (DSS)-induced UC mouse model. DP7 significantly ameliorated key disease parameters, including disease activity index, weight loss, and shortened colon length, while preserving colonic epithelial integrity and reducing inflammatory infiltration. Further analysis revealed potential targets of DP7, highlighting the significant role of Muribaculaceae bacteria during inflammatory states. To further explore the role of the gut microbiota in DP7's efficacy, fecal microbiota transplantation (FMT) was performed using feces from DP7-treated mice. FMT successfully ameliorated colitis in recipient mice, providing further evidence for the crucial role of the gut microbiome in IBD treatment and DP7's ability to modulate the gut microbiota for therapeutic benefit. Moreover, our findings suggest that DP7's modulation of the immune system is intricately linked to the complex microbial environment. Our findings demonstrate that DP7 effectively mitigates inflammation, attenuates barrier dysfunction, and shapes the gut microbiota, suggesting its potential as a therapeutic agent for UC.}, } @article {pmid39896483, year = {2025}, author = {Gray, SM and Wood, MC and Mulkeen, SC and Ahmed, S and Thaker, SD and Chen, B and Sander, WR and Bibeva, V and Zhang, X and Yang, J and Herzog, JW and Zhang, S and Dogan, B and Simpson, KW and Sartor, RB and Montrose, DC}, title = {Dietary protein source mediates colitis pathogenesis through bacterial modulation of bile acids.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.24.634824}, pmid = {39896483}, issn = {2692-8205}, abstract = {Evidence-based dietary recommendations for individuals with inflammatory bowel diseases (IBD) are limited. Red meat consumption is associated with increased IBD incidence and relapse in patients, suggesting that switching to a plant-based diet may limit gut inflammation. However, the mechanisms underlying the differential effects of these diets remain poorly understood. Feeding diets containing plant- or animal-derived proteins to murine colitis models revealed that mice given a beef protein (BP) diet exhibited the most severe colitis, while mice fed pea protein (PP) developed mild inflammation. The colitis-promoting effects of BP were microbially-mediated as determined by bacterial elimination or depletion and microbiota transplant studies. In the absence of colitis, BP-feeding reduced abundance of Lactobacillus johnsonii and Turicibacter sanguinis and expanded Akkermansia muciniphila , which localized to the mucus in association with decreased mucus thickness and quality. BP-fed mice had elevated primary and conjugated fecal bile acids (BAs), and taurocholic acid administration to PP-fed mice worsened colitis. Dietary psyllium protected against BP-mediated inflammation, restored BA-modulating commensals and normalized BA ratios. Collectively, these data suggest that the protein component of red meat may be responsible, in part, for the colitis-promoting effects of this food source and provide insight into dietary factors that may influence IBD severity.}, } @article {pmid39895632, year = {2025}, author = {Gazzaniga, FS and Kasper, DL}, title = {The gut microbiome and cancer response to immune checkpoint inhibitors.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {3}, pages = {}, pmid = {39895632}, issn = {1558-8238}, mesh = {*Gastrointestinal Microbiome/drug effects/immunology ; Humans ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Animals ; *Neoplasms/immunology/drug therapy/microbiology/therapy ; Mice ; *Fecal Microbiota Transplantation ; Immunotherapy ; }, abstract = {Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy, yet only a fraction of patients respond. Remarkably, gut bacteria impact the efficacy of ICIs in fighting tumors outside of the gut. Certain strains of commensal gut bacteria promote antitumor responses to ICIs in a variety of preclinical mouse tumor models. Patients with cancer who respond to ICIs have a different microbiome compared with that of patients who don't respond. Fecal microbiota transplants (FMTs) from patients into mice phenocopy the patient tumor responses: FMTs from responders promote response to ICIs, whereas FMTs from nonresponders do not promote a response. In patients, FMTs from patients who have had a complete response to ICIs can overcome resistance in patients who progress on treatment. However, the responses to FMTs are variable. Though emerging studies indicate that gut bacteria can promote antitumor immunity in the absence of ICIs, this Review will focus on studies that demonstrate relationships between the gut microbiome and response to ICIs. We will explore studies investigating which bacteria promote response to ICIs in preclinical models, which bacteria are associated with response in patients with cancer receiving ICIs, the mechanisms by which gut bacteria promote antitumor immunity, and how microbiome-based therapies can be translated to the clinic.}, } @article {pmid39895628, year = {2025}, author = {Si, W and Zhao, X and Li, R and Li, Y and Ma, C and Zhao, X and Bugno, J and Qin, Y and Zhang, J and Liu, H and Wang, L}, title = {Lactobacillus rhamnosus GG induces STING-dependent IL-10 in intestinal monocytes and alleviates inflammatory colitis in mice.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {3}, pages = {}, pmid = {39895628}, issn = {1558-8238}, mesh = {Animals ; *Interleukin-10/immunology/genetics/metabolism ; *Lacticaseibacillus rhamnosus/immunology ; Mice ; *Colitis/immunology/therapy/pathology/microbiology ; *Membrane Proteins/genetics/immunology/metabolism ; *Monocytes/immunology/metabolism ; Signal Transduction/immunology ; Probiotics/administration & dosage/pharmacology ; Protein Serine-Threonine Kinases/metabolism/genetics/immunology ; Gastrointestinal Microbiome/immunology ; Transcription Factor RelA/metabolism/genetics/immunology ; Mice, Knockout ; Fecal Microbiota Transplantation ; }, abstract = {Preclinical and clinical observations indicate that the probiotic Lactobacillus rhamnosus GG (LGG) can modulate colonic inflammation. However, the underlying mechanisms have not been explored in depth. Here, we demonstrate that oral administration of live LGG alleviated inflammatory colitis by increasing IL-10 expression in intestinal Ly6C+ monocytes. Mechanistically, LGG induced IL-10 production via the stimulator of IFN genes (STING)/TBK1/NF-κB (RELA) signaling pathway in intestinal Ly6C+ monocytes, enhancing their immune-suppressive function. Elevated IL-10 subsequently activated IL-10 signaling in Ly6C+ monocytes, resulting in an IL-10-based autocrine regulatory loop and inhibition of proinflammatory cytokine production. Furthermore, LGG shifted the gut microbial community and its metabolic functions, leading to intestinal immune responses against colitis. Fecal microbiota transplantation from LGG-colonized mice alleviated immune checkpoint blockade-associated colitis. Our findings highlight the importance of STING signaling in IL-10-dependent antiinflammatory immunity and establish an empirical basis for developing oral administration of live LGG as an efficient and safe therapeutic strategy against inflammatory colitis.}, } @article {pmid39180326, year = {2025}, author = {Feuerstadt, P and Chopra, T and Knapple, W and Van Hise, NW and Dubberke, ER and Baggott, B and Guthmueller, B and Bancke, L and Gamborg, M and Steiner, TS and Van Handel, D and Khanna, S}, title = {PUNCH CD3-OLS: A Phase 3 Prospective Observational Cohort Study to Evaluate the Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA) in Adults With Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {80}, number = {1}, pages = {43-51}, pmid = {39180326}, issn = {1537-6591}, support = {//Ferring Pharmaceuticals/ ; }, mesh = {Humans ; *Clostridium Infections/drug therapy ; Male ; Female ; Middle Aged ; Prospective Studies ; *Fecal Microbiota Transplantation ; Adult ; Aged ; *Clostridioides difficile ; *Anti-Bacterial Agents/therapeutic use/administration & dosage ; Feces/microbiology ; Canada ; Recurrence ; Treatment Outcome ; Gastrointestinal Microbiome ; United States ; Young Adult ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA)-the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the US Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment.

METHODS: PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24-72 hours of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively.

RESULTS: Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups.

CONCLUSIONS: RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date, and findings support use of RBL to prevent rCDI in a broad patient population.

CLINICAL TRIALS REGISTRATION: NCT03931941.}, } @article {pmid39892949, year = {2025}, author = {McGann, C and Phyu, R and Bittinger, K and Mukhopadhyay, S}, title = {Role of the Microbiome in Neonatal Infection: Pathogenesis and Implications for Management.}, journal = {Clinics in perinatology}, volume = {52}, number = {1}, pages = {147-166}, doi = {10.1016/j.clp.2024.10.010}, pmid = {39892949}, issn = {1557-9840}, mesh = {Humans ; Infant, Newborn ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; *Anti-Bacterial Agents/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Neonatal Sepsis/microbiology/therapy ; Microbiota ; }, abstract = {The human microbiome refers to the collective genome of microorganisms, including bacteria, fungi, and viruses residing on human body surfaces that are in contact with the environment. Together these communities protect against invasive infections. Conversely, when disrupted, the microbiome can be the source of pathogens causing invasive infection. Interventions to manipulate it via probiotics, antibiotics, and fecal transplantation are available. The risk benefit of these interventions remains unclear. In this review, the authors discuss evidence linking the gut microbiome to neonatal sepsis and also discuss the challenges for translating this knowledge into better clinical care.}, } @article {pmid39890521, year = {2025}, author = {Rafie, E and Zugman, M and Pal, SK and Routy, B and Elkrief, A}, title = {What Is the Role of Fecal Microbiota Transplantation in Immunotherapy Trials? Current Perspectives and Future Directions.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2024.12.009}, pmid = {39890521}, issn = {2405-4569}, abstract = {Immune checkpoint inhibitors (ICIs) are rapidly transforming the treatment landscape of genitourinary and other immunogenic malignancies. Despite these advances, biomarkers for the prediction of ICI response remain to be established. The gut microbiome has been identified as a modulator of immune regulation and a potential regulator of response to ICIs. Fecal microbiota transplantation (FMT) has emerged as a potential novel therapeutic tool to enhance ICI response, as demonstrated in several trials, spanning across genitourinary malignancies as well as others. While safety and clinical potential of FMT have been demonstrated, FMT parameters including optimal treatment regimens, bowel preparation protocols, patient selection, and donor-host compatibility need to be defined. Furthermore, targeted interventions including probiotic supplementation represent promising therapeutic avenues meriting further study.}, } @article {pmid39889629, year = {2025}, author = {Zhu, W and Hu, Y and Shi, Y and Bao, H and Cheng, X and Jiang, M and Peng, Z and Song, J and Fang, F and Jian, C and Yuan, W and Chen, J and Shu, X}, title = {Sleep deprivation accelerates Parkinson's disease via modulating gut microbiota associated microglial activation and oxidative stress.}, journal = {Microbiological research}, volume = {293}, number = {}, pages = {128077}, doi = {10.1016/j.micres.2025.128077}, pmid = {39889629}, issn = {1618-0623}, abstract = {The interplay between Parkinson's disease (PD) and sleep disturbances suggests that sleep problems constitute a risk factor for PD progression, but the underlying mechanisms remain unclear. Microglial activation and oxidative stress are considered to play an important role in the pathogenesis of aging and neurodegenerative diseases. We hypothesized that sleep deprivation (SD) could exacerbate PD progression via modulating microglial activation and oxidative stress. To test this hypothesis, we established a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), then subjected the mice to SD. A battery of behavioral tests, including rotarod, pole, adhesive removal, and open field tests, were used to assess motor function. Our study showed that SD exacerbated motor deficits, loss of tyrosine hydroxylase (TH), microglial activation and oxidative stress damage in PD model mice. Fecal microbiota transplantation experiments revealed that SD mediated PD progression, microglial activation and oxidative stress via the gut microbiota. 16S rRNA sequencing analysis indicated that SD increased the abundances of bacteria such as Bacteroidaceae, while decreasing the abundances of bacteria including Lactobacillus. Non-targeted metabolomic analysis of gut microbiota-derived metabolites revealed that SD significantly increased the production of adenosine (ADO), a purine metabolite. Probiotic supplementation reversed the effects of SD on motor deficits, dopaminergic neuron loss, microglial activation and oxidative stress damage in PD mice; it also decreased SD-induced ADO production. Administration of Adenosine A2A receptor (A2AR) inhibitors, Istradefylline (Ist), attenuated the roles of SD and ADO in promoting microglial activation, oxidative stress and PD progression. Taken together, our findings indicate that SD accelerates PD progression via regulating microbiota associated microglial activation and oxidative stress, suggesting that efforts to improve sleep quality can be used to prevent and treat PD.}, } @article {pmid39887665, year = {2025}, author = {Zeng, X and Sun, L and Xie, H and Gong, S and Lu, C and Xu, Z and Guan, H and Han, B and Wang, W and Zhang, Z and Zhou, J and Wang, S and Chen, Y and Xiao, W}, title = {Lactobacillus johnsonii Generates Cyclo(pro-trp) and Promotes Intestinal Ca[2+] Absorption to Alleviate CKD-SHPT.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2414678}, doi = {10.1002/advs.202414678}, pmid = {39887665}, issn = {2198-3844}, support = {82270585//National Natural Science Foundation of China/ ; }, abstract = {Patients with chronic kidney disease (CKD) are at a high risk of developing secondary hyperparathyroidism (SHPT), which may cause organ dysfunction and increase patient mortality. The main clinical interventions for CKD-SHPT involve calcium supplements to boost absorption, but ineffective for some patients, and the reasons remain unclear. Here, CKD mice are divided into high and low groups based on intact parathyroid hormone (iPTH) levels. The high group exhibits significant changes in gut microbes, including a decrease in Lactobacillus, an increase in parathyroid hyperplasia, and a decrease in intestinal calcium. Fecal microbiota transplantation and L. johnsonii colonization indicate a link between gut microbes and CKD-SHPT. Clinically, higher L. johnsonii levels are correlated with milder hyperparathyroidism CKD-SHPT. The receiver operating characteristic (ROC) curve for L. johnsonii abundance and surgical risk is 0.81, with the calibration curve confirming predictive accuracy, and decision curve analysis revealing good clinical applicability. In vivo and in vitro experiments show that cyclo(pro-trp) enhance calcium inflow and lower iPTH levels in intestinal epithelial cells via a calcium-sensing receptor and transient receptor potential vanilloid 4 pathways. This study identified the crucial role of L. johnsonii in CKD-SHPT, unveiling a new mechanism for calcium imbalance and offering novel strategies for SHPT treatment and drug development.}, } @article {pmid39887373, year = {2025}, author = {Byrd, DA and Damerell, V and Gomez Morales, MF and Hogue, SR and Lin, T and Ose, J and Himbert, C and Ilozumba, MN and Kahlert, C and Shibata, D and Toriola, AT and Li, CI and Figueiredo, J and Stephens, WZ and Warby, CA and Hardikar, S and Siegel, EM and Round, J and Ulrich, CM and Gigic, B}, title = {The gut microbiome is associated with disease-free survival in stage I-III colorectal cancer patients.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.35342}, pmid = {39887373}, issn = {1097-0215}, support = {//ERA-NET on Translational Cancer Research (TRANSCAN)/ ; //Heidelberger Stiftung Chirurgie, Heidelberg University Hospital/ ; //Medizinische Fakultät Heidelberg, Universität Heidelberg/ ; //Matthias-Lackas Foundations/ ; //Stiftung LebensBlicke/ ; R01 CA189184/NH/NIH HHS/United States ; U01 CA206110/NH/NIH HHS/United States ; //Rahel Goitein-Straus-Program/ ; 01KD2101D//German Federal Ministry of Education and Research/ ; 01KT1503//German Federal Ministry of Education and Research/ ; }, abstract = {Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States, with recurrence being a frequent cause of mortality. Approaches to improve disease-free survival (DFS) are urgently needed. The gut microbiome, reflected in fecal samples, is likely mechanistically linked to CRC progression and may serve as a non-invasive biomarker. Accordingly, we leveraged baseline fecal samples from N = 166 stage I-III CRC patients in the ColoCare Study, a prospective cohort of newly diagnosed CRC patients. We sequenced the V3 and V4 regions of the 16S rRNA gene to characterize fecal bacteria. We calculated estimates of alpha diversity, beta diversity, and a priori- and exploratory-selected bacterial presence/absence and relative abundance. Associations of microbial metrics with DFS were estimated using multivariable Cox proportional hazards models. We found that alpha diversity was strongly associated with improved DFS, most strongly among rectal cancer patients (Shannon HRrectum = 0.40 95% CI = 0.19, 0.87; p = .02). Overall microbiome composition differences (beta diversity), as characterized by principal coordinate axes, were statistically significantly associated with DFS. Peptostreptococcus was statistically significantly associated with worse DFS (HR = 1.62, 95% CI = 1.13, 2.31; p = .01 per 1-SD) and Order Clostridiales was associated with improved DFS (HR = 0.62, 95% CI = 0.43-0.88; p = .01 per 1-SD). In exploratory analyses, Coprococcus and Roseburia were strongly associated with improved DFS. Overall, higher bacterial diversity and multiple bacteria were strongly associated with DFS. Metagenomic sequencing to elucidate species, gene, and functional level details among larger, diverse patient populations are critically needed to support the microbiome as a biomarker of CRC outcomes.}, } @article {pmid39887250, year = {2025}, author = {Tang, X and Zeng, T and Deng, W and Zhao, W and Liu, Y and Huang, Q and Deng, Y and Xie, W and Huang, W}, title = {Gut microbe-derived betulinic acid alleviates sepsis-induced acute liver injury by inhibiting macrophage NLRP3 inflammasome in mice.}, journal = {mBio}, volume = {}, number = {}, pages = {e0302024}, doi = {10.1128/mbio.03020-24}, pmid = {39887250}, issn = {2150-7511}, abstract = {UNLABELLED: Sepsis-induced acute liver injury (SALI) is a prevalent and life-threatening complication associated with sepsis. The gut microbiota plays a crucial role in the maintenance of health and the development of diseases. The impact of physical exercise on gut microbiota modulation has been well-documented. However, the potential impact of gut microbiome on exercise training-induced protection against SALI remains uncertain. Here, we discovered exercise training ameliorated SALI and systemic inflammation in septic mice. Notably, gut microbiota pre-depletion abolished the protective effects of exercise training in SALI mice. Fecal microbiota transplantation treatment revealed that exercise training-associated gut microbiota contributed to the beneficial effect of exercise training on SALI. Exercise training modulated the metabolism of Ligilactobacillus and enriched betulinic acid (BA) levels in mice. Functionally, BA treatment conferred protection against SALI by inhibiting the hepatic inflammatory response in mice. BA bound and inactivated hnRNPA2B1, thus suppressing NLRP3 inflammasome activation in macrophages. Collectively, this study reveals gut microbiota is involved in the protective effects of exercise training against SALI, and gut microbiota-derived BA inhibits the hepatic inflammatory response via the hnRNPA2B1-NLRP3 axis, providing a potential therapeutic strategy for SALI.

IMPORTANCE: Sepsis is characterized by a dysregulated immune response to an infection that leads to multiple organ dysfunction. The occurrence of acute liver injury is frequently observed during the initial stage of sepsis and is directly linked to mortality in the intensive care unit. The preventive effect of physical exercise on SALI is well recognized, yet the underlying mechanism remains poorly elucidated. Exercise training alters the gut microbiome in mice, increasing the abundance of Ligilactobacillus and promoting the generation of BA. Additionally, BA supplementation can suppress the NLRP3 inflammasome activation in macrophages by directly binding to hnRNPA2B1, thereby mitigating SALI. These results highlight the beneficial role of gut microbiota-derived BA in inhibiting the hepatic inflammatory response, which represents a crucial stride toward implementing microbiome-based therapeutic strategies for the clinical management of sepsis.}, } @article {pmid39885417, year = {2025}, author = {Abdel-Raoof Fouda, M and Abdel-Wahhab, M and Abdelkader, AE and Ibrahim, ME and Elsheikh, TA and Aldeweik, HM and Elfeky, N}, title = {Effect of gut microbiota changes on cytokines IL-10 and IL-17 levels in liver transplantation patients.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {140}, pmid = {39885417}, issn = {1471-2334}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Liver Transplantation ; Male ; Female ; *Interleukin-17/blood ; *Interleukin-10/blood ; Middle Aged ; Adult ; Feces/microbiology ; Bacteria/classification/isolation & purification ; Dysbiosis/microbiology ; Aged ; }, abstract = {BACKGROUND: Liver transplantation (LT) is a critical intervention for individuals with end-stage liver disease; yet, post-transplant problems, especially infections, graft rejection, and chronic liver disease, are often linked to systemic inflammation. Cytokines, small signaling molecules, significantly influence immune responses during and post-liver transplantation. Nonetheless, the intricate relationships among cytokines, immune responses, and the gut microbiota, especially gut dysbiosis, are still inadequately comprehended. Thus, this study aims to identify the gut microbiota (GM) and determine their relationship to cytokines (IL-17 and IL-10) in LT patients, due to their importance in enhancing the recovery rate.

RESULT: The research included 31 liver transplant (LT) patients from the Gastroenterology Surgical Center at Mansoura University, resulting in the collection of 174 stool and blood samples from all participants. Fourteen bacterial species have been identified in samples collected at three intervals: one week before, one week post, and two weeks post LT. A change in gut microbiota composition was noted, characterized by a rise in potentially pathogenic bacteria such as Enterococci and Enterobacteriaceae (including Escherichia coli and Klebsiella) and a reduction in beneficial bacteria such as Bacteroidetes and Firmicutes. The examination of patient demographic and clinical data revealed no significant correlations between sex, age, or diagnostic categories and gut microbiota composition. The findings of the Multivariate Analysis of Variance (MANOVA) indicated a substantial effect of gut microbiota composition on cytokine levels (IL-10 and IL-17), with all tests producing p-values of 0.001. The assessment of cytokine levels indicated fluctuating variations at several time points following surgery. IL-10 levels in the GM groups exhibited a statistically significant elevation during the second week post-surgery (p = 0.036), suggesting a potential recovery-related anti-inflammatory response. In contrast, IL-17 levels rose in the NI group over time, indicating a transition to a pro-inflammatory condition.

CONCLUSION: This study emphasizes the pivotal role of the gut microbiota in regulating immune responses following transplantation.}, } @article {pmid39881980, year = {2024}, author = {Renk, H and Schoppmeier, U and Müller, J and Kuger, V and Neunhoeffer, F and Gille, C and Peter, S}, title = {Oxygenation and intestinal perfusion and its association with perturbations of the early life gut microbiota composition of children with congenital heart disease.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1468842}, pmid = {39881980}, issn = {1664-302X}, abstract = {BACKGROUND: Early life gut microbiota is known to shape the immune system and has a crucial role in immune homeostasis. Only little is known about composition and dynamics of the intestinal microbiota in infants with congenital heart disease (CHD) and potential influencing factors.

METHODS: We evaluated the intestinal microbial composition of neonates with CHD (n = 13) compared to healthy controls (HC, n = 30). Fecal samples were analyzed by shotgun metagenomics. Different approaches of statistical modeling were applied to assess the impact of influencing factors on variation in species composition. Unsupervised hierarchical clustering of the microbial composition of neonates with CHD was used to detect associations of distinct clusters with intestinal tissue oxygenation and perfusion parameters, obtained by the "oxygen to see" (O2C) method.

RESULTS: Overall, neonates with CHD showed an intestinal core microbiota dominated by the genera Enterococcus (27%) and Staphylococcus (20%). Furthermore, a lower abundance of the genera Bacteroides (8% vs. 14%), Parabacteroides (1% vs. 3%), Bifidobacterium (4% vs. 12%), and Escherichia (8% vs. 23%) was observed in CHD compared to HCs. CHD patients that were born by vaginal delivery showed a lower fraction of the genera Bacteroides (15% vs. 21%) and Bifidobacterium (7% vs. 22%) compared to HCs and in those born by cesarean section, these genera were not found at all. In infants with CHD, we found a significant impact of oxygen saturation (SpO2) on relative abundances of the intestinal core microbiota by multivariate analysis of variance (F[8,2] = 24.9, p = 0.04). Statistical modeling suggested a large proportional shift from a microbiota dominated by the genus Streptococcus (50%) in conditions with low SpO2 towards the genus Enterococcus (61%) in conditions with high SpO2. We identified three distinct compositional microbial clusters, corresponding neonates differed significantly in intestinal blood flow and global gut perfusion.

CONCLUSION: Early life differences in gut microbiota of CHD neonates versus HCs are possibly linked to oxygen levels. Delivery method may affect microbiota stability. However, further studies are needed to assess the effect of potential interventions including probiotics or fecal transplants on early life microbiota perturbations in neonates with CHD.}, } @article {pmid39880356, year = {2025}, author = {Wang, S and Yan, K and Dong, Y and Chen, Y and Song, J and Chen, Y and Liu, X and Qi, R and Zhou, X and Zhong, J and Li, J}, title = {The influence of microplastics on hypertension-associated cardiovascular injury via the modulation of gut microbiota.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {}, number = {}, pages = {125760}, doi = {10.1016/j.envpol.2025.125760}, pmid = {39880356}, issn = {1873-6424}, abstract = {Microplastics (MPs) have been found to interfere with the gut microbiota and compromise the integrity of the gut barrier. Excessive exposure to MPs markedly elevates the risk of cardiovascular disease, yet their influence on hypertension remains elusive, calling for investigation into their potential impacts on blood pressure (BP) regulation. In the present study, an increase in the concentration of MPs was observed in the fecal samples of individuals suffering from hypertension, as compared to the controls. Oral administration of MPs led to obvious increases in systolic, diastolic and mean BP levels in mice. MPs were associated with promoting myocardial hypertrophy, fibrosis, and cardiac remodeling through alterations in gut microbial composition, such as Prevotella and Coprobacillus, or fecal metabolites Betaine and Glycyrrhetinic acid. The hypertensive damage mediated by MPs was significantly mitigated by the high-fiber diet or antibiotics that targeted the gut microbiota. Notablely, fecal microbiota transplantation from mice treated with MPs led to an increase in systolic BP levels and the development of cardiac dysfunction. Our findings offer valuable insights into the complex interplay between MPs and the gut microbiome in the context of hypertension, and suggest potential strategies for reducing the vascular and cardiac injury caused by MPs.}, } @article {pmid39879970, year = {2025}, author = {Stallmach, A}, title = {[The gastrointestinal microbiome - vision and mission].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {150}, number = {4}, pages = {157-162}, doi = {10.1055/a-2303-3368}, pmid = {39879970}, issn = {1439-4413}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Germany ; Dysbiosis ; Clostridium Infections/therapy ; }, abstract = {The gastrointestinal microbiome influences physiological functions and is altered in a variety of diseases. The causality of "dysbiosis" in the pathogenesis is not always proven; association studies are often involved. Patients with IBD, bacteria, fungi, bacteriophages, and archaea show disease-typical patterns associated with metabolome disturbances. Fecal microbiome transfer (FMT) for treating various diseases is the subject of numerous clinical studies. Currently, recurrent Clostridioides difficile infection (rCDI) is the only confirmed indication recommended in medical guidelines. In Germany, the FMT is subject to the Medicines Act and may only be carried out as part of individual healing attempts or clinical studies. For patient safety, repeated donor screening, ideally with the construction of a chair bench, is necessary. This significantly limits the nationwide availability of the FMT in Germany. Microbiota-based therapeutics prepared from the stool of tested donors have recently been approved by the US Food and Drug Administration (FDA) for the prevention of rCDI. More microbiome-based medicines can be expected in the future.}, } @article {pmid39879969, year = {2025}, author = {Weirauch, T and Vehreschild, MJGT}, title = {[Nosocomial gastrointestinal infections and Clostridioides difficile].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {150}, number = {4}, pages = {149-156}, doi = {10.1055/a-2303-3321}, pmid = {39879969}, issn = {1439-4413}, mesh = {Humans ; *Cross Infection/epidemiology ; *Clostridium Infections/therapy/epidemiology ; *Anti-Bacterial Agents/therapeutic use ; *Fecal Microbiota Transplantation ; Clostridioides difficile ; Germany ; Diarrhea/microbiology ; Fidaxomicin/therapeutic use ; Vancomycin/therapeutic use ; }, abstract = {German surveillance data from 2022 reported a prevalence of nosocomial infections among hospitalized patients of 5,2%. Clostridioides-difficile-infections (CDI) are the most frequent cause of nosocomial diarrhea. They are usually caused by antibiotic exposure and the subsequent changes in the gut microbiota. Clinical manifestation ranges from asymptomatic colonization over moderate diarrhea to severe pseudomembranous colitis. According to the current German Gastrointestinal Infection Guidelines, fidaxomicin is the preferred treatment option for CDI, especially in patients at high risk of recurrence or those already suffering from recurrence. Vancomycin can also be used as an alternative for initial CDI treatment. Fecal microbiota transplantation is considered a treatment approach for patients with multiple recurrences.}, } @article {pmid39879083, year = {2025}, author = {Carroll, A and Bell, MJ and Bleach, ECL and Turner, D and Williams, LK}, title = {Impact of dairy calf management practices on the intestinal tract microbiome pre-weaning.}, journal = {Journal of medical microbiology}, volume = {74}, number = {1}, pages = {}, doi = {10.1099/jmm.0.001957}, pmid = {39879083}, issn = {1473-5644}, mesh = {Animals ; Cattle ; *Gastrointestinal Microbiome/physiology ; *Weaning ; *Animal Husbandry/methods ; Dairying ; }, abstract = {Introduction. Microbiota in the gastrointestinal tract (GIT) consisting of the rumen and hindgut (the small intestine, cecum and colon) in dairy calves play a vital role in their growth and development. This review discusses the development of dairy calf intestinal microbiomes with an emphasis on the impact that husbandry and rearing management have on microbiome development, health and growth of pre-weaned dairy calves.Discussion. The diversity and composition of the microbes that colonize the lower GIT (small and large intestine) can have a significant impact on the growth and development of the calf, through influence on nutrient metabolism, immune modulation, resistance or susceptibility to infection, production outputs and behaviour modification in adult life. The colonization of the calf intestinal microbiome dynamically changes from birth, increasing microbial richness and diversity until weaning, where further dynamic and drastic microbiome change occurs. In dairy calves, neonatal microbiome development prior to weaning is influenced by direct and indirect factors, some of which could be considered stressors, such as maternal interaction, environment, diet, husbandry and weaning practices. The specific impact of these can dictate intestinal microbial colonization, with potential lifelong consequences.Conclusion. Evidence suggests the potential detrimental effect that sudden changes and stress may have on calf health and growth due to management and husbandry practices, and the importance of establishing a stable yet diverse intestinal microbiome population at an early age is essential for calf success. The possibility of improving the health of calves through intestinal microbiome modulation and using alternative strategies including probiotic use, faecal microbiota transplantation and novel approaches of microbiome tracking should be considered to support animal health and sustainability of dairy production systems.}, } @article {pmid39878866, year = {2025}, author = {Zheng, Y and Yu, Y and Chen, M and Zhang, H and Wang, W and Fan, X and Sun, L and Tang, L and Ta, D}, title = {Abdominal LIPUS Stimulation Prevents Cognitive Decline in Hind Limb Unloaded Mice by Regulating Gut Microbiota.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39878866}, issn = {1559-1182}, abstract = {Weightlessness usually causes disruption of the gut microbiota and impairs cognitive function. There is a close connection between gut microbiota and neurological diseases. Low-intensity pulsed ultrasound (LIPUS) has a beneficial effect on reducing intestinal inflammation. So we wondered if abdominal LIPUS stimulation can have a positive impact on weightlessness induced cognitive decline by reducing intestinal dysfunction. The findings revealed that the hind limb unloaded mice exhibited evident disruption in intestinal structure and gut microbial homeostasis, along with impairment in their learning and memory capabilities. However, 4-week abdominal LIPUS treatment improved intestinal function in hind limb unloaded mice, characterized by upregulation of tight junction proteins ZO-1 and Occludin expression in the colon, increased diversity and abundance of intestinal microbiota, decreased serum lipopolysaccharide (LPS), and increased short chain fatty acids in colon contents. The hind limb unloaded mice treated with LIPUS exhibited heightened activity levels, improved exploratory tendencies, and significantly enhanced learning and memory faculties, and elevated expression of neuroadaptation-related proteins such as PSD95, GAP43, P-CREB, BDNF, and its receptor TRKB in the hippocampus. Furthermore, the hind limb unloaded mice receiving fecal transplants from the mice whose abdomens were irradiated with LIPUS displayed enhanced cognitive abilities and improved intestinal structure, akin to the outcomes observed in hind limb unloaded mice who received LIPUS abdominal treatment directly. The above results indicate that LIPUS enhances intestinal structure and microbiota, which helps alleviate cognitive impairment caused by weightlessness. LIPUS could be a potential strategy to simultaneously improve gut dysfunction and cognitive decline in astronauts or bedridden patients.}, } @article {pmid39779879, year = {2025}, author = {Pribyl, AL and Hugenholtz, P and Cooper, MA}, title = {A decade of advances in human gut microbiome-derived biotherapeutics.}, journal = {Nature microbiology}, volume = {10}, number = {2}, pages = {301-312}, pmid = {39779879}, issn = {2058-5276}, mesh = {Humans ; *Gastrointestinal Microbiome ; Biological Therapy/methods ; Bacteria/genetics/classification ; Fecal Microbiota Transplantation ; Feces/microbiology ; Probiotics/therapeutic use ; }, abstract = {Microbiome science has evolved rapidly in the past decade, with high-profile publications suggesting that the gut microbiome is a causal determinant of human health. This has led to the emergence of microbiome-focused biotechnology companies and pharmaceutical company investment in the research and development of gut-derived therapeutics. Despite the early promise of this field, the first generation of microbiome-derived therapeutics (faecal microbiota products) have only recently been approved for clinical use. Next-generation therapies based on readily culturable and as-yet-unculturable colonic bacterial species (with the latter estimated to comprise 63% of all detected species) have not yet progressed to pivotal phase 3 trials. This reflects the many challenges involved in developing a new class of drugs in an evolving field. Here we discuss the evolution of the live biotherapeutics field over the past decade, from the development of first-generation products to the emergence of rationally designed second- and third-generation live biotherapeutics. Finally, we present our outlook for the future of this field.}, } @article {pmid39877812, year = {2021}, author = {Zhu, W and Dykstra, K and Zhang, L and Xia, Z}, title = {Gut Microbiome as Potential Therapeutics in Multiple Sclerosis.}, journal = {Current treatment options in neurology}, volume = {23}, number = {11}, pages = {}, pmid = {39877812}, issn = {1092-8480}, support = {R01 NS098023/NS/NINDS NIH HHS/United States ; R01 NS124882/NS/NINDS NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: The gut microbiome is an emerging arena to investigate multiple sclerosis (MS) pathogenesis and potential therapeutics. In this review, we summarize the available data and postulate the feasibilities of potential MS therapeutic approaches that modulate the gut microbiome.

RECENT FINDINGS: Growing evidence indicates dysbiosis in the gut bacterial ecosystem in MS. Diet and other interventions produce biologically significant changes in the gut bacterial communities and functions, can potentially regulate the immune system, and benefit people with MS. While well-conducted investigations of the therapeutic mechanisms for targeting gut microbiome in animal models and humans remain limited, promising connections between various mechanisms of gut microbiome regulation and beneficial effects on MS outcomes are emerging.

SUMMARY: To date, studies examining the microbiome-based therapies in MS remain limited in number and follow-up duration. There is a clear need to determine the long-term efficacy and safety of these approaches, and to identify their underlying mechanisms of actions.}, } @article {pmid39875017, year = {2025}, author = {Qin, L and Fan, B and Zhou, Y and Zheng, J and Diao, R and Wang, F and Liu, J}, title = {Targeted Gut Microbiome Therapy: Applications and Prospects of Probiotics, Fecal Microbiota Transplantation and Natural Products in the Management of Type 2 Diabetes.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107625}, doi = {10.1016/j.phrs.2025.107625}, pmid = {39875017}, issn = {1096-1186}, abstract = {Type 2 diabetes mellitus (T2DM) is considered as one of the most pressing public health challenges worldwide. Studies have shown significant differences in the gut microbiota between healthy individuals and T2DM patients, suggesting that gut microorganisms may play a key role in the onset and progression of T2DM. This review systematically summarizes the relationship between gut microbiota and T2DM, and explores the mechanisms through which gut microorganisms may alleviate T2DM. Additionally, it evaluates the potential of probiotics, fecal microbiota transplantation (FMT)/virome transplantation (FVT), and natural products in modulating gut microbiota to treat T2DM. Although existing studies have suggested that these interventions may delay or even halt the progression of T2DM, most research remained limited to animal models and observational clinical studies, with a lack of high-quality clinical data. This has led to an imbalance between theoretical research and clinical application. Although some studies have explored the regulatory role of the gut virome on the gut microbiota, research in this area remains in its early stages. Based on these current studies, future research should be focused on large-scale, long-term clinical studies and further investigation on the potential role of the gut virome in T2DM. In conclusion, this review aims to summarize the current evidence and explore the applications of gut microbiota in T2DM treatment, as well as providing recommendations for further investigation in this field.}, } @article {pmid39874238, year = {2025}, author = {Scher, JU and Nayak, R and Clemente, JC}, title = {Microbiome research in autoimmune and immune-mediated inflammatory diseases: lessons, advances and unmet needs.}, journal = {Annals of the rheumatic diseases}, volume = {84}, number = {1}, pages = {9-13}, doi = {10.1136/ard-2024-225735}, pmid = {39874238}, issn = {1468-2060}, mesh = {Humans ; *Autoimmune Diseases/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology/physiology ; *Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Microbiota/immunology ; Arthritis, Rheumatoid/immunology/microbiology ; Lupus Erythematosus, Systemic/immunology/microbiology ; Immune System Diseases/immunology/microbiology ; }, abstract = {The increasing prevalence of autoimmune and immune-mediated diseases (AIMDs) underscores the need to understand environmental factors that contribute to their pathogenesis, with the microbiome emerging as a key player. Despite significant advancements in understanding how the microbiome influences physiological and inflammatory responses, translating these findings into clinical practice remains challenging. This viewpoint reviews the progress and obstacles in microbiome research related to AIMDs, examining molecular techniques that enhance our understanding of microbial contributions to disease. We discuss significant discoveries linking specific taxa and metabolites to diseases such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis, highlighting the role of gut dysbiosis and host-microbiome interactions. Furthermore, we explore the potential of microbiome-based therapeutics, including faecal microbiota transplantation and pharmacomicrobiomics, while addressing the challenges of identifying robust microbial targets. We advocate for integrative, transdisease studies and emphasise the need for diverse cohort research to generalise findings across populations. Understanding the microbiome's role in AIMDs will pave the way for personalised medicine and innovative therapeutic strategies.}, } @article {pmid39873952, year = {2025}, author = {Pezeshki, B and Abdulabbas, HT and Alturki, AD and Mansouri, P and Zarenezhad, E and Nasiri-Ghiri, M and Ghasemian, A}, title = {Synergistic Interactions Between Probiotics and Anticancer Drugs: Mechanisms, Benefits, and Challenges.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39873952}, issn = {1867-1314}, abstract = {Research into the role of probiotics-often referred to as "living supplements"-in cancer therapy is still in its early stages, and uncertainties regarding their effectiveness remain. Relevantly, chemopreventive and therapeutic effects of probiotics have been determined. There is also substantial evidence supporting their potential in cancer treatment such as immunotherapy. Probiotics employ various mechanisms to inhibit cancer initiation and progression. These include colonizing and protecting the gastrointestinal tract (GIT), producing metabolites, inducing apoptosis and autophagy, exerting anti-inflammatory properties, preventing metastasis, enhancing the effectiveness of immune checkpoint inhibitors (ICIs), promoting cancer-specific T cell infiltration, arresting the cell cycle, and exhibiting direct or indirect synergistic effects with anticancer drugs. Additionally, probiotics have been shown to activate tumor suppressor genes and inhibit pro-inflammatory transcription factors. They also increase reactive oxygen species production within cancer cells. Synergistic interactions between probiotics and various anticancer drugs, such as cisplatin, cyclophosphamide, 5-fluorouracil, trastuzumab, nivolumab, ipilimumab, apatinib, gemcitabine, tamoxifen, sorafenib, celecoxib and irinotecan have been observed. The combination of probiotics with anticancer drugs holds promise in overcoming drug resistance, reducing recurrence, minimizing side effects, and lowering treatment costs. In addition, fecal microbiota transplantation (FMT) and prebiotics supplementation has increased cytotoxic T cells within tumors. However, probiotics may leave some adverse effects such as risk of infection and gastrointestinal effects, antagonistic effects with drugs, and different responses among patients. These findings highlight insights for considering specific strains and engineered probiotic applications, preferred doses and timing of treatment, and personalized therapies to enhance the efficacy of cancer therapy. Accordingly, targeted interventions and guidelines establishment needs extensive randomized controlled trials as probiotic-based cancer therapy has not been approved by Food and Drug Administration (FDA).}, } @article {pmid39873191, year = {2025}, author = {An, L and Li, S and Chang, Z and Lei, M and He, Z and Xu, P and Zhang, S and Jiang, Z and Iqbal, MS and Sun, X and Liu, H and Duan, X and Wu, W}, title = {Gut microbiota modulation via fecal microbiota transplantation mitigates hyperoxaluria and calcium oxalate crystal depositions induced by high oxalate diet.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2457490}, pmid = {39873191}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Hyperoxaluria/therapy/metabolism ; *Fecal Microbiota Transplantation ; *Calcium Oxalate/metabolism/chemistry ; Rats ; Male ; *Oxalates/metabolism/urine ; Diet ; Rats, Sprague-Dawley ; Kidney/metabolism/microbiology/pathology ; Bacteria/classification/metabolism/genetics/isolation & purification ; Disease Models, Animal ; Kidney Calculi/therapy/prevention & control/microbiology/metabolism/diet therapy ; Feces/microbiology/chemistry ; }, abstract = {Hyperoxaluria, including primary and secondary hyperoxaluria, is a disorder characterized by increased urinary oxalate excretion and could lead to recurrent calcium oxalate kidney stones, nephrocalcinosis and eventually end stage renal disease. For secondary hyperoxaluria, high dietary oxalate (HDOx) or its precursors intake is a key reason. Recently, accumulated studies highlight the important role of gut microbiota in the regulation of oxalate homeostasis. However, the underlying mechanisms involving gut microbiota and metabolite disruptions in secondary hyperoxaluria remain poorly understood. Here, we investigated the therapeutic efficacy of fecal microbiota transplantation (FMT) sourced from healthy rats fed with standard pellet diet against urinary oxalate excretion, renal damage and calcium oxalate (CaOx) crystal depositions via using hyperoxaluria rat models. We observed dose-dependent increases in urinary oxalate excretion and CaOx crystal depositions due to hyperoxaluria, accompanied by significant reductions in gut microbiota diversity characterized by shifts in Ruminococcaceae_UCG-014 and Parasutterella composition. Metabolomic analysis validated these findings, revealing substantial decreases in key metabolites associated with these microbial groups. Transplanting microbes from healthy rats effectively reduced HDOx-induced urinary oxalate excretion and CaOx crystal depositions meanwhile restoring Ruminococcaceae_UCG-014 and Parasutterella populations and their associated metabolites. Furthermore, FMT treatment could significantly decrease the urinary oxalate excretion and CaOx crystal depositions in rat kidneys via, at least in part, upregulating the expressions of intestinal barrier proteins and oxalate transporters in the intestine. In conclusion, our study emphasizes the effectiveness of FMT in countering HDOx-induced hyperoxaluria by restoring gut microbiota and related metabolites. These findings provide insights on the complex connection between secondary hyperoxaluria caused by high dietary oxalate and disruptions in gut microbiota, offering promising avenues for targeted therapeutic strategies.}, } @article {pmid39870907, year = {2025}, author = {Misselwitz, B and Haller, D}, title = {[The intestinal microbiota in inflammatory bowel diseases].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {}, number = {}, pages = {}, pmid = {39870907}, issn = {2731-7099}, abstract = {BACKGROUND: The intestinal microbiota comprises all living microorganisms in the gastrointestinal tract and is crucial for its function. Clinical observations and laboratory findings confirm a central role of the microbiota in chronic inflammatory bowel diseases (IBD). However, many mechanistic details remain unclear.

OBJECTIVES: Changes in the microbiota and the causal relationship with the pathogenesis of IBD are described and current and future diagnostic and therapeutic options are discussed.

MATERIALS AND METHODS: Narrative review.

RESULTS: The intestinal microbiota is altered in composition, diversity, and function in IBD patients, but specific (universal) IBD-defining bacteria have not been identified. The healthy microbiota has numerous anti-inflammatory functions such as the production of short-chain fatty acids or competition with pathogens. In contrast, the IBD microbiota promotes inflammation through the destruction of the intestinal barrier and direct interaction with the immune system. The balance between pro- and anti-inflammatory effects of the microbiota appears to be crucial for the development of intestinal inflammation. Microbiota-based IBD diagnostics show promise but are not yet ready for clinical use. Probiotics and fecal microbiota transplantation have clinical effects, especially in ulcerative colitis, but the potential of microbiota-based therapies is far from being fully realized.

CONCLUSION: IBD dysbiosis remains undefined so far. It is unclear how the many parallel pro- and anti-inflammatory mechanisms contribute to IBD pathogenesis. An inadequate mechanistic understanding hinders the development of microbiota-based diagnostics and therapies.}, } @article {pmid39870349, year = {2025}, author = {Vázquez-Cuesta, S and Olmedo, M and Kestler, M and Álvarez-Uría, A and De la Villa, S and Alcalá, L and Marín, M and Rodríguez-Fernández, S and Sánchez-Martínez, C and Muñoz, P and Bouza, E and Reigadas, E}, title = {Prospective analysis of biomarkers associated with successful faecal microbiota transplantation in recurrent Clostridioides difficile Infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2025.01.026}, pmid = {39870349}, issn = {1469-0691}, abstract = {OBJECTIVES: Faecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection (R-CDI). This study aimed to identify calprotectin and microbiome characteristics as potential biomarkers of FMT success.

METHODS: We conducted a prospective study of patients who underwent oral FMT (single dose of 4-5 capsules) for R-CDI (January 2018 to December 2022). Samples were collected at three time points: at CDI diagnosis, within 24 hours prior to FMT administration, and 30 days post-FMT. Calprotectin levels were assessed and the V4 region of the 16S rRNA gene was sequenced to analyse the microbiota composition. Sequencing data analysis and statistical analysis were performed using MOTHUR and R.

RESULTS: Ninety-seven patients underwent FMT (totalling 105 procedures). A total of 221 samples were processed, including 21 donor samples, 24 capsule contents, and 176 patient faecal samples (39 at diagnosis, 63 pre-FMT, and 74 post-FMT). FMT achieved an overall success rate of 85.1% (86/101 cases). The abundance of Bacteroides, Ruminococcus, Megamonas, and certain Prevotella operational taxonomic units (OTUs) was significantly higher in capsules associated with 100% success compared to less effective capsules. FMT engraftment was observed in 95% of patients with favourable outcomes versus 62% of those with recurrences (p = 0.006). Additionally, a negative correlation was found between calprotectin levels and specific microbial genera, suggesting an association with successful outcomes.

CONCLUSIONS: This study highlights differences in the evolution of faecal microbiota, bacterial engraftment, and inflammation markers (e.g., calprotectin) between patients with varying FMT outcomes. Potential biomarkers for successful FMT were identified, providing valuable insights for optimizing FMT strategies.}, } @article {pmid39870263, year = {2025}, author = {Ren, P and Liu, M and Wei, B and Tang, Q and Wang, Y and Xue, C}, title = {Fucoidan exerts antitumor effects by regulating gut microbiota and tryptophan metabolism.}, journal = {International journal of biological macromolecules}, volume = {300}, number = {}, pages = {140334}, doi = {10.1016/j.ijbiomac.2025.140334}, pmid = {39870263}, issn = {1879-0003}, abstract = {Fucoidan, a water-soluble polysaccharide derived from marine organisms, has garnered significant attention for its ability to regulate gut microbiota and its anti-tumor properties. However, the existence of a correlation between the anti-tumor effect of fucoidan and its regulation of the gut microbiota remains unknown. In pursuit of this objective, we culled the gut microbiota of mice with broad-spectrum antibiotics to generate pseudo-sterile tumor-bearing mice. Subsequently, fecal microbial transplants were introduced into the pseudo-sterile tumor-bearing mice. The antitumor effects of fucoidan were found to be dependent on the gut microbiota. Fucoidan promoted the proliferation of Akkermansia, Bifidobacterium and Lactobacillus, which have immunomodulatory effects. Furthermore, through regulation of gut microbiota, fucoidan influenced the metabolic process of tryptophan and facilitated its conversion to indole-3-acetic acid. In addition, fucoidan decreased the kynurenine/tryptophan ratio in serum, increased the proportion of CD8+ T cells, and suppressed the expression level of IDO1 in tumor tissues. Our results confirm that fucoidan enhances anti-tumor immune responses and subsequently exhibits anti-tumor effects by modulating the gut microbiota. Our research contributes to the comprehension of the mechanism of anti-tumor effects of fucoidan and facilitates the development of fucoidan as a dietary supplement for cancer patients.}, } @article {pmid39230037, year = {2025}, author = {Vaughn, BP and Khoruts, A and Fischer, M}, title = {Diagnosis and Management of Clostridioides difficile in Inflammatory Bowel Disease.}, journal = {The American journal of gastroenterology}, volume = {120}, number = {2}, pages = {313-319}, doi = {10.14309/ajg.0000000000003076}, pmid = {39230037}, issn = {1572-0241}, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy ; *Inflammatory Bowel Diseases/complications/diagnosis/microbiology/therapy ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Risk Factors ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Recurrence ; Broadly Neutralizing Antibodies ; Antibodies, Monoclonal ; }, abstract = {Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI), which can lead to worse IBD outcomes. The diagnosis of CDI in patients with IBD is complicated by higher C. difficile colonization rates and shared clinical symptoms of intestinal inflammation. Traditional risk factors for CDI, such as antibiotic exposure, may be lacking in patients with IBD because of underlying intestinal microbiota dysbiosis. Although CDI disproportionately affects people with IBD, patients with IBD are typically excluded from CDI clinical trials creating a knowledge gap in the diagnosis and management of these 2 diseases. This narrative review aims to provide a comprehensive overview of the diagnosis, treatment, and prevention of CDI in patients with IBD. Distinguishing CDI from C. difficile colonization in the setting of an IBD exacerbation is important to avoid treatment delays. When CDI is diagnosed, extended courses of anti- C. difficile antibiotics may lead to better CDI outcomes. Regardless of a diagnosis of CDI, the presence of C. difficile in a patient with IBD should prompt a disease assessment of the underlying IBD. Microbiota-based therapies and bezlotoxumab seem to be effective in preventing CDI recurrence in patients with IBD. Patients with IBD should be considered at high risk of CDI recurrence and evaluated for a preventative strategy when diagnosed with CDI. Ultimately, the comanagement of CDI in a patient with IBD requires a nuanced, patient-specific approach to distinguish CDI from C. difficile colonization, prevent CDI recurrence, and manage the underlying IBD.}, } @article {pmid39869428, year = {2025}, author = {Kayal, M and Boland, B}, title = {Approach to Therapy for Chronic Pouchitis.}, journal = {Annual review of medicine}, volume = {76}, number = {1}, pages = {167-173}, doi = {10.1146/annurev-med-032224-120544}, pmid = {39869428}, issn = {1545-326X}, mesh = {*Pouchitis/etiology/therapy ; Humans ; Chronic Disease ; *Proctocolectomy, Restorative/adverse effects/methods ; *Anti-Bacterial Agents/therapeutic use ; *Colitis, Ulcerative/surgery ; Colonic Pouches/adverse effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; }, abstract = {Chronic pouchitis (CP) occurs in approximately 20% of patients with ulcerative colitis after total proctocolectomy with ileal pouch anal anastomosis and is categorized as antibiotic dependent, antibiotic refractory, or Crohn's disease-like. The management of CP is challenging because of limited evidence and few randomized controlled trials. In this review, we discuss the medical management of CP and its supporting data delineated by type of therapy.}, } @article {pmid39869016, year = {2025}, author = {Martin Fuentes, A}, title = {The role of the microbiome in skin cancer development and treatment.}, journal = {Current opinion in oncology}, volume = {}, number = {}, pages = {}, doi = {10.1097/CCO.0000000000001120}, pmid = {39869016}, issn = {1531-703X}, abstract = {PURPOSE OF REVIEW: Recent research underscores the significant influence of the skin and gut microbiota on melanoma and nonmelanoma skin cancer (NMSC) development and treatment outcomes. This review aims to synthesize current findings on how microbiota modulates immune responses, particularly enhancing the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs).

RECENT FINDINGS: The microbiota's impact on skin cancer is multifaceted, involving immune modulation, inflammation, and metabolic interactions. Beneficial strains like Bifidobacterium and Lactobacillus have shown potential in supporting anti-PD-1 and anti-CTLA-4 therapies by promoting T-cell activation and immune surveillance. Evidence from preclinical and clinical studies, including fecal microbiota transplantation (FMT), highlights improved response rates in patients with microbiota-rich profiles. Notably, certain bacterial metabolites, such as inosine, contribute to enhanced antitumor activity by stimulating IFN-γ in CD8+ T cells.

SUMMARY: Understanding the interplay between microbiota and skin cancer treatment opens promising avenues for adjunctive therapies. Probiotic and prebiotic interventions, FMT, and microbiota modulation are emerging as complementary strategies to improve immunotherapy outcomes and address treatment resistance in melanoma and NMSC.}, } @article {pmid39868555, year = {2025}, author = {Chatterjee, J and Qi, X and Mu, R and Li, X and Eligator, T and Ouyang, M and Bozeman, SL and Rodgers, R and Aggarwal, S and Campbell, DE and Schriefer, LA and Baldridge, MT and Gutmann, DH}, title = {Intestinal Bacteroides drives glioma progression by regulating CD8+ T cell tumor infiltration.}, journal = {Neuro-oncology}, volume = {}, number = {}, pages = {}, doi = {10.1093/neuonc/noaf024}, pmid = {39868555}, issn = {1523-5866}, abstract = {BACKGROUND: The intestinal microbiota regulates normal brain physiology and the pathogenesis of several neurological disorders. While prior studies suggested that this regulation operates through immune cells, the underlying mechanisms remain unclear. Leveraging two well characterized murine models of low-grade glioma (LGG) occurring in the setting of the neurofibromatosis type 1 (NF1) cancer predisposition syndrome, we sought to determine the impact of the gut microbiome on optic glioma progression.

METHODS: Nf1-mutant mice genetically engineered to develop optic pathway gliomas (Nf1OPG mice) by 3 months of age were reared under germ-free (GF) conditions, treated with specific cocktails of antibiotics, or given fecal matter transplants (FMTs). Intestinal microbial species were identified by 16S genotyping. Neutralizing TGFβ antibodies were delivered systemically, while in vitro experiments used isolated murine microglia and T cells. Single cell RNA sequencing analysis was performed using established methods.

RESULTS: Nf1 OPG mice raised in a GF environment or postnatally treated with vancomycin did not harbor optic gliomas or exhibit OPG-induced retinal nerve fiber layer thinning, which was reversed following conventionally raised mouse FMT or colonization with Bacteroides species. Moreover, this intestinal microbiota-regulated gliomagenesis was mediated by circulating TGFβ, such that systemic TGFβ neutralization reduced Nf1-OPG growth. TGFβ was shown to act on tumor-associated monocytes to induce Ccl3 expression and recruit CD8+ T cells necessary for glioma growth.

CONCLUSIONS: Taken together, these findings establish, for the first time, a mechanistic relationship between Bacteroides in the intestinal microbiome and NF1-LGG pathobiology, suggesting both future predictive risk assessment strategies and therapeutic opportunities.}, } @article {pmid39868290, year = {2025}, author = {Weagley, J and Makimaa, H and Cárdenas, LAC and Romani, A and Sullender, M and Aggarwal, S and Hogarty, M and Rodgers, R and Kennedy, E and Foster, L and Schriefer, LA and Baldridge, MT}, title = {Dynamics of Bacterial and Viral Transmission in Experimental Microbiota Transplantation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.15.633206}, pmid = {39868290}, issn = {2692-8205}, abstract = {Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transplantation of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of fecal or cecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, fecal transplantation, and cecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored microbial populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transplanted control mice. While all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. This study provides valuable insights into microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transplantation in mouse models.}, } @article {pmid39864578, year = {2025}, author = {Attiq, A}, title = {Early-Life Antibiotic Exposures: Paving the Pathway for Dysbiosis-Induced Disorders.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {177298}, doi = {10.1016/j.ejphar.2025.177298}, pmid = {39864578}, issn = {1879-0712}, abstract = {Microbiota encompasses a diverse array of microorganisms inhabiting specific ecological niches. Gut microbiota significantly influences physiological processes, including gastrointestinal motor function, neuroendocrine signalling, and immune regulation. They play a crucial role in modulating the central nervous system and bolstering body defence mechanisms by influencing the proliferation and differentiation of innate and adaptive immune cells. Given the potential consequences of antibiotic therapy on gut microbiota equilibrium, there is a need for prudent antibiotic use to mitigate associated risks. Observational studies have linked increased antibiotic usage to various pathogenic conditions, including obesity, inflammatory bowel disease, anxiety-like effects, asthma, and pulmonary carcinogenesis. Addressing dysbiosis incidence requires proactive measures, including prophylactic use of β-lactamase drugs (SYN-004, SYN-006, and SYN-007), hydrolysing the β-lactam in the proximal GIT for maintaining intestinal flora homeostasis. Prebiotic and probiotic supplementations are crucial in restoring intestinal flora equilibrium by competing with pathogenic bacteria for nutritional resources and adhesion sites, reducing luminal pH, neutralising toxins, and producing antimicrobial agents. Faecal microbiota transplantation (FMT) shows promise in restoring gut microbiota composition. Rational antibiotic use is essential to preserve microflora and improve patient compliance with antibiotic regimens by mitigating associated side effects. Given the significant implications on gut microbiota composition, concerted intervention strategies must be pursued to rectify and reverse the occurrence of antibiotic-induced dysbiosis. Here, antibiotics-induced microbiota dysbiosis mechanisms and their systemic implications are reviewed. Moreover, proposed interventions to mitigate the impact on gut microflora are also discussed herein.}, } @article {pmid39863610, year = {2025}, author = {Reddi, S and Senyshyn, L and Ebadi, M and Podlesny, D and Minot, SS and Gooley, T and Kabage, AJ and Hill, GR and Lee, SJ and Khoruts, A and Rashidi, A}, title = {Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1034}, pmid = {39863610}, issn = {2041-1723}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; ACT9016-24//Leukemia and Lymphoma Society (Leukemia & Lymphoma Society)/ ; }, mesh = {Humans ; *Graft vs Host Disease/prevention & control/microbiology ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Middle Aged ; Adult ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Double-Blind Method ; *Tissue Donors ; *Transplantation, Homologous/adverse effects ; Feces/microbiology ; Acute Disease ; Aged ; Young Adult ; }, abstract = {Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase. The primary and key secondary endpoints were microbiota engraftment and severe aGVHD, respectively. Three cohorts of patients (20 total) received FMT, each from a different donor. FMT was safe and effective in restoring microbiota diversity and commensal species. Microbiota engraftment, determined from shotgun sequencing data, correlated with larger microbiota compositional shifts toward donor and better clinical outcomes. Donor 3 yielded a median engraftment rate of 66%, higher than donors 1 (P = 0.02) and 2 (P = 0.03) in multivariable analysis. Three patients developed severe aGVHD; all 3 had received FMT from donor 1. Donor 3 was selected as the sole donor for the randomized phase. Our findings suggest a clinically relevant donor effect and demonstrate feasibility of evidence-based donor selection. FMT is a holistic microbiota restoration approach that can be performed as a precision therapeutic. ClinicalTrials.gov identifier NCT06026371.}, } @article {pmid39863438, year = {2025}, author = {Jin, J and Cai, X and Rao, P and Xu, J and Li, J}, title = {Microbiota and immune dynamics in rheumatoid arthritis: Mechanisms and therapeutic potential.}, journal = {Best practice & research. Clinical rheumatology}, volume = {}, number = {}, pages = {102035}, doi = {10.1016/j.berh.2025.102035}, pmid = {39863438}, issn = {1532-1770}, abstract = {Rheumatoid arthritis (RA) is a complex autoimmune disease with growing evidence implicating the microbiota as a critical contributor to its pathogenesis. This review explores the multifaceted roles of microbial dysbiosis in RA, emphasizing its impact on immune cell modulation, autoantibody production, gut barrier integrity, and joint inflammation. Animal models reveal how genetic predisposition and environmental factors interact with specific microbial taxa to influence disease susceptibility. Dysbiosis-driven metabolic disruptions, including alterations in short-chain fatty acids and bile acids, further exacerbate immune dysregulation and systemic inflammation. Emerging therapeutic strategies-probiotics, microbial metabolites, fecal microbiota transplantation, and antibiotics-offer innovative avenues for restoring microbial balance and mitigating disease progression. By integrating microbiota-targeted approaches with existing treatments, this review highlights the potential to revolutionize RA management through precision medicine and underscores the need for further research to harness the microbiota's therapeutic potential.}, } @article {pmid39863236, year = {2025}, author = {Qin, N and Liu, H and Wang, X and Liu, Y and Chang, H and Xia, X}, title = {Sargassum fusiforme polysaccharides protect mice against Citrobacter rodentium infection via intestinal microbiota-driven microRNA-92a-3p-induced Muc2 production.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {140271}, doi = {10.1016/j.ijbiomac.2025.140271}, pmid = {39863236}, issn = {1879-0003}, abstract = {Sargassum fusiforme, widely consumed in Asian countries, has been proven to have various biological activities. However, the impacts and mechanisms of Sargassum fusiforme polysaccharides (SFPs) on intestinal bacterial infection are not yet fully understood. Our findings indicate that SFPs pretreatment ameliorates intestinal inflammation by reducing C. rodentium colonization, increasing colon length and levels of IL-10 and IL-22, decreasing IL-1β, IL-6, TNF-α, and IL-17 levels, inhibiting colonic crypt elongation and hyperplasia, and enhancing the intestinal mucosal barrier. The protective effects against intestinal bacterial infection are linked to enhanced clearance of C. rodentium and improvements in the intestinal mucosal barrier and C. rodentium-induced intestinal microbiota dysbiosis. Fecal microbiota transplantation experiments were conducted to evaluate the functional impact of microbiota induced by SFPs. The results suggest that intestinal microbiota modified by SFPs effectively countered C. rodentium infection. In addition, our study identified that miRNA-92a-3p is partially complementary to the 3'-UTR of the Notch1 gene, thereby repressing the Notch1-Hes1 signaling pathway and enhancing Muc2 secretion. Taken together, these findings reveal that SFPs protect mice from C. rodentium infection by activating the miR-92a-3p/Notch1-Hes1 regulatory axis driven by the intestinal microbiota, which stimulates Muc2 production to maintain intestinal barrier homeostasis.}, } @article {pmid39862968, year = {2025}, author = {Huang, P and Di, L and Cui, S and Wang, X and Cao, T and Jiang, S and Huang, L}, title = {Postoperative delirium after cardiac surgery associated with perioperative gut microbiota dysbiosis: Evidence from human and antibiotic-treated mouse model.}, journal = {Anaesthesia, critical care & pain medicine}, volume = {}, number = {}, pages = {101484}, doi = {10.1016/j.accpm.2025.101484}, pmid = {39862968}, issn = {2352-5568}, abstract = {BACKGROUND: Research links gut microbiota to postoperative delirium (POD) through the gut-brain axis. However, changes in gut microbiota and fecal short-chain fatty acids (SCFAs) in POD patients during the perioperative period and their association with POD are unclear.

METHODS: We conducted a nested case-control study among patients undergoing off-pump coronary artery bypass grafting, focusing on POD as the main outcome. POD patients were matched 1:1 with non-POD patients based on sociodemographic characteristics, health, and diet. Fecal samples were collected pre- and post-surgery to assess gut microbiota and SCFA changes. Postoperative fecal samples were transplanted into antibiotic-treated mice to evaluate delirium-like behavior and neuroinflammation.

RESULTS: Out of 120 patients, 60 were matched. Before surgery, gut microbiota in both groups was similar. After surgery, POD patients had lower alpha diversity and distinct microbiota compared to non-POD patients. LEfSe analysis showed POD was linked to increased opportunistic pathogens (Enterococcus) and decreased SCFA producers (Bacteroides, Ruminococcus, etc.). SCFAs were significantly reduced in POD patients and negatively correlated with delirium severity and plasma inflammation. Mice receiving fecal transplants from POD patients exhibited delirium-like behavior and neuroinflammation.

CONCLUSIONS: Postoperative delirium is associated with gut microbiota dysbiosis, marked by an increase in opportunistic pathogens and a decrease in SCFA-producing genera.

REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300070477.}, } @article {pmid39862808, year = {2025}, author = {Xiao, Y and He, X and Zhang, H and Wu, X and Ai, R and Xu, J and Wen, Q and Zhang, F and Cui, B}, title = {Washed microbiota transplantation effectively improves nutritional status in gastrointestinal disease-related malnourished children.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {132}, number = {}, pages = {112679}, doi = {10.1016/j.nut.2024.112679}, pmid = {39862808}, issn = {1873-1244}, abstract = {BACKGROUND AND AIM: Gut microbiota dysbiosis plays a critical role in malnutrition caused by food intolerance and intestinal inflammation in children, which needs to be addressed. We assessed the efficacy and safety of washed microbiota transplantation (WMT) for gastrointestinal disease-related malnourished children.

METHODS: This was a prospective observational study involving gastrointestinal disease-related malnourished pediatric patients who underwent WMT. The primary outcome was the clinical response rate at 3 mo post-WMT. Clinical response was defined as an improvement in the children's nutritional status of one level or more. The secondary outcomes were changes in gastrointestinal symptoms, laboratory nutritional indicators, and adverse events during the WMT procedure.

RESULTS: 29 patients undergoing 74 WMTs were included for analysis. In total, 48.3% (14/29) of patients achieved clinical response post-WMT. Gastrointestinal symptoms, including diarrhea, mucous stool, abdominal pain, abdominal distention, and hematochezia, were significantly relieved post-WMT (all P < 0.05). Serum albumin and prealbumin levels were increased significantly post-WMT (P = 0.028 and 0.028, respectively). Eight self-limiting and transient adverse events, including diarrhea, abdominal pain, and abdominal distension, occurred after WMT.

CONCLUSION: This study indicated that WMT might be effective and safe for improving nutritional status and gastrointestinal symptoms in gastrointestinal disease-related malnourished children at 3-mo follow-up. WMT was expected to be a new therapeutic option for these patients.}, } @article {pmid39861773, year = {2025}, author = {Ortiz-Islas, E and Montes, P and Rodríguez-Pérez, CE and Ruiz-Sánchez, E and Sánchez-Barbosa, T and Pichardo-Rojas, D and Zavala-Tecuapetla, C and Carvajal-Aguilera, K and Campos-Peña, V}, title = {Evolution of Alzheimer's Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy.}, journal = {Pharmaceutics}, volume = {17}, number = {1}, pages = {}, pmid = {39861773}, issn = {1999-4923}, support = {CF-2023-G-971 and CBF-2023-2024-1982//Ciencia de Frontera/ ; }, abstract = {Alzheimer's disease (AD) represents an escalating global health crisis, constituting the leading cause of dementia among the elderly and profoundly impairing their quality of life. Current FDA-approved drugs, such as rivastigmine, donepezil, galantamine, and memantine, offer only modest symptomatic relief and are frequently associated with significant adverse effects. Faced with this challenge and in line with advances in the understanding of the pathophysiology of this neurodegenerative condition, various innovative therapeutic strategies have been explored. Here, we review novel approaches inspired by advanced knowledge of the underlying pathophysiological mechanisms of the disease. Among the therapeutic alternatives, immunotherapy stands out, employing monoclonal antibodies to specifically target and eliminate toxic proteins implicated in AD. Additionally, the use of medicinal plants is examined, as their synergistic effects among components may confer neuroprotective properties. The modulation of the gut microbiota is also addressed as a peripheral strategy that could influence neuroinflammatory and degenerative processes in the brain. Furthermore, the therapeutic potential of emerging approaches, such as the use of microRNAs to regulate key cellular processes and nanotherapy, which enables precise drug delivery to the central nervous system, is analyzed. Despite promising advances in these strategies, the incidence of Alzheimer's disease continues to rise. Therefore, it is proposed that achieving effective treatment in the future may require the integration of combined approaches, maximizing the synergistic effects of different therapeutic interventions.}, } @article {pmid39859091, year = {2025}, author = {Almonajjed, MB and Wardeh, M and Atlagh, A and Ismaiel, A and Popa, SL and Rusu, F and Dumitrascu, DL}, title = {Impact of Microbiota on Irritable Bowel Syndrome Pathogenesis and Management: A Narrative Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {1}, pages = {}, pmid = {39859091}, issn = {1648-9144}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation/methods ; *Probiotics/therapeutic use ; Brain-Gut Axis/physiology ; Dysbiosis/therapy/complications ; Quality of Life ; Synbiotics/administration & dosage ; Prebiotics/administration & dosage ; }, abstract = {Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, affecting 3-5% of the global population and significantly impacting patients' quality of life and healthcare resources. Alongside physical symptoms such as abdominal pain and altered bowel habits, many individuals experience psychological comorbidities, including anxiety and depression. Recent research has highlighted the critical role of the gut microbiota in IBS, with dysbiosis, characterized by an imbalance in microbial diversity, frequently observed in patients. The gut-brain axis, a bidirectional communication network between the gut and central nervous system, plays a central role in the development of IBS symptoms. Although interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) have demonstrated potential in modulating the gut microbiota and alleviating symptoms, their efficacy remains an area of ongoing investigation. This review examines the interactions between the gut microbiota, immune system, and brain, emphasizing the need for personalized therapeutic strategies. Future research should aim to identify reliable microbiota-based biomarkers for IBS and refine microbiome-targeted therapies to enhance patient outcomes.}, } @article {pmid39858858, year = {2025}, author = {Onisiforou, A and Charalambous, EG and Zanos, P}, title = {Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer's Disease Pathogenesis-From Gut Microbiota and Viruses to Brain Biofilms.}, journal = {Microorganisms}, volume = {13}, number = {1}, pages = {}, pmid = {39858858}, issn = {2076-2607}, support = {#101031962//European Commission Marie Skłodowska-Curie fellowship/ ; EXCELLENCE/0421/0543//Research & Innovation Foundation of Cyprus - Excellence Hubs 2021/ ; NA//IDSA Foundation/ ; }, abstract = {For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as the primary driver of the disease. However, the consistent failure of Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores the need to rethink our approach to AD treatment. Emerging evidence points to microbial infections as environmental factors in AD pathoetiology. Although a definitive causal link remains unestablished, the collective evidence is compelling. This review explores unconventional perspectives and emerging paradigms regarding microbial involvement in AD pathogenesis, emphasizing the gut-brain axis, brain biofilms, the oral microbiome, and viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes brain Aβ accumulation, emphasizing gut-brain signaling pathways. Viral infections like Herpes Simplex Virus Type 1 (HSV-1) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead to AD by modulating host processes like the immune system. Aβ peptide's antimicrobial function as a response to microbial infection might inadvertently promote AD. We discuss potential microbiome-based therapies as promising strategies for managing and potentially preventing AD progression. Fecal microbiota transplantation (FMT) restores gut microbial balance, reduces Aβ accumulation, and improves cognition in preclinical models. Probiotics and prebiotics reduce neuroinflammation and Aβ plaques, while antiviral therapies targeting HSV-1 and vaccines like the shingles vaccine show potential to mitigate AD pathology. Developing effective treatments requires standardized methods to identify and measure microbial infections in AD patients, enabling personalized therapies that address individual microbial contributions to AD pathogenesis. Further research is needed to clarify the interactions between microbes and Aβ, explore bacterial and viral interplay, and understand their broader effects on host processes to translate these insights into clinical interventions.}, } @article {pmid39858421, year = {2024}, author = {Gabrielli, M and Zileri Dal Verme, L and Zocco, MA and Nista, EC and Ojetti, V and Gasbarrini, A}, title = {The Role of the Gastrointestinal Microbiota in Parkinson's Disease.}, journal = {Biomolecules}, volume = {15}, number = {1}, pages = {}, pmid = {39858421}, issn = {2218-273X}, mesh = {*Parkinson Disease/microbiology/metabolism ; Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology ; *Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Helicobacter Infections/microbiology ; Prebiotics ; Brain-Gut Axis/physiology ; Helicobacter pylori ; }, abstract = {BACKGROUND/OBJECTIVES: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons leading to debilitating motor and non-motor symptoms. Beyond its well-known neurological features, emerging evidence underscores the pivotal role of the gut-brain axis and gastrointestinal microbiota in PD pathogenesis. Dysbiosis has been strongly linked to PD and is associated with increased intestinal permeability, chronic inflammation, and the production of neurotoxic metabolites that may exacerbate neuronal damage.

METHODS: This review delves into the complex interplay between PD and dysbiosis, shedding light on two peculiar subsets of dysbiosis, Helicobacter pylori infection and small-intestinal bacterial overgrowth. These conditions may not only contribute to PD progression but also influence therapeutic responses such as L-dopa efficacy.

CONCLUSIONS: The potential to modulate gut microbiota through probiotics, prebiotics, and synbiotics; fecal microbiota transplantation; and antibiotics represents a promising frontier for innovative PD treatments. Despite this potential, the current evidence is limited by small sample sizes and methodological variability across studies. Rigorous, large-scale, randomized placebo-controlled trials with standardized treatments in terms of composition, dosage, and duration are urgently needed to validate these findings and pave the way for microbiota-based therapeutic strategies in PD management.}, } @article {pmid39858303, year = {2024}, author = {Morado, F and Nanda, N}, title = {A Review of Therapies for Clostridioides difficile Infection.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39858303}, issn = {2079-6382}, abstract = {Clostridioides difficile is an urgent public health threat that affects approximately half a million patients annually in the United States. Despite concerted efforts aimed at the prevention of Clostridioides difficile infection (CDI), it remains a leading cause of healthcare-associated infections. CDI is associated with significant clinical, social, and economic burdens. Therefore, it is imperative to provide optimal and timely therapy for CDI. We conducted a systematic literature review and offer treatment recommendations based on available evidence for the treatment and prevention of CDI.}, } @article {pmid39857680, year = {2025}, author = {Radoš, L and Golčić, M and Mikolašević, I}, title = {The Relationship Between the Modulation of Intestinal Microbiota and the Response to Immunotherapy in Patients with Cancer.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857680}, issn = {2227-9059}, abstract = {The intestinal microbiota is an important part of the human body, and its composition can affect the effectiveness of immunotherapy. In the last few years, the modulation of intestinal microbiota in order to improve the effectiveness of immunotherapy has become a current topic in the scientific community, but there is a lack of research in this area. In this review, the goal was to analyze the current relevant literature related to the modulation of intestinal microbiota and the effectiveness of immunotherapy in the treatment of cancer. The effects of antibiotics, probiotics, diet, and fecal microbial transplantation were analyzed separately. It was concluded that the use of antibiotics, especially broad-spectrum types or larger quantities, causes dysbiosis of the intestinal microbiota, which can reduce the effectiveness of immunotherapy. While dysbiosis could be repaired by probiotics and thus improve the effectiveness of immunotherapy, the use of commercial probiotics without evidence of intestinal dysbiosis has not yet been sufficiently tested to confirm its safety for cancer for immunotherapy-treated cancer patients. A diet consisting of sufficient amounts of fiber, as well as a diet with higher salt content positively correlates with the success of immunotherapy. Fecal transplantation is a safe and realistic adjuvant option for the treatment of cancer patients with immunotherapy, but more clinical trials are necessary. Modulating the microbiota composition indeed changes the effectiveness of immunotherapy, but in the future, more human studies should be organized to precisely determine the types and procedures of microbiota modulation.}, } @article {pmid39857657, year = {2024}, author = {Li, W and Gao, W and Yan, S and Yang, L and Zhu, Q and Chu, H}, title = {Gut Microbiota as Emerging Players in the Development of Alcohol-Related Liver Disease.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857657}, issn = {2227-9059}, support = {National Nature Science Foundation of China (No.81974078, No.81570530, and No.81370550)//Ling Yang/ ; National Key R&D Program of China (No.2022YFA1305600)//Huikuan Chu/ ; Ministry of Science and Technology of China (No.2023YFC2413804)//Ling Yang/ ; Natural Science Foundation of Hubei Province (No.2019ACA1333)//Ling Yang/ ; }, abstract = {The global incidence and mortality rates of alcohol-related liver disease are on the rise, reflecting a growing health concern worldwide. Alcohol-related liver disease develops due to a complex interplay of multiple reasons, including oxidative stress generated during the metabolism of ethanol, immune response activated by immunogenic substances, and subsequent inflammatory processes. Recent research highlights the gut microbiota's significant role in the progression of alcohol-related liver disease. In patients with alcohol-related liver disease, the relative abundance of pathogenic bacteria, including Enterococcus faecalis, increases and is positively correlated with the level of severity exhibited by alcohol-related liver disease. Supplement probiotics like Lactobacillus, as well as Bifidobacterium, have been found to alleviate alcohol-related liver disease. The gut microbiota is speculated to trigger specific signaling pathways, influence metabolite profiles, and modulate immune responses in the gut and liver. This research aimed to investigate the role of gut microorganisms in the onset and advancement of alcohol-related liver disease, as well as to uncover the underlying mechanisms by which the gut microbiota may contribute to its development. This review outlines current treatments for reversing gut dysbiosis, including probiotics, fecal microbiota transplantation, and targeted phage therapy. Particularly, targeted therapy will be a vital aspect of future alcohol-related liver disease treatment. It is to be hoped that this article will prove beneficial for the treatment of alcohol-related liver disease.}, } @article {pmid39855927, year = {2025}, author = {Wang, X and Zhao, D and Bi, D and Li, L and Tian, H and Yin, F and Zuo, T and Ianiro, G and Han, YW and Li, N and Chen, Q and Qin, H}, title = {Fecal microbiota transplantation: transitioning from chaos and controversial realm to scientific precision era.}, journal = {Science bulletin}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.scib.2025.01.029}, pmid = {39855927}, issn = {2095-9281}, abstract = {With the popularization of modern lifestyles, the spectrum of intestinal diseases has become increasingly diverse, presenting significant challenges in its management. Traditional pharmaceutical interventions have struggled to keep pace with these changes, leaving many patients refractory to conventional pharmaceutical treatments. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for enterogenic diseases. Still, controversies persist regarding its active constituents, mechanism of action, scheme of treatment evaluation, indications, and contraindications. In this review, we investigated the efficacy of FMT in addressing gastrointestinal and extraintestinal conditions, drawing from follow-up data on over 8000 patients. We systematically addressed the controversies surrounding FMT's clinical application. We delved into key issues such as its technical nature, evaluation methods, microbial restoration mechanisms, and impact on the host-microbiota interactions. Additionally, we explored the potential colonization patterns of FMT-engrafted new microbiota throughout the entire intestine and elucidated the specific pathways through which the new microbiota modulates host immunity, metabolism, and genome.}, } @article {pmid39855612, year = {2025}, author = {Sutanto, H and Elisa, E and Rachma, B and Fetarayani, D}, title = {Gut Microbiome Modulation in Allergy Treatment: The Role of Fecal Microbiota Transplantation.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2025.01.005}, pmid = {39855612}, issn = {1555-7162}, abstract = {The prevalence of allergic diseases has been rising, paralleling lifestyle changes and environmental exposures that have altered human microbiome composition. This review article examines the intricate relationship between the gut microbiome and allergic diseases, emphasizing the potential of fecal microbiota transplantation as a promising novel treatment approach. It explains how reduced microbial exposure in modern societies contributes to immune dysregulation and the increasing incidence of allergies. The discussion also addresses immune homeostasis and its modulation by the gut microbiome, highlighting the shift from eubiosis to dysbiosis in allergic conditions. Furthermore, this article reviews existing studies and emerging research on the role of fecal microbiota transplantation in restoring microbial balance, providing insights into its mechanisms, efficacy, and safety.}, } @article {pmid39854760, year = {2025}, author = {Chen, S and Zhang, D and Li, D and Zeng, F and Chen, C and Bai, F}, title = {Microbiome characterization of patients with Crohn disease and the use of fecal microbiota transplantation: A review.}, journal = {Medicine}, volume = {104}, number = {4}, pages = {e41262}, doi = {10.1097/MD.0000000000041262}, pmid = {39854760}, issn = {1536-5964}, support = {2021818//Hainan Province Clinical Medical Center/ ; YSPTZX202313//The specific research fund of The Innovation Platform for Academicians of Hainan Province/ ; 22A200078//Hainan Provincial Health Industry Research Project/ ; Qhyb2022-133//Hainan Provincial Postgraduate Innovation Research Project/ ; }, mesh = {Humans ; *Crohn Disease/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; }, abstract = {Inflammatory bowel disease is a chronic inflammatory condition predominantly affecting the intestines, encompassing both ulcerative colitis and Crohn disease (CD). As one of the most common gastrointestinal disorders, CD's pathogenesis is closely linked with the intestinal microbiota. Recently, fecal microbiota transplantation (FMT) has gained attention as a potential treatment for CD, with the effective reestablishment of intestinal microecology considered a crucial mechanism of FMT therapy. This article synthesizes the findings of population-based cohort studies to enhance our understanding of gut microbial characteristics in patients with CD. It delves into the roles of "beneficial" and "pathogenic" bacteria in CD's development. This article systematically reviews and compares data on clinical response rates, remission rates, adverse events, and shifts in bacterial microbiota. Among these studies, gut microbiome analysis was conducted in only 7, and a single study examined the metabolome. Overall, FMT has demonstrated a partial restoration of typical CD-associated microbiological alterations, leading to increased α-diversity in responders and a moderate shift in patient microbiota toward the donor profile. Several factors, including donor selection, delivery route, microbial state (fresh or frozen), and recipient condition, are identified as pivotal in influencing FMT's effectiveness. Future prospective clinical studies with larger patient cohorts and improved methodologies are imperative. In addition, standardization of FMT procedures, coupled with advanced genomic techniques such as macroproteomics and culture genomics, is necessary. These advancements will further clarify the bacterial microbiota alterations that significantly contribute to FMT's therapeutic effects in CD treatment, as well as elucidate the underlying mechanisms of action.}, } @article {pmid39854205, year = {2025}, author = {Yang, CJ and Peng, YS and Sung, PC and Hsieh, SY}, title = {Protocol for oral fecal gavage to reshape the gut microbiota in mice.}, journal = {STAR protocols}, volume = {6}, number = {1}, pages = {103585}, doi = {10.1016/j.xpro.2024.103585}, pmid = {39854205}, issn = {2666-1667}, abstract = {Fecal microbiota transplantation (FMT) is clinically applied, while oral FMT (oral fecal gavage [OFG]) is preferred for experimental mice. Here, we present a protocol for OFG in antibiotic-pretreated mice, demonstrating the progressive, time-dependent evolution of the gut microbiota in the recipients. We describe steps for fecal sample collection and preparation procedures, oral gavage, and monitoring gut microbiota changes. This protocol serves as a general guide for reshaping the gut microbiota in recipient mice for various experimental applications. For complete details on the use and execution of this protocol, please refer to Yang et al.[1].}, } @article {pmid39854158, year = {2025}, author = {Lau, RI and Su, Q and Ng, SC}, title = {Long COVID and gut microbiome: insights into pathogenesis and therapeutics.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2457495}, doi = {10.1080/19490976.2025.2457495}, pmid = {39854158}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Fecal Microbiota Transplantation ; *COVID-19/therapy/microbiology ; *Probiotics/therapeutic use ; *Dysbiosis/therapy/microbiology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Prebiotics/administration & dosage ; }, abstract = {Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.}, } @article {pmid39851261, year = {2025}, author = {Zhao, X and Qiu, Y and Liang, L and Fu, X}, title = {Interkingdom signaling between gastrointestinal hormones and the gut microbiome.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2456592}, doi = {10.1080/19490976.2025.2456592}, pmid = {39851261}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Animals ; *Dysbiosis/microbiology ; *Gastrointestinal Hormones/metabolism ; *Bacteria/metabolism/classification/genetics ; Fecal Microbiota Transplantation ; Signal Transduction ; Homeostasis ; Inflammatory Bowel Diseases/microbiology/metabolism ; Gastrointestinal Tract/microbiology/metabolism ; }, abstract = {The interplay between the gut microbiota and gastrointestinal hormones plays a pivotal role in the health of the host and the development of diseases. As a vital component of the intestinal microecosystem, the gut microbiota influences the synthesis and release of many gastrointestinal hormones through mechanisms such as modulating the intestinal environment, producing metabolites, impacting mucosal barriers, generating immune and inflammatory responses, and releasing neurotransmitters. Conversely, gastrointestinal hormones exert feedback regulation on the gut microbiota by modulating the intestinal environment, nutrient absorption and utilization, and the bacterial biological behavior and composition. The distributions of the gut microbiota and gastrointestinal hormones are anatomically intertwined, and close interactions between the gut microbiota and gastrointestinal hormones are crucial for maintaining gastrointestinal homeostasis. Interventions leveraging the interplay between the gut microbiota and gastrointestinal hormones have been employed in the clinical management of metabolic diseases and inflammatory bowel diseases, such as bariatric surgery and fecal microbiota transplantation, offering promising targets for the treatment of dysbiosis-related diseases.}, } @article {pmid39850178, year = {2024}, author = {Gandhi, DN and Pande, DN and Harikrishna, A and Advilkar, A and Basavan, I and Ansari, R}, title = {Beyond the Brain: Attention Deficit/Hyperactivity Disorder and the Gut-Brain Axis.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e76291}, pmid = {39850178}, issn = {2168-8184}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental condition, predominantly affecting children, characterized by inattention, hyperactivity, and impulsivity. A growing body of evidence has highlighted the potential influence of the gut microbiota on the onset and presentation of ADHD symptoms. The gut microbiota, a diverse microbial ecosystem residing within the gastrointestinal tract, exerts multiple effects on systemic physiology, including immune modulation, metabolic regulation, and neuronal signalling. The bidirectional gut-brain axis serves as a conduit for communication between gut microbes and the central nervous system, implicating its disruption in neurodevelopmental disorders such as ADHD. This comprehensive literature review aims to shed light on how alterations in the gut microbiota influence the development and manifestation of ADHD symptoms. Examining potential mechanisms involving gut microbial metabolites and their impact on neurotransmitter modulation, neuro-endocrine signalling and neuroinflammation, we dissect the intricate interplay shaping ADHD pathology. Insights into these complex interactions hold promise for personalized therapeutic interventions aimed at modulating the gut microbiota to ameliorate ADHD symptoms. Discussions encompass dietary interventions, faecal microbiota-targeted therapies, and emerging probiotic approaches, underscoring their potential as adjunctive or alternative strategies in managing ADHD. Further research elucidating the precise mechanisms driving these interactions may pave the way for targeted and personalized interventions for individuals grappling with ADHD.}, } @article {pmid39848238, year = {2025}, author = {Szajewska, H}, title = {An Overview of Early-Life Gut Microbiota Modulation Strategies.}, journal = {Annals of nutrition & metabolism}, volume = {}, number = {}, pages = {1-6}, doi = {10.1159/000541492}, pmid = {39848238}, issn = {1421-9697}, abstract = {BACKGROUND: The gut microbiota, or microbiome, is essential for human health. Early-life factors such as delivery mode, diet, and antibiotic use shape its composition, impacting both short- and long-term health outcomes. Dysbiosis, or alterations in the gut microbiota, is linked to conditions such as allergies, asthma, obesity, diabetes, inflammatory bowel disease, and necrotizing enterocolitis in preterm infants.

SUMMARY: This article reviews current strategies to influence the early-life gut microbiome and their potential health impacts. It also briefly summarizes guidelines on using biotics for gastrointestinal and allergic diseases in children. Key strategies include vaginal or fecal microbiota transplantation for cesarean-born infants, breastfeeding, and biotic-supplemented formulas. While vaginal microbial transfer and maternal fecal microbiota transplantation show short-term benefits, further research is needed to determine long-term safety and efficacy. Breast milk, rich in human milk oligosaccharides, promotes a healthy microbiota and offers protection against infections. Biotic-supplemented formulas can improve the gut microbiota in formula-fed infants and show clinical effects, though each biotic must be evaluated separately. Probiotics given as dietary supplements outside of infant formulas show promise for treating gastrointestinal disorders but require further investigation.}, } @article {pmid39845805, year = {2024}, author = {Shen, Y and Gao, Y and Yang, G and Zhao, Z and Zhao, Y and Gao, L and Li, S}, title = {Anti-colorectal cancer effect of total minor ginsenosides produced by lactobacilli transformation of major ginsenosides by inducing apoptosis and regulating gut microbiota.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1496346}, pmid = {39845805}, issn = {1663-9812}, abstract = {OBJECTIVE: Minor ginsenosides have demonstrated promising anticancer effects in previous reports. Total minor ginsenosides (TMG) were obtained through the fermentation of major ginsenosides with Lactiplantibacillus plantarum, and potential anticancer effects of TMGs on the mouse colon cancer cell line CT26.WT, in vitro and in vivo, were investigated.

MATERIALS AND METHODS: We employed the Cell Counting Kit-8 (CCK-8), TdT-mediated dUTP nick end labeling (TUNEL), and Western blot analysis in vitro to explore the anti-proliferative and pro-apoptotic functions of TMG in CT26.WT cells. In vivo, a xenograft model was established by subcutaneously injecting mice with CT26.WT cells and administering a dose of 100 mg/kg/day TMG to the tumor-bearing mice. The level of apoptosis and expression of various proteins in the tumor tissues were detected by immunohistochemistry and Western blot. High-throughput 16S rRNA sequencing was used to determine the alterations in the gut microbiota.

RESULTS: In vitro studies demonstrated that TMG significantly inhibited proliferation and promoted apoptosis in CT26.WT cells. Interestingly, TMG induced apoptosis in CT26.WT cells by affecting the Bax/Bcl-2/caspase-3 pathway. Furthermore, the result of the transplanted tumor model indicated that TMG substantially enhanced the activities of Bax and caspase-3, reduced the activity of Bcl-2, and suppressed the expression of Raf/MEK/ERK protein levels. Fecal analysis revealed that TMG reconstructed the gut microbiota in colorectal cancer-affected mice by augmenting the abundance of the advantageous bacterium Lactobacillus and decreasing the abundance of the harmful bacterium Proteus.

CONCLUSION: TMG can exhibit potent anti-colorectal cancer effects through diverse apoptotic mechanisms, with their mode of action closely related to the regulation of gut microbiota.}, } @article {pmid39845049, year = {2024}, author = {Wu, R and Mai, Z and Song, X and Zhao, W}, title = {Hotspots and research trends of gut microbiome in polycystic ovary syndrome: a bibliometric analysis (2012-2023).}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1524521}, pmid = {39845049}, issn = {1664-302X}, abstract = {INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common gynecological condition affecting individuals of reproductive age and is linked to the gut microbiome. This study aimed to identify the hotspots and research trends within the domain of the gut microbiome in PCOS through bibliometric analysis.

METHODS: Utilizing bibliometric techniques, we examined the literature on the gut microbiome in PCOS from the Web of Science Core Collection spanning the period from 2012 to 2023. Analytical tools such as CiteSpace, VOSviewer, and Bibliometric R packages were employed to evaluate various metrics, including countries/regions, institutions, authors, co-cited authors, authors' H-index, journals, co-references, and keywords.

RESULTS: A total of 191 publications were identified in the field of gut microbiome in PCOS, with an increase in annual publications from 2018 to 2023. People's Republic of China was the most productive country, followed by the United States of America (USA), India. Shanghai Jiao Tong University, Fudan University, and Beijing University of Chinese Medicine were the top three most publications institutions. Thackray VG was identified as the most prolific author, holding the highest H-index, while Liu R received the highest total number of citations. The journal "Frontiers in Endocrinology" published the most articles in this domain. The most frequently co-cited reference was authored by Qi XY. The analysis of keyword burst detection identified "bile acids" (2021-2023) as the leading frontier keyword. Additionally, "gut dysbiosis," "phenotypes," "adolescents," "metabolomics," "metabolites," "fecal microbiota transplantation," and "IL-22" have emerged as the primary keywords reflecting recent research trends.

CONCLUSION: This bibliometric analysis explores how the gut microbiome influences endocrine and metabolic disorders related to PCOS, emphasizing its role in the development of PCOS and treatments targeting the gut microbiome. The findings serve as a valuable resource for researchers, enabling them to identify critical hotspots and emerging areas of investigation in this field.}, } @article {pmid39844078, year = {2025}, author = {Fan, X and Li, J and Gao, Y and Li, L and Zhang, H and Bi, Z}, title = {The mechanism of enterogenous toxin methylmalonic acid aggravating calcium-phosphorus metabolic disorder in uremic rats by regulating the Wnt/β-catenin pathway.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {19}, pmid = {39844078}, issn = {1528-3658}, mesh = {Animals ; Rats ; *Wnt Signaling Pathway ; *Calcium/metabolism ; Male ; *Phosphorus/metabolism ; *Uremia/metabolism/etiology ; *Methylmalonic Acid/metabolism ; Podocytes/metabolism/pathology ; Gastrointestinal Microbiome/drug effects ; Disease Models, Animal ; Rats, Sprague-Dawley ; Apoptosis/drug effects ; beta Catenin/metabolism ; Kidney/pathology/metabolism ; }, abstract = {BACKGROUND: Uremia (UR) is caused by increased UR-related toxins in the bloodstream. We explored the mechanism of enterogenous toxin methylmalonic acid (MMA) in calcium-phosphorus metabolic disorder in UR rats via the Wnt/β-catenin pathway.

METHODS: The UR rat model was established by 5/6 nephrectomy. The fecal bacteria of UR rats were transplanted into Sham rats. Sham rats were injected with exogenous MMA or Salinomycin (SAL). Pathological changes in renal/colon tissues were analyzed. MMA concentration, levels of renal function indicators, serum inflammatory factors, Ca[2+]/P[3+], and parathyroid hormone, intestinal flora structure, fecal metabolic profile, intestinal permeability, and glomerular filtration rate (GFR) were assessed. Additionally, rat glomerular podocytes were cultured, with cell viability and apoptosis measured.

RESULTS: Intestinal flora richness and diversity in UR rats were decreased, along with unbalanced flora structure. Among the screened 133 secondary differential metabolites, the MMA concentration rose, showing the most significant difference. UR rat fecal transplantation caused elevated MMA concentration in the serum and renal tissues of Sham rats. The intestinal flora metabolite MMA or exogenous MMA promoted intestinal barrier impairment, increased intestinal permeability, induced glomerular podocyte loss, and reduced GFR, causing calcium-phosphorus metabolic disorder. The intestinal flora metabolite MMA or exogenous MMA induced inflammatory responses and facilitated glomerular podocyte apoptosis by activating the Wnt/β-catenin pathway, which could be counteracted by repressing the Wnt/β-catenin pathway.

CONCLUSIONS: Enterogenous toxin MMA impelled intestinal barrier impairment in UR rats, enhanced intestinal permeability, and activated the Wnt/β-catenin pathway to induce glomerular podocyte loss and reduce GFR, thus aggravating calcium-phosphorus metabolic disorder.}, } @article {pmid39840995, year = {2025}, author = {Hua, D and Yang, Q and Li, X and Zhou, X and Kang, Y and Zhao, Y and Wu, D and Zhang, Z and Li, B and Wang, X and Qi, X and Chen, Z and Cui, G and Hong, W}, title = {The combination of Clostridium butyricum and Akkermansia muciniphila mitigates DSS-induced colitis and attenuates colitis-associated tumorigenesis by modulating gut microbiota and reducing CD8[+] T cells in mice.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0156724}, doi = {10.1128/msystems.01567-24}, pmid = {39840995}, issn = {2379-5077}, abstract = {UNLABELLED: The gut microbiota is closely associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). Probiotics such as Clostridium butyricum (CB) or Akkermansia muciniphila (AKK) have the potential to treat inflammatory bowel disease (IBD) or colorectal cancer (CRC). However, research on the combined therapeutic effects and immunomodulatory mechanisms of CB and AKK in treating IBD or CRC has never been studied. This study evaluates the potential of co-administration of CB and AKK in treating DSS/AOM-induced IBD and colitis-associated CRC. Our results indicate that compared to mono-administration, the co-administration of CB and AKK not only significantly alleviates symptoms such as weight loss, colon shortening, and increased Disease Activity Index in IBD mice but also regulates the gut microbiota composition and effectively suppresses colonic inflammatory responses. In the colitis-associated CRC mice model, a combination of CB and AKK significantly alleviates weight loss and markedly reduces inflammatory infiltration of macrophages and cytotoxic T lymphocytes (CTLs) in the colon, thereby regulating anti-tumor immunity and inhibiting the occurrence of inflammation-induced CRC. In addition, we found that the combined probiotic therapy of CB and AKK can enhance the sensitivity of colitis-associated CRC mice to the immune checkpoint inhibitor anti-mouse PD-L1 (aPD-L1), significantly improving the anti-tumor efficacy of immunotherapy and the survival rate of colitis-associated CRC mice. Furthermore, fecal microbiota transplantation therapy showed that transplanting feces from CRC mice treated with the co-administration of CB and AKK into other CRC mice alleviated the tumor loads in the colon and significantly extended their survival rate. Our study suggests that the combined use of two probiotics, CB and AKK, can not only alleviate chronic intestinal inflammation but also inhibit the progression to CRC. This may be a natural and relatively safe method to support the gut microbiota and enhance the host's immunity against cancer.

IMPORTANCE: Our study suggests that the combined administration of CB and AKK probiotics, as opposed to a single probiotic strain, holds considerable promise in preventing the advancement of IBD to CRC. This synergistic effect is attributed to the ability of this probiotic combination to more effectively modulate the gut microbiota, curb inflammatory reactions, bolster the efficacy of immunotherapeutic approaches, and optimize treatment results via fecal microbiota transplantation.}, } @article {pmid39840614, year = {2025}, author = {Liu, W and Wang, J and Yang, H and Li, C and Lan, W and Chen, T and Tang, Y}, title = {The Metabolite Indole-3-Acetic Acid of Bacteroides Ovatus Improves Atherosclerosis by Restoring the Polarisation Balance of M1/M2 Macrophages and Inhibiting Inflammation.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2413010}, doi = {10.1002/advs.202413010}, pmid = {39840614}, issn = {2198-3844}, support = {82360105//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 20232ACB206001//Natural Science Foundation of Jiangxi Province/ ; 20223BBG71010//Key Research and Development Program of Jiangxi Province/ ; 2024SSY07061//Jiangxi Province Key Laboratory of bioengineering drugs/ ; }, abstract = {Emerging research has highlighted the significant role of the gut microbiota in atherosclerosis (AS), with microbiota-targeted interventions offering promising therapeutic potential. A central component of this process is gut-derived metabolites, which play a crucial role in mediating the distal functioning of the microbiota. In this study, a comprehensive microbiome-metabolite analysis using fecal and serum samples from patients with atherosclerotic cardiovascular disease and volunteers with risk factors for coronary heart disease and culture histology is performed, and identified the core strain Bacteroides ovatus (B. ovatus). Fecal microbiota transplantation experiments further demonstrated that the gut microbiota significantly influences AS progression, with B. ovatus alone exerting effects comparable to volunteer feces from volunteers. Notably, B. ovatus alleviated AS primarily by restoring the intestinal barrier and enhancing bile acid metabolism, particularly through the production of indole-3-acetic acid (IAA), a tryptophan-derived metabolite. IAA inhibited the TLR4/MyD88/NF-κB pathway in M1 macrophages, promoted M2 macrophage polarisation, and restored the M1/M2 polarisation balance, ultimately reducing aortic inflammation. These findings clarify the mechanistic interplay between the gut microbiota and AS, providing the first evidence that B. ovatus, a second-generation probiotic, can improve bile acid metabolism and reduce inflammation, offering a theoretical foundation for future AS therapeutic applications involving this strain.}, } @article {pmid39840031, year = {2024}, author = {Lim, MY and Hong, S and Nam, YD}, title = {Understanding the role of the gut microbiome in solid tumor responses to immune checkpoint inhibitors for personalized therapeutic strategies: a review.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1512683}, pmid = {39840031}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Immune Checkpoint Inhibitors/therapeutic use ; *Neoplasms/immunology/therapy/drug therapy/microbiology ; *Precision Medicine ; Animals ; Immunotherapy/methods ; Treatment Outcome ; }, abstract = {Immunotherapy, especially immune checkpoint inhibitor (ICI) therapy, has yielded remarkable outcomes for some patients with solid cancers, but others do not respond to these treatments. Recent research has identified the gut microbiota as a key modulator of immune responses, suggesting that its composition is closely linked to responses to ICI therapy in cancer treatment. As a result, the gut microbiome is gaining attention as a potential biomarker for predicting individual responses to ICI therapy and as a target for enhancing treatment efficacy. In this review, we discuss key findings from human observational studies assessing the effect of antibiotic use prior to ICI therapy on outcomes and identifying specific gut bacteria associated with favorable and unfavorable responses. Moreover, we review studies investigating the possibility of patient outcome prediction using machine learning models based on gut microbiome data before starting ICI therapy and clinical trials exploring whether gut microbiota modulation, for example via fecal microbiota transplantation or live biotherapeutic products, can improve results of ICI therapy in patients with cancer. We also briefly discuss the mechanisms through which the gut microbial-derived products influence immunotherapy effectiveness. Further research is necessary to fully understand the complex interactions between the host, gut microbiota, and immunotherapy and to develop personalized strategies that optimize responses to ICI therapy.}, } @article {pmid39839105, year = {2024}, author = {Correa Lopes, B and Turck, J and Tolbert, MK and Giaretta, PR and Suchodolski, JS and Pilla, R}, title = {Prolonged storage reduces viability of Peptacetobacter (Clostridium) hiranonis and core intestinal bacteria in fecal microbiota transplantation preparations for dogs.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1502452}, pmid = {39839105}, issn = {1664-302X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has been described useful as an adjunct treatment for chronic enteropathy in dogs. Different protocols can be used to prepare and store FMT preparations, however, the effect of these methods on microbial viability is unknown. We aimed (1) to assess the viability of several core intestinal bacterial species by qPCR and (2) to assess Peptacetobacter (Clostridium) hiranonis viability through culture to further characterize bacterial viability in different protocols for FMT preparations.

METHODS: Bacterial abundances were assessed in feces from six healthy dogs by qPCR after propidium monoazide (PMA-qPCR) treatment for selective quantitation of viable bacteria. Conservation methods tested included lyophilization (stored at 4°C and at -20°C) and freezing with glycerol-saline solution (12.5%) and without any cryoprotectant (stored at -20°C). Additionally, the abundance of P. hiranonis was quantified using bacterial culture.

RESULTS: Using PMA-qPCR, the viability of Faecalibacterium, Escherichia coli, Streptococcus, Blautia, Fusobacterium, and P. hiranonis was reduced in lyophilized fecal samples kept at 4°C and -20°C up to 6 months (p < 0.05). In frozen feces without cryoprotectant, only Streptococcus and E. coli were not significantly reduced for up to 3 months (p > 0.05). Lastly, no differences were observed in the viability of those species in glycerol-preserved samples up to 6 months (p > 0.05). When using culture to evaluate the viability of P. hiranonis, we observed that P. hiranonis abundance was lower in lyophilized samples kept at 4°C than -20°C; and P. hiranonis abundance was higher in glycerol-preserved samples for up to 6 months than in samples preserved without glycerol for up to 3 months. Moreover, the highest abundance of P. hiranonis was observed in glycerol-preserved feces. After 3 months, P. hiranonis was undetectable by culture in 83% (5/6) of the frozen samples without glycerol.

DISCUSSION: While the lyophilization procedure initially reduced P. hiranonis abundance, P. hiranonis viability was stable thereafter for up to 6 months at -20°C. The higher bacterial viability detected in fecal samples preserved with glycerol confirms the use of this cryoprotectant as a reliable method to keep bacteria alive in the presence of fecal matrix for FMT purposes.}, } @article {pmid39838262, year = {2025}, author = {Ye, J and Shi, R and Wu, X and Fan, H and Zhao, Y and Hu, X and Wang, L and Bo, X and Li, D and Ge, Y and Wang, D and Xia, B and Zhao, Z and Xiao, C and Zhao, B and Wang, Y and Liu, X}, title = {Stevioside mitigates metabolic dysregulation in offspring induced by maternal high-fat diet: the role of gut microbiota-driven thermogenesis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2452241}, doi = {10.1080/19490976.2025.2452241}, pmid = {39838262}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Female ; *Diet, High-Fat/adverse effects ; Pregnancy ; Mice ; *Diterpenes, Kaurane/pharmacology/metabolism ; *Glucosides/pharmacology/metabolism ; *Thermogenesis/drug effects ; *Mice, Inbred C57BL ; Pregnancy in Obesity/metabolism ; Male ; Prenatal Exposure Delayed Effects/microbiology ; Bacteria/classification/metabolism/isolation & purification/genetics/drug effects ; Lactobacillus/metabolism ; Lipid Metabolism/drug effects ; Obesity/metabolism/microbiology ; Dietary Supplements ; }, abstract = {Maternal obesity poses a significant threat to the metabolic profiles of offspring. Microorganisms acquired from the mother early in life critically affect the host's metabolic functions. Natural non-nutritive sweeteners, particularly stevioside (STV), play a crucial role in reducing obesity and affecting gut microbiota composition. Based on this, we hypothesized that maternal STV supplementation could improve the health of mothers and offspring by altering their gut microbiota. Our study found that maternal STV supplementation reduced obesity during pregnancy, decreased abnormal lipid accumulation in offspring mice caused by maternal obesity, and modified the gut microbiota of both dams and offspring, notably increasing the abundance of Lactobacillus apodemi (L. apodemi). Co-housing and fecal microbiota transplant experiments confirmed that gut microbiota mediated the effects of STV on metabolic disorders. Furthermore, treatment with L. apodemi alone replicated the beneficial effects of STV, which were associated with increased thermogenesis. In summary, maternal STV supplementation could alleviate lipid metabolic disorders in offspring by enhancing L. apodemi levels and promoting thermogenic activity, potentially involving changes in bile acid metabolism pathways.}, } @article {pmid39837364, year = {2025}, author = {Liu, H and Yang, S and Zhang, Q and Wang, S and Zhang, B and Xu, Y and Fu, X and Zhou, S and Zhang, P and Wang, H and Di, L and Xu, X and Xu, X and Liu, C and Yang, C and Wang, Y and Jiang, R}, title = {S-ketamine alleviates morphine-induced hyperalgesia via decreasing the gut Enterobacteriaceae levels: Comparison with R-ketamine.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2025.01.022}, pmid = {39837364}, issn = {1873-7544}, abstract = {BACKGROUND: Opioid-induced hyperalgesia (OIH) is a serious complication during the pain treatment. Ketamine has been commonly reported to treat OIH, but the mechanisms remain unclear. Gut microbiota is recently recognized as one of the important mechanisms underlying the occurrence and treatment of OIH. However, whether ketamine enantiomers could alleviate OIH through gut microbiota that still needs to be clarified.

METHODS: The OIH model was established by morphine injection for 3 consecutive days, followed by hierarchical clustering analysis of behavioral results into susceptible or resilient group. Broad-spectrum antibiotic cocktail (ABx) was used to eradicated the gut microbiota of mice. Subsequently, fecal microbiota transplantation (FMT) was performed. S- or R-ketamine was administered as pretreatment 30 min before morphine injection. Fecal samples were collected for 16S rRNA gene sequencing after completion of all behavioral tests.

RESULTS: Approximately 60% of the mice developed OIH after morphine exposure with abnormal locomotion and anxiety-like behaviors. Pseudo germ-free mice treated with ABx did not develop hyperalgesia, whereas pseudo germ-free mice that received fecal microbiota transplantation from OIH mice developed hyperalgesia. Interestingly, S-ketamine but not R-ketamine rescued mice from OIH. The principal co-ordinates analysis (PCoA) suggested that the distribution of gut microbiota differed among the groups. Importantly, levels of Enterobacteriaceae were increased in OIH susceptible group, while decreased after S-ketamine treatment.

CONCLUSION: S-ketamine but not R-ketamine was able to alleviate morphine-induced OIH, and this mechanism is probably related to decreasing the levels of gut Enterobacteriaceae.}, } @article {pmid39836853, year = {2024}, author = {Aristizábal, AM and Montaña, LP and Gutiérrez, J and Medina, D and Franco, AA and Manzi, E and Zapata, ÁD and Mosquera, W}, title = {Intra-mesenteric steroids for steroid-refractory graft-versus-host disease in pediatric patients: A safe option.}, journal = {Biomedica : revista del Instituto Nacional de Salud}, volume = {44}, number = {Sp. 2}, pages = {63-71}, doi = {10.7705/biomedica.7394}, pmid = {39836853}, issn = {2590-7379}, mesh = {Humans ; *Graft vs Host Disease/drug therapy/etiology ; Child ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Adolescent ; Male ; Female ; Child, Preschool ; *Methylprednisolone/therapeutic use/administration & dosage ; Retrospective Studies ; Drug Resistance ; Infant ; Glucocorticoids/therapeutic use ; }, abstract = {INTRODUCTION: Graft-versus-host disease is a serious complication after hematopoietic stem cell transplantation and is a major cause of death post-transplantation. Approximately 50% of acute graft-versus-host disease patients do not respond to systemic steroids and their prognosis is poor regardless of the treatment. This study describes our experience with pediatric patients diagnosed with steroid-refractory graft-versus-host disease who received intra-mesenteric steroid treatment.

OBJECTIVE: To determine the outcomes of intra-mesenteric steroid use in the management of pediatric patients diagnosed with refractory graft-versus-host disease.

MATERIALS AND METHODS: The study included patients under 18 years old with allogeneic hematopoietic stem cell transplantation who underwent intra-mesenteric steroid injection for resistant gastrointestinal graft-versus-host disease between January, 2016, and December, 2021. Methylprednisolone was administered via intra-arterial injection through the celiac trunk and the superior and inferior mesenteric arteries.

RESULTS: We collected data on 21 patients: nine (90%) responded with a subjective decrease in fecal output and a reduction in bilirubin and transaminases. Seven patients required a second intra-mesenteric injection and presented a complete response in 85% of the cases. Only one patient experienced local complications after the procedure. Twelve patients (57%) died with one death due to acute graft-versus-host disease.

CONCLUSION: Reports in the adult population have shown an approximately 50% response rate with few complications, making it a second-line management standard. As far as we know, this is the largest pediatric cohort reported in Latin America. Our findings suggest that intra-mesenteric steroid administration for managing hepatic and gastrointestinal graftversus-host disease may be considered an early adjuvant treatment in patients with steroidrefractory graft-versus-host disease.}, } @article {pmid39836604, year = {2025}, author = {Wu, X and Wei, J and Ran, W and Liu, D and Yi, Y and Gong, M and Liu, X and Gong, Q and Li, H and Gao, J}, title = {The Gut Microbiota-Xanthurenic Acid-Aromatic Hydrocarbon Receptor Axis Mediates the Anticolitic Effects of Trilobatin.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2412234}, doi = {10.1002/advs.202412234}, pmid = {39836604}, issn = {2198-3844}, support = {GCC[2023]042//Guizhou Province/ ; HZ(2024)302//Science and technology project of Zunyi/ ; ZYSE-2022-02//Zunyi Medical University/ ; [2021]1350-037//Talent project of Guizhou platform/ ; 2022(2022JH2/101300058)//Liaoning Province/ ; }, abstract = {Current treatments for ulcerative colitis (UC) remain limited, highlighting the need for novel therapeutic strategies. Trilobatin (TLB), a naturally derived food additive, exhibits potential anti-inflammatory properties. In this study, a dextran sulfate sodium (DSS)-induced animal model is used to investigate the effects of TLB on UC. It is found TLB significantly alleviates DSS-induced UC in mice, as evidenced by a reduction in the disease activity index, an increase in colon length, improvement in histopathological lesions. Furthermore, TLB treatment results in a decrease in proinflammatory cytokines and an increase in anti-inflammatory cytokines. TLB mitigates UC by modulating the intestinal microbiota, particularly Akkermansia, which enhances tryptophan metabolism and upregulates the production of xanthurenic acid (XANA). To confirm the role of TLB-induced microbiota changes, experiments are performed with pseudogerm-free mice and fecal transplantation. It is also identified XANA as a key metabolite that mediates TLB's protective effects. Both TLB and XANA markedly activate the aromatic hydrocarbon receptor (AhR). Administration of an AhR antagonist abrogates their protective effects, thereby confirming the involvement of AhR in the underlying mechanism. In conclusion, the study reveals a novel mechanism through which TLB alleviates UC by correcting microbiota imbalances, regulating tryptophan metabolism, enhancing XANA production, and activating AhR.}, } @article {pmid39834471, year = {2024}, author = {Song, Y and Liu, S and Zhang, L and Zhao, W and Qin, Y and Liu, M}, title = {The effect of gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review and network meta-analysis.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1470185}, pmid = {39834471}, issn = {2296-861X}, abstract = {BACKGROUND: The incidence of NAFLD is increasing. Preclinical evidences indicate that modulation of the gut microbiome could be a promising target in nonalcoholic fatty liver disease.

METHOD: A systematic review and network meta-analysis was conducted to compare the effect of probiotics, synbiotics, prebiotics, fecal microbiota transplant, and antibiotics on the liver-enzyme, metabolic effects and liver-specific in patients with NAFLD. The randomized controlled trails (RCTs), limited to English language were searched from database such as Pubmed, Embase, Web of science and Cochrane Library from inception to November 2024. Review Manager 5.3 was used to to draw a Cochrane bias risk. Inconsistency test and publication-bias were assessed by Stata 14.0. Random effect model was used to assemble direct and indirect evidences. The effects of the intervention were presented as mean differences with 95% confidence interval.

RESULTS: A total of 1921 patients from 37 RCTs were eventually included in our study. 23 RCTs evaluated probiotics, 10 RCTs evaluated synbiotics, 4 RCTs evaluated prebiotics, 3 RCTs evaluated FMT and one RCT evaluated antibiotics. Probiotics and synbiotics were associated with a significantly reduction in alanine aminotransferase [ALT, (MD: -5.09; 95%CI: -9.79, -0.39), (MD: -7.38, 95CI%: -11.94, -2.82)] and liver stiffness measurement by elastograph [LSM, (MD: -0.37;95%CI: -0.49, -0.25), (MD: -1.00;95%CI: -1.59, -0.41)]. In addition to, synbiotics was superior to probiotics in reducing LSM. Synbiotics was associated with a significant reduction of Controlled Attenuation Parameter [CAP, (MD: -39.34; 95%CI: -74.73, -3.95)]. Both probiotics and synbiotics were associated with a significant reduction of aspartate transaminase [AST, (MD: -7.81; 95%CI: -15.49, -0.12), (MD: -13.32; 95%CI: -23, -3.64)]. Probiotics and Allogenic FMT was associated with a significant reduction of Homeostatic Model Assessment for Insulin Resistance [HOMA-IR, (MD: -0.7, 95%CI: -1.26, -0.15), (MD: -1.8, 95%CI: -3.53, - 0.07)]. Probiotics was associated with a significant reduction of body mass index [BMI, MD: -1.84, 95%CI: -3.35, -0.33].

CONCLUSION: The supplement of synbiotics and probiotics maybe a promising way to improve liver-enzyme, LSM, and steatosis in patients with NAFLD. More randomized controlled trials are needed to determine the efficacy of FMT and antibiotics on NAFLD. And the incidence of adverse events of MTTs should be further explored.

https://www.crd.york.ac.uk/prospero/, CRD42023450093.}, } @article {pmid39829898, year = {2025}, author = {Ni, M and Fan, Y and Liu, Y and Li, Y and Qiao, W and Davey, LE and Zhang, XS and Ksiezarek, M and Mead, E and Touracheau, A and Jiang, W and Blaser, MJ and Valdivia, RH and Fang, G}, title = {Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39829898}, issn = {2692-8205}, abstract = {The human gut microbiome within the gastrointestinal tract continuously adapts to variations in diet, medications, and host physiology. A central strategy for genetic adaptation is epigenetic phase variation (ePV) mediated by bacterial DNA methylation, which can regulate gene expression, enhance clonal heterogeneity, and enable a single bacterial strain to exhibit variable phenotypic states. Genome-wide and site-specific ePV have been well characterized in human pathogens' antigenic variation and virulence factor production. However, the role of ePV in facilitating adaptation within the human microbiome remains poorly understood. Here, we comprehensively cataloged genome-wide and site-specific ePV in human infant and adult gut microbiomes. First, using long-read metagenomic sequencing, we detected genome-wide ePV mediated by complex structural variations of DNA methyltransferases, highlighting the ones associated with antibiotics or fecal microbiota transplantation. Second, we analyzed an extensive collection of public short-read metagenomic sequencing datasets, uncovering a greater prevalence of genome-wide ePV in the human gut microbiome. Third, we quantitatively detected site-specific ePVs using single-molecule methylation analysis to identify dynamic variations associated with antibiotic treatment or probiotic engraftment. Finally, we performed an in-depth assessment of an Akkermansia muciniphila isolate from an infant, highlighting that ePV can regulate gene expression and enhance the bacterial adaptive capacity by employing a bet-hedging strategy to increase tolerance to differing antibiotics. Our findings indicate that epigenetic modifications are a common and broad strategy used by bacteria in the human gut to adapt to their environment.}, } @article {pmid39829204, year = {2025}, author = {Liu, C and Wong, PY and Barua, N and Li, B and Wong, HY and Zhang, N and Chow, SKH and Wong, SH and Yu, J and Ip, M and Cheung, WH and Duque, G and Brochhausen, C and Sung, JJY and Wong, RMY}, title = {From Clinical to Benchside: Lacticaseibacillus and Faecalibacterium Are Positively Associated With Muscle Health and Alleviate Age-Related Muscle Disorder.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e14485}, doi = {10.1111/acel.14485}, pmid = {39829204}, issn = {1474-9726}, support = {C4032-21GF//Collaborative Research Fund, HKSAR Research Grants Council/ ; 14116223//General Research Fund, HKSAR Research Grants Council/ ; }, abstract = {Sarcopenia is an age-related muscle disorder that increases risks of adverse clinical outcomes, but its treatments are still limited. Gut microbiota is potentially associated with sarcopenia, and its role is still unclear. To investigate the role of gut microbiota in sarcopenia, we first compared gut microbiota and metabolites composition in old participants with or without sarcopenia. Fecal microbiota transplantation (FMT) from human donors to antibiotic-treated recipient mice was then performed. Specific probiotics and their mechanisms to treat aged mice were identified. Old people with sarcopenia had different microbial composition and metabolites, including Paraprevotella, Lachnospira, short-chain fatty acids, and purine. After FMT, mice receiving microbes from people with sarcopenia displayed lower muscle mass and strength compared with those receiving microbes from non-sarcopenic donors. Lacticaseibacillus rhamnosus (LR) and Faecalibacterium prausnitzii (FP) were positively related to muscle health of old people, and enhanced muscle mass and function of aged mice. Transcriptomics showed that genes related to tricarboxylic acid cycle (TCA) were enriched after treatments. Metabolic analysis showed increased substrates of TCA cycle in both LR and FP supernatants. Muscle mitochondria density, ATP content, NAD[+]/NADH, mitochondrial dynamics and biogenesis proteins, as well as colon tight junction proteins of aged mice were improved by both probiotics. LR and the combination of two probiotics also benefit intestinal immune health by reducing CD8[+] IFNγ[+] T cells. Gut microbiota dysbiosis is a pathogenesis of sarcopenia, and muscle-related probiotics could alleviate age-related muscle disorders mainly through mitochondria improvement. Further clinical translation is warranted.}, } @article {pmid39827989, year = {2025}, author = {Cheng, CK and Ye, L and Wang, Y and Wang, YL and Xia, Y and Wong, SH and Chen, S and Huang, Y}, title = {Exercised gut microbiota improves vascular and metabolic abnormalities in sedentary diabetic mice through gut‒vascular connection.}, journal = {Journal of sport and health science}, volume = {}, number = {}, pages = {101026}, doi = {10.1016/j.jshs.2025.101026}, pmid = {39827989}, issn = {2213-2961}, abstract = {BACKGROUND: Exercise elicits cardiometabolic benefits, reducing the risks of cardiovascular diseases and type 2 diabetes. This study aimed to investigate the vascular and metabolic effects of gut microbiota from exercise-trained donors on sedentary mice with type 2 diabetes and the potential mechanism.

METHODS: Leptin receptor-deficient diabetic (db/db) and nondiabetic (db/m[+]) mice underwent running treadmill exercise for 8 weeks, during which fecal microbiota transplantation (FMT) was parallelly performed from exercise-trained to sedentary diabetic (db/db) mice. Endothelial function, glucose homeostasis, physical performance, and vascular signaling of recipient mice were assessed. Vascular and intestinal stresses, including inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, were investigated. RNA sequencing analysis on mouse aortic and intestinal tissues was performed. Gut microbiota profiles of recipient mice were evaluated by metagenomic sequencing.

RESULTS: Chronic exercise improved vascular and metabolic abnormalities in donor mice. Likewise, FMT from exercised donors retarded body weight gain and slightly improved grip strength and rotarod performance in recipient mice. Exercise-associated FMT enhanced endothelial function in different arteries, suppressed vascular and intestinal stresses, and improved glucose homeostasis in recipient mice, with noted microRNA-181b upregulation in aortas and intestines. Altered gut microbiota profiles and gut-derived factors (e.g., short-chain fatty acids and glucagon-like peptide-1) as well as improved intestinal integrity shall contribute to the cardiometabolic benefits, implying a gut‒vascular connection.

CONCLUSION: This proof-of-concept study indicates that exercised microbiota confers cardiometabolic benefits on sedentary db/db mice, extending the beneficial mechanism of exercise through gut‒vascular communication. The findings open up new therapeutic opportunities for cardiometabolic diseases and shed light on the development of exercise mimetics by targeting the gut microbiota.}, } @article {pmid39827465, year = {2025}, author = {Zhang, Y and Hao, R and Chen, J and Huang, K and Li, S and Cao, H and Guan, X}, title = {Gut-Derived Ursodeoxycholic Acid from Saponins of Quinoa Regulated Colitis via Inhibiting the TLR4/NF-κB Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c09151}, pmid = {39827465}, issn = {1520-5118}, abstract = {Alteration of the gut microbiota and its metabolites plays a key role in the development of inflammatory bowel disease (IBD). Here, we investigated the mechanism of saponins, a byproduct from quinoa (SQ) processing, in regulating IBD. SQ ameliorated gut microbiota dysbiosis revealed by 16S rRNA sequencing and improved colonic antioxidant activities and barrier integrity in dextran sulfate sodium (DSS)-treated mice. Broad-spectrum antibiotics further proved that the gut-protective effects of SQ were mediated by gut microbiota. Next, fecal microbiota transplantation (FMT) of SQ-induced gut microbiota/metabolites to inoculate DSS-treated mice alleviated colitis significantly. Untargeted metabolomics and lipidomics revealed that ursodeoxycholic acid (UDCA) was enriched as a microbial metabolite after SQ supplementation. UDCA was then found to attenuate DSS-induced colitis in vivo by targeting the TLR4/NF-κB pathway, which was also verified in a Caco-2 cell model treated with a TLR4 agonist/antagonist. Overall, our findings established that gut microbiota-UDCA-TLR4/NF-κB signaling plays a key role in mediating the protective effects of SQ.}, } @article {pmid39826789, year = {2025}, author = {Du, X and Liu, L and Yang, L and Zhang, Y and Dong, K and Li, Y and Chen, Y and Yang, Q and Zhu, X and Li, Q}, title = {Cumulative experience meets modern science: Remarkable effects of TongXieYaoFang formula on facilitating intestinal mucosal healing and secretory function.}, journal = {Journal of ethnopharmacology}, volume = {341}, number = {}, pages = {119370}, doi = {10.1016/j.jep.2025.119370}, pmid = {39826789}, issn = {1872-7573}, abstract = {TongXieYaoFang (TXYF), a classical formula used in Traditional Chinese Medicine, is renowned for its efficacy in treating chronic abdominal pain and diarrhoea. Modern research suggests that fundamental relief from these symptoms depends on complete intestinal mucosal healing, which normalises gut secretory functions. Consensus between traditional and modern medical theories indicates that TXYF is particularly suitable for treating the remission phase of ulcerative colitis (UC). Unfortunately, its potential in the remission phase has not received sufficient attention, and its use has been largely limited to a supportive role during the acute phase.

AIM OF THE STUDY: This study aimed to elucidate the efficacy of TXYF in promoting intestinal mucosal healing and enhancing gut secretory function during the non-acute damage phase, as well as to identify the underlying mechanisms contributing to its effects.

METHODS: A mouse model of dextran sulphate sodium salt (DSS)-induced colitis was optimised to specifically evaluate the effects of TXYF on mucosal healing during the repair phase. The effects of TXYF on murine colon function were assessed by measuring faecal pellet count and water content, and further evaluated through immunohistochemical analyses. The underlying mechanisms of action of TXYF were elucidated using mouse intestinal organoid cultures, intestinal stem cell (ISCs) transplantation, immunofluorescence, and western blotting. Active components of TXYF were identified via LC-MS/MS analysis and integrated with network pharmacology for bioinformatics assessment.

RESULTS: TXYF significantly promoted mucosal healing, as reflected by reduced disease activity scores, increased colon length, enhanced epithelial proliferation, and decreased histological damage. Furthermore, TXYF enhanced the recovery of critical intestinal functions, including barrier integrity, absorption, secretion, and motility. Notably, the improvement in the secretory function was particularly pronounced. Mechanistically, these therapeutic effects were mediated by the upregulation of the Atonal homolog 1/SAM pointed domain containing ETS transcription factor/Mucin 2 pathway, which facilitates the differentiation and maturation of ISCs into goblet cells, thereby contributing to both mucosal repair and enhanced secretory function.

CONCLUSIONS: Our study demonstrated that TXYF significantly promotes intestinal mucosal healing and enhances secretory function. These findings offer a solid basis for exploring the potential applications of TXYF in UC management during the remission phase.}, } @article {pmid39809266, year = {2025}, author = {Wang, D and Jiang, Y and Jiang, J and Pan, Y and Yang, Y and Fang, X and Liang, L and Li, H and Dong, Z and Fan, S and Ma, D and Zhang, XS and Li, H and He, Y and Li, N}, title = {Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia.}, journal = {Cell reports. Medicine}, volume = {6}, number = {1}, pages = {101919}, doi = {10.1016/j.xcrm.2024.101919}, pmid = {39809266}, issn = {2666-3791}, mesh = {*Gastrointestinal Microbiome/genetics ; *Autism Spectrum Disorder/metabolism/microbiology/genetics ; *gamma-Aminobutyric Acid/metabolism ; Humans ; Animals ; Female ; Male ; Mice ; Child ; Child, Preschool ; Metabolomics/methods ; RNA, Ribosomal, 16S/genetics ; Escherichia/metabolism/genetics ; Feces/microbiology ; Glutamic Acid/metabolism ; Mice, Inbred C57BL ; Escherichia coli/genetics/metabolism ; Metabolome ; }, abstract = {Gut microbiota (GM) alterations have been implicated in autism spectrum disorder (ASD), yet the specific functional architecture remains elusive. Here, employing multi-omics approaches, we investigate stool samples from two distinct cohorts comprising 203 children with mild ASD or typical development. In our screening cohort, regression-based analysis for metabolomic profiling identifies an elevated γ-aminobutyric acid (GABA) to glutamate (Glu) ratio as a metabolic signature of ASD, independent of age and gender. In the validating cohort, we affirm the GABA/Glu ratio as an ASD diagnostic indicator after adjusting for geography, age, gender, and specific food-consuming frequency. Integrated analysis of metabolomics, 16S rRNA sequencing, and metagenomics reveals a correlation between overrepresented Escherichia and disrupted GABA metabolism. Furthermore, we observe social behavioral impairments in weaning mice transplanted with E. coli, suggesting a potential link to ASD symptomatology. Collectively, these findings provide insights into potential diagnostic and therapeutic strategies aimed at evaluating and restoring gut microbial neurotransmitter homeostasis.}, } @article {pmid39826698, year = {2025}, author = {Song, Y and Cui, Y and Zhong, Y and Wang, Y and Zheng, X}, title = {Fecal microbiota transplantation combined with inulin promotes the development and function of early immune organs in chicks.}, journal = {Journal of biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jbiotec.2025.01.012}, pmid = {39826698}, issn = {1873-4863}, abstract = {Modern management of chicks hinders the vertical transmission of intestinal microbiota, which is closely related to immunity. Inulin is a substrate that can be utilized by the microbiota. This study aimed to determine whether fecal microbiota transplantation (FMT) combined with inulin played a "1+1>2" role in enhancing the development and function of immune organs. Chicks were treated with 1% inulin and/or fecal microbiota suspension on days 1-6. The growth performance, immune organ development, and immune indicators were evaluated on days 7, 14, and 21. Results showed that the combination of FMT and inulin significantly increased the immune organ index on day 7 and promoted the morphological structure and the expression of proliferating cell nuclear antigen (PCNA) in immune organs on days 7, 14, and 21. Each treatment increased the gene expression of interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-2 (IL-2), B cell-activating factor receptor (BAFFR), B cell linker (BLNK), C-X-C Motif Chemokine Ligand 12 (CXCL12), C-X-C Motif Chemokine Receptor 4 (CXCR4), and Biotin (Bu-1) to varying degrees. FMT combined with inulin significantly increased the expression of IgA-positive cells on days 7 and 14. In conclusion, the synergistic effect of FMT and inulin had beneficial impacts on the development and function of immune organs.}, } @article {pmid39826450, year = {2025}, author = {Zhu, Z and Zuo, S and Zhu, Z and Wang, C and Du, Y and Chen, F}, title = {THSWD upregulates the LTF/AMPK/mTOR/Becn1 axis and promotes lysosomal autophagy in hepatocellular carcinoma cells by regulating gut flora and metabolic reprogramming.}, journal = {International immunopharmacology}, volume = {148}, number = {}, pages = {114091}, doi = {10.1016/j.intimp.2025.114091}, pmid = {39826450}, issn = {1878-1705}, abstract = {THSWD has the effect of reducing inflammation, improving microcirculation, and regulating immune status in patients with hepatocellular carcinoma. Regardless of its clear therapeutic effect, the underlying mechanism of action against hepatocellular carcinoma is not clear. To identify critical gut microbiota and its associated metabolites related to THSWD inhibition against hepatocellular carcinoma progression, we assessed the microbe-dependent anti-hepatocellular carcinoma effects of THSWD through 16 s rRNA gene sequencing, fecal microbial transplantation and antibiotic treatment. Metabolic analyses, transcriptomic analyses, and molecular experiments were performed to explore how THSWD modulates the gut microbiota against hepatocellular carcinoma progression. As confirmed by in vivo and in vitro assays, THSWD reduced tumour growth rate and promoted apoptosis in hepatocellular carcinoma cells in hepatocellular carcinoma model mice, and liver and kidney indexes were detected and confirmed the safety of THSWD. Transcriptomic analysis revealed that the targets of THSWD were significantly enriched in multiple lysosomal autophagy signalling pathways, suggesting that lysosomal autophagy is probably associated with THSWD's therapeutic effect. Based on the integrated data analysis, THSWD delays hepatocellular carcinoma progression by increasing the intestinal microbiota Duncaniella and augmenting the metabolite glabrol, and the joint analysis of metabolic and genomic data suggests that this metabolite is associated with lysosomal autophagy, and cellular experiments confirmed that the The differential metabolite glabrol induces apoptosis in hepatocellular carcinoma cells by triggering the lysosomal autophagy-mediated apoptosis signalling pathway. Supplementation with glabrol metabolites up regulates the LTF/AMPK/mTOR/Beclin1 axis and promotes hepatocellular carcinoma cells with lysosomal autophagy and induced apoptosis in hepatocellular carcinoma cells.}, } @article {pmid39826104, year = {2025}, author = {Lin, A and Jiang, A and Huang, L and Li, Y and Zhang, C and Zhu, L and Mou, W and Liu, Z and Zhang, J and Cheng, Q and Wei, T and Luo, P}, title = {From chaos to order: optimizing fecal microbiota transplantation for enhanced immune checkpoint inhibitors efficacy.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2452277}, doi = {10.1080/19490976.2025.2452277}, pmid = {39826104}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Immune Checkpoint Inhibitors/therapeutic use ; *Gastrointestinal Microbiome ; *Neoplasms/therapy/microbiology ; Animals ; Immunotherapy/methods ; Tumor Microenvironment/drug effects ; Treatment Outcome ; Combined Modality Therapy ; }, abstract = {The integration of fecal microbiota transplantation (FMT) with immune checkpoint inhibitors (ICIs) presents a promising approach for enhancing cancer treatment efficacy and overcoming therapeutic resistance. This review critically examines the controversial effects of FMT on ICIs outcomes and elucidates the underlying mechanisms. We investigate how FMT modulates gut microbiota composition, microbial metabolite profiles, and the tumor microenvironment, thereby influencing ICIs effectiveness. Key factors influencing FMT efficacy, including donor selection criteria, recipient characteristics, and administration protocols, are comprehensively discussed. The review delineates strategies for optimizing FMT formulations and systematically monitoring post-transplant microbiome dynamics. Through a comprehensive synthesis of evidence from clinical trials and preclinical studies, we elucidate the potential benefits and challenges of combining FMT with ICIs across diverse cancer types. While some studies report improved outcomes, others indicate no benefit or potential adverse effects, emphasizing the complexity of host-microbiome interactions in cancer immunotherapy. We outline critical research directions, encompassing the need for large-scale, multi-center randomized controlled trials, in-depth microbial ecology studies, and the integration of multi-omics approaches with artificial intelligence. Regulatory and ethical challenges are critically addressed, underscoring the imperative for standardized protocols and rigorous long-term safety assessments. This comprehensive review seeks to guide future research endeavors and clinical applications of FMT-ICIs combination therapy, with the potential to improve cancer patient outcomes while ensuring both safety and efficacy. As this rapidly evolving field advances, maintaining a judicious balance between openness to innovation and cautious scrutiny is crucial for realizing the full potential of microbiome modulation in cancer immunotherapy.}, } @article {pmid39825784, year = {2025}, author = {Zhang, R and Sun, X and Lu, H and Zhang, X and Zhang, M and Ji, X and Yu, X and Tang, C and Wu, Z and Mao, Y and Zhu, J and Ji, M and Yang, Z}, title = {Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway.}, journal = {Microbial biotechnology}, volume = {18}, number = {1}, pages = {e70083}, pmid = {39825784}, issn = {1751-7915}, support = {2024YQFH05//"YiQi''funding project/ ; }, mesh = {*Akkermansia ; *Phosphatidylinositol 3-Kinases/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Proto-Oncogene Proteins c-akt/metabolism ; Animals ; *Disulfiram/pharmacology ; *RNA, Ribosomal, 16S/genetics ; *Chemical and Drug Induced Liver Injury/prevention & control ; Male ; Apoptosis/drug effects ; Signal Transduction/drug effects ; Disease Models, Animal ; Hepatocytes/drug effects ; Mice ; DNA, Ribosomal/genetics/chemistry ; }, abstract = {Acetaminophen induced acute liver injury (ALI) has a high incidence and is a serious medical problem, but there is a lack of effective treatment. The enterohepatic axis is one of the targets of recent attention due to its important role in liver diseases. Disulfiram (DSF) is a multitarget drug that has been proven to play a role in a variety of liver diseases and can affect intestinal flora, but whether it can alleviate ALI is not clear. We utilised bacterial 16S rRNA gene profiling, antimicrobial treatments, and faecal microbiota transplantation tests to explore whether DSF therapy for ALI is dependent on gut microbiota. Our findings indicate that DSF primarily restores intestinal microbiome balance by modulating the abundance of Akkermansia muciniphila (A. muciniphila), leading to significant alleviation of ALI symptoms in a gut microbiota dependent manner. We also found that A. muciniphila can promote the activation of PI3K/Akt pathway, correct the Bcl-2/Bax ratio, and further inhibit hepatocyte apoptosis. In conclusion, DSF ameliorates ALI by modulating the intestinal microbiome and activating the PI3K/AKT pathway through A. muciniphila.}, } @article {pmid39824679, year = {2025}, author = {Elyas, S and Barata, P and Vaishampayan, U}, title = {Clinical Applications of Microbiome in Renal Cell Carcinoma.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2024.12.006}, pmid = {39824679}, issn = {2405-4569}, abstract = {Advancements in microbiome research reveal its impact on cancer treatment outcomes, particularly in renal cell carcinoma (RCC). While immune checkpoint inhibitors (ICIs) have improved survival in metastatic RCC, composition of the gut microbiome has the potential to influence their efficacy. Antibiotic-induced microbiome disruptions correlate with diminished outcomes, while strains such as Akkermansia muciniphila, Clostridium butyricum, and others enhance immune responses and progression-free survival. Some prebiotics such as inulin gel can alter the gut flora to overcome the resistant strains occurring in response to immune therapy. This mini-review explores microbiome-targeted interventions, such as pre/probiotics and fecal microbiota transplantation, for overcoming ICI resistance. Although promising, prospective randomized trials are needed to standardize clinical applications and optimize microbiome-targeted treatments. The standard use of gut-modulating therapy cannot be recommended at present outside of clinical trials. A double-blind placebo-controlled randomized trial of ICI ± gut modulating therapy is being planned in frontline therapy of advanced RCC (BIOFRONT trial by the Southwest Oncology Group).}, } @article {pmid39821840, year = {2025}, author = {Vinterberg, JE and Oddsdottir, J and Nye, M and Pinton, P}, title = {Management of Recurrent Clostridioides difficile Infection (rCDI): A Systematic Literature Review to Assess the Feasibility of Indirect Treatment Comparison (ITC).}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, pmid = {39821840}, issn = {2193-8229}, abstract = {Recurrent Clostridioides difficile infection (rCDI) is a major cause of increased morbidity, mortality, and healthcare costs. Fecal-microbiota-based therapies are recommended for rCDI on completion of standard-of-care (SoC) antibiotics to prevent further recurrence: these therapies include conventional fecal-microbiota transplantation and the US Food and Drug Administration-approved therapies REBYOTA® (RBL) and VOWST Oral Spores™ (VOS). As an alternative to microbiota-based therapies, bezlotoxumab, a monoclonal antibody, is used as adjuvant to SoC antibiotics to prevent rCDI. There are no head-to-head clinical trials comparing different microbiota-based therapies or bezlotoxumab for rCDI. To address this gap, we conducted a systematic literature review to identify clinical trials on rCDI treatments and assess the feasibility of using them to conduct an indirect treatment comparison (ITC). The feasibility analysis determined that trial heterogeneity, particularly relating to inclusion criteria, may significantly compromise ITC and prevent cross-trial comparisons. Our analysis underlines the need to adopt standardized protocols to ensure comparability across trials.}, } @article {pmid39821715, year = {2025}, author = {Berry, P and Khanna, S}, title = {The evolving landscape of live biotherapeutics in the treatment of Clostridioides difficile infection.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {39821715}, issn = {0975-0711}, abstract = {Clostridioides difficile (C. difficile) infection (CDI) is common after antibiotic exposure and presents significant morbidity, mortality and healthcare costs worldwide. The rising incidence of recurrent CDI, driven by hypervirulent strains, widespread antibiotic use and increased community transmission, has led to an urgent need for novel therapeutic strategies. Conventional antibiotic treatments, although effective, face limitations due to rising antibiotic resistance and high recurrence rates, which can reach up to 60% after multiple infections. This has prompted exploration of alternative therapies such as fecal microbiota-based therapies, including fecal microbiota transplantation (FMT) and live biotherapeutics (LBPs), which demonstrate superior efficacy in preventing recurrence. They are aimed at restoring the gut microbiota. Fecal microbiota, live-jslm and fecal microbiota spores, live-brpk have been approved by the U.S. Food and Drug Administration in individuals aged 18 years or older for recurrent CDI after standard antimicrobial treatment. They have demonstrated high efficacy and a favorable safety profile in clinical trials. Another LBP under study includes VE-303, which is not derived from human donor stool. This review provides a comprehensive overview of the current therapeutic landscape for CDI, including its epidemiology, pathophysiology, risk factors, diagnostic modalities and treatment strategies. The review delves into the emerging role of live biotherapeutics, with a particular focus on fecal microbiota-based therapies. We explore their development, mechanisms of action, clinical applications and potential to revolutionize CDI management.}, } @article {pmid39821305, year = {2025}, author = {Shi, L and Duan, Y and Fang, N and Zhang, N and Yan, S and Wang, K and Hou, T and Wang, Z and Jiang, X and Gao, Q and Zhang, S and Li, Y and Zhang, Y and Gong, Y}, title = {Lactobacillus gasseri prevents ibrutinib-associated atrial fibrillation through butyrate.}, journal = {Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/europace/euaf018}, pmid = {39821305}, issn = {1532-2092}, abstract = {Ibrutinib, a widely used anti-cancer drug, is known to significantly increase the susceptibility to atrial fibrillation (AF). While it is recognized that drugs can reshape the gut microbiota, influencing both therapeutic effectiveness and adverse events, the role of gut microbiota in ibrutinib-induced AF remains largely unexplored. Utilizing 16S rRNA gene sequencing, fecal microbiota transplantation, metabonomics, electrophysiological examination, and molecular biology methodologies, we sought to validate the hypothesis that gut microbiota dysbiosis promotes ibrutinib-associated AF and to elucidate the underlying mechanisms. We found that ibrutinib administration predisposes rats to AF. Interestingly, ibrutinib-associated microbial transplantation conferred increased susceptibility to AF in rats. Notably, ibrutinib induced a significantly decrease in the abundance of Lactobacillus gasseri (L. gasseri), and oral supplementation of L. gasseri or its metabolite, butyrate, effectively prevented rats from ibrutinib-induced AF. Mechanistically, butyrate inhibits the generation of reactive oxygen species (ROS), thereby ameliorating atrial structural remodeling. Furthermore, we demonstrated that ibrutinib inhibited the growth of L. gasseri by disrupting the intestinal barrier integrity. Collectively, our findings provide compelling experimental evidence supporting the potential efficacy of targeting gut microbes in preventing ibrutinib-associated AF, opening new avenues for therapeutic interventions.}, } @article {pmid39747680, year = {2025}, author = {Menon, R and Bhattarai, SK and Crossette, E and Prince, AL and Olle, B and Silber, JL and Bucci, V and Faith, J and Norman, JM}, title = {Multi-omic profiling a defined bacterial consortium for treatment of recurrent Clostridioides difficile infection.}, journal = {Nature medicine}, volume = {31}, number = {1}, pages = {223-234}, pmid = {39747680}, issn = {1546-170X}, mesh = {*Clostridium Infections/therapy/microbiology ; Humans ; *Clostridioides difficile ; *Recurrence ; *Gastrointestinal Microbiome ; *Anti-Bacterial Agents/therapeutic use ; Feces/microbiology ; Male ; Female ; Fecal Microbiota Transplantation ; Middle Aged ; Bile Acids and Salts/metabolism ; Adult ; Aged ; Multiomics ; }, abstract = {Donor-derived fecal microbiota treatments are efficacious in preventing recurrent Clostridioides difficile infection (rCDI), but they have inherently variable quality attributes, are difficult to scale and harbor the risk of pathogen transfer. In contrast, VE303 is a defined consortium of eight purified, clonal bacterial strains developed for prevention of rCDI. In the phase 2 CONSORTIUM study, high-dose VE303 was well tolerated and reduced the odds of rCDI by more than 80% compared to placebo. VE303 organisms robustly colonized the gut in the high-dose group and were among the top taxa associated with non-recurrence. Multi-omic modeling identified antibiotic history, baseline stool metabolites and serum cytokines as predictors of both on-study CDI recurrence and VE303 colonization. VE303 potentiated early recovery of the host microbiome and metabolites with increases in short-chain fatty acids, secondary bile acids and bile salt hydrolase genes after antibiotic treatment for CDI, which is considered important to prevent CDI recurrences. These results support the idea that VE303 promotes efficacy in rCDI through multiple mechanisms.}, } @article {pmid39816955, year = {2025}, author = {Wang, Q and Ji, J and Xiao, S and Wang, J and Yan, X and Fang, L}, title = {Explore Alteration of Lung and Gut Microbiota in a Murine Model of OVA-Induced Asthma Treated by CpG Oligodeoxynucleotides.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {445-461}, pmid = {39816955}, issn = {1178-7031}, abstract = {AIM: We sought to investigate the impact of CpG oligodeoxynucleotides (CpG-ODN) administration on the lung and gut microbiota in asthmatic mice, specifically focusing on changes in composition, diversity, and abundance, and to elucidate the microbial mechanisms underlying the therapeutic effects of CpG-ODN and identify potential beneficial bacteria indicative of its efficacy.

METHODS: HE staining were used to analyze inflammation in lung, colon and small intestine tissues. High-throughput sequencing technology targeting 16S rRNA was employed to analyze the composition, diversity, and correlation of microbiome in the lung, colon and small intestine of control, model and CpG-ODN administration groups.

RESULTS: (1) Histopathologically, both lung and intestinal tissue in asthmatic mice exhibited significant structural damage and inflammatory response, whereas the structure of both lung and intestinal tissue approached normal levels, accompanied by a notable improvement in the inflammatory response after CpG-ODN treatment. (2) In the specific microbiota composition analysis, bacterial dysbiosis observed in the asthmatic mice, accompanied by enrichment of Proteobacteria found to cause lung and intestinal epithelial damage and inflammatory reaction. After CpG-ODN administration, bacterial dysbiosis was improved, and a notable enrichment of beneficial bacteria, indicating a novel microecology. Meanwhile Oscillospira and Clostridium were identified as two biomarkers of the CpG-ODN treatment. (3) Heatmap analysis revealed significant correlations among lung, small intestine, and colon microbiota.

CONCLUSION: CpG-ODN treatment can ameliorate OVA-induced asthma in mice. One side, preserving the structural integrity of the lung and intestine, safeguarding the mucosal physical barrier, the other side, improving the dysbiosis of lung and gut microbiota in asthmatic mice. Beneficial bacteria and metabolites take up microecological advantages, regulate immune cells and participate in the mucosal immune response to protect the immune barrier. Meanwhile, Oscillospira and Clostridium as biomarkers for CpG-ODN treatment, has reference significance for exploring precise Fecal microbiota transplantation treatment for asthma.}, } @article {pmid39814666, year = {2025}, author = {Shekhar, S and Schwarzer, M and Dhariwal, A and Petersen, FC}, title = {Nasal microbiota transplantation: a gateway to novel treatments.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2024.12.010}, pmid = {39814666}, issn = {1878-4380}, abstract = {Two recent studies have highlighted the potential of nasal microbiota transplantation (NMT) to treat chronic rhinosinusitis (CRS). Here we evaluate these findings and propose that lessons from fecal microbiota transplantation (FMT) could guide NMT development, with possible implications for combating antimicrobial resistance in respiratory infections.}, } @article {pmid39813598, year = {2025}, author = {Ren, M and Xia, Y and Pan, H and Zhou, X and Yu, M and Ji, F}, title = {Duodenal-jejunal bypass ameliorates MASLD in rats by regulating gut microbiota and bile acid metabolism through FXR pathways.}, journal = {Hepatology communications}, volume = {9}, number = {2}, pages = {}, pmid = {39813598}, issn = {2471-254X}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Rats ; *Bile Acids and Salts/metabolism ; *Duodenum/surgery/metabolism/microbiology ; Male ; *Fecal Microbiota Transplantation ; Jejunum/surgery/metabolism ; Rats, Sprague-Dawley ; Disease Models, Animal ; Fatty Liver/metabolism ; Anti-Bacterial Agents/pharmacology ; Diet, High-Fat ; Gastric Bypass ; Insulin Resistance ; }, abstract = {BACKGROUND: Although bariatric and metabolic surgical methods, including duodenal-jejunal bypass (DJB), were shown to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical trials and experimental rodent models, their underlying mechanisms remain unclear. The present study therefore evaluated the therapeutic effects and mechanisms of action of DJB in rats with MASLD.

METHODS: Rats with MASLD were randomly assigned to undergo DJB or sham surgery. Rats were orally administered a broad-spectrum antibiotic cocktail (Abx) or underwent fecal microbiota transplantation to assess the role of gut microbiota in DJB-induced improvement of MASLD. Gut microbiota were profiled by 16S rRNA gene sequencing and metagenomic sequencing, and bile acids (BAs) were analyzed by BA-targeted metabolomics.

RESULTS: DJB alleviated hepatic steatosis and insulin resistance in rats with diet-induced MASLD. Abx depletion of bacteria abrogated the ameliorating effects of DJB on MASLD. Fecal microbiota transplantation from rats that underwent DJB improved MASLD in high-fat diet-fed recipients by reshaping the gut microbiota, especially by significantly reducing the abundance of Clostridium. This, in turn, suppressed secondary BA biosynthesis and activated the hepatic BA receptor, farnesoid X receptor. Inhibition of farnesoid X receptor attenuated the ameliorative effects of post-DJB microbiota on MASLD.

CONCLUSIONS: DJB ameliorates MASLD by regulating gut microbiota and BA metabolism through hepatic farnesoid X receptor pathways.}, } @article {pmid39812804, year = {2025}, author = {Sobral, J and Empadinhas, N and Esteves, AR and Cardoso, SM}, title = {Impact of Nutrition on the Gut Microbiota: Implications for Parkinson's Disease.}, journal = {Nutrition reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/nutrit/nuae208}, pmid = {39812804}, issn = {1753-4887}, support = {//Portuguese national funds/ ; //FCT/ ; }, abstract = {Parkinson's disease (PD) is a multifactorial neurodegenerative disease that is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and by the anomalous accumulation of α-synuclein aggregates into Lewy bodies and Lewy neurites. Research suggests 2 distinct subtypes of PD: the brain-first subtype if the pathology arises from the brain and then spreads to the peripheral nervous system (PNS) and the body-first subtype, where the pathological process begins in the PNS and then spreads to the central nervous system. This review primarily focuses on the body-first subtype. The influence of the gut microbiota on the development of PD has been the subject of growing interest among researchers. It has been suggested that gut inflammation may be closely associated with pathogenesis in PD, therefore leading to the hypothesis that gut microbiota modulation could play a significant role in this process. Nutrition can influence gut health and alter the risk and progression of PD by altering inflammatory markers. This review provides an overview of recent research that correlates variations in gut microbiota composition between patients with PD and healthy individuals with the impact of certain nutrients and dietary patterns, including the Mediterranean diet, the Western diet, and the ketogenic diet. It explores how these diets influence gut microbiota composition and, consequently, the risk of PD. Last, it examines fecal transplantation and the use of prebiotics, probiotics, or synbiotics as potential therapeutic strategies to balance the gut microbiome, aiming to reduce the risk or delay the progression of PD.}, } @article {pmid39812540, year = {2025}, author = {Cerna, C and Vidal-Herrera, N and Silva-Olivares, F and Álvarez, D and González-Arancibia, C and Hidalgo, M and Aguirre, P and González-Urra, J and Astudillo-Guerrero, C and Jara, M and Porras, O and Cruz, G and Hodar, C and Llanos, P and Urrutia, P and Ibacache-Quiroga, C and Nevzorova, Y and Cubero, FJ and Fuenzalida, M and Thomas-Valdés, S and Jorquera, G}, title = {Fecal Microbiota Transplantation from Young-Trained Donors Improves Cognitive Function in Old Mice Through Modulation of the Gut-Brain Axis.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1089}, pmid = {39812540}, issn = {2152-5250}, abstract = {The gut-brain axis is a bidirectional communication pathway that modulates cognitive function. A dysfunctional gut-brain axis has been associated with cognitive impairments during aging. Therefore, we propose evaluating whether modulation of the gut microbiota through fecal microbiota transplantation (FMT) from young-trained donors (YT) to middle-aged or aged mice could enhance brain function and cognition in old age. Twelve-month-old male mice received an initial FMT from YT (YT-Tr) or age-matched donors (Auto-Tr) following antibiotic treatment. Three months later, the mice received a second FMT as reinforcement. Additionally, 18-month-old mice received Auto-Tr, YT-Tr, or FMT from young sedentary donors (YS-Tr). Cognitive function was assessed using novel object recognition and object location memory tests. Long-term potentiation (LTP) in hippocampal brain slices was studied, while neuroinflammation and synaptic plasticity were analyzed in hippocampal samples via qPCR and immunoblot. Gut permeability was evaluated in ileum and colon sections, serum samples were analyzed for cytokine levels, and fecal samples were used to measure short-chain fatty acid (SCFA) levels and perform 16S rRNA gene sequencing. We observed that YT-Tr, whether performed in middle age or old age, improved cognitive function in aged mice. Recognition and spatial memory were significantly enhanced in YT-Tr mice compared to Auto-Tr and YS-Tr groups. Intact LTP was observed in YT-Tr mice at 18 months of age, whereas LTP was impaired in the Auto-Tr group. Neuroinflammation was reduced, and synaptic plasticity modulators such as PSD-95 and FNDC5/Irisin were upregulated in the hippocampus of YT-Tr mice compared to both YS-Tr and Auto-Tr groups. A significant reduction in ileal and colon permeability was detected in YT-Tr animals, along with elevated cecal levels of butyrate and valerate compared to Auto-Tr. Moreover, YT-Tr decreased pro-inflammatory factors and increased anti-inflammatory factors in the serum of aged mice. Beta diversity analysis revealed significant differences in microbial community composition between YT-Tr and Auto-Tr animals, with higher abundances of Akkermansia, Prevotellaceae_UCG-001, and Odoribacter in YT-Tr mice. In conclusion, our study demonstrates that FMT from young-trained donors improves cognitive function and synaptic plasticity by modulating gut permeability, inflammation, SCFA levels, and gut microbiota composition in aged mice.}, } @article {pmid39812347, year = {2025}, author = {Gustafson, KL and Rodriguez, TR and McAdams, ZL and Coghill, LM and Ericsson, AC and Franklin, CL}, title = {Failure of colonization following gut microbiota transfer exacerbates DSS-induced colitis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447815}, pmid = {39812347}, issn = {1949-0984}, support = {T32 GM008396/GM/NIGMS NIH HHS/United States ; T32 OD011126/OD/NIH HHS/United States ; U42 OD010918/OD/NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Colitis/microbiology/chemically induced/pathology ; *Dextran Sulfate ; Mice ; *Disease Models, Animal ; *Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; Bacteria/classification/isolation & purification/genetics/metabolism ; Female ; Specific Pathogen-Free Organisms ; Feces/microbiology ; Inflammatory Bowel Diseases/microbiology ; Male ; }, abstract = {To study the impact of differing specific pathogen-free gut microbiomes (GMs) on a murine model of inflammatory bowel disease, selected GMs were transferred using embryo transfer (ET), cross-fostering (CF), and co-housing (CH). Prior work showed that the GM transfer method and the microbial composition of donor and recipient GMs can influence microbial colonization and disease phenotypes in dextran sodium sulfate-induced colitis. When a low richness GM was transferred to a recipient with a high richness GM via CH, the donor GM failed to successfully colonize, and a more severe disease phenotype resulted when compared to ET or CF, where colonization was successful. By comparing CH and gastric gavage for fecal material transfer, we isolated the microbial component of this effect and determined that differences in disease severity and survival were associated with microbial factors rather than the transfer method itself. Mice receiving a low richness GM via CH and gastric gavage exhibited greater disease severity and higher expression of pro-inflammatory immune mediators compared to those receiving a high richness GM. This study provides valuable insights into the role of GM composition and colonization in disease modulation.}, } @article {pmid39812329, year = {2025}, author = {Zhang, Y and Wang, A and Zhao, W and Qin, J and Zhang, Y and Liu, B and Yao, C and Long, J and Yuan, M and Yan, D}, title = {Microbial succinate promotes the response to metformin by upregulating secretory immunoglobulin a in intestinal immunity.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2450871}, pmid = {39812329}, issn = {1949-0984}, mesh = {*Metformin/pharmacology ; Animals ; *Immunoglobulin A, Secretory/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Succinic Acid/metabolism ; Up-Regulation/drug effects ; Diabetes Mellitus, Type 2/immunology/drug therapy/metabolism/microbiology ; Bacteroides thetaiotaomicron/drug effects ; Intestines/immunology/microbiology/drug effects ; Male ; Fecal Microbiota Transplantation ; Female ; Hypoglycemic Agents/pharmacology ; Mice, Inbred C57BL ; Mice, Knockout ; }, abstract = {Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus; however, many patients respond poorly to this drug in clinical practice. The potential involvement of microbiota-mediated intestinal immunity and related signals in metformin responsiveness has not been previously investigated. In this study, we successfully constructed a humanized mouse model by fecal transplantation of the gut microbiota from clinical metformin-treated - responders and non-responders, and reproduced the difference in clinical phenotypes of responsiveness to metformin. The abundance of Bacteroides thetaiotaomicron, considered a representative differential bacterium of metformin responsiveness, and the level of secretory immunoglobulin A (SIgA) in intestinal immunity increased significantly in responder recipient mice following metformin treatment. In contrast, no significant alterations in B. thetaiotaomicron and SIgA were observed in non-responder recipient mice. The study of IgA[-/-] mice confirmed that downregulated expression or deficiency of SIgA resulted in non-response to metformin, meaning that metformin was unable to improve dysfunctional glucose metabolism and reduce intestinal and adipose tissue inflammation, ultimately leading to systemic insulin resistance. Furthermore, supplementation with succinate, a microbial product of B. thetaiotaomicron, potentially reversed the non-response to metformin by inducing the production of SIgA. In conclusion, we demonstrated that upregulated SIgA, which could be regulated by succinate, was functionally involved in metformin response through its influence on immune cell-mediated inflammation and insulin resistance. Conversely, an inability to regulate SIgA may result in a lack of response to metformin.}, } @article {pmid39812000, year = {2025}, author = {Zhao, H and Fu, X and Wang, Y and Shang, Z and Li, B and Zhou, L and Liu, Y and Liu, D and Yi, B}, title = {Therapeutic Potential of Vanillic Acid in Ulcerative Colitis Through Microbiota and Macrophage Modulation.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e202400785}, doi = {10.1002/mnfr.202400785}, pmid = {39812000}, issn = {1613-4133}, support = {81760587//National Natural Science Foundation of China/ ; 81760731)//National Natural Science Foundation of China/ ; }, abstract = {This study investigated the protective effects of the dietary polyphenol vanillic acid (VA) on dextran sulfate sodium-induced acute ulcerative colitis (UC) in mice, focusing on its impact on the gut microbiota and inflammatory responses. VA was supplemented following dextran sulfate sodium administration, and key indicators, including body weight, disease activity index, colon length, spleen index, and inflammatory markers, were assessed. VA supplementation significantly alleviated UC symptoms, preserved intestinal barrier integrity, and reduced pro-inflammatory cytokine levels. Additionally, VA positively altered the gut microbiota composition, promoting beneficial bacteria such as Akkermansia muciniphila while suppressing the arachidonic acid metabolism pathway. Fecal microbiota transplantation confirmed that the VA-modified gut microbiota contributed to these protective effects. VA also facilitated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, further mitigating inflammation. These findings highlight the potential of VA as a natural dietary intervention for UC, emphasizing its role in regulating the gut microbiota and inflammatory pathways, which may have significant nutritional relevance in managing inflammatory bowel diseases.}, } @article {pmid39816646, year = {2023}, author = {Karukappadath, RM and Sirbu, D and Zaky, A}, title = {Drug-resistant bacteria in the critically ill: patterns and mechanisms of resistance and potential remedies.}, journal = {Frontiers in antibiotics}, volume = {2}, number = {}, pages = {1145190}, pmid = {39816646}, issn = {2813-2467}, abstract = {Antimicrobial resistance in the intensive care unit is an ongoing global healthcare concern associated with high mortality and morbidity rates and high healthcare costs. Select groups of bacterial pathogens express different mechanisms of antimicrobial resistance. Clinicians face challenges in managing patients with multidrug-resistant bacteria in the form of a limited pool of available antibiotics, slow and potentially inaccurate conventional diagnostic microbial modalities, mimicry of non-infective conditions with infective syndromes, and the confounding of the clinical picture of organ dysfunction associated with sepsis with postoperative surgical complications such as hemorrhage and fluid shifts. Potential remedies for antimicrobial resistance include specific surveillance, adequate and systematic antibiotic stewardship, use of pharmacokinetic and pharmacodynamic techniques of therapy, and antimicrobial monitoring and adequate employment of infection control policies. Novel techniques of combating antimicrobial resistance include the use of aerosolized antibiotics for lung infections, the restoration of gut microflora using fecal transplantation, and orally administered probiotics. Newer antibiotics are urgently needed as part of the armamentarium against multidrug-resistant bacteria. In this review we discuss mechanisms and patterns of microbial resistance in a select group of drug-resistant bacteria, and preventive and remedial measures for combating antibiotic resistance in the critically ill.}, } @article {pmid39811933, year = {2025}, author = {Zhang, L and Wang, K and Huang, L and Deng, B and Chen, C and Zhao, K and Wang, W}, title = {Ganoderic Acid A Alleviates Severe Acute Pancreatitis by Modulating Gut Homeostasis and Inhibiting TLR4-NLRP3 Signaling.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {2}, pages = {1563-1579}, pmid = {39811933}, issn = {1520-5118}, mesh = {Animals ; *Toll-Like Receptor 4/metabolism/genetics ; Mice ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Signal Transduction/drug effects ; *Pancreatitis/drug therapy/metabolism/immunology ; Male ; *Mice, Inbred C57BL ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Homeostasis/drug effects ; *Heptanoic Acids/pharmacology ; Mice, Knockout ; Pancreas/immunology/metabolism/drug effects ; Rats ; Lanosterol/analogs & derivatives ; }, abstract = {Background Severe acute pancreatitis (SAP) manifests as a critical state marked by acute abdominal symptoms, often associated with intestinal barrier dysfunction, exacerbating SAP retroactively. Ganoderic acid A (GAA) demonstrates anti-inflammatory properties in various inflammatory disorders. Nonetheless, its potential therapeutic impact on SAP and the underlying mechanisms remain unexplored. Methods In both wild-type and TLR4[-/-] mice, experimental SAP was induced using caerulein plus lipopolysaccharide. Caerulein injections were administered intraperitoneally following 7 days of intragastric GAA administration. Additionally, the potential mechanisms by which GAA ameliorates SAP were further investigated using fecal microbiota transplantation and TLR4-overexpressing IEC-6 cells. Results We observed that GAA treatment significantly ameliorated serum levels of amylase, lipase, and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in SAP mice. Pretreatment with GAA mitigated pathological injuries and reduced M1 macrophage and neutrophil infiltration in pancreatic or ileal tissues. Additionally, GAA treatment down-regulated TLR4-MAPK/NF-κB signaling and NLRP3 inflammasome activation in the pancreatic and ileal tissues of SAP mice. The results further revealed that the gavage of GAA decreased bacterial translocation (Escherichia coli and EUB338), repaired intestinal barrier dysfunction (ZO-1, occludin, DAO, and FITC), increased lysozyme and MUC2 expression, and raised the levels of short-chain fatty acids. Analysis of the gut microbiome showed that the beneficial effects of GAA treatment were associated with improvements in pancreatitis-associated gut microbiota dysbiosis, characterized by notable increases in α-diversity and the abundance of probiotics such as Akkermansia, GCA-900066575, and Parvibacter. Fecal transplantation experiments further confirmed that GAA exerts protective effects by modulating intestinal flora. The protective role of GAA in intestinal and pancreatic injuries is mediated by the inhibition of TLR4 signaling, as further evidenced in TLR4-deficient mice and TLR4-overexpressed IEC-6 cells. The results of docking indicated that GAA interacts with TLR4 via a hydrophobic interaction. Conclusions The study demonstrates that GAA significantly alleviates SAP through its anti-inflammatory and antioxidant capacities, as well as by restoring intestinal homeostasis, thereby providing insights into novel treatments for SAP.}, } @article {pmid39811913, year = {2025}, author = {Ribeiro, G and Schellekens, H and Cuesta-Marti, C and Maneschy, I and Ismael, S and Cuevas-Sierra, A and Martínez, JA and Silvestre, MP and Marques, C and Moreira-Rosário, A and Faria, A and Moreno, LA and Calhau, C}, title = {A Menu for Microbes: Unraveling Appetite Regulation and Weight Dynamics Through the Microbiota-Brain Connection Across the Lifespan.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00227.2024}, pmid = {39811913}, issn = {1522-1547}, support = {UIDB/4255/2020//Centro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS)/ ; UIDP/4255/2020//Centro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS)/ ; UIDP/04923/2020//Comprehensive Health Research Centre/ ; UIDB/04923/2020//Comprehensive Health Research Centre/ ; SFI/12/RC/2273 _P2//Science Foundation Ireland (SFI)/ ; TC20180025//Food for Health Ireland EI Technology Centre/ ; GOIPG/2023/4836//Irish Research Council (IrishResearch)/ ; CD22/00011//Ministerio de Ciencia e Innovación (MCIN)/ ; MV23/00115//Instituto Carlos III de Salud/ ; Y2020/6600//Comunidad de Madrid (Community of Madrid)/ ; 2020.06333.BD//Fundacao para a Ciencia e a Technologia/ ; }, abstract = {Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut microbiota-targeted approaches such as pre- pro- post- and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is (1) to provide an overview of the role of the microbiota-gut-brain-axis in appetite regulation across the lifespan and (2) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.}, } @article {pmid39811513, year = {2025}, author = {Wang, Y and Liu, J}, title = {Interplay between creeping fat and gut microbiota: A brand-new perspective on fecal microbiota transplantation in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {2}, pages = {100024}, pmid = {39811513}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/therapy/immunology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Animals ; *Dysbiosis ; Mice ; *Disease Models, Animal ; Mesentery ; Adipose Tissue ; Recurrence ; Permeability ; Treatment Outcome ; Intestinal Mucosa/microbiology ; }, abstract = {Inflammatory bowel disease, particularly Crohn's disease (CD), has been linked to modifications in mesenteric adipose tissue (MAT) and the phenomenon known as "creeping fat" (CrF). The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD. Notably, the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence, indicating the significant role of MAT in the pathogenesis of CD. While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD, the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous. This manuscript commentary discusses a recent basic research conducted by Wu et al. In their study, intestinal bacteria from individuals were transplanted into CD model mice, revealing that fecal microbiota transplantation (FMT) from healthy donors alleviated CD symptoms, whereas FMT from CD patients exacerbated these symptoms. Importantly, FMT was found to affect intestinal permeability, barrier function, and the levels of proinflammatory factors and adipokines. Collectively, these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD. However, the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota. Overall, the gut microbiota plays a crucial role in the histopathology of CD, and thus, targeting MAT and CrF may represent a promising avenue for treatment in this patient population.}, } @article {pmid39811502, year = {2025}, author = {Qiao, T and Wen, XH}, title = {Exploring gut microbiota as a novel therapeutic target in Crohn's disease: Insights and emerging strategies.}, journal = {World journal of gastroenterology}, volume = {31}, number = {2}, pages = {100827}, pmid = {39811502}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/therapy/immunology ; Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Dysbiosis ; Enteral Nutrition/methods ; Disease Progression ; Animals ; }, abstract = {Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.}, } @article {pmid39810863, year = {2024}, author = {Uździcki, AW and Wawrzynowicz-Syczewska, M}, title = {Impact of liver transplantation on intestinal and systemic inflammation markers in patients with colitis ulcerosa concomitant with primary sclerosing cholangitis.}, journal = {Przeglad gastroenterologiczny}, volume = {16}, number = {4}, pages = {439-445}, pmid = {39810863}, issn = {1895-5770}, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is an uncommon, chronic liver disease characterised by fibrosis and strictures of a bile ducts, causing cholestasis. In the long term it can lead to complete stenosis leading in turn to liver cirrhosis. In patients with severe form of the disease, the recommended treatment is liver transplantation. Because PSC frequently coexists with ulcerative colitis (UC), it is crucial to determine the effect of liver transplantation on the course of UC.

AIM: The aim was to determine the impact of liver transplantation on intestinal and systemic inflammation markers with UC concomitant with PSC (PSC-UC).

MATERIAL AND METHODS: Sixty-three patients with PSC-UC were enrolled, 25 of whom underwent liver transplantation (OLTx) due to PSC progression. Clinical symptoms, faecal calprotectin levels, C-reactive protein (CRP) serum concentration, erythrocyte sedimentation rate, and white blood cell count (WBC) were obtained.

RESULTS: Faecal calprotectin was significantly higher in the post-OLTx group. Mean calprotectin values were 163% higher - 474 ng/ml and 180 ng/ml (p = 0.024) in the post-OLTx group and in the PSC-UC group without the transplantation, respectively. Calprotectin levels exceeded the upper limit of normal (defined as 200 ng/l) in 66% of liver recipients and in 18% of non-transplanted patients (OR = 9.33, p = 0.011). In the post-OLTx group, also CRP concentration (11.01 mg/l vs. 6.54 mg/l, p = 0.30) and WBC (7.58 K/ml vs. 5.72 K/ml, p = 0.006) were higher than in the PSC-UC group without transplantation.

CONCLUSIONS: We found significantly higher inflammation markers in PSC-UC patients who underwent liver transplantation due to PSC. The effect was strongest in faecal calprotectin levels. In PSC-UC patients after liver transplantation, intensification of UC treatment may be needed, despite the lack of worsening of clinical symptoms.}, } @article {pmid39809955, year = {2025}, author = {Kumar, D and Bishnoi, M and Kondepudi, KK and Sharma, SS}, title = {Gut Microbiota-Based Interventions for Parkinson's Disease: Neuroprotective Mechanisms and Current Perspective.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39809955}, issn = {1867-1314}, abstract = {Recent evidence links gut microbiota alterations to neurodegenerative disorders, including Parkinson's disease (PD). Replenishing the abnormal composition of gut microbiota through gut microbiota-based interventions "prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT)" has shown beneficial effects in PD. These interventions increase gut metabolites like short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1), which may protect dopaminergic neurons via the gut-brain axis. Neuroprotective effects of these interventions are mediated by several mechanisms, including the enhancement of neurotrophin and activation of the PI3K/AKT/mTOR signaling pathway, GLP-1-mediated gut-brain axis signaling, Nrf2/ARE pathway, and autophagy. Other pathways, such as free fatty acid receptor activation, synaptic plasticity improvement, and blood-brain and gut barrier integrity maintenance, also contribute to neuroprotection. Furthermore, the inhibition of the TLR4/NF-кB pathway, MAPK pathway, GSK-3β signaling pathway, miR-155-5p-mediated neuroinflammation, and ferroptosis could account for their protective effects. Clinical studies involving gut microbiota-based interventions have shown therapeutic benefits in PD patients, particularly in improving gastrointestinal dysfunction and some neurological symptoms. However, the effectiveness in alleviating motor symptoms remains mild. Large-scale clinical trials are still needed to confirm these findings. This review emphasizes the neuroprotective mechanisms of gut microbiota-based interventions in PD as supported by both preclinical and clinical studies.}, } @article {pmid39806466, year = {2025}, author = {Khemiri, H and Ben Fraj, I and Lorusso, A and Mekki, N and Mangone, I and Gdoura, M and Di Pasqual, A and Cammà, C and Di Lollo, V and Cherni, A and Touzi, H and Sadraoui, A and Meddeb, Z and Hogga, N and Ben Mustapha, I and Barbouche, MR and Ouederni, M and Triki, H and Haddad-Boubaker, S}, title = {SARS-CoV-2 excretion and genetic evolution in nasopharyngeal and stool samples from primary immunodeficiency and immunocompetent pediatric patients.}, journal = {Virology journal}, volume = {22}, number = {1}, pages = {9}, pmid = {39806466}, issn = {1743-422X}, mesh = {Humans ; *SARS-CoV-2/genetics/immunology ; *Feces/virology ; *Nasopharynx/virology ; *COVID-19/virology/immunology ; Child ; Male ; Female ; Child, Preschool ; *RNA, Viral/genetics ; *Virus Shedding ; Infant ; Phylogeny ; Evolution, Molecular ; Primary Immunodeficiency Diseases/genetics ; Adolescent ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Primary Immunodeficiency disorders (PID) can increase the risk of severe COVID-19 and prolonged infection. This study investigates the duration of SARS-CoV-2 excretion and the genetic evolution of the virus in pediatric PID patients as compared to immunocompetent (IC) patients.

MATERIALS AND METHODS: A total of 40 nasopharyngeal and 24 stool samples were obtained from five PID and ten IC children. RNA detection was performed using RT-qPCR, and whole-genome sequencing was conducted with the NexSeq 1000 platform. Data analysis used the nextflow/viralrecon pipeline. Hotspot amino acid frequencies were investigated using GraphPad Prism v10. Phylodynamic analysis was conducted with BEAST software.

RESULTS: In IC children, the viral excretion period lasted up to 14 days in nasopharyngeal swabs, with an average duration of 7 days, and ranged from 7 to 14 days in stool samples. In PID patients, the viral RNA was detected in nasopharyngeal for periods between 7 and 28 days, with an average duration of 15 days, and up to 28 days in stool samples. Two SARS-CoV-2 variants were detected in PID patients: Delta (AY.122) and Omicron (BA.1.1). Patients with antibody and combined deficiencies, exhibited the most prolonged shedding periods in both nasopharyngeal and stool samples and one patient presented complications and fatal outcome. Specific Hotspot amino acid changes were detected in PID: A2821V and R550H (ORF1ab).

CONCLUSION: Our findings underscore the prolonged excretion of SARS-CoV-2 RNA in patients with antibody and combined deficiencies. Thus, specialized care is essential for effectively managing PID patients.}, } @article {pmid39805780, year = {2024}, author = {Ye, LJ and Xu, XF and Chen, SY and Zhang, H and Gan, YX and Meng, T and Ding, R and Li, J and Cao, G and Wang, KL}, title = {[Regulation of Bifidobacterium-short chain fatty acid metabolism and improvement of intestinal toxicity of vinegar-processed Euphorbiae Pekinensis Radix].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {49}, number = {23}, pages = {6331-6341}, doi = {10.19540/j.cnki.cjcmm.20240912.301}, pmid = {39805780}, issn = {1001-5302}, mesh = {Mice ; Animals ; *Fatty Acids, Volatile/metabolism ; *Acetic Acid ; Humans ; Caco-2 Cells ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology/chemistry ; *Bifidobacterium/drug effects ; RAW 264.7 Cells ; Intestines/drug effects ; Male ; Intestinal Mucosa/metabolism/drug effects ; Feces/microbiology/chemistry ; }, abstract = {To explore the mechanism by which vinegar-processed Euphorbiae Pekinensis Radix regulates gut microbiota and reduces intestinal toxicity, this study aimed to identify key microbial communities related to vinegar-induced detoxification and verify their functions. Using a derivatization method, the study measured the content of short-chain fatty acids(SCFAs) in feces before and after vinegar-processing of Euphorbiae Pekinensis Radix. Combined with the results of previous gut microbiota sequencing, correlation analysis was used to identify key microbial communities related to SCFAs content. Through single-bacterium transplantation experiments, the role of key microbial communities in regulating SCFAs metabolism and alleviating the intestinal toxicity of Euphorbiae Pekinensis Radix was clarified. Fecal extracts were then added to a co-culture system of Caco-2 and RAW264.7 cells, and toxicity differences were evaluated using intestinal tight junction proteins and inflammatory factors as indicators. Additionally, the application of a SCFAs receptor blocker helped confirm the role of SCFAs in reducing intestinal toxicity during vinegar-processing of Euphorbiae Pekinensis Radix. The results of this study indicated that vinegar-processing of Euphorbiae Pekinensis Radix improved the decline in SCFAs content caused by the raw material. Correlation analysis revealed that Bifidobacterium was positively correlated with the levels of acetic acid, propionic acid, isobutyric acid, n-butyric acid, isovaleric acid, and n-valeric acid. RESULTS:: from single-bacterium transplantation experiments demonstrated that Bifidobacterium could mitigate the reduction in SCFAs content induced by raw Euphorbiae Pekinensis Radix, enhance the expression of tight junction proteins, and reduce intestinal inflammation. Similarly, cell experiment results confirmed that fecal extracts from Bifidobacterium-transplanted mice alleviated inflammation and increased the expression of tight junction proteins in intestinal epithelial cells. The use of the free fatty acid receptor-2 inhibitor GLPG0974 verified that this improvement effect was related to the SCFAs pathway. This study demonstrates that Bifidobacterium is the key microbial community responsible for reducing intestinal toxicity in vinegar-processed Euphorbiae Pekinensis Radix. Vinegar-processing increases the abundance of Bifidobacterium, elevates the intestinal SCFAs content, inhibits intestinal inflammation, and enhances the expression of tight junction proteins, thereby improving the intestinal toxicity of Euphorbiae Pekinensis Radix.}, } @article {pmid39804518, year = {2025}, author = {Claytor, JD and Lin, DL and Magnaye, KM and Guerrero, YS and Langelier, CR and Lynch, SV and El-Nachef, N}, title = {Effect of Fecal Microbiota Transplant on Antibiotic Resistance Genes Among Patients with Chronic Pouchitis.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {39804518}, issn = {1573-2568}, abstract = {BACKGROUND: Pouchitis is common among patients with ulcerative colitis (UC) who have had colectomy with ileal pouch-anal anastomosis. Antibiotics are first-line therapy for pouch inflammation, increasing the potential for gut colonization with multi-drug resistant organisms (MDRO). Fecal microbial transplant (FMT) is being studied in the treatment of pouchitis and in the eradication of MDRO. Prior work using aerobic antibiotic culture disks suggests that some patients with chronic pouchitis may regain fluoroquinolone sensitivity after FMT. However, gut MDRO include anaerobic, fastidious organisms that are difficult to culture using traditional methods.

AIM: We aimed to assess whether FMT reduced the abundance of antibiotic resistance genes (ARG) or affected resistome diversity, evenness, or richness in patients with chronic pouchitis.

METHODS: We collected clinical characteristics regarding infections and antibiotic exposures for 18 patients who had previously been enrolled in an observational study investigating FMT as a treatment for pouchitis. Twenty-six pre- and post-FMT stool samples were analyzed using FLASH (Finding Low Abundance Sequences by Hybridization), a CRISPR/Cas9-based shotgun metagenomic sequence enrichment technique that detects acquired and chromosomal bacterial ARGs. Wilcoxon rank sum tests were used to assess differences in clinical characteristics, ARG counts, resistome diversity and ARG richness, pre- and post-FMT.

RESULTS: All 13 of the patients with sufficient stool samples for analysis had recently received antibiotics for pouchitis prior to a single endoscopic FMT. Fecal microbiomes of all patients had evidence of multi-drug resistance genes and ESBL resistance genes at baseline; 62% encoded fluoroquinolone resistance genes. A numerical decrease in overall ARG counts was noted post-FMT, but no statistically significant differences were noted (P = 0.19). Richness and diversity were not significantly altered. Three patients developed infections during the 5-year follow-up period, none of which were associated with MDRO.

CONCLUSION: Antibiotic resistance genes are prevalent among antibiotic-exposed patients with chronic pouchitis. FMT led to a numerical decrease, but no statistically significant change in ARG, nor were there significant changes in the diversity, richness, or evenness of ARGs. Further investigations to improve FMT engraftment and to optimize FMT delivery in patients with inflammatory pouch disorders are warranted.}, } @article {pmid39801363, year = {2025}, author = {Chevalier, C and Tournier, BB and Marizzoni, M and Park, R and Paquis, A and Ceyzériat, K and Badina, AM and Lathuiliere, A and Saleri, S and Cillis, F and Cattaneo, A and Millet, P and Frisoni, GB}, title = {Fecal Microbiota Transplantation (FMT) From a Human at Low Risk for Alzheimer's Disease Improves Short-Term Recognition Memory and Increases Neuroinflammation in a 3xTg AD Mouse Model.}, journal = {Genes, brain, and behavior}, volume = {24}, number = {1}, pages = {e70012}, pmid = {39801363}, issn = {1601-183X}, support = {1216//Velux Stiftung/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; *Alzheimer Disease/therapy/microbiology ; Humans ; Female ; *Gastrointestinal Microbiome ; Memory, Short-Term/physiology ; Neuroinflammatory Diseases/therapy/metabolism ; Disease Models, Animal ; Hippocampus/metabolism ; Aged ; }, abstract = {Human microbiota-associated murine models, using fecal microbiota transplantation (FMT) from human donors, help explore the microbiome's role in diseases like Alzheimer's disease (AD). This study examines how gut bacteria from donors with protective factors against AD influence behavior and brain pathology in an AD mouse model. Female 3xTgAD mice received weekly FMT for 2 months from (i) an 80-year-old AD patient (AD-FMT), (ii) a cognitively healthy 73-year-old with the protective APOEe2 allele (APOEe2-FMT), (iii) a 22-year-old healthy donor (Young-FMT), and (iv) untreated mice (Mice-FMT). Behavioral assessments included novel object recognition (NOR), Y-maze, open-field, and elevated plus maze tests; brain pathology (amyloid and tau), neuroinflammation (in situ autoradiography of the 18 kDa translocator protein in the hippocampus); and gut microbiota were analyzed. APOEe2-FMT improved short-term memory in the NOR test compared to AD-FMT, without significant changes in other behavioral tests. This was associated with increased neuroinflammation in the hippocampus, but no effect was detected on brain amyloidosis and tauopathy. Specific genera, such as Parabacteroides and Prevotellaceae_UGC001, were enriched in the APOEe2-FMT group and associated with neuroinflammation, while genera like Desulfovibrio were reduced and linked to decreased neuroinflammation. Gut microbiota from a donor with a protective factor against AD improved short-term memory and induced neuroinflammation in regions strategic to AD. The association of several genera with neuroinflammation in the APOEe2-FMT group suggests a collegial effect of the transplanted microbiome rather than a single-microbe driver effect. These data support an association between gut bacteria, glial cell activation, and cognitive function in AD.}, } @article {pmid39800714, year = {2025}, author = {Sall, I and Foxall, R and Felth, L and Maret, S and Rosa, Z and Gaur, A and Calawa, J and Pavlik, N and Whistler, JL and Whistler, CA}, title = {Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446423}, pmid = {39800714}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Morphine/administration & dosage ; *Dysbiosis/microbiology ; Mice ; *Butyrates/metabolism ; Male ; *Fecal Microbiota Transplantation ; *Drug Tolerance ; *Analgesics, Opioid/administration & dosage/metabolism ; *Mice, Inbred C57BL ; Bacteria/metabolism/classification/genetics/drug effects ; Probiotics/administration & dosage ; }, abstract = {The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.}, } @article {pmid39800223, year = {2025}, author = {Lista, S and Munafò, A and Caraci, F and Imbimbo, C and Emanuele, E and Minoretti, P and Pinto-Fraga, J and Merino-País, M and Crespo-Escobar, P and López-Ortiz, S and Monteleone, G and Imbimbo, BP and Santos-Lozano, A}, title = {Gut microbiota in Alzheimer's disease: Understanding molecular pathways and potential therapeutic perspectives.}, journal = {Ageing research reviews}, volume = {104}, number = {}, pages = {102659}, doi = {10.1016/j.arr.2025.102659}, pmid = {39800223}, issn = {1872-9649}, abstract = {Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.}, } @article {pmid39800192, year = {2025}, author = {Bajaj, JS and Fagan, A and Gavis, EA and Sterling, RK and Gallagher, ML and Lee, H and Matherly, SC and Siddiqui, MS and Bartels, A and Mousel, T and Davis, BC and Puri, P and Fuchs, M and Moutsoglou, DM and Thacker, LR and Sikaroodi, M and Gillevet, PM and Khoruts, A}, title = {Microbiota transplant for hepatic encephalopathy in cirrhosis: The THEMATIC trial.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2024.12.047}, pmid = {39800192}, issn = {1600-0641}, abstract = {BACKGROUND: Preventing hepatic encephalopathy (HE) recurrence in cirrhosis, which is associated with an altered gut-liver-brain axis, is an unmet need. Fecal microbiota transplantation (FMT) is beneficial in phase-1 studies, but route and dose-related questions remain.

METHODS: We performed a phase-2 randomized, placebo-controlled, double-blind, clinical trial of capsule and enema FMT in cirrhosis and HE on lactulose and rifaximin. Subjects were randomized into 4 groups receiving 3 active and 0-placebo, 2 active and 1-placebo, 1 active and 2-placebo, or all 3-placebo doses. Each patient received two capsule and one enema FMT and were followed for six months.

PRIMARY OUTCOME: FMT-related serious adverse events/AEs using intention-to-treat analysis. Secondary outcomes were HE recurrence, all-cause hospitalizations, death, donor engraftment, and quality-of-life (QOL). FMT was from a vegan or omnivorous donor.

RESULTS: 60 patients (15/group) with similar baseline characteristics were enrolled.

PRIMARY OUTCOMES: FMT was safe without any FMT-related SAEs/ AEs.

SECONDARY OUTCOMES: Overall SAEs (p=0.96) or death (p=1.0) were similar. There were significant differences in HE recurrence between groups (p=0.035, Cramer's V=0.39). Post-hoc, recurrence was highest in all-placebo vs FMT [40% vs 9%, OR:0.15 (95% CI: 0.04, 0.64)]. Within FMT, HE-recurrence rates were similar regardless of route, doses, or donor type. QOL improved in FMT-recipient groups. Engraftment was highest in those with high pre-FMT Lachnospiraceae and lower in those whose HE recurred.

CONCLUSIONS: In a Phase 2 double-blind, placebo-controlled, randomized clinical trial in cirrhosis with HE on maximal therapy, FMT regardless of dose, route, or donor was safe without any FMT-related adverse events. On post-hoc analysis, groups differed on HE recurrence, which was highest in the placebo-only group and linked with lower baseline Lachnospiraceae and reduced donor engraftment.}, } @article {pmid39798925, year = {2025}, author = {Aleksandrova, RR and Nieuwenhuis, LM and Karmi, N and Zhang, S and Swarte, JC and Björk, JR and Gacesa, R and Blokzijl, H and Connelly, MA and Weersma, RK and Lisman, T and Festen, EAM and de Meijer, VE and , }, title = {Gut microbiome dysbiosis is not associated with portal vein thrombosis in patients with end-stage liver disease: a cross-sectional study.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtha.2024.12.036}, pmid = {39798925}, issn = {1538-7836}, abstract = {BACKGROUND: Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in ESLD patients is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a pro-inflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development.

OBJECTIVES: We investigated whether gut microbiome diversity, bacterial species, metabolic pathways, and TMAO levels are associated with PVT in ESLD patients.

METHODS: Fecal samples, plasma samples and data from ESLD patients and healthy controls were collected through the TransplantLines Biobank and Cohort Study. PVT was defined as a thrombus in the portal vein within a year prior to or after fecal sample collection. Fecal samples were analyzed using Shotgun Metagenomic Sequencing, and TMAO levels were measured in plasma using a Vantera® Clinical Analyzer.

RESULTS: 102 ESLD patients, of which 23 with PVT, and 246 healthy controls were included. No significant difference in gut microbiome diversity was found between patients with PVT and without PVT (P=0.18). Both ESLD groups had significantly lower alpha-diversity compared with controls. Bacteroides fragilis and three Clostridiales species were increased in patients with PVT compared to without PVT. TMAO levels between the three groups were not significantly different.

CONCLUSION: We observed profound differences in gut microbiota between ESLD patients and controls, but minimal differences between ESLD patients with or without PVT. In our cohort, a gut-derived pro-inflammatory state was not associated with presence of PVT in ESLD patients.}, } @article {pmid39797102, year = {2024}, author = {Díez-Madueño, K and de la Cueva Dobao, P and Torres-Rojas, I and Fernández-Gosende, M and Hidalgo-Cantabrana, C and Coto-Segura, P}, title = {Gut Dysbiosis and Adult Atopic Dermatitis: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {1}, pages = {}, pmid = {39797102}, issn = {2077-0383}, abstract = {Background/Objectives: Research on the relationship between gut microbiota (GM) and atopic dermatitis (AD) has seen a growing interest in recent years. The aim of this systematic review was to determine whether differences exist between the GM of adults with AD and that of healthy adults (gut dysbiosis). Methods: We conducted a systematic review based on the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed using PubMed, EMBASE, and Web of Science. Observational and interventional studies were analyzed. Results: Although the studies showed heterogeneous results, some distinguishing characteristics were found in the intestinal microbial composition of adults with dermatitis. Even though no significant differences in diversity were found between healthy and affected adults, certain microorganisms, such as Bacteroidales, Enterobacteriaceae, and Clostridium (perfringens), were more characteristic of the fecal microbiota in adults with AD. Healthy individuals exhibited lower abundances of aerobic bacteria and higher abundances of short-chain fatty acid-producing species and polyamines. Clinical trials showed that the consumption of probiotics (Bifidobacterium and/or Lactobacillus), fecal microbiota transplants, and balneotherapy modified the fecal microbiota composition of participants and were associated with significant improvements in disease management. Conclusions: In anticipation of forthcoming clinical trials, it is essential to conduct meta-analyses that comprehensively evaluate the effectiveness and safety of interventions designed to modify intestinal flora in the context of AD. Preliminary evidence suggests that certain interventions may enhance adult AD management.}, } @article {pmid39796717, year = {2024}, author = {Kumari, S and Srilatha, M and Nagaraju, GP}, title = {Effect of Gut Dysbiosis on Onset of GI Cancers.}, journal = {Cancers}, volume = {17}, number = {1}, pages = {}, pmid = {39796717}, issn = {2072-6694}, abstract = {Dysbiosis in the gut microbiota plays a significant role in GI cancer development by influencing immune function and disrupting metabolic functions. Dysbiosis can drive carcinogenesis through pathways like immune dysregulation and the release of carcinogenic metabolites, and altered metabolism, genetic instability, and pro-inflammatory signalling, contributing to GI cancer initiation and progression. Helicobacter pylori infection and genotoxins released from dysbiosis, lifestyle and dietary habits are other factors that contribute to GI cancer development. Emerging diagnostic and therapeutic approaches show promise in colorectal cancer treatment, including the multitarget faecal immunochemical test (mtFIT), standard FIT, and faecal microbiota transplantation (FMT) combined with PD-1 inhibitors. We used search engine databases like PubMed, Scopus, and Web of Science. This review discusses the role of dysbiosis in GI cancer onset and explores strategies such as FMT, probiotics, and prebiotics to enhance the immune response and improve cancer therapy outcomes.}, } @article {pmid39796536, year = {2024}, author = {Cuffaro, F and Lamminpää, I and Niccolai, E and Amedei, A}, title = {Nutritional and Microbiota-Based Approaches in Amyotrophic Lateral Sclerosis: From Prevention to Treatment.}, journal = {Nutrients}, volume = {17}, number = {1}, pages = {}, pmid = {39796536}, issn = {2072-6643}, support = {PNRR-MAD-2022-12375798//Ministero della Salute/ ; PE0000006//Ministry of University and Research (MUR)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy ; Probiotics/therapeutic use ; Brain-Gut Axis/physiology ; Fecal Microbiota Transplantation ; Fatty Acids, Omega-3 ; Prebiotics/administration & dosage ; Oxidative Stress ; Nutritional Status ; Diet, Mediterranean ; Antioxidants ; }, abstract = {Metabolic alterations, including hypermetabolism, lipid imbalances, and glucose dysregulation, are pivotal contributors to the onset and progression of Amyotrophic Lateral Sclerosis (ALS). These changes exacerbate systemic energy deficits, heighten oxidative stress, and fuel neuroinflammation. Simultaneously, gastrointestinal dysfunction and gut microbiota (GM) dysbiosis intensify disease pathology by driving immune dysregulation, compromising the intestinal barrier, and altering gut-brain axis (GBA) signaling, and lastly advancing neurodegeneration. Therapeutic and preventive strategies focused on nutrition offer promising opportunities to address these interconnected pathophysiological mechanisms. Diets enriched with antioxidants, omega-3 fatty acids, and anti-inflammatory compounds-such as the Mediterranean diet-have shown potential in reducing oxidative stress and systemic inflammation. Additionally, microbiota-targeted approaches, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, are emerging as innovative tools to restore microbial balance, strengthen gut integrity, and optimize GBA function. This review highlights the critical need for personalized strategies integrating immunonutrition and microbiota modulation to slow ALS progression, improve quality of life, and develop preventive measures for neurodegenerative and neuroinflammatory diseases. Future research should prioritize comprehensive dietary and microbiota-based interventions to uncover their therapeutic potential and establish evidence-based guidelines for managing ALS and related disorders.}, } @article {pmid39796390, year = {2025}, author = {Yu, R and Zhang, H and Chen, R and Lin, Y and Xu, J and Fang, Z and Ru, Y and Fan, C and Wu, G}, title = {Fecal Microbiota Transplantation from Methionine-Restricted Diet Mouse Donors Improves Alzheimer's Learning and Memory Abilities Through Short-Chain Fatty Acids.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39796390}, issn = {2304-8158}, support = {LQ22H260002//Natural Science Foundation of Zhejiang Province/ ; 82103836//National Natural Science Foundation of China/ ; }, abstract = {Alzheimer's disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer's learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.}, } @article {pmid39795549, year = {2024}, author = {Tsuji, K and Uchida, N and Nakanoh, H and Fukushima, K and Haraguchi, S and Kitamura, S and Wada, J}, title = {The Gut-Kidney Axis in Chronic Kidney Diseases.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {39795549}, issn = {2075-4418}, support = {24K11411//the Japanese Society for the Promotion of Science (JSPS)/Grant-in-Aid for Young Scientists/ ; }, abstract = {The gut-kidney axis represents the complex interactions between the gut microbiota and kidney, which significantly impact the progression of chronic kidney disease (CKD) and overall patient health. In CKD patients, imbalances in the gut microbiota promote the production of uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which impair renal function and contribute to systemic inflammation. Mechanisms like endotoxemia, immune activation and oxidative stress worsen renal damage by activating pro-inflammatory and oxidative pathways. Insights into these mechanisms highlight the impact of gut-derived metabolites, bacterial translocation, and immune response changes on kidney health, suggesting new potential approaches for CKD treatment. Clinical applications, such as dietary interventions, prebiotics, probiotics and fecal microbiota transplantation, are promising in adjusting the gut microbiota to alleviate CKD symptoms and slow disease progression. Current research highlights the clinical relevance of the gut-kidney axis, but further study is essential to clarify these mechanisms' diagnostic biomarkers and optimize therapeutic interventions. This review emphasizes the importance of an integrated approach to CKD management, focusing on the gut microbiota as a therapeutic target to limit kidney injury.}, } @article {pmid39736240, year = {2025}, author = {Qiu, M and Geng, H and Zou, C and Zhao, X and Zhao, C and Xie, J and Wang, J and Zhang, N and Hu, Y and Fu, Y and Wang, J and Hu, X}, title = {Intestinal inflammation exacerbates endometritis through succinate production by gut microbiota and SUCNR1-mediated proinflammatory response.}, journal = {International immunopharmacology}, volume = {146}, number = {}, pages = {113919}, doi = {10.1016/j.intimp.2024.113919}, pmid = {39736240}, issn = {1878-1705}, mesh = {Animals ; Female ; *Gastrointestinal Microbiome ; *Endometritis/microbiology/immunology/pathology/metabolism ; *Succinic Acid/metabolism ; Mice ; *Lipopolysaccharides/immunology ; *Mice, Inbred C57BL ; Dysbiosis/immunology ; Receptors, G-Protein-Coupled/metabolism/genetics ; Dextran Sulfate ; Uterus/pathology/immunology/microbiology/metabolism ; Inflammation/immunology ; Disease Models, Animal ; Intestines/immunology/microbiology/pathology ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Endometritis poses higher health risks to women. Clinical practice has found that gastrointestinal dysfunction is more likely to lead to the occurrence of endometritis. However, the mechanism is unclear. This study explored the influence and mechanism of DSS-induced intestinal inflammation on endometritis. Our findings demonstrate that DSS-induced intestinal inflammation can worsen LPS-induced endometritis in mice, and this effect is dependent on the gut microbiota, as depleting the gut microbiota eliminates this protective effect. Similarly, FMT from DSS-treated mice to recipient mice exacerbates LPS-induced endometritis. In addition, treatment of DSS disrupted an imbalance of succinate-producing and succinate-consuming bacteria and increased the levels of succinate in the gut and uterine tissues. Furthermore, treatment with succinate aggravates LPS-induced endometritis by activating the succinate receptor 1 (SUCNR1), evidenced by inhibition of the activation of SUCNR1 reversed the inflammatory response in uterine tissues induced by succinate during endometritis induced by LPS. Collectively, the results suggested that dysbiosis of the gut microbiota exacerbates LPS-induced endometritis by production and migration of succinate from gut to uterine tissues via the gut-uterus axis, then activates the SUCNR1. This identifies gut-derived succinate as a novel target for treating endometritis, and it indicates that targeting the gut microbiota and its metabolism could be a potential strategy for intervention in endometritis.}, } @article {pmid39792405, year = {2024}, author = {Guo, Z and He, M and Shao, L and Li, Y and Xiang, X and Wang, Q}, title = {The role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease.}, journal = {Journal of cancer research and therapeutics}, volume = {20}, number = {7}, pages = {1964-1973}, doi = {10.4103/jcrt.jcrt_33_24}, pmid = {39792405}, issn = {1998-4138}, mesh = {Humans ; *Graft vs Host Disease/therapy/etiology/microbiology ; *Fecal Microbiota Transplantation/methods ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; *Gastrointestinal Microbiome ; Transplantation, Homologous/methods ; Acute Disease ; Treatment Outcome ; }, abstract = {Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most important methods for treating a wide range of hematologic malignancies and bone marrow failure diseases. However, graft-versus-host disease (GVHD), a major complication associated with this method, can seriously affect the survival and quality of life of patients. Acute GVHD (aGVHD) occurs within 100 days after transplantation, and gastrointestinal aGVHD (GI-aGVHD) is one of the leading causes of nonrecurrent death after allo-HSCT. In recent years, fecal microbiota transplantation (FMT) has been attempted as an emerging treatment method for various diseases, including aGVHD after HSCT. Studies have shown encouraging preliminary clinical results after the application of FMT in aGVHD, particularly steroid-resistant aGVHD. Additionally, several studies have demonstrated that the gut microbiota plays an important immunomodulatory role in the pathogenesis of GVHD. Consensus guidelines recommend FMT as a secondary option for the treatment of aGVHD. This article aims to review FMT treatment for GI-aGVHD after allo-HSCT.}, } @article {pmid39791180, year = {2025}, author = {Shakya, R and Sivakumar, PM and Prabhakar, PK}, title = {Gut Microbiota and Diabetes: Pioneering New Treatment Frontiers.}, journal = {Endocrine, metabolic & immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303342579241119155225}, pmid = {39791180}, issn = {2212-3873}, abstract = {Diabetes Mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and poses significant global health challenges. Conventional treatments, such as insulin therapy and lifestyle modifications, have shown limited efficacy in addressing the multifactorial nature of DM. Emerging evidence suggests that gut microbiota, a diverse community of microorganisms critical for metabolism and immune function, plays a pivotal role in metabolic health. Dysbiosis, an imbalance in gut microbiota composition, has been linked to insulin resistance, obesity, and DM. Gut microbiota influences glucose metabolism through mechanisms, including short-chain fatty acid production, gut permeability regulation, and immune system interactions, indicating a bidirectional relationship between microbial health and metabolism. Clinical and experimental studies demonstrate that modulating gut microbiota through dietary interventions (prebiotics, probiotics, synbiotics) improves glycemic control and insulin sensitivity in DM patients. Fecal Microbiota Transplantation (FMT) has also shown promise in restoring healthy gut microbiota and alleviating DM-related metabolic disturbances. However, challenges remain, including the need for personalized treatments due to individual microbiota variability and the unknown long-term effects of these interventions. Future research should focus on elucidating the mechanisms by which gut microbiota influences metabolism and refining personalized approaches to enhance DM management.}, } @article {pmid39791141, year = {2025}, author = {Li, X and Sun, B and Qin, Y and Yue, F and Lü, X}, title = {Amelioration of Obesity-Related Disorders in High-Fat Diet-Fed C57BL/6 Mice Following Fecal Microbiota Transplantation From DL-Norvaline-Dosed Mice.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e202400577}, doi = {10.1002/mnfr.202400577}, pmid = {39791141}, issn = {1613-4133}, support = {2023-ZDLNY-35//Shaanxi Province Science and Technology Plan Project/ ; 2022A02006//Major Scientific and Technological Special Project of Xinjiang Uygur Autonomous Region/ ; }, abstract = {Fecal microbiota transplantation (FMT) could significantly alter the recipient's gut bacteria composition and attenuate obesity and obesity-related metabolic syndromes. DL-norvaline is a nonproteinogenic amino acid and possesses anti-obesity potential. However, the specific mechanisms by which gut microbiota might mediate beneficial effects of DL-norvaline have not been completely elucidated. In this study, DL-norvaline-mediated FMT upregulated the beneficial bacteria (Clostridia_UCG_014, Christensenellales, Bacilli, Ileibacterium, Dubosiella, Lactobacillus, Muribaculaceae, and Bacteroidaceae) and downregulated the harmful bacteria (Tuzzerella and Marinifilaceae), further intestinal inflammation, oxidative stress, and intestinal barrier were alleviated as well as short chain fatty acids levels were increased, thus alleviating glucose and insulin metabolism, improving biochemical indexes and energy metabolism and decreasing body weight gain and tissue weight. However, heat-inactivated FMT did not demonstrate any of those improvements in obese mice. Notably, both DL-norvaline-mediated FMT and heat-inactivated FMT increased Bacteroidaceae and Muribaculaceae, this being a signature of alterations to the gut microbiota marker caused by DL-norvaline. Therefore, the beneficial effects of DL-norvaline were transmissible via FMT. This study highlighted the pivotal involvement of the gut microbiota in the development of obesity and provided a novel insight into the underlying mechanisms of FMT, thereby potentially enhancing the efficacy and refinement of FMT utilization.}, } @article {pmid39791120, year = {2024}, author = {Huang, H and Yang, Y and Wang, X and Wen, B and Yang, X and Zhong, W and Wang, Q and He, F and Li, J}, title = {Gut virome dysbiosis impairs antitumor immunity and reduces 5-fluorouracil treatment efficacy for colorectal cancer.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1501981}, pmid = {39791120}, issn = {2234-943X}, abstract = {INTRODUCTION: Despite the established influence of gut bacteria, the role of the gut virome in modulating colorectal cancer (CRC) patient chemotherapy response remains poorly understood. In this study, we investigated the impact of antiviral (AV) drug-induced gut virome dysbiosis on the efficacy of 5-FU in CRC treatment.

METHODS: Using a subcutaneous CRC mouse model, we assessed tumor growth and immune responses following AV treatment, fecal microbiota transplantation (FMT), and 5-FU administration.

RESULTS: AV therapy reduced the abundance of gut DNA and RNA viruses, leading to accelerated tumor growth, shortened survival, and diminished chemotherapy efficacy. FMT restored the gut virome, improving tumor suppression and extending the survival of 5-FU-treated mice. Metagenomic sequencing revealed significant changes in virome composition, AV treatment expanded Kahnovirus, Petivirales, and Enterogokushovirus, whereas FMT enriched Peduovirus STYP1, Mahlunavirus rarus, and Jouyvirus ev207. AV treatment reduced the number of dendritic cells and CD8+ T cells in peripheral blood and tumor tissues, impairing antitumor immunity, FMT reversed these deficiencies. To further investigate the underlying mechanisms, we examined the TLR3-IRF3-IFN-β pathway, essential for recognizing viral RNA and triggering immune responses. AV treatment downregulated this pathway, impairing immune cell recruitment and reducing chemotherapy efficacy, while activation of TLR3 with Poly(I:C) restored pathway function and enhanced the effectiveness of 5-FU.

DISCUSSION: These findings suggest the importance of maintaining gut virome integrity or activating TLR3 as adjunct strategies to enhance chemotherapy outcomes in CRC patients.}, } @article {pmid39791110, year = {2025}, author = {Høyer, KL and Dahl Baunwall, SM and Kornum, DS and Klinge, MW and Drewes, AM and Yderstræde, KB and Thingholm, LB and Mortensen, MS and Mikkelsen, S and Erikstrup, C and Hvas, CL and Krogh, K}, title = {Faecal microbiota transplantation for patients with diabetes type 1 and severe gastrointestinal neuropathy (FADIGAS): a randomised, double-blinded, placebo-controlled trial.}, journal = {EClinicalMedicine}, volume = {79}, number = {}, pages = {103000}, pmid = {39791110}, issn = {2589-5370}, abstract = {BACKGROUND: Diabetic gastroenteropathy is associated with nausea, vomiting, bloating, pain, constipation, and diarrhoea. Current therapies are scarce. We tested faecal microbiota transplantation (FMT) for patients with type 1 diabetes and gastroenteropathy.

METHODS: In a randomised, double-blinded, placebo-controlled pilot trial, adults with type 1 diabetes and moderate-to-severe gastrointestinal symptoms were randomised (1:1) to encapsulated FMT or placebo. Each patient received around 25 capsules containing 50 g of faeces, administered in a single dose. The placebo capsules contained glycerol, saline and food colouring. All patients received FMT as a second intervention. The primary endpoint was number of adverse events of severity grade 2 or more assessed by the Common Terminology Criteria for Adverse Events during the week following the first intervention. Secondary endpoints included gastrointestinal symptoms and quality of life assessed four weeks after treatment. Public trial registration, ClinicalTrials.govNCT04749030.

FINDINGS: We randomised 20 patients to FMT or placebo. Following this intervention, 26 adverse events of grade 2 or more occurred. Four patients in the FMT group reported seven adverse events, and five patients in the placebo group reported 19, with no differences between the groups. The most frequent adverse events were diarrhoea, bloating, and abdominal pain. No serious adverse events were related to the treatment. Patients who received FMT reduced their median Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome score from 58 (IQR 54-65) to 35 (32-48), whereas patients receiving placebo reduced their score from 64 (55-70) to 56 (50-77) (p = 0.01). The Irritable Bowel Syndrome Impact Scale score improved from 108 (101-123) to 140 (124-161) with FMT and 77 (53-129) to 92 (54-142) with placebo (p = 0.02). The Patient Assessment of Gastrointestinal Symptom Severity Index declined from a median of 42 (28-47) to 25 (14-31) after FMT and 47 (31-69) to 41 (36-64) after placebo (p = 0.03).

INTERPRETATION: FMT was safe and improved clinical outcomes for patients with type 1 diabetes suffering from bowel symptoms.

FUNDING: Steno Collaborative Grant.}, } @article {pmid39788762, year = {2025}, author = {Augustijn, QJJ and Grefhorst, A and de Groen, P and Wortelboer, K and Seegers, JFM and Gül, IS and Suenaert, P and Verheij, J and de Vos, WM and Herrema, H and Nieuwdorp, M and Holleboom, AG}, title = {Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e088290}, doi = {10.1136/bmjopen-2024-088290}, pmid = {39788762}, issn = {2044-6055}, mesh = {Humans ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Adult ; Male ; Randomized Controlled Trials as Topic ; Capsules ; Female ; Middle Aged ; Fatty Liver/therapy ; Feces/microbiology ; Freeze Drying ; }, abstract = {BACKGROUND: The spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, affecting 30% of the world's population, with a significant risk of hepatic and cardiometabolic complications. Different stages of MASLD are accompanied by distinct gut microbial profiles, and several microbial components have been implicated in MASLD pathophysiology. Indeed, earlier studies demonstrated that hepatic necroinflammation was reduced in individuals with MASLD after allogenic faecal microbiota transplantation (FMT) from healthy donors on a vegan diet. Here, we further investigate the therapeutic potential of gut microbiome modulation using a syntrophic combination of next-generation beneficial bacteria with FMT in individuals with advanced MASLD.

METHODS AND ANALYSIS: This trial is a randomised, double-blind, placebo-controlled study investigating the therapeutic potential of lyophilised faecal microbiota capsules (LFMCs) in individuals with metabolic dysfunction-associated steatohepatitis. In this study, 48 participants will be randomised 1:1 to receive either healthy vegan donor LFMCs or placebo for 24 weeks. In addition, all participants will be supplemented with a set of next-generation beneficial bacteria, including Anaerobutyricum soehngenii, pasteurised Akkermansia muciniphila and Bifidobacterium animalis subsp. lactis, as well as fructo-oligosaccharides. A liver biopsy will be performed at baseline and at the end of the trial. In addition, participants will be assessed through MRI, FibroScan, blood tests, faecal samples and continuous glucose monitoring. The first participant was enrolled on 25 April 2023.

ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Ethics Committee of the University Medical Centre of Amsterdam. The results of this study will be disseminated through peer-reviewed journals.

TRIAL REGISTRATION NUMBER: The trial is registered on clinicaltrials.gov (NCT05821010).}, } @article {pmid39788096, year = {2025}, author = {Wang, W and Pi, Z and Yu, Y and Zhang, F}, title = {The butterfly effect of the strain richness influences the efficacy of microbiota transplantation.}, journal = {Cell host & microbe}, volume = {33}, number = {1}, pages = {3-5}, doi = {10.1016/j.chom.2024.12.010}, pmid = {39788096}, issn = {1934-6069}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Animals ; Feces/microbiology ; Bacteria/classification ; }, abstract = {Strain-level variation in the gut microbiome modulates its impact on host health. Recently in Nature, Chen-Liaw et al. propose that strain richness is a crucial element in the gut ecosystem, thus influencing efficacy of fecal microbiota transplantation, and provide a theoretical foundation for optimizing microbiota-based treatments and developing microbiota medicine.}, } @article {pmid39787138, year = {2025}, author = {Luo, Y and Zhou, S and Zhang, X and Lin, Y and Liu, J and Cheng, W and Zeng, Y}, title = {The role of the microbiota and metabolites in the treatment of pulmonary fibrosis with UC-MSCs: Integrating fecal metabolomics and 16S rDNA analysis.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0313989}, pmid = {39787138}, issn = {1932-6203}, mesh = {Animals ; Mice ; *Pulmonary Fibrosis/therapy/metabolism/pathology/microbiology ; *Metabolomics/methods ; *Feces/microbiology ; *RNA, Ribosomal, 16S/genetics ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/metabolism ; Gastrointestinal Microbiome ; Male ; DNA, Ribosomal/genetics ; Mice, Inbred C57BL ; Disease Models, Animal ; Lung/pathology/metabolism/microbiology ; Bleomycin ; Microbiota ; Cytokines/metabolism ; }, abstract = {INTRODUCTION: Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease characterized by a lack of effective therapies. Mesenchymal stem cells (MSCs) have garnered significant interest in the realm of lung regeneration due to their abundant availability, ease of isolation, and capacity for expansion. The objective of our study was to investigate the potential therapeutic role of umbilical cord-derived MSCs (UC-MSCs) in the management of PF, with a focus on the alterations in the gut microbiota and its metabolites during the use of UC-MSCs for the treatment of pulmonary fibrosis, as well as the possible mechanisms involved.

METHODS: Bleomycin injection was utilized to establish a mouse model of lung fibrosis, followed by the application of 16S rDNA sequencing and LC-MS/MS metabolomics to explore the underlying mechanism of UC-MSC treatment for lung fibrosis. Seventy-five mice were allocated into five groups, namely Control, Model, and low/medium/high dose of UC-MSCs groups, and survival metrics, lung morphology, and the levels of the inflammatory cytokines TNF-α, IL-1β, IL-6, and TGF-β1 were subsequently evaluated. Fecal samples from six mice in each of the Control group, Model group, and UC-MSCs-M groups were collected randomly for 16S rDNA sequencing to analyze the gut microbiota and nontargeted metabolomics.

RESULTS: In comparison to IPF model mice, the three treatment groups exhibited increased survival rates, restored alveolar morphology, and reduced levels of the inflammatory cytokines TNF-α, IL-1β, IL-6, and TGF-β1, confirming the anti-inflammatory properties of UC-MSCs in IPF treatment. The findings from the 16S rDNA assay indicate that UC-MSCs treatment effectively lower α-diversity induced such as Chao 1 and ACE, as well as β-diversity, leading to a decrease in microbiota abundance. The findings from the metabolomics analysis revealed that the metabolites exhibiting notable variances were primarily composed of Lipids and lipid-like molecules, Organoheterocyclic compounds, Organic acids and derivatives, and Benzenoids, indicating the potential of UC-MSCs to exert antifibrotic effects via these metabolic pathways.

CONCLUSION: Umbilical cord-derived mesenchymal stem cells (UC-MSCs) ameliorate bleomycin-induced pulmonary fibrosis symptoms in mice by exerting anti-inflammatory effects and mitigating pulmonary fibrosis through the modulation of gut microbiota disorders and their metabolism. These findings offer novel insights into the potential mechanisms and clinical utility of stem cell therapy for pulmonary fibrosis.}, } @article {pmid39786379, year = {2024}, author = {Yang, Q and Zhu, Y and Jian, X and Qiu, Y and Zhu, Y and Zhao, L and He, Y and An, G and Qiu, L and Guo, J and He, N and Abudumijiti, H and Hu, C and Chen, X and Huang, S and Feng, X and Li, X and Liu, J and Xu, Y and Zhou, W}, title = {Targeting Enterobacter cloacae attenuates osteolysis by reducing ammonium in multiple myeloma.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2024025694}, pmid = {39786379}, issn = {1528-0020}, abstract = {Multiple myeloma (MM)-induced bone disease affects not only patients' quality of life but also their overall survival. Our previous work demonstrated that the gut microbiome plays a crucial role in MM progression and drug resistance. However, the role of altered gut microbiota in MM bone disease remains unclear. In this study, we show that intestinal E. cloacae is significantly enriched in MM patients with osteolysis. Through fecal microbial transplantation and single bacterial colonization experiments in a 5TGM1 MM mouse model, we found that intestinal colonization of E. cloacae promotes osteolysis by increasing circulating ammonium levels. Elevated ammonium promotes osteoclastogenesis by increasing Trap protein levels in osteoclast precursors and by acetylating and stabilizing CCL3 protein in MM cells. Inhibition of ammonium synthesis, using E. cloacae with a deleted dcd gene, along with probiotic supplementation, alleviated osteolysis in MM. Overall, our work suggests that E. cloacae promotes osteolysis in MM by synthesizing ammonium. This establishes a novel mechanism and potential intervention strategy for managing MM with osteolysis.}, } @article {pmid39780269, year = {2025}, author = {Li, X and Ding, Q and Wan, X and Wu, Q and Ye, S and Lou, Y}, title = {Fecal microbiota transplantation attenuates Alzheimer's disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation.}, journal = {Behavioral and brain functions : BBF}, volume = {21}, number = {1}, pages = {2}, pmid = {39780269}, issn = {1744-9081}, support = {Grant No. Y20220029//Health Project of the Science and Technology Department of Wenzhou/ ; 231104408302408//Industry-university Cooperative education program of Ministry of Education/ ; First Class, Category A//the Key Discipline of Zhejiang Province in Medical Technology/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Myeloid Differentiation Factor 88/metabolism ; Mice ; *Alzheimer Disease/therapy/microbiology ; *Mice, Transgenic ; *Toll-Like Receptor 4/metabolism ; *NF-kappa B/metabolism ; *Signal Transduction/physiology ; *Presenilin-1/genetics ; Amyloid beta-Protein Precursor/genetics ; Gastrointestinal Microbiome/physiology ; Inflammation/therapy/metabolism ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD. Additionally, disruption of the gut microbiota has been found to be associated with AD, and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach. However, the precise mechanism of FMT in the treatment of AD remains elusive. In this study, FMT was performed by transplanting fecal microbiota from healthy wild-type mice into APP/PS1 mice (APPswe, PSEN1dE9) to assess the effectiveness of FMT in mitigating AD-associated inflammation and to reveal its precise mechanism of action. The results demonstrated that FMT treatment improved cognitive function and reduced the expression levels of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway in mice, which was accompanied by the restoration of gut microbial dysbiosis. These findings suggest that FMT has the potential to ameliorate AD symptoms and delay the disease progression in APP/PS1 mice.}, } @article {pmid39779925, year = {2025}, author = {He, X and Hu, M and Xu, Y and Xia, F and Tan, Y and Wang, Y and Xiang, H and Wu, H and Ji, T and Xu, Q and Wang, L and Huang, Z and Sun, M and Wan, Y and Cui, P and Liang, S and Pan, Y and Xiao, S and He, Y and Song, R and Yan, J and Quan, X and Wei, Y and Hong, C and Liao, W and Li, F and El-Omar, E and Chen, J and Qi, X and Gao, J and Zhou, H}, title = {The gut-brain axis underlying hepatic encephalopathy in liver cirrhosis.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {39779925}, issn = {1546-170X}, support = {82372305//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Up to 50-70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut-brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus, increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R. gnavus showed brain phenylethylamine (PEA) accumulation, along with memory impairment, symmetrical tremors and cortex-specific neuron loss, typically found in patients with HE. This accumulation of PEA was primarily driven by decreased monoamine oxidase-B activity in both the liver and serum due to cirrhosis. Targeting PDC or PEA reversed the neurological symptoms induced by R. gnavus. Furthermore, fecal microbiota transplantation from patients with HE to germ-free cirrhotic mice replicated these symptoms and further corroborated the efficacy of targeting PDC or PEA. Clinically, high baseline PEA levels were linked to a sevenfold increased risk of HE after intrahepatic portosystemic shunt procedures. Our findings expand the understanding of the gut-liver-brain axis and identify a promising therapeutic and predictive target for HE.}, } @article {pmid39779878, year = {2025}, author = {Keskey, RC and Xiao, J and Hyoju, S and Lam, A and Kim, D and Sidebottom, AM and Zaborin, A and Dijkstra, A and Meltzer, R and Thakur, A and Zhang, K and Chen, HJ and Beloborodova, NV and Pautova, AK and Wolfe, K and Patel, B and Thewissen, R and Zaborina, O and Alverdy, JC}, title = {Enterobactin inhibits microbiota-dependent activation of AhR to promote bacterial sepsis in mice.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {39779878}, issn = {2058-5276}, support = {R01GMO62344-22//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, abstract = {Sepsis is a major cause of morbidity and mortality, but our understanding of the mechanisms underlying survival or susceptibility is limited. Here, as pathogens often subvert host defence mechanisms, we hypothesized that this might influence the outcome of sepsis. We used microbiota analysis, faecal microbiota transplantation, antibiotic treatment and caecal metabolite analysis to show that gut-microbiota-derived tryptophan metabolites including indoles increased host survival in a mouse model of Serratia marcescens sepsis. Infection in macrophage-specific aryl hydrocarbon receptor (AhR) knockout mice revealed that AhR activation induced transcriptional reprogramming in macrophages and increased bacterial clearance and host survival. However, culture supernatants from multiple bacterial pathogens inhibited AhR activation in vitro. We showed that the secreted siderophore, enterobactin, inhibited AhR activation in vitro and increased sepsis mortality in vivo. By contrast, oral or systemic tryptophan supplementation increased survival. These findings show that sepsis survival depends upon the interplay between pathogen inhibition and the activation of AhR by a microbiota-derived metabolite.}, } @article {pmid39779854, year = {2025}, author = {Won, TH and Arifuzzaman, M and Parkhurst, CN and Miranda, IC and Zhang, B and Hu, E and Kashyap, S and Letourneau, J and Jin, WB and Fu, Y and Guzior, DV and , and Quinn, RA and Guo, CJ and David, LA and Artis, D and Schroeder, FC}, title = {Host metabolism balances microbial regulation of bile acid signalling.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {39779854}, issn = {1476-4687}, abstract = {Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development[1], metabolism[2-4], immune responses[5-7] and cognitive function[8]. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear[9,10]. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA-methylcysteamine (BA-MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues. This host-dependent MCY conjugation inverts BA function in the hepatobiliary system. Whereas microbiota-derived free BAs function as agonists of the farnesoid X receptor (FXR) and negatively regulate BA production, BA-MCYs act as potent antagonists of FXR and promote expression of BA biosynthesis genes in vivo. Supplementation with stable-isotope-labelled BA-MCY increased BA production in an FXR-dependent manner, and BA-MCY supplementation in a mouse model of hypercholesteraemia decreased lipid accumulation in the liver, consistent with BA-MCYs acting as intestinal FXR antagonists. The levels of BA-MCY were reduced in microbiota-deficient mice and restored by transplantation of human faecal microbiota. Dietary intervention with inulin fibre further increased levels of both free BAs and BA-MCY levels, indicating that BA-MCY production by the host is regulated by levels of microbiota-derived free BAs. We further show that diverse BA-MCYs are also present in human serum. Together, our results indicate that BA-MCY conjugation by the host balances host-dependent and microbiota-dependent metabolic pathways that regulate FXR-dependent physiology.}, } @article {pmid39779737, year = {2025}, author = {Corcione, S and Ferrocino, I and Lupia, T and Busca, A and Bianco, G and Dellacasa, C and Giaccone, L and Brunello, L and Butera, S and Costa, C and Bruno, B and De Rosa, FG}, title = {Influence of ESBL colonization status on gut microbiota composition during allogenic hematopoietic stem cell transplantation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {1275}, pmid = {39779737}, issn = {2045-2322}, support = {Project no. PE00000007, INF-ACT//EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; Pilot Projects ; *beta-Lactamases/metabolism ; *Transplantation, Homologous/adverse effects ; Aged ; Feces/microbiology ; Italy ; Anti-Bacterial Agents/therapeutic use/pharmacology ; }, abstract = {After allogeneic HSCT (allo-HSCT), the diversity of the intestinal microbiota significantly decreases. The changes can be rapid and are thought to be caused by chemotherapy, antibiotics, or intestinal inflammation. Most patients are exposed to prophylactic and therapeutic antibiotics during neutropenia and several patients are colonized by ESBL bacteria. We investigated the changes in gut microbiota composition in allo-HSCT, aiming at investigating if the acquisition of ESBL colonization may affect gut microbiome diversity during allo-HSCT. This was a single-center prospective pilot study. All patients consecutively admitted to the Haematological Unit of the City of Health and Science, Molinette Hospital in Turin, Italy, and undergoing allo-HSCT between August 2017 to August 2020 were enrolled in the study. Microbiome analysis on fecal samples were collected every 7 days from hospital admission to discharge and until 1 year after HSCT. 48 patients were enrolled in the study. At baseline 14 patients (29.16%) were colonized by MDR bacteria, mostly extended-spectrum beta-lactamase (ESBL)-producing gram negatives (N = 11; 78.57%). During allo-HSCT, one patient had a positive rectal swab for a carbapenemase-producing Klebsiella pneumoniae and eight patients lost the colonization during the hospital stay. Microbiota composition was compared between patients colonized by ESBL at baseline and non-colonized patients. Patients colonized by ESBL had a greater abundances of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus Mogibacteriaceae, Peptostreptococceae and Oscillospira, while non-colonized ESBL patients had a greater abundance of Actinomycetales, Staphylococcus and Sutterella. Moreover, microbiota composition of colonized by ESBL that retained colonization after HSCT showed an increased in abundances of Akkermansia, Dialister, Erysipelotrichaceae and Methanobrevibacter when compared with patients that become negative at rectal swabs. From a clinical perspective, the evolution of this prospective pilot study will be to investigate markers of gut barrier functions, SCFA productions and to correlate the predictivity of these parameters with risk of invasive infections and clinical outcomes in allo-HSCT population.}, } @article {pmid39778887, year = {2025}, author = {Pérez-Accino, J and Salavati, M and Glendinning, L and Salavati Schmitz, S}, title = {Effect of a single rectal fecal microbiota transplantation on clinical severity and fecal microbial communities in dogs with chronic inflammatory enteropathy.}, journal = {Journal of veterinary internal medicine}, volume = {39}, number = {1}, pages = {e17264}, pmid = {39778887}, issn = {1939-1676}, support = {//Fiona and Ian Russel Fund/ ; }, mesh = {Animals ; Dogs ; *Dog Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation/veterinary ; *Feces/microbiology ; Male ; Female ; Inflammatory Bowel Diseases/veterinary/therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; Gastrointestinal Microbiome ; Chronic Disease ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been advocated as a treatment for chronic enteropathy (CE) in dogs. However, so far only short-term clinical effects have been reported whereas the effect on the microbiota remains unexplored.

HYPOTHESIS/OBJECTIVES: Assess if a single FMT enema can lead to clinical improvement in dogs with CE when accompanied by presumed favorable microbiota changes. The effect of glycerol as a cryopreservative when storing FMT preparations also was assessed.

ANIMALS: Seven dogs with CE that received FMTs from 2 healthy donor dogs.

MATERIALS AND METHODS: Six dogs received a single FMT, 1 dog received 3 consecutive FMTs. Canine chronic enteropathy clinical activity index (CCECAI) and fecal samples were obtained before (Day 0), and 7, 30 and 90 days after FMT. Samples were stored with and without 10% glycerol. Sequencing of microbiota (16S rRNA, Illumina) was performed and compared by accepted analysis pipelines.

RESULTS: Median CCECAI before FMT was 8 (range, 5-14), decreased to a median of 3 (range, 1-12) within 1 week and a median of 1 (range, 0-12) by Day 30 (P < .01), with an average duration of response of approximately 10 weeks. Significant variation in the donors' microbiota composition was observed across different donations. Recipient microbiota composition or diversity did not change over time. Glycerol addition was associated with a difference in microbiota composition (P ≤ .001).

A single FMT can be considered an appropriate treatment in dogs with CE, but consistent microbiota changes were not observed.}, } @article {pmid39778639, year = {2025}, author = {Chen, C and Wang, J and Cheng, M and Xie, H and Li, W and Zhang, C}, title = {Muribaculum intestinale-derived 3-hydroxybutyric acid from Heterophyllin B attenuated pulmonary fibrosis through IDO1-mediated ferroptosis.}, journal = {Pharmacological research}, volume = {212}, number = {}, pages = {107587}, doi = {10.1016/j.phrs.2025.107587}, pmid = {39778639}, issn = {1096-1186}, abstract = {Pulmonary fibrosis (PF) is a fatal disease with increasing incidence, poor prognosis, and unclear pathogenesis. Our previous research demonstrated the beneficial effects of the natural cyclopeptide Heterophyllin B (HB) in PF. However, the precise mechanism by which HB exerts its effects in PF remains unclear. Our study revealed HB's beneficial effects in alleviating PF symptoms and restoring the intestinal mucosal barrier. Subsequently, the microbiota-dependent antifibrotic efficacy of HB was verified using various delivery routes, antibiotic treatments, and faecal microbiota transplantation. Functionally, 16S rRNA sequencing, untargeted metabolomics, and co-incubation experiments revealed that the antifibrotic efficacy of HB was primarily contingent on the enrichment of Muribaculum intestinale and its metabolite, 3-hydroxybutyric acid. Mechanistically, indoleamine 2,3- dioxygenase 1 (IDO1)-mediated ferroptosis was identified as a pivotal process in initiating PF, and the anti-fibrotic efficacy of HB relies on suppressing IDO1-mediated ferroptosis. Conversely, IDO1 deficiency alleviated the symptoms of bleomycin-induced PF and ferroptosis in mice. Coincidentally, both IDO1 overexpression and ferroptosis were observed in the pulmonary tissue of patients with idiopathic PF. Collectively, this study revealed that HB alleviates PF by eliminating intestinal microecology and metabolism and highlights the feasibility of targeting IDO1 for PF treatment.}, } @article {pmid39777251, year = {2025}, author = {Quaglio, AE and Magro, DO and Imbrizi, M and De Oliveira, EC and Di Stasi, LC and Sassaki, LY}, title = {Creeping fat and gut microbiota in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {1}, pages = {102042}, pmid = {39777251}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology/therapy ; Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Dysbiosis/immunology ; *Fecal Microbiota Transplantation ; *Intra-Abdominal Fat/immunology ; *Probiotics/therapeutic use ; *Disease Progression ; Prebiotics/administration & dosage ; Fibrosis ; Animals ; Mesentery ; }, abstract = {In this article, we explored the role of adipose tissue, especially mesenteric adipose tissue and creeping fat, and its association with the gut microbiota in the pathophysiology and progression of Crohn's disease (CD). CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, influenced by genetic predisposition, gut microbiota dysbiosis, and environmental factors. Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD. Further, visceral adipose tissue, particularly creeping fat, a mesenteric adipose tissue characterized by hypertrophy and fibrosis, has been implicated in CD pathogenesis, inflammation, and fibrosis. The bacteria from the gut microbiota may translocate into mesenteric adipose tissue, contributing to the formation of creeping fat and influencing CD progression. Although creeping fat may be a protective barrier against bacterial invasion, its expansion can damage adjacent tissues, leading to complications. Modulating gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and prebiotics has shown potential in managing CD. However, more research is needed to clarify the mechanisms linking gut dysbiosis, creeping fat, and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.}, } @article {pmid39777148, year = {2024}, author = {An, Y and He, L and Xu, X and Piao, M and Wang, B and Liu, T and Cao, H}, title = {Gut microbiota in post-acute COVID-19 syndrome: not the end of the story.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1500890}, pmid = {39777148}, issn = {1664-302X}, abstract = {The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to major global health concern. However, the focus on immediate effects was assumed as the tip of iceberg due to the symptoms following acute infection, which was defined as post-acute COVID-19 syndrome (PACS). Gut microbiota alterations even after disease resolution and the gastrointestinal symptoms are the key features of PACS. Gut microbiota and derived metabolites disorders may play a crucial role in inflammatory and immune response after SARS-CoV-2 infection through the gut-lung axis. Diet is one of the modifiable factors closely related to gut microbiota and COVID-19. In this review, we described the reciprocal crosstalk between gut and lung, highlighting the participation of diet and gut microbiota in and after COVID-19 by destroying the gut barrier, perturbing the metabolism and regulating the immune system. Therefore, bolstering beneficial species by dietary supplements, probiotics or prebiotics and fecal microbiota transplantation (FMT) may be a novel avenue for COVID-19 and PACS prevention. This review provides a better understanding of the association between gut microbiota and the long-term consequences of COVID-19, which indicates modulating gut dysbiosis may be a potentiality for addressing this multifaceted condition.}, } @article {pmid39776845, year = {2024}, author = {Zhuang, L and You, Y and Zeng, S and Yu, Z and Wang, H and Chen, M and Wen, W}, title = {Fecal microbiota transplantation in severe pneumonia: a case report on overcoming pan-drug resistant Klebsiella pneumoniae infection.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1451751}, pmid = {39776845}, issn = {2296-858X}, abstract = {OBJECTIVE: To evaluate the therapeutic potential of fecal microbiota transplantation (FMT) in treating severe pneumonia patients with concurrent pan-drug resistant Klebsiella pneumoniae infection.

METHODS: A case report of a 95-year-old female patient with severe pneumonia, complicated by pan-resistant bacterial infections, is presented. The patient was diagnosed with severe pneumonia caused by COVID-19, along with co-infections of Staphylococcus hominis, Enterococcus faecalis, Candida tropicalis, Pseudomonas aeruginosa, ESBL-producing pan-drug resistant Klebsiella pneumoniae and pan-resistant Acinetobacter baumannii. During hospitalization, the patient underwent comprehensive treatments, including antimicrobials, mechanical ventilation, and fiberoptic bronchoscopic alveolar lavage. FMT was administered following the failure of conventional treatments to resolve recurrent diarrhea, increased sputum production, and persistent pan-drug resistant Klebsiella pneumoniae infection.

RESULTS: Post-FMT, the patient exhibited significant clinical improvement, including reduced sputum production, cessation of diarrhea, and the normalization of respiratory symptoms. Gut microbiota analysis revealed that FMT enhanced the abundance of beneficial microbiota and suppressed Klebsiella pneumoniae, and the patient was successfully discharged after 133 days of hospitalization.

CONCLUSION: FMT emerged as a pivotal intervention in the management of this severe pneumonia case, suggesting its efficacy in restoring gut microbiota balance and aiding recovery from multi-drug-resistant infections. This case underscores the potential of FMT as a therapeutic option in severe pulmonary infections, especially in the context of antibiotic resistance in severe pneumonia patients.}, } @article {pmid39776440, year = {2024}, author = {Fang, L and Ning, J}, title = {Recent advances in gut microbiota and thyroid disease: pathogenesis and therapeutics in autoimmune, neoplastic, and nodular conditions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1465928}, pmid = {39776440}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; *Thyroid Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation ; Animals ; Bacteria/classification/metabolism ; Neoplasms/therapy/microbiology ; Dysbiosis/therapy/microbiology ; }, abstract = {This review synthesizes key findings from the past five years of experimental literature, elucidating the gut microbiome's significant influence on the pathogenesis of thyroid diseases. A pronounced shift in the gut microbiota composition has been consistently observed, with a significant reduction in bacteria such as Bifidobacterium, Bacillaceae, Megamonas, and Clostridium, and a notable increase in bacteria, including Bacteroides, Proteobacteria, Actinobacteria, Desulfobacterota, and Klebsiella. These alterations are implicated in the development and progression of thyroid diseases by impacting metabolic pathways including bile acid and cytokine production, including a decrease in short-chain fatty acids (SCFAs) that are crucial for immune regulation and thyroid hormone homeostasis. The review also highlights the therapeutic implications of probiotics in managing thyroid conditions. Evidence suggests that probiotic adjunct therapy can modulate the gut microbiota, leading to improvements in thyroid function and patient outcomes. The use of specific probiotic strains, such as Lactiplantibacillus plantarum 299v and Bifidobacterium longum, has demonstrated potential in enhancing the effects of traditional treatments and possibly restoring a balanced gut microbiota. Notably, fecal microbiota transplantation (FMT) has emerged as a promising intervention in Graves' Disease (GD), demonstrating the potential to recalibrate the gut microbiota, thereby influencing neurotransmitters and trace elements via the gut-brain and gut-thyroid axes. The integration of microbiome-based therapies with traditional treatments is anticipated to usher in a new era of personalized thyroid disease management, offering a more nuanced approach to patient care. By integrating this body of work, the review offers an innovative perspective on the gut microbiome's broad impact on thyroid diseases and the therapeutic applications of probiotics.}, } @article {pmid39775925, year = {2025}, author = {Bloem, MN and Baaleman, DF and Thapar, N and Roberts, SE and Koppen, IJN and Benninga, MA}, title = {Prevalence of functional defecation disorders in European children: A systematic review and meta-analysis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.12437}, pmid = {39775925}, issn = {1536-4801}, support = {//None/ ; }, abstract = {OBJECTIVES: Functional defecation disorders (FDDs) are common among children worldwide. The prevalence of these disorders has not been clearly described in Europe. This study performed a systematic review and meta-analysis on the prevalence of FDD in European children and assessed geographical, age, and sex distribution and associated factors.

METHODS: PubMed, Embase, Psycinfo, Cochrane Library, and Cinahl were searched from 1999 to July 2023. Included studies were (1) prospective or cross-sectional studies of European population-based samples; (2) reporting the prevalence of infant dyschezia (ID) according to Rome II, III, or IV criteria or functional constipation (FC) or functional non-retentive fecal incontinence (FNRFI) according to Rome III or IV criteria; (3) aged 0-18 years; and (4) published in English, Dutch or Spanish. PRISMA guidelines for extracting data and assessing data quality were followed.

RESULTS: Twenty-eight studies were included. Pooled prevalence was 6.9% (95% confidence interval [CI]: 3.1%-11.9%) for ID in infants 0-12 months (9 studies, n = 5611), 8.17% (95% CI: 6.33%-10.22%) for FC in children <4 years (25 studies, n = 35,189), 11.39% (95% CI: 9.34%-14.11%) for FC in children 4-18 years, and 0.24% (95% CI: 0.07%-0.49%) for FNRFI in children 4-18 years (7 studies, n = 16,873). No sex predominance was found for FC. FC prevalence did not differ significantly when diagnosed according to Rome III versus IV. FC prevalence differed between countries, with greatest rates in Italy, Germany, and Spain. No meta-analysis could be performed on other factors associated with FDD.

CONCLUSIONS: FDD is common in European children. Future longitudinal studies are needed to provide better insight into associated factors in pathogenesis.}, } @article {pmid39775370, year = {2025}, author = {Lai, Y and Qiu, R and Zhou, J and Ren, L and Qu, Y and Zhang, G}, title = {Fecal Microbiota Transplantation Alleviates Airway Inflammation in Asthmatic Rats by Increasing the Level of Short-Chain Fatty Acids in the Intestine.}, journal = {Inflammation}, volume = {}, number = {}, pages = {}, pmid = {39775370}, issn = {1573-2576}, support = {(No. 2021JJ30513, No. 2017JJ3245)//Natural Science Foundation of Hunan Province/ ; No. 20B444//Education Department of Hunan Province/ ; (No. 81603705)//National Natural Science Foundation of China/ ; (No. 2017M612567)//Postdoctoral Science Foundation of China/ ; (2024XJZA008)//Hunan University of Chinese Medicine research project/ ; }, abstract = {Asthma is a prevalent chronic inflammatory disorder of the respiratory tract that not only manifests with respiratory symptoms but also often involves intestinal flora disorders and gastrointestinal dysfunction. Recent studies have confirmed the close relationship between the gut and lungs, known as the "gut-lung axis" theory. Fecal microbiota transplantation (FMT), a method for restoring normal intestinal flora, has shown promise in treating common gastrointestinal diseases. The "gut-lung axis" theory suggests that FMT may have significant therapeutic potential for asthma. In this study, we established an Ovalbumin (OVA)-induced rat model of asthma to investigate the protective effect of FMT on airway inflammation and the restoration of intestinal short-chain fatty acids (SCFAs), aiming to explore its underlying mechanism. Rats in the Control group underwent fecal treatment via gavage (Control-FMT, C-FMT group), while rats in the Asthma group underwent fecal treatment via gavage after asthma induction (Asthma-FMT, A-FMT group). Following a two-week period of continuous intragastric administration, various measurements were conducted to assess pulmonary function, peripheral blood neutrophil, lymphocyte, and eosinophil content, lung tissue pathology, and collagen fiber deposition in the lungs. Additionally, neutrophil and eosinophil content in bronchoalveolar lavage fluid (BALF), expression levels of Interleukin-4 (IL-4), IL-5, IL-13, IL-17, IL-33, leukotrienes (LT), thymic stromal lymphopoietin (TSLP), prostaglandin D2 (PGD2) protein and mRNA in lung tissue, and SCFAs content in stool were evaluated. In the C-FMT group, lung function significantly improved, inflammatory cell content in peripheral blood and BALF decreased, lung tissue pathology and collagen fiber deposition significantly improved, the protein and mRNA levels of lung inflammatory factors IL-4, IL-5, IL-13, IL-17, IL-33, LT, TSLP, PGD2 were significantly decreased, and SCFAs such as acetate (C2), propionate (C3), butyrate (C4), isobutyric acid (I-C4), valeric acid (C5), and isovaleric acid (I-C5) content in stool significantly increased. However, the indexes in the A-FMT group did not show significant recovery, and the treatment effect on asthma symptoms in rats was inferior to that in the C-FMT group. Asthma induced intestinal flora disorders in rats, and FMT treatment improved the inflammatory response in asthmatic rat models and corrected their intestinal SCFAs disorders. Encouraging the recovery of intestinal SCFAs may play a significant role, and beneficial bacteria present in feces may improve asthma symptoms by promoting the remodeling of intestinal flora. This experiment provides further scientific evidence supporting the "gut-lung axis" theory.}, } @article {pmid39773995, year = {2024}, author = {Mullish, BH and Innes, AJ and Roberts, LA and Anim-Burton, S and Webber, L and Johnson, NA and Ghani, R and Farshi, P and Khan, AB and Kinsella, F and Kottaridis, P and Krishnamurthy, P and Nicholson, E and Palanicawandar, R and Wheeler, G and Davies, F and Marchesi, JR and Pavlů, J}, title = {Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial.}, journal = {BMJ open}, volume = {14}, number = {12}, pages = {e093120}, doi = {10.1136/bmjopen-2024-093120}, pmid = {39773995}, issn = {2044-6055}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Double-Blind Method ; *Transplantation, Homologous ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; Adult ; Randomized Controlled Trials as Topic ; Transplantation Conditioning/methods ; Fecal Microbiota Transplantation/methods ; Hematologic Neoplasms/therapy ; Female ; Male ; }, abstract = {INTRODUCTION: Lower diversity of the gut microbiome prior to allogeneic haematopoietic cell transplantation (HCT) correlates with reduced survival after the intervention. Most patients undergoing HCT for a haematological malignancy have previously received intensive chemotherapy, resulting in prolonged neutropenic episodes requiring broad-spectrum antibiotics; use of these has been linked to reduced microbiome diversity. Intestinal microbiota transplant (IMT) is a novel treatment approach that restores this diversity. We hypothesised that IMT performed prior to initiation of HCT conditioning restores microbiome diversity during the early stages of HCT, leading to decreased frequency of complications and improved outcomes of HCT.

METHODS AND ANALYSIS: 50 adult patients receiving allogeneic HCT will be recruited into this phase IIa trial and randomised 1:1 to receive capsulised IMT or matched placebo shortly prior to initiation of HCT conditioning and followed for up to 12 months. The primary outcome will be to assess the increase in alpha diversity between pre-IMT and that measured at ~42 days after IMT administration (day +28 of HCT), comparing the difference between patients receiving IMT compared with placebo. Secondary outcomes will include tolerability, the dynamics of gut microbiome diversity metrics and taxonomy over all time points assessed, as well as clinical outcomes (including burden of invasive infections, days of fever, admission to intensive care, development of graft-vs-host disease and mortality).

ETHICS AND DISSEMINATION: This study was approved by a UK Research Ethics Committee (REC reference: 23/NE/0105). Dissemination of results will be in concert with patient and public involvement group input and is expected to be primarily via abstract presentation at conferences and manuscripts in peer-reviewed journals.

TRIAL REGISTRATION NUMBERS: NCT6355583; EudraCT: 2022-003617-10.}, } @article {pmid39773319, year = {2025}, author = {Prince, N and Peralta Marzal, LN and Roussin, L and Monnoye, M and Philippe, C and Maximin, E and Ahmed, S and Salenius, K and Lin, J and Autio, R and Adolfs, Y and Pasterkamp, RJ and Garssen, J and Naudon, L and Rabot, S and Kraneveld, AD and Perez-Pardo, P}, title = {Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447822}, doi = {10.1080/19490976.2024.2447822}, pmid = {39773319}, issn = {1949-0984}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; Male ; *Mice, Inbred C57BL ; *Brain-Gut Axis/physiology ; *Mice, Inbred BALB C ; Child ; Autism Spectrum Disorder/microbiology ; Dysbiosis/microbiology ; Feces/microbiology ; Disease Models, Animal ; Autistic Disorder/microbiology/physiopathology ; Female ; Social Behavior ; Species Specificity ; Bacteria/classification/isolation & purification/genetics/metabolism ; }, abstract = {Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.}, } @article {pmid39772953, year = {2025}, author = {Teigen, LM and Hoeg, A and Zehra, H and Shah, P and Johnson, R and Hutchison, K and Kocher, M and Lin, AW and Johnson, AJ and Vaughn, BP}, title = {Nutritional optimization of fecal microbiota transplantation in humans: a scoping review.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446378}, doi = {10.1080/19490976.2024.2446378}, pmid = {39772953}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Diet ; Clostridium Infections/therapy/microbiology ; Feces/microbiology ; Dietary Supplements ; }, abstract = {Diet constitutes a major source of nutrient flow to the gut microbes. As such, it can be used to help shape the gut microbiome. Fecal microbiota transplantation (FMT) is an increasingly promising therapy in disease states beyond recurrent Clostridioides difficile infection, but diet is largely overlooked for its potential to help optimize this therapy. Therefore, the aim of this scoping review is to present the literature landscape that captures pre- and post-FMT dietary intake in humans, identify research gaps, and provide recommendations for future research. A comprehensive search strategy was developed and searches were run in five databases. Studies were included if they discussed adults who underwent FMT for any recognized treatment indication and had dietary intake as a study objective, this search encompassed studies with interventions that included foods and dietary supplements. The initial screening identified a total of 7721 articles, of which 18 met the inclusion criteria for this review. Studies were heterogeneous, but taken together, they introduce a framework that defines important nutritional considerations for both donors and FMT recipients in the period around FMT dosing. This framework is summarized with this review and highlights the opportunities available to develop FMT-based precision nutrition strategies to optimize its clinical efficacy.}, } @article {pmid39772388, year = {2025}, author = {Wouters, S and Moors, H and Verslegers, M and Leys, N and Malhotra-Kumar, S and Kumar-Singh, S and Mysara, M}, title = {Protocol for fecal microbiota transplantation: A microaerophilic approach for mice housed in a specific pathogen-free facility.}, journal = {STAR protocols}, volume = {6}, number = {1}, pages = {103517}, doi = {10.1016/j.xpro.2024.103517}, pmid = {39772388}, issn = {2666-1667}, abstract = {Recently, studies have emerged exploring the potential application of fecal microbiota transplantation (FMT) in pre-clinical settings. Here, we present a protocol for FMT for mice housed in a specific pathogen-free (SPF) facility. We describe steps for sample collection, microaerophilic processing of freshly collected fecal pellets, and administration through oral gavage. We then detail procedures for the engraftment of the bacterial community. This protocol focuses on age- and gender-matched, healthy donor mice using a mobile and cost-effective alternative to an anoxic cabinet.}, } @article {pmid39771031, year = {2024}, author = {Olga, B and Boicean, A and Fleacă, SR and Blanca, G and Florin, S and Corina, RF and Iulian, RF and Adelaida, S and Sabrina, B and Dura, H and Corina, P and Cristian, A and Onisor, DM}, title = {Importance of Fecal Microbiota Transplantation and Molecular Regulation as Therapeutic Strategies in Inflammatory Bowel Diseases.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/nu16244411}, pmid = {39771031}, issn = {2072-6643}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Inflammatory Bowel Diseases/therapy/microbiology/immunology ; *MicroRNAs/metabolism ; *Gastrointestinal Microbiome ; Gene Expression Regulation ; Animals ; Intestinal Mucosa/microbiology/metabolism/immunology ; }, abstract = {Noncoding RNAs, particularly microRNAs (miRNAs) and small interfering RNAs (siRNAs), have emerged as key players in the pathogenesis and therapeutic strategies for inflammatory bowel disease (IBD). MiRNAs, small endogenous RNA molecules that silence target mRNAs to regulate gene expression, are closely linked to immune responses and inflammatory pathways in IBD. Notably, miR-21, miR-146a, and miR-155 are consistently upregulated in IBD, influencing immune cell modulation, cytokine production, and the intestinal epithelial barrier. These miRNAs serve as biomarkers for disease progression and severity, as well as therapeutic targets for controlling inflammation. This comprehensive review highlights the intricate interplay between the gut microbiota, fecal microbiota transplantation (FMT), and miRNA regulation. It concludes that microbiota and FMT influence miRNA activity, presenting a promising avenue for personalized IBD treatment.}, } @article {pmid39771027, year = {2024}, author = {Gruenbaum, BF and Merchant, KS and Zlotnik, A and Boyko, M}, title = {Gut Microbiome Modulation of Glutamate Dynamics: Implications for Brain Health and Neurotoxicity.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/nu16244405}, pmid = {39771027}, issn = {2072-6643}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Glutamic Acid/metabolism ; *Brain-Gut Axis/physiology ; *Brain/metabolism ; Animals ; Fecal Microbiota Transplantation ; Blood-Brain Barrier/metabolism ; Neurotoxicity Syndromes/etiology/metabolism ; Depression/metabolism/microbiology ; }, abstract = {The gut-brain axis plays an integral role in maintaining overall health, with growing evidence suggesting its impact on the development of various neuropsychiatric disorders, including depression. This review explores the complex relationship between gut microbiota and glutamate (Glu) regulation, highlighting its effect on brain health, particularly in the context of depression following certain neurological insults. We discuss how microbial populations can either facilitate or limit Glu uptake, influencing its bioavailability and predisposing to neuroinflammation and neurotoxicity. Additionally, we examine the role of gut metabolites and their influence on the blood-brain barrier and neurotransmitter systems involved in mood regulation. The therapeutic potential of microbiome-targeted interventions, such as fecal microbiota transplantation, is also highlighted. While much research has explored the role of Glu in major depressive disorders and other neurological diseases, the contribution of gut microbiota in post-neurological depression remains underexplored. Future research should focus on explaining the mechanisms linking the gut microbiota to neuropsychiatric outcomes, particularly in conditions such as post-stroke depression, post-traumatic brain-injury depression, and epilepsy-associated depression. Systematic reviews and human clinical studies are needed to establish causal relationships and assess the efficacy of microbiome-targeted therapies in improving the neuropsychiatric sequalae after neurological insults.}, } @article {pmid39770958, year = {2024}, author = {Puca, P and Del Gaudio, A and Becherucci, G and Sacchetti, F and Sofo, L and Lopetuso, LR and Papa, A and Cammarota, G and Scaldaferri, F}, title = {Diet and Microbiota Modulation for Chronic Pouchitis: Evidence, Challenges, and Opportunities.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/nu16244337}, pmid = {39770958}, issn = {2072-6643}, mesh = {*Pouchitis/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Chronic Disease ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; Colitis, Ulcerative/microbiology/therapy ; Proctocolectomy, Restorative/adverse effects ; Diet/methods ; Diet, Mediterranean ; }, abstract = {Chronic pouchitis occurs in about 50% of patients undergoing a restorative proctocolectomy for ulcerative colitis. This affection represents a significant therapeutic challenge, particularly for symptomatic patients who do not respond to antibiotic treatments and biologic therapies. Several dietary approaches, including low FODMAP diets and the Mediterranean diet, have shown promising results in improving symptoms and disease burden. The rationale for dietary intervention lies in the reduction in inflammation and modulation of gut microbiota. However, conflicting results and methodological heterogeneity jeopardize the transition of these approaches from the field of research to clinical practice. Together with a nutritional approach, innovative methods of microbiota modulation, including probiotics and fecal microbiota transplantation, are emerging as safe and effective strategies in managing chronic pouchitis. This narrative review analyzes recent advancements in nutritional therapies and microbiota modulation as innovative and complementary approaches for managing chronic pouchitis. After examining microbiota modulation strategies, specifically the effectiveness of probiotics, prebiotics, and fecal microbiota transplantation in restoring microbial diversity and their potential role in alleviating symptoms, the review assesses the available clinical evidence concerning dietary interventions and their impact on gut microbiota. A comprehensive understanding of interventions aimed at modulating the microbiota is crucial for enhancing the effectiveness of conventional therapies. Such strategies may lead to significant improvements in patients' quality of life and their perception of the disease. However, the variability in microbiota composition, the use of restrictive diets, and the lack of standardized methods for evaluating these interventions remain significant challenges. Future research is essential to improve our understanding of the underlying mechanisms and optimize clinical application.}, } @article {pmid39770742, year = {2024}, author = {Park, SH and Lee, JH and Lee, S and Shin, J and Cha, B and Hong, JT and Kwon, KS}, title = {Factors for Treatment Failure After Fecal Microbiota Transplantation in Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/microorganisms12122539}, pmid = {39770742}, issn = {2076-2607}, support = {2023AR05//Seoul Clinical Laboratories/ ; }, abstract = {Recently, fecal microbiota transplantation (FMT) has been introduced as an effective treatment option for Clostridioides difficile infection (CDI). However, the risk factors associated with FMT treatment failure have not been well demonstrated. Therefore, we aimed to investigate the risk factors of treatment failure or recurrence after FMT for CDI. This retrospective study included 124 patients with CDI who underwent FMT at Inha University Hospital between November 2017 and August 2021 and were followed up for 8 weeks after FMT for symptoms of CDI. FMT failure was defined as diarrhea recurrence or a positive stool test. We assessed the risk factors for treatment failure, including comorbidities, antibiotic use pre- and post-FMT, and the number of CDI episodes before FMT. Ninety-three patients (75%) experienced symptom improvement <7 days after FMT, while treatment failure occurred in 40 patients (32.3%). Multivariate analysis revealed that males had a lower symptom improvement rate <7 days after FMT (p = 0.049). Patients using antibiotics after FMT showed a higher rate of recurrence or treatment failure in <8 weeks (p = 0.032). Patients requiring antibiotics after FMT should be considered at higher risk of treatment failure. Careful antibiotic stewardship, particularly minimizing non-essential antibiotic use before and after FMT, may significantly enhance treatment outcomes. Further large-scale prospective studies are warranted to confirm these findings and develop targeted antibiotic management protocols for improving the efficacy of FMT in CDI treatment.}, } @article {pmid39770703, year = {2024}, author = {Islam, MZ and Jozipovic, D and Lopez, PA and Krych, L and Correia, BSB and Bertram, HC and Hansen, AK and Hansen, CHF}, title = {Wild-Mouse-Derived Gut Microbiome Transplantation in Laboratory Mice Partly Alleviates House-Dust-Mite-Induced Allergic Airway Inflammation.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/microorganisms12122499}, pmid = {39770703}, issn = {2076-2607}, support = {R288-2018-1123//Lundbeck Foundation/ ; N/A//Sigrid Rigmor Morans Mindefond/ ; }, abstract = {Laboratory mice are instrumental for preclinical research but there are serious concerns that the use of a clean standardized environment for specific-pathogen-free (SPF) mice results in poor bench-to-bedside translation due to their immature immune system. The aim of the present study was to test the importance of the gut microbiota in wild vs. SPF mice for evaluating host immune responses in a house-dust-mite-induced allergic airway inflammation model without the influence of pathogens. The wild mouse microbiome reduced histopathological changes and TNF-α in the lungs and serum when transplanted to microbiota-depleted mice compared to mice transplanted with the microbiome from SPF mice. Moreover, the colonic gene expression of Gata3 was significantly lower in the wild microbiome-associated mice, whereas Muc1 was more highly expressed in both the ileum and colon. Intestinal microbiome and metabolomic analyses revealed distinct profiles associated with the wild-derived microbiome. The wild-mouse microbiome thus partly reduced sensitivity to house-dust-mite-induced allergic airway inflammation compared to the SPF mouse microbiome, and preclinical studies using this model should consider using both 'dirty' rewilded and SPF mice for testing new therapeutic compounds due to the significant effects of their respective microbiomes and derived metabolites on host immune responses.}, } @article {pmid39770634, year = {2024}, author = {Chun, M and Tun, KM and Vongsavath, T and Verma, R and Batra, K and Limsui, D and Jenkins, E}, title = {Fecal Microbiota Transplantation for Chronic Pouchitis: A Systematic Review and Meta-Analysis.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/microorganisms12122430}, pmid = {39770634}, issn = {2076-2607}, abstract = {Pouchitis is a common complication after ileal-pouch anal anastomosis in patients with medically refractory ulcerative colitis. There has been a lack of high-level evidence focusing on the safety and efficacy outcomes of fecal microbiota transplantation (FMT). We aim to evaluate outcomes and complications of fecal microbiota transplantation (FMT) for chronic pouchitis. Databases were systematically searched to retrieve English-only, original studies, published from inception to 31 March 2024, investigating chronic pouchitis only. Primary outcomes included overall remission, clinical response, remission, relapse, and complications. Seven studies with 94 patients were included. The pooled overall remission rate was 15% (95% CI: 0-29%, p < 0.001), the clinical response rate was 33% (95% CI: 19-46%, p = 0.14), the clinical remission rate was 14% (95% CI: 19-46%, p < 0.001), and the clinical relapse rate was 36% (95% CI: 16-55%, p = 0.11). The pooled proportion of patients with mild adverse events after FMT treatment was 39% (95% CI: 6-71%, p < 0.001). No severe adverse events or deaths were reported. Although FMT is an effective treatment for chronic pouchitis, there is still a high rate of mild adverse events. High-level evidence for FMT is still sparse, limiting recommendations for clinical use.}, } @article {pmid39767682, year = {2024}, author = {Farhadi Rad, H and Tahmasebi, H and Javani, S and Hemati, M and Zakerhamidi, D and Hosseini, M and Alibabaei, F and Banihashemian, SZ and Oksenych, V and Eslami, M}, title = {Microbiota and Cytokine Modulation: Innovations in Enhancing Anticancer Immunity and Personalized Cancer Therapies.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/biomedicines12122776}, pmid = {39767682}, issn = {2227-9059}, abstract = {The gut microbiota plays a crucial role in modulating anticancer immunity, significantly impacting the effectiveness of various cancer therapies, including immunotherapy, chemotherapy, and radiotherapy. Its impact on the development of cancer is complex; certain bacteria, like Fusobacterium nucleatum and Bacteroides fragilis, can stimulate the growth of tumors by causing immunological evasion and inflammation, while advantageous strains, like Faecalibaculum rodentium, have the ability to suppress tumors by modifying immune responses. Cytokine activity and immune system regulation are intimately related. Cytokines including TGF-β, IL-6, and IL-10 promote tumor development by inhibiting efficient immune surveillance. The gut microbiome exhibits a delicate balance between pro- and anti-tumorigenic factors, as evidenced by the enhancement of anti-tumor immunity by cytokines such as IL-12 and IFN-γ. Improved immunotherapy responses are linked to a diverse microbiota, which is correlated with higher tumor infiltration and cytotoxic T-cell activation. Because microbial metabolites, especially short-chain fatty acids, affect cytokine expression and immune cell activation inside the tumor microenvironment, this link highlights the need to maintain microbial balance for optimal treatment effects. Additionally, through stimulating T-cell activation, bacteria like Lactobacillus rhamnosus and Bifidobacterium bifidum increase cytokine production and improve the efficacy of immune checkpoint inhibitors (ICIs). An option for overcoming ICI resistance is fecal microbiota transplantation (FMT), since research suggests that it improves melanoma outcomes by increasing CD8+ T-cell activation. This complex interaction provides an opportunity for novel cancer therapies by highlighting the possibility of microbiome modification as a therapeutic approach in personalized oncology approaches.}, } @article {pmid39767577, year = {2024}, author = {Munteanu, C and Onose, G and Rotariu, M and Poștaru, M and Turnea, M and Galaction, AI}, title = {Role of Microbiota-Derived Hydrogen Sulfide (H2S) in Modulating the Gut-Brain Axis: Implications for Alzheimer's and Parkinson's Disease Pathogenesis.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/biomedicines12122670}, pmid = {39767577}, issn = {2227-9059}, support = {CNFIS - FDI - 2024 - F - 0099//Supporting the institutional capacity for research and innovation through transdisciplinary biotechnologies (InovBiotech)/ ; }, abstract = {Microbiota-derived hydrogen sulfide (H2S) plays a crucial role in modulating the gut-brain axis, with significant implications for neurodegenerative diseases such as Alzheimer's and Parkinson's. H2S is produced by sulfate-reducing bacteria in the gut and acts as a critical signaling molecule influencing brain health via various pathways, including regulating inflammation, oxidative stress, and immune responses. H2S maintains gut barrier integrity at physiological levels and prevents systemic inflammation, which could impact neuroinflammation. However, as H2S has a dual role or a Janus face, excessive H2S production, often resulting from gut dysbiosis, can compromise the intestinal barrier and exacerbate neurodegenerative processes by promoting neuroinflammation and glial cell dysfunction. This imbalance is linked to the early pathogenesis of Alzheimer's and Parkinson's diseases, where the overproduction of H2S exacerbates beta-amyloid deposition, tau hyperphosphorylation, and alpha-synuclein aggregation, driving neuroinflammatory responses and neuronal damage. Targeting gut microbiota to restore H2S homeostasis through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation presents a promising therapeutic approach. By rebalancing the microbiota-derived H2S, these strategies may mitigate neurodegeneration and offer novel treatments for Alzheimer's and Parkinson's diseases, underscoring the critical role of the gut-brain axis in maintaining central nervous system health.}, } @article {pmid39766423, year = {2024}, author = {Menezes, AA and Shah, ZA}, title = {A Review of the Consequences of Gut Microbiota in Neurodegenerative Disorders and Aging.}, journal = {Brain sciences}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/brainsci14121224}, pmid = {39766423}, issn = {2076-3425}, support = {R01NS112642/NS/NINDS NIH HHS/United States ; }, abstract = {Age-associated alterations in the brain lead to cognitive deterioration and neurodegenerative disorders (NDDs). This review with a particular focus on Alzheimer's disease (AD), emphasizes the burgeoning significance of the gut microbiota (GMB) in neuroinflammation and its impact on the gut-brain axis (GBA), a communication conduit between the gut and the central nervous system (CNS). Changes in the gut microbiome, including diminished microbial diversity and the prevalence of pro-inflammatory bacteria, are associated with AD pathogenesis. Promising therapies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, may restore gut health and enhance cognitive performance. Clinical data remain insufficient, necessitating further research to elucidate causes, enhance therapy, and consider individual variances. This integrative approach may yield innovative therapies aimed at the GMB to improve cognitive function and brain health in older people.}, } @article {pmid39766170, year = {2024}, author = {Ciernikova, S and Sevcikova, A and Novisedlakova, M and Mego, M}, title = {Insights into the Relationship Between the Gut Microbiome and Immune Checkpoint Inhibitors in Solid Tumors.}, journal = {Cancers}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/cancers16244271}, pmid = {39766170}, issn = {2072-6694}, support = {1/0071/24//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, abstract = {Immunotherapy with immune checkpoint inhibitors represents a revolutionary approach to the treatment of solid tumors, including malignant melanoma, lung cancer, and gastrointestinal malignancies. Anti-CTLA-4 and anti-PD-1/PDL-1 therapies provide prolonged survival for cancer patients, but their efficacy and safety are highly variable. This review focuses on the crucial role of the gut microbiome in modulating the efficacy and toxicity of immune checkpoint blockade. Studies suggest that the composition of the gut microbiome may influence the response to immunotherapy, with specific bacterial strains able to promote an anti-tumor immune response. On the other hand, dysbiosis may increase the risk of adverse effects, such as immune-mediated colitis. Interventions aimed at modulating the microbiome, including the use of probiotics, prebiotics, fecal microbial transplantation, or dietary modifications, represent promising strategies to increase treatment efficacy and reduce toxicity. The combination of immunotherapy with the microbiome-based strategy opens up new possibilities for personalized treatment. In addition, factors such as physical activity and nutritional supplementation may indirectly influence the gut ecosystem and consequently improve treatment outcomes in refractory patients, leading to enhanced patient responses and prolonged survival.}, } @article {pmid39766032, year = {2024}, author = {Altrawy, A and Khalifa, MM and Abdelmaksoud, A and Khaled, Y and Saleh, ZM and Sobhy, H and Abdel-Ghany, S and Alqosaibi, A and Al-Muhanna, A and Almulhim, J and El-Hashash, A and Sabit, H and Arneth, B}, title = {Metabolites in the Dance: Deciphering Gut-Microbiota-Mediated Metabolic Reprogramming of the Breast Tumor Microenvironment.}, journal = {Cancers}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/cancers16244132}, pmid = {39766032}, issn = {2072-6694}, abstract = {Breast cancer (BC), a major cause of death among women worldwide, has traditionally been linked to genetic and environmental factors. However, emerging research highlights the gut microbiome's significant role in shaping BC development, progression, and treatment outcomes. This review explores the intricate relationship between the gut microbiota and the breast tumor microenvironment, emphasizing how these microbes influence immune responses, inflammation, and metabolic pathways. Certain bacterial species in the gut either contribute to or hinder BC progression by producing metabolites that affect hormone metabolism, immune system pathways, and cellular signaling. An imbalance in gut bacteria, known as dysbiosis, has been associated with a heightened risk of BC, with metabolites like short-chain fatty acids (SCFAs) and enzymes such as β-glucuronidase playing key roles in this process. Additionally, the gut microbiota can impact the effectiveness of chemotherapy, as certain bacteria can degrade drugs like gemcitabine and irinotecan, leading to reduced treatment efficacy. Understanding the complex interactions between gut bacteria and BC may pave the way for innovative treatment approaches, including personalized microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, offering new hope for more effective prevention, diagnosis, and treatment of BC.}, } @article {pmid39765038, year = {2024}, author = {Wang, C and Peng, M and Gao, Z and Fu, F and Li, G and Su, D and Huang, L and Guo, J and Shan, Y}, title = {Citrus aurantium 'Changshan-huyou' physiological premature fruit drop: A promising prebiotic to tackle obesity.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {136}, number = {}, pages = {156347}, doi = {10.1016/j.phymed.2024.156347}, pmid = {39765038}, issn = {1618-095X}, abstract = {BACKGROUND: Presently, the mitigation and governance of obesity have surfaced as significant public health dilemmas on a global scale. A wealth of studies indicated that the host gut microbiota is instrumental in regulating the interplay between high-fat diet (HFD) intake and the pathogenesis of obesity. Physiological premature fruit drop, a major byproduct of citrus, is rich in a variety of bioactive constituents, yet its potential has remained underutilized for an extended period.

PURPOSE: The objective of this investigation is to examine the chemical constituents of Citrus aurantium'Changshan-huyou' premature fruit drop (HYFD) and investigate its anti-obesity effects, elucidating its potential pathways.

METHODS: Volatile compounds and flavonoids in HYFD were analyzed using chromatographic and mass spectrometric techniques. Furthermore, this study utilized biochemical assays and histopathological examinations to evaluate the effects of HYFD on HFD-fed mice. The impact of HYFD on the gut microbiota of the mice was examined through 16S rRNA gene sequencing, and fecal microbiota transplantation was employed to validate the role of the gut microbial community in host obesity prevention. Concurrently, transcriptome was employed to identify differentially expressed genes, providing further insights into the molecular mechanisms through which HYFD manifests its anti-obesity effects.

RESULTS: Our findings demonstrated that HYFD supplementation significantly alleviated adiposity and ameliorated the dysbiosis of gut microbiota in HFD-induced mice. HYFD rectified the HFD-induced gut microbiota dysregulation, enhanced the presence of beneficial microbial taxa linked to lipid metabolism, including Parabacteroides and Alistipes, and elevated concentrations of the anti-obesity short-chain fatty acids, comprising caproic acid and isocaproic acid. Additionally, transcriptomic analyses confirmed that HYFD prevented obesity in mice by enhancing fatty acid catabolism via the activation of the AMPK/PPARα/CPT1a signaling pathway.

CONCLUSION: Our results provided novel insights into the mechanism of citrus physiological premature fruit drop and its potential role in preventing obesity, while sparking greater interest in leveraging more biomass waste.}, } @article {pmid39764653, year = {2024}, author = {Mao, Y and Huang, Y and Zhang, W and Liang, H and Liu, F and Luo, Q and Xu, C and Qin, Y and Liu, J and Tang, S and Liu, H and Ge, X}, title = {FMT reduces systemic inflammatory response in severe acute pancreatitis by increasing the abundance of intestinal Bifidobacteria and fecal bacteria.}, journal = {Biomolecules & biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2024.11445}, pmid = {39764653}, issn = {2831-090X}, abstract = {Severe acute pancreatitis (SAP) is one of the leading causes of hospital admissions for gastrointestinal diseases, with a rising incidence worldwide. Intestinal microbiota dysbiosis caused by SAP exacerbates systemic inflammatory response syndrome and organ dysfunction. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic option for gastrointestinal diseases. In this study, fecal samples from healthy, control, and FMT-treated groups were analyzed using 16S rRNA sequencing to assess microbiome abundance and diversity. Composition and functional prediction analyses were conducted to explore the mechanisms underlying FMT in SAP. FMT significantly improved clinical parameters in SAP patients, including leukocyte count, C-reactive protein (CRP), neutrophil granulocyte count, lactate dehydrogenase (LDH), and calcitonin (P < 0.05). Organ failure rates significantly increased in the control group but decreased in the FMT group after treatment (P < 0.05). Fecal microbiota sequencing revealed that FMT significantly upregulated the abundance of Bifidobacterium longum among all SAP patients (P < 0.05). Receiver operating characteristic (ROC) curve analysis indicated that Bifidobacterium longum might play a critical role in the efficacy of FMT, with an area under the curve (AUC) value of 0.84. Additionally, there was a negative correlation between Bifidobacterium longum abundance and procalcitonin (PCT) levels, as well as a negative correlation between Escherichia coli abundance and both CT and Ca values (P < 0.05). The relative abundances of Bifidobacterium longum and Escherichia coli were significantly higher in the FMT group compared to the Bifidobacterium triple viable group (P < 0.05). In conclusion, this research supports FMT as a safe and effective intervention for treating SAP patients.}, } @article {pmid39764615, year = {2025}, author = {Harris, SC and Bajaj, JS}, title = {Interaction of the Gut-Liver-Brain Axis and the sterolbiome with sexual dysfunction in patients with cirrhosis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446390}, doi = {10.1080/19490976.2024.2446390}, pmid = {39764615}, issn = {1949-0984}, mesh = {Humans ; *Liver Cirrhosis/complications/metabolism ; *Gastrointestinal Microbiome ; *Brain-Gut Axis/physiology ; *Sexual Dysfunction, Physiological/metabolism/etiology/physiopathology ; *Liver/metabolism ; Sterols/metabolism ; Brain/metabolism ; Gonadal Steroid Hormones/metabolism ; Animals ; Quality of Life ; }, abstract = {There is a complex interplay between the gut microbes, liver, and central nervous system, a gut-liver-brain axis, where the brain impacts intestinal and hepatic function while the gut and liver can impact cognition and mental status. Dysregulation of this axis can be seen in numerous diseases. Hepatic encephalopathy, a consequence of cirrhosis, is perhaps the best studied perturbation of this system. However, patients with cirrhosis have been shown to have increased incidence of other disorders of mental health which may be otherwise less clinically identifiable. Sexual dysfunction affects a large proportion of patients with cirrhosis and is associated with decreased quality of life. Screening for sexual dysfunction in patients with cirrhosis is often overlooked, and even when identified, treatment options are limited, particularly in patients with advanced liver disease. The mechanism by which patients with cirrhosis develop sexual dysfunction is multifactorial, but a key driver of this clinical manifestation is alterations in circulating sex hormones. In patients with cirrhosis, low serum sex hormones have been shown to be associated with higher mortality regardless of MELD score. The gut microbiome has been shown to have an immense metabolic capacity to metabolize steroid hormones. This "sterolbiome" has already been implicated in other disease processes and has been linked to low circulating sex hormones, suggesting a new mechanism by which sex hormones may be altered in disease states where the gut-liver-brain axis is disrupted. The aim of this review is to cover sex hormone changes and sexual dysfunction in cirrhosis, examine the gut microbiome and its metabolic capacity, particularly for steroid hormones, and consider how microbial changes using fecal microbiota transplant could modulate sexual dysfunction.}, } @article {pmid39764447, year = {2024}, author = {Wang, J and Zhuang, P and Lin, B and Zheng, J and Li, H and Tang, W and Ye, W and Chen, X and Zheng, M}, title = {Comparative analysis of gut microbiota in metabolic syndrome and obese children from Southeastern China.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1503302}, pmid = {39764447}, issn = {1664-302X}, abstract = {The prevalence of childhood obesity is rising globally, with some obese children progressing to develop metabolic syndrome (MS). However, the specific differences between these groups remain unclear. To investigate the differences in gut microbiota, we conducted physiological and biochemical assessments, alongside 16S rRNA sequencing, in a cohort of 32 children from Southeastern China, which included 4 normal-weight children, 5 with mild obesity, 9 with moderate obesity, 9 with severe obesity, and 5 with metabolic syndrome. Our results indicated that waist circumference, serum triglycerides, total cholesterol, non-HDL levels, and the prevalence of fatty liver were significantly elevated in both obese and MS children compared to their normal-weight peers, with the MS group exhibiting more pronounced abnormalities. Conversely, HDL levels showed a contrasting trend. Additionally, alpha diversity of gut microbiota increased with weight, while beta diversity analysis revealed significant compositional differences between children with MS and those who were normal weight or obese. At the class and genus levels, we found that the relative abundance of c_Gammaproteobacteria increased with weight, whereas c_Bacteroidia and g_Bacteroides decreased. Notably, g_Faecalibacterium was significantly less abundant in the MS group compared to the other cohorts. LEfSe and functional analyses identified distinct gut microbiota and functional differences between children with MS and those with normal weight or obesity. Furthermore, gavage experiments in mice showed that gut microbiota from obese and MS subjects significantly increased serum triglycerides and cholesterol levels, leading to hepatocellular damage. In contrast, fecal gavage from normal-weight individuals into obese model mice significantly reduced serum triglycerides and the number of degenerative liver cells, as well as the extent of fat accumulation. These findings provide critical insights into the understanding and management of obesity and metabolic syndrome in pediatric populations.}, } @article {pmid39762283, year = {2025}, author = {Feng, C and Wu, Y and Zhang, X and Wang, S and Wang, J and Yang, H}, title = {Maternal milk fat globule membrane enriched gut L. murinus and circulating SCFAs to improve placental efficiency and fetal development in intrauterine growth restricted mice model.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2449095}, doi = {10.1080/19490976.2024.2449095}, pmid = {39762283}, issn = {1949-0984}, mesh = {Animals ; Female ; Pregnancy ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Placenta/metabolism ; *Fetal Growth Retardation/metabolism ; *Glycoproteins/metabolism ; *Fatty Acids, Volatile/metabolism ; *Lipid Droplets/metabolism ; *Glycolipids/metabolism ; *Fetal Development/drug effects ; *Disease Models, Animal ; Lactobacillus ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; }, abstract = {Intrauterine growth restriction (IUGR) caused by placental dysfunctions leads to fetal growth defects. Maternal microbiome and its metabolites have been reported to promote placental development. Milk fat globule membrane (MFGM) is known for its diverse bioactive functions, while the effects of gestational MFGM supplementation on the maternal gut microbiota, placental efficiency, and fetal development remained unclear. In this study, low protein diet-induced IUGR decreased the litter birth weight, fetal birth weight, and the fetal/placental ratio in pregnant mice, while gestational MFGM supplementation restored these impairments. Meanwhile, MFGM supplementation during gestation enriched intestinal Lactobacillus murinus (L. murinus) and increased luminal and circulating short chain fatty acids (SCFAs) in IUGR pregnant mice, which improved placental efficiency and fetal development due to an enhanced antioxidant capacity and a decreased inflammation. In addition, fecal microbiota transplantation (FMT) with MFGM-derived microbiota reprinted the promoted phenotypes of maternal litter characteristics, gut L. murinus enrichment, placental efficiency, and fetal gut development in MFGM-fed pregnant mice, which were also recapitulated by exogenous administration with L. murinus or SCFAs cocktail. Mechanically, MFGM, MFGM-derived microbiota, L. murinus, or SCFAs cocktail activated IUGR-induced depressive phosphorylation of PI3K-Akt signaling in the placenta. Moreover, in vitro placental cells cultivation under amino acid shortage model (AAS) or oxygen-glucose shortage model (OGS) was used to validate that MFGM-derived key microbial and circulating SCFAs cocktails can alleviate placental oxidative stress and inflammation via activating PI3K/Akt signaling. Taken together, gestational MFGM supplementation enriched intestinal L. murinus and circulating SCFAs of IUGR pregnant mice, thereby improving placental efficiency, fetal growth, and intestinal functions of IUGR fetus. Our findings will provide theoretical support for the application of MFGM in the maternal-placental-fetal nutrition to address pregnancy malnutrition-induced IUGR.}, } @article {pmid39762111, year = {2025}, author = {Al-Shakhshir, S and Quraishi, MN and Mullish, B and Patel, A and Vince, A and Rowe, A and Homer, V and Jackson, N and Gyimah, D and Shabir, S and Manzoor, S and Cooney, R and Alrubaiy, L and Quince, C and van Schaik, W and Hares, M and Beggs, AD and Efstathiou, E and Rimmer, P and Weston, C and Iqbal, T and Trivedi, PJ}, title = {FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e095392}, doi = {10.1136/bmjopen-2024-095392}, pmid = {39762111}, issn = {2044-6055}, mesh = {Adult ; Female ; Humans ; Male ; *Cholangitis, Sclerosing/therapy ; Clinical Trials, Phase II as Topic ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/therapy/microbiology ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity. However, the longevity of such changes and the impact on markers of disease activity and disease progression have not been studied. The aim of this clinical trial is to determine the effects of repeated FMT as a treatment for PSC-IBD.

METHODS AND ANALYSIS: FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO) is a phase IIa randomised placebo-controlled trial to assess the efficacy and safety of repeated colonic administration of FMT in patients with non-cirrhotic PSC-IBD. Fifty-eight patients will be recruited from six sites across England and randomised in a 1:1 ratio between active FMT or FMT placebo arms. FMT will be manufactured by the University of Birmingham Microbiome Treatment Centre, using stool collected from rigorously screened healthy donors. A total of 8 weekly treatments will be delivered; the first through colonoscopic administration (week 1) and the remaining seven via once-weekly enema (up to week 8). Participants will then be followed on a 12-weekly basis until week 48 from the first treatment visit. The primary efficacy outcome will be to determine the effect of FMT on serum alkaline phosphatase values over time (end of study at 48 weeks). Key secondary outcomes will be to evaluate the impact of FMT on other liver biochemical parameters, PSC risk scores, circulating and imaging markers of liver fibrosis, health-related quality of life measures, IBD activity and the incidence of PSC-related clinical events. Key translational objectives will be to identify mucosal metagenomic, metatranscriptomic, metabolomic and immunological pathways associated with the administration of FMT.

ETHICS AND DISSEMINATION: The protocol was approved by the South Central-Hampshire B Research Ethics Committee (REC 23/SC/0147). Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

TRIAL REGISTRATION NUMBER: The trial was registered at ClinicalTrials.gov on 23 February 2024 (NCT06286709). Weblink: Study Details | FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis | ClinicalTrials.gov.}, } @article {pmid39761011, year = {2024}, author = {Jain, V and Dalby, MJ and Alexander, EC and Burford, C and Acford-Palmer, H and Serghiou, IR and Teng, NMY and Kiu, R and Gerasimidis, K and Zafeiropoulou, K and Logan, M and Verma, A and Davenport, M and Hall, LJ and Dhawan, A}, title = {Association of gut microbiota and gut metabolites and adverse outcomes in biliary atresia: A longitudinal prospective study.}, journal = {Hepatology communications}, volume = {8}, number = {11}, pages = {}, pmid = {39761011}, issn = {2471-254X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Biliary Atresia/surgery/microbiology/metabolism ; *Feces/microbiology ; Male ; Female ; Prospective Studies ; Infant ; Longitudinal Studies ; Portoenterostomy, Hepatic ; RNA, Ribosomal, 16S/genetics ; Enterococcus ; Case-Control Studies ; Infant, Newborn ; Bifidobacterium/isolation & purification ; }, abstract = {BACKGROUND: The Kasai portoenterostomy (KPE) aims to re-establish bile flow in biliary atresia (BA); however, BA remains the commonest indication for liver transplantation in pediatrics. Gut microbiota-host interplay is increasingly associated with outcomes in chronic liver disease. This study characterized fecal microbiota and fatty acid metabolites in BA.

METHODS: Fecal samples were prospectively collected in newly diagnosed BA infants (n = 55) before and after KPE. Age-matched healthy control (n = 19) and cholestatic control (n = 21) fecal samples were collected. Fecal 16S rRNA gene amplicon sequencing for gut microbiota and gas chromatography for fecal fatty acids was performed.

RESULTS: Increased abundance of Enterococcus in pre-KPE BA and cholestatic control infants, compared to healthy infants, was demonstrated. At the early post-KPE time points, increased alpha diversity was revealed in BA versus healthy cohorts. A lower relative abundance of Bifidobacterium and increased Enterococcus, Clostridium, Fusobacterium, and Pseudomonas was seen in infants with BA. Fecal acetate was reduced, and fecal butyrate and propionate were elevated in early post-KPE BA infants. Higher post-KPE alpha diversity was associated with nonfavorable clinical outcomes (6-month jaundice and liver transplantation). A higher relative abundance of post-KPE Streptococcus and Fusobacterium and a lower relative abundance of Dorea, Blautia, and Oscillospira were associated with nonfavorable clinical outcomes. Blautia inversely correlated to liver disease severity, and Bifidobacterium inversely correlated to fibrosis biomarkers. Bifidobacterium abundance was significantly lower in infants experiencing cholangitis within 6 months after KPE.

CONCLUSIONS: Increased diversity, enrichment of pathogenic, and depletion of beneficial microbiota early post-KPE are all factors associated with nonfavorable BA outcomes. Manipulation of gut microbiota in the early postsurgical period could provide therapeutic potential.}, } @article {pmid39760535, year = {2025}, author = {Saha, S and Schnabl, B}, title = {Modulating the microbiome in chronic liver diseases- current evidence on the role of fecal microbiota transplantation.}, journal = {Expert review of gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1080/17474124.2025.2450707}, pmid = {39760535}, issn = {1747-4132}, abstract = {INTRODUCTION: The gut microbiota has a complex relationship with the human host and is key to maintaining health. Disruption of the healthy diverse gut microbial milieu plays an important role in the pathogenesis of several diseases including Clostridioides difficile infection (CDI), inflammatory bowel disease, irritable bowel syndrome, alcohol-related liver disease and metabolic-dysfunction associated steatotic liver disease (MASLD). Fecal microbiota transplantation (FMT) is highly effective in treating CDI, though its utility in other diseases is still being explored.

AREAS COVERED: In this narrative review, we explore the role of gut microbiota in liver diseases, focusing on key changes in the microbial composition and function. We summarize current evidence on the role of FMT, identifying gaps in current research and outlining future directions for investigation. We comprehensively searched PubMed through 15 October 2024 to identify relevant studies.

EXPERT OPINION: While data from available studies shows promise, more research is necessary before we can use FMT for liver diseases. Key areas that require further study are- determining the optimal FMT regimen for each disease, establishing efficacy and safety with larger clinical trials, ensuring safe and equitable access to the FMT product and mechanistic insights into the reasons for success or failure of FMT.}, } @article {pmid39759692, year = {2024}, author = {Muzaffer, M and Masarath, A and Mohammed, F}, title = {Biliary Atresia: A Case Report.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e75087}, pmid = {39759692}, issn = {2168-8184}, abstract = {Biliary atresia (BA) is a serious hepatobiliary disorder that occurs due to progressive inflammation and scarring obstruction in the bile ducts, posing a threat to life. This condition usually appears in infants, and timely identification is fundamental for a better prognosis. If left untreated, individuals will inevitably experience liver damage and mortality. This case report describes a nine-month-old female infant presenting with jaundice, icteric sclera, yellowish skin, acholic feces, and hepatomegaly. Elevated liver enzymes and a hepatobiliary iminodiacetic acid (HIDA) scan confirmed BA. Histopathological examination revealed fibrosis, cholestatic disease, and an atretic gallbladder. A modified Kasai portoenterostomy (KPE) with Roux-en-Y jejunojejunostomy was performed, and the infant was discharged with supportive care. However, seven months post-Kasai portoenterostomy, the infant presented with persistent jaundice and progressive deterioration of liver function, indicative of a failed Kasai procedure. Consequently, she was scheduled to undergo liver transplantation (LT) as a definitive treatment. BA is a rare disorder that is observed across nearly all ethnic groups, though the incidence rates vary significantly. This case highlights the efficacy of liver transplantation in treating failed Kasai procedures and demonstrates the potential for enhanced outcomes in infants with end-stage liver disease.}, } @article {pmid39758967, year = {2025}, author = {Thorndal, C and Kragsnaes, MS and Nilsson, AC and Holm, DK and dePont Christensen, R and Ellingsen, T and Kjeldsen, J and Bjørsum-Meyer, T}, title = {Safety and efficacy of faecal microbiota transplantation in patients with acute uncomplicated diverticulitis: study protocol for a randomised placebo-controlled trial.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848241309868}, pmid = {39758967}, issn = {1756-283X}, abstract = {BACKGROUND: Little is known about the involvement of gut microbiota in the disease course of diverticulitis and the potential benefits of manipulating the gut milieu. We propose to conduct a randomised placebo-controlled feasibility trial of faecal microbiota transplantation (FMT) given as capsules to patients with acute uncomplicated diverticulitis.

OBJECTIVES: The objective is primarily to investigate the feasibility of clinical safety, explore efficacy associated with FMT in this patient population, and examine changes in patient-reported quality of life and the composition and function of the gut microbiota.

DESIGN: Study protocol for a randomised placebo-controlled trial.

METHODS AND ANALYSIS: Participants with acute, uncomplicated diverticulitis, as confirmed by computed tomography (CT) scan, will be recruited from Odense University Hospital (Denmark) and randomly assigned to either the intervention group or the control group. The intervention group will consist of 20 patients who receive encapsulated FMT. The control group will also consist of 20 patients, receiving placebo capsules. Primary safety endpoint: Patient safety is monitored by (a) the number of re-admissions and (b) the number of adverse events within 3 months of FMT/placebo; Primary efficacy endpoint: Reduction in the proportion of patients treated with antibiotics within 3 months following FMT/placebo; Secondary outcome: Change from baseline to 3 months in the GI-QLI questionnaire. Results will be analysed using an intention-to-treat approach. Adverse events or unintended consequences will be reported.

ETHICS AND DISCUSSION: This is the first study to investigate the safety and efficacy of FMT in patients with acute uncomplicated diverticulitis. The project has the potential to broaden the knowledge and literature on the role of the intestinal microbiota in diverticulitis, and we believe it will elevate our understanding of cause and effect.

TRIAL REGISTRATION: Informed consent is obtained from all participants. The study is approved by the regional ethics committee (ref. S-20230023) and the Danish Data Protection Agency (ref. 24/2435). The trial was registered on clinicaltrials.gov (NCT06254625) on 10th February 2024.}, } @article {pmid39758313, year = {2024}, author = {Liu, B and Zhang, Z and Zhao, J and Li, X and Wang, Y and Liu, L and Qiao, W and Chen, L}, title = {Lactiplantibacillus plantarum HM-P2 influences gestational gut microbiome and microbial metabolism.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1489359}, pmid = {39758313}, issn = {2296-861X}, abstract = {INTRODUCTION: Human milk-derived probiotics are beneficial bacteria that provide gestational health benefits, for both pregnant women and their offspring. The study aims to investigate whether the administration of human milk-derived probiotic L. plantarum HM-P2 could effectively influence gestational health.

METHODS: The gestational humanized microbiome model was built by fecal microbiome transplant from gestational women into germ-free (GF) mice.

RESULTS: HM-P2 was successfully planted and increased the top crypt depth of the colon, and microbes such as L. reuteri, Anaerofilum sp. An201, and Gemmiger were up-regulated in the HM-P2 group throughout gestation. HM-P2 significantly promoted the contents of intestinal caproic acid, bile acids, and tryptophan catabolites such as serotonin. Gut microbes were associated with these bile acids and tryptophans.

DISCUSSION: HM-P2 could modulate the microbial community and microbial metabolites in gestational humanized GF mice. This probiotic strain could be a potential gestational dietary supplement with health benefits.}, } @article {pmid39757809, year = {2025}, author = {Huang, ST and Hu, YH and Gao, YC and Zhou, DD and Chen, MY and Wang, L and Song, JY and Zhou, HH and Zhang, W and Huang, WH}, title = {Hypoglycemic Effect of Ginsenoside Compound K Mediated by N-Acetylserotonin Derived From Gut Microbiota.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8385}, pmid = {39757809}, issn = {1099-1573}, support = {82074000//National Natural Science Foundation of China/ ; 82073945//National Natural Science Foundation of China/ ; 81874329//National Natural Science Foundation of China/ ; 2023YFC3405200//National Key Research and Development Program of China/ ; 2021YFA1301200//National Key Research and Development Program of China/ ; 2024JJ5585//Hunan Provincial Natural Science Foundation of China/ ; 2023SK2083//Scientific Research Project of Furong Laboratory of Central South University/ ; }, abstract = {Ginsenoside compound K (GCK) has been proved to have great hypoglycemic effect pertinent to gut microbiota. However, the improvement of high-fat-diet (HFD)-induced type 2 diabetes (T2D) as well as the mechanism of GCK mediated by gut microbiota is not well-known. This study aimed to investigate the hypoglycemic effects and mechanism of GCK on a HFD-induced diabetic mouse model. HFD-induced pseudo-germ free (GF) T2D mice model and fecal microbiota transplantation (FMT) experiments were performed to clarify the role of gut microbiota in the hypoglycemic effect of GCK. Differential metabolites were screened by untargeted metabolomics analysis and their functions were verified by suppling to T2D mice. The level of glucagon-like peptide-1 (GLP-1) in plasma was detected by ELISA analysis to explore the potential hypoglycemic mechanism of GCK. The results showed GCK alleviated metabolic disorders and altered gut microbiota in HFD-induced diabetic mice, which was transmitted to pseudo-GF diabetic mice via FMT experiment to reproduce the hypoglycemic effect. Non-targeted metabolites analysis on cecal content samples indicated that N-acetylserotonin (NAS) was markedly increased after GCK treatment. Moreover, gavage with NAS improved insulin sensitivity and increased the secretion of GLP-1 in HFD mice. Our study showed that GCK had hypoglycemic effect through modifying gut microbiota profiling.}, } @article {pmid39757609, year = {2024}, author = {Bhat, MM and Hussain, MS and Bisht, AS and Agrawal, M and Sultana, A and Khurrana, N and Kumar, R}, title = {Frontiers in Pulmonary Hypertension: A Comprehensive Insight of Etiological Advances.}, journal = {Current reviews in clinical and experimental pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724328325178241210174545}, pmid = {39757609}, issn = {2772-4336}, abstract = {Pulmonary hypertension (PH) is a severe, progressive disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular failure and increased mortality. Despite advancements in management, the median survival for PH patients remains 5-7 years, with an inhospital mortality rate of approximately 6%. The core pathological feature of PH is pulmonary vascular remodeling (PVR), a multifactorial process involving endothelial dysfunction, inflammation, and aberrant immune responses. While current therapies target endothelial dysfunction, they fall short of preventing PVR or halting disease progression. Emerging research highlights the potential of immune-inflammatory pathways, oxygen-sensing mechanisms, and gut microbiota modulation as therapeutic targets. Integrating nutritional strategies, probiotics, and fecal microbiota transplantation (FMT) as adjunctive therapies also shows promise. These factors may collectively influence PVR, offering novel insights into therapeutic avenues for PH management in the future.}, } @article {pmid39756658, year = {2025}, author = {Chen, Q and Liu, F and Zhang, G and Qu, Q and Chen, Y and Li, M and Huang, Q and Fu, H and Zhu, X and He, Y and Huang, X and Zhang, X}, title = {Progesterone Regulates Gut Microbiota Mediating Bone Marrow MSCs Injury in ITP Patients during Pregnancy.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtha.2024.12.027}, pmid = {39756658}, issn = {1538-7836}, abstract = {BACKGROUND: Immune thrombocytopenia during pregnancy (PITP) is the most common cause of platelet reduction in early and mid-pregnancy. However, the pathogenesis of PITP is still unclear.

OBJECTIVES: To determine the characteristics of bone marrow mesenchymal stem cells (BM-MSCs) in PITP patients and to explore the associations between metabolites, the gut microbiota, and BM-MSCs in PITP.

METHODS: The characteristics of BM-MSCs were detected through in vitro and in vivo experiments. Non-targeted metabolomics was used to screen metabolites. The features of the gut microbiota were analyzed by 16S rDNA sequencing. PITP and a fecal microbiota transplantation (FMT) mouse model were established to explore the associations between metabolites, the gut microbiota, and BM-MSCs.

RESULTS: BM-MSCs from PITP patients had significant senescence and apoptosis, as well as impaired immunoregulatory function. Metabolomic analysis indicated that progesterone was the most significant specific metabolite in PITP patients. In vivo studies showed that progesterone mediated the MSCs injury. Further analysis of the gut microbiota and FMT experiments revealed that progesterone mediated BM-MSCs injury by regulating the the composition of the gut microbiota in the PITP. RNA-seq analysis of BM-MSCs from FMT mice revealed abnormal expression of genes related to cell aging and the NOD-like receptor signaling pathway.

CONCLUSION: In conclusion, BM-MSCs in the PITP were significantly impaired, which was associated with increased progesterone and changes in the gut microbiota regulated by progesterone. Intervening with the gut microbiota may become a new treatment for PITP.}, } @article {pmid39754054, year = {2025}, author = {Azhar Ud Din, M and Lin, Y and Lyu, C and Yi, C and Fang, A and Mao, F}, title = {Advancing therapeutic strategies for graft-versus-host disease by targeting gut microbiome dynamics in allogeneic hematopoietic stem cell transplantation: current evidence and future directions.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {2}, pmid = {39754054}, issn = {1528-3658}, mesh = {*Graft vs Host Disease/etiology/microbiology ; Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; *Transplantation, Homologous ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Hematopoietic stem cell transplantation (HSCT) is a highly effective therapy for malignant blood illnesses that pose a high risk, as well as diseases that are at risk due to other variables, such as genetics. However, the prevalence of graft-versus-host disease (GVHD) has impeded its widespread use. Ensuring the stability of microbial varieties and associated metabolites is crucial for supporting metabolic processes, preventing pathogen intrusion, and modulating the immune system. Consequently, it significantly affects the overall well-being and susceptibility of the host to disease. Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) may experience a disruption in the balance between the immune system and gut bacteria when treated with medicines and foreign cells. This can lead to secondary intestinal inflammation and GVHD. Thus, GM is both a reliable indicator of post-transplant mortality and a means of enhancing GVHD prevention and treatment after allo-HSCT. This can be achieved through various strategies, including nutritional support, probiotics, selective use of antibiotics, and fecal microbiota transplantation (FMT) to target gut microbes. This review examines research advancements and the practical use of intestinal bacteria in GVHD following allo-HSCT. These findings may offer novel insights into the prevention and treatment of GVHD after allo-HSCT.}, } @article {pmid39747695, year = {2025}, author = {Wang, X and Fang, Y and Liang, W and Cai, Y and Wong, CC and Wang, J and Wang, N and Lau, HC and Jiao, Y and Zhou, X and Ye, L and Mo, M and Yang, T and Fan, M and Song, L and Zhou, H and Zhao, Q and Chu, ES and Liang, M and Liu, W and Liu, X and Zhang, S and Shang, H and Wei, H and Li, X and Xu, L and Liao, B and Sung, JJY and Kuang, M and Yu, J}, title = {Gut-liver translocation of pathogen Klebsiella pneumoniae promotes hepatocellular carcinoma in mice.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {39747695}, issn = {2058-5276}, support = {82173191//National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund)/ ; }, abstract = {Hepatocellular carcinoma (HCC) is accompanied by an altered gut microbiota but whether the latter contributes to carcinogenesis is unclear. Here we show that faecal microbiota transplantation (FMT) using stool samples from patients with HCC spontaneously initiate liver inflammation, fibrosis and dysplasia in wild-type mice, and accelerate disease progression in a mouse model of HCC. We find that HCC-FMT results in gut barrier injury and translocation of live bacteria to the liver. Metagenomic analyses and bacterial culture of liver tissues reveal enrichment of the gut pathogen Klebsiella pneumoniae in patients with HCC and mice transplanted with the HCC microbiota. Moreover, K. pneumoniae monocolonization recapitulates the effect of HCC-FMT in promoting liver inflammation and hepatocarcinogenesis. Mechanistically, K. pneumoniae surface protein PBP1B interacts with and activates TLR4 on HCC cells, leading to increased cell proliferation and activation of oncogenic signalling. Targeting gut colonization using K. oxytoca or TLR4 inhibition represses K. pneumoniae-induced HCC progression. These findings indicate a role for an altered gut microbiota in hepatocarcinogenesis.}, } @article {pmid39746875, year = {2025}, author = {Faith, JJ}, title = {Assessing live microbial therapeutic transmission.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447836}, doi = {10.1080/19490976.2024.2447836}, pmid = {39746875}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/microbiology/therapy/drug therapy ; *Clostridioides difficile/drug effects/physiology/genetics ; *Gastrointestinal Microbiome ; Feces/microbiology ; Animals ; }, abstract = {The development of fecal microbiota transplantation and defined live biotherapeutic products for the treatment of human disease has been an empirically driven process yielding a notable success of approved drugs for the treatment of recurrent Clostridioides difficile infection. Assessing the potential of this therapeutic modality in other indications with mixed clinical results would benefit from consistent quantitative frameworks to characterize drug potency and composition and to assess the impact of dose and composition on the frequency and duration of strain engraftment. Monitoring these drug properties and engraftment outcomes would help identify minimally sufficient sets of microbial strains to treat disease and provide insights into the intersection between microbial function and host physiology. Broad and correct usage of strain detection methods is essential to this advancement. This article describes strain detection approaches, where they are best applied, what data they require, and clinical trial designs that are best suited to their application.}, } @article {pmid39746695, year = {2024}, author = {He, H and Zhang, JP and Wei, ZJ and Lu, Y and Zhao, YL and Sun, RJ}, title = {[Role of human herpesvirus infection in refractory gastrointestinal graft-versus-host-disease after hematopoietic stem cell transplantation and the diagnosis and treatment thereof].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {45}, number = {11}, pages = {1016-1021}, doi = {10.3760/cma.j.cn121090-20240906-00339}, pmid = {39746695}, issn = {0253-2727}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; Adult ; Middle Aged ; *Graft vs Host Disease/diagnosis/etiology ; Retrospective Studies ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Herpesviridae Infections/diagnosis ; Transplantation, Homologous ; Cytomegalovirus/isolation & purification ; Herpesvirus 6, Human/isolation & purification ; }, abstract = {Objective: This study aimed to investigate the role of human herpesvirus (HHV) infection in refractory intestinal graft-versus-host disease (GI-GVHD) after hematopoietic stem cell transplantation (HSCT) and its diagnosis and treatment. Methods: This study retrospectively analyzed patients presenting with refractory GI-GVHD after allogeneic HSCT (allo-HSCT) with concomitant colonoscopy and mucosal biopsy at Lu Daopei Hospital, Yanda, Hebei, from March 2022 to July 2024. Human herpesvirus 6 (HHV6), HHV7, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) detection with the RQ-PCR method. The intestinal mucosa was pathologically assessed and immunohistochemistry was utilized to detect the CMV early antigen, CMV late antigen, and EBV by in situ hybridization. Results: This study included 42 patients, consisting of 25 males and 17 females with a median age of 26 (1-59) years. All were histopathologically diagnosed as GI-GVHD. Among them, 34 (81.0%) cases had combined viral enteritis, with 52.4% positive for EBV, 38.1% positive for HHV6, 26.2% positive for CMV, and 14.3% positive for HHV7. Further, 17 (40.5%) cases had mixed viral infections, including 5 EBV+ HHV6, 3 CMV+HHV6, 3 CMV+EBV, 2 CMV+EBV+HHV6, 2 EBV+HHV6+HHV7, 1 EBV+HHV7, and 1 HHV6 + HHV7 cases. Furthermore, 17 (40.5%) had a single viral infection, including 9 EBV, 3 CMV, 3 HHV6, and 2 HHV7 cases. Moreover, 17 (40.5%) patients exhibited a positive histopathological viral test, including 7 (16.6%) CMV-positive and 12 (28.5%) EBV-positive cases. The same positive virus was detected in the feces of all 34 patients with positive tissue homogenate virus, and the positive rate of the same virus in the blood was 17.6%. Tissue homogenized virus testing was utilized as the diagnostic criterion for enterocolitis: blood tests for CMV, EBV, HHV6, and HHV7 demonstrated a sensitivity of 45.4%, 4.5%, 6.3%, and 0%, and specificity of 90.3%, 95%, 100%, and 110%, respectively. Additionally, fecal tests for CMV, EBV, HHV6, and HHV7 demonstrated a sensitivity and specificity of 100%. Treatment based on etiology caused ORR and CR rates for diarrhea of 76.1% (32/42) and 66.6% (28/42), respectively. The median follow-up of 42 patients was 13 (1 - 49) months, and 28 patients survived, with an expected 2-year survival rate of 61.9%. Conclusion: In addition to GVHD itself, intestinal human herpesvirus infection is one of the reasons for the refractory nature of GI-GVHD. Viral testing in blood and tissues reveals significant segregation, and the possibility of comorbid viral enteritis cannot be excluded even if a patient with GI-GVHD tests negative for blood viruses.}, } @article {pmid39744736, year = {2024}, author = {Jeyaraman, N and Jeyaraman, M and Dhanpal, P and Ramasubramanian, S and Ragavanandam, L and Muthu, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Gut microbiome and orthopaedic health: Bridging the divide between digestion and bone integrity.}, journal = {World journal of orthopedics}, volume = {15}, number = {12}, pages = {1135-1145}, pmid = {39744736}, issn = {2218-5836}, abstract = {The gut microbiome, a complex ecosystem of microorganisms in the digestive tract, has emerged as a critical factor in human health, influencing metabolic, immune, and neurological functions. This review explores the connection between the gut microbiome and orthopedic health, examining how gut microbes impact bone density, joint integrity, and skeletal health. It highlights mechanisms linking gut dysbiosis to inflammation in conditions such as rheumatoid arthritis and osteoarthritis, suggesting microbiome modulation as a potential therapeutic strategy. Key findings include the microbiome's role in bone metabolism through hormone regulation and production of short-chain fatty acids, crucial for mineral absorption. The review also considers the effects of diet, probiotics, and fecal microbiota transplantation on gut microbiome composition and their implications for orthopedic health. While promising, challenges in translating microbiome research into clinical practice persist, necessitating further exploration and ethical consideration of microbiome-based therapies. This interdisciplinary research aims to link digestive health with musculoskeletal integrity, offering new insights into the prevention and management of bone and joint diseases.}, } @article {pmid39744230, year = {2025}, author = {Singh, A and Chandrasekar, SV and Valappil, VT and Scaria, J and Ranjan, A}, title = {Tumor immunomodulation by nanoparticle and focused ultrasound alters gut microbiome in a sexually dimorphic manner.}, journal = {Theranostics}, volume = {15}, number = {1}, pages = {216-232}, pmid = {39744230}, issn = {1838-7640}, mesh = {Animals ; Female ; Male ; *Gastrointestinal Microbiome/immunology ; Mice ; *Nanoparticles/administration & dosage ; *Immunomodulation ; Calreticulin/metabolism ; Cell Line, Tumor ; Immunogenic Cell Death/drug effects ; Mice, Inbred C57BL ; Mouth Neoplasms/immunology/microbiology/therapy ; Sex Characteristics ; Cytokines/metabolism ; }, abstract = {Background: Local immunomodulation with nanoparticles (NPs) and focused ultrasound (FUS) is recognized for triggering anti-tumor immunity. However, the impact of these tumor immunomodulations on sex-specific microbiome diversity at distant sites and their correlation with therapeutic effectiveness remains unknown. Here, we conducted local intratumoral therapy using immunogenic cell death-enhancing Calreticulin-Nanoparticles (CRT-NPs) and FUS in male and female mice. We identified immune-related microbiome populations, aiming to translate our findings into clinical applications. Methods: CRT-NPs were synthesized by loading CRT-delivering plasmids into cationic liposomes. Local tumor therapy was performed using CRT-NP and FUS-based histotripsy (HT) on poorly immunogenic Mouse Oral Squamous Cell Carcinoma (MOC2) in the flank regions of male and female mice. Fecal samples were collected and analyzed before and three weeks post-treatment. The microbiome features were then correlated with immune cell dynamics within tumors and systemic cytokine responses to identify prognostic biomarkers in both male and female subjects. Results: Intratumorally administered CRT-NP induced tumor remission and immune cell activation in both male and female mice, whereas HT was ineffective in males and showed efficacy only in females. Turicibacter and Peptococcus inversely correlated with tumor growth, while Enterorhabdus, Subdologranulum, Desulfovibrio, and Aldercreutzia-Asaccharobacter showed direct correlations with tumor growth. HT induced higher levels of Turicibacter in MOC2-bearing females, while males displayed increased Enterorhabdus and Streptococcus populations. Independent of sex, treatments promoting CD4+ T helper cells, functional CD8+ T cells, and total macrophage infiltration correlated with higher levels of Gastrophilales, Romboutsia, Turicibacter, and Peptococcus. Alternatively, Enterorhabdus, Desulfovibrio, Streptococcus, and Staphylococcus corresponded to poor treatment outcomes in both sexes. Conclusion: An enhanced abundance of Enterorhabdus, Desulfovibrio, Streptococcus, and Staphylococcus in response to immunomodulatory therapies could serve as predictive biomarkers in a sex-independent manner. These findings could also be potentially extended to the realm of personalized interventions through fecal transplantations to reverse immunosuppressive phenotypes in males and improve patient outcomes.}, } @article {pmid39741383, year = {2024}, author = {van Rheenen, PF and Kolho, KL and Russell, RK and Aloi, M and Deganello, A and Hussey, S and Junge, N and De Laffolie, J and Deneau, MR and Fitzpatrick, E and Griffiths, AM and Hojsak, I and Nicastro, E and Nita, A and Pakarinen, M and Ricciuto, A and de Ridder, L and Sonzogni, A and Tenca, A and Samyn, M and Indolfi, G}, title = {Primary sclerosing cholangitis in children with inflammatory bowel disease: An ESPGHAN position paper from the Hepatology Committee and the IBD Porto group.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.12378}, pmid = {39741383}, issn = {1536-4801}, support = {//European Society for Paediatric Gastroenterology Hepatology and Nutrition/ ; }, abstract = {OBJECTIVE: We aimed to provide an evidence-supported approach to diagnose, monitor, and treat children with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC).

METHODS: The core group formulated seven PICO-structured clinical questions. A systematic literature search from inception to December 2022 was conducted by a medical librarian using MEDLINE and EMBASE. Core messages from the literature were phrased as position statements and then circulated to a sounding board composed of international experts in pediatric gastroenterology and hepatology, histopathology, adult gastroenterology and hepatology, radiology, and surgery. Statements reaching at least 80% agreement were considered as final. The other statements were refined and then subjected to a second online vote or rejection.

RESULTS: Regular screening for gamma-glutamyltransferase (GGT) is essential for detecting possible biliary disease in children with IBD. MR cholangiopancreatography is the radiological modality of choice for establishing the diagnosis of PSC. Liver biopsy is relevant in the evaluation of small duct PSC or autoimmune hepatitis. Children who do not have known IBD at the time of PSC diagnosis should undergo initial screening with fecal calprotectin for asymptomatic colitis, and then at least once yearly thereafter. Children with a cholestatic liver enzyme profile can be considered for treatment with ursodeoxycholic acid and can continue if there is a meaningful reduction or normalization in GGT. Oral vancomycin may have a beneficial effect on GGT and intestinal inflammation, but judicious use is recommended due to the lack of long-term studies. Children with PSC-IBD combined with convincing features of autoimmune hepatitis may benefit from corticosteroids and antimetabolites.

CONCLUSIONS: We present state-of-the-art guidance on the diagnostic criteria, follow-up strategies, and therapeutic strategies and point out research gaps in children and adolescents with PSC-IBD.}, } @article {pmid39739648, year = {2024}, author = {Lei, J and Lv, L and Zhong, L and Xu, F and Su, W and Chen, Y and Wu, Z and He, S and Chen, Y}, title = {The Gut Microbiota Affects Anti-TNF Responsiveness by Activating the NAD[+] Salvage Pathway in Ulcerative Colitis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2413128}, doi = {10.1002/advs.202413128}, pmid = {39739648}, issn = {2198-3844}, support = {82100548//National Natural Science Foundation of China/ ; CSTB2022NSCQ-MSX0094//Natural Science Foundation of Chongqing Municipality/ ; }, abstract = {Approximately 50% of the patients with ulcerative colitis (UC) are primarily nonresponsive to anti-tumor necrosis factor (TNF) therapy or lose their responsiveness over time. The gut microbiota plays an important role in the resistance of UC to anti-TNF therapy; however, the underlying mechanism remains unknown. Here, it is found that the transplantation of gut fecal microbiota from patients with UC alters the diversity of the gut microbiota in dextran sulfate sodium-induced colitis mice and may affect the therapeutic responsiveness of mice to infliximab. Furthermore, the abundances of Romboutsia and Fusobacterium increase in the tissues of patients with UC who do not respond to anti-TNF therapy. Differentially abundant metabolites are mainly enriched in nicotinate and nicotinamide metabolism in NCM460 cells after Fusobacterium nucleatum infection. Mechanistically, F. nucleatum promotes the nicotinamide adenine dinucleotide (NAD[+]) salvage pathway by upregulating NAMPT expression, which subsequently leads to the activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway and promotes the secretion of inflammatory factors, ultimately inhibiting the therapeutic response to anti-TNF drugs. These findings demonstrate that the gut microbiota can influence the response to anti-TNF therapy in patients with UC and highlight the therapeutic potential of targeting F. nucleatum and its associated pathways for preventing and treating drug resistance in UC.}, } @article {pmid39738016, year = {2024}, author = {Li, Z and Gu, M and Zaparte, A and Fu, X and Mahen, K and Mrdjen, M and Li, XS and Yang, Z and Ma, J and Thoudam, T and Chandler, K and Hesler, M and Heathers, L and Gorse, K and Van, TT and Wong, D and Gibson, AM and Wang, Z and Taylor, CM and Quijada, P and Makarewich, CA and Hazen, SL and Liangpunsakul, S and Brown, JM and Lefer, DJ and Welsh, DA and Sharp, TE}, title = {Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {10788}, pmid = {39738016}, issn = {2041-1723}, support = {R01 AA029984/AA/NIAAA NIH HHS/United States ; P50 AA024333/AA/NIAAA NIH HHS/United States ; UH2 AA026226/AA/NIAAA NIH HHS/United States ; P60 AA009803/AA/NIAAA NIH HHS/United States ; R21 AA027199/AA/NIAAA NIH HHS/United States ; U01 AA026917/AA/NIAAA NIH HHS/United States ; UH3 AA026903/AA/NIAAA NIH HHS/United States ; R01AA030312//U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)/ ; T32 AR065972/AR/NIAMS NIH HHS/United States ; T32 HL069766/HL/NHLBI NIH HHS/United States ; R25 HL145817/HL/NHLBI NIH HHS/United States ; HL160569//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HL171221//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL167831/HL/NHLBI NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL146098/HL/NHLBI NIH HHS/United States ; R01 HL146514/HL/NHLBI NIH HHS/United States ; R01 HL151398/HL/NHLBI NIH HHS/United States ; NSF 2018936//National Science Foundation (NSF)/ ; RF1 NS133812/NS/NINDS NIH HHS/United States ; P20 GM103424/GM/NIGMS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; U24 DK1132746//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01 DK130227/DK/NIDDK NIH HHS/United States ; R01 DK120679/DK/NIDDK NIH HHS/United States ; KC2210163//U.S. Department of Defense (United States Department of Defense)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Male ; *Glutamine/metabolism/analogs & derivatives ; *Cardiovascular Diseases/metabolism/microbiology/etiology ; Mice ; Humans ; Mice, Inbred C57BL ; Myocytes, Cardiac/metabolism/drug effects ; Ethanol/pharmacology/metabolism ; Oxidative Stress/drug effects ; Fecal Microbiota Transplantation ; Alcoholism/metabolism ; Disease Models, Animal ; Female ; Glutamates/metabolism ; Endothelial Cells/metabolism/drug effects ; Middle Aged ; }, abstract = {The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology. Fecal microbiota transplantation from pair-/alcohol-fed mice into naïve male mice demonstrates the transmissibility of PAGln production and the CVD phenotype. Independent of alcohol exposure, pharmacological-mediated increases in PAGln elicits direct cardiac and vascular dysfunction. PAGln induced hypercontractility and altered calcium cycling in isolated cardiomyocytes providing evidence of improper relaxation which corresponds to elevated filling pressures observed in vivo. Furthermore, PAGln directly induces vascular endothelial cell activation through induction of oxidative stress leading to endothelial cell dysfunction. We thus reveal that the alcohol-induced microbial reorganization and resultant GMM elevation, specifically PAGln, directly contributes to CVD.}, } @article {pmid39736988, year = {2024}, author = {Wang, F and Wang, Z and Qu, L}, title = {The changes of intestinal flora and metabolites in atopic dermatitis mice.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1462491}, pmid = {39736988}, issn = {1664-302X}, abstract = {INTRODUCTION: Atopic dermatitis (AD) is an allergic disease caused by various factors that can affect an individual's appearance and cause psychological stress. Therefore, it is necessary to investigate the underlying mechanisms and develop effective treatment strategies. The gut microbiota and bacterial metabolism play crucial roles in human diseases. However, their specific role in AD remains unclear.

METHODS: In this study, we established a mouse model of AD and found that 2,4-dinitrofluorobenzene disrupted the skin barrier in mice. The species composition of intestinal bacteria was then analyzed by fecal 16s rRNA sequencing. The metabolic level of mice was analyzed by untargeted and targeted metabolomics in stool.

RESULTS: The levels of filaggrin and aquaporin 3 proteins in the model mice and total superoxide dismutase, catalase and malondialdehyde levels were significantly altered. Additionally, inflammatory factors such as tumor necrosis factor-alpha showed a significant increase. Using 16S rRNA gene sequencing, we identified 270 bacterial species with altered abundances of Ruminococcaceae and Bifidobacteriaceae. The untargeted metabolomic analysis detected 1,299 metabolites. Targeted analysis of free fatty acids revealed 49 metabolites with notable increases in linoleic and linolenic acid levels. Fecal bacterial transplantation experiments have demonstrated that oxidative stress, inflammation, and skin barrier damage were alleviated after transplantation.

DISCUSSION: These findings suggested that the metabolite linoleic acid negatively correlated with Ruminococcaceae and Bifidobacteriaceae may influence AD development. Perturbations in the intestinal bacteria and flora contributed to the development of AD, and the mouse model could serve as a valuable tool for further investigation of therapeutic approaches for managing ADS.}, } @article {pmid39736924, year = {2025}, author = {Yuan, C}, title = {Molecular mechanisms and therapeutic strategies of gut microbiota modulation in Sarcopenia (Review).}, journal = {Oncology letters}, volume = {29}, number = {3}, pages = {104}, pmid = {39736924}, issn = {1792-1082}, abstract = {Sarcopenia is an age-related disease that is characterized by a decline in muscle mass and function with significant epidemiological and clinical implications. In recent years, gut microbiota has gained attention as an important regulatory factor in human health. To the best of our knowledge, this is the first study to introduce the definition and epidemiological background of sarcopenia and analyze the potential impact of the gut microbiota on muscle metabolism and growth, including aspects such as gut microbiota metabolites, muscle protein synthesis and energy metabolism. Additionally, this article summarizes the current research progress in gut microbiota interventions for the treatment of sarcopenia, such as probiotics, prebiotics and fecal microbiota transplantation and discusses future research directions and potential therapeutic strategies.}, } @article {pmid39735707, year = {2024}, author = {Chu, C and Behera, TR and Huang, Y and Qiu, W and Chen, J and Shen, Q}, title = {Research progress of gut microbiome and diabetic nephropathy.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1490314}, pmid = {39735707}, issn = {2296-858X}, abstract = {Diabetic nephropathy is an important complication of diabetic microvascular injury, and it is also an important cause of end-stage renal disease. Its high prevalence and disability rate significantly impacts patients' quality of life while imposing substantial social and economic burdens. Gut microbiota affects host metabolism, multiple organ functions, and regulates host health throughout the life cycle. With the rapid development of technology, researchers have found that gut microbiota is closely related to the progression of diabetic kidney disease. This review explores the role of gut microbiome in diabetic nephropathy summarizing proposed mechanisms of progression and focusing on microbial metabolites, intestinal barrier disruption, inflammation, filtration barrier damage and renal fibrosis. This review also examines the mechanism and limitations of current treatments, including drugs, fecal microbiota transplantation, and lifestyle changes, offering new perspectives on prevention and treatment.}, } @article {pmid39735647, year = {2024}, author = {Wang, H and Li, S and Zhang, L and Zhang, N}, title = {The role of fecal microbiota transplantation in type 2 diabetes mellitus treatment.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1469165}, pmid = {39735647}, issn = {1664-2392}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Diabetes Mellitus, Type 2/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {In contemporary microbial research, the exploration of interactions between microorganisms and multicellular hosts constitutes a burgeoning field. The gut microbiota is increasingly acknowledged as a pivotal contributor to various disorders within the endocrine system, encompassing conditions such as diabetes and thyroid diseases. A surge in research activities has been witnessed in recent years, elucidating the intricate interplay between the gut microbiota and disorders of the endocrine system. Simultaneously, fecal microbiota transplantation (FMT) has emerged as a focal point, garnering substantial attention in both biomedical and clinical spheres. Research endeavors have uncovered the remarkable therapeutic efficacy of FMT across diverse diseases, with particular emphasis on its application in addressing type 2 diabetes mellitus (T2DM) and associated com-plications. Consequently, this manuscript accentuates the intimate connection between the gut microbiota and disorders within the endocrine system, with a specific focus on exploring the potential of FMT as an intervention in the therapeutic landscape of T2DM and its complications. Furthermore, the article scrutinizes concerns inherent in treatment modalities centered around the gut microbiota, proposing viable solutions to address these issues.}, } @article {pmid39735273, year = {2024}, author = {Patnaik, S and Durairajan, SSK and Singh, AK and Krishnamoorthi, S and Iyaswamy, A and Mandavi, SP and Jeewon, R and Williams, LL}, title = {Role of Candida species in pathogenesis, immune regulation, and prognostic tools for managing ulcerative colitis and Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {48}, pages = {5212-5220}, pmid = {39735273}, issn = {2219-2840}, mesh = {Humans ; *Crohn Disease/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; *Colitis, Ulcerative/microbiology/immunology/diagnosis/therapy ; *Dysbiosis/immunology/microbiology ; Prognosis ; Candida albicans/immunology/pathogenicity/isolation & purification ; Immunity, Mucosal ; Candida/immunology/pathogenicity/isolation & purification ; Candidiasis/immunology/microbiology/diagnosis ; Host-Pathogen Interactions ; Intestinal Mucosa/microbiology/immunology ; }, abstract = {The gut microbiome plays a key role in the pathogenesis and disease activity of inflammatory bowel disease (IBD). While research has focused on the bacterial microbiome, recent studies have shifted towards host genetics and host-fungal interactions. The mycobiota is a vital component of the gastrointestinal microbial community and plays a significant role in immune regulation. Among fungi, Candida species, particularly Candida albicans (C. albicans), have been extensively studied due to their dual role as gut commensals and invasive pathogens. Recent findings indicate that various strains of C. albicans exhibit considerable differences in virulence factors, impacting IBD's pathophysiology. Intestinal fungal dysbiosis and antifungal mucosal immunity may be associated to IBD, especially Crohn's disease (CD). This article discusses intestinal fungal dysbiosis and antifungal immunity in healthy individuals and CD patients. It discusses factors influencing the mycobiome's role in IBD pathogenesis and highlights significant contributions from the scientific community aimed at enhancing understanding of the mycobiome and encouraging further research and targeted intervention studies on specific fungal populations. Our article also provided insights into a recent study by Wu et al in the World Journal of Gastroenterology regarding the role of the gut microbiota in the pathogenesis of CD.}, } @article {pmid39735176, year = {2025}, author = {Bhatia, Z and Kumar, S and Seshadri, S}, title = {Fecal microbiota transplantation as a potential therapeutic approach to improve impaired glucose tolerance via gut microbiota modulation in rat model.}, journal = {Journal of diabetes and metabolic disorders}, volume = {24}, number = {1}, pages = {28}, pmid = {39735176}, issn = {2251-6581}, abstract = {OBJECTIVES: To investigate the impact of diet-induced gut microbiota alterations on type 2 diabetes and assess the therapeutic potential of Fecal Microbiota Transplantation (FMT) in restoring a balanced gut microenvironment.

METHODS: To induce type 2 diabetes, rats were fed a high-sugar high-fat diet (HSFD) for 90 days. After diabetes induction, animals were divided into an HSFD control group, a metformin group (100 mg/kg), and an FMT group (100 mg/kg), receiving treatment for an additional 90 days. Fasting blood glucose levels, glucose tolerance, serum markers (HbA1C, free fatty acids, lipopolysaccharides, pro-inflammatory and anti-inflammatory cytokines), and gut microbiota profiles via cecal metagenome sequencing were analyzed post-treatment.

RESULTS: FMT effectively restored gut microbiota composition to a profile similar to healthy controls, rebalancing the Firmicutes/Bacteroidetes ratio and increasing beneficial taxa, including Prevotella ruminicola, Akkermansia muciniphila, Roseburia, and Faecalibacterium prausnitzii. These microbial shifts corresponded with significant metabolic improvements: FMT reduced inflammatory markers (LPS and FFA), lowered HbA1c, and improved glucose tolerance. Enhanced gut barrier integrity observed in FMT-treated animals likely contributed to reduced endotoxemia and systemic inflammation, distinguishing FMT's metabolic effects from those of metformin. Notably, FMT addressed the dysbiosis associated with HSFD, promoting microbial resilience and mitigating the metabolic disruptions linked to type 2 diabetes.

CONCLUSION: These findings underscore the potential of FMT as a targeted therapeutic approach to modulate gut microbiota composition and mitigate metabolic dysregulation induced by high sugar high fat diet.}, } @article {pmid39733842, year = {2024}, author = {Mamun, AA and Geng, P and Wang, S and Shao, C and Xiao, J}, title = {IUPHAR review: Targeted therapies of signaling pathways based on the gut microbiome in autism spectrum disorders: Mechanistic and therapeutic applications.}, journal = {Pharmacological research}, volume = {211}, number = {}, pages = {107559}, doi = {10.1016/j.phrs.2024.107559}, pmid = {39733842}, issn = {1096-1186}, abstract = {Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by impairments in social interaction, communication and repetitive activities. Gut microbiota significantly influences behavior and neurodevelopment by regulating the gut-brain axis. This review explores gut microbiota-influenced treatments for ASD, focusing on their therapeutic applications and mechanistic insights. In addition, this review discusses the interactions between gut microbiota and the immune, metabolic and neuroendocrine systems, focusing on crucial microbial metabolites including short-chain fatty acids (SCFAs) and several neurotransmitters. Furthermore, the review explores various therapy methods including fecal microbiota transplantation, dietary modifications, probiotics and prebiotics and evaluates their safety and efficacy in reducing ASD symptoms. The discussion shows the potential of customized microbiome-based therapeutics and the integration of multi-omics methods to understand the underlying mechanisms. Moreover, the review explores the intricate relationship between gut microbiota and ASD, aiming to develop innovative therapies that utilize the gut microbiome to improve the clinical outcomes of ASD patients. Microbial metabolites such as neurotransmitter precursors, tryptophan metabolites and SCFAs affect brain development and behavior. Symptoms of ASD are linked to changes in these metabolites. Dysbiosis in the gut microbiome may impact neuroinflammatory processes linked to autism, negatively affecting immune signaling pathways. Research indicates that probiotics and prebiotics can improve gut microbiota and alleviate symptoms in ASD patients. Fecal microbiota transplantation may also improve behavioral symptoms and restore gut microbiota balance. The review emphasizes the need for further research on gut microbiota modification as a potential therapeutic approach for ASD, highlighting its potential in clinical settings.}, } @article {pmid39733798, year = {2024}, author = {Luo, Y and Li, M and Luo, D and Tang, B}, title = {Gut Microbiota: An Important Participant in Childhood Obesity.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {}, number = {}, pages = {100362}, doi = {10.1016/j.advnut.2024.100362}, pmid = {39733798}, issn = {2156-5376}, abstract = {Increasing prevalence of childhood obesity has emerged as a critical global public health concern. Recent studies have challenged the previous belief that obesity was solely a result of excessive caloric intake. Alterations in early-life gut microbiota can contribute to childhood obesity through their influence on nutrient absorption and metabolism, initiation of inflammatory responses, and regulation of gut-brain communication. The gut microbiota is increasingly acknowledged to play a crucial role in human health, as certain beneficial bacteria have been scientifically proven to possess the capacity to reduce body fat content and enhance intestinal barrier function, and their metabolic products to exhibit anti-inflammatory effect. Examples of such microbes include bifidobacteria, Akkermansia muciniphila, and Lactobacillus reuteri. In contrast, an increase in Enterobacteriaceae and Propionate-producing bacteria (Prevotellaceae and Veillonellaceae) has been implicated in the induction of low-grade systemic inflammation and disturbances in lipid metabolism, which can predispose individuals to obesity. Studies have demonstrated that modulating the gut microbiota through diet, lifestyle changes, prebiotics, probiotics, or fecal microbiota transplantation may contribute to gut homeostasis and the management of obesity and its associated comorbidities. This review elucidates the impact of alterations in gut microbiota composition during early-life on childhood obesity and explores the mechanisms by which gut microbiota contributes to the pathogenesis of obesity, and specifically focuses on recent advances in utilizing short-chain fatty acids for regulating gut microbiota and ameliorating obesity. Additionally, it discusses the therapeutic strategies for childhood obesity from the perspective of gut microbiota, aiming to provide a theoretical foundation for interventions targeting pediatric obesity based on gut microbiota. Statement of Significance: We provide a summary of the factors, mechanisms, and therapeutic strategies pertaining to the impact of gut microbiota alterations on childhood obesity, with particularly emphasis recent advancements in leveraging short-chain fatty acids for modulating gut microbiota composition and ameliorating obesity-related concerns.}, } @article {pmid39732757, year = {2024}, author = {Jasiński, M and Biliński, J and Maciejewska, M and Ostrowska, K and Rusicka-Krzewska, P and Konarski, W and Podsiadły, E and Snarski, E and Basak, GW}, title = {Impact of gut colonization by antibiotic-resistant bacteria on the outcomes of autologous stem cell transplantation in multiple myeloma.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {31221}, pmid = {39732757}, issn = {2045-2322}, mesh = {Humans ; *Multiple Myeloma/therapy/microbiology ; Male ; Middle Aged ; Female ; *Transplantation, Autologous ; Aged ; Retrospective Studies ; *Gastrointestinal Microbiome ; Adult ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Drug Resistance, Bacterial ; Treatment Outcome ; }, abstract = {Patients undergoing autologous stem cell transplantation (auto-SCT) face elevated risks of infections. Additionally, patients colonized in the gastrointestinal tract with antibiotic-resistant bacteria (ARB) are at higher risk of infection with ARB and other infections. Therefore, patients colonized with ARB before auto-SCT should present with an exceptionally high incidence of infections. According to current literature, ARB colonization is the surrogate marker for dysbiosis, which is known to be associated with a diagnosis of multiple myeloma (MM). Given that, this retrospective study aimed to assess the influence of ARB colonization on infection rates, hematopoiesis regeneration, mucositis, overall survival, and progression-free survival following auto-SCT in MM. Data from 138 MM patients undergoing 141 auto-SCT were analyzed, with 15% showing ARB colonization. Among colonized patients, ESBL-producing gram-negative rods predominated. Patients with gut ARB colonization had significantly higher infection rates than non-colonized individuals (52 vs. 26%, P = 0.02), particularly bloodstream infections (43% vs. 14%, P = 0.004). Colonized patients also tended to exhibit shorter survival rates although there was no statistical significance (1-year and 2-year OS; non-colonized vs. colonized; 97 and 92% vs. 90 and 86%; p = 0.054). Based on our results, gut colonization before auto-SCT negatively affects treatment outcomes.}, } @article {pmid39732731, year = {2024}, author = {Lu, Y and Huangfu, S and Ma, C and Ding, Y and Zhang, Y and Zhou, C and Liao, L and Li, M and You, J and Chen, Y and Wang, D and Chen, A and Jiang, B}, title = {Exosomes derived from umbilical cord mesenchymal stem cells promote healing of complex perianal fistulas in rats.}, journal = {Stem cell research & therapy}, volume = {15}, number = {1}, pages = {414}, pmid = {39732731}, issn = {1757-6512}, support = {BE2022674//General Program of Jiangsu Province Social Development-oriented Special Fund Project/ ; No. 82004365//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Exosomes/metabolism ; Rats ; *Mesenchymal Stem Cells/metabolism/cytology ; *Wound Healing ; *Rats, Sprague-Dawley ; *Umbilical Cord/cytology ; *Rectal Fistula/therapy/metabolism ; Humans ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Disease Models, Animal ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Mesenchymal Stem Cell Transplantation/methods ; }, abstract = {BACKGROUND: Complex perianal fistulas, challenging to treat and prone to recurrence, often require surgical intervention that may cause fecal incontinence and lower quality of life due to large surgical wounds and potential sphincter damage. Human umbilical cord-derived MSCs (hUC-MSCs) and their exosomes (hUCMSCs-Exo) may promote wound healing.

METHODS: This study assessed the efficacy, mechanisms, and safety of these exosomes in treating complex perianal fistulas in SD rats. We established a rat model, divided rats with fistulas into the control and the exosome groups. We assessed treatment efficacy through ultrasound, clinical observations, and histopathological analysis. We also evaluated the activation of the HIF-1α/TGF-β/Smad signaling pathway via PCR and Western blot and assessed serological markers for HIF-1α and inflammatory indices through ELISA. We analyzed gut microbiota and the systemic metabolic environment via untargeted metabolomics.

RESULTS: The hUCMSCs-Exo effectively promoted healing of wound, regulated the immune balance enhanced collagen synthesis and angiogenesis in the perianal fistulas model of rats, and regulated the gut microbiota and metabolomic profiles. Results of PCR and Western blot analyses indicated that the exosomes activated HIF-1α/TGF-β/Smad signaling pathways. To the dosages tested, the 10ug/100ul concentration (medium dose) was found to be the most effective to the treatment of complex perianal fistulas.

CONCLUSIONS: The hUCMSCs-Exo significantly promoted the healing of wound in perianal fistulas of rats and demonstrated higher safety. The underlying mechanism facilitating the healing process was likely associated with the activation of the HIF-1α/TGF-β/Smad signaling pathway.}, } @article {pmid39732352, year = {2024}, author = {Kamath, S and Sokolenko, E and Collins, K and Chan, NSL and Mills, N and Clark, SR and Marques, FZ and Joyce, P}, title = {IUPHAR themed review: The gut microbiome in schizophrenia.}, journal = {Pharmacological research}, volume = {211}, number = {}, pages = {107561}, doi = {10.1016/j.phrs.2024.107561}, pmid = {39732352}, issn = {1096-1186}, abstract = {Gut microbial dysbiosis or altered gut microbial consortium, in schizophrenia suggests a pathogenic role through the gut-brain axis, influencing neuroinflammatory and neurotransmitter pathways critical to psychotic, affective, and cognitive symptoms. Paradoxically, conventional psychotropic interventions may exacerbate this dysbiosis, with antipsychotics, particularly olanzapine, demonstrating profound effects on microbial architecture through disruption of bacterial phyla ratios, diminished taxonomic diversity, and attenuated short-chain fatty acid synthesis. To address these challenges, novel therapeutic strategies targeting the gut microbiome, encompassing probiotic supplementation, prebiotic compounds, faecal microbiota transplantation, and rationalised co-pharmacotherapy, show promise in attenuating antipsychotic-induced metabolic disruptions while enhancing therapeutic efficacy. Harnessing such insights, precision medicine approaches promise to transform antipsychotic prescribing practices by identifying patients at risk of metabolic side effects based on their microbial profiles. This IUPHAR review collates the current literature landscape of the gut-brain axis and its intricate relationship with schizophrenia while advocating for integrating microbiome assessments and therapeutic management. Such a fundamental shift in proposing microbiome-informed psychotropic prescriptions to optimise therapeutic efficacy and reduce adverse metabolic impacts would align antipsychotic treatments with microbiome safety, prioritising 'gut-neutral' or gut-favourable drugs to safeguard long-term patient outcomes in schizophrenia therapy.}, } @article {pmid39731142, year = {2024}, author = {Yang, Y and Wang, L and Zhuang, T and Xu, T and Ji, M and Wang, Q}, title = {Washed microbiota transplantation stopped recurrent sepsis in a patient with myelofibrosis: a case report.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {78}, pmid = {39731142}, issn = {1757-4749}, abstract = {BACKGROUND: Sepsis represents the most prevalent infectious complication and the primary cause of mortality in myeloproliferative neoplasms (MPN). The risk of sepsis and the difficulty of treatment are significantly increased in MPN patients due to the need for immunomodulators and antibiotics.

CASE PRESENTATION: On June 9, 2023, a 69-year-old male was admitted to the hospital. Following a battery of tests, the diagnosis of sepsis due to Escherichia coli was ultimately established. The patient was administered amoxicillin clavulanate potassium intravenously. In light of the patient's recurrent sepsis and the likelihood that the source of infection is the intestinal tract, we advised that the patient undergo washed microbiota transplantation (WMT) via a colonic transendoscopic enteral tube (TET).

CONCLUSIONS: WMT as the new method of fecal microbiota transplantation (FMT) successfully cured the recurrent sepsis in this case, indicating the novel option for challenging the refractory or serious infections.}, } @article {pmid39729440, year = {2024}, author = {Cibulkova, I and Rehorova, V and Soukupova, H and Waldauf, P and Cahova, M and Manak, J and Matejovic, M and Duska, F}, title = {Allogenic faecal microbiota transplantation for antibiotic-associated diarrhoea in critically ill patients (FEBATRICE)-Study protocol for a multi-centre randomised controlled trial (phase II).}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0310180}, pmid = {39729440}, issn = {1932-6203}, mesh = {Female ; Humans ; Male ; *Anti-Bacterial Agents/adverse effects/therapeutic use ; *Critical Illness ; *Diarrhea/therapy/microbiology ; Dysbiosis/therapy/microbiology ; *Fecal Microbiota Transplantation/methods/adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; Prospective Studies ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; }, abstract = {BACKGROUND: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea.

METHODS: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota.

DISCUSSION: Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims.

TRIAL REGISTRATION: www.clinicaltrials.gov (NCT05430269).}, } @article {pmid39728458, year = {2024}, author = {Voziki, A and Deda, O and Kachrimanidou, M}, title = {The Efficacy of Fecal Microbiota Transplantation in Mouse Models Infected with Clostridioides difficile from the Perspective of Metabolic Profiling: A Systematic Review.}, journal = {Metabolites}, volume = {14}, number = {12}, pages = {}, pmid = {39728458}, issn = {2218-1989}, abstract = {Objectives: This systematic review evaluates the effectiveness of fecal microbiota transplantation (FMT) in treating Clostridioides difficile infection (CDI) in mouse models using a metabolomics-based approach. Methods: A comprehensive search was conducted in three databases (PubMed, Scopus, Google Scholar) from 10 April 2024 to 17 June 2024. Out of the 460 research studies reviewed and subjected to exclusion criteria, only 5 studies met all the inclusion criteria and were analyzed. Results: These studies consistently showed that FMT effectively restored gut microbiota and altered metabolic profiles, particularly increasing short-chain fatty acids (SCFAs) and secondary bile acids, which inhibited C. difficile growth. FMT proved superior to antibiotic and probiotic treatments in re-establishing a healthy gut microbiome, as evidenced by significant changes in the amino acid and carbohydrate levels. Despite its promise, variability in the outcomes-due to factors such as immune status, treatment protocols, and donor microbiome differences-underscores the need for standardization. Rather than pursuing immediate standardization, the documentation of factors such as donor and recipient microbiome profiles, preparation methods, and administration details could help identify optimal configurations for specific contexts and patient needs. In all the studies, FMT was successful in restoring the metabolic profile in mice. Conclusions: These findings align with the clinical data from CDI patients, suggesting that FMT holds potential as a therapeutic strategy for gut health restoration and CDI management. Further studies could pave the way for adoption in clinical practice.}, } @article {pmid39726974, year = {2024}, author = {Ebrahimi, R and Farsi, Y and Nejadghaderi, SA}, title = {Fecal microbiota transplantation for glaucoma; a potential emerging treatment strategy.}, journal = {Current research in microbial sciences}, volume = {7}, number = {}, pages = {100314}, pmid = {39726974}, issn = {2666-5174}, abstract = {Glaucoma is the primary cause of irreversible blindness globally. Different glaucoma subtypes are identified by their underlying mechanisms, and treatment options differ by its pathogenesis. Current management includes topical medications to lower intraocular pressure and surgical procedures like trabeculoplasty and glaucoma drainage implants. Fecal microbiota transplantation (FMT) is an almost effective and safe treatment option for recurrent Clostridium difficile infection. The relationship between bacterial populations, metabolites, and inflammatory pathways in retinal diseases indicates possible therapeutic strategies. Thus, incorporating host microbiota-based therapies could offer an additional treatment option for glaucoma patients. Here, we propose that combining FMT with standard glaucoma treatments may benefit those affected by this condition. Also, the potential safety, efficacy, cost-effectiveness and clinical applications are discussed.}, } @article {pmid39726854, year = {2025}, author = {Minerbi, A and Khoutorsky, A and Shir, Y}, title = {Decoding the connection: unraveling the role of gut microbiome in fibromyalgia.}, journal = {Pain reports}, volume = {10}, number = {1}, pages = {e1224}, pmid = {39726854}, issn = {2471-2531}, abstract = {The gut microbiome is emerging as a critical player in the pathophysiology of fibromyalgia, offering mechanistic insights as well as potential diagnostic and therapeutic applications.}, } @article {pmid39725607, year = {2025}, author = {Wang, P and Wang, R and Zhao, W and Zhao, Y and Wang, D and Zhao, S and Ge, Z and Ma, Y and Zhao, X}, title = {Gut microbiota-derived 4-hydroxyphenylacetic acid from resveratrol supplementation prevents obesity through SIRT1 signaling activation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446391}, doi = {10.1080/19490976.2024.2446391}, pmid = {39725607}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Sirtuin 1/metabolism ; *Obesity/metabolism/prevention & control/microbiology ; *Resveratrol/pharmacology/administration & dosage ; Mice ; *Phenylacetates/pharmacology/metabolism ; *Signal Transduction/drug effects ; *Diet, High-Fat/adverse effects ; Male ; *Mice, Inbred C57BL ; Dysbiosis/microbiology/prevention & control ; Adipose Tissue, White/metabolism/drug effects ; Anti-Obesity Agents/pharmacology/administration & dosage ; Dietary Supplements ; Bacteria/classification/metabolism/drug effects/genetics ; Fecal Microbiota Transplantation ; }, abstract = {Resveratrol (RSV), a natural polyphenol, has been suggested to influence glucose and lipid metabolism. However, the underlying molecular mechanism of its action remains largely unknown due to its multiple biological targets and low bioavailability. In this study, we demonstrate that RSV supplementation ameliorates high-fat-diet (HFD)-induced gut microbiota dysbiosis, enhancing the abundance of anti-obesity bacterial strains such as Akkermansia, Bacteroides and Blautia. The critical role of gut microbiota in RSV-mediated anti-obesity effects was confirmed through antibiotic-induced microbiome depletion and fecal microbiota transplantation (FMT), which showed that RSV treatment effectively mitigates body weight, histopathological damage, glucose dysregulation and systematic inflammation associated with HFD. Metabolomics analysis revealed that RSV supplementation significantly increases the levels of the gut microbial flavonoid catabolite 4-hydroxyphenylacetic acid (4-HPA). Notably, 4-HPA was sufficient to reverse obesity and glucose intolerance in HFD-fed mice. Mechanistically,4-HPA treatment markedly regulates SIRT1 signaling pathways and induces the expression of beige fat and thermogenesis-specific markers in white adipose tissue (WAT). These beneficial effects of 4-HPA are partially abolished by EX527, a known SIRT1 inhibitor. Collectively, our findings indicate that RSV improve obesity through a gut microbiota-derived 4-HPA-SIRT1 axis, highlighting gut microbiota metabolites as a promising target for obesity prevention.}, } @article {pmid39725475, year = {2024}, author = {Yang, RF and Wu, W and Zhang, P}, title = {Research Progress on Obesity-Associated Kidney Diseases.}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {}, number = {}, pages = {}, doi = {10.3881/j.issn.1000-503X.16098}, pmid = {39725475}, issn = {1000-503X}, abstract = {The pathogenesis of obesity-associated kidney disease (OAKD) involves many aspects,including the overactivation of the renin-angiotensin-aldosterone system,insulin resistance,chronic inflammation,disorder of lipid metabolism and imbalance of gut microecology.Treatment strategies for OAKD focus on lifestyle adjustments,pharmacotherapy,bariatric surgery,and fecal microbiota transplantation.A deeper understanding of the hazards of OAKD and its pathogenesis will contribute to the development of personalized and precise strategies for prevention,diagnosis and treatment of OAKD in the future.}, } @article {pmid39724461, year = {2024}, author = {Mahmoudian, F and Gheshlagh, SR and Hemati, M and Farhadi, S and Eslami, M}, title = {The influence of microbiota on the efficacy and toxicity of immunotherapy in cancer treatment.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {86}, pmid = {39724461}, issn = {1573-4978}, mesh = {Animals ; Humans ; *Dysbiosis/immunology/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods/adverse effects ; *Neoplasms/immunology/microbiology/therapy ; }, abstract = {Immunotherapy, which uses the body's immune system to fight cancer cells, has gained attention recently as a breakthrough in cancer treatment. Although significant progress has been made, obstacles still exist since cancers are skilled at avoiding immune monitoring. The gut microbiota is being looked at more and more in modern research as a critical component in improving the results of immunotherapy. Through modulating both innate and adaptive immune responses, the gut microbiome has a significant impact on cancer immunotherapy. The effectiveness of treatment and the way the immune system responds are significantly influenced by some microorganisms and the metabolites they produce, especially short-chain fatty acids. On the other hand, dysbiosis and persistent inflammation in the gut environment might unintentionally accelerate the growth of tumors, which makes the complex relationship between the makeup of the microbiota and cancer treatment more challenging. Gut microbiota plays a crucial role in immunotherapy effectiveness. Improved microbial diversity leads to better treatment responses, with some taxa like Bacteroides and Ruminococcaceae being linked to better responses to immune checkpoint inhibitors. Dysbiotic conditions can worsen immune-related side effects and reduce treatment effectiveness. Strategies manipulating gut microbiota, such as fecal microbiota transplantation, antibiotic therapies, and dietary interventions, could optimize immunotherapy response and prognosis. However, standardizing these interventions for different cancer types and patient populations is challenging due to individual microbiome differences. Future research should combine microbiome research with AI and rigorous clinical trials for individualized cancer treatments.}, } @article {pmid39717506, year = {2025}, author = {Bloom, PP and Chung, RT}, title = {The future of clinical trials of gut microbiome therapeutics in cirrhosis.}, journal = {JHEP reports : innovation in hepatology}, volume = {7}, number = {1}, pages = {101234}, pmid = {39717506}, issn = {2589-5559}, abstract = {The last two decades have witnessed an explosion of microbiome research, including in hepatology, with studies demonstrating altered microbial composition in liver disease. More recently, efforts have been made to understand the association of microbiome features with clinical outcomes and to develop therapeutics targeting the microbiome. While microbiome therapeutics hold much promise, their unique features pose certain challenges for the design and conduct of clinical trials. Herein, we will briefly review indications for microbiome therapeutics in cirrhosis, currently available microbiome therapeutics, and the biological pathways targeted by these therapies. We will then focus on the best practices and important considerations for clinical trials of gut microbiome therapeutics in cirrhosis.}, } @article {pmid39716346, year = {2024}, author = {Li, Y and Wang, K and Shen, D and Liu, J and Li, S and Liu, L and Nagaoka, K and Li, C}, title = {Mogroside V protects Lipopolysaccharides-induced lung inflammation chicken via suppressing inflammation mediated by the Th17 through the gut-lung axis.}, journal = {Journal of animal science}, volume = {}, number = {}, pages = {}, doi = {10.1093/jas/skae388}, pmid = {39716346}, issn = {1525-3163}, abstract = {Lipopolysaccharide (LPS) exposure triggers pulmonary inflammation, leading to compromised lung function in broiler. As amplified by policy restrictions on antibiotic usage, seeking antibiotic alternatives has become imperative. Mogroside V (MGV) has been reported to have a beneficial role in livestock and poultry production due to its remarkable anti-inflammatory effects. Despite evidence showcasing MGV's efficacy against LPS-triggered lung inflammation, its precise mechanism of action remains elusive. In this study, we transplanted normal fecal microbiota (CF), fecal microbiota modified by MGV (MF), and sterile fecal filtrate (MS) into broiler with LPS-induced pneumonia. The results showed that through fecal microbiota transplantation, transplanting MGV-induced microbial populations significantly mitigated tissue damage induced by LPS and enhanced the mRNA level of pulmonary tight junction proteins and mucoprotein (P < 0.01). The expression levels of RORα (P < 0.001), Foxp3 (P < 0.01) and PD-L1 (P < 0.01) were significantly increased in the MF group than CF group. The concentrations of IL-6 and IL-17 in broilers lung tissue of MF group were lower than those in broilers of CF group (P < 0.05). Furthermore, the concentration of TGF-β in broilers serum of MS and MF groups was higher than those in broilers of control group (P < 0.05). Microbial community analysis demonstrated that at genus level, the harmful bacterial populations Escherichia-shigella and Helicobacter following FMT treatment was significantly reduced in MF group (P < 0.05), potentially mediating its protective effects. Compared with CF group, valerate content and FFAR2 mRNA expression levels in MF group were significantly increased (P < 0.05). The study suggests that MGV via the gut-lung axis, attenuates Th17-mediated inflammation, offering promise as a therapeutic strategy against LPS-induced lung inflammation in chickens.}, } @article {pmid39715825, year = {2024}, author = {Bornbusch, SL and Crosier, A and Gentry, L and Delaski, KM and Maslanka, M and Muletz-Wolz, CR}, title = {Fecal microbiota transplants facilitate post-antibiotic recovery of gut microbiota in cheetahs (Acinonyx jubatus).}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {1689}, pmid = {39715825}, issn = {2399-3642}, support = {NSF IOS-2131060//National Science Foundation (NSF)/ ; }, mesh = {*Acinonyx ; *Gastrointestinal Microbiome ; Animals ; *Anti-Bacterial Agents/pharmacology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Male ; Female ; }, abstract = {Burgeoning study of host-associated microbiomes has accelerated the development of microbial therapies, including fecal microbiota transplants (FMTs). FMTs provide host-specific microbial supplementation, with applicability across host species. Studying FMTs can simultaneously provide comparative frameworks for understanding microbial therapies in diverse microbial systems and improve the health of managed wildlife. Ex-situ carnivores, including cheetahs (Acinonyx jubatus), often suffer from intractable gut infections similar to those treated with antibiotics and FMTs in humans, providing a valuable system for testing FMT efficacy. Using an experimental approach in 21 cheetahs, we tested whether autologous FMTs facilitated post-antibiotic recovery of gut microbiota. We used 16S rRNA sequencing and microbial source tracking to characterize antibiotic-induced microbial extirpations and signatures of FMT engraftment for single versus multiple FMTs. We found that antibiotics extirpated abundant bacteria and FMTs quickened post-antibiotic recovery via engraftment of bacteria that may facilitate protein digestion and butyrate production (Fusobacterium). Although multiple FMTs better sustained microbial recovery compared to a single FMT, one FMT improved recovery compared to antibiotics alone. This study elucidated the dynamics of microbiome modulation in a non-model system and improves foundations for reproducible, low-cost, low-dose, and minimally invasive FMT protocols, emphasizing the scientific and applied value of FMTs across species.}, } @article {pmid39715151, year = {2024}, author = {Nie, P and Hu, L and You, T and Jia, T and Xu, H}, title = {Lead Mediated Lipopolysaccharides Exacerbates Fatty Liver Processes in High-Fat Diets-Induced Mice.}, journal = {Environmental toxicology}, volume = {}, number = {}, pages = {}, doi = {10.1002/tox.24463}, pmid = {39715151}, issn = {1522-7278}, support = {82060606//National Natural Science Foundation of China/ ; }, abstract = {Obesity leads to a variety of health risks, and lead, which is ranked second in Agency for Toxic Substances and Disease Registry's priority list of harmful substances, may be more harmful to individuals that are obese. C57BL/6 mice were fed a normal diet or a high-fat diet with or without exposure to 1 g/L lead exposure in drinking water for 8 consecutive weeks. Serum and hepatic biochemistry analysis, histopathological observation, and RT-qPCR were used to explore the potential mechanism of liver damage in obese individuals after Pb exposure, and fecal microbiota transplantation was performed to investigate the role of the gut microbiota in the progression of fatty liver disease. We found that the progression of fatty liver disease induced by high-fat diets was accelerated by chronic lead intake. In addition, the occurrences of liver injury in recipient mice suggested the role of the gut microbiota. These findings indicated that the combination of lead and a HFD exacerbated hepatic lipotoxicity by activating LPS-mediated inflammation, and that gut microbiota disorders and impaired intestinal barrier function play pivotal roles in the progression of fatty liver disease.}, } @article {pmid39714951, year = {2024}, author = {Li, W and Wang, Y and Shi, Y and He, F and Zhao, Z and Liu, J and Gao, Z and Zhang, J and Shen, X}, title = {The gut microbiota mediates memory impairment under high-altitude hypoxia via the gut-brain axis in mice.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.17365}, pmid = {39714951}, issn = {1742-4658}, support = {81973073//National Natural Science Foundation of China/ ; 82173481//National Natural Science Foundation of China/ ; 82204089//National Natural Science Foundation of China/ ; }, abstract = {Hypoxia is a predominant risk factor at high altitudes, and evidence suggests that high-altitude hypoxia alters the gut microbiota, which plays an essential regulatory role in memory function. However, the causal relationship between the gut microbiota and memory impairment under hypoxic conditions remains unclear. In this study, we employed a high-altitude hypoxia model combined with fecal microbiota transplantation (FMT) approach in mice to explore the effects of the gut microbiota on memory impairment in a hypoxic environment. We observed that high-altitude hypoxia exposure reduced short- and long-term memory and hippocampus-dependent fear memory abilities, along with decreased relative abundance of Ligilactobacillus and Muribaculum. Moreover, hypoxic conditions increased intestinal and blood-brain barrier permeability. FMT from hypoxia-exposed mice into naïve antibiotic-treated mice resulted in similar memory impairments, Ligilactobacillus and Muribaculum abundance changes, and increased intestinal/blood-brain barrier permeability. Correlation analysis showed a robust positive association between Ligilactobacillus and Muribaculum with hippocampus-dependent contextual fear memory. Likewise, Ligilactobacillus was positively correlated with short-term memory. Therefore, Ligilactobacillus and Muribaculum may be key microbes in reducing memory ability in hypoxia, with the intestinal and blood-brain barriers as primary pathways. Our findings provide further evidence for the potential regulatory mechanism by which gut microbiota dysbiosis may contribute to memory impairment in a high-altitude environment.}, } @article {pmid39712898, year = {2024}, author = {Tang, M and Wu, Y and Liang, J and Yang, S and Huang, Z and Hu, J and Yang, Q and Liu, F and Li, S}, title = {Gut microbiota has important roles in the obstructive sleep apnea-induced inflammation and consequent neurocognitive impairment.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1457348}, pmid = {39712898}, issn = {1664-302X}, abstract = {Obstructive sleep apnea (OSA) is a state of sleep disorder, characterized by repetitive episodes of apnea and chronic intermittent hypoxia. OSA has an extremely high prevalence worldwide and represents a serious challenge to public health, yet its severity is frequently underestimated. It is now well established that neurocognitive dysfunction, manifested as deficits in attention, memory, and executive functions, is a common complication observed in patients with OSA, whereas the specific pathogenesis remains poorly understood, despite the likelihood of involvement of inflammation. Here, we provide an overview of the current state of the art, demonstrating the intimacy of OSA with inflammation and cognitive impairment. Subsequently, we present the recent findings on the investigation of gut microbiota alteration in the OSA conditions, based on both patients-based clinical studies and animal models of OSA. We present an insightful discussion on the role of changes in the abundance of specific gut microbial members, including short-chain fatty acid (SCFA)-producers and/or microbes with pathogenic potential, in the pathogenesis of inflammation and further cognitive dysfunction. The transplantation of fecal microbiota from the mouse model of OSA can elicit inflammation and neurobehavioral disorders in naïve mice, thereby validating the causal relationship to inflammation and cognitive abnormality. This work calls for greater attention on OSA and the associated inflammation, which require timely and effective therapy to protect the brain from irreversible damage. This work also suggests that modification of the gut microbiota using prebiotics, probiotics or fecal microbiota transplantation may represent a potential adjuvant therapy for OSA.}, } @article {pmid39712559, year = {2024}, author = {Özdemir, Ö}, title = {Relation between dysbiosis and inborn errors of immunity.}, journal = {World journal of methodology}, volume = {14}, number = {4}, pages = {96380}, pmid = {39712559}, issn = {2222-0682}, abstract = {Inborn errors of immunity (IEI) disorders, formerly primary immune deficiency diseases, are a heterogeneous group of disorders with variable hereditary transitions, clinical manifestations, complications and varying disease severity. Many of the clinical symptoms, signs and complications in IEI patients can be attributed to inflammatory and immune dysregulatory processes due to loss of microbial diversity (dysbiosis). For example, in common variable immunodeficiency patients, the diversity of bacteria, but not fungi, in the gut microbiota has been found to be reduced and significantly altered. Again, this was associated with a more severe disease phenotype. Compromise of the STAT3/Th17 pathway in hyper-IgE syndrome may lead to dysbiosis of the oral microbiota in these patients, causing Candida albicans to switch from commensal to pathogenic. Modification of the microbiota can be used as a therapeutic approach in patients with IEI. Prebiotics, probiotics, postbiotics and fecal microbiota transplantation can be used to restore the balance of the gut microbiota and reduce pathogenicity in IEI patients. Clinical trials are currently underway to understand the impact of this dysbiosis on the phenotype of IEI diseases and its role in their treatment.}, } @article {pmid39712189, year = {2024}, author = {Lusk, S and Memos, NK and Rauschmayer, A and Ray, RS}, title = {The microbiome is dispensable for normal respiratory function and chemoreflexes in mice.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1481394}, pmid = {39712189}, issn = {1664-042X}, abstract = {Increasing evidence indicates an association between microbiome composition and respiratory homeostasis and disease, particularly disordered breathing, such as obstructive sleep apnea. Previous work showing respiratory disruption is limited by the methodology employed to disrupt, eliminate, or remove the microbiome by antibiotic depletion. Our work utilized germ-free mice born without a microbiome and described respiratory alterations. We used whole-body flow through barometric plethysmography to assay conscious and unrestrained C57BL/6J germ-free (GF, n = 24) and specific-pathogen-free (SPF, n = 28) adult mice (with an intact microbiome) in normoxic (21% O2,79% N2) conditions and during challenges in hypercapnic (5% CO2, 21% O2, 74% N2) and hypoxic (10% O2, 90% N2) environments. Following initial plethysmography analysis, we performed fecal transplants to test the ability of gut microbiome establishment to rescue any observed phenotypes. Data were comprehensively analyzed using our newly published respiratory analysis software, Breathe Easy, to identify alterations in respiratory parameters, including ventilatory frequency, tidal volume, ventilation, apnea frequency, and sigh frequency. We also considered possible metabolic changes by analyzing oxygen consumption, carbon dioxide production, and ventilatory equivalents of oxygen. We also assayed GF and SPF neonates in an autoresuscitation assay to understand the effects of the microbiome on cardiorespiratory stressors in early development. We found several differences in baseline and recovery cardiorespiratory parameters in the neonates and differences in body weight at both ages studied. However, there was no difference in the overall survival of the neonates, and in contrast to prior studies utilizing gut microbial depletion, we found no consequential respiratory alterations in GF versus SPF adult mice at baseline or following fecal transplant in any groups. Interestingly, we did see alterations in oxygen consumption in the GF adult mice, which suggests an altered metabolic demand. Results from this study suggest that microbiome alteration in mice may not play as large a role in respiratory outcomes when a less severe methodology to eliminate the microbiome is utilized.}, } @article {pmid39711145, year = {2024}, author = {Qian, M and Jiang, Z and Xu, C and Wang, L and Hu, N}, title = {Changes in the gut microbiota and derived fecal metabolites may play a role in tacrolimus-induced diabetes in mice.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/17460913.2024.2444761}, pmid = {39711145}, issn = {1746-0921}, abstract = {AIMS: A notable scarcity of research has focused on examining alterations in gut microbiota and its metabolites within tacrolimus (TAC)-induced diabetes models.

METHODS: Tacrolimus-induced changes in glucose and lipid metabolism indices were analyzed through different routes of administration. The potential role of gut microbiota and its metabolites in TAC-induced diabetes was investigated using 16S rRNA sequencing and non-targeted metabolomics.

RESULTS: After intraperitoneal(ip) and oral(po) administration of TAC, the α-diversity index of gut microbiota was significantly increased. The gut microbiota of the three groups of mice was significantly separated, and there were significant changes in composition and functional genes. Fecal metabolites changed significantly after TAC administration by different routes, and 53 metabolites (38 down-regulated and 15 up-regulated) were identified (CON vs. TACip). Similarly, 29 metabolites (8 down-regulated and 21 up-regulated) were identified (CON vs. TACpo). KEGG pathway analysis identified 4 and 13 significantly altered metabolic pathways, respectively. Correlation analysis suggested that microbiota and metabolites were involved in the pathogenesis of TAC-induced diabetes.

CONCLUSION: This study investigated the alterations in gut microbiota and fecal metabolites in TAC-induced diabetic mice and evaluated the correlation between these changes. These findings provide valuable insights into potential biomarkers in the development of TAC-induced diabetes.}, } @article {pmid39710789, year = {2024}, author = {Wang, Y and Bai, M and Peng, Q and Li, L and Tian, F and Guo, Y and Jing, C}, title = {Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease.}, journal = {European journal of medical research}, volume = {29}, number = {1}, pages = {614}, pmid = {39710789}, issn = {2047-783X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neovascularization, Pathologic/metabolism/microbiology ; Neoplasms/microbiology/metabolism/immunology ; Inflammation/metabolism ; Cardiovascular Diseases/microbiology/metabolism/etiology ; Animals ; Neurodegenerative Diseases/microbiology/metabolism ; Angiogenesis ; }, abstract = {The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator. This abstract aims to elucidate the connection between the gut microbiota and angiogenesis in various diseases. The gut microbiota influences angiogenesis through various mechanisms, including the production of metabolites that directly or indirectly affect vascularization. For example, short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are known to regulate immune responses and inflammation, thereby affecting angiogenesis. In the context of cardiovascular diseases, the gut microbiota promotes atherosclerosis and vascular dysfunction by producing trimethylamine N-oxide (TMAO) and other metabolites that promote inflammation and endothelial dysfunction. Similarly, in neurodegenerative diseases, the gut microbiota may influence neuroinflammation and the integrity of the blood-brain barrier, thereby affecting angiogenesis. In cases of fractures and wound healing, the gut microbiota promotes angiogenesis by activating inflammatory responses and immune effects, facilitating the healing of tissue damage. In cancer, the gut microbiota can either inhibit or promote tumor growth and angiogenesis, depending on the specific bacterial composition and their metabolites. For instance, some bacteria can activate inflammasomes, leading to the production of inflammatory factors that alter the tumor immune microenvironment and activate angiogenesis-related signaling pathways, affecting tumor angiogenesis and metastasis. Some bacteria can directly interact with tumor cells, activating angiogenesis-related signaling pathways. Diet, as a modifiable factor, significantly influences angiogenesis through diet-derived microbial metabolites. Diet can rapidly alter the composition of the microbiota and its metabolic activity, thereby changing the concentration of microbial-derived metabolites and profoundly affecting the host's immune response and angiogenesis. For example, a high animal protein diet promotes the production of pro-atherogenic metabolites like TMAO, activating inflammatory pathways and interfering with platelet function, which is associated with the severity of coronary artery plaques, peripheral artery disease, and cardiovascular diseases. A diet rich in dietary fiber promotes the production of SCFAs, which act as ligands for cell surface or intracellular receptors, regulating various biological processes, including inflammation, tissue homeostasis, and immune responses, thereby influencing angiogenesis. In summary, the role of the gut microbiota in angiogenesis is multifaceted, playing an important role in disease progression by affecting various biological processes such as inflammation, immune responses, and multiple signaling pathways. Diet-derived microbial metabolites play a crucial role in linking the gut microbiota and angiogenesis. Understanding the complex interactions between diet, the gut microbiota, and angiogenesis has the potential to uncover novel therapeutic targets for managing these conditions. Therefore, interventions targeting the gut microbiota and its metabolites, such as through fecal microbiota transplantation (FMT) and the application of probiotics to alter the composition of the gut microbiota and enhance the production of beneficial metabolites, present a promising therapeutic strategy.}, } @article {pmid39710683, year = {2024}, author = {Yarahmadi, A and Afkhami, H and Javadi, A and Kashfi, M}, title = {Understanding the complex function of gut microbiota: its impact on the pathogenesis of obesity and beyond: a comprehensive review.}, journal = {Diabetology & metabolic syndrome}, volume = {16}, number = {1}, pages = {308}, pmid = {39710683}, issn = {1758-5996}, abstract = {Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis-an imbalance in the microbiome-leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges.}, } @article {pmid39706182, year = {2024}, author = {Jiang, Y and Huang, Z and Sun, W and Huang, J and Xu, Y and Liao, Y and Jin, T and Li, Q and Ho, IHT and Zou, Y and Zhu, W and Li, Q and Qin, F and Zhang, X and Shi, S and Zhang, N and Yang, S and Xie, W and Wu, S and Tan, L and Zhang, L and Chen, H and Gin, T and Chan, MTV and Wu, WKK and Xiao, L and Liu, X}, title = {Roseburia intestinalis-derived butyrate alleviates neuropathic pain.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2024.11.013}, pmid = {39706182}, issn = {1934-6069}, abstract = {Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles. Functionally, fecal microbiota transplantation from patients with PHN to mice heightened pain sensitivity. Administration of Roseburia intestinalis, a bacterium both depleted in patients with shingles and PHN, alleviated peripheral nerve injury-induced pain in mice. R. intestinalis enhanced vagal neurotransmission to the nucleus tractus solitarius (NTS) to suppress the central amygdala (CeA), a brain region involved in pain perception. R. intestinalis-generated butyrate activated vagal neurons through the receptor, G protein-coupled receptor 41 (GPR41). Vagal knockout of Gpr41 abolished the effects of R. intestinalis on the NTS-CeA circuit and reduced pain behaviors. Overall, we established a microbiota-based model for PHN risk assessment and identified R. intestinalis as a potential pain-alleviating probiotic.}, } @article {pmid39703540, year = {2024}, author = {Finnegan, YE and Neill, HR and Prpa, EJ and Pot, B}, title = {"Gut" to grips with the science of the microbiome - a symposium report.}, journal = {Gut microbiome (Cambridge, England)}, volume = {5}, number = {}, pages = {e11}, pmid = {39703540}, issn = {2632-2897}, abstract = {The latest Yakult Science Study Day was held virtually on 2 November 2023. Aimed at healthcare professionals, researchers, and students, a variety of experts explored the latest gut microbiome research and what it means in practice. The morning sessions discussed the role of the microbiome in health and disease, the rapid advancements in DNA sequencing and implications for personalised nutrition, the current state of evidence on health benefits associated with fermented foods, prebiotics and probiotics and the challenges involved in interpreting research in this area. The afternoon session considered the emerging research on the microbiota-gut-brain axis in mediating effects of food on mood, the bidirectional impact of menopause on the gut microbiota, and the interplay between the gut and skin with implications for the treatment of rare and common skin disorders. The session ended with an update on the use of faecal microbiota transplant in both research and clinical practice. Undoubtedly, the gut microbiome is emerging as a key conductor of human health, both in relation to gastrointestinal and non-gastrointestinal outcomes. As research continues to elucidate mechanisms of action and confirm their effects in human trials, the gut microbiome should be a key consideration within a holistic approach to health moving forward.}, } @article {pmid39703374, year = {2024}, author = {Chen, T and Wang, N and Hao, Y and Fu, L}, title = {Fecal microbiota transplantation from postmenopausal osteoporosis human donors accelerated bone mass loss in mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1488017}, pmid = {39703374}, issn = {2235-2988}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Humans ; Mice ; *Gastrointestinal Microbiome ; Female ; *Feces/microbiology ; *Osteoporosis, Postmenopausal/microbiology ; Disease Models, Animal ; Bacteria/classification/isolation & purification/genetics ; Bone Density ; Middle Aged ; Zonula Occludens-1 Protein/metabolism ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVES: To investigate the effect of gut microbiota from postmenopausal osteoporosis patients on bone mass in mice.

METHODS: Fecal samples were collected from postmenopausal women with normal bone mass (Con, n=5) and postmenopausal women with osteoporosis (Op, n=5). Microbial composition was identified by shallow shotgun sequencing. Then fecal samples were transplanted into pseudo-sterile mice previously treated with antibiotics for 4 weeks. These mice were categorized into two groups: the Vehicle group (n=7) received fecal samples from individuals with normal bone mass, and the FMT group (n=7) received fecal samples from individuals with osteoporosis. After 8 weeks, bone mass, intestinal microbial composition, intestinal permeability and inflammation were assessed, followed by a correlation analysis.

RESULTS: The bone mass was significantly reduced in the FMT group. Microbiota sequencing showed that Shannon index (p < 0.05) and Simpson index (p < 0.05) were significantly increased in Op groups, and β diversity showed significant differences. the recipient mice were similar. linear discriminant analysis effect size (LEfSe) analysis of mice showed that Halobiforma, Enterorhabdus, Alistipes, and Butyricimonas were significantly enriched in the FMT group. Lachnospiraceae and Oscillibacter were significantly enriched in the Vehicle group. H&E staining of intestinal tissues showed obvious intestinal mucosal injury in mice. Intestinal immunohistochemistry showed that the expression of Claudin and ZO-1 in the intestinal tissue of the FMT group mice was decreased. The FITC-Dextran (FD-4) absorption rate and serum soluble CD14 (sCD14) content were increased in FMT mice. Correlation analysis showed that these dominant genera were significantly associated with bone metabolism and intestinal permeability, and were associated with the enrichment of specific enzymes. Serum and bone tissue inflammatory cytokines detection showed that the expression of TNF-α and IL-17A in the FMT group were significantly increased.

CONCLUSION: Overall, our findings suggested gut microbiota from postmenopausal osteoporosis patients accelerate bone mass loss in mice. Aberrant gut microbiota might play a causal role in the process of bone mass loss mediated by inflammation after the destruction of the intestinal barrier.}, } @article {pmid39702789, year = {2024}, author = {Kaur, S and Patel, BCK and Collen, A and Malhotra, R}, title = {The microbiome and the eye: a new era in ophthalmology.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {39702789}, issn = {1476-5454}, abstract = {The human microbiome has progressively been recognised for its role in various disease processes. In ophthalmology, complex interactions between the gut and distinct ocular microbiota within each structure and microenvironment of the eye has advanced our knowledge on the multi-directional relationships of these ecosystems. Increasingly, studies have shown that modulation of the microbiome can be achieved through faecal microbiota transplantation and synbiotics producing favourable outcomes for ophthalmic diseases. As ophthalmologists, we are obliged to educate our patients on measures to cultivate a healthy gut microbiome through a range of holistic measures. Further integrative studies combining microbial metagenomics, metatranscriptomics and metabolomics are necessary to fully characterise the human microbiome and enable targeted therapeutic interventions.}, } @article {pmid38659831, year = {2024}, author = {Sall, IJ and Foxall, R and Felth, L and Maret, S and Rosa, Z and Gaur, A and Calawa, J and Pavlik, N and Whistler, J and Whistler, CA}, title = {Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.04.15.589671}, pmid = {38659831}, issn = {2692-8205}, support = {F31 DA056222/DA/NIDA NIH HHS/United States ; P20 GM103506/GM/NIGMS NIH HHS/United States ; R15 DA058187/DA/NIDA NIH HHS/United States ; R21 DA049565/DA/NIDA NIH HHS/United States ; }, abstract = {The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.}, } @article {pmid39701930, year = {2024}, author = {Wen, J and Wang, S and Sun, K and Wang, H and Yuan, Z and Deng, W}, title = {Chang-Wei-Qing Combined with PD-1 Inhibitor Alleviates Colitis-Associated Colorectal Tumorigenesis by Modulating the Gut Microbiota and Restoring Intestinal Barrier.}, journal = {Biological procedures online}, volume = {26}, number = {1}, pages = {32}, pmid = {39701930}, issn = {1480-9222}, support = {ptkwws202002//Shanghai Putuo District Health and Health System Science and Technology Innovation Project/ ; 2021tszk01//Shanghai Putuo District Health and Health System Clinical Specialty Construction Project/ ; ZY[2021-2023]-0302//Shanghai Municipal Health Commission's Shanghai Further Accelerating Traditional Chinese Medicine Development Three-Year Action Plan Project/ ; }, abstract = {Chang-Wei-Qing (CWQ) is a widely recognized Traditional Chinese Medicine (TCM) formulation composed of Astragalus, Codonopsis, Atractylodes, Poria, Coix seed, Akebia trifoliata Koidz, Sargentodoxa cuneata, and Vitis quinquangularis Rehd. This formulation has garnered significant interest for its positive effects in mitigating colorectal cancer, and when combined with PD-1, it affects some gut microbiota associated with tumor infiltrating lymphocytes cells. However, the biological rationale underlying the suppression of colitis-associated colorectal cancer (CAC) in AOM/DSS-treated mice by CWQ combined with PD-1 inhibitor remains to be explored. Our aim is to explore the chemopreventive effect of CWQ combined with PD-1 inhibitor on CAC, with a focus on modulating the gut microbiota. A mouse model of CAC was established using azoxymethane (AOM) and dextran sulfate sodium (DSS) treatment. Pathological evaluation of tissue samples included immunohistochemistry and hematoxylin and eosin staining. Intestinal barrier function was assessed by transmission electron microscopy. Fecal microbiota and metabolites were analyzed through 16 S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Mice treated with antibiotics served as models for fecal microbiota transplantation. CWQ combined with PD-1 inhibitor suppressed CAC in AOM/DSS-treated mice. This combined therapy effectively alleviated gut dysbiosis in the CAC model by increasing microbial diversity, enriching probiotic populations such as Limosilactobacillus and Bifidobacterium, and reducing pathogenic bacteria like Desulfovibrio. Additionally, CWQ combined with PD-1 inhibitor downregulated metabolites associated with the NF-kappa B signaling pathway. The combined treatment also significantly improved intestinal barrier function in CAC mice. Transmission electron microscopy of the CWQ combined with PD-1 inhibitor group showed enhanced cellular integrity, a relatively normal mitochondrial structure with intact membranes, and a more abundant, unexpanded endoplasmic reticulum, underscoring the protective effects of this combination on intestinal barrier integrity. Transcriptomic analysis further demonstrated that the combined therapy upregulated genes involved in tight and adherens junctions, while downregulating genes linked to innate immune responses. CWQ combined with PD-1 inhibitor can ameliorate dysbiosis in the AOM/DSS mouse model, with the metabolites of the gut microbiome potentially possessing anti-inflammatory activity. Moreover, CWQ combined with PD-1 inhibitor improves intestinal barrier function, thereby effectively inhibiting the occurrence and development of CAC.}, } @article {pmid39699275, year = {2024}, author = {Wang, Y and Xue, Y and Xu, H and Zhu, Q and Qin, K and He, Z and Huang, A and Mu, M and Tao, X}, title = {Pediococcus acidilactici Y01 reduces HFD-induced obesity via altering gut microbiota and metabolomic profiles and modulating adipose tissue macrophage M1/M2 polarization.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo04301d}, pmid = {39699275}, issn = {2042-650X}, abstract = {Obesity-related metabolic syndrome is intimately associated with infiltrated adipose tissue macrophages (ATMs), gut microbiota, and metabolic disorders. Pediococcus acidilactici holds the potential to mitigate obesity; however, there exist strain-specific functionalities and diverse mechanisms, which deserve extensive exploration. This study aims to explore the potential of P. acidilactici Y01, isolated from traditional sour whey, in alleviating HFD-induced metabolic syndrome in mice and elucidating its underlying mechanism. The results showed that P. acidilactici Y01 could inhibit the increase of body weight gain, the deposition of fat, lipid disorders and chronic low-grade inflammation, improve glucose tolerance and insulin resistance, and could reduce adipose tissue inflammation by decreasing M1-type ATMs and increasing M2-type ATMs. Meanwhile, P. acidilactici Y01 significantly increased the abundance of potentially beneficial intestinal bacteria, such as Akkermansia, Alistipes, Bifidobacterium, Lachnospiraceae_NK4A136_group, Lactobacillus, norank_f__Muribaculaceae, and Parabacteroides, and partially restored the levels of metabolites, such as phosphatidylcholines, glycerophosphocholines, sphingolipids and unsaturated fatty acids. The fecal microbiota transplantation experiment demonstrated that P. acidilactici Y01 ameliorated obesity-related metabolic syndrome by modulating the polarization of M1/M2 ATMs mediated by gut microbiota. Overall, as a dietary supplement, P. acidilactici Y01 has good potential in the prevention and treatment of obesity.}, } @article {pmid39699220, year = {2024}, author = {Li, T and Hu, G and Fu, S and Qin, D and Song, Z}, title = {Phillyrin ameliorates DSS-induced colitis in mice via modulating the gut microbiota and inhibiting the NF-κB/MLCK pathway.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0200624}, doi = {10.1128/spectrum.02006-24}, pmid = {39699220}, issn = {2165-0497}, abstract = {Phillyrin (PHY), also known as forsythin, is an active constituent isolated from the fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae). It exhibits anti-inflammatory, anti-viral, and antioxidant properties. However, the precise impact of PHY on colitis induced by dextran sodium sulfate (DSS) and its mechanism remain elusive. The present investigation revealed that PHY (12.5, 25.0, and 50.0 mg/kg) exhibited significant therapeutic efficacy in protecting mice against DSS-induced colitis. This effect was manifested as reduced weight loss, a shortened colon, increased secretion of inflammatory factors, increased intestinal permeability, and an enhanced disease activity index in mice with ulcerative colitis (UC). Molecular investigations have determined that PHY mitigates the nuclear translocation of nuclear factor kappa B, thereby downregulating myosin light-chain kinase-driven myosin light-chain phosphorylation. This mechanism results in the preservation of the integrity of the intestinal barrier. The outcomes of 16S rRNA sequencing suggest that PHY (50 mg/kg) augmented the relative abundance of certain probiotic strains, including Lactobacillaceae and Lachnospiraceae. Additionally, PHY supplementation elevated the short-chain fatty acid contents within the intestinal contents of mice with UC. In conclusion, pre-treatment with PHY may ameliorate the DSS-induced UC in mice by lowering the expression of inflammatory factors, protecting intestinal barrier function, and enhancing the structure of the intestinal flora.IMPORTANCEThe protective effect of phillyrin on DSS-induced colitis was explained for the first time, and the anti-inflammatory effect of phillyrin was demonstrated by fecal microbiota transplantation experiments mainly through intestinal flora.}, } @article {pmid39694919, year = {2025}, author = {Zhang, Y and Ji, X and Chang, K and Yin, H and Zhao, M and Zhao, L}, title = {The regulatory effect of chitooligosaccharides on islet inflammation in T2D individuals after islet cell transplantation: the mechanism behind Candida albicans abundance and macrophage polarization.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2442051}, pmid = {39694919}, issn = {1949-0984}, mesh = {Animals ; *Candida albicans/drug effects ; *Oligosaccharides/pharmacology ; Mice ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Macrophages/drug effects/immunology ; *Diabetes Mellitus, Type 2/microbiology ; *Islets of Langerhans Transplantation ; *Myeloid Differentiation Factor 88/metabolism/genetics ; *Inflammation ; Male ; Mice, Inbred C57BL ; Chitosan/pharmacology ; Islets of Langerhans/drug effects ; STAT6 Transcription Factor/metabolism/genetics ; NF-kappa B/metabolism/genetics ; }, abstract = {Islet cell transplantation (ICT) represents a promising therapeutic approach for addressing diabetes mellitus. However, the islet inflammation during transplantation significantly reduces the surgical outcome rate, which is related to the polarization of macrophages. Chitooligosaccharides (COS) was previously reported which could modulate the immune system, alleviate inflammation, regulate gut microecology, and repair the intestinal barrier. Therefore, we hypothesized COS could relieve pancreatic inflammation by regulating macrophage polarization and gut microbiota. First, 18S rDNA gene sequencing was performed on fecal samples from the ICT population, showing abnormally increased amount of Candida albicans, possibly causing pancreatic inflammation. Functional oligosaccharides responsible for regulating macrophage polarization and inhibiting the growth of Candida albicans were screened. Afterwards, human flora-associated T2D (HMA-T2D) mouse models of gut microbiota were established, and the ability of the selected oligosaccharides were validated in vivo to alleviate inflammation and regulate gut microbiota. The results indicated that ICT significantly decreased the alpha diversity of gut fungal, altered fungal community structures, and increased Candida albicans abundance. Moreover, Candida albicans promoted M1 macrophage polarization, leading to islet inflammation. COS inhibited Candida albicans growth, suppressed the MyD88-NF-κB pathway, activated STAT6, inhibited M1, and promoted M2 macrophage polarization. Furthermore, COS-treated HMA-T2D mice displayed lower M1 macrophage differentiation and higher M2 macrophage numbers. Additionally, COS also enhanced ZO-1 and Occludin mRNA expression, reduced Candida albicans abundance, and balanced gut microecology. This study illustrated that COS modulated macrophage polarization via the MyD88/NF-κB and STAT6 pathways, repaired the intestinal barrier, and reduced Candida albicans abundance to alleviate islet inflammation.}, } @article {pmid39691426, year = {2024}, author = {Yu, J and Chen, YX and Wang, JW and Wu, HT}, title = {Research progress on the relationship between traumatic brain injury and brain-gut-microbial axis.}, journal = {Ibrain}, volume = {10}, number = {4}, pages = {477-487}, pmid = {39691426}, issn = {2769-2795}, abstract = {Traumatic brain injury (TBI) is a common disease with a high rate of death and disability, which poses a serious threat to human health; thus, the effective treatment of TBI has been a high priority. The brain-gut-microbial (BGM) axis, as a bidirectional communication network for information exchange between the brain and gut, plays a crucial role in neurological diseases. This article comprehensively explores the interrelationship between the BGM axis and TBI, including its physiological effects, basic pathophysiology, and potential therapeutic strategies. It highlights how the bidirectional regulatory pathways of the BGM axis could provide new insights into clinical TBI treatment and underscores the necessity for advanced research and development of innovative clinical treatments for TBI.}, } @article {pmid39686442, year = {2024}, author = {Liu, F and Zhang, H and Fan, L and Yu, Q and Wang, S}, title = {Hotspots and development trends of gut microbiota in atopic dermatitis: A bibliometric analysis from 1988 to 2024.}, journal = {Medicine}, volume = {103}, number = {50}, pages = {e40931}, pmid = {39686442}, issn = {1536-5964}, mesh = {*Dermatitis, Atopic/microbiology/therapy ; *Gastrointestinal Microbiome ; Humans ; *Bibliometrics ; Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a prevalent inflammatory skin condition that commonly occurs in children. More and more scientific evidence suggests that gut microbiota plays an important role in the pathogenesis of AD, whereas there is no article providing a comprehensive summary and analysis. We aimed to analyze documents on AD and gut microbiota and identify hotspots and development trends in this field.

METHODS: Articles and reviews in the field of AD and gut microbiota from January 1, 1988 to October 20, 2024 were obtained from the Web of Science Core Collection database. Biblioshiny was utilized for evaluating and visualizing the core authors, journals, countries, documents, trend topics, and hotspots in this field.

RESULTS: Among 1672 documents, it indicated that the number of annual publications generally increased. The United States had the highest production, impact, and international collaboration. Journal of Allergy and Clinical Immunology was the journal of the maximum publications. Based on keyword co-occurrence and clustering analysis, "stratum-corneum lipids," "probiotics," "prebiotics," "fecal microbiota transplantation," "phage therapy," "short chain fatty-acids," "biologic therapy," and "skin inflammation" represented current trend topics. The pathological and molecular mechanisms and associated therapeutic methods for AD and gut microbiota were the research hotspots. The incorporation of microbiota-based therapies alongside conventional treatments can contribute to better clinical outcomes.

CONCLUSION: We highlighted that gut microbiota may exacerbate symptoms of AD through various aspects, including immunity, metabolites, and neuroendocrine pathways. More efforts are required to investigate the safety and efficacy of gut microbial management methods for the prevention and treatment of AD.}, } @article {pmid39684918, year = {2024}, author = {Li, C and Chen, S and Wang, Y and Su, Q}, title = {Microbiome-Based Therapeutics for Insomnia.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684918}, issn = {1422-0067}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/therapy/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; Animals ; Synbiotics ; }, abstract = {Insomnia poses considerable risks to both physical and mental health, leading to cognitive impairment, weakened immune function, metabolic dysfunction, cardiovascular issues, and reduced quality of life. Given the significant global increase in insomnia and the growing scientific evidence connecting gut microbiota to this disorder, targeting gut microbiota as an intervention for insomnia has gained popularity. In this review, we summarize current microbiome-based therapeutics for insomnia, including dietary modifications; probiotic, prebiotic, postbiotic, and synbiotic interventions; and fecal microbiota transplantation. Moreover, we assess the capabilities and weaknesses of these technologies to offer valuable insights for future studies.}, } @article {pmid39684788, year = {2024}, author = {Moreno, RJ and Ashwood, P}, title = {An Update on Microbial Interventions in Autism Spectrum Disorder with Gastrointestinal Symptoms.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684788}, issn = {1422-0067}, support = {HD090214/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; *Autism Spectrum Disorder/therapy/microbiology ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; *Dysbiosis/therapy/microbiology ; *Prebiotics ; Gastrointestinal Diseases/therapy/microbiology ; Anti-Bacterial Agents/therapeutic use ; Animals ; }, abstract = {In the United States, autism spectrum disorder (ASD) affects 1 in 33 children and is characterized by atypical social interactions, communication difficulties, and intense, restricted interests. Microbial dysbiosis in the gastrointestinal (GI) tract is frequently observed in individuals with ASD, potentially contributing to behavioral manifestations and correlating with worsening severity. Moreover, dysbiosis may contribute to the increased prevalence of GI comorbidities in the ASD population and exacerbate immune dysregulation, further worsening dysbiosis. Over the past 25 years, research on the impact of microbial manipulation on ASD outcomes has gained substantial interest. Various approaches to microbial manipulation have been preclinically and clinically tested, including antibiotic treatment, dietary modifications, prebiotics, probiotics, and fecal microbiota transplantation. Each method has shown varying degrees of success in reducing the severity of ASD behaviors and/or GI symptoms and varying long-term efficacy. In this review, we discuss these microbiome manipulation methods and their outcomes. We also discuss potential microbiome manipulation early in life, as this is a critical period for neurodevelopment.}, } @article {pmid39682952, year = {2024}, author = {Ma, H and Mueed, A and Ma, Y and Ibrahim, M and Su, L and Wang, Q}, title = {Fecal Microbiota Transplantation Activity of Floccularia luteovirens Polysaccharides and Their Protective Effect on Cyclophosphamide-Induced Immunosuppression and Intestinal Injury in Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {23}, pages = {}, pmid = {39682952}, issn = {2304-8158}, support = {2021YFD1600401//National Key Research and Development Program of China/ ; }, abstract = {Floccularia luteovirens polysaccharides (FLP1s) have potential biological activities. Our previous study showed that FLP1s positively regulated gut immunity and microbiota. However, it is still unclear whether FLP1s mediate gut microbiota in immunosuppressed mice. This research aims to explore the relationship between FLP1-mediated gut microbes and intestinal immunity in immunosuppressed mice through fecal microbiota transplantation (FMT). The results demonstrated that FLP1s exhibited prebiotic and anti-immunosuppressive effects on CTX-induced immunosuppressed mice. FFLP1 treatment (microbiota transplantation from the fecal sample) remarkably elevated the production of sIgA and secretion of the anti-inflammatory cytokines IL-4, TNF-α, and IFN-γ in the intestine of CTX-treated mice, inducing activation of the MAPK pathway. Moreover, FFLP1s mitigated oxidative stress by activating the Nrf2/Keap1 signaling pathway and strengthened the intestinal barrier function by upregulating the expression level of tight junction proteins (occludin, claudin-1, MUC-2, and ZO-1). Furthermore, FFPL1s restored gut dysbiosis in CTX-treated immunosuppressed mice by increasing the abundance of Alloprevotella, Lachnospiraceae, and Bacteroides. They also modified the composition of fecal metabolites, leading to enhanced regulation of lipolysis in adipocytes, the cGMP-PKG pathway, the Rap1 signaling pathway, and ovarian steroidogenesis, as indicated by KEGG pathway analysis. These findings indicate that FLP1s could modulate the response of the intestinal immune system through regulation of the gut microbiota, thus promoting immune activation in CTX-treated immunosuppressed mice. FLP1s can serve as a natural protective agent against CTX-induced immune injury.}, } @article {pmid39682542, year = {2024}, author = {Morales, C and Ballestero, L and Del Río, P and Barbero-Herranz, R and Olavarrieta, L and Gómez-Artíguez, L and Galeano, J and Avendaño-Ortiz, J and Basterra, J and Del Campo, R}, title = {Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {23}, pages = {}, pmid = {39682542}, issn = {2075-4418}, support = {XX//Mikrobiomik/ ; }, abstract = {BACKGROUND/OBJECTIVES: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent Clostridioides difficile infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification. However, despite the high amount of data generated from the ongoing research studies relating microbiota and health, there is not yet a consensus defining what is a "healthy" microbiota. To date, knowledge of the composition of the microbiota is not a requirement to be a faecal donor. The aim of this work was to evaluate whether the analysis of the composition of the microbiota by massive sequencing of 16S rDNA could be useful in the selection of the faecal donors.

METHODS: Samples from 10 certified donors from Mikrobiomik Healthcare Company were collected and sequenced using 16S rDNA in a MiSeq (Illumina) platform. Alpha (Chao1 and Shannon indices) and beta diversity (Bray-Curtis) were performed using the bioinformatic web server Microbiome Analyst. The differences in microbial composition at the genera and phyla levels among the donors were evaluated.

RESULTS: The microbial diversity metric by alpha diversity indexes showed that most donors exhibited a similar microbial diversity and richness, whereas beta diversity by 16S rDNA sequencing revealed significant inter-donor differences, with a more stable microbial composition over time in some donors. The phyla Bacillota and Bacteroidota were predominant in all donors, while the density of other phyla, such as Actinomycota and Pseudomonota, varied among individuals. Each donor exhibited a characteristic genera distribution pattern; however, it was possible to define a microbiome core consisting of the genera Agathobacter, Eubacterium, Bacteroides, Clostridia UCG-014 and Akkermansia. Conclusions: The results suggest that donor certification does not need to rely exclusively on their microbiota composition, as it is unique to each donor. While one donor showed greater microbial diversity and richness, clear criteria for microbial normality and health have yet to be established. Therefore, donor certification should focus more on clinical and lifestyle aspects.}, } @article {pmid39681213, year = {2024}, author = {Liu, X and Tan, X and Yu, Y and Niu, J and Zhao, B and Wang, Q}, title = {Short chain fatty acids mediates complement C1q pathway alleviation of perioperative neurocognitive disorders.}, journal = {Neuropharmacology}, volume = {}, number = {}, pages = {110266}, doi = {10.1016/j.neuropharm.2024.110266}, pmid = {39681213}, issn = {1873-7064}, abstract = {Perioperative neurocognitive disorders (PND) is one of the most common postoperative complications, which can lead to a harmful impact on self-dependence, longer hospital stays, increased medical costs, morbidity, and mortality amongst older adults. Microglia can modulate synapse elimination involved in the complement component protein 1q (C1q) pathway to induce cognitive dysfunction, which is significantly improved by short chain fatty acids (SCFAs) treatment. Here we investigate the effects of SCFAs treatment on PND via mediating C1q complement pathway. High-throughput sequencing of 16S rDNA from fecal samples of male SD rats was applied to assess the changes in gut microbiota. Fecal microbiota transplantation (FMT) was performed to investigate whether gut microbiota from PND rats could alter cognitive impairment. The blood from the rat tail vein was collected to measure the SCFAs concentrations. Hippocampal and brain tissue samples were obtained to perform Western blots, Golgi and immunofluorescence staining. Primary microglia treated with SCFAs or Histone deacetylase inhibitor were cultured to measure microglial activation states and the expression of acetylated histone. The 16S rDNA sequencing results showed that PND rats had the significant changes in the species diversity of the gut microbiota and the metabolite of specifc species. Gut microbiota from PND rats could alter spatial learning and memory, and meanwhile, the changed SCFAs concentrations in plasma were involved. The synapse elimination in PND rats was strikingly reversed by SCFAs treatment involved in modulation complement C1q via suppressing neuroinflammation. This suggests that a link between gut microbiota dysbiosis and cognitive function impairment is involved in synapse elimination via mediating complement C1q pathway. SCFAs treatment can alleviate PND, the mechanisms of which may be associated with regulating complement C1q pathway.}, } @article {pmid39680691, year = {2024}, author = {Yang, JC and Lagishetty, V and Aja, E and Arias-Jayo, N and Chang, C and Hauer, M and Katzka, W and Zhou, Y and Sedighian, F and Koletic, C and Liang, F and Dong, TS and Situ, J and Troutman, R and Buri, H and Bhute, S and Simpson, CA and Braun, J and Jacob, N and Jacobs, JP}, title = {Biogeographical distribution of gut microbiome composition and function is partially recapitulated by fecal transplantation into germ-free mice.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrae250}, pmid = {39680691}, issn = {1751-7370}, abstract = {Fecal microbiota transplantation has been vital for establishing whether host phenotypes can be conferred through the microbiome. However, whether the existing microbial ecology along the mouse gastrointestinal tract can be recapitulated in germ-free mice colonized with stool remains unknown. We first identified microbes and their predicted functions specific to each of six intestinal regions in three cohorts of specific pathogen-free mice spanning two facilities. Of these region-specific microbes, the health-linked genus Akkermansia was consistently enriched in the lumen of the small intestine compared to the colon. Predictive functional modeling on 16S rRNA gene amplicon sequencing data recapitulated in shotgun sequencing data revealed increased microbial central metabolism, lipolytic fermentation, and cross-feeding in the small intestine, whereas butyrate synthesis was colon-enriched. Neuroactive compound metabolism also demonstrated regional specificity, including small intestine-enriched gamma-aminobutyric acid degradation and colon-enriched tryptophan degradation. Specifically, the jejunum and ileum stood out as sites with high predicted metabolic and neuromodulation activity. Differences between luminal and mucosal microbiomes within each site of the gastrointestinal tract were largely facility-specific, though there were a few consistent patterns in microbial metabolism in specific pathogen-free mice. These included luminal enrichment of central metabolism and cross-feeding within both the small intestine and the colon, and mucosal enrichment of butyrate synthesis within the colon. Across three cohorts of germ-free mice colonized with mice or human stool, compositional and functional region specificity were inconsistently reproduced. These results underscore the importance of investigating the spatial variation of the gut microbiome to better understand its impact on host physiology.}, } @article {pmid39680624, year = {2024}, author = {Zuo, H and Jiang, W and Gao, J and Ma, Z and Li, C and Peng, Y and Jin, J and Zhan, X and Lv, W and Liu, X and Hu, J and Zhang, M and Jia, Y and Xu, Z and Tang, J and Zheng, R and Zuo, B}, title = {SYISL Knockout Promotes Embryonic Muscle Development of Offspring by Modulating Maternal Gut Microbiota and Fetal Myogenic Cell Dynamics.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2410953}, doi = {10.1002/advs.202410953}, pmid = {39680624}, issn = {2198-3844}, support = {32221005//National Natural Science Foundation of China/ ; 31900448//National Natural Science Foundation of China/ ; 2021YFA0805903//National Key Research and Development Program of China/ ; 2021CFA018//Natural Science Foundation of Hubei Province/ ; 2021-620-000-001-030//Agricultural Innovation Fund of Hubei Province/ ; 2022ESOF007//Open Fund of Hubei Key Laboratory of Embryonic Stem Cell Research/ ; 2023ZD04072//Biological Breeding-National Science and Technology Major Project/ ; }, abstract = {Embryonic muscle fiber formation determines post-birth muscle fiber totals. The previous research shows SYISL knockout significantly increases muscle fiber numbers and mass in mice, but the mechanism remains unclear. This study confirms that the SYISL gene, maternal gut microbiota, and their interaction significantly affect the number of muscle fibers in mouse embryos through distinct mechanisms, as SYISL knockout alters maternal gut microbiota composition and boosts butyrate levels in embryonic serum. Both fecal microbiota transplantation and butyrate feeding significantly increase muscle fiber numbers in offspring, with butyrate inhibiting histone deacetylases and increasing histone acetylation in embryonic muscle. Combined analysis of RNA-seq between wild-type and SYISL knockout mice with ChIP-seq for H3K9ac and H3K27ac reveals that SYISL and maternal microbiota interaction regulates myogenesis via the butyrate-HDAC-H3K9ac/H3K27ac pathway. Furthermore, scRNA-seq analysis shows that SYISL knockout alone significantly increases the number and proportion of myogenic cells and their dynamics, independently of regulating histone acetylation levels. Cell communication analysis suggests that this may be due to the downregulation of signaling pathways such as MSTN and TGFβ. Overall, multiple pathways are highlighted through which SYISL influences embryonic muscle development, offering valuable insights for treating muscle diseases and improving livestock production.}, } @article {pmid39679941, year = {2024}, author = {Wu, Q and Wang, J and Tu, C and Chen, P and Deng, Y and Yu, L and Xu, X and Fang, X and Li, W}, title = {Gut microbiota of patients insusceptible to olanzapine-induced fatty liver disease relieves hepatic steatosis in rat.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00167.2024}, pmid = {39679941}, issn = {1522-1547}, support = {82173903//MOST | National Natural Science Foundation of China (NSFC)/ ; 81903686//Natural Science Foundation for Young Scientists of Shanxi Province (Young Scientists Fund of the National Natural Science Foundation of China)/ ; }, abstract = {Olanzapine-induced fatty liver disease continues to pose vital therapeutic challenges in the treatment of psychiatric disorders. In addition, we observed that some patients were less prone to hepatic steatosis induced by olanzapine. Therefore, we aimed to investigate the role and the underlying mechanism of the intestinal flora in olanzapine-mediated hepatic side effects and explore the possible countermeasures. Our results showed that patients with different susceptibilities to olanzapine-induced fatty liver disease had different gut microbial diversity and composition. Furthermore, we performed fecal microbiota treatment (FMT), and confirmed that the gut microbiome of patients less prone to the fatty liver caused by olanzapine exhibited an alleviation against fatty liver disease in rats. In terms of mechanism, we revealed that the crosstalk of leptin with the gut-short-chain fatty acid (SCFA)-liver axis play a critical role in olanzapine-related fatty degeneration in liver. These findings propose a promising strategy for overcoming the issues associated with olanzapine application and will hopefully inspire future in-depth research of fecal microbiota-based therapy in olanzapine-induced fatty liver disease.}, } @article {pmid39679465, year = {2024}, author = {Wang, M and Ma, Y and Zeng, B and Yang, W and Huang, C and Tang, B}, title = {Influence of the Gut Microbiota, Metabolism and Environment on Neuropsychiatric Disorders.}, journal = {Current reviews in clinical and experimental pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724328335219241202142003}, pmid = {39679465}, issn = {2772-4336}, abstract = {The two-way communication between intestinal microbiota and the central nervous system (the microbiota-gut-brain axis) is involved in the regulation of brain function, neurodevelopment, and aging. The microbiota-gut-brain axis dysfunction may be a predisposition factor for Parkinson's disease (PD), Alzheimer's disease (AD), Autism spectrum disorder (ASD), and other neurological diseases. However, it is not clear whether gut microbiota dysfunction contributes to neuropsychiatric disorders. Changes in the gut microbiota may modulate or modify the effects of environmental factors on neuropsychiatric disorders. Factors that impact neuropsychiatric disorders also influence the gut microbiota, including diet patterns, exercise, stress and functional gastrointestinal disorders. These factors change microbiome composition and function, along with the metabolism and immune responses that cause neuropsychiatric disorders. In this review, we summarized epidemiological and laboratory evidence for the influence of the gut microbiota, metabolism and environmental factors on neuropsychiatric disorders incidence and outcomes. Furthermore, the role of gut microbiota in the two-way interaction between the gut and the brain was also reviewed, including the vagus nerve, microbial metabolism, and immuno-inflammatory responses. We also considered the therapeutic strategies that target gut microbiota in the treatment of neuropsychiatric disorders, including prebiotics, probiotics, Fecal microbiota transplant (FMT), and antibiotics. Based on these data, possible strategies for microbiota-targeted intervention could improve people's lives and prevent neuropsychiatric disorders in the future.}, } @article {pmid39679306, year = {2024}, author = {Hasnaoui, A and Trigui, R and Giuffrida, M}, title = {Gut microbiota and mesenteric adipose tissue interactions in shaping phenotypes and treatment strategies for Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {46}, pages = {4969-4976}, pmid = {39679306}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology/therapy ; Humans ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology ; *Fecal Microbiota Transplantation ; *Phenotype ; *Mesentery ; Adipose Tissue/immunology/microbiology/metabolism ; Bacterial Translocation ; Cytokines/metabolism ; }, abstract = {In this letter, we commented on the article by Wu et al. We examined the interactions between mesenteric adipose tissue, creeping fat, and gut microbiota in Crohn's disease (CD), a condition marked by chronic gastrointestinal inflammation with a rising global incidence. The pathogenesis of CD involves complex genetic, environmental, and microbial factors. Dysbiosis, which is an imbalance in gut microbial communities, is frequently observed in CD patients, highlighting the pivotal role of the gut microbiota in disease progression and the inflammatory response. Recent studies have shown that mesenteric adipose tissue and creeping fat actively contribute to inflammation by producing proinflammatory cytokines. The relationship between creeping fat and altered microbiota can shift from a potentially protective role to one that encourages bacterial translocation, further complicating disease management. Recent research has suggested that fecal microbiota transplantation could help restore microbial balance, offering a promising therapeutic strategy to improve clinical disease response.}, } @article {pmid39265742, year = {2025}, author = {Herner, A and Nennstiel, S and Ramser, M and Turina, M and Schlag, C}, title = {New therapeutic approach for anastomotic leaks after ileoanal J-pouch construction in patients with ulcerative colitis.}, journal = {Gastrointestinal endoscopy}, volume = {101}, number = {1}, pages = {222-223}, doi = {10.1016/j.gie.2024.09.004}, pmid = {39265742}, issn = {1097-6779}, } @article {pmid39679283, year = {2024}, author = {Chen, J and Yang, H and Qin, Y and Zhou, X and Ma, Q}, title = {Tryptophan Ameliorates Metabolic Syndrome by Inhibiting Intestinal Farnesoid X Receptor Signaling: The Role of Gut Microbiota-Bile Acid Crosstalk.}, journal = {Research (Washington, D.C.)}, volume = {7}, number = {}, pages = {0515}, pmid = {39679283}, issn = {2639-5274}, abstract = {Background and Aims: Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood. Methods and Results: In this study, experiments involving a high-fat diet (HFD) and fecal microbiota transplantation (FMT) were conducted to investigate the role of Trp in regulating metabolic disorders. In a mouse model, Trp supplementation inhibited intestinal farnesoid X receptor (FXR) signaling and promoted hepatic bile acid (BA) synthesis and excretion, accompanied by elevated levels of conjugated BAs and the ratio of non-12-OH to 12-OH BAs in hepatic and fecal BA profiles. As Trp alters the gut microbiota and the abundance of bile salt hydrolase (BSH)-enriched microbes, we collected fresh feces from Trp-supplemented mice and performed FMT and sterile fecal filtrate (SFF) inoculations in HFD-treated mice. FMT and SFF not only displayed lipid-lowering properties but also inhibited intestinal FXR signaling and increased hepatic BA synthesis. This suggests that the gut microbiota play a beneficial role in improving BA metabolism through Trp. Furthermore, fexaramine (a gut-specific FXR agonist) reversed the therapeutic effects of Trp, suggesting that Trp acts through the FXR signaling pathway. Finally, validation in a finishing pig model revealed that Trp improved lipid metabolism, enlarged the hepatic BA pool, and altered numerous glycerophospholipid molecules in the hepatic lipid profile. Conclusion: Our studies suggest that Trp inhibits intestinal FXR signaling mediated by the gut microbiota-BA crosstalk, which in turn promotes hepatic BA synthesis, thereby ameliorating MS.}, } @article {pmid39679259, year = {2024}, author = {Feng, M and Zou, Z and Shou, P and Peng, W and Liu, M and Li, X}, title = {Gut microbiota and Parkinson's disease: potential links and the role of fecal microbiota transplantation.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1479343}, pmid = {39679259}, issn = {1663-4365}, abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and seriously affects the quality of life of elderly patients. PD is characterized by the loss of dopaminergic neurons in the substantia nigra as well as abnormal accumulation of α-synuclein in neurons. Recent research has deepened our understanding of the gut microbiota, revealing that it participates in the pathological process of PD through the gut-brain axis, suggesting that the gut may be the source of PD. Therefore, studying the relationship between gut microbiota and PD is crucial for improving our understanding of the disease's prevention, diagnosis, and treatment. In this review, we first describe the bidirectional regulation of the gut-brain axis by the gut microbiota and the mechanisms underlying the involvement of gut microbiota and their metabolites in PD. We then summarize the different species of gut microbiota found in patients with PD and their correlations with clinical symptoms. Finally, we review the most comprehensive animal and human studies on treating PD through fecal microbiota transplantation (FMT), discussing the challenges and considerations associated with this treatment approach.}, } @article {pmid39677507, year = {2024}, author = {Li, Y and Xiao, P and Ding, H and Wang, H and Xu, Q and Wang, R and Zheng, L and Song, X and Wang, Y and Zhang, T}, title = {Fecal Microbiota Transplantation in Children with Autism.}, journal = {Neuropsychiatric disease and treatment}, volume = {20}, number = {}, pages = {2391-2400}, pmid = {39677507}, issn = {1176-6328}, abstract = {PURPOSE: This research aimed to explore the clinical efficacy of fecal microbiota transplantation (FMT) in treating children with autism spectrum disorder (ASD).

METHODS: In this single-arm prospective study, every participant received FMT therapy, followed by an 8-week follow-up. Children unable to swallow lyophilized capsules (Caps) received fecal solution through transendoscopic enteral tube (TET) or nasal jejunal tube (NJT) approaches. All participants underwent assessments of ASD core symptoms, gastrointestinal (GI) symptoms and sleep status initially, after treatment and during follow-up. The study outcomes included the changes in scores of the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Gastrointestinal Symptoms Rating Scale (GSRS) and Sleep Disturbance Scale for Children (SDSC), as well as the adverse events (AEs).

RESULTS: 98 participants were involved, consisting of 80 males and 18 females, with a median age of 7 years. 73 children received the FMT in the form of Caps, while 13 patients underwent the procedure through TET and 12 patients via NJT. Improvements were observed in all outcome measures for Caps and NJT groups at both the post-treatment and 8-week follow-up evaluations. Adjusted between-group analyses at post-treatment and follow-up showed that Caps and NJT group had greater reduction in ABC, CARS and SRS scores compared with TET group, while NJT group had greater reduction in SDSC scores compared with Caps and TET group. The incidence of AEs was 8.2% in the Caps group, 23.1% in the TET group, and 8.3% in the NJT group, with no serious AEs reported.

CONCLUSION: FMT treatment can improve the core symptoms, GI symptoms and sleep disturbances in children with ASD. The upper GI tract routes, including Caps and NJT, may be more effective and safe compared to the lower GI tract route of TET.}, } @article {pmid39674485, year = {2024}, author = {Ni, Z and Chen, L and Qian, X and Yong, Y and Wu, M and Yihao, L and Li, J and Wang, Y and Li, L and Shao, Y and Chen, A}, title = {Preliminary characterization of Ramaria botrytoides polysaccharide RB-P1-1 and analysis of its hypoglycemic effects by altering the gut microbiota and metabolites in mice with type 2 diabetes mellitus.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {138774}, doi = {10.1016/j.ijbiomac.2024.138774}, pmid = {39674485}, issn = {1879-0003}, abstract = {Gut microbiota has a symbiotic relationship with the host and is closely linked to the development of type 2 diabetes mellitus (T2DM). Polysaccharides are natural bioactive compounds with beneficial effects on T2DM; however, the mechanisms underlying their effects remain unclear. This study investigated the hypoglycemic effects of a purified polysaccharide, RB-P1-1, from Ramaria botrytoides and assessed its association with gut microbiota and metabolite changes using 16S rDNA sequencing and liquid chromatography-mass spectrometry, respectively. Hypoglycemic effects were evaluated after microbial community restoration via fecal microbiota transplantation. RB-P1-1 significantly improved hyperglycemia profiles and reshaped gut microbiota, increasing the abundance of Alistipes, Bacteroides, Ruminococcus, Odoribacter, Akkermansia, and Turicibacter. RB-P1-1 modulated microbiota metabolites associated with hypoglycemic effects, including pyridoxamine, L-histidine, quercetin, 3-phosphonopropionic acid, oleoylethanolamide, 3-ketocholanic acid, 4-phenylbutyric acid, LysoPC(P-16:0/0:0), LysoPC(18:2), and short-chain fatty acids, and altered various metabolic pathways involved in T2DM development. Gut microbiota that showed altered abundance were correlated with metabolites that showed altered concentration. Gut microbiota isolated from the RB-P1-1-treated group alleviated the symptoms associated with T2DM. These results suggest RB-P1-1 is an effective active ingredient in the treatment of T2DM by modulating gut microbiota and metabolites.}, } @article {pmid39674267, year = {2024}, author = {Cheng, X and Yang, J and Wang, Z and Zhou, K and An, X and Xu, ZZ and Lu, H}, title = {Modulating intestinal viruses: A potential avenue for improving metabolic diseases with unresolved challenges.}, journal = {Life sciences}, volume = {}, number = {}, pages = {123309}, doi = {10.1016/j.lfs.2024.123309}, pmid = {39674267}, issn = {1879-0631}, abstract = {The gut microbiome affects the occurrence and development of metabolic diseases, with a significant amount of research focused on intestinal bacteria. As an important part of the gut microbiome, gut viruses were studied recently, particularly through fecal virome transplantation (FVT), revealing manipulating the gut virus could reverse overweight and glucose intolerance in mice. And human cohort studies found gut virome changed significantly in patients with metabolic disease. By summarizing those studies, we compared the research and analytical methods, as well as the similarities and differences in their results, and analyzed the reasons for these discrepancies. FVT provided potential value to improve metabolic diseases, but the mechanisms involved and the effect of FVT on humans should be investigated further. The potential methods of regulating intestinal virome composition and the possible mechanisms of intestinal virome changes affecting metabolic diseases were also discussed.}, } @article {pmid39672770, year = {2024}, author = {Facchin, S and Cardin, R and Patuzzi, I and Carlotto, C and Minotto, M and Barberio, B and Zingone, F and Besutti, VM and Castagliuolo, I and Cattelan, A and Savarino, EV}, title = {Long-term stability and efficacy of frozen fecal microbiota transplant (FMT) product at 24 months.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2024.11.025}, pmid = {39672770}, issn = {1878-3562}, abstract = {BACKGROUND: Freezing donor fecal microbiota has improved fecal microbiota transplantation (FMT) for recurrent C. difficile infection (CDI), achieving short-term effectiveness similar to fresh-samples. Research shows frozen fecal matter remains effective for up to 12-months at -80 °C.

OBJECTIVE: To assess how long-term-freezing and thawing affect the viability, microbial composition, and clinical efficacy of frozen-stools for FMT.

METHODS: Stool samples from three donors were processed into 18 aliquots, thawed at intervals over two years, and analyzed for cell viability and microbial load. Microbiota composition was assessed through 16S-sequencing, with diversity evaluated using the Shannon-index and Principal-Coordinates-Analysis based on Bray-Curtis-distance (α/β-diversity). The same donors provided fecal material for a total of 23 FMT procedures, including 15 for CDI and 8 off-label.

RESULTS: We found that donor stools frozen for two years contained viable bacteria comparable to fresh samples, with anaerobic and aerobic species remaining viable for 24 months. Despite a reduction in colony-forming-units, FMT was successful in 71.4 % and 100 % of the cases at one year and at the end of follow-up, respectively. Most bacterial changes occurred among anaerobic species (Blautia producta and Bifidobacterium adolescentis), increasing post-thawing. Notably, specific taxa, (C. aerofaciens and Erysipelotrichaceae_Cc115), showed significant unexplained increase.

CONCLUSION: Long-term-stool-storage enhances FMT accessibility without compromising its success, despite taxonomic changes after 24 months.}, } @article {pmid39672439, year = {2024}, author = {Chen, P and Chen, F and Hou, T and Hu, X and Xia, C and Zhang, J and Shen, S and Li, C and Li, K}, title = {Administration time modify the anxiolytic and antidepressant effects of inulin via gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {288}, number = {}, pages = {138698}, doi = {10.1016/j.ijbiomac.2024.138698}, pmid = {39672439}, issn = {1879-0003}, abstract = {An imbalance in the microbiota-gut-brain axis exerts an essential effect on the pathophysiology of depressive and anxiety disorders. Our previous research revealed that the timing of inulin administration altered its effects on chronic unpredictable mild stress (CUMS)-induced anxiety and depression. However, it is still unclear if the gut-brain axis is primarily responsible for these effects. In this study, fecal microbiota transplantation (FMT) confirmed that inulin administration at different times alleviated CUMS-induced anxiety- and depression-like behaviors via the gut-brain axis. The time of administration seemed to modify the anxiolytic and antidepressant effects of inulin, and inulin intervention in the evening was more pronounced in inhibiting the inflammatory responses than that of morning inulin intervention. Serum metabolomics analysis showed that the main differential metabolites, including fenofibric acid, 4'-Hydroxyfenoprofen glucuronide and 5-(4-Hydroxybenzyl)thiazolidine-2,4-dione may be vital for the anxiolytic and antidepressant effects of different inulin treatment times. Our results suggested that inulin administration in the evening was more effective in alleviating the inflammatory responses and improving amino acids metabolism. This study provides a new potential link between the microbiota-gut-brain axis and chrono-nutrition, demonstrating that a more appropriate administration time results in a better intervention effect.}, } @article {pmid39672393, year = {2024}, author = {He, P and He, H and Su, C and Liu, Y and Wang, J and Wu, Y and Wang, B and Wang, S and Zhao, J}, title = {Amomum villosum Lour. alleviates pre-eclampsia by inducing enrichment of Bifidobacterium bifidum through vanillic acid to inhibit placental ferroptosis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {119217}, doi = {10.1016/j.jep.2024.119217}, pmid = {39672393}, issn = {1872-7573}, abstract = {Amomum villosum Lour. (AVL), a traditional Chinese medicine, is widely used to pregnancy-related vomiting and prevent miscarriage. Pre-eclampsia (PE) is a severe pregnancy syndrome. Recent studies have demonstrated interactions between PE and the digestive system. However, it is uncertain that AVL against PE was associated with the gut.

AIM OF THE STUDY: The current research examined the curative impact of AVL on PE and underly mechanisms based on the gut-placenta axis.

MATERIALS AND METHODS: A water decoction of AVL (WOA) was extracted in boiling water, and then the decoction was converted into dried particles by freeze drying. An NG-nitro-L-arginine methyl ester (L-NAME)-induced PE mouse model was established and the preventative activity of WOA was evaluated. Furthermore, the gut microbial composition and structure were analyzed using 16S rRNA gene sequencing. Fecal microbiota transplantation (FMT) experiment was applied to confirm the efficacy of gut microbiota remodeled by WOA.

RESULTS: WOA presented protective efficacy against PE. Notably, WOA induced a significant decrease in maternal hypertension and urine protein levels and promoted fetal intrauterine growth in a dose-dependent manner, thereby improving adverse pregnancy outcomes. Moreover, WOA modulated the angiogenic imbalance by decreasing the ratio between sFlt-1 (soluble fms-like tyrosine kinase 1) and PlGF (placental growth factor) to repair placental injury and inhibited placental ferroptosis by increasing the protein levels of FPN1, FTH1, xCT, and GPX4. Tight junction proteins (ZO-1, Occludin, Claudin1) in the placenta and colon were significantly upregulated by WOA, leading to enhanced placental and gut barriers. WOA rescued intestinal dysbiosis by enriching Bifidobacterium and Akkermansia. Fecal microbiota transplantation (FMT) experiments revealed that the protection of WOA on placenta and gut were dependent on the gut microbial composition. Furthermore, supplementation with both Bifidobacterium bifidum (B. bifidum) and vanillic acid (VA, the major component of WOA) ameliorated PE symptoms. Intriguingly, results from both in vivo and in vitro analyses indicated that the B. bifidum population was enriched by VA.

CONCLUSIONS: This research is the first to demonstrate that WOA prevents PE by enriching Bifidobacterium bifidum, strengthening the gut-placenta barrier, and inhibiting placental ferroptosis. Our findings provide compelling evidence for the vital involvement of the gut-placental axis in the protection of AVL on PE, presenting a novel target for the clinic.}, } @article {pmid39671402, year = {2024}, author = {, }, title = {Retraction: Fecal microbiota transplantation for treatment of recurrent C. difficile infection: An updated randomized controlled trial meta-analysis.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0316040}, pmid = {39671402}, issn = {1932-6203}, } @article {pmid39670752, year = {2024}, author = {Peterson, D and Weidenmaier, C and Timberlake, S and Gura Sadovsky, R}, title = {Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0199924}, doi = {10.1128/spectrum.01999-24}, pmid = {39670752}, issn = {2165-0497}, abstract = {The gut microbiome plays a key role in bile acid (BA) metabolism, where a diversity of metabolic products contribute to human health and disease. In particular, Inflammatory Bowel Disease (IBD) is characterized by a low concentration of secondary bile acids (SBAs), whose transformation from primary bile acids (PBAs) is an essential function performed solely by gut bacteria. BA-transformation activity mediated by the bile acid inducible (bai) operon has been functionally characterized in the genus Clostridium, and homologous bai gene sequences have been found in metagenome-assembled genomes (MAGs) belonging to other taxa in the human gut, but it is unclear which species of bai-carrying bacteria perform physiologically significant amounts of bile acid transformation in healthy and sick individuals. Here, we analyzed hundreds of stool samples with paired metagenomic and metabolomic data from IBD patients and controls and found that the abundance of the bai operon in metagenomic samples was highly predictive of that sample's high- or low-SBA metabolic state. We further found that bai genes from the Clostridium species best characterized as BA transformers were more prevalent in IBD patients than in non-IBD controls, while bai genes from uncharacterized taxa known only from MAGs were much more physiologically relevant in non-IBD samples. These un-isolated clades of BA-transforming bacteria merit further research; as beyond their prevalence in the human population, we found some cases in which they engrafted in IBD patients who had undergone fecal microbiota transplantation and experienced a clinical response.IMPORTANCEIn this paper, we identify specific bacteria that perform an important metabolic function in the human gut and demonstrate that in the guts of a large subset of patients with IBD, these bacteria are missing and the function is defective. This is a rare example where the correlation between the absence of specific bacteria and the dysfunction of metabolism is directly observed, not in mice nor in the lab, but in physiologic microbial communities in the human gut. Our results point to a path for studying how a small but important set of bacteria is affected by conditions in the IBD gut and perhaps to the development of interventions to mitigate the loss of these bacteria in IBD.}, } @article {pmid39669573, year = {2024}, author = {Yan, J and Yang, L and Ren, Q and Zhu, C and Du, H and Wang, Z and Qi, Y and Xian, X and Chen, D}, title = {Gut microbiota as a biomarker and modulator of anti-tumor immunotherapy outcomes.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1471273}, pmid = {39669573}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/therapy/immunology ; *Immunotherapy/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; Animals ; Biomarkers, Tumor ; Probiotics/therapeutic use ; Treatment Outcome ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; }, abstract = {Although immune-checkpoint inhibitors (ICIs) have significantly improved cancer treatment, their effectiveness is limited by primary or acquired resistance in many patients. The gut microbiota, through its production of metabolites and regulation of immune cell functions, plays a vital role in maintaining immune balance and influencing the response to cancer immunotherapies. This review highlights evidence linking specific gut microbial characteristics to increased therapeutic efficacy in a variety of cancers, such as gastrointestinal cancers, melanoma, lung cancer, urinary system cancers, and reproductive system cancers, suggesting the gut microbiota's potential as a predictive biomarker for ICI responsiveness. It also explores the possibility of enhancing ICI effectiveness through fecal microbiota transplantation, probiotics, prebiotics, synbiotics, postbiotics, and dietary modifications. Moreover, the review underscores the need for extensive randomized controlled trials to confirm the gut microbiota's predictive value and to establish guidelines for microbiota-targeted interventions in immunotherapy. In summary, the article suggests that a balanced gut microbiota is key to maximizing immunotherapy benefits and calls for further research to optimize microbiota modulation strategies for cancer treatment. It advocates for a deeper comprehension of the complex interactions between gut microbiota, host immunity, and cancer therapy, aiming for more personalized and effective treatment options.}, } @article {pmid39668679, year = {2024}, author = {Vitarelli, A and Minafra, P and Vulpi, M and Piana, A and Torre, G and Carbonara, U and Divenuto, L and Papapicco, G and Chiaradia, F and Alba, S and Lucarelli, G and Battaglia, M and Ditonno, P}, title = {A new approach to repair recurrent vescicourethral anastomotic strictures after radical prostatectomy: The use of prerectal access.}, journal = {Urologia}, volume = {}, number = {}, pages = {3915603241300877}, doi = {10.1177/03915603241300877}, pmid = {39668679}, issn = {1724-6075}, abstract = {BACKGROUND: Vesicourethral anastomosis stenosis (VUAS) is a well-known complication of prostate cancer treatments, observed in up to 26% of the cases after radical prostatectomy. Conservative management, with single or even repeated transurethral dilation or endoscopic incision of the stenosis, is successful in many cases, but up to 9% of patients are destined to fail after endoscopic treatment. In these cases, a revision of the vesicourethral anastomosis is necessary and can be realized with different surgical approaches. We aim to describe the technique and the outcomes of a new prerectal approach for VUAS repair.

METHODS: Twelve patients with recalcitrant VUAS following radical prostatectomy were enrolled between May 2014 and September 2018 for prerectal transperineal re-anastomosis. The evaluated outcomes were: the rate of successful anatomical repair at 3 months after surgery and at the last follow-up, postoperative incontinence and complications rate, and the need for further treatments.

RESULTS: No major intraoperative complications occurred. After a median follow-up of 46 months (IQR 36-55), 10 patients (83.3%) achieved a good anatomical repair even if one man required an endoscopic urethrotomy, while two patients (16.67%) with a history of pelvic radiotherapy developed a surgical site infection that required toilette and external urinary diversion. Among the others, nine (75%) developed severe stress urinary incontinence, with resolution of their condition. No patient reported significant postoperative pain or fecal incontinence.

CONCLUSIONS: The prerectal approach to VUAS repair allows direct access to the posterior urethra and the anastomosis, providing a better mobilization of the bladder neck for tension-free anastomosis. However, patients with a history of pelvic radiotherapy have a higher risk of complications. Postoperative incontinence is very common, but urinary continence could be restored with subsequent artificial urinary sphincter placement.}, } @article {pmid39667939, year = {2024}, author = {Dang, H and Feng, P and Zhang, S and Peng, L and Xing, S and Li, Y and Wen, X and Zhou, L and Goswami, S and Xiao, M and Barker, N and Sansonetti, P and Kundu, P}, title = {Maternal gut microbiota influence stem cell function in offspring.}, journal = {Cell stem cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.stem.2024.10.003}, pmid = {39667939}, issn = {1875-9777}, abstract = {The maternal microbiome influences child health. However, its impact on a given offspring's stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring's stem cells, we manipulated maternal microbiota using Akkermansia muciniphila. Different maternal microbiomes had distinct effects on proliferation and differentiation of neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients' offspring. The progeny of germ-free mice selectively colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal microbiomes enriched the levels of circulating short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings' stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings' stem cells and represent a promising target for interventions.}, } @article {pmid39667762, year = {2024}, author = {Zhang, QW and Yang, MJ and Liao, CY and Taha, R and Li, QY and Abdelmotalab, MI and Zhao, SY and Xu, Y and Jiang, ZZ and Chu, CH and Huang, X and Jiao, CH and Sun, LX}, title = {Atractylodes macrocephala Koidz polysaccharide ameliorates DSS-induced colitis in mice by regulating the gut microbiota and tryptophan metabolism.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.17409}, pmid = {39667762}, issn = {1476-5381}, support = {82074115//National Natural Science Foundation of China/ ; 82174072//National Natural Science Foundation of China/ ; JSPH-MB-2022-2 supporting//Clinical Capability Enhancement Project Medical/ ; JSPH-MB-2022-2//Clinical Capability Enhancement Project/ ; }, abstract = {BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS-induced colitis, and we aimed to investigate the underlying mechanisms in this study.

EXPERIMENTAL APPROACH: PAMK was used to treat DSS-induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan-metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic-mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis.

KEY RESULTS: PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan-metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance.

CONCLUSION AND IMPLICATIONS: Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS-induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.}, } @article {pmid39667450, year = {2024}, author = {Fu, Q and Yang, Y and Tian, Q and Zhu, Y and Xu, H and Wang, J and Huang, Q}, title = {Exploring the mechanism of Paotianxiong polysaccharide in the treatment of chronic kidney disease combining metabolomics and microbiomics technologies.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {138629}, doi = {10.1016/j.ijbiomac.2024.138629}, pmid = {39667450}, issn = {1879-0003}, abstract = {A close relationship between the pathogenesis of chronic kidney disease (CKD) and abnormalities in the gut-kidney axis. Paotianxiong polysaccharides (PTXP) that have demonstrated therapeutic effects on CKD. However, the specific mechanism by which PTXP ameliorates CKD through the gut-kidney axis remains to be explored. In this study, the microbiomes and metabolomics were combined to investigate the impact of PTXP on intestinal flora structure and metabolism, further unveiling the relationship through correlation analysis. The results showed that PTXP intervention significantly modulated renal function abnormalities in CKD rats and significantly modulates gut microbial disorders, evidenced by an increased abundance of Lactobacillus murinus, Bacteroides fragilis, and a decreased abundance of Bifidobacterium pseudolongum. Furthermore, PTXP reversed the changes in intestinal metabolites, such as linoleic acid and docosahexaenoic acid, induced by CKD and identified unsaturated fatty acid metabolism as a key metabolic pathway. Correlation analyses also revealed associations among gut microorganisms, metabolites, and renal function indexes, confirming that PTXP alleviated CKD through the gut-kidney axis. Moreover, the above conclusions were verified by fecal bacteria transplantation experiments. These findings provide insights into the mechanism of PTXP for the treatment of CKD and provide new targets for the treatment of CKD.}, } @article {pmid39666007, year = {2025}, author = {Shang, J and Del Valle, DM and Britton, GJ and Mead, KR and Rajpal, U and Chen-Liaw, A and Mogno, I and Li, Z and Menon, R and Gonzalez-Kozlova, E and Elkrief, A and Peled, JU and Gonsalves, TR and Shah, NJ and Postow, M and Colombel, JF and Gnjatic, S and Faleck, DM and Faith, JJ}, title = {Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis.}, journal = {The Journal of experimental medicine}, volume = {222}, number = {1}, pages = {}, pmid = {39666007}, issn = {1540-9538}, support = {U24 CA224319/CA/NCI NIH HHS/United States ; U01 DK124165/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; F30 CA261144/CA/NCI NIH HHS/United States ; //Memorial Sloan-Kettering Cancer Center/ ; K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08HL143189/NH/NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/immunology/drug effects ; Animals ; Humans ; *Colitis/microbiology/immunology/chemically induced ; Mice ; *Immunotherapy/adverse effects/methods ; Female ; Male ; Immune Checkpoint Inhibitors/adverse effects/pharmacology ; Mice, Inbred C57BL ; Middle Aged ; Aged ; Feces/microbiology ; Neoplasms/immunology/microbiology/therapy/drug therapy ; }, abstract = {Immunotherapy-related colitis (irC) frequently emerges as an immune-related adverse event during immune checkpoint inhibitor therapy and is presumably influenced by the gut microbiota. We longitudinally studied microbiomes from 38 ICI-treated cancer patients. We compared 13 ICI-treated subjects who developed irC against 25 ICI-treated subjects who remained irC-free, along with a validation cohort. Leveraging a preclinical mouse model, predisease stools from irC subjects induced greater colitigenicity upon transfer to mice. The microbiota during the first 10 days of irC closely resembled inflammatory bowel disease microbiomes, with reduced diversity, increased Proteobacteria and Veillonella, and decreased Faecalibacterium, which normalized before irC remission. These findings highlight the irC gut microbiota as functionally distinct but phylogenetically similar to non-irC and healthy microbiomes, with the exception of an acute, transient disruption early in irC. We underscore the significance of longitudinal microbiome profiling in developing clinical avenues to detect, monitor, and mitigate irC in ICI therapy cancer patients.}, } @article {pmid39664442, year = {2024}, author = {Chen, L and Zhang, K and Liu, J and Li, X and Liu, Y and Ma, H and Yang, J and Li, J and Chen, L and Hsu, C and Zeng, J and Xie, X and Wang, Q}, title = {The role of the microbiota-gut-brain axis in methamphetamine-induced neurotoxicity: Disruption of microbial composition and short-chain fatty acid metabolism.}, journal = {Acta pharmaceutica Sinica. B}, volume = {14}, number = {11}, pages = {4832-4857}, pmid = {39664442}, issn = {2211-3835}, abstract = {Methamphetamine (METH) abuse is associated with significant neurotoxicity, high addiction potential, and behavioral abnormalities. Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders. However, the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored. In this study, we employed fecal microbiota transplantation (FMT) and antibiotic (Abx) intervention to manipulate the gut microbiota in mice administered METH. Furthermore, we supplemented METH-treated mice with short-chain fatty acids (SCFAs) and pioglitazone (Pio) to determine the protective effects on gut microbiota metabolism. Finally, we assessed the underlying mechanisms of the gut-brain neural circuit in vagotomized mice. Our data provide compelling evidence that modulation of the gut microbiome through FMT or microbiome knockdown by Abx plays a crucial role in METH-induced neurotoxicity, behavioral disorders, gut microbiota disturbances, and intestinal barrier impairment. Furthermore, our findings highlight a novel prevention strategy for mitigating the risks to both the nervous and intestinal systems caused by METH, which involves supplementation with SCFAs or Pio.}, } @article {pmid39664063, year = {2024}, author = {Li, L and Cai, F and Guo, C and Liu, Z and Qin, J and Huang, J}, title = {Gut microbiome and NAFLD: impact and therapeutic potential.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1500453}, pmid = {39664063}, issn = {1664-302X}, abstract = {Non-Alcoholic Fatty Liver Disease (NAFLD) affects approximately 32.4% of the global population and poses a significant health concern. Emerging evidence underscores the pivotal role of the gut microbiota-including bacteria, viruses, fungi, and parasites-in the development and progression of NAFLD. Dysbiosis among gut bacteria alters key biological pathways that contribute to liver fat accumulation and inflammation. The gut virome, comprising bacteriophages and eukaryotic viruses, significantly shapes microbial community dynamics and impacts host metabolism through complex interactions. Similarly, gut fungi maintain a symbiotic relationship with bacteria; the relationship between gut fungi and bacteria is crucial for overall host health, with certain fungal species such as Candida in NAFLD patients showing detrimental associations with metabolic markers and liver function. Additionally, the "hygiene hypothesis" suggests that reduced exposure to gut parasites may affect immune regulation and metabolic processes, potentially influencing conditions like obesity and insulin resistance. This review synthesizes current knowledge on the intricate interactions within the gut microbiota and their associations with NAFLD. We highlight the therapeutic potential of targeting these microbial communities through interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Addressing the complexities of NAFLD requires comprehensive strategies that consider the multifaceted roles of gut microorganisms in disease pathology.}, } @article {pmid39664050, year = {2024}, author = {Alhamlan, FS and Albadawi, IA and Al-Qahtani, AA and Awartani, KA and Obeid, DA and Tulbah, AM}, title = {Cervicovaginal and gastrointestinal microbiomes in gynecological cancers and their roles in therapeutic intervention.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1489942}, pmid = {39664050}, issn = {1664-302X}, abstract = {Cancer remains a significant global health concern, and understanding factors that regulate cancer development is important. The microbiome, with its potential role in cancer development, progression, and treatment, has garnered increasing attention in recent years. The cervicovaginal and gastrointestinal microbiomes in females constitute complex biological ecosystems. Although the gut microbiome has been extensively studied, little is known about the cervicovaginal microbiome. The microbiome plays a crucial role in maintaining local microenvironments and tissue homeostasis, but dysbiosis can disrupt this fine balance and contribute to pathological ramifications leading to cancer. This review explores the current understanding of the microbiome's correlation with gynecological cancers and highlights the potential of microbiome-based interventions to improve outcomes in these cancers. In addition, this review underscores the gaps and limitations in the literature, such as findings in specific ethnicities compared with understudied ethnicities. In addition, discrepancies in molecular techniques and terminology (microbiome vs. microbiota) used in the literature are addressed. Emerging evidence linking gynecological cancers and dysbiosis underscores microbiota as a potential target for cancer prevention and therapy. Manipulating the microbiome, such as through the use of probiotics, prebiotics, antibiotics, or vaginal and fecal transplantation, has demonstrated benefits in the treatment of chronic and inflammatory conditions. Further translational research in this field is needed to integrate the benefits of beneficial microorganisms in the fight against gynecological cancers.}, } @article {pmid39662821, year = {2024}, author = {Groenewegen, B and van Lingen, E and Kovynev, A and van den Berg, AJ and Berssenbrugge, EKL and Sanders, IMJG and van Prehn, J and van Nood, E and Goorhuis, A and Kuijper, EJ and Smits, WK and Wiese, M and Keller, JJ and Ducarmon, QR and Terveer, EM and , }, title = {The presence of Clostridioides difficile in faeces before and after faecal microbiota transplantation and its relation with recurrent C. difficile infection and the gut microbiota in a Dutch cohort.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2024.12.003}, pmid = {39662821}, issn = {1469-0691}, abstract = {OBJECTIVES: To study the presence of Clostridioides difficile in faeces of patients with recurrent C. difficile infection (rCDI) before and after faecal microbiota transplantation (FMT) and to identify risk factors for faecal C. difficile and CDI recurrence.

METHODS: N=83 faecal sample triads (pre-FMT (∼one day), post-FMT (∼three weeks), and a corresponding FMT donor sample), and n=22 long-term (∼1-3 years) follow-up faecal samples (LTFU) were collected from FMT-treated patients. The presence of C. difficile in faeces was assessed by enrichment broth culture and PCR (tcdB gene) and associated with patient characteristics, FMT outcome, duration of pre-FMT vancomycin, FMT donor, post-FMT antibiotic use, and faecal microbiota composition (shotgun metagenomics).

RESULTS: The FMT cure rate for rCDI was 92.8% (77/83), with six early CDI recurrences (
CONCLUSIONS: While eradication of C. difficile is not required for clinical cure of rCDI by FMT, it is associated with reduced prevalence of early CDI recurrence, as are the full completion of pre-FMT vancomycin (at least 10 days) and avoiding post-FMT antibiotics.}, } @article {pmid39659943, year = {2024}, author = {Zhao, W and Chen, Y and Xiao, J and Tang, Z and Wang, L and Ren, Y and Chen, Y}, title = {Updated outcomes and exploratory analysis of RENMIN-215: tislelizumab plus fruquintinib and fecal microbiota transplantation in refractory microsatellite stable metastatic colorectal cancer.}, journal = {American journal of cancer research}, volume = {14}, number = {11}, pages = {5351-5364}, pmid = {39659943}, issn = {2156-6976}, abstract = {Primary analysis of the open-label, single-arm, phase II RENMIN-215 trial (primary data cutoff date: July 10, 2023) showed promising efficacy and tolerable safety with tislelizumab plus fruquintinib and fecal microbiota transplantation (FMT) in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Here, we reported updated survival and safety results with a median follow-up of 34.0 months (data cut-off May 20, 2024), as well as patient-reported outcomes and laboratory analysis. Twenty patients with MSS mCRC resistant or refractory to at least second-line therapy were enrolled and received tislelizumab plus fruquintinib and FMT. The primary endpoint was progression-free survival. Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate, safety, health-related quality of life questionnaire and exploratory laboratory tests. In addition, 94 mCRC patients who received third-line or above immunotherapy in real world were screened for propensity score matching (PSM) analysis to compare efficacy. Our results showed that the median OS was 13.7 months (95% CI, 9.3-17.7), and the ORR was 20.0% (95% CI, 5.7-43.7). After PSM, the median OS benefit of the study regimen remained statistically significant (HR = 0.26; 95% CI, 0.07-0.95; P = 0.042). Patients with primary tumor surgery had better clinical outcomes. No new safety concerns were detected. Seven (35.0%) patients had one or more grade 3 treatment-related adverse events. The majority of patients had improved or stable global health status (GHS). Median time to deterioration for GHS was 7.7 months. Peripheral blood lymphocyte analysis showed that increased gamma-delta 2 T cells were positively associated with improved response and survival. To conclude, the updated results provide further evidence of sustained antitumor activity of tislelizumab plus fruquintinib and FMT in heavily pretreated MSS mCRC patients with a consistent safety profile.}, } @article {pmid39659426, year = {2024}, author = {Abildinova, GZ and Benberin, VV and Vochshenkova, TA and Afshar, A and Mussin, NM and Kaliyev, AA and Zhussupova, Z and Tamadon, A}, title = {The gut-brain-metabolic axis: exploring the role of microbiota in insulin resistance and cognitive function.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1463958}, pmid = {39659426}, issn = {1664-302X}, abstract = {The gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic-pituitary-adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.}, } @article {pmid39658705, year = {2024}, author = {Wang, Z and Wang, Z and Lu, T and Yuan, G and Chen, W and Jin, J and Jiang, X and Yan, W and Yuan, K and Zou, G and Bao, Y and Shi, J and Liu, X and Wei, H and Han, Y and Lu, L}, title = {Gut microbiota regulate insomnia-like behaviors via gut-brain metabolic axis.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {39658705}, issn = {1476-5578}, support = {82288101//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Sleep interacts reciprocally with the gut microbiota. However, mechanisms of the gut microbe-brain metabolic axis that are responsible for sleep behavior have remained largely unknown. Here, we showed that the absence of the gut microbiota can alter sleep behavior. Sleep deprivation reduced butyrate levels in fecal content and the hypothalamus in specific pathogen-free mice but not in germ-free mice. The microbial metabolite butyrate can promote sleep by modulating orexin neuronal activity in the lateral hypothalamic area in mice. Insomnia patients had lower serum butyrate levels and a deficiency in butyrate-producing species within the gut microbiota. Transplantation of the gut microbiota from insomnia patients to germ-free mice conferred insomnia-like behaviors, accompanied by a decrease in serum butyrate levels. The oral administration of butyrate rescued sleep disturbances in recipient mice. Overall, these findings reveal the causal role of microbial metabolic pathways in modulating insomnia-like behaviors, suggesting potential therapeutic strategies for treating sleep disorders.}, } @article {pmid39658176, year = {2025}, author = {Guo, B and Zhang, W and Zhang, J and Zou, J and Dong, N and Liu, B}, title = {Euglena gracilis polysaccharide modulated gut dysbiosis of obese individuals via acetic acid in an in vitro fermentation model.}, journal = {Food research international (Ottawa, Ont.)}, volume = {199}, number = {}, pages = {115385}, doi = {10.1016/j.foodres.2024.115385}, pmid = {39658176}, issn = {1873-7145}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Dysbiosis ; *Fermentation ; *Acetic Acid/metabolism ; Humans ; *Obesity/metabolism/microbiology ; *Polysaccharides/pharmacology/metabolism ; *Euglena gracilis/metabolism ; Prebiotics ; Male ; Feces/microbiology ; Adult ; Bacteria/metabolism/classification/drug effects ; Lipid Metabolism/drug effects ; Female ; }, abstract = {Gut dysbiosis is a characteristic feature of obesity and targeting gut microbiota presents a promising approach to attenuate obesity. Euglena gracilis polysaccharide (EGP) has emerged as a potential prebiotic capable of promoting health-beneficial bacteria. However, its effects on the gut dysbiosis of obese individuals remain unclear. This study investigated the impacts of EGP on gut microbiota from both non-obese and obese individuals using an in vitro fermentation model. Results showed that EGP significantly altered the gut microbiota composition and metabolism. Specifically, EGP improved the relative abundance of Paeniclostridium, Clostridium_sensu_stricto_1 and Paraclostridium of the non-obese individuals and Providencia, Enterococcus and Bacteroides of the obese individuals. Metabolomics results showed EGP significantly altered the lipid metabolism especially in the obese group with enriched bile secretion and cholesterol metabolism pathways. Noting that acetic acid was significantly increased in both groups, these acetic acid favorable microbiota from non-obese individuals was collected with acetic acid supplementation. Transplantation of these acetic acid-induced microbiota (AAiM) notably improved the richness and diversity of fecal microbiota of the obese individuals, enhancing the growth of probiotics like Bacteroides and Bifidobacterium. Consequently, AAiM significantly restructured macronutrients (including amino acids, carbohydrates and lipids) metabolism of the gut microbiota from obese individuals. Altogether, this study underscores the potential of EGP and acetic acid favorable microbiota in manipulating obesity-associated gut dysbiosis via acetic acid production.}, } @article {pmid39656490, year = {2024}, author = {Balakrishnan, R and Kang, SI and Lee, JY and Rho, YK and Kim, BK and Choi, DK}, title = {Gut Microbiota-Immune System Interactions in Health and Neurodegenerative Diseases: Insights into Molecular Mechanisms and Therapeutic Applications.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1362}, pmid = {39656490}, issn = {2152-5250}, abstract = {The human body contains approximately 100 trillion microorganisms, predominantly within the gastrointestinal tract, collectively called the gut microbiota. Investigations have revealed the bidirectional communication between the gut microbiota and the brain, characterized as the "microbiota-gut-brain axis." This axis represents an important regulator of brain development and function, immune system development, and nutrient metabolism, making it a target for efforts to alleviate the development and progression of neurodegenerative diseases (NDDs). Despite extensive biomedical and clinical research, our understanding of the causes, optimal treatment, and progression of NDDs remains limited. This paper aims to summarize the available knowledge on the role played by gut microbiota and how it is connected to the progression of neurodegenerative conditions; in particular, the relationship between the microbiota and gut-brain communications and the gut microbiota and neuro-immune conditions is reviewed. We discuss how and why the gut immune system communicates with the brain and how this communication impacts neurodegeneration. Next, we examine the alterations in the gut microbiota, immune response, and brain changes associated with gut dysbiosis. Finally, we highlight the preclinical and clinical evidence for probiotics, prebiotics, fecal microbiota transplantation, dietary supplements, natural drugs, and exercise intervention as potential therapeutic approaches that could lead to a new treatment paradigm for NDDs.}, } @article {pmid39653685, year = {2024}, author = {Li, X and Zheng, P and Zou, Y and Guan, L and Li, N and Liu, J and Lu, N and Zhu, Y and He, C}, title = {Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2436949}, pmid = {39653685}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Obesity/metabolism ; Mice ; *Inulin/pharmacology/administration & dosage ; *Diet, High-Fat/adverse effects ; *Mice, Inbred C57BL ; Male ; *Pancreas/pathology/metabolism/drug effects ; *Pancreatitis/metabolism ; Dysbiosis/microbiology ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Bacteria/classification/isolation & purification/metabolism/genetics ; }, abstract = {Obesity is a definitive factor of severity and mortality of acute pancreatitis (AP), and gut microbiota dysbiosis is involved in its pathogenesis. However, the effect of gut microbiota modulation by dietary components on high fat diet (HFD)-induced severe AP remains unclear. Here, we found that the inulin, a soluble dietary fiber, mitigated pancreatic injury and systematic inflammation in mice fed HFD, which was dependent on gut microbiota as this protective effect was attenuated in germ-free mice. Inulin treatment suppressed the overgrowth of pathogenic bacteria Escherichia Shigella, Enterococcus, Klebsiella, while increased the abundance of probiotics Akkermansia. Fecal microbiota transplantation from inulin-treated mice to recipient mice reduced pancreatic damage and remodeled intestinal homeostasis. Additionally, inulin increased fecal short chain fatty acids (SCFAs), strengthened gut barrier and restored Paneth cells. The beneficial effect of inulin on improving pancreatic damage and leaky gut was diminished after the suppression of SCFAs. Notably, SCFAs administration, especially butyrate, to HFD mice blocked pancreatic and intestinal injury with the inhibition of histone deacetylase 3 (HDAC3), and pharmacological HDAC3 inhibition mimicked the ameliorative effect of SCFAs. Mechanically, butyrate modulated macrophage M1/M2 polarization balance by suppressing HDAC3 and subsequent acetylation of histone H3K27. Collectively, our data offer new insights into the gut microbiota-pancreas axis that may be leveraged to augment the potential supplementation of prebiotic inulin in the management of obesity associated severe AP.}, } @article {pmid39653155, year = {2024}, author = {Zhao, Y and Sun, S and Liu, J and Zheng, M and Liu, M and Liu, J and Liu, H}, title = {Investigation of the protective mechanism of paeoniflorin against hyperlipidemia by an integrated metabolomics and gut microbiota strategy.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109831}, doi = {10.1016/j.jnutbio.2024.109831}, pmid = {39653155}, issn = {1873-4847}, abstract = {The prevalence of hyperlipidemia is gradually increasing globally, posing a serious threat to public health. Previous studies have shown that paeoniflorin (PF) effectively improved abnormal lipid metabolism in atherosclerotic mice. However, the anti-hyperlipidemia effect and potential mechanism of paeoniflorin remain unclear. The gut microbiota (GM) is closely related to hyperlipidemia. This study was aimed to investigate effects of PF on improving the health of high-fat diet (HFD)-induced hyperlipidemic mice by modulating GM. A hyperlipidemic mouse model was established using an HFD, and the hypolipidemic effect of PF was detected in vivo. Besides16S ribosomal RNA sequencing and SCFAs metabolic analysis were performed to explore the lipid-lowering mechanism of PF. Importantly, fecal microbiota transplantation (FMT) experiments were conducted to verify the lipid-lowering mechanism of PF. The results showed that PF significantly inhibited the development of hyperlipidemia, reduced serum lipid and inflammatory cytokine levels, and improved liver steatosis. In addition, 16S rRNA sequencing revealed that PF treatment significantly increased the relative abundance of Lactobacillus, Coprococcus, Blautia, Roseburia, and Bacteroides while reducing the relative abundance of Prevotella. Meanwhile, the results of targeted metabolomics indicate that PF therapy can effectively restore butyric acid and propionic acid levels in the intestine. The FMT experiments further demonstrated that PF improved hyperlipidemia by regulating GM and its metabolites. The above results provide a valuable theoretical basis for the development and application of PF as a functional food for hyperlipidemia.}, } @article {pmid39652283, year = {2024}, author = {Lou, L and Zhou, L and Wang, Y}, title = {Gut Microbiota: A Modulator and Therapeutic Target for Chronic Pain.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39652283}, issn = {1559-1182}, abstract = {Chronic pain is a prevalent condition, impacting nearly one-fifth of the global population. Despite the availability of various clinical treatments, each comes with inherent limitations, and few offer a complete cure, resulting in a significant social and economic burden. Therefore, it is important to determine the pathogenesis and causes of chronic pain. Numerous studies have shown a close link between the intestinal microflora and chronic pain. The gut microbiota can exert their effects on chronic pain through both central and peripheral mechanisms and is able to communicate with the brain through its own components or metabolites. They also can regulate chronic pain by affecting pro- and anti-inflammatory cells. This review is aimed at reviewing the connection between gut flora and different types of chronic pain, including visceral pain, neuropathic pain, inflammatory pain, musculoskeletal pain, migraine, and chronic cancer pain; exploring the central and peripheral mechanisms of the influence of gut flora on chronic pain; and attempting to provide novel treatment options for chronic pain, that is, the gut microbiota can be regulated by probiotics, fecal microbial transplantation, and natural products to treat chronic pain. By examining the intricate relationship between gut flora and chronic pain, the review sought to pave the way for new treatment strategies that target the gut microbiota, offering hope for more effective pain management.}, } @article {pmid39651062, year = {2024}, author = {Kaundal, S and Patil, AN and Ks, L and Sharma, V and Arora, A and Singh, C and Jandial, A and Jain, A and Prakash, G and Khadwal, A and Malhotra, P and Lad, DP}, title = {A role for diet and gut microbiota metabolites in autologous hematopoietic cell transplant recipients.}, journal = {Blood cell therapy}, volume = {7}, number = {4}, pages = {101-105}, pmid = {39651062}, issn = {2432-7026}, abstract = {INTRODUCTION: The gut microbiome has an established role in allogeneic hematopoietic cell transplantation (allo-HCT), but not in an auto-HCT setting. We have hypothesized that fecal short-chain fatty acids (SCFA) and urinary 3-indoxyl sulfate (3-IS), which are metabolites derived from the action of the gut microbiome on dietary fiber, play a role in auto-HCT outcomes.

METHODS: This was a single-center prospective study involving auto-HCT recipients. Baseline patient and disease details, diet diaries, and antibiotic exposure were recorded in consenting patients. Serial (pre-HCT, week two, and week four post-HCT) SCFA and urine 3-IS levels were measured using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). HCT outcomes were correlated with these metabolites.

RESULTS: Thirty patients (myeloma, n=13; lymphoma, n=17) were analyzed. The levels of urinary 3-IS, fecal acetate, propionate, and butyrate were found to be decreased at week two and were recovered by week four post-HCT. Those with low median nadir fecal butyrate levels at week two also had significantly lower pre-HCT and week four butyrate levels. Recipients with low butyrate levels had more grade ≥2 mucositis (80% vs. 33%, p=0.01) and low fiber intake (10.4 g vs. 13.6 g, p=0.04). They also had more carbapenem exposure (93% vs. 47%, p=0.005) and prolonged antibiotics (11 days vs. 8 days, p=0.008). There were no differences in the time to neutrophil or platelet engraftment, mortality, or disease response.

CONCLUSION: Low pre-HCT fecal butyrate levels tend to persist post-HCT and they are associated with mucositis, dietary fiber intake, and antibiotic exposure. The gut microbiome and its modulation may play a role in auto-HCT settings.}, } @article {pmid39651029, year = {2024}, author = {Suresh, SB and Malireddi, A and Abera, M and Noor, K and Ansar, M and Boddeti, S and Nath, TS}, title = {Gut Microbiome and Its Role in Parkinson's Disease.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73150}, pmid = {39651029}, issn = {2168-8184}, abstract = {Parkinson's disease (PD) afflicted more than 8.5 million people globally in 2019, as the prevalence of the condition more than doubled during the preceding 25 years. Both non-motor symptoms, such as mood disorders and cognitive impairment, and motor symptoms, such as tremors and rigidity, are indicative of this progressive neurodegenerative disease. Recent data indicates a significant role for the gut microbiome in PD pathogenesis and progression, emphasizing the microbiota-gut-brain axis. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, this systematic review summarizes our current knowledge about the function of the gut microbiome in PD, highlighting recurrent microbial alterations and assessing microbiome-based treatment strategies. The review revealed several consistent patterns in the gut microbiota of PD patients, including reduced microbial diversity and specific taxonomic alterations, including a drop in Firmicutes abundance and an increase in Proteobacteria abundance. Functional changes in the gut microbiome, such as altered short-chain fatty acid (SCFA) production and tryptophan metabolism, were also noted. These microbial changes were observed even in early-stage and drug-naïve PD patients, suggesting they are not merely a consequence of disease progression or medication use. The review highlighted potential mechanisms linking gut microbiome alterations to PD, including increased intestinal permeability, neuroinflammation, and modulation of alpha-synuclein aggregation. Probiotics, prebiotics, and fecal microbiota transplantation are a few interventions that try to modify the gut microbiome and might be possible to halt the advancement of PD and enhance patients' quality of life with the condition. Future research should focus on establishing causality through large-scale longitudinal studies, standardizing microbiome analysis methods, and exploring personalized microbiome-based therapies.}, } @article {pmid39650985, year = {2024}, author = {Ina, EA and Ziton, S and Dourvetakis, K and Corallo, JP}, title = {Loop Ileostomy With Colonic Lavage: Case Report of an Alternative to Total Colectomy in the Setting of Fulminant Clostridium difficile Colitis.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73141}, pmid = {39650985}, issn = {2168-8184}, abstract = {Fulminant Clostridium difficile colitis is a severe and potentially life-threatening form of Clostridium difficile-associated bacterial disease leading to inflammation and damage to the colon. Complications such as toxic megacolon, sepsis, and multi-organ failure commonly occur in individuals with compromised immune systems and recent antibiotic use. Management of Clostridium difficile colitis involves optimization of fluid and electrolyte balance, and elimination of bacteria commonly by administering vancomycin or fidaxomicin. In cases where pharmacological management has been ineffective, fecal microbiota transplantation and surgical intervention demonstrated success. Historically, surgical intervention has involved a total abdominal colectomy with end ileostomy; however, other surgical options have shown increasing benefits with preservation of the colon. This case report aims to provide an example of an alternative management strategy for fulminant Clostridium difficile infections, via the use of a loop ileostomy and colonic lavage. The combination of loop ileostomy and colonic lavage promotes bowel rest, removes toxins, and promotes healing while decreasing inflammation. As with all management modalities, it is essential to recognize the associated complications. The potential benefits should be carefully weighed against the risks on a case-by-case basis with the help of a multidisciplinary team as illustrated through this case report. Overall, early recognition and treatment of fulminant Clostridium difficile colitis using loop ileostomy and colonic lavage prevents further disease progression and improves patient outcomes.}, } @article {pmid39649613, year = {2024}, author = {Moreau, GB and Young, M and Behm, B and Tanyüksel, M and Ramakrishnan, G and Petri, WA}, title = {FMT Restores Colonic Protein Biosynthesis and Cell Proliferation in Patients with Recurrent Clostridioides difficile Disease.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.28.24318101}, pmid = {39649613}, abstract = {Recurrent C. difficile infection (CDI) is a major health threat with significant mortality and financial costs. Fecal Microbiota Transplantation (FMT) is an effective therapy, however the mechanisms by which it acts, particularly on the host, are poorly understood. Here we enrolled a prospective cohort of human patients with recurrent CDI (n=16) undergoing FMT therapy. Colonic biopsies were collected and bulk RNA sequencing was performed to compare changes in host gene expression pre- and two months post-FMT. Transcriptional profiles were significantly altered after FMT therapy, with many differentially expressed genes (∼15% of annotated genes detected). Enrichment analysis determined that these changes were reflective of increased protein production post-FMT, with enrichment of pathways such as Ribosome Biogenesis, Protein Processing, and signaling pathways (Myc, mTORc1, E2F) associated with cell proliferation and protein biosynthesis. Histology of H&E-stained biopsies identified a significant increase in colonic crypt length post-FMT, suggesting that this treatment promotes cell proliferation. Crypt length was significantly correlated with enriched Myc and mTOR signaling pathways as well as genes associated with polyamine biosynthesis, providing a potential mechanism through which this may occur. Finally, signaling pathways upstream of Myc and mTOR, notably IL-33 Signaling and EGFR ligands, were significantly upregulated, suggesting that FMT may utilize these signals to promote cell proliferation and restoration of the intestine.}, } @article {pmid39647752, year = {2024}, author = {Li, K and Ran, X and Han, J and Ding, H and Wang, X and Li, Y and Guo, W and Li, X and Guo, W and Fu, S and Bi, J}, title = {Astragalus polysaccharide alleviates mastitis disrupted by Staphylococcus aureus infection by regulating gut microbiota and SCFAs metabolism.}, journal = {International journal of biological macromolecules}, volume = {286}, number = {}, pages = {138422}, doi = {10.1016/j.ijbiomac.2024.138422}, pmid = {39647752}, issn = {1879-0003}, abstract = {Polysaccharides, key bioactive compounds derived from Chinese herbs, are increasingly recognized for their therapeutic potential in modulating gut microbiota to treat various diseases. However, their efficacy in alleviating mammary inflammation and oxidative stress and protecting the blood-milk barrier (BMB) compromised by Staphylococcus aureus (S. au) infection remains uncertain. As evidence for the gut-mammary axis grows, identifying natural prebiotic components that affect this axis is crucial. This study reveals that Astragalus polysaccharide (APS), the primary active constituent of Astragalus, effectively mitigates S. au infection in murine mammary glands, suppresses inflammatory responses, reduces oxidative stress, and restores BMB integrity. The involvement of APS in modulating gut microbiota was substantiated through gut microbial depletion experiments and fecal microbiota transplantation (FMT). Notably, APS uniquely enriched Ruminococcus bromii (R. bromii) in the gut, facilitating the metabolism of short-chain fatty acids (SCFAs), particularly acetate and butyrate, which are pivotal to APS's protective effects. Collectively, these results propose a novel therapeutic approach for the treatment and prevention of S. au-induced mastitis, leveraging APS and R. bromii as prebiotics and probiotics, respectively.}, } @article {pmid39647571, year = {2024}, author = {Sharma, A and Kapur, S and Kancharla, P and Yang, T}, title = {Sex Differences in Gut Microbiota, Hypertension, and Cardiovascular Risk.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {177183}, doi = {10.1016/j.ejphar.2024.177183}, pmid = {39647571}, issn = {1879-0712}, abstract = {The intricate ecosystem of the gut microbiome exhibits sex-specific differences, influencing the susceptibility to cardiovascular diseases (CVD). Imbalance within the gut microbiome compromises the gut barrier, activates inflammatory pathways, and alters the production of metabolites, all of which initiate chronic diseases including CVD. In particular, the interplay between lifestyle choices, hormonal changes, and metabolic byproducts uniquely affects sex-specific gut microbiomes, potentially shaping the risk profiles for hypertension and CVD differently in men and women. Understanding the gut microbiome's role in CVD risk offers informative reasoning behind the importance of developing tailored preventative strategies based on sex-specific differences in CVD risk. Furthermore, insight into the differential impact of social determinants and biological factors on CVD susceptibility emphasizes the necessity for more nuanced approaches. This review also outlines specific dietary interventions that may enhance gut microbiome health, offering a glimpse into potential therapeutic avenues for reducing CVD risk that require greater awareness. Imbalance in natural gut microbiomes may explain etiologies of chronic diseases; we advocate for future application to alter the gut microbiome as possible treatment of the aforementioned diseases. This review mentions the idea of altering the gut microbiome through interventions such as fecal microbiota transplantation (FMT), a major application of microbiome-based therapy that is first-line for Clostridium difficile infections and patient-specific probiotics highlights more innovative approaches to hypertension and CVD prevention. Through increased analysis of gut microbiota compositions along with patient-centric probiotics and microbiome transfers, this review advocates for future preventative strategies for hypertension.}, } @article {pmid39647535, year = {2024}, author = {Casañas-Martínez, M and Barbero-Herranz, R and Alegre-González, D and Mosquera-Lozano, JD and Campo, RD and , }, title = {Fecal Microbiota Transplantation in a Long-Standing Auto-Brewery Syndrome with Complex Symptomatology.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2024.12.005}, pmid = {39647535}, issn = {1600-0641}, } @article {pmid39645284, year = {2024}, author = {Dean, NJ and d'Arienzo, PD and Ibraheim, H and Lee, KA and Olsson-Brown, AC and Pinato, DJ and Powell, N}, title = {The role of the gut microbiome in regulating the response to immune checkpoint inhibitor therapy.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101944}, doi = {10.1016/j.bpg.2024.101944}, pmid = {39645284}, issn = {1532-1916}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Neoplasms/drug therapy/microbiology/immunology ; Immunotherapy/methods ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use/pharmacology ; }, abstract = {Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet the proportion of patients who achieve long-term disease control remain suboptimal. Over the past decade, the gut microbiome has been shown to influence immune-mediated tumour suppression as well as responses to ICI therapies. Compositional differences in gut microbiome may account for the differences in outcomes from immune checkpoint blockade. Identifying microbiota species associated with favourable/unfavourable outcomes and modelling their dynamics throughout the course of ICI treatment could help develop predictive biomarkers of immunotherapy response, and manipulating the gut microbiome represent a novel approach to enhancing ICI effectiveness. Clinically, this raises the prospect of using gut microbiome-based therapies to overcome primary resistance to ICIs, mitigate the effects of microbiome-altering drugs such as antibiotics or proton pump inhibitors, and improve overall survival in patients across numerous different cancer types.}, } @article {pmid39645282, year = {2024}, author = {Józefczuk, P and Biliński, J and Minkowska, A and Łaguna, P}, title = {Gut microbiome in children undergoing hematopoietic stem cell transplantation.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101955}, doi = {10.1016/j.bpg.2024.101955}, pmid = {39645282}, issn = {1532-1916}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome/physiology ; Child ; Animals ; }, abstract = {Hematopoietic stem cell transplantation (HSCT) is used in children as a treatment for various cancers, e.g. acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or other diseases, e.g. severe congenital immunodeficiency, metabolic disorders, hence the patient population is quite diverse. There is an increasing interest on the role of the microbiome in peri-transplant period. In this review, concepts of HSCT with the focus on the importance of microbiome composition, its changes during treatment and possible microbiota oriented interventions will be discussed. This paper analyzes data in pediatric population, but in view of interesting results and absence of analogous data for pediatric patients, it also looks at studies performed on adult population and pre-clinical trials on animals discussing possible translation to children.}, } @article {pmid39645278, year = {2024}, author = {Garcia-Mateo, S and Rondinella, D and Ponziani, FR and Miele, L and Gasbarrini, A and Cammarota, G and Lanas, Á and Gomollón, F}, title = {Gut microbiome and metabolic dysfunction-associated steatotic liver disease: Pathogenic role and potential for therapeutics.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101924}, doi = {10.1016/j.bpg.2024.101924}, pmid = {39645278}, issn = {1532-1916}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; Non-alcoholic Fatty Liver Disease/microbiology/therapy/metabolism ; Dysbiosis ; Diet, Mediterranean ; }, abstract = {Gut microbiota plays key functions in the human body, and its alteration is associated with several human disorders. Moreover, its manipulation is being investigated as a potential therapeutic strategy. In this narrative review we will dissect the involvement of the gut microbiota and of the gut-liver axis on metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, we will review the effects of lifestyle interventions commonly used for MASLD (i.e. Mediterranean diet and physical exercise) on gut microbiome, to understand if their beneficial effect can be microbially mediated. Finally, we will discuss the role and the available evidence of therapeutic microbiome modulators, including prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT), in the management of MASLD.}, } @article {pmid39643421, year = {2025}, author = {Zhang, S and Zhou, R and Xie, X and Xiong, S and Li, L and Li, Y}, title = {Polysaccharides from Lycium barbarum, yam, and sunflower ameliorate colitis in a structure and intrinsic flora-dependent manner.}, journal = {Carbohydrate polymers}, volume = {349}, number = {Pt A}, pages = {122905}, doi = {10.1016/j.carbpol.2024.122905}, pmid = {39643421}, issn = {1879-1344}, mesh = {Animals ; *Dioscorea/chemistry ; Mice ; *Mice, Inbred C57BL ; *Gastrointestinal Microbiome/drug effects ; *Colitis/drug therapy/chemically induced ; *Helianthus/chemistry ; Female ; *Polysaccharides/pharmacology/chemistry ; Lycium/chemistry ; Mice, Inbred ICR ; Disease Models, Animal ; Cytokines/metabolism ; Drugs, Chinese Herbal/pharmacology/chemistry ; }, abstract = {Polysaccharides have been suggested to ameliorate metabolic diseases. However, their differential colitis-mitigating effects in mouse models with different colony structures remain poorly understood. Therefore, this study investigated the effects of polysaccharides from Lycium barbarum (LBP), sunflower (SP), and yam (YP) on colitis in C57BL/6 J (B6) mice born via vaginal delivery (VD) and in both caesarean section (CS)- and VD-born Institute of Cancer Research (ICR) mice. LBP was mainly composed of glucose (30.2 %), galactose (27.5 %), and arabinose (26.9 %). The main components of SP and YP were galacturonic acid (75.8 %) and glucose (98.1 %), respectively. Interestingly, LBP effectively alleviated body weight loss, reduced inflammatory cytokine levels, and restored intestinal barrier function in all three mouse models. Moreover, LBP decreased the abundance of norank_f__norank_o__Clostridia_UCG-014, Coriobacteriaceae_UCG-002, and norank_f_Eubacterium_coprostanoligenes_group in B6 mice, and the abundance of these genera positively correlated with pro-inflammatory cytokine levels. LBP increased the abundance of Lactobacillus, which was positively correlated with the levels of the protective factor, IL-10, in CS-born ICR mice. Collectively, our study suggests the potential application of LBP in the treatment of ulcerative colitis. We also provide an alternative method for restoring intestinal homeostasis in CS-born offspring.}, } @article {pmid39643403, year = {2025}, author = {Zhang, Y and Ji, W and Qin, H and Chen, Z and Zhou, Y and Zhou, Z and Wang, J and Wang, K}, title = {Astragalus polysaccharides alleviate DSS-induced ulcerative colitis in mice by restoring SCFA production and regulating Th17/Treg cell homeostasis in a microbiota-dependent manner.}, journal = {Carbohydrate polymers}, volume = {349}, number = {Pt A}, pages = {122829}, doi = {10.1016/j.carbpol.2024.122829}, pmid = {39643403}, issn = {1879-1344}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/chemically induced/immunology ; *Th17 Cells/drug effects/immunology ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Dextran Sulfate ; *Polysaccharides/pharmacology/chemistry ; *T-Lymphocytes, Regulatory/drug effects/immunology/metabolism ; *Mice, Inbred C57BL ; Homeostasis/drug effects ; Fatty Acids, Volatile/metabolism ; Male ; Astragalus Plant/chemistry ; Astragalus propinquus/chemistry ; Fecal Microbiota Transplantation ; }, abstract = {Natural polysaccharides from Astragalus membranaceus have been shown to relieve ulcerative colitis (UC). However, the mechanism and causal relationship between the gut microbiota and Astragalus polysaccharides (APS) treatment of UC are unclear. The results of the present study showed that APS ameliorated colonic injury and the disruption of the gut microbiota and restored intestinal immune homeostasis in mice with DSS-induced colitis. Meanwhile, we found that APS treatment was ineffective in antibiotic-treated colitis mice but was effective when FMT (Fecal microbiota transplantation) was performed on UC mice using APS-treated mice as donors. APS increased the proportion of relevant microbiota that produce SCFAs and both direct administration of APS and administration of APS-adjusted gut microbiota significantly promoted the production of SCFAs in colitis mice. We demonstrated that APS dually inhibited NF-κB activation via the TLR4 and HDAC3 pathways and improved the balance in Th17/Treg cells in UC mice. In conclusion, our study revealed that APS is a promising prebiotic agent for the maintenance of intestinal health and demonstrated that APS may ameliorate colitis in a gut microbiota-dependent manner.}, } @article {pmid39640634, year = {2024}, author = {Nezhadi, J and Fadaee, M and Ahmadi, S and Kafil, HS}, title = {Microbiota transplantation.}, journal = {Heliyon}, volume = {10}, number = {20}, pages = {e39047}, pmid = {39640634}, issn = {2405-8440}, abstract = {Microbiota refers to a collection of living microorganisms, including bacteria, yeasts, and viruses, that coexist in various sites of the human body. Microbiota can perform multiple functions in the body, which have an essential effect on human health and homeostasis. For example, the microbiota can digest polysaccharides, produce vitamins, modulate the immune system, and protect the body against pathogens. Various factors can occasionally alter the microbiota population in the human body, a condition known as dysbiosis. Dysbiosis can disrupt the homeostasis of a person's body and cause disease. Recent years have witnessed efforts to restore the microbiota population of an individual's body to its original state and eradicate dysbiosis through microbiota transplantation. The noteworthy point is that different methods such as fecal microbiota transplantation, vaginal microbiota transplantation (VMT), skin microbiota transplantation (SMT), oral microbiota transplantation (OMT), washed microbiota transplantation (WMT), and sinonasal microbiota transplantation (SiMT) are used for microbiota transplantation (MT). According to the results of studies and the usefulness of MT in improving a person's health, the purpose of this study is to investigate different methods of MT to eliminate dysbiosis.}, } @article {pmid39640340, year = {2024}, author = {Ma, BDY and Chan, TYH and Lo, BWY}, title = {Unveiling the hidden culprit: How the brain-gut axis fuels neuroinflammation in ischemic stroke.}, journal = {Surgical neurology international}, volume = {15}, number = {}, pages = {394}, pmid = {39640340}, issn = {2229-5097}, abstract = {BACKGROUND: The brain-gut axis represents a bidirectional communication network between the gut microbiome and the central nervous system that plays an important role in homeostasis. Compelling evidence now confirms that ischemic stroke disrupts this delicate balance by inducing gut dysbiosis.

METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and Google Scholar for articles published between January 2000 and January 2023 using relevant keywords. Studies were limited to English and included original studies, literature, and systematic reviewers from peer-reviewed journals which discussed gut microbiota composition in models/subjects with ischemic stroke or assessed stroke impact on gut microbiota. Comments, meeting abstracts, and case reports were excluded. From the 80 relevant articles, we summarized key findings related to gut microbiota changes after stroke and their association with stroke outcomes.

RESULTS: Emerging preclinical evidence underscores the pivotal role of the gut microbiome in glial cell development and function. Germ-free models exhibit compromised microglial activation and impaired cellular debris clearance, exacerbating tissue damage following ischemic stroke. Targeted interventions, including prebiotics, probiotics, and fecal microbiota transplantation, have demonstrated efficacy in rescuing glial phenotypes in preclinical stroke models. Beyond its local effects, the gut microbiome significantly influences systemic immunity. Ischemic stroke polarizes pro-inflammatory phenotypes of neutrophils and T cells, amplifying neurovascular inflammation. Microbiota manipulation modulates leukocyte trafficking and metabolic signaling, offering potential avenues to mitigate infarct pathology.

CONCLUSION: Our review demonstrates that in preclinical stroke models, modulating the lipopolysaccharide, short-chain fatty acid, and trimethylamine N-oxide pathways through the gut-brain axis reduces infarct sizes and edema and improves functional recovery after ischemic stroke. Further exploration of this important axis may unveil additional adjunctive stroke therapies by elucidating the complex interplay between the microbiome and the brain. Rigorously controlled clinical studies are now warranted to translate these promising preclinical findings and investigate whether manipulating the microbiome-brain relationship can help improve outcomes for stroke patients. Overall, continued research on the gut-brain axis holds exciting possibilities for developing novel treatment strategies that may enhance recovery after stroke.}, } @article {pmid39640265, year = {2024}, author = {Wang, H and Deng, F and Luo, M and Wang, X}, title = {Case report: Fecal microbiota transplant for Clostridium difficile infection in a pregnant patient with acute severe ulcerative colitis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1417003}, pmid = {39640265}, issn = {1664-3224}, mesh = {Humans ; Female ; *Fecal Microbiota Transplantation ; Pregnancy ; *Colitis, Ulcerative/therapy/immunology/microbiology ; Adult ; *Clostridium Infections/therapy/immunology ; Clostridioides difficile ; Gastrointestinal Microbiome ; Pregnancy Complications, Infectious/therapy/microbiology ; Treatment Outcome ; Acute Disease ; Severity of Illness Index ; }, abstract = {Ulcerative colitis (UC) is a chronic colonic mucosal inflammation characterized by reduced gut microbial diversity. Patients with UC at pregnancy are prone to suffer from severe disease progression due to the changes of hormone and immune regulation. Fecal microbiota transplant (FMT) is a promising therapy for UC and recurrent Clostridium difficile infection (CDI). However, acute severe ulcerative colitis (ASUC) treatment especially in patients at pregnancy is clinically challenging. Herein, we report a 34-year-old pregnant woman who manifested with numerous bloody stools and markedly elevated serological inflammatory indicators and was diagnosed with ASUC and concurrent CDI. The use of intravenous injection steroids and anti-TNF-α therapy failed to improve her condition. Frozen encapsulated FMT therapy was finally performed to this patient with clearly improved symptoms and indications of safe delivery without UC flares or complications, and markedly increased diversity of the gut microbiota was also shown in this patient after FMT. This report firstly describes FMT as a safe salvage therapy for a pregnant patient with CDI and ASUC refractory to intravenous steroids and anti-TNF therapy.}, } @article {pmid39638178, year = {2024}, author = {Gong, JZ and Huang, JJ and Pan, M and Jin, QW and Fan, YM and Shi, WQ and Huang, SY}, title = {Cathepsin L of Fasciola hepatica meliorates colitis by altering the gut microbiome and inflammatory macrophages.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {138270}, doi = {10.1016/j.ijbiomac.2024.138270}, pmid = {39638178}, issn = {1879-0003}, abstract = {Helminths can relieve the development of autoimmune diseases and inflammatory diseases, by inducing anti-inflammatory innate immune responses. Here, we report that CL7, a Cathepsin L protein secreted by Fasciola hepatica, inhibited the activation of the NF-κB and MAPK signaling resulting in reduced secretion of inflammatory mediators in macrophages. Furthermore，we found that CL7 could prevent dextran sulfate sodium (DSS) induced ulcerative colitis (UC). CL7 and ESP administration restored DSS-induced body weight loss, colon shortening, and injury, significantly decreased the disease activity index (DAI) and alleviated colonic epithelial injury. CL7 noticeably suppressed the DSS-triggered M1 polarization upregulation and inhibited IL-17 and other inflammatory mediator production in UC mice. Additionally, CL7 ameliorated DSS-induced microbiota dysbiosis. Results of Antibiotic treatment (ABX) and fecal microbial transplants (FMT) suggested that the gut microbiota played an important role in CL7 treating UC. These findings propose that CL7 could be a promising strategy for UC therapy.}, } @article {pmid39635024, year = {2024}, author = {Skladany, L and Kubanek, N and Adamcova Selcanova, S and Zilincanova, D and Havaj, D and Sulejova, K and Soltys, K and Messingerova, L and Lichvar, M and Laffers, L and Zilincan, M and Honsova, E and Liptak, P and Banovcin, P and Bures, J and Koller, T and Golubnitschaja, O and Arab, JP}, title = {3PM-guided innovation in treatments of severe alcohol-associated hepatitis utilizing fecal microbiota transplantation.}, journal = {The EPMA journal}, volume = {15}, number = {4}, pages = {677-692}, pmid = {39635024}, issn = {1878-5077}, abstract = {RATIONALE: Severe alcohol-associated hepatitis (SAH) is the most critical, acute, inflammatory phenotype within the alcohol-associated liver disease (ALD) spectrum, characterized by high 30- and 90-day mortality. Since several decades, corticosteroids (CS) are the only approved pharmacotherapy offering highly limited survival benefits. Contextually, there is an evident demand for 3PM innovation in the area meeting patients' needs and improving individual outcomes. Fecal microbiota transplantation (FMT) has emerged as one of the new potential therapeutic options. In this study, we aimed to address the crucial 3PM domains in order to assess (i) the impact of FMT on mortality in SAH patients beyond CS, (ii) to identify factors associated with the outcome to be improved (iii) the prediction of futility, (iv) prevention of suboptimal individual outcomes linked to increased mortality, and (v) personalized allocation of therapy.

METHODS: We conducted a prospective study (NCT04758806) in adult patients with SAH who were non-responders (NR) to or non-eligible (NE) for CS between January 2018 and August 2022. The intervention consisted of five 100 ml of FMT, prepared from 30 g stool from an unrelated healthy donor and frozen at - 80 °C, administered daily to the upper gastrointestinal (GI) tract. We evaluated the impact of FMT on 30- and 90-day mortality which we compared to the control group selected by the propensity score matching and treated by the standard of care; the control group was derived from the RH7 registry of patients hospitalized at the liver unit (NCT04767945). We have also scrutinized the FMT outcome against established and potential prognostic factors for SAH - such as the model for end-stage liver disease (MELD), Maddrey Discriminant Function (MDF), acute-on-chronic liver failure (ACLF), Liver Frailty Index (LFI), hepatic venous-portal pressure gradient (HVPG) and Alcoholic Hepatitis Histologic Score (AHHS) - to see if the 3PM method assigns them a new dimension in predicting response to therapy, prevention of suboptimal individual outcomes, and personalized patient management.

RESULTS: We enrolled 44 patients with SAH (NR or NE) on an intention-to-treat basis; we analyzed 33 patients per protocol for associated factors (after an additional 11 being excluded for receiving less than 5 doses of FMT), and 31 patients by propensity score matching for corresponding individual outcomes, respectively. The mean age was 49.6 years, 11 patients (33.3%) were females. The median MELD score was 29, and ACLF of any degree had 27 patients (81.8%). FMT improved 30-day mortality (p = 0.0204) and non-significantly improved 90-day mortality (p = 0.4386). Univariate analysis identified MELD ≥ 30, MDF ≥ 90, and ACLF grade > 1 as significant predictors of 30-day mortality, (p = 0.031; p = 0.014; p = 0.034). Survival was not associated with baseline LFI, HVPG, or AHHS.

In the most difficult-to-treat sub-cohort of patients with SAH (i.e., NR/NE), FMT improved 30-day mortality. Factors associated with benefit included MELD ≤ 30, MDF ≤ 90, and ACLF < 2. These results support the potential of gut microbiome as a therapeutic target in the context of 3PM research and vice versa - to use 3PM methodology as the expedient unifying template for microbiome research. The results allow for immediate impact on the innovative concepts of (i) personalized phenotyping and stratification of the disease for the clinical research and practice, (ii) multilevel predictive diagnosis related to personalized/precise treatment allocation including evidence-based (ii) prevention of futile and sub-optimally effective therapy, as well as (iii) targeted prevention of poor individual outcomes in patients with SAH. Moreover, our results add to the existing evidence with the potential to generate new research along the SAH's pathogenetic pathways such as diverse individual susceptibility to alcohol toxicity, host-specific mitochondrial function and systemic inflammation, and the role of gut dysbiosis thereof.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00381-5.}, } @article {pmid39633321, year = {2024}, author = {Farias, RM and Jiang, Y and Levy, EJ and Hwang, C and Wang, J and Burton, EM and Cohen, L and Ajami, N and Wargo, JA and Daniel, CR and McQuade, JL}, title = {Diet and Immune Effects Trial (DIET)- a randomized, double-blinded dietary intervention study in patients with melanoma receiving immunotherapy.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {1493}, pmid = {39633321}, issn = {1471-2407}, support = {R25 CA203650/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Melanoma/therapy/immunology/diet therapy ; Double-Blind Method ; *Gastrointestinal Microbiome/immunology ; Female ; Male ; Immunotherapy/methods ; Dietary Fiber/administration & dosage ; Adult ; Middle Aged ; Immune Checkpoint Inhibitors/therapeutic use ; Quality of Life ; Aged ; Diet ; Skin Neoplasms/diet therapy/immunology/therapy ; }, abstract = {BACKGROUND: Gut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and tolerance. Building on this, we are now conducting a phase II randomized trial of HFDI versus a healthy control diet in melanoma patients receiving ICB.

METHODS: This is a randomized, double-blind, fully controlled feeding study that will enroll 45 melanoma patients starting standard-of-care (SOC) ICB in three settings: adjuvant, neoadjuvant, and unresectable. Patients are randomized 2:1 to the HFDI (target fiber 50 g/day from whole foods) or healthy control diet (target fiber 20 g/day) stratified by BMI and cohort. All meals are prepared by the MD Anderson Bionutrition Core and are isocaloric and macronutrient-controlled. The intervention includes a 1-week equilibration period and then up to 11 weeks of diet intervention. Longitudinal blood, stool and tumor tissue (if available) are collected throughout the trial and at 12 weeks post intervention.

DISCUSSION: This DIET study is the first fully controlled feeding study among cancer patients who are actively receiving immunotherapy. The goal of the current study is to establish the effects of dietary intervention on the structure and function of the gut microbiome in patients with melanoma treated with SOC immunotherapies. The secondary endpoints include changes in systemic and tumor immunity, changes in the metabolic profile, quality of life, symptoms, disease response and immunotherapy toxicity.

TRIAL REGISTRATION: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT04645680. First posted 2020-11-27; last verified 2024-06.}, } @article {pmid39633000, year = {2024}, author = {Yang, D and Fu, S and Shi, Y}, title = {Gut microbiota modulation: a novel mechanism in arb-mediated hypertension treatment.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {}, number = {}, pages = {}, pmid = {39633000}, issn = {1348-4214}, } @article {pmid39631325, year = {2024}, author = {Zhang, Y and Liu, Q and Xie, H and Zhang, W and Lin, X and Zhang, H and Yu, H and Ma, Y and Zhang, C and Geng, H and Shi, N and Cui, L and Li, B and Li, YF}, title = {Fecal microbiota transplantation as an effective way in treating methylmercury-poisoned rats.}, journal = {The Science of the total environment}, volume = {957}, number = {}, pages = {177850}, doi = {10.1016/j.scitotenv.2024.177850}, pmid = {39631325}, issn = {1879-1026}, abstract = {Methylmercury (MeHg) can cause devastating neurotoxicity in animals and human beings. Gut microbiota dysbiosis has been found in MeHg-poisoned animals. Fecal microbiota transplantation (FMT) has been shown to improve clinical outcomes in a variety of diseases such as epilepsy, amyotrophic lateral sclerosis (ALS) and autism. The aim of this study was to investigate the effects of FMT on MeHg-poisoned rats. FMT treatment was applied to MeHg-poisoned rats for 14 days. The neurobehavior, weight changes, dopamine (DA), the total Hg and MeHg level were evaluated. Besides, the gut microbiota and metabolites change in feces were also checked. It was found that FMT helped weight gain, alleviated the neurological disorders, enhanced fecal mercury excretion and MeHg demethylation, reconstructed gut microbiome and promoted the production of gut-brain axis related-metabolites in MeHg-poisoned rats. This study elaborates on the therapeutic efficacy of FMT in treating of MeHg-poisoned rats, which sheds lights on the treatment of neurological diseases like Minamata Disease and even Parkinson's Disease.}, } @article {pmid39630000, year = {2024}, author = {Barbosa, IG and Miranda, AS and Berk, M and Teixeira, AL}, title = {The involvement of the microbiota-gut-brain axis in the pathophysiology of mood disorders and therapeutic implications.}, journal = {Expert review of neurotherapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1080/14737175.2024.2438646}, pmid = {39630000}, issn = {1744-8360}, abstract = {INTRODUCTION: There is a growing body of evidence implicating gut-brain axis dysfunction in the pathophysiology of mood disorders. Accordingly, gut microbiota has become a promising target for the development of biomarkers and novel therapeutics for bipolar and depressive disorders.

AREAS COVERED: We describe the observed changes in the gut microbiota of patients with mood disorders and discuss the available studies assessing microbiota-based strategies for their treatment.

EXPERT OPINION: Microbiota-targeted interventions, such as symbiotics, prebiotics, paraprobiotics, and fecal microbiota transplants seem to attenuate the severity of depressive symptoms. The available results must be seen as preliminary and need to be replicated and/or confirmed in larger and independent studies, also considering the pathophysiological and clinical heterogeneity of mood disorders.}, } @article {pmid39629909, year = {2024}, author = {Sin, HCL and Haifer, C}, title = {Faecal transplantation: the good, the bad and the ugly.}, journal = {Internal medicine journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/imj.16559}, pmid = {39629909}, issn = {1445-5994}, abstract = {There continues to be significant interest from both clinicians and patients in using faecal transplantation, as the integral role of the gut microbiome is increasingly recognised in various disease conditions, both within and beyond the gut. This Clinical Perspectives article provides an overview of existing literature, factors limiting the use of faecal microbial transplantation in clinical practice and exciting new advancements on the horizon.}, } @article {pmid39628464, year = {2024}, author = {Hu, X and Wu, Q and Huang, L and Xu, J and He, X and Wu, L}, title = {Clinical efficacy of washed microbiota transplantation on metabolic syndrome and metabolic profile of donor outer membrane vesicles.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1465499}, pmid = {39628464}, issn = {2296-861X}, abstract = {OBJECT: To clarify the clinical efficacy of washed microbiota transplantation (WMT) for metabolic syndrome (MetS), and explore the differences in the metabolic profile of bacterial outer membrane vesicles (OMVs) in donor fecal bacteria suspension received by MetS patients with good and poor outcomes, and to construct a predictive model for the efficacy of WMT for MetS using differential metabolites.

METHODS: Medical data 65 MetS patients who had completed at least 2 courses of WMT from 2017.05 to 2023.07 were collected. Fecal bacteria suspension of WMT donors were collected, and the clinical data of MetS patients treated with WMT during this period were collected as well. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared. OMVs were isolated from donor fecal bacteria suspension and off-target metabolomic sequencing was performed by Liquid Chromatograph Mass Spectrometer (LC-MS).

RESULTS: Compared with baseline, Body mass index (BMI), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) of MetS patients showed significant decreases after the 1st (short-term) and 2nd (medium-term) courses, and fasting blood glucose (FBG) also showed significant decreases after the 1st session. There was a significant difference between the Marked Response OMVs and the Moderate Response OMVs. It was showed that 960 metabolites were significantly up-regulated in Marked Response OMVs and 439 metabolites that were significantly down-regulated. The ROC model suggested that 9-carboxymethoxymethylguanine, AUC = 0.8127, 95% CI [0.6885, 0.9369], was the most potent metabolite predicting the most available metabolite for efficacy.

CONCLUSION: WMT had significant short-term and medium-term clinical efficacy in MetS. There were differences in the structure of metabolites between Marked Response OMVs and Moderate Response OMVs. The level of 9-Carboxy methoxy methylguanine in Marked Response OMVs can be a good predictor of the efficacy of WMT in the treatment of MetS.}, } @article {pmid39624719, year = {2024}, author = {Xiang, A and Chang, Y and Shi, L and Zhou, X}, title = {Mapping the relationship between alcohol use disorder and gut microbiota: a 20-year bibliometric study.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1457969}, pmid = {39624719}, issn = {1664-302X}, abstract = {BACKGROUND: Alcohol use disorder (AUD) is a psychiatric disorder that is widespread worldwide. Alcohol use is a significant contributor to the global burden of death, disability and disease. Modulation of the gut microbiota is a promising approach to improve the efficacy and minimize the adverse effects of colorectal cancer treatment. The relationship between the presence of microbes and AUD has been widely validated. However, few studies have examined this relationship using bibliometric methods. Therefore, this study analyzes the research hotspots and trends in human gut microbiology and AUD over the last two decades from a bibliometric perspective. This study aims at provide new directions for basic and clinical research in this field.

OBJECTIVE: A comprehensive discussion of the relationship between the current state of research and trends in AUD and intestinal flora.

METHODS: We collected publications from the Web of Science Core Collection database from 2003 to 2023 according to established inclusion criteria. We analyzed countries, institutions, authors, and research contributions using CiteSpace, VOSviewer, and Scimago Graphics to visualize research trends in the field.

RESULTS: A total of 2,102 publications were obtained, with a rapid increase in the number of publications since 2016. The United States and China are major contributors to the field and have established a network of partners in several countries. Five hundred ninety-five academic journals published articles on the topic. The author with the highest number of publications is Prof. Bernd Schnabl of the Department of Gastroenterology at the University of California, San Diego. In addition to "gut flora" and "AUD," high frequency words in the keyword co-occurrence network analysis included alcoholic liver disease, tryptophan metabolism, enterohepatic axis, and fecal microbial transplantation.

CONCLUSION: The results of this study provide a bibliometric analysis and visualization of key research areas in the gut microbiota and AUD over the past 20 years. The results suggest that the role of the gut microbiota in AUD and its potential mechanisms, especially therapeutic targets, should be closely monitored and could become a hot topic in the field.}, } @article {pmid39621384, year = {2024}, author = {Hoeg, A and Kuchma, N and Krane, A and Graiziger, C and Thomas, J and Kelly, CR and Khoruts, A}, title = {Oral Capsule FMT Combined With Bezlotoxumab Is a Successful Rescue Protocol Following Failure of FMT Alone in the Treatment of Recurrent C. difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000002108}, pmid = {39621384}, issn = {1539-2031}, abstract = {GOALS: Evaluate the benefit of adding bezlotoxumab to repeat fecal microbiota transplantation (FMT) in patients with recurrent Clostridioides difficile infections after the failure of FMT alone.

BACKGROUND: The initial failure of FMT in breaking the cycle of recurrent Clostridium difficile(C. difficile) infections is associated with a greater risk of subsequent failure. Our previous analysis showed that FMT failure is associated with delayed repair of fecal microbiota at 1 week after administration. We hypothesized that increasing the symptom-free interval by adding bezlotoxumab would improve the outcomes of a second FMT.

STUDY: A new rescue protocol that combines FMT with bezlotoxumab for patients who previously failed FMT alone was implemented in 2 academic medical centers. The clinical outcomes of a new protocol were captured in a prospective registry. The results were compared in a retrospective analysis of clinical outcomes of prior experience with repeat FMT by itself. All FMT preparations were standardized for dose. Bezlotoxumab administration was synchronized temporally with the second FMT to maximize its duration of action.

RESULTS: Our historical cure rate of second FMT in treatment of recurrent C. difficile infection was 48% (15/31 patients). Addition of bezlotoxumab to the second FMT resulted in a cure rate of 89% (24/27 patients).

CONCLUSIONS: Addition of bezlotoxumab markedly improved the cure rate of the second FMT following initial FMT failure. The rationale for the protocol design highlights the importance of understanding the pharmacokinetics of both bezlotoxumab and FMT. Similar principles may apply to other live biotherapeutic products that are becoming available for prevention of C. difficile infection recurrence.}, } @article {pmid39619696, year = {2024}, author = {Kang, P and Bae, GS and Jeon, E and Choi, J and Hwang, EH and Kim, G and Baek, SH and Shim, K and An, YJ and Lim, KS and Kim, Y and Oh, T and Hong, JJ and Lee, WK and Kim, SH and Koo, BS}, title = {Comprehensive effects of fecal microbiota transplantation on cynomolgus macaques across various fecal conditions.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1458923}, pmid = {39619696}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) and probiotics therapies represent key clinical options, yet their complex effects on the host are not fully understood. We evaluated the comprehensive effects of FMT using diarrheal or normal feces, as well as probiotic therapies, on multiple anatomical sites in healthy cynomolgus macaques through colonoscopy and surgery. Our research revealed that FMT led to a partial microbiome transplantation without exhibiting the donor's fecal clinical characteristics. Notably, FMT increased insulin and C-peptide levels in each animal according time series, regardless of fecal conditions. Immunologically, a reduction in neutrophil-to-lymphocyte ratio were exclusively observed in femoral veins of FMT group. In blood chemistry analyses, reductions in aspartate aminotransferase, blood urea nitrogen, and creatinine were observed in the femoral veins, while elevated levels of alanine aminotransferase and calcium were exclusively detected in the portal veins. These changes were not observed in the probiotic group. Also, short chain fatty acids were significantly higher increase in portal veins rather than femoral veins. Transcriptome analysis of liver tissues showed that metabolic pathways were primarily affected by both FMT and probiotics therapies. In summary, FMT therapy significantly influenced metabolic, immunologic and transcriptomic responses in normal macaque models, regardless of fecal conditions. Also, these macaque models, which utilize surgery and colonoscopy, serve as a human-like preclinical platform for evaluating long-term effects and anatomically specific responses to gut-targeted interventions, without the need for animal sacrifice.}, } @article {pmid39619695, year = {2024}, author = {Han, X and Zhang, BW and Zeng, W and Ma, ML and Wang, KX and Yuan, BJ and Xu, DQ and Geng, JX and Fan, CY and Gao, ZK and Arshad, M and Gao, S and Zhao, L and Liu, SL and Mu, XQ}, title = {Suppressed oncogenic molecules involved in the treatment of colorectal cancer by fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1451303}, pmid = {39619695}, issn = {1664-302X}, abstract = {Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index. The diameter and number of cancerous foci were significantly decreased in CRC mice treated with FMT, along with the restoration of the intestinal mucosal structure and the lessening of the gland arrangement disorder. Key factors in oxidative stress (TXN1, TXNRD1, and HIF-1α); cell cycle regulators (IGF-1, BIRC5, CDK8, HDAC2, EGFR, and CTSL); and a critical transcription factor of the innate immune signal pathway (IRF5) were among the repressed oncogenic targets engaged in the FMT treatment of CRC. Correlation analysis revealed that their expressions were positively correlated with uncultured_bacterium_o_Mollicutes_RF39, Rikenellaceae_RC9_gut_group, and negatively correlated with Bacillus, Marvinbryantia, Roseburia, Angelakisella, Enterorhabdus, Bacteroides, Muribaculum, and genera of uncultured_bacterium_f_Eggerthellaceae, uncultured_bacterium_f_Xanthobacteraceae, Prevotellaceae_UCG-001, uncultured_bacterium_f_Erysipelotrichaceae, uncul-tured_bacterium_f_Lachnospiraceae, uncultured_bacterium_f_Ruminococcaceae, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-005, and uncultured_bacterium_f_Peptococcaceae. This study provides more evidence for the application of FMT in the clinical treatment of CRC.}, } @article {pmid39619660, year = {2024}, author = {Xi, M and Ruan, Q and Zhong, S and Li, J and Qi, W and Xie, C and Wang, X and Abuduxiku, N and Ni, J}, title = {Periodontal bacteria influence systemic diseases through the gut microbiota.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1478362}, pmid = {39619660}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Diabetes Mellitus/microbiology ; Alzheimer Disease/microbiology ; Bacteria/classification/genetics/pathogenicity ; Cardiovascular Diseases/microbiology ; Mouth/microbiology ; Animals ; }, abstract = {Many systemic diseases, including Alzheimer disease (AD), diabetes mellitus (DM) and cardiovascular disease, are associated with microbiota dysbiosis. The oral and intestinal microbiota are directly connected anatomically, and communicate with each other through the oral-gut microbiome axis to establish and maintain host microbial homeostasis. In addition to directly, periodontal bacteria may also be indirectly involved in the regulation of systemic health and disease through the disturbed gut. This paper provides evidence for the role of periodontal bacteria in systemic diseases via the oral-gut axis and the far-reaching implications of maintaining periodontal health in reducing the risk of many intestinal and parenteral diseases. This may provide insight into the underlying pathogenesis of many systemic diseases and the search for new preventive and therapeutic strategies.}, } @article {pmid39617896, year = {2024}, author = {Feng, R and Zhu, Q and Wang, A and Wang, H and Wang, J and Chen, P and Zhang, R and Liang, D and Teng, J and Ma, M and Ding, X and Wang, X}, title = {Effect of fecal microbiota transplantation on patients with sporadic amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled trial.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {566}, pmid = {39617896}, issn = {1741-7015}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Fecal Microbiota Transplantation/methods ; Double-Blind Method ; Female ; Male ; Middle Aged ; Aged ; Gastrointestinal Microbiome/physiology ; Treatment Outcome ; Quality of Life ; Adult ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the progressive loss of motor neurons. Recent insights into ALS pathogenesis underscore the pivotal role of the gut microbiome, prompting an investigation into the potential therapeutic impact of fecal microbiota transplantation (FMT) on sporadic ALS patients.

METHODS: Conducted as a double-blind, placebo-controlled, parallel-group, randomized clinical trial, the study enrolled 27 participants from October 2022 to April 2023. The participants were followed up for 6 months from February 2023 to October 2023, during in-person visits at baseline, week 15, week 23, and week 35. The participants, evenly randomized, received either healthy donor FMT (FMT, n = 14) or a mixture of 0.9% saline and food coloring (E150c) as sham transplantation (placebo, n = 13). The primary outcome measured the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score from baseline to week 35. Secondary outcomes included changes in gastrointestinal and respiratory functions, muscle strength, autonomic function, cognition, quality of life, intestinal microbiome composition, and plasm neurofilament light chain protein (NFL). Efficacy and safety outcomes were assessed in the intention-to-treat population.

RESULTS: A total of 27 randomized patients (47% women; mean age, 67.2 years), 24 participants completed the entire study. Notably, ALSFRS-R score changes exhibited no significant differences between FMT (6.1 [SD, 3.11]) and placebo (6.41[SD, 2.73]) groups from baseline to week 35. Secondary efficacy outcomes, encompassing respiratory function, muscle strength, autonomic function, cognition, quality of life, and plasm NFL, showed no significant differences. Nevertheless, the FMT group exhibited improvements in constipation, depression, and anxiety symptoms. FMT induced a shift in gut microbiome community composition, marked by increased abundance of Bifidobacterium, which persisted until week 15 (95% CI, 0.04 to 0.28; p = 0.01). Gastrointestinal adverse events were the primary manifestations of FMT-related side effects.

CONCLUSIONS: In this clinical trial involving 27 sporadic ALS patients, FMT did not significantly slow the decline in ALSFRS-R score. Larger multicenter trials are needed to confirm the efficacy of FMT in sporadic ALS patients and to explore the underlying biological mechanisms.

TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR 2200064504.}, } @article {pmid39471905, year = {2025}, author = {Salia, S and Burke, FF and Hinks, ME and Randell, AM and Matheson, MA and Walling, SG and Swift-Gallant, A}, title = {Gut microbiota transfer from the preclinical maternal immune activation model of autism is sufficient to induce sex-specific alterations in immune response and behavioural outcomes.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {813-823}, doi = {10.1016/j.bbi.2024.10.030}, pmid = {39471905}, issn = {1090-2139}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; Female ; Male ; Mice ; *Disease Models, Animal ; *Mice, Inbred C57BL ; *Autism Spectrum Disorder/immunology/microbiology ; *Behavior, Animal/physiology ; Pregnancy ; Fecal Microbiota Transplantation ; Autistic Disorder/immunology/microbiology ; Sex Characteristics ; Social Behavior ; Sex Factors ; Anxiety/immunology/microbiology ; Cytokines/metabolism ; }, abstract = {The gut microbiome plays a vital role in health and disease, including neurodevelopmental disorders like autism spectrum disorder (ASD). ASD affects 4:1 males-to-females, and sex differences are apparent in gut microbiota composition among ASD individuals and in animal models of this condition, such as the maternal immune activation (MIA) mouse model. However, few studies have included sex as a biological variable when assessing the role of gut microbiota in mediating ASD symptoms. Using the MIA model of ASD, we assessed whether gut microbiota contributes to the sex differences in the presentation of ASD-like behaviors. Gut microbiota transplantation from MIA or vehicle/control male and female mice into healthy, otherwise unmanipulated, 4-week-old C57Bl/6 mice was performed for 6 treatments over 12 days. Colonization with male, but not female, MIA microbiota was sufficient to reduce sociability, decrease microbiota diversity and increase neuroinflammation with more pronounced deficits in male recipients. Colonization with both male and female donor microbiota altered juvenile ultrasonic vocalizations and anxiety-like behavior in recipients of both sexes, and there was an accompanied change in the gut microbiota and serum cytokine IL-4 and IL-7 levels of all recipients of MIA gut microbiota. In addition to the increases in gut microbes associated with pathological states, the female donor microbiota profile also had increases in gut microbes with known neural protective effects (e.g., Lactobacillus and Rikenella). These results suggest that gut reactivity to environmental insults, such as in the MIA model, may play a role in shaping the sex disparity in ASD development.}, } @article {pmid39617011, year = {2024}, author = {Berzack, S and Galor, A}, title = {Microbiome-based therapeutics for ocular diseases.}, journal = {Clinical & experimental optometry}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/08164622.2024.2422479}, pmid = {39617011}, issn = {1444-0938}, abstract = {The relationship between the gut microbiome and ocular health has garnered increasing attention within the scientific community. Recent research has focused on the gut-eye axis, examining whether imbalances within the gut microbiome can influence the development, progression and severity of ocular diseases, including dry eye disease, uveitis, and glaucoma. Dysbiosis within the gut microbiome is linked to immune dysregulation, chronic inflammation, and epithelial barrier dysfunction, all of which contribute to ocular pathology. This review synthesises current evidence on these associations, exploring how gut microbiome alterations drive disease mechanisms. Furthermore, it examines the therapeutic potential of microbiome-targeted interventions, including antibiotics, prebiotics, probiotics, and faecal microbiota transplantation, all of which aim to restore microbial balance and modulate immune responses. As the prevalence of these conditions continues to rise, a deeper understanding of the gut-eye axis may facilitate the development of novel, targeted therapies to address unmet needs in the management of ocular diseases.}, } @article {pmid39614243, year = {2024}, author = {Gan, G and Zhang, R and Zeng, Y and Lu, B and Luo, Y and Chen, S and Lei, H and Cai, Z and Huang, X}, title = {Fecal microbiota transplantation validates the importance of gut microbiota in an ApoE[-/-] mouse model of chronic apical periodontitis-induced atherosclerosis.}, journal = {BMC oral health}, volume = {24}, number = {1}, pages = {1455}, pmid = {39614243}, issn = {1472-6831}, support = {2022QNA073//Fujian Provincial Health Technology Project/ ; 2022GGA042//Fujian Provincial Health Technology Project/ ; 2023J01709//Fujian Province Natural Science Founding of China/ ; 81970926//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Atherosclerosis/microbiology/etiology ; *Gastrointestinal Microbiome ; Mice ; *Fecal Microbiota Transplantation ; *Periapical Periodontitis/microbiology/metabolism ; *Disease Models, Animal ; *Methylamines/blood/metabolism ; Apolipoproteins E ; Male ; Mice, Inbred C57BL ; Oxygenases/metabolism ; }, abstract = {BACKGROUND: Chronic apical periodontitis (CAP) has been linked to the development of atherosclerosis, although the underlying mechanisms remain unclear. This study aimed to investigate the role of gut microbiota disruption in CAP-induced atherosclerosis development, focusing on trimethylamine N-oxide (TMAO)-related metabolites.

METHODS: The study utilized fecal microbiota transplantation (FMT) to transfer gut microbiota from mice with CAP to healthy mice. Atherosclerosis development was assessed by analyzing lesions in the aortic arch and aortic root. Serum lipid and inflammatory factor levels were measured. Composition and diversity of gut microbiota were analyzed using targeted metabolomics, with a focus on the ratio of Firmicutes to Bacteroidetes. The expression of hepatic flavin-containing monooxygenase 3 (FMO3) and serum TMAO levels were also evaluated.

RESULTS: Mice receiving gut microbiota from CAP mice showed increased atherosclerotic lesions compared to controls, without significant differences in serum lipid or inflammatory factor levels. Alterations in gut microbiota composition were observed, characterized by an increase in the Firmicutes to Bacteroidetes ratio. Peptostreptococcaceae abundance positively correlated with atherosclerosis severity, while Odoribacteraceae showed a negative correlation. No significant differences were found in hepatic FMO3 expression or serum TMAO levels.

CONCLUSIONS: The study confirms the role of gut microbiota disruption in CAP-mediated atherosclerosis development, independent of serum lipid or TMAO levels. Alterations in gut microbiota composition, particularly increased Firmicutes to Bacteroidetes ratio and specific bacterial families, were associated with atherosclerosis severity. These findings highlight the intricate interplay between gut microbiota and cardiovascular health in the context of CAP.}, } @article {pmid39612216, year = {2024}, author = {Wang, T and Luo, Y and Kong, X and Fang, L and Zhu, L and Yu, B and Zheng, P and Huang, Z and Mao, X and Jie, Y and Luo, J and Yan, H and He, J}, title = {Multiomics comparative analysis of feces AMRGs of Duroc pigs and Tibetan and the effect of fecal microbiota transplantation on AMRGs upon antibiotic exposure.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0198324}, doi = {10.1128/spectrum.01983-24}, pmid = {39612216}, issn = {2165-0497}, abstract = {UNLABELLED: Fecal matter is recognized as both a reservoir and a transmission source for various antimicrobial resistance genes (AMRGs). However, the transcriptional activity of AMRGs in swine feces is not well understood. In addition, the effect of fecal microbiota transplantation (FMT) on the excretion of AMRGs has rarely been reported. Our study explored the diversity, abundance, transcriptional activity, and bacterial hosts of AMRGs in Tibetan and Duroc pig feces using metagenomic and metatranscriptomic sequencing technologies. We discovered a significantly higher genomic abundance of AMRGs in the feces of Duroc pigs compared to Tibetan pigs (P < 0.001), although the transcript levels did not show a significant difference. The results showed that the core composition of AMRGs in pig feces varied considerably, with the most transcriptionally active AMRGs being oqxB, tetQ, Bla1, dfrA1, and amrB. Furthermore, the Firmicutes phylum is the main host of AMRGs. By transplanting fecal flora from Tibetan and Duroc pigs into the intestines of Duroc Landrace Yorkshire (DLY) piglets after acute antibiotic exposure, we found that only Tibetan pig fecal flora significantly reduced AMRGs in the feces of DLY piglets (P < 0.05). The effectiveness of Tibetan pig fecal microorganisms in removing AMRGs from DLY pig feces was mainly influenced by microbial communities, especially the Bacteroidota phylum. These findings offer valuable insights for the prevention and control of AMRG pollution.

IMPORTANCE: To the best of our knowledge, this study represents the first comprehensive analysis of antimicrobial resistance gene (AMRGs) expression in the fecal microbiota of Tibetan and Duroc pigs, employing an integrated metagenomic and metatranscriptomic approach. Our findings indicate a higher risk of AMRGs transmission in the feces of Duroc pigs compared to Tibetan pigs. Given the escalating antimicrobial resistance crisis, novel therapeutic interventions are imperative to mitigate gut colonization by pathogens and AMRGs. In this regard, we investigated the impact of fecal microbiota from Tibetan and Duroc pig sources on AMRGs excretion in Duroc Landrace Yorkshire (DLY) piglets' feces following acute antibiotic exposure. Remarkably, only fecal microbiota sourced from Tibetan pigs exhibited a reduction in AMRGs excretion in DLY piglets' feces. This underscores the significance of evaluating the presence of AMRGs within donor fecal microbiota for effective AMRGs decolonization strategies.}, } @article {pmid39608831, year = {2024}, author = {Tang, JMF and Habib, F and Rahmdil, M and Apostolou, N}, title = {Autologous faecal microbiota transplantation via double barrel stoma to treat chronic diversion colitis.}, journal = {BMJ case reports}, volume = {17}, number = {11}, pages = {}, doi = {10.1136/bcr-2024-262806}, pmid = {39608831}, issn = {1757-790X}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis/therapy/microbiology/surgery ; *Ileostomy ; Male ; Transplantation, Autologous ; Middle Aged ; Treatment Outcome ; Chronic Disease ; Female ; }, abstract = {Diversion colitis is a common phenomenon affecting patients after defunctioning ileostomy. We present a complex case of diversion colitis where the patient was deemed unsuitable for restorative surgery due to multiple areas of stricturing in a long defunctioned colonic segment. Despite initial treatments with rectally administered topical mesalazine, butyrate enemas and topical steroid therapy, the patient remained symptomatic with rectal bleeding and mucus discharge. Furthermore, the appearance of colitis could be appreciated on endoscopy and radiological investigations with changes in histology consistent with moderate-severe diversion colitis. This article describes our experience in the use of autologous faecal transplant administered via the efferent loop of a double-barrel ileostomy to successfully treat diversion colitis refractory to standard topical therapy.}, } @article {pmid39607612, year = {2024}, author = {Qasem, HH and El-Sayed, WM}, title = {The bacterial microbiome and cancer: development, diagnosis, treatment, and future directions.}, journal = {Clinical and experimental medicine}, volume = {25}, number = {1}, pages = {12}, pmid = {39607612}, issn = {1591-9528}, mesh = {Humans ; *Neoplasms/therapy/microbiology/diagnosis ; *Dysbiosis ; *Microbiota ; Bacteria/classification/genetics ; Probiotics/therapeutic use ; }, abstract = {The term "microbiome" refers to the collection of bacterial species that reside in the human body's tissues. Sometimes, it is used to refer to all microbial entities (bacteria, viruses, fungi, and others) which colonize the human body. It is now generally acknowledged that the microbiome plays a critical role in the host's physiological processes and general well-being. Changes in the structure and/or function of the microbiome (dysbiosis) are linked to the development of many diseases including cancer. The claim that because of their negatively charged membrane, cancer cells are more vulnerable to some bacteria than normal cells and that is how the link between these bacteria and cancer evolved has been refuted. Furthermore, the relationship between the microbiome and cancer is more evident in the emerging field of cancer immunotherapy. In this narrative review, we detailed the correlation between the presence/absence of specific bacterial species and the development, diagnosis, prognosis, and treatment of some types of cancer including colorectal, lung, breast, and prostate cancer. In addition, we discussed the mechanisms of microbiome-cancer interactions including genotoxin production, the role of free radicals, modification of signaling pathways in host cells, immune modulation, and modulation of drug metabolism by microbiome. Future directions and clinical application of microbiome in the early detection, prognosis, and treatment of cancer emphasizing on the role of fecal transplantation, probiotics, prebiotics, and microbiome biomarkers were also considered.}, } @article {pmid39606629, year = {2024}, author = {Zhang, Z and Yang, M and Zhou, T and Chen, Y and Zhou, X and Long, K}, title = {Emerging trends and hotspots in intestinal microbiota research in sepsis: bibliometric analysis.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1510463}, pmid = {39606629}, issn = {2296-858X}, abstract = {BACKGROUND: The association between the gut microbiota and sepsis has garnered attention in the field of intestinal research in sepsis. This study utilizes bibliometric methods to visualize and analyze the literature on gut microbiota research in sepsis from 2011 to 2024, providing a scientific foundation for research directions and key issues in this domain.

METHODS: Original articles and reviews of gut microbiota research in sepsis, which published in English between 2011 and 2024, were obtained from the Web of Science Core Collection on June 21, 2024. Python, VOSviewer, and CiteSpace software were used for the visual analysis of the retrieved data.

RESULTS: A total of 1,031 articles were analyzed, originating from 72 countries or regions, 1,614 research institutions, and 6,541 authors. The articles were published in 434 different journals, covering 89 different research fields. The number of publications and citations in this research area showed a significant growth trend from 2011 to 2024, with China, the United States, and the United Kingdom being the main research forces. Asada Leelahavanichkul from Thailand was identified as the most prolific author, making him the most authoritative expert in this field. "Nutrients" had the highest number of publications, while "Frontiers in Cellular and Infection Microbiology," "Frontiers in Immunology" and "the International Journal of Molecular Sciences" have shown increasing attention to this field in the past 2 years. Author keywords appearing more than 100 times included "gut microbiota (GM)," "sepsis" and "microbiota." Finally, this study identified "lipopolysaccharides (LPS)," "short-chain fatty acids (SCFAs)," "probiotics," "fecal microbiota transplantation (FMT)" and "gut-liver axis" as the research hotspots and potential frontier directions in this field.

CONCLUSION: This bibliometric study summarizes current important perspectives and offers comprehensive guidance between sepsis and intestinal microbiota, which may help researchers choose the most appropriate research directions.}, } @article {pmid39605286, year = {2024}, author = {Yerushalmy-Feler, A and Spencer, EA and Dolinger, MT and Suskind, DL and Mitrova, K and Hradsky, O and Conrad, MA and Kelsen, JR and Uhlig, HH and Tzivinikos, C and Ancona, S and Wlazlo, M and Hackl, L and Shouval, DS and Bramuzzo, M and Urlep, D and Olbjorn, C and D'Arcangelo, G and Pujol-Muncunill, G and Yogev, D and Kang, B and Gasparetto, M and Rungø, C and Kolho, KL and Hojsak, I and Norsa, L and Rinawi, F and Sansotta, N and Magen Rimon, R and Granot, M and Scarallo, L and Trindade, E and Velasco Rodríguez-Belvís, M and Turner, D and Cohen, S}, title = {Upadacitinib for Induction of Remission in Pediatric Ulcerative Colitis: An International Multi‑center Study.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjae182}, pmid = {39605286}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U.

METHODS: In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical and laboratory data as well as adverse events (AEs) were recorded at week 8 post induction.

RESULTS: One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. AEs were recorded in 37 children, including one serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n=13), acne (n=12), and infections (n=10, five of whom with herpes viruses).

CONCLUSION: Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.}, } @article {pmid39605077, year = {2024}, author = {Zou, P and Bi, Y and Tong, Z and Wu, T and Li, Q and Wang, K and Fan, Y and Zhao, D and Wang, X and Shao, H and Huang, H and Ma, S and Qian, Y and Zhang, G and Liu, X and Jin, Q and Ru, Q and Qian, Z and Sun, W and Chen, Q and You, L and Wang, F and Zhang, X and Qiu, Z and Lin, Q and Lv, J and Zhang, Y and Geng, J and Mao, R and Liu, J and Zheng, Y and Ding, F and Wang, H and Gao, H}, title = {Comparisons of efficacy and safety of 400 or 800 ml bacterial count fecal microbiota transplantation in the treatment of recurrent hepatic encephalopathy: a multicenter prospective randomized controlled trial in China.}, journal = {Trials}, volume = {25}, number = {1}, pages = {799}, pmid = {39605077}, issn = {1745-6215}, mesh = {Humans ; *Hepatic Encephalopathy/therapy/microbiology ; Prospective Studies ; *Fecal Microbiota Transplantation/adverse effects ; China ; *Quality of Life ; Treatment Outcome ; *Recurrence ; Multicenter Studies as Topic ; Male ; Bacterial Load ; Randomized Controlled Trials as Topic ; Middle Aged ; Adult ; Female ; }, abstract = {BACKGROUND: Hepatic encephalopathy (HE) represents a critical complications of end-stage liver disease, serving as an independent predictor of mortality among patients with cirrhosis. Despite effective treatment with rifaximin, some patients with HE still progress to recurrent episodes, posing a significant therapeutic challenge. Recurrent HE is defined as experiencing two or more episodes within a 6-month period. Previous research has suggested that FMT may emerge as a promising treatment for recurrent HE. However, there remains a critical need to explore the optimal dosage. This trial aims to abscess the efficacy and safety of two FMT dosages: 800 ml or 400 ml total bacterial count, including mortality and quality of life.

METHODS: This multicenter, prospective, randomized controlled trial will enroll 100 eligible patients from 31 hospitals in China. Participants will be randomly assigned in a 1:1 ratio to either the high-dose group (800 ml total bacterial count) or the low-dose group (400 ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48 weeks, including mortality and quality of life.

DISCUSSION: If either or both dosages of FMT demonstrate safe and effective treatment of recurrent HE, leading to improve quality of life and survival at 24 and 48 weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications.

TRIAL REGISTRATION: NCT05669651 on ClinicalTrials.gov. Registered on 29 December 2022. CHiCTR2200067135 on China Registered Clinical Trial Registration Center. Registered on 27 December 2022.}, } @article {pmid39269772, year = {2024}, author = {Rahal, Z and Liu, Y and Peng, F and Yang, S and Jamal, MA and Sharma, M and Moreno, H and Damania, AV and Wong, MC and Ross, MC and Sinjab, A and Zhou, T and Chen, M and Tarifa Reischle, I and Feng, J and Chukwuocha, C and Tang, E and Abaya, C and Lim, JK and Leung, CH and Lin, HY and Deboever, N and Lee, JJ and Sepesi, B and Gibbons, DL and Wargo, JA and Fujimoto, J and Wang, L and Petrosino, JF and Ajami, NJ and Jenq, RR and Moghaddam, SJ and Cascone, T and Hoffman, K and Kadara, H}, title = {Inflammation Mediated by Gut Microbiome Alterations Promotes Lung Cancer Development and an Immunosuppressed Tumor Microenvironment.}, journal = {Cancer immunology research}, volume = {12}, number = {12}, pages = {1736-1752}, doi = {10.1158/2326-6066.CIR-24-0469}, pmid = {39269772}, issn = {2326-6074}, support = {R01 CA205608/CA/NCI NIH HHS/United States ; R01 CA248731/CA/NCI NIH HHS/United States ; R01CA248731//National Cancer Institute (NCI)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Tumor Microenvironment/immunology ; *Lung Neoplasms/immunology/microbiology/pathology ; Mice ; Humans ; *Inflammation/immunology ; Adenocarcinoma of Lung/immunology/microbiology/pathology ; Lipocalin-2/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Mice, Knockout ; }, abstract = {Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely coupled with tobacco-associated lung adenocarcinoma in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice exacerbates protumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on lung adenocarcinoma development remains poorly understood. In this study, we investigated the role of gut microbiome changes in lung adenocarcinoma development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of proinflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagated systemically, exerting immunosuppression within the tumor microenvironment, augmenting tumor growth through an IL6-dependent mechanism and dampening response to immunotherapy. Corroborating our preclinical findings, we found that patients with lung adenocarcinoma with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in lung adenocarcinoma and present new potential targets for interception and therapy.}, } @article {pmid39604726, year = {2024}, author = {Chen-Liaw, A and Aggarwala, V and Mogno, I and Haifer, C and Li, Z and Eggers, J and Helmus, D and Hart, A and Wehkamp, J and Lamousé-Smith, ESN and Kerby, RL and Rey, FE and Colombel, JF and Kamm, MA and Olle, B and Norman, JM and Menon, R and Watson, AR and Crossett, E and Terveer, EM and Keller, JJ and Borody, TJ and Grinspan, A and Paramsothy, S and Kaakoush, NO and Dubinsky, MC and Faith, JJ}, title = {Gut microbiota strain richness is species specific and affects engraftment.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {39604726}, issn = {1476-4687}, abstract = {Despite the fundamental role of bacterial strain variation in gut microbiota function[1-6], the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments. Active therapeutic administration of supraphysiologic numbers of strains per species increases recipient SR, which then converges back to the population average after dosing is ceased. Stratifying engraftment outcomes by high or low SR shows that SR predicts microbial addition or replacement in faecal transplants. Together, these results indicate that properties of the gut ecosystem govern the number of strains of each species colonizing the gut and thereby influence strain addition and replacement in faecal microbiota transplantation and defined live biotherapeutic products.}, } @article {pmid39604623, year = {2024}, author = {Procházková, N and Laursen, MF and La Barbera, G and Tsekitsidi, E and Jørgensen, MS and Rasmussen, MA and Raes, J and Licht, TR and Dragsted, LO and Roager, HM}, title = {Gut physiology and environment explain variations in human gut microbiome composition and metabolism.}, journal = {Nature microbiology}, volume = {9}, number = {12}, pages = {3210-3225}, pmid = {39604623}, issn = {2058-5276}, support = {NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Feces/microbiology ; Adult ; Hydrogen-Ion Concentration ; Male ; Female ; Bacteria/classification/metabolism/genetics/isolation & purification ; Gastrointestinal Transit/physiology ; Young Adult ; Middle Aged ; Diet ; Fermentation ; Gastrointestinal Tract/microbiology/metabolism ; Methane/metabolism ; Healthy Volunteers ; }, abstract = {The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals. We observed substantial daily fluctuations, with intra-individual variations in gut microbiome and metabolism associated with changes in stool moisture and faecal pH, and inter-individual variations accounted for by whole-gut and segmental transit times and pH. Metabolites derived from microbial carbohydrate fermentation correlated negatively with the gut passage time and pH, while proteolytic metabolites and breath methane showed a positive correlation. Finally, we identified associations between segmental transit time/pH and coffee-, diet-, host- and microbial-derived metabolites. Our work suggests that gut physiology and environment are key to understanding the individuality of the human gut microbial composition and metabolism.}, } @article {pmid39604327, year = {2024}, author = {Saeed, H and Díaz, LA and Gil-Gómez, A and Burton, J and Bajaj, J and Romero-Gomez, M and Arrese, M and Arab, JP and Khan, MQ}, title = {Microbiome-Centered Therapies for the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Clinical and molecular hepatology}, volume = {}, number = {}, pages = {}, doi = {10.3350/cmh.2024.0811}, pmid = {39604327}, issn = {2287-285X}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus (T2DM). This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies' potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.}, } @article {pmid39603188, year = {2024}, author = {Xie, C and Liang, Q and Cheng, J and Yuan, Y and Xie, L and Ji, J}, title = {Transplantation of fecal microbiota from low to high residual feed intake chickens: Impacts on RFI, microbial community and metabolites profiles.}, journal = {Poultry science}, volume = {104}, number = {1}, pages = {104567}, doi = {10.1016/j.psj.2024.104567}, pmid = {39603188}, issn = {1525-3171}, abstract = {Improving feed efficiency is vital to bolster profitability and sustainability in poultry production. Although several studies have established links between gut microbiota and feed efficiency, the direct effects remain unclear. In this study, two distinct lines of Huiyang bearded chickens, exhibiting significant differences in residual feed intake (RFI), were developed after 15 generations of selective breeding. Fecal microbiota transplantation (FMT) from low RFI (LRFI) chickens to high RFI (HRFI) chickens resulted in a reduction trend in RFI, decreasing from 5.65 to 4.49 in the HRFI recipient chickens (HFMT). Microbiota composition and functional profiles in LRFI and HFMT chickens formed a distinct cluster compared to HRFI chickens. Using 16S rDNA sequencing and RandomForest analysis, Slackia, Peptococcus, Blautia, and Dorea were identified as key microbial markers associated with feed efficiency. Additionally, untargeted metabolomics identified common differential metabolites between HFMT and LRFI vs. HRFI groups. Correlation analysis showed significant correlations between these microbial markers and differential metabolites. These findings provide a foundation for microbiome-based strategies to improve feed efficiency in poultry.}, } @article {pmid39600755, year = {2024}, author = {Castro-Vidal, ZA and Mathew, F and Ibrahim, AA and Shubhangi, F and Cherian, RR and Choi, HK and Begum, A and Ravula, HK and Giri, H}, title = {The Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Various Neurocognitive Disorders.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72451}, pmid = {39600755}, issn = {2168-8184}, abstract = {This review explores the critical role of the human microbiome in neurological and neurodegenerative disorders, focusing on gut-brain axis dysfunction caused by dysbiosis, an imbalance in gut bacteria. Dysbiosis has been linked to diseases such as Alzheimer's disease, Parkinson's disease (PD), multiple sclerosis (MS), and stroke. The gut microbiome influences the central nervous system (CNS) through signaling molecules, including short-chain fatty acids, neurotransmitters, and metabolites, impacting brain health and disease progression. Emerging therapies, such as fecal microbiota transplantation (FMT), have shown promise in restoring microbial balance and alleviating neurological symptoms, especially in Alzheimer's and PD. Additionally, nutritional interventions such as probiotics, prebiotics, and specialized diets are being investigated for their ability to modify gut microbiota and improve patient outcomes. This review highlights the therapeutic potential of gut microbiota modulation but emphasizes the need for further clinical trials to establish the safety and efficacy of these interventions in neurological and mental health disorders.}, } @article {pmid39600698, year = {2024}, author = {Liu, X and Li, B and Liang, L and Han, J and Mai, S and Liu, L}, title = {From microbes to medicine: harnessing the power of the microbiome in esophageal cancer.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1450927}, pmid = {39600698}, issn = {1664-3224}, mesh = {Humans ; *Esophageal Neoplasms/therapy/microbiology/immunology ; *Dysbiosis/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; Probiotics/therapeutic use ; Microbiota/immunology ; }, abstract = {Esophageal cancer (EC) is a malignancy with a high incidence and poor prognosis, significantly influenced by dysbiosis in the esophageal, oral, and gut microbiota. This review provides an overview of the roles of microbiota dysbiosis in EC pathogenesis, emphasizing their impact on tumor progression, drug efficacy, biomarker discovery, and therapeutic interventions. Lifestyle factors like smoking, alcohol consumption, and betel nut use are major contributors to dysbiosis and EC development. Recent studies utilizing advanced sequencing have revealed complex interactions between microbiota dysbiosis and EC, with oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promoting inflammation and suppressing immune responses, thereby driving carcinogenesis. Altered esophageal microbiota, characterized by reduced beneficial bacteria and increased pathogenic species, further exacerbate local inflammation and tumor growth. Gut microbiota dysbiosis also affects systemic immunity, influencing chemotherapy and immunotherapy efficacy, with certain bacteria enhancing or inhibiting treatment responses. Microbiota composition shows potential as a non-invasive biomarker for early detection, prognosis, and personalized therapy. Novel therapeutic strategies targeting the microbiota-such as probiotics, dietary modifications, and fecal microbiota transplantation-offer promising avenues to restore balance and improve treatment efficacy, potentially enhancing patient outcomes. Integrating microbiome-focused strategies into current therapeutic frameworks could improve EC management, reduce adverse effects, and enhance patient survival. These findings highlight the need for further research into microbiota-tumor interactions and microbial interventions to transform EC treatment and prevention, particularly in cases of late-stage diagnosis and poor treatment response.}, } @article {pmid39600557, year = {2024}, author = {Wohl, P and Krausova, A and Wohl, P and Fabian, O and Bajer, L and Brezina, J and Drastich, P and Hlavaty, M and Novotna, P and Kahle, M and Spicak, J and Gregor, M}, title = {Limited validity of Mayo endoscopic subscore in ulcerative colitis with concomitant primary sclerosing cholangitis.}, journal = {World journal of gastrointestinal endoscopy}, volume = {16}, number = {11}, pages = {607-616}, pmid = {39600557}, issn = {1948-5190}, abstract = {BACKGROUND: Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear.

AIM: To assess the accuracy of MES in UC and PSC-UC patients, we performed histological scoring using Nancy histological index (NHI).

METHODS: MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy. NHI and inflammation were evaluated in biopsies from the cecum, rectum, and terminal ileum. In addition, perinuclear anti-neutrophil cytoplasmic antibodies, fecal calprotectin, body mass index, and other relevant clinical characteristics were collected.

RESULTS: The median MES and NHI were similar for UC patients (MES grade 2 and NHI grade 2 in the rectum) but were different for PSC-UC patients (MES grade 0 and NHI grade 2 in the cecum). There was a correlation between MES and NHI for UC patients (Spearman's r = 0.40, P = 0.029) but not for PSC-UC patients. Histopathological examination revealed persistent microscopic inflammation in 88% of PSC-UC patients with MES grade 0 (46% of all PSC-UC patients). Moreover, MES overestimated the severity of active inflammation in an additional 11% of PSC-UC patients.

CONCLUSION: MES insufficiently identifies microscopic inflammation in PSC-UC. This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.}, } @article {pmid39599742, year = {2024}, author = {Al-Habsi, N and Al-Khalili, M and Haque, SA and Elias, M and Olqi, NA and Al Uraimi, T}, title = {Health Benefits of Prebiotics, Probiotics, Synbiotics, and Postbiotics.}, journal = {Nutrients}, volume = {16}, number = {22}, pages = {}, pmid = {39599742}, issn = {2072-6643}, support = {(SR/AGR/Food/23/01)//His Majesty Trust Funds/ ; }, mesh = {Humans ; *Prebiotics/administration & dosage ; *Probiotics/administration & dosage ; *Synbiotics/administration & dosage ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Functional Food ; }, abstract = {The trillions of microbes that constitute the human gut microbiome play a crucial role in digestive health, immune response regulation, and psychological wellness. Maintaining gut microbiota is essential as metabolic diseases are associated with it. Functional food ingredients potentially improving gut health include prebiotics, probiotics, synbiotics, and postbiotics (PPSPs). While probiotics are living bacteria that provide health advantages when ingested sufficiently, prebiotics are non-digestible carbohydrates that support good gut bacteria. Synbiotics work together to improve immunity and intestinal health by combining probiotics and prebiotics. Postbiotics have also demonstrated numerous health advantages, such as bioactive molecules created during probiotic fermentation. According to a recent study, PPSPs can regulate the synthesis of metabolites, improve the integrity of the intestinal barrier, and change the gut microbiota composition to control metabolic illnesses. Additionally, the use of fecal microbiota transplantation (FMT) highlights the potential for restoring gut health through microbiota modulation, reinforcing the benefits of PPSPs in enhancing overall well-being. Research has shown that PPSPs provide several health benefits, such as improved immunological function, alleviation of symptoms associated with irritable bowel disease (IBD), decreased severity of allergies, and antibacterial and anti-inflammatory effects. Despite encouraging results, many unanswered questions remain about the scope of PPSPs' health advantages. Extensive research is required to fully realize the potential of these functional food components in enhancing human health and well-being. Effective therapeutic and prophylactic measures require further investigation into the roles of PPSPs, specifically their immune-system-modulating, cholesterol-lowering, antioxidant, and anti-inflammatory characteristics.}, } @article {pmid39598283, year = {2024}, author = {Mederle, AL and Dima, M and Stoicescu, ER and Căpăstraru, BF and Levai, CM and Hațegan, OA and Maghiari, AL}, title = {Impact of Gut Microbiome Interventions on Glucose and Lipid Metabolism in Metabolic Diseases: A Systematic Review and Meta-Analysis.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {39598283}, issn = {2075-1729}, abstract = {BACKGROUND: The gut microbiome is increasingly recognized as a key player in metabolic health, influencing glucose and lipid metabolism through various mechanisms. However, the efficacy of gut microbiota-targeted interventions, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and diet-based treatments, remains unclear for specific metabolic outcomes. In this study, the aim was to evaluate the impact of these interventions on the glucose and lipid parameters in individuals with metabolic diseases such as diabetes mellitus (DM), obesity, and metabolic syndrome.

METHODS: This systematic review and meta-analysis included 41 randomized controlled trials that investigated the effects of gut microbiota-targeted treatments on metabolic parameters such as fasting glucose, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. A comprehensive search was conducted using databases like PubMed, Google Scholar, and Scopus, focusing on interventions targeting the gut microbiota. A meta-analysis was performed using random-effects models, with effect sizes calculated for each outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool.

RESULTS: Gut microbiota-targeted interventions significantly reduced fasting glucose, HbA1c, HOMA-IR, total cholesterol, LDL-C, and triglycerides, with moderate heterogeneity observed across studies. The interventions also led to modest increases in HDL-C levels. Probiotic and synbiotic interventions showed the most consistent benefits in improving both glucose and lipid profiles, while FMT yielded mixed results. Short-term interventions showed rapid microbial shifts but less pronounced metabolic improvements, whereas longer-term interventions had more substantial metabolic benefits.

CONCLUSIONS: In this study, it is demonstrated that gut microbiota-targeted interventions can improve key metabolic outcomes, offering a potential therapeutic strategy for managing metabolic diseases. However, the effectiveness of these interventions varies depending on the type, duration, and population characteristics, highlighting the need for further long-term studies to assess the sustained effects of microbiota modulation on metabolic health.}, } @article {pmid39597729, year = {2024}, author = {Alexandrescu, L and Suceveanu, AP and Stanigut, AM and Tofolean, DE and Axelerad, AD and Iordache, IE and Herlo, A and Nelson Twakor, A and Nicoara, AD and Tocia, C and Dumitru, A and Dumitru, E and Condur, LM and Aftenie, CF and Tofolean, IT}, title = {Intestinal Insights: The Gut Microbiome's Role in Atherosclerotic Disease: A Narrative Review.}, journal = {Microorganisms}, volume = {12}, number = {11}, pages = {}, pmid = {39597729}, issn = {2076-2607}, abstract = {Recent advances have highlighted the gut microbiota as a significant contributor to the development and progression of atherosclerosis, which is an inflammatory cardiovascular disease (CVD) characterized by plaque buildup within arterial walls. The gut microbiota, consisting of a diverse collection of microorganisms, impacts the host's metabolism, immune responses, and lipid processing, all of which contribute to atherosclerosis. This review explores the complex mechanisms through which gut dysbiosis promotes atherogenesis. We emphasize the potential of integrating microbiota modulation with traditional cardiovascular care, offering a holistic approach to managing atherosclerosis. Important pathways involve the translocation of inflammatory microbial components, modulation of lipid metabolism through metabolites such as trimethylamine-N-oxide (TMAO), and the production of short-chain fatty acids (SCFAs) that influence vascular health. Studies reveal distinct microbial profiles in atherosclerosis patients, with increased pathogenic bacteria (Megamonas, Veillonella, Streptococcus) and reduced anti-inflammatory genera (Bifidobacterium, Roseburia), highlighting the potential of these profiles as biomarkers and therapeutic targets. Probiotics are live microorganisms that have health benefits on the host. Prebiotics are non-digestible dietary fibers that stimulate the growth and activity of beneficial gut bacteria. Interventions targeting microbiota, such as probiotics, prebiotics, dietary modifications, and faecal microbiota transplantation (FMT), present effective approaches for restoring microbial equilibrium and justifying cardiovascular risk. Future research should focus on longitudinal, multi-omics studies to clarify causal links and refine therapeutic applications.}, } @article {pmid39597606, year = {2024}, author = {Qiao, Y and Feng, Q and Wang, Q and Zhao, Q and Zhu, S and Zhao, F and Wang, Z and Zhang, R and Wang, J and Yu, Y and Han, H and Dong, H}, title = {Alteration in the Gut Microbiota of Chickens Resistant to Eimeria tenella Infection.}, journal = {Microorganisms}, volume = {12}, number = {11}, pages = {}, pmid = {39597606}, issn = {2076-2607}, support = {Grant No. 2023YFD18024//National Key Research and Development Program of China/ ; XZ202401ZY0052//Key Research and Development of Science and Technology Plan in Tibet Autonomous Region/ ; Grant No. 32373038//National Natural Science Foundation of China/ ; NPRC-2019-194-30//National Parasitic Resources Center/ ; }, abstract = {Avian coccidiosis, caused by several species of Eimeria, is a widespread and economically important poultry disease that inflicts severe losses in the poultry industry. Understanding the interplay between Eimeria and gut microbiota is critical for controlling coccidiosis and developing innovative treatments to ensure good poultry health. In the present study, chickens were immunized six times with a low dose of Eimeria tenella, resulting in complete immunity against Eimeria infection. The results of fecal microbiota transplantation showed that the gut microbiota of immunized chickens induced a certain degree of resistance to coccidial infection. To investigate the types of intestinal microbiota involved in the development of resistance to Eimeria, the intestinal contents and fecal samples from both immunized and unimmunized groups were collected for 16S rRNA gene sequencing. The results showed that, at the genus level, the abundance of the Eubacterium coprostanoligenes group, Erysipelatoclostridium, Shuttleworthia, and Colidextribacter was significantly increased in the intestinal content of immunized chickens, whereas the abundance of Eisenbergiella was significantly decreased. In fecal samples, the abundance of Clostridiaceae and Muribaculaceae significantly increased, whereas that of Bacillales significantly decreased. These findings will help to elucidate the interactions between E. tenella and the gut microbiota of chickens, providing a basis for isolating E. tenella-resistant strains from the gut microbiome and developing new vaccines against coccidiosis.}, } @article {pmid39597084, year = {2024}, author = {Ko, Y and Alaedin, S and Fernando, D and Zhou, J and Ho, V}, title = {A Review of Fecal Microbiota Transplantation in Children-Exploring Its Role in the Treatment of Inflammatory Bowel Diseases.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {11}, pages = {}, pmid = {39597084}, issn = {1648-9144}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Child ; *Inflammatory Bowel Diseases/therapy/microbiology ; Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {Background and Objectives: There is an increasing use of fecal matter transplantation (FMT) worldwide as research into the impact of the gut microbiome in various disease states is growing. FMT is the transfer of stool from a healthy human donor to a patient for the purpose of restoring intestinal dysbiosis. This review will assess the efficacy and safety of FMT in the treatment of pediatric inflammatory bowel diseases (IBDs) and explore the future directions of the use of FMT in children. Materials and Methods: A systematic review was performed where a literature search of publications published prior to 15 September 2023 was performed. Efficacy outcomes and safety data as well as microbiome analysis were reviewed from the studies where applicable. Results: Nine studies on UC and two studies on CD satisfied eligibility criteria and individually analysed. Most of the studies provided microbiome analyses. Conclusions: FMT is a safe treatment for paediatric IBD, and is shown to be effective in inducing clinical response by some studies. However the lack of randomized controlled trials limited the results of our study.}, } @article {pmid39596154, year = {2024}, author = {Sevcikova, A and Martiniakova, M and Omelka, R and Stevurkova, V and Ciernikova, S}, title = {The Link Between the Gut Microbiome and Bone Metastasis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596154}, issn = {1422-0067}, support = {2/0069/22//Scientific Grant Agency of the Ministry of Education, Research, Development, and Youth of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 1/0071/24//Scientific Grant Agency of the Ministry of Education, Research, Development, and Youth of the Slovak Republic and Slovak Academy of Sciences/ ; KEGA 034UKF-4/2022//Ministry of Education, Research, Development, and Youth of the Slovak Republic/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Bone Neoplasms/secondary/microbiology ; Animals ; Dysbiosis/microbiology ; Probiotics ; }, abstract = {The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors and extensive blood flow, especially affecting patients with thyroid, prostate, breast, lung, and kidney cancers, where bone metastases severely reduce the quality of life. While the involvement of the gut microbiome in bone metastasis formation is still being explored, proposed mechanisms suggest that intestinal dysbiosis may alter the bone microenvironment via the gut-immune-bone axis, fostering a premetastatic niche and immunosuppressive milieu suitable for cancer cell colonization. Disruption in the delicate balance of bone modeling and remodeling may further create a favorable environment for metastatic growth. This review focuses on the link between beneficial or dysbiotic microbiome composition and bone homeostasis, as well as the role of the microbiome in bone metastasis development. It also provides an overview of clinical trials evaluating the impact of gut microbial community structure on bone parameters across various conditions or health-related issues. Dietary interventions and microbiota modulation via probiotics, prebiotics, and fecal microbiota transplantation help support bone health and might offer promising strategies for addressing bone-related complications in cancer.}, } @article {pmid39595097, year = {2024}, author = {López-Tenorio, II and Aguilar-Villegas, ÓR and Espinoza-Palacios, Y and Segura-Real, L and Peña-Aparicio, B and Amedei, A and Aguirre-García, MM}, title = {Primary Prevention Strategy for Non-Communicable Diseases (NCDs) and Their Risk Factors: The Role of Intestinal Microbiota.}, journal = {Biomedicines}, volume = {12}, number = {11}, pages = {}, pmid = {39595097}, issn = {2227-9059}, support = {CF 2023-2024 -734//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; IN21222//Universidad Nacional Autónoma de México/ ; }, abstract = {Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. These conditions have numerous health consequences and significantly impact patients' lifestyles. Effective long-term treatment is essential since NCDs are irreversible. Therefore, primary healthcare must be both exclusive and of the highest quality, ensuring comprehensive care. The primary goal should be to improve quality of life with a focus on patients, families, and communities, as most of these diseases can be prevented and controlled, although not cured. Several factors have been linked to individual health, including social, cultural, and economic aspects, lifestyle, and certain environmental factors, including work, that can have positive or negative effects. More of these variables may contribute to the onset of NCDs, which are defined by their chronic nature, propensity for prolongation, and generally slow rate of progression. Examples of NCDs include hypertension, type 2 diabetes (T2D), dyslipidemia, and fatty liver disease linked to metabolic dysfunction. The onset of these diseases has been associated with an imbalance in certain microbial niches, such as the gut, which hosts billions of microorganisms performing multiple metabolic functions, such as the production of metabolites like bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). Therefore, lifestyle changes and personal habits can significantly impact the gut microbiota (GM), potentially preventing chronic diseases associated with metabolism. NCDs are highly prevalent worldwide, prompting increased attention to strategies for modifying the intestinal microbiota (IM). Approaches such as probiotics, prebiotics, synbiotics, and fecal transplantation (FMT) have demonstrated improvements in the quality of life for individuals with these conditions. Additionally, lifestyle changes and the adoption of healthy habits can significantly impact IM and may help prevent chronic diseases related to metabolism. Therefore, the main aim of this review is to analyze and understand the importance of microbiota intervention in the prevention of non-communicable diseases. R3:A1.}, } @article {pmid39594528, year = {2024}, author = {Scarpellini, E and Scarcella, M and Tack, JF and Scarlata, GGM and Zanetti, M and Abenavoli, L}, title = {Gut Microbiota and Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, doi = {10.3390/antiox13111386}, pmid = {39594528}, issn = {2076-3921}, abstract = {Background: The gut microbiota constitutes a complex microorganism community that harbors bacteria, viruses, fungi, protozoa, and archaea. The human gut bacterial microbiota has been extensively proven to participate in human metabolism, immunity, and nutrient absorption. Its imbalance, namely "dysbiosis", has been linked to disordered metabolism. Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the features of deranged human metabolism and is the leading cause of liver cirrhosis and hepatocellular carcinoma. Thus, there is a pathophysiological link between gut dysbiosis and MASLD. Aims and Methods: We aimed to review the literature data on the composition of the human bacterial gut microbiota and its dysbiosis in MASLD and describe the concept of the "gut-liver axis". Moreover, we reviewed the approaches for gut microbiota modulation in MASLD treatment. Results: There is consolidated evidence of particular gut dysbiosis associated with MASLD and its stages. The model explaining the relationship between gut microbiota and the liver has a bidirectional organization, explaining the physiopathology of MASLD. Oxidative stress is one of the keystones in the pathophysiology of MASLD and fibrosis generation. There is promising and consolidated evidence for the efficacy of pre- and probiotics in reversing gut dysbiosis in MASLD patients, with therapeutic effects. Few yet encouraging data on fecal microbiota transplantation (FMT) in MASLD are available in the literature. Conclusions: The gut dysbiosis characteristic of MASLD is a key target in its reversal and treatment via diet, pre/probiotics, and FMT treatment. Oxidative stress modulation remains a promising target for MASLD treatment, prevention, and reversal.}, } @article {pmid39593402, year = {2024}, author = {Tian, B and Pan, Y and Zhang, X and Wu, Y and Luo, X and Yang, K}, title = {Etiolated-green tea attenuates colonic barrier dysfunction and inflammation in high-fat diet-induced mice by modulating gut microbiota.}, journal = {Food research international (Ottawa, Ont.)}, volume = {197}, number = {Pt 1}, pages = {115192}, doi = {10.1016/j.foodres.2024.115192}, pmid = {39593402}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diet, High-Fat/adverse effects ; *Tea/chemistry ; Mice ; Male ; *Colon/microbiology/metabolism/drug effects ; *Mice, Inbred C57BL ; *Inflammation ; Fatty Acids, Volatile/metabolism ; Dysbiosis ; Obesity/metabolism ; NF-kappa B/metabolism ; Intestinal Mucosa/metabolism/drug effects ; Fecal Microbiota Transplantation ; Toll-Like Receptor 4/metabolism ; Signal Transduction/drug effects ; Receptors, G-Protein-Coupled/metabolism ; Tight Junctions/drug effects/metabolism ; }, abstract = {Colonic barrier dysfunction and inflammation arising from dysbiosis gut microbiota (GM) are strongly associated with a high-fat diet (HFD). Yellow leaf green tea (YLGT), a novel variety of etiolated-green tea, improving the intestinal barrier and inflammation is related to the regulation of GM disorders. To explore the ameliorative mechanism of YLGT, mice were fed an HFD with or without YLGT at doses of 150, 300, and 450 mg kg[-1] for 12 weeks. YLGT rectified the GM imbalance, enriched short-chain fatty acid (SCFA)-producing bacteria and gut SCFA contents, activated G protein-coupled receptors, inhibited TLR4/NF-κB signaling pathway, strengthened the tight junction, and repaired the damaged intestinal barrier. The fecal microbiota transplantation experiment further confirmed that the GM was a key element in the anti-obesity and anti-intestinal inflammation effect of YLGT. YLGT has great promise in attenuating obesity-induced intestinal dysfunction. This research provides novel insights into the new mechanism of YLGT on HFD-induced obesity.}, } @article {pmid39592752, year = {2024}, author = {Chatthanathon, P and Leelahavanichkul, A and Cheibchalard, T and Wilantho, A and Hirankarn, N and Somboonna, N}, title = {Author Correction: Comparative time-series analyses of gut microbiome profiles in genetically and chemically induced lupus-prone mice and the impacts of fecal transplantation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {29391}, doi = {10.1038/s41598-024-79960-5}, pmid = {39592752}, issn = {2045-2322}, } @article {pmid39592644, year = {2024}, author = {Hunthai, S and Usawachintachit, M and Taweevisit, M and Srisa-Art, M and Anegkamol, W and Tosukhowong, P and Rattanachaisit, P and Chuaypen, N and Dissayabutra, T}, title = {Publisher Correction: Unraveling the role of gut microbiota by fecal microbiota transplantation in rat model of kidney stone disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {29360}, doi = {10.1038/s41598-024-78864-8}, pmid = {39592644}, issn = {2045-2322}, } @article {pmid39592438, year = {2024}, author = {Zhang, S and Wen, H and Chen, Y and Ning, J and Hu, D and Dong, Y and Yao, C and Yuan, B and Yang, S}, title = {Crosstalk between gut microbiota and tumor: tumors could cause gut dysbiosis and metabolic imbalance.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13763}, pmid = {39592438}, issn = {1878-0261}, support = {82303747//National Natural Science Foundation of China/ ; 2020GXLH-Y-010//Key Research and Development Projects of Shaanxi Province/ ; 2022JM-509//Natural Science Basic Research Program of Shaanxi Province/ ; }, abstract = {Gut microbiota has a proven link with the development and treatment of cancer. However, the causality between gut microbiota and cancer development is still unknown and deserves exploration. In this study, we aimed to explore the alterations in gut microbiota in murine tumor models and the crosstalk between the tumor and the gut microbiota. The subcutaneous and intravenous murine tumor models using both the colorectal cancer cell line MC38 and lung cancer cell line LLC were constructed. Then fecal samples before and after tumor inoculation were collected for whole metagenomics sequencing. Both subcutaneous and metastatic tumors markedly elevated the α-diversity of the gut microbiota. Relative abundance of Ligilactobacillus and Lactobacillus was reduced after subcutaneously inoculating tumor cells, whereas Bacteroides and Duncaniella were reduced in metastatic tumors, regardless of tumor type. At the species level, Lachnospiraceae bacterium was enriched after both subcutaneous and intravenous tumors inoculation, whereas levels of Muribaculaceae bacterium Isolate-110 (HZI), Ligilactobacillus murinus and Bacteroides acidifaciens reduced. Metabolic function analysis showed that the reductive pentose phosphate cycle, urea cycle, ketone body biosynthesis, ectoine biosynthesis, C4-dicarboxylic acid cycle, isoleucine biosynthesis, inosine 5'-monophosphate (IMP), and uridine 5'-monophosphate (UMP) biosynthesis were elevated after tumor inoculation, whereas the cofactor and vitamin biosynthesis were deficient. Principal coordinates analysis (PCoA) showed that subcutaneous and metastatic tumors partially shared the same effect patterns on gut microbiota. Furthermore, fecal microbiota transplantation revealed that this altered microbiota could influence tumor growth. Taken together, this study demonstrated that both colorectal cancer (MC38) and non-colorectal cancer (LLC) can cause gut dysbiosis and metabolic imbalance, regardless of tumor type and process of tumor inoculation, and this dysbiosis influenced the tumor growth. This research gives novel insights into the crosstalk between tumors and the gut microbiota.}, } @article {pmid39591377, year = {2024}, author = {Tafader, A and Bajaj, JS}, title = {Present and future of fecal microbiome transplantation in cirrhosis.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {}, number = {}, pages = {}, doi = {10.1097/LVT.0000000000000542}, pmid = {39591377}, issn = {1527-6473}, abstract = {Over the last few decades, there have been tremendous advances in our understanding of the role of the gut microbiome in cirrhosis and the clinical sequelae that follows. Progressive dysbiosis and immune dysregulation occurs in patients with cirrhosis. In fact, alterations in the gut microbiome occur long before a diagnosis of cirrhosis is made. Understandably, our attention has recently been diverted towards potential modulators of the gut microbiome and the gut-liver axis as targets for treatment. The goal of this review is to highlight the utility of manipulating the gut microbiome with a focus on fecal microbiome transplantation (FMT) in patients with cirrhosis. In addition, we will provide an overview of disease-specific microbial alterations and the resultant impact this has on cirrhosis-related complications.}, } @article {pmid39590350, year = {2024}, author = {Chen, Z and Liao, Y and Chai, S and Yang, Y and Ga, Q and Ge, R and Wang, S and Liu, S}, title = {Modification of Intestinal Flora Can Improve Host Metabolism and Alleviate the Damage Caused by Chronic Hypoxia.}, journal = {Current issues in molecular biology}, volume = {46}, number = {11}, pages = {12733-12745}, pmid = {39590350}, issn = {1467-3045}, support = {[2130122.1779.36]//Qinghai Province Cattle Industry Science and Technology Innovation Platform under Grant/ ; }, abstract = {Prolonged exposure to hypoxic conditions can lead to reduced appetite, stunted growth, systemic inflammation, and pulmonary hypertension. Previous studies have indicated a correlation between gut dysbiosis and the development of hypoxia-related hazards. We designed an experiment to investigate the effect of microbiota on mitigating hypoxic damage. Gut microbiota from high-altitude-adapted species (Ochotona curzoniae) were transplanted into Sprague Dawley (SD) rats, which were then housed in a simulated 6000 m altitude environment for 30 days. After the experiment, we conducted analyses on average daily weight gain (ADG), feed conversion ratio (FCR), mean pulmonary artery pressure (mPAP), gut flora, and fecal metabolism. The results demonstrated that the ADG in the transplantation group (2.98 ± 0.17 g) was significantly higher than in the control groups (2.68 ± 0.19 g and 2.26 ± 0.13 g) (p < 0.05). The FCR was reduced in the transplantation group (6.30 ± 0.33 g) compared to the control groups (8.20 ± 1.15 g and 8.83 ± 0.45 g) (p < 0.05). The mPAP was decreased in the transplantation group (38.1 ± 1.13 mmHg) compared to the control groups (43.4 ± 1.30 mmHg and 43.5 ± 1.22 mmHg) (p < 0.05). Multi-omics analysis revealed that Lachnospiraceae, Desulfovibrionaceae, and specific amino acid metabolic pathways play crucial roles in hypoxia and are associated with both inflammation and nutritional metabolism. This study proposes a novel approach to the treatment of hypoxic pulmonary hypertension and holds potential significance for improving high-altitude developmental potential.}, } @article {pmid39589553, year = {2025}, author = {Kellogg, TD and Ceglia, S and Mortzfeld, BM and Tanna, TM and Zeamer, AL and Mancini, MR and Foley, SE and Ward, DV and Bhattarai, SK and McCormick, BA and Reboldi, A and Bucci, V}, title = {Succinate-producing microbiota drives tuft cell hyperplasia to protect against Clostridioides difficile.}, journal = {The Journal of experimental medicine}, volume = {222}, number = {1}, pages = {}, doi = {10.1084/jem.20232055}, pmid = {39589553}, issn = {1540-9538}, support = {PRMP W81XWH2020013//Congressionally Directed Medical Research Programs/ ; /GATES/Bill & Melinda Gates Foundation/United States ; U01AI172987/NH/NIH HHS/United States ; //Kenneth Rainin Foundation/ ; //American Association of Immunologists/ ; //Charles A. King Trust/ ; }, mesh = {Animals ; *Clostridioides difficile ; Mice ; *Succinic Acid/metabolism ; *Hyperplasia ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/pharmacology ; Colon/microbiology/pathology/metabolism ; Mice, Knockout ; Cytokines/metabolism ; Tuft Cells ; }, abstract = {The role of microbes and their metabolites in modulating tuft cell (TC) dynamics in the large intestine and the relevance of this pathway to infections is unknown. Here, we uncover that microbiome-driven colonic TC hyperplasia protects against Clostridioides difficile infection. Using selective antibiotics, we demonstrate increased type 2 cytokines and TC hyperplasia in the colon but not in the ileum. We demonstrate the causal role of the microbiome in modulating this phenotype using fecal matter transplantation and administration of consortia of succinate-producing bacteria. Administration of succinate production-deficient microbes shows a reduced response in a Pou2f3-dependent manner despite similar intestinal colonization. Finally, antibiotic-treated mice prophylactically administered with succinate-producing bacteria show increased protection against C. difficile-induced morbidity and mortality. This effect is nullified in Pou2f3-/- mice, confirming that the protection occurs via the TC pathway. We propose that activation of TCs by the microbiota in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by pathogens.}, } @article {pmid39589476, year = {2024}, author = {Ma, G and Chen, Z and Li, Z and Xiao, X}, title = {Unveiling the neonatal gut microbiota: exploring the influence of delivery mode on early microbial colonization and intervention strategies.}, journal = {Archives of gynecology and obstetrics}, volume = {}, number = {}, pages = {}, pmid = {39589476}, issn = {1432-0711}, support = {No. 81771664//National Natural Science Foundation of China/ ; }, abstract = {Recent research has emphasized the critical importance of establishing the neonatal gut microbiota for overall health and immune system development, prompting deeper studies about the early formation of neonatal gut microbiota and its influencing factors. Various factors, including maternal and environmental factors, affect the early formation of neonatal gut microbiota, in which delivery mode has been considered as one of the most crucial influencing factors. In recent years, the increasing trend of cesarean section during childbirth has become a serious challenge for global public health. This review thoroughly analyzes the effects of vaginal delivery and cesarean section on the establishment of neonatal gut microbiota and the potential long-term impacts. In addition, we analyze and discuss interventions such as probiotics, prebiotics, vaginal seeding, fecal microbiota transplantation, and breastfeeding to address the colonization defects of the neonatal gut microbiota caused by cesarean section, aiming to provide theoretical basis for the prevention and treatment of colonization defects and related diseases in infants caused by cesarean section in clinical practice and to provide a theoretical foundation for optimizing the development of neonatal gut microbiota.}, } @article {pmid39589434, year = {2024}, author = {Liu, L and Zhu, JW and Wu, JL and Li, MZ and Lu, ML and Yu, Y and Pan, L}, title = {Insomnia and intestinal microbiota: a narrative review.}, journal = {Sleep & breathing = Schlaf & Atmung}, volume = {29}, number = {1}, pages = {10}, pmid = {39589434}, issn = {1522-1709}, support = {No. ZR2021MH360//Natural Science Foundation of Shandong Province/ ; No. 82370092//National Natural Science Foundation of China/ ; No. 2023SHFZ033//Science and Technology Innovation Project of Binzhou Social Development/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Sleep Initiation and Maintenance Disorders/therapy/physiopathology/microbiology ; Fecal Microbiota Transplantation ; Brain-Gut Axis/physiology ; Probiotics/therapeutic use ; }, abstract = {PURPOSE: The intestinal microbiota and insomnia interact through the microbiota-gut-brain axis. The purpose of this review is to summarize and analyze the changes of intestinal microbiota in insomnia, the interaction mechanisms between intestinal microbiota and insomnia and the treatment methods based on the role of microbiota regulation in insomnia, in order to reveal the feasibility of artificial intervention of intestinal microbiota to improve insomnia.

METHODS: Pubmed/ Embase were searched through March 2024 to explore the relevant studies, which included the gut microbiota characteristics of insomnia patients, the mechanisms of interaction between insomnia and gut microbiota, and the relationship between gut microbiota and insomnia treatment.

RESULTS: Numerous studies implicated insomnia could induce intestinal microbiota disorder by activating the immune response, the hypothalamic-pituitary-adrenal axis, the neuroendocrine system, and affecting bacterial metabolites, resulting in intestinal ecological imbalance, intestinal barrier destruction and increased permeability. The intestinal microbiota exerted an influence on the central nervous system through its interactions with intestinal neurons, releasing neurotransmitters and inflammatory factors, which in turn, can exacerbate symptoms of insomnia. Artificial interventions of gut microbiota included probiotics, traditional Chinese medicine, fecal microbiota transplantation, diet and exercise, whose main pathway of action is to improve sleep by affecting the release of neurotransmitters and gut microbial metabolites.

CONCLUSION: There is an interaction between insomnia and gut microbiota, and it is feasible to diagnose and treat insomnia by focusing on changes in the gut microbiota of patients with insomnia. Large cross-sectional studies and fecal transplant microbiota studies are still needed in the future to validate its safety and efficacy.}, } @article {pmid39588934, year = {2024}, author = {Gil-Gómez, A and Muñoz-Hernández, R and Martínez, F and Jiménez, F and Romero-Gómez, M}, title = {Hepatic encephalopathy: experimental drugs in development and therapeutic potential.}, journal = {Expert opinion on investigational drugs}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/13543784.2024.2434053}, pmid = {39588934}, issn = {1744-7658}, abstract = {INTRODUCTION: Hepatic encephalopathy (HE) presents a complex pathophysiology, creating multiple potential treatment avenues. This review covers current and emerging treatments for HE.

AREAS COVERED: Standard therapies, including non-absorbable disaccharides and rifaximin, are widely used but show inconsistent efficacy. Alternatives such as polyethylene glycol and L-ornithine L-aspartate have been effective in certain cases. Advancements in understanding HE reveal a growing need for personalized treatments. Novel approaches targeting immune modulation and neuroinflammation are under investigation, though clinical translation is slow. Nutritional interventions and fecal microbiota transplantation show potential but lack robust evidence. Innovative therapies like gene and cell therapies, as well as extracellular vesicles from mesenchymal stem cells, present promising avenues for liver disease treatment, potentially benefiting HE.

EXPERT OPINION: A key challenge in HE research is the design of randomized clinical trials, which often suffer from small sample sizes, heterogeneity in patient population, and inconsistent blinding. Additionally, the multifactorial nature of HE, together with a high spontaneous response rate, complicates efforts to isolate treatment effects. Despite current limitations, ongoing research and technological advances hold promise for more effective and individualized HE treatments in the future.}, } @article {pmid39588716, year = {2024}, author = {Tiwari, A and Ika Krisnawati, D and Susilowati, E and Mutalik, C and Kuo, TR}, title = {Next-Generation Probiotics and Chronic Diseases: A Review of Current Research and Future Directions.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c08702}, pmid = {39588716}, issn = {1520-5118}, abstract = {The burgeoning field of microbiome research has profoundly reshaped our comprehension of human health, particularly highlighting the potential of probiotics and fecal microbiota transplantation (FMT) as therapeutic interventions. While the benefits of traditional probiotics are well-recognized, the efficacy and mechanisms remain ambiguous, and FMT's long-term effects are still being investigated. Recent advancements in high-throughput sequencing have identified gut microbes with significant health benefits, paving the way for next-generation probiotics (NGPs). These NGPs, engineered through synthetic biology and bioinformatics, are designed to address specific disease states with enhanced stability and viability. This review synthesizes current research on NGP stability, challenges in delivery, and their applications in preventing and treating chronic diseases such as diabetes, obesity, and cardiovascular diseases. We explore the physiological characteristics, safety profiles, and mechanisms of action of various NGP strains while also addressing the challenges and opportunities presented by their integration into clinical practice. The potential of NGPs to revolutionize microbiome-based therapies and improve clinical outcomes is immense, underscoring the need for further research to optimize their efficacy and ensure their safety.}, } @article {pmid39588509, year = {2024}, author = {Zhang, A and Chen, S and Zhu, Y and Wu, M and Lu, B and Zhou, X and Zhu, Y and Xu, X and Liu, H and Zhu, F and Lin, R}, title = {Intestinal microbiome changes and mechanisms of maintenance hemodialysis patients with constipation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1495364}, pmid = {39588509}, issn = {2235-2988}, mesh = {Humans ; *Constipation/microbiology ; *Gastrointestinal Microbiome ; *Renal Dialysis ; *Feces/microbiology ; Male ; *RNA, Ribosomal, 16S/genetics ; Middle Aged ; Female ; *Bacteria/classification/isolation & purification/genetics ; Aged ; Adult ; }, abstract = {BACKGROUND: Constipation is a common symptom in maintenance hemodialysis patients and greatly affects the quality of survival of hemodialysis patients. Fecal microbiota transplantation and probiotics are feasible treatments for functional constipation, but there is still a gap in the research on the characteristics of gut flora in patients with maintenance hemodialysis combined with constipation. The aim of this study is to clarify the characteristics of the intestinal flora and its changes in maintenance hemodialysis patients with constipation.

METHODS: Fecal samples were collected from 45 participants, containing 15 in the maintenance hemodialysis constipation group,15 in the maintenance hemodialysis non-constipation group and 15 in the healthy control group. These samples were analyzed using 16S rRNA gene sequencing. The feature of the intestinal microbiome of maintenance hemodialysis constipation group and the microbiome differences among the three groups were elucidated by species annotation analysis, α-diversity analysis, β-diversity analysis, species difference analysis, and predictive functional analysis.

RESULTS: The alpha diversity analysis indicated that maintenance hemodialysis constipation group was less diverse and homogeneous than maintenance hemodialysis non-constipation group and healthy control group. At the genus level, the top ten dominant genera in maintenance hemodialysis constipation group patients were Enterococcus, Escherichia-Shigella, Bacteroides, Streptococcus, Bifidobacterium, Ruminococcus_gnavus_group, Lachnospiraceae_unclassified, Faecalibacterium, Akkermansia and UCG-002. Compared with non-constipation group, the Enterococcus, Rhizobiales_unclassified, Filomicrobium, Eggerthella, Allobaculum, Prevotella_7, Gordonibacter, Mitochondria_unclassified, Lachnoanaerobaculum were significantly higher in constipation group (p<0.05). Compared with non-constipation group, the Kineothrix, Rhodopirellula, Weissella were significantly lower in constipation group (p<0.05). The predictive functional analysis revealed that compared with non-constipation group, constipation group was significantly enriched in pathways associated with pyruate metabolism, flavonoid biosynthesis.

CONCLUSIONS: This study describes for the first time the intestinal microbiome characteristics of maintenance hemodialysis patients with constipation. The results of this study suggest that there is a difference in the intestinal flora between maintenance hemodialysis patients with constipation and maintenance hemodialysis patients without constipation.}, } @article {pmid39588438, year = {2024}, author = {Dandamudi, BJ and Dimaano, KAM and Shah, N and AlQassab, O and Al-Sulaitti, Z and Nelakuditi, B and Mohammed, L}, title = {Neurodegenerative Disorders and the Gut-Microbiome-Brain Axis: A Literature Review.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72427}, pmid = {39588438}, issn = {2168-8184}, abstract = {Neurodegenerative diseases are severe, age-related conditions with complex etiologies that result in significant morbidity and mortality. The gut microbiome, a dynamic symbiotic environment comprising commensal organisms, represents the largest reservoir of these organisms within the human body. It produces short-chain fatty acids, endogenous signals, and neuroactive compounds, which can modulate neuronal function, plasticity, and behavior. Emerging evidence suggests that the gut microbiome plays a pivotal role in neurodevelopment, aging, and brain diseases, including Alzheimer's disease, Parkinson's disease, and stroke. Communication between the gut and brain occurs through a bidirectional channel known as the gut-microbiome-brain axis, which is being explored for therapeutic potential in neurodegenerative disorders. This literature review was conducted through a comprehensive search of five electronic databases - PubMed, Scopus, Ovid Medline, Cochrane Review, and Google Scholar - from inception to June 2024, focusing on English-language studies. Keywords included "gut-brain axis", "microbiome dysbiosis", "neurodegeneration", and disorder-specific terms such as "Alzheimer's disease" and "Parkinson's disease", paired with "gut microbiome". The review examines current knowledge on the relationship between gut microbiota and neurodegenerative disorders, emphasizing potential mechanisms and therapeutic options. Results indicate that gut dysbiosis, characterized by microbial imbalance, is intricately associated with neurodegenerative disease pathogenesis by influencing immune responses, increasing blood-brain barrier permeability, and generating neurotoxic metabolites. Therapeutic approaches targeting the gut microbiome, including probiotics, prebiotics, and fecal microbiota transplantation, show promise in restoring microbial balance and slowing disease progression. However, further research is essential to validate these findings and develop effective clinical interventions.}, } @article {pmid39587707, year = {2024}, author = {Ilozumba, MN and Lin, T and Hardikar, S and Byrd, DA and Round, JL and Stephens, WZ and Holowatyj, AN and Warby, CA and Damerell, V and Li, CI and Figueiredo, JC and Toriola, AT and Shibata, D and Fillmore, GC and Pickron, B and Siegel, EM and Kahlert, C and Florou, V and Gigic, B and Ose, J and Ulrich, CM}, title = {Fusobacterium nucleatum Abundance is Associated with Cachexia in Colorectal Cancer Patients: The ColoCare Study.}, journal = {Cancer medicine}, volume = {13}, number = {22}, pages = {e70431}, pmid = {39587707}, issn = {2045-7634}, support = {//the German Ministry of Education and Research project PerMiCCion (01KD2101D)/ ; //German Cancer Research Center/ ; //the German Consortium of Translational Cancer Research, (DKTK)/ ; R01 CA189184/CA/NCI NIH HHS/United States ; R01 CA207371/CA/NCI NIH HHS/United States ; R01 CA211705/CA/NCI NIH HHS/United States ; R01 CA254108/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; //University of Utah Immunology, Inflammation, and Infectious Disease Initiative/ ; //Huntsman Cancer Foundation/ ; //Stiftung LebensBlicke, Matthias Lackas Stiftung, Claussen-Simon Stiftung/ ; //the Rahel-Goitein-Straus-Program, Medical Faculty Heidelberg University/ ; //ERA-NET (European Research Area Network) on Translational Cancer Research (TRANSCAN) project/ ; //Cancer Control and Population Health Sciences (CCPS) at the University of Utah/ ; }, mesh = {Humans ; *Colorectal Neoplasms/complications/microbiology ; Male ; *Cachexia/etiology/microbiology ; *Fusobacterium nucleatum/isolation & purification ; Female ; Aged ; Middle Aged ; *Feces/microbiology ; Fusobacterium Infections/complications/microbiology ; Neoplasm Staging ; Risk Factors ; }, abstract = {BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and indicates poor prognosis. The impact of Fusobacterium nucleatum (Fn), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established.

METHODS: We evaluated the association between Fn abundance in pre-surgical stool samples and onset of cachexia at 6 months post-surgery in n = 87 patients with stages I-III CRC in the ColoCare Study.

RESULTS: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4-fold increased risk of cachexia onset at 6 months post-surgery (OR = 4.82, 95% CI = 1.15, 20.10, p = 0.03).

CONCLUSION: Our findings suggest that high fecal Fn abundance was associated with an increased risk of cachexia at 6 months post-surgery in CRC patients. This is the first study to link Fn abundance with cachexia in CRC patients, offering novel insights into biological mechanisms and potential management of cancer cachexia. Due to the small sample size, our results should be interpreted with caution. Future studies with larger sample sizes are needed to validate these findings.}, } @article {pmid39587339, year = {2024}, author = {Castells-Nobau, A and Puig, I and Motger-Albertí, A and de la Vega-Correa, L and Rosell-Díaz, M and Arnoriaga-Rodríguez, M and Escrichs, A and Garre-Olmo, J and Puig, J and Ramos, R and Ramió-Torrentà, L and Pérez-Brocal, V and Moya, A and Pamplona, R and Jové, M and Sol, J and Martin-Garcia, E and Martinez-Garcia, M and Deco, G and Maldonado, R and Fernández-Real, JM and Mayneris-Perxachs, J}, title = {Microviridae bacteriophages influence behavioural hallmarks of food addiction via tryptophan and tyrosine signalling pathways.}, journal = {Nature metabolism}, volume = {6}, number = {11}, pages = {2157-2186}, pmid = {39587339}, issn = {2522-5812}, support = {PI15/01934//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; CD20/00051//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; RD16/0017/0020//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; PI20/01090//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; CP18/00009//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; PI23/00575//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; SLT017_20_000164//Generalitat de Catalunya (Government of Catalonia)/ ; 2021SGR00990//Generalitat de Catalunya (Government of Catalonia)/ ; 2017 SGR-669//Generalitat de Catalunya (Government of Catalonia)/ ; SLT002/16/00250//Government of Catalonia | Departament de Salut, Generalitat de Catalunya/ ; LCF/PR/HR22/52420017//"la Caixa" Foundation (Caixa Foundation)/ ; PNSD- 2019I006//Ministerio de Sanidad, Servicios Sociales e Igualdad (Ministry of Health, Social Services and Equality)/ ; PNSD- 2021I076//Ministerio de Sanidad, Servicios Sociales e Igualdad (Ministry of Health, Social Services and Equality)/ ; }, abstract = {Food addiction contributes to the obesity pandemic, but the connection between how the gut microbiome is linked to food addiction remains largely unclear. Here we show that Microviridae bacteriophages, particularly Gokushovirus WZ-2015a, are associated with food addiction and obesity across multiple human cohorts. Further analyses reveal that food addiction and Gokushovirus are linked to serotonin and dopamine metabolism. Mice receiving faecal microbiota and viral transplantation from human donors with the highest Gokushovirus load exhibit increased food addiction along with changes in tryptophan, serotonin and dopamine metabolism in different regions of the brain, together with alterations in dopamine receptors. Mechanistically, targeted tryptophan analysis shows lower anthranilic acid (AA) concentrations associated with Gokushovirus. AA supplementation in mice decreases food addiction and alters pathways related to the cycle of neurotransmitter synthesis release. In Drosophila, AA regulates feeding behaviour and addiction-like ethanol preference. In summary, this study proposes that bacteriophages in the gut microbiome contribute to regulating food addiction by modulating tryptophan and tyrosine metabolism.}, } @article {pmid39586550, year = {2024}, author = {Novelle, MG and Naranjo, B and López-Cánovas, JL and Díaz-Ruiz, A}, title = {Fecal Microbiota Transplantation, a tool to transfer healthy longevity.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {102585}, doi = {10.1016/j.arr.2024.102585}, pmid = {39586550}, issn = {1872-9649}, abstract = {The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors via standard - lifestyle and pharmacological - antiaging interventions reshape gut microbiome, with the resulting benefits being also FMT-transferable. Finally, we expose the current clinical uses of FMT in the context of aging therapy and address FMT challenges - regulatory landscape, protocol standardization, and health risks - that require refinement to effectively utilize microbiome interventions in the elderly.}, } @article {pmid39586125, year = {2024}, author = {Ye, H and Wang, H and Han, B and Chen, K and Wang, X and Ma, F and Cheng, L and Zheng, S and Zhao, X and Zhu, J and Li, J and Hong, M}, title = {Guizhi Shaoyao Zhimu decoction inhibits neutrophil extracellular traps formation to relieve rheumatoid arthritis via gut microbial outer membrane vesicles.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {136}, number = {}, pages = {156254}, doi = {10.1016/j.phymed.2024.156254}, pmid = {39586125}, issn = {1618-095X}, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with a high disability rate. Accumulating studies suggest that neutrophil extracellular traps (NETs) play a crucial role in the pathogenesis of RA and targeting NETs has emerged as a potential therapeutic strategy for RA. As a traditional Chinese medicine, Guizhi-Shaoyao-Zhimu Decoction (GSZD) has exhibited good efficacy in the treatment of rheumatoid arthritis (RA), while the underly mechanism especially the possibility that GSZD alter NETs formation to relieve RA remains unknown.

PURPOSE: Our study aimed to investigate relationship between GSZD and NETs in RA treatment and revealed underlying mechanism.

METHODS: We constructed collagen-induced arthritis (CIA) model and treated CIA mice with GZSY to validate therapeutic effects of GSZD and examine whether GZSD could inhibit NETs formation in RA. And 16S rRNA sequencing and Fecal microbiota transplantation (FMT) experiment were performed to determine whether GSZD could reduce NETs formation to alleviate RA in gut microbiota-associated manner and identify crucial bacterium in response to GSZD administration. CIA mice treated with effective bacteria and its outer membrane vesicles (OMVs) with oral administration to investigate protective effect against RA and NETs regulative efficiency. We utilized small interfering RNA in vivo and vitro to silence gene mediating effect of GZSD-gut microbiota-NETs.

RESULTS: GSZD could inhibit NETs formation and relive arthritis in CIA mice. Additionally, GSZD alter gut microbiota composition and significantly increase intestinal Parabacteroides goldsteinii (P.goldsteinii) abundance. Mechanistically, P.goldsteinii enriched by GSZD secreted outer membrane vesicles (OMVs) to translocate into joints and activate Cav-1-Nrf2 axis, leading to reduced NETs formation and alleviate arthritis. In clinical, the abundance of P.goldsteinii exhibited negative correlation with NETs indexes and RA disease activities.

CONCLUSION: Our findings suggest that GSZD inhibits NETs formation to relieve RA in P.goldsteinii-Cav-1-Nrf2 associated manner, which could provide new sight of the prevention and treatment of RA.}, } @article {pmid39583974, year = {2024}, author = {Naito, Y and Takagi, T}, title = {Role of gut microbiota in inflammatory bowel disease pathogenesis.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {75}, number = {3}, pages = {175-177}, pmid = {39583974}, issn = {0912-0009}, abstract = {The role of the gut microbiota, especially bacterial flora, in the pathogenesis of inflammatory bowel disease (IBD) is becoming clearer. Advances in gut microbiota analysis and the use of gnotobiotics models have underscored the importance of gut bacteria and their metabolites in the progression of IBD. Fecal microbiota transplantation has shown promise in clinical trials for ulcerative colitis started as Advanced Medical Care B in Japan, raising expectations for its outcomes. This review explores the gut microbiota's role in IBD, encompassing both current knowledge and future prospects.}, } @article {pmid39582897, year = {2024}, author = {Wang, Z and Wu, X and Wang, Y and Wen, Q and Cui, B and Zhang, F}, title = {Colonic transendoscopic enteral tubing is revolutionizing intestinal therapeutics, diagnosis, and microbiome research.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241301574}, pmid = {39582897}, issn = {1756-283X}, abstract = {The intestine, as a crucial organ of the human body, has remained enigmatic despite the remarkable advancements in modern medical technology. Over the past decades, the invention of endoscopic technology has made the noninvasive intervention of the intestine a reality, expanding diagnostic and therapeutic options for diseases. However, due to the single-treatment feature of endoscopic procedures, continuous or repeated medication administration, sampling, and decompression drainage within the intestine have yet to be fulfilled. These limitations persisted until the invention of colonic transendoscopic enteral tubing (TET) in 2014, which realized repeated fecal microbiota transplantation, medication administration, and decompression drainage for the treatment of colon perforation and intestinal obstruction, as well as in situ dynamic sampling. These breakthroughs have not gone unnoticed, gaining global attention and recommendations from guidelines and consensuses. TET has emerged as a novel microbial research tool that offers new paradigms for human microbiome research. This review aims to update the research progress based on TET.}, } @article {pmid39581510, year = {2024}, author = {Zhang, X and Klöhn, M and Ouwerkerk-Mahadevan, S and Jagst, M and Vereyken, L and Verboven, P and Goovaerts, Q and Todt, D and Jonckers, THM and Coelmont, L and Fletcher, H and Das, K and Samby, K and Neyts, J and Steinmann, E and Koul, A and Kaptein, SJF}, title = {A pan-genotypic hepatitis E virus replication inhibitor with high potency in a rat infection model.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.10.043}, pmid = {39581510}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Hepatitis E virus (HEV) constitutes a substantial public health burden with ∼20 million human infections annually, including 3.3 million symptomatic cases. Appropriate treatment options for, in particular, HEV-infected immunocompromised patients and pregnant women are lacking, underscoring the urgent need for potent and safe antiviral drugs.

METHODS: HEV subgenomic replicon systems were used to screen a small library of pre-selected nucleoside analogues, originally developed in a hepatitis C virus (HCV) antiviral program. Antiviral activity of the selected hit on HEV infection was evaluated in a variety of cell culture systems; the efficacy of the compound was assessed in the athymic nude rat HEV infection model.

RESULTS: Compound JNJ-9117 exerts pan-genotype antiviral activity against HEV in different cell types as well as in primary human hepatocytes. A high level of conservation is observed between three crucial motifs in the catalytic domain of the HCV and HEV polymerases. This suggests a mechanism of action that is identical to that of the molecule against HCV, whereby the 5'-triphosphate of JNJ-9117 acts as a chain terminator during viral RNA synthesis. JNJ-9117 has a favorable pharmacokinetic and safety profile in rats and results in a pronounced antiviral effect in a chronic rat HEV infection model, both in a prophylactic and therapeutic setting. The combination of JNJ-9117 and ribavirin (each at an intentionally selected suboptimal/inactive dose) was in infected rats highly effective in lowering viral RNA load in liver and feces to (almost) undetectable levels.

CONCLUSIONS: JNJ-9117 has a profile that holds promise for the treatment of life-threatening HEV infections in humans. Phase 1 studies with JNJ-9117 have been initiated in healthy human volunteers.}, } @article {pmid39581509, year = {2024}, author = {Chen, S and Wen, Q and Zhang, F}, title = {An Unusual Cause of Diarrhea and Hematochezia.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.11.007}, pmid = {39581509}, issn = {1528-0012}, } @article {pmid39580105, year = {2024}, author = {Fülöpová, N and Brückner, K and Muselík, J and Pavloková, S and Franc, A}, title = {Development and evaluation of innovative enteric-coated capsules for colon-specific delivery of hydrophilic biomaterials.}, journal = {International journal of pharmaceutics}, volume = {}, number = {}, pages = {124991}, doi = {10.1016/j.ijpharm.2024.124991}, pmid = {39580105}, issn = {1873-3476}, abstract = {OBJECTIVE: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract.

METHODS: Hard gelatin capsules and DRcaps[TM]capsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit® E, and polyvinyl acetate) and external (Eudragit® S, Acryl-EZE®, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms.

RESULTS: Combining suitable internal (ethylcellulose 1.0 %) and external (Eudragit® S 20.0 %) coating of DRcaps[TM] capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720 min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480 min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields.

CONCLUSION: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery.}, } @article {pmid39579562, year = {2024}, author = {Yang, Y and Wu, R and Qian, C and Wu, D and Ou, J}, title = {Mume fructus alters the abundance of intestinal microbiota and alleviates damaged intestinal barrier and inflammation in rats with DSS induced colitis.}, journal = {Molecular immunology}, volume = {176}, number = {}, pages = {60-72}, doi = {10.1016/j.molimm.2024.11.008}, pmid = {39579562}, issn = {1872-9142}, abstract = {The gut microbiota plays a crucial role in the development of colitis by influencing the immune response and inflammation in the colon. Previous research has shown that Mume Fructus, a traditional Chinese medicine, can alleviate colitis by reducing the activity of inflammatory pathways. However, the specific connection between Mume Fructus-treated colitis and regulation of gut flora remains unclear, prompting further investigation. This research aims to delve deeper into the possible impact of the gut microbiota in colitis when treated with the aqueous decoction of Mume Fructus (MF). The effects of MF on rats with DSS-induced colitis were assessed through examination of pathological indicators, intestinal barrier proteins, and analysis of 16S rDNA sequencing to investigate its impact on the gut microbiota. In addition, the colon contents of rats after the administration of MF were transplanted into rats with colitis, and the effect of MF on intestinal flora was verified, and "beneficial bacteria" were identified by 16S rDNA sequencing and Spearman's correlation analysis. In summary, our findings suggest that MF has the potential to ameliorate symptoms of colitis through modulation of intestinal microbiota and restoration of intestinal barrier function.}, } @article {pmid39574673, year = {2024}, author = {Wolfe, TM and Jo, J and Pinkham, NV and Garey, KW and Walk, ST}, title = {Microbiome impact of ibezapolstat and other Clostridioides difficile infection relevant antibiotics using humanized mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.06.622322}, pmid = {39574673}, issn = {2692-8205}, abstract = {BACKGROUND: Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for treatment of Clostridioides difficile infection (CDI). Previous studies demonstrated IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics.

METHODS: Groups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare gut microbiome perturbation between treatment and no-drug control groups.

RESULTS: Among the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversity following FDX- and IBZ-treated groups were less pronounced compared to those observed in VAN-or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of Bacteroidota (phylum), with IBZ additionally increasing the relative abundance of Actinomycetota (phylum).

CONCLUSION: In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity compared to VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.}, } @article {pmid39574251, year = {2024}, author = {Shen, CL and Deshmukh, H and Santos, JM and Elmassry, MM and Presto, P and Driver, Z and Bhakta, V and Yakhnitsa, V and Kiritoshi, T and Ji, G and Lovett, J and Hamood, A and Neugebauer, V}, title = {Fecal Microbiota Transplantation Modulates Gut Microbiome Composition and Glial Signaling in Brain and Colon of Rats with Neuropathic Pain: Evidence for Microbiota-Gut-Brain Axis.}, journal = {The Journal of frailty & aging}, volume = {13}, number = {4}, pages = {319-330}, doi = {10.14283/jfa.2024.65}, pmid = {39574251}, issn = {2260-1341}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Neuralgia/therapy/microbiology/metabolism ; Rats ; Male ; *Brain-Gut Axis/physiology ; Neuroglia/metabolism ; Colon/microbiology ; Brain/metabolism ; Rats, Sprague-Dawley ; Disease Models, Animal ; Signal Transduction ; }, abstract = {Despite evidence linking the gut microbiome to neuropathic pain (NP), it is not known if altering gut microbiota can alleviate NP via the microbiome-gut-brain axis. This study examined if healthy gut microbiota of sham male rats (Sham+V) and dysbiotic gut microbiota of NP rats (spinal nerve ligation: NP, SNL+V) can be disrupted and restored, respectively, via fecal microbiota transplant (FMT) from the opposite group [Sham+(SNL-FMT) and SNL+(Sham-FMT), respectively]. All groups received FMT daily for two weeks, followed by three weeks without FMT. SNL rats showed higher mechanical hypersensitivity [SNL+V vs. Sham+V] throughout the study. After two weeks, the FMT of healthy gut microbiota decreased mechanical hypersensitivity in SNL rats [SNL+(Sham-FMT) vs. SNL+V]. A temporal shift in microbiome profiles after 2-week FMT treatment was observed in Sham+(SNL-FMT) and SNL+(Sham-FMT) groups, while the microbiome profile shifted back a certain extent after FMT ceased. At the end of study, the Sham+(SNL-FMT) group acquired low abundance of UCG-001, Odoribacter, and Peptococcaceae, and high abundance of UBA1819 and Victivallis. The SNL+(Sham-FMT) group maintained high abundance of Butyricimonas and Escherichia-Shigella. The SNL+(Sham-FMT) group had altered glial and macrophage activation/inflammation markers in the brain/colon than the SNL+V group. Relative to the SNL+V group, the SNL+(Sham-FMT) group had significantly lower gene expressions of GFAP (hypothalamus), IBA-1 (colon), and NF-κB (amygdala/colon), but higher gene expressions of complex I (amygdala/hypothalamus) and claudin-3 (amygdala/hypothalamus/colon). In conclusion, FMT containing healthy microbiota given to SNL rats attenuates mechanical hypersensitivity, modulates microbiota composition, and mitigates downstream glial activation/inflammation markers in a NP model.}, } @article {pmid39571844, year = {2024}, author = {Yu, L and Lin, F and Yu, Y and Deng, X and Shi, X and Lu, X and Lu, Y and Wang, D}, title = {Rehmannia glutinosa polysaccharides enhance intestinal immunity of mice through regulating the microbiota.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 3}, pages = {137878}, doi = {10.1016/j.ijbiomac.2024.137878}, pmid = {39571844}, issn = {1879-0003}, abstract = {The Rehmannia glutinosa polysaccharides (RGP) have various benefits such as enhancing immune cell activity, decreasing oxidative stress and delaying or inhibiting tumor occurrence. Although much research has been directed at understanding the role of RGP, its influence on gut immunity is largely understudied. Here, we aimed to dissect the immune-regulating effects of RGP in the mice intestines. In vivo experiments involving the oral administration of RGP to mice at dosages of 100, 200, and 400 mg/kg over seven consecutive days revealed that RGP therapy significantly increased the percentages of CD3[+] T lymphocytes and CD19[+] B lymphocytes in intestines and improved the integrity of the mucosal barrier. Moreover, RGP modified the gut microbiota composition by enhancing the abundance of beneficial bacteria like Lactobacillus and Akkermansia. Fecal microbiota transplantation (FMT) experiments further revealed that RGP modulated the host's intestinal immunological function by altering the gut microbiota composition. These findings indicate that RGP may control the immunological function of the intestines.}, } @article {pmid39571733, year = {2024}, author = {Yu, J and Feng, L and Luo, Z and Yang, J and Zhang, Q and Liu, C and Liang, D and Xie, Y and Li, H and Gong, J and He, Z and Lan, P}, title = {Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.11.024}, pmid = {39571733}, issn = {2090-1224}, abstract = {INTRODUCTION: The intricate interplay of interleukin-10 (IL-10) and gut microbiota influences tumor development and progression, yet the impacts on colorectal cancer (CRC) metastasis remain incompletely understood.

METHODS: The impact of Il10 deficiency on CRC metastasis was first evaluated in CRC metastasis tumor samples and mouse model. Antibiotic sterilization and fecal microbiota transplantation (FMT) experiment were used to assess the role of gut microbiota in IL-10 mediated CRC metastasis, and full-length 16S rDNA sequencing analysis further identified the potential target bacteria influencing CRC metastasis. The inhibitory effect of Parabacteroides distasonis (P. distasonis) on CRC metastasis was evaluated by oral administration in mice. Key metabolites involved in P. distasonis inhibition of CRC metastasis was identified by widely-targeted metabolome analysis and validated both in vivo and in vitro. The underlying mechanisms of P-hydroxyphenyl acetic acid (4-HPAA) inhibiting CRC metastasis was investigated via RNA-sequencing and validated in cellular experiments.

RESULTS: We revealed that serum IL-10 levels were markedly elevated in metastatic CRC patients compared to non-metastatic cases. In parallel, Il10-deficiency (Il10[-/]) in mice resulted in decreased CRC metastasis in a gut microbiota-dependent manner. Mechanistically, Il10[-/-] mice reshaped gut microbiota composition, notably enriching P. distasonis. The enriched P. distasonis produced 4-HPAA, which activated the aryl hydrocarbon receptor (AHR) and subsequently inhibited the expression of VEGFA, a typical oncogene, thereby sequentially suppressing CRC metastasis. Importantly, engineered bacteria capable of producing 4-HPAA effectively hindered CRC metastasis. Furthermore, AHR depletion significantly disrupted the 4-HPAA-induced reduction in CRC cell migration and the inhibition of metastasis in both in vitro and in vivo lung metastasis mouse models.

CONCLUSIONS: These findings demonstrate the significance of IL-10 deficiency in suppressing CRC metastasis through the 4-HPPA-AHR-VEGFA axis mediated by gut P. distasonis, suggesting that P. distasonis or 4-HPAA supplementation could offer a promising therapeutic strategy for CRC metastasis prevention.}, } @article {pmid39571265, year = {2024}, author = {Mansouri, P and Mansouri, P and Behmard, E and Najafipour, S and Kouhpayeh, A and Farjadfar, A}, title = {Novel targets for mucosal healing in inflammatory bowel disease therapy.}, journal = {International immunopharmacology}, volume = {144}, number = {}, pages = {113544}, doi = {10.1016/j.intimp.2024.113544}, pmid = {39571265}, issn = {1878-1705}, abstract = {Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal tract, primarily manifesting as ulcerative colitis (UC) or Crohn's disease (CD). Both inflammation and disruption of the intestinal epithelial barrier are key factors in IBD pathogenesis. Substantial evidence has revealed a significant association between aberrant immune responses and impairment of the intestinal epithelial barrier in IBD pathogenesis. The components of the intestinal epithelium, particularly goblet cells and Paneth cells, are crucial to gut homeostasis, as they secrete mucin, antimicrobial peptides (AMPs), and cytokines. Furthermore, impairment of epithelial integrity, which is regulated by tight junctions, is a hallmark of IBD pathology. While common treatments for IBD, such as anti-inflammatory drugs, target various signaling pathways with varying efficacies, therapeutic approaches focused on mucosal and epithelial barrier healing have been largely neglected. Moreover, high costs, side effects, and insufficient or inconsistent therapeutic outcomes remain major drawbacks of conventional anti-IBD drugs. Recent studies on epithelial barrier regeneration and permeability reduction have introduced promising therapeutic targets, including farnesoid X receptor (FXR), urokinase-type plasminogen activator (uPA)-urokinase-type plasminogen activator receptor (uPAR) interaction, fecal microbiota transplantation (FMT), and insulin receptor (INSR). Notably, the simultaneous targeting of intestinal inflammation and promotion of epithelial barrier healing shows promise for efficient IBD treatment. Future research should explore targeted therapies and combination treatments, including natural remedies, microbiota colonization, stem cell approaches, and computer-aided drug design. It is also crucial to focus on accurate prognosis and developing a thorough understanding of IBD development mechanisms.}, } @article {pmid39570086, year = {2024}, author = {Justice, J and Kankaria, RA and Johnson, DB}, title = {Immune checkpoint inhibition of metastatic melanoma: achieving high efficacy in the face of high toxicity.}, journal = {Expert review of clinical pharmacology}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/17512433.2024.2431513}, pmid = {39570086}, issn = {1751-2441}, abstract = {INTRODUCTION: Immune checkpoint inhibitors (ICIs) have advanced the treatment of metastatic melanoma by blocking immune system down-regulators enhancing T-cell-mediated anti-tumor responses. However, many ICIs induce immune-related adverse effects (irAEs) that can impact many organ systems.

AREAS COVERED: Strategies used to manage irAEs include corticosteroids, anti-tumor necrosis factor alpha (TNF-α) agents, other biological therapies, fecal microbiota transplantation (FMT), and emerging regimens. In this review, we describe current evidence for the efficacy of ICIs, acute and chronic immune toxicities, and strategies to manage toxicities for patients treated with ICIs.

EXPERT OPINION: IrAE management will likely evolve by developing more tailored approaches to prevent toxicities, improving non-steroidal management strategies and tailoring the dose of steroids, and identifying biomarkers of severe toxicities.}, } @article {pmid39569890, year = {2024}, author = {Jang, S and Yu, J and Park, S and Lim, H and Koh, H and Park, YR}, title = {Development of Time-Aggregated Machine Learning Model for Relapse Prediction in Pediatric Crohn's Disease.}, journal = {Clinical and translational gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ctg.0000000000000794}, pmid = {39569890}, issn = {2155-384X}, support = {//Ministry of Health and Welfare/ ; }, abstract = {INTRODUCTION: Pediatric Crohn's disease (CD) easily progresses to an active disease compared to adult CD, making it important to predict and minimize CD relapses. However, prediction of relapse at various time points (TPs) during pediatric CD remains understudied. We aimed to develop a real-time aggregated model to predict pediatric CD relapse in different TPs and time windows (TWs).

METHODS: This retrospective study was conducted on children diagnosed with CD between 2015 and 2022 at Severance Hospital. Laboratory test results and demographic data were collected starting at 3 months after diagnosis, and cohorts were formed using data from six different TPs at 1-month intervals. Relapse-defined as a pediatric CD activity index ≥30 points-was predicted, and TWs were 3-7 months with 1-month intervals. The feature importance of the variables in each setting was determined.

RESULTS: Data from 180 patients were used to construct cohorts corresponding to the TPs. We identified the optimal TP and TW to reliably predict pediatric CD relapse with an area under the receiver operating characteristic curve score of 0.89 when predicting with a 3-month TW at a 3-month TP. Variables such as C-reactive protein levels and lymphocyte fraction were found to be important factors.

DISCUSSION: We developed a time-aggregated model to predict pediatric CD relapse in multiple TPs and TWs. This model identified important variables that predicted relapse in pediatric CD to support real-time clinical decision making.}, } @article {pmid39568727, year = {2024}, author = {Alam, M and Abbas, K and Mustafa, M and Usmani, N and Habib, S}, title = {Microbiome-based therapies for Parkinson's disease.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1496616}, pmid = {39568727}, issn = {2296-861X}, abstract = {The human gut microbiome dysbiosis plays an important role in the pathogenesis of Parkinson's disease (PD). The bidirectional relationship between the enteric nervous system (ENS) and central nervous system (CNS) under the mediation of the gut-brain axis control the gastrointestinal functioning. This review article discusses key mechanisms by which modifications in the composition and function of the gut microbiota (GM) influence PD progression and motor control loss. Increased intestinal permeability, chronic inflammation, oxidative stress, α-synuclein aggregation, and neurotransmitter imbalances are some key factors that govern gastrointestinal pathology and PD progression. The bacterial taxa of the gut associated with PD development are discussed with emphasis on the enteric nervous system (ENS), as well as the impact of gut bacteria on dopamine production and levodopa metabolism. The pathophysiology and course of the disease are associated with several inflammatory markers, including TNF-α, IL-1β, and IL-6. Emerging therapeutic strategies targeting the gut microbiome include probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). The article explored how dietary changes may affect the gut microbiota (GM) and the ways that can affect Parkinson's disease (PD), with a focus on nutrition-based, Mediterranean, and ketogenic diets. This comprehensive review synthesizes current evidence on the role of the gut microbiome in PD pathogenesis and explores its potential as a therapeutic target. Understanding these complex interactions may assist in the development of novel diagnostic tools and treatment options for this neurodegenerative disorder.}, } @article {pmid39567117, year = {2025}, author = {Lu, X and Jing, Y and Zhang, N and Chen, L and Tai, J and Cao, Y}, title = {Structural characterization and anti-obesity effect of a novel water-soluble galactomannan isolated from Eurotium cristatum.}, journal = {Carbohydrate polymers}, volume = {348}, number = {Pt B}, pages = {122870}, doi = {10.1016/j.carbpol.2024.122870}, pmid = {39567117}, issn = {1879-1344}, mesh = {Animals ; *Galactose/analogs & derivatives ; *Mannans/chemistry/pharmacology/isolation & purification ; Mice ; *Anti-Obesity Agents/pharmacology/chemistry/isolation & purification ; *Obesity/drug therapy ; Male ; *Diet, High-Fat ; *Eurotium/chemistry ; *Solubility ; Gastrointestinal Microbiome/drug effects ; Water/chemistry ; Mice, Inbred C57BL ; }, abstract = {Obesity is a serious public health challenge worldwide, the present study is aimed to investigate the structural characteristic and anti-obesity effect of a water-soluble galactomannan (PEC) extracted from Eurotium cristatum (E. cristatum). Detailed analysis of the PEC structure showed a weight-average molecular weight of 32,305 Da and a composition of mainly mannose, galactose and small amounts of glucose. Nuclear magnetic resonance spectroscopy combined with methylation analysis indicated that the main chain of PEC is →5)-β-D-Galf-(1 → 6)-α-D-Manp-(1 → glycosidic bond, and the branched chain →2)-α-D-Manp-(1 → through →2,6)-α-D-Manp-(1 → is connected to the main chain by an O-2 bond. Furthermore, PEC was found to ameliorate body weight gain, metabolic disorders, and to modulate the gut microbiota in HFD-fed mice. Fecal microbiota transplantation trial confirmed that PEC prevented obesity development and metabolic disorders by reversing gut dysbiosis in HFD-fed mice. This is the first report of the isolation of PEC from E. cristatum, and the findings suggested that PEC exerted its antiobesity and related beneficial effects by regulating the gut microbiota. In conclusion, as a polysaccharide, PEC could reduce obesity by modulating the gut microbiota and has potential been a prophylactic agent for obesity and related metabolic diseases.}, } @article {pmid39566790, year = {2024}, author = {Liu, Z and Wang, M and Li, J and Liang, Y and Jiang, K and Hu, Y and Gong, W and Guo, X and Guo, Q and Zhu, B}, title = {Hizikia fusiforme polysaccharides synergized with fecal microbiota transplantation to alleviate gut microbiota dysbiosis and intestinal inflammation.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 4}, pages = {137851}, doi = {10.1016/j.ijbiomac.2024.137851}, pmid = {39566790}, issn = {1879-0003}, abstract = {Ulcerative colitis (UC) is closely associated with disruptions in gut microbiota. Restoring balance to gut microbiota and reducing intestinal inflammation has become a promising therapeutic approach for UC. However, challenges remain, including limited efficacy in some treatments. This study explores the synergistic effects and underlying mechanisms of Hizikia fusiforme polysaccharides (HFP) combined with fecal microbiota transplantation (FMT) to improve UC symptoms. Seven-week-old C57/BL6J mice were induced with UC using dextran sodium sulfate (DSS). Supplementation with either FMT alone or in combination with HFP effectively alleviated UC symptoms, reduced colonic inflammation, and corrected gut microbiota imbalance. Notably, HFP combined with FMT yielded showed better effects in ameliorating DSS-induced UC in mice than did FMT alone. Enrichment of probiotics, such as Bifidobacterium, and upregulation of beneficial metabolites, such as betaine, were identified as potential mechanisms for the enhanced effects of HFP combined with FMT against DSS-induced UC. These findings suggest that the combination of Hizikia fusiforme polysaccharides with FMT has potential applications in rectifying dysbiosis and ameliorating inflammatory bowel diseases.}, } @article {pmid39564459, year = {2024}, author = {Zhao, J and Liu, J and Feng, J and Liu, X and Hu, Q}, title = {The gut microbiota-brain connection: insights into major depressive disorder and bipolar disorder.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1421490}, pmid = {39564459}, issn = {1664-0640}, abstract = {Major depressive disorder (MDD) and bipolar disorder (BD) are two of the most prevalent mood disorders that seriously jeopardize both physical and mental health. The current diagnosis of MDD and BD relies primarily on clinical symptoms. However, correctly differentiating between MDD and BD during depressive episode states remains a substantial clinical challenge. The human gut hosts a large and diverse microbiota, which plays a pivotal role in various physiological processes. Emerging evidence suggests that the gut microbiota (GM) exerts beneficial effects on mental health disorders, including MDD, BD, and schizophrenia, through the microbe-gut-brain axis (MGBA). In recent years, the relationship between GM and mood disorders has garnered considerable attention, leading to intensive research in this area. The MGBA is a bidirectional communication system between the gut and the brain. Growing evidence indicates that the brain can influence the GM, which in turn may modulate the brain through this axis. This review aims to explore the changes in the GM of patients with MDD and BD and evaluate the effects of different treatments on their GM, including medication, probiotic, prebiotic and synbiotic interventions, and fecal microbiota transplantation (FMT). By doing so, we seek to identify potential disease-specific biomarkers, improve differential diagnosis, and offer novel therapeutic avenues for these disorders.}, } @article {pmid39562050, year = {2024}, author = {Li, N and Li, Y and Huang, Z and Cao, Z and Cao, C and Gao, X and Zuo, T}, title = {Faecal phageome transplantation alleviates intermittent intestinal inflammation in IBD and the timing of transplantation matters: a preclinical proof-of-concept study in mice.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-333598}, pmid = {39562050}, issn = {1468-3288}, } @article {pmid39557804, year = {2024}, author = {Lee, JY and Kim, Y and Kim, J and Kim, JK}, title = {Fecal Microbiota Transplantation: Indications, Methods, and Challenges.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {}, number = {}, pages = {}, pmid = {39557804}, issn = {1976-3794}, support = {RS-2024-00340833//National Research Foundation of Korea/ ; }, abstract = {Over the past two decades, as the importance of gut microbiota to human health has become widely known, attempts have been made to treat diseases by correcting dysbiosis of gut microbiota through fecal microbiota transplantation (FMT). Apart from current knowledge of gut microbiota, FMT to treat disease has a long history, from the treatment of food poisoning in the fourth century to the treatment of Clostridioides difficile infections in the twentieth century. In 2013, FMT was recognized as a standard treatment for recurrent C. difficile because it consistently showed high efficacy. Though recurrent C. difficile is the only disease internationally recognized for FMT efficacy, FMT has been tested for other diseases and shown some promising preliminary results. Different FMT methods have been developed using various formulations and administration routes. Despite advances in FMT, some issues remain to be resolved, such as donor screening, manufacturing protocols, and unknown components in the fecal microbiota. In this review, we discuss the mechanisms, clinical indications, methods, and challenges of current FMT. We also discuss the development of alternative therapies to overcome the challenges of FMT.}, } @article {pmid39555931, year = {2024}, author = {Wang, J and Xiang, J-H and Peng, X-Y and Liu, M and Sun, L-J and Zhang, M and Zhang, L-Y and Chen, Z-B and Tang, Z-Q and Cheng, L}, title = {Characteristic alterations of gut microbiota and serum metabolites in patients with chronic tinnitus: a multi-omics analysis.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0187824}, doi = {10.1128/spectrum.01878-24}, pmid = {39555931}, issn = {2165-0497}, abstract = {Chronic tinnitus is a central nervous system disorder. Currently, the effects of gut microbiota on tinnitus remain unexplored. To explore the connection between gut microbiota and tinnitus, we conducted 16S rRNA sequencing of fecal microbiota and serum metabolomic analysis in a cohort of 70 patients with tinnitus and 30 healthy volunteers. We used the weighted gene co-expression network method to analyze the relationship between the gut microbiota and the serum metabolites. The random forest technique was utilized to select metabolites and gut taxa to construct predictive models. A pronounced gut dysbiosis in the tinnitus group, characterized by reduced bacterial diversity, an increased Firmicutes/Bacteroidetes ratio, and some opportunistic bacteria including Aeromonas and Acinetobacter were enriched. In contrast, some beneficial gut probiotics decreased, including Lactobacillales and Lactobacillaceae. In serum metabolomic analysis, serum metabolic disturbances in tinnitus patients and these differential metabolites were enriched in pathways of neuroinflammation, neurotransmitter activity, and synaptic function. The predictive models exhibited great diagnostic performance, achieving 0.94 (95% CI: 0.85-0.98) and 0.96 (95% CI: 0.86-0.99) in the test set. Our study suggests that changes in gut microbiota could potentially influence the occurrence and chronicity of tinnitus, and exert regulatory effects through changes in serum metabolites. Overall, this research provides new perceptions into the potential role of gut microbiota and serum metabolite in the pathogenesis of tinnitus, and proposes the "gut-brain-ear" concept as a pathomechanism underlying tinnitus, with significant clinical diagnostic implications and therapeutic potential.IMPORTANCETinnitus affects millions of people worldwide. Severe cases may lead to sleep disorders, anxiety, and depression, subsequently impacting patients' lives and increasing societal healthcare expenditures. However, tinnitus mechanisms are poorly understood, and effective therapeutic interventions are currently lacking. We discovered the gut microbiota and serum metabolomics changes in patients with tinnitus, and provided the potential pathological mechanisms of dysregulated gut flora in chronic tinnitus. We proposed the innovative concept of the "gut-brain-ear axis," which underscores the exploration of gut microbiota impact on susceptibility to chronic tinnitus through serum metabolic profile modulation. We also reveal novel biomarkers associated with chronic tinnitus, offering a new conceptual framework for further investigations into the susceptibility of patients, potential treatment targets for tinnitus, and assessing patient prognosis. Subsequently, gut microbiota and serum metabolites can be used as molecular markers to assess the susceptibility and prognosis of tinnitus.Furthermore, fecal transplantation may be used to treat tinnitus.}, } @article {pmid39555739, year = {2024}, author = {Liu, X and Kang, W and Li, J and Li, X and Yang, P and Shi, M and Wang, Z and Wang, Y and Medina, ADPA and Liu, D and Zhu, F and Shen, H and Huang, K and Chen, X and Liu, Y}, title = {Melatonin Ameliorates Cadmium-Induced Liver Fibrosis Via Modulating Gut Microbiota and Bile Acid Metabolism.}, journal = {Journal of pineal research}, volume = {76}, number = {8}, pages = {e70005}, doi = {10.1111/jpi.70005}, pmid = {39555739}, issn = {1600-079X}, support = {//This study was funded by the National Natural Science Foundation of China (32102741) and Fundamental Research Funds for the Central Universities (Grant No. KJYQ2024010; KYT2023004)./ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Bile Acids and Salts/metabolism ; *Melatonin/pharmacology ; Mice ; *Liver Cirrhosis/metabolism/chemically induced/pathology ; Male ; *Cadmium/toxicity ; Mice, Knockout ; Mice, Inbred C57BL ; Receptors, Cytoplasmic and Nuclear/metabolism ; }, abstract = {Cadmium (Cd) is a widespread environmental contaminant with high toxicity to human health. Melatonin has been shown to improve Cd-induced liver damage. However, its mechanism has not yet been elucidated. In this study, we aimed to investigate the effects of melatonin on Cd-induced liver damage and fibrosis. A combination of 16S rRNA gene sequencing and mass spectrometry-based metabolomics was adopted to investigate changes in the gut microbiome and its metabolites on the regulation of melatonin in Cd-induced liver injury and fibrosis of mice. Further, nonabsorbable antibiotics, a fecal microbiota transplantation (FMT) program and intestine-specific farnesoid X receptor (FXR) knockout mice were employed to explore the mechanism of melatonin (MT) on liver injury and fibrosis in Cd treated mice. MT significantly improved hepatic inflammation, bile duct hyperplasia, liver damage, and liver fibrosis, with a notable decrease in liver bile acid levels in Cd-exposed mice. MT treatment remodeled the gut microbiota, improved gut barrier function, and reduced the production of gut-derived lipopolysaccharide (LPS). MT significantly decreased the intestinal tauro-β-muricholic acid levels, which are known as FXR antagonists. Notably, MT prominently activated the intestinal FXR signaling, subsequently inhibiting liver bile acid synthesis and decreasing hepatic inflammation in Cd-exposed mice. However, MT could not ameliorate Cd-induced liver damage and fibrosis in Abx-treated mice. Conversely, MT still exerted a protective effect on Cd-induced liver damage and fibrosis in FMT mice. Interestingly, MT failed to reverse liver damage and fibrosis in Cd-exposed intestinal epithelial cell-specific FXR gene knockout mice, indicating that intestinal FXR signaling mediated the protective effect of MT treatment. MT improves Cd-induced liver damage and fibrosis through reshaping the intestinal flora, activating the intestinal FXR-mediated suppression of liver bile acid synthesis and reducing LPS leakage in mice.}, } @article {pmid39552646, year = {2024}, author = {Dong, X and Su, Y and Luo, Z and Li, C and Gao, J and Han, X and Yao, S and Wu, W and Tian, L and Bai, Y and Wang, G and Ren, W}, title = {Fecal microbiota transplantation alleviates cognitive impairment by improving gut microbiome composition and barrier function in male rats of traumatic brain injury following gas explosion.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1485936}, pmid = {39552646}, issn = {1664-302X}, abstract = {BACKGROUND: Dysbiosis of gut microbiota (GM) is intricately linked with cognitive impairment and the incidence of traumatic brain injury (TBI) in both animal models and human subjects. However, there is limited understanding of the impact and mechanisms of fecal microbiota transplantation (FMT) on brain and gut barrier function in the treatment of TBI induced by gas explosion (GE).

METHODS: We have employed FMT technology to establish models of gut microbiota dysbiosis in male rats, and subsequently conducted non-targeted metabolomics and microbiota diversity analysis to explore the bacteria with potential functional roles.

RESULTS: Hematoxylin-eosin and transmission electron microscopy revealed that GE induced significant pathological damage and inflammation responses, as well as varying degrees of mitochondrial impairment in neuronal cells in the brains of rats, which was associated with cognitive decline. Furthermore, GE markedly elevated the levels of regulatory T cell (Tregs)-related factors interleukin-10, programmed death 1, and fork head box protein P3 in the brains of rats. Similar changes in these indicators were also observed in the colon; however, these alterations were reversed upon transfer of normal flora into the GE-exposed rats. Combined microbiome and metabolome analysis indicated up-regulation of Clostridium_T and Allobaculum, along with activation of fatty acid biosynthesis after FMT. Correlation network analysis indirectly suggested a causal relationship between FMT and alleviation of GE-induced TBI. FMT improved intestinal structure and up-regulated expression of tight junction proteins Claudin-1, Occludin, and ZO-1, potentially contributing to its protective effects on both brain and gut.

CONCLUSION: Transplantation of gut microbiota from healthy rats significantly enhanced cognitive function in male rats with traumatic brain injury caused by a gas explosion, through the modulation of gut microbiome composition and the improvement of both gut and brain barrier integrity via the gut-brain axis. These findings may offer a scientific foundation for potential clinical interventions targeting gas explosion-induced TBI using FMT.}, } @article {pmid39548908, year = {2024}, author = {Gopal, RK and Ganesh, PS and Pathoor, NN}, title = {Synergistic Interplay of Diet, Gut Microbiota, and Insulin Resistance: Unraveling the Molecular Nexus.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2400677}, doi = {10.1002/mnfr.202400677}, pmid = {39548908}, issn = {1613-4133}, abstract = {This comprehensive review explores the intricate relationship between gut microbiota, diet, and insulin resistance, emphasizing the novel roles of diet-induced microbial changes in influencing metabolic health. It highlights how diet significantly influences gut microbiota composition, with different dietary patterns fostering diverse microbial communities. These diet-induced changes in the microbiome impact human metabolism by affecting inflammation, energy balance, and insulin sensitivity, particularly through microbial metabolites like short-chain fatty acids (SCFAs). Focusing the key mediators like endotoxemia and systemic inflammation, and introduces personalized microbiome-based therapeutic strategies, it also investigates the effects of dietary components-fiber, polyphenols, and lipids-on microbiota and insulin sensitivity, along with the roles of protein intake and amino acid metabolism. The study compares the effects of Western and Mediterranean diets on the microbiota-insulin resistance axis. Therapeutic implications, including probiotics, fecal microbiota transplantation (FMT), and personalized diets, are discussed. Key findings reveal that high-fat diets, especially those rich in saturated fats, contribute to dysbiosis and increased intestinal permeability, while high-fiber diets promote beneficial bacteria and SCFAs. The review underscores the future potential of food and microbiota interventions for preventing or managing insulin resistance.}, } @article {pmid39548468, year = {2024}, author = {Song, Q and Gao, Y and Liu, K and Tang, Y and Man, Y and Wu, H}, title = {Gut microbial and metabolomics profiles reveal the potential mechanism of fecal microbiota transplantation in modulating the progression of colitis-associated colorectal cancer in mice.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {1028}, pmid = {39548468}, issn = {1479-5876}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Metabolomics ; Humans ; *Disease Progression ; *Colitis-Associated Neoplasms/microbiology/pathology/metabolism ; Mice, Inbred C57BL ; Male ; Colorectal Neoplasms/microbiology/pathology/metabolism ; Dextran Sulfate ; Metabolome ; Mice ; Female ; Azoxymethane ; Wnt Signaling Pathway ; Feces/microbiology ; }, abstract = {PURPOSE: Intestinal flora promotes the pathogenesis of colorectal cancer (CRC) through microorganisms and their metabolites. This study aimed to investigate the composition of intestinal flora in different stages of CRC progression and the effect of fecal microbiota transplantation (FMT) on CRC mice.

METHODS: The fecal microbiome from healthy volunteers (HC), colorectal adenoma (CRA), inflammatory bowel disease (IBD), and CRC patients were analyzed by 16s rRNA gene sequencing. In an azoxymethane (AOM)/dextran-sulfate-sodium (DSS)-induced CRC mouse, the effect of FMT from HC, CRA, CRC, and IBD patients on CRC mice was assessed by histological analysis. Expression of inflammation- EMT-associated proteins and Wnt/β-catenin pathway were assessed using qRT-PCR and western blot. The ratio of the fecal microorganisms and metabolomics alteration after FMT were also assessed.

RESULT: Prevotella, Faecalibacterium, Phascolarctobacterium, Veillonella, Alistipes, Fusobacterium, Oscillibacter, Blautia, and Ruminococcus abundance was different among HC, IBD, CRC, and CRA patients. HC-FMT alleviated disease progression and inflammatory response in CRC mice, inhibited splenic T help (Th)1 and Th17 cell numbers, and suppressed the EMT and Wnt/β-catenin pathways in tumor tissues of CRC mice. IBD-FMT, CRA-FMT, and CRC-FMT played deleterious roles; the CRC-FMT mice exhibited the most malignant phenotype. Compared with the non-FMT CRC mice, Muribaculaceae abundance was lower after FMT, especially lowest in the IBD-FMT group; while Lactobacillus abundance was higher after FMT and especially high in HC-FMT. Akkermansia and Ileibacterium abundance increased after FMT-HC compared to other groups. Metabolite correlation analysis revealed that Muribaculaceae abundance was significantly correlated with metabolites such as Betaine, LysoPC, and Soyasaponin III. Lactobacillus abundance was positively correlated with Taurocholic acid 3-sulfate, and Ileibacterium abundance was positively correlated with Linoleoyl ethanolamide.

CONCLUSION: The different intestinal microbiota communities of HC, IBD, CRA, and CRC patients may be attributed to the different modulation effects of FMT on CRC mice. CRC-FMT promoted, while HC-FMT inhibited the progress of CRC. Increased linoleoyl ethanolamide levels and abundance of Muribaculaceae, Akkermansia, and Ileibacterium and reduced Fusobacterium might participate in inhibiting CRC initiation and development. This study demonstrated that FMT intervention could restore the intestinal microbiota and metabolomics of CRC mice, suggesting FMT as a potential strategy for CRC therapy.}, } @article {pmid39548040, year = {2024}, author = {Wang, J and Yang, R and Zhong, H and Liu, YJ}, title = {Fecal microbiota transplants in pediatric autism: opportunities and challenges.}, journal = {World journal of pediatrics : WJP}, volume = {}, number = {}, pages = {}, pmid = {39548040}, issn = {1867-0687}, support = {82070823//National Natural Science Foundation of China/ ; }, } @article {pmid39547534, year = {2024}, author = {Birch, CR and Paaske, SE and Jensen, MB and Baunwall, SMD and Ehlers, LH and Hvas, CL}, title = {Cost-effectiveness of faecal microbiota transplantation compared with vancomycin monotherapy for early Clostridioides difficile infection: economic evaluation alongside a randomised controlled trial.}, journal = {The Journal of hospital infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhin.2024.11.003}, pmid = {39547534}, issn = {1532-2939}, abstract = {For Clostridioides difficile infection (CDI), faecal microbiota transplantation (FMT) is currently recommended for patients with three or more CDI episodes. A recent randomised controlled trial (RCT) show that FMT may be considered early, defined as intervention during the first or second CDI episode. Compared with standard care for first or second CDI, patients randomised to FMT had €1,645 lower hospital costs over 26 weeks owing to fewer admissions and hospital contacts and less medication use.}, } @article {pmid39547500, year = {2024}, author = {Huang, ZB and Zhang, GP and Lu, CX and Gong, C and Gao, X and Lin, Y and Su, P and Xu, W and Lin, Y and Lin, N and Wu, X and Chen, X and Zheng, T and Zheng, X}, title = {Gut microbiota-derived 3-indoleacetic acid confers a protection against sepsis-associated encephalopathy through microglial aryl hydrocarbon receptors.}, journal = {Experimental neurology}, volume = {384}, number = {}, pages = {115055}, doi = {10.1016/j.expneurol.2024.115055}, pmid = {39547500}, issn = {1090-2430}, abstract = {BACKGROUND: The gut microbiota significantly contributes to the pathogenesis of central nervous system disorders. Among the bioactive molecules produced by the gut microbiota, 3-indoleacetic acid (IAA) has been shown to attenuate oxidative stress and inflammatory responses. This experiment aimed to determine the impacts of IAA on sepsis-associated encephalopathy (SAE) and the underlying mechanisms.

METHODS: A total of 34 septic patients and 24 healthy controls were included in the analysis of the clinical correlation between fecal IAA and septic encephalopathy. Fecal microbiota transplantation was used to verify the role of the gut microbiota and its metabolites in SAE. Male C57BL/6 mice aged six to eight weeks, pre-treated with IAA via oral gavage, were subjected to the cecal ligation and puncture (CLP) procedures. This treatment was administered either in combination with an aryl hydrocarbon receptor (AhR) antagonist, CH223191, or a CSF1R inhibitor, PLX3397, to eliminate microglia. Both immunofluorescence staining and enzyme-linked immunosorbent assays were used to evaluate microglia activation and inflammatory cytokine secretion. Behavioral assessments were conducted to quantify neurological deficits.

RESULTS: A decreased fecal level of IAA was observed in the patients with sepsis-associated delirium (SAD), a manifestation of SAE. A reduced IAA level was significantly associated with worsen clinical outcomes. Fecal microbiota transplantation from the SAD patients induced an SAE-like phenotype in mice, but supplementing exogenous IAA improved the SAE-like phenotype, mediated by microglia. IAA effectively binded with the aryl hydrocarbon receptor (AhR). Furthermore, IAA increased the nuclear activity of AhR in the lipopolysaccharide (LPS)-treated microglial cells, leading to reduced secretion of inflammatory cytokines. The AhR inhibitor CH223191 counteracted the protective effect of IAA against SAE in mice.

CONCLUSIONS: Gut microbiota-derived IAA confers a protection against SAE by activating AhR in microglia, improving neuronal and cognitive impairments. Thus, IAA holds the promise as a potential therapeutic agent for managing SAE.}, } @article {pmid39547012, year = {2024}, author = {Wang, J and Hou, Y and Mu, L and Yang, M and Ai, X}, title = {Gut microbiota contributes to the intestinal and extraintestinal immune homeostasis by balancing Th17/Treg cells.}, journal = {International immunopharmacology}, volume = {143}, number = {Pt 3}, pages = {113570}, doi = {10.1016/j.intimp.2024.113570}, pmid = {39547012}, issn = {1878-1705}, abstract = {Gut microbiota is generally considered to play an important role in host health due to its extensive immunomodulatory activities. Th17 and Treg cells are two important CD4+ T cell subsets involved in immune regulation, and their imbalance is closely tied to many immune diseases. Recently, abundant researches have highlighted the importance of gut microbiota in supporting intestinal and extraintestinal immunity through the balance of Th17 and Treg cells. Here, we presented a comprehensive review of these findings. This review first provided an overview of gut microbiota, along with Th17/Treg cell differentiation and cytokine production. Subsequently, the review summarized the regulatory effects of gut microbiota (in terms of species, components, and metabolites) on the Th17/Treg cell balance in the local intestines and extraintestinal organs, such as lung, liver, brain, kidney, and bone. Specifically, the Th17 and Treg cells that can be modulated by gut microbiota originate not only from the gut and extraintestinal organs, but also from peripheral blood and spleen. Then, the microbial therapeutics, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), were also reviewed because of their therapeutic potentials in addressing intestinal and extraintestinal diseases via the Th17/Treg axis. Finally, the review discussed the clinical applications and future study prospects of microbial therapeutics by targeting the Th17/Treg cell balance. In conclusion, this review focused on elucidating the regulatory effects of gut microbiota in balancing Th17/Treg cells to maintain intestinal and extraintestinal immune homeostasis, contributing to the further development and promotion of microbial therapeutics.}, } @article {pmid39546851, year = {2024}, author = {Peña-Ocaña, BA and Silva-Flores, M and Shotaro, T and García-Gálvez, L and Hernández-Esquivel, L and Robledo-Cadena, DX and Barrera-Oviedo, D and Pérez-Torres, I and Tostado-Islas, O and Maeda, T and Rodríguez-Zavala, JS and Marín-Hernández, Á and García-Contreras, R and Jasso-Chávez, R}, title = {Transplant of gut microbiota ameliorates metabolic and heart disorders in rats fed with a hypercaloric diet by modulating microbial metabolism and diversity.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {181}, number = {}, pages = {117667}, doi = {10.1016/j.biopha.2024.117667}, pmid = {39546851}, issn = {1950-6007}, abstract = {Metabolic syndrome (MS) is a cluster of metabolic disorders which have a tight correlation with dysbiosis of gut microbiota (GM) that have to be treated to avoid higher risks for health. In this work, probiotics obtained from healthy cultured GM were provided to rats with metabolic syndrome (MSR) as therapy in treating MS through the correction of dysbiosis. MSR showed obesity, high blood pressure, abnormal blood chemistry parameters and high heart rate respect to control rats (CNTR). Cultivated GM from feces of MSR in media favoring anaerobic species, showed dysbiosis as judged by differences in the 16S rRNA metabarcoding analysis and by affected intermediary metabolism (methane and SCFA production, nutrients consumption and enzyme activities) compared to CNTR. The metabarcoding analysis of cultured healthy GM identified 211 species, which were further transplanted alive in MSR once a week for 9 weeks. Thereafter, in transplanted MSR the excess of Clostridium and Lactobacillus diminished, while Prevotella, Eubacterium, Faecalibacterium and methanogens, among others increased, leading to the recovery of the microbial metabolic capacity. The presence of butyric acid-producing bacteria in the transplanted GM correlated with increased levels of anti-inflammatory cytokines. Therefore, transplanted MSR recovered the normal levels of weight, blood glucose, triglycerides and cholesterol as well as the heart function. Data suggested that the great diversity of species contained in the GM transplanted restored the microbial metabolism, consuming excessive nutrients and secondary metabolites produced by MS. The use of cultivated GM as probiotics may be a safer alternative for the treatment of different diseases.}, } @article {pmid39545921, year = {2024}, author = {Ullern, A and Holm, K and Røssevold, AH and Andresen, NK and Bang, C and Lingjærde, OC and Naume, B and Hov, JR and Kyte, JA}, title = {Gut microbiota diversity is prognostic and associated with benefit from chemo-immunotherapy in metastatic triple-negative breast cancer.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13760}, pmid = {39545921}, issn = {1878-0261}, support = {2017100//Helse Sør-Øst RHF/ ; 2017122//Helse Sør-Øst RHF/ ; 182632//Kreftforeningen/ ; 214972/WT_/Wellcome Trust/United Kingdom ; 802544/ERC_/European Research Council/International ; }, abstract = {The gut microbiota influences multiple aspects of human health and disease. Several studies have indicated an association between the gut microbiota and response to immune checkpoint inhibitors in various cancers, but there is scarce data from breast cancer. The randomized ALICE trial demonstrated improved progression-free survival (PFS) from adding the programmed cell death 1 ligand 1 (PD-L1) inhibitor atezolizumab (atezo) to immunomodulating chemotherapy (chemo) in metastatic triple-negative breast cancer (mTNBC), even for PD-L1[negative] disease. Herein, we investigated the microbiota composition and dynamics in the ALICE patients and their association with clinical outcome, by analyzing fecal samples collected at baseline and after 8 weeks. We applied 16S (V3-V4) rRNA sequencing to characterize the diversity and taxonomic composition. Kaplan-Meier and Cox proportional hazard models were used for time-to-event analyses. We found that high alpha diversity by Faith's phylogenetic diversity (PD) at baseline was associated with prolonged PFS in the total study population and in the atezo-chemo arm, but not in the placebo-chemo arm. Moreover, Faith's PD appeared to be predictive of benefit from atezolizumab. Patients with high Faith's PD exhibited a PFS hazard ratio of 0.34 (P = 0.018) in favor of the atezo-chemo arm, compared to 0.83 (P = 0.62) in the low Faith's PD group. Faith's PD was significantly reduced during treatment. At baseline, Bifidobacterium was significantly overrepresented in patients without clinical benefit in the atezo-chemo arm, but not in the placebo-chemo arm. These findings suggest that alpha diversity by Faith's PD should be further investigated as a prognostic and predictive biomarker in patients with mTNBC receiving chemo-immunotherapy.}, } @article {pmid39543390, year = {2024}, author = {Islam, J and Ohtani, N and Shimizu, Y and Tanimizu, M and Goto, Y and Sato, M and Makino, E and Shimada, T and Ueda, C and Matsuo, A and Suyama, Y and Sakai, Y and Karrow, NA and Yoneyama, H and Hirakawa, R and Furukawa, M and Tanaka, H and Nochi, T}, title = {Freeze-dried fecal microorganisms as an effective biomaterial for the treatment of calves suffering from diarrhea.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28078}, pmid = {39543390}, issn = {2045-2322}, support = {Livestock Promotional Subsidy//Japan Racing Association/ ; 20K15478//Japan Society for the Promotion of Science/ ; 22H00393//Japan Society for the Promotion of Science/ ; 18H03969//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Cattle ; *Diarrhea/therapy/microbiology/veterinary ; *Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; *Freeze Drying ; Gastrointestinal Microbiome ; Cattle Diseases/therapy/microbiology ; Biocompatible Materials ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic modality for treating neonatal calf diarrhea. Several practical barriers, including donor selection, fecal collection, and a limited timeframe for FMT, are the main constraints to using fresh feces for implementing on-farm FMT. We report the utility of FMT with pretreated ready-to-use frozen (F) or freeze-dried (FD) microorganisms for treating calf diarrhea. In total, 19 FMT (F-FMT, n = 10 and FD-FMT, n = 9) treatments were conducted. Both FMT treatments were 100% clinically effective; however, multi-omics analysis showed that FD-FMT was superior to F-FMT. Machine learning analysis with SourceTracker confirmed that donor microbiota was retained four times better in the recipient calves treated with FD-FMT than F-FMT. A predictive model based on receiver operating characteristic curve analysis and area under the curve showed that FD-FMT was more discriminative than F-FMT of the observed changes in microbiota and metabolites during disease recovery. These results provide new insights into establishing methods for preparing fecal microorganisms to increase the quality of FMT in animals and may contribute to FMT in humans.}, } @article {pmid39541983, year = {2024}, author = {Urtecho, G and Moody, T and Huang, Y and Sheth, RU and Richardson, M and Descamps, HC and Kaufman, A and Lekan, O and Zhang, Z and Velez-Cortes, F and Qu, Y and Cohen, L and Ricaurte, D and Gibson, TE and Gerber, GK and Thaiss, CA and Wang, HH}, title = {Spatiotemporal dynamics during niche remodeling by super-colonizing microbiota in the mammalian gut.}, journal = {Cell systems}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cels.2024.10.007}, pmid = {39541983}, issn = {2405-4720}, abstract = {While fecal microbiota transplantation (FMT) has been shown to be effective in reversing gut dysbiosis, we lack an understanding of the fundamental processes underlying microbial engraftment in the mammalian gut. Here, we explored a murine gut colonization model leveraging natural inter-individual variations in gut microbiomes to elucidate the spatiotemporal dynamics of FMT. We identified a natural "super-donor" consortium that robustly engrafts into diverse recipients and resists reciprocal colonization. Temporal profiling of the gut microbiome showed an ordered succession of rapid engraftment by early colonizers within 72 h, followed by a slower emergence of late colonizers over 15-30 days. Moreover, engraftment was localized to distinct compartments of the gastrointestinal tract in a species-specific manner. Spatial metagenomic characterization suggested engraftment was mediated by simultaneous transfer of spatially co-localizing species from the super-donor consortia. These results offer a mechanism of super-donor colonization by which nutritional niches are expanded in a spatiotemporally dependent manner. A record of this paper's transparent peer review process is included in the supplemental information.}, } @article {pmid39540836, year = {2024}, author = {Charles, P and Kumar, S and Girish Kumar, CP and Parameswaran, S and Viswanathan, P and Nachiappa Ganesh, R}, title = {Association of gut microbiota with allograft injury in kidney transplant recipients: a comparative profiling through 16S metagenomics and quantitative PCR.}, journal = {Journal of medical microbiology}, volume = {73}, number = {11}, pages = {}, doi = {10.1099/jmm.0.001934}, pmid = {39540836}, issn = {1473-5644}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; *RNA, Ribosomal, 16S/genetics ; Female ; Middle Aged ; *Metagenomics/methods ; Adult ; Prospective Studies ; Longitudinal Studies ; *Graft Rejection/microbiology ; Real-Time Polymerase Chain Reaction/methods ; Bacteria/classification/genetics/isolation & purification ; Feces/microbiology ; Allografts/microbiology ; Transplant Recipients ; }, abstract = {Introduction. The existence of a mutual relationship between gut microbiota and immune homeostasis highlights its importance in the context of kidney transplantation.Gap statement. The translational utility of gut microbiota as a biomarker for allograft injury has not been assessed before.Aim. In this study, we aimed to characterize the gut microbial diversity in kidney transplant recipients and investigate the alterations in the gut microbial composition in association with allograft injury such as histopathological graft rejection and calcineurin inhibitor toxicity. In addition, we compared the gut microbial quantitation using 16S metagenomics and quantitative PCR (qPCR) to assess its translational utility.Methodology. In this prospective longitudinal cohort study, we enrolled 38 kidney transplant recipients and collected serial faecal specimens (n=114), once before the induction therapy, and twice after transplant, during the first and third month. We characterized the gut microbial composition through 16S rRNA sequencing and qPCR from the DNA isolates of the samples. The recipients were clinically followed up for a median of 600 days post-transplant. Histopathological evidence of allograft rejection and calcineurin inhibitor toxicity were used for the correlational analysis with gut microbial diversity.Results. Significant differences in the gut microbial diversity were observed between the pre- and post-transplant samples. Pre-transplant gut microbiota revealed a higher relative abundance of phylum Bacteroidetes in the allograft rejection group, and a higher relative abundance of phylum Firmicutes was observed in the histopathological features of calcineurin inhibitor toxicity (hCNI toxicity) group. We found a high concordance between 16S metagenomics and qPCR outputs for assessing the gut microbial diversity. Furthermore, the receiver operating characteristic curve analysis has also proven that the pre-transplant levels of gut microbial dysbiosis, as a potential predictive biomarker for allograft injury.Conclusion. Our pilot study found a strong statistical association of gut microbial dysbiosis with kidney allograft injury, highlighting the potential of gut microbiota as a predictive biomarker and that qPCR serves as a more reliable and economic tool for assessing dysbiosis paving the way for its translational utility.}, } @article {pmid39539436, year = {2024}, author = {Abood, NA and Kadhim, DJ and Hussein, RJ}, title = {Medication-related burden among Iraqi patients with ulcerative colitis: a cross-sectional study.}, journal = {Journal of medicine and life}, volume = {17}, number = {8}, pages = {800-805}, pmid = {39539436}, issn = {1844-3117}, mesh = {Humans ; *Colitis, Ulcerative/drug therapy ; Iraq ; Male ; Cross-Sectional Studies ; Female ; Adult ; Surveys and Questionnaires ; Middle Aged ; Cost of Illness ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurring periods of inflammation and remission, primarily affecting the colon. The concept of medication-related burden, which refers to the adverse effects experienced by patients due to conventional medical treatments, is relatively new in the field. This study aimed to measure medication-related burden among patients with ulcerative colitis in Iraq. The study was conducted at the Gastroenterology and Hepatology Teaching Hospital, Medical City, Baghdad, Iraq, from December 2022 to May 2023. We used the Arabic version of the Living with Medicines Questionnaire version 3 (LMQ-3) to explore medication-related burdens experienced by patients with UC. Eighty-six patients with ulcerative colitis were included. The mean of the total medication-related burden score was 107.5 ± 20.7. The findings showed that 45.3% of patients with UC had a moderate degree of medication-related burden, followed by minimum burden (44.2%), high burden (5.8%), and no burden (4.7%). The lowest median burden scores emerged in five domains: interactions with healthcare professionals, practical difficulties with medication use, medication side effects, medication effectiveness, and the impact on daily life. Conversely, the highest-burden scores were noted in the cost, concerns about medication use, and autonomy to vary the regimen domains. In multivariate analysis, none of the patient-related variables was independently correlated with the total medication-related burden score. A large proportion of the patients with UC who participated in the current study reported varying degrees of medication-related burden, with the majority having a minimum to moderate medication-related burden.}, } @article {pmid39539028, year = {2024}, author = {Kovynev, A and Ying, Z and Zhang, S and Olgiati, E and Lambooij, JM and Visentin, C and Guigas, B and Ducarmon, QR and Rensen, PCN and Schönke, M}, title = {Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice.}, journal = {Journal of pineal research}, volume = {76}, number = {8}, pages = {e70003}, doi = {10.1111/jpi.70003}, pmid = {39539028}, issn = {1600-079X}, support = {//This work was supported by the Novo Nordisk Foundation (grant NNF18OC0032394 to M.S.), The Netherlands Cardiovascular Research Initiative CVON-GENIUS-2 (grant to P.C.N.R.), the Chinese Scholarship Council (grants to Z.Y. and S.Z.). A.K. is supported by a PhD grant from Leiden University Medical Center (to M.S.)./ ; }, mesh = {Animals ; Mice ; Male ; *Physical Conditioning, Animal ; *Gastrointestinal Microbiome ; *Liver/metabolism ; Fatty Liver/therapy/metabolism ; Non-alcoholic Fatty Liver Disease/metabolism/therapy ; Diet, High-Fat ; Mice, Transgenic ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; L-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as Akkermansia, Lachnospiraceae, and Rikenella. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis.}, } @article {pmid38978509, year = {2024}, author = {Cantón, R and De Lucas Ramos, P and García-Botella, A and García-Lledó, A and Hernández-Sampelayo, T and Gómez-Pavón, J and González Del Castillo, J and Martín-Delgado, MC and Martín Sánchez, FJ and Martínez-Sellés, M and Molero García, JM and Moreno Guillén, S and Rodríguez-Artalejo, FJ and Reigadas, E and Del Campo, R and Serrano, S and Ruiz-Galiana, J and Bouza, E}, title = {Human intestinal microbiome: Role in health and disease.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {37}, number = {6}, pages = {438-453}, doi = {10.37201/req/056.2024}, pmid = {38978509}, issn = {1988-9518}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {The study of the microbiota and the microbiome, and specifically the intestinal one, has determined great interest due to the possible association of their alterations with numerous diseases. These include entities as diverse as Crohn's disease, autism, diabetes, cancer or situations as prevalent today as obesity. In view of this situation, different recommendations have been performed regarding the use of probiotics, prebiotics, and postbiotics as modulators of the microbiota and the microbiome, seeking both preventive and therapeutic effects, and faecal material transfer (FMT) is proposed as an alternative. The latter has emerged as the only proven beneficial intervention on the intestinal microbiome, specifically in the treatment of recurrent colitis associated with Clostridioides difficile (R-CDI). In the rest of the entities, the lowering of laboratory costs has favored the study of the microbiome, which is resolved by delivering reports with catalogs of microorganisms, metabolites or supposed biomarkers without consensus on their composition associated with healthy or diseased microbiota and the disease. There is still insufficient evidence in any disease for interventions on the microbiome beyond FMT and R-CDI. Multi- and multi-disciplinary work with extensive research and the application of artificial intelligence in this field may shed light on the questions raised currently. Ethical issues must also be resolved in light of possible interventions within the umbrella of personalized medicine.}, } @article {pmid39538028, year = {2024}, author = {Emile, SH and Wignakumar, A and Horesh, N and Garoufalia, Z and Strassmann, V and Boutros, M and Wexner, SD}, title = {Systematic literature review and meta-analysis of surgical treatment of complete rectal prolapse in male patients.}, journal = {Techniques in coloproctology}, volume = {28}, number = {1}, pages = {158}, pmid = {39538028}, issn = {1128-045X}, mesh = {Adult ; Humans ; Male ; Middle Aged ; Constipation/etiology/surgery/epidemiology ; Digestive System Surgical Procedures/methods/adverse effects ; Fecal Incontinence/etiology/epidemiology ; Operative Time ; Perineum/surgery ; Postoperative Complications/etiology/epidemiology ; *Rectal Prolapse/surgery ; Rectum/surgery ; Recurrence ; Surgical Mesh ; Treatment Outcome ; }, abstract = {BACKGROUND: Rectal prolapse often affects women but may also affect men. This systematic review aimed to provide outcomes of surgery for complete rectal prolapse reported in studies with a predominantly male population.

METHODS: This PRISMA-compliant systematic literature review searched PubMed and Scopus between January 2000 and February 2024; Google Scholar was queried for studies reporting outcomes of complete rectal prolapse surgery in predominately (> 90%) male populations. Main outcome measures were recurrence, complications, operative time, and bowel function.

RESULTS: Eight studies (452 patients; median age 45.6 years) were included; 80.5% of patients underwent abdominal procedures whereas 19.5% underwent perineal procedures. The prevalence of recurrence was 11.2% after ventral mesh rectopexy (VMR), 0.8% after posterior mesh rectopexy (PMR), 0 after resection rectopexy, and 19.3% after perineal procedures. The prevalence of complications was 13.9% after VMR, 13.1% after PMR, 43.3% after resection rectopexy, and 17.4% after perineal procedures. The most improvement in constipation was noted after resection rectopexy (83.3-100%) and in fecal incontinence (FI) was noted after posterior mesh rectopexy (86.4-90%). Abdominal procedures had lower rates of recurrence (6% vs. 19.3%, RR 0.50, 95% CI 0.21-1.18, p = 0.113), similar complication rates (14.3% vs. 13.6%, RR 0.41, 95% CI 0.06-2.9, p = 0.374), and longer operative times (116 ± 47.2 vs. 74.2 ± 23.6 min, p < 0.001).

CONCLUSIONS: Treatment of rectal prolapse in male patients undergoing abdominal procedures was associated with longer operative times, lower recurrence rates, and similar complications to perineal procedures. PMR and resection rectopexy had the lowest recurrence. The most improvement in FI and constipation was noted after PMR and resection rectopexy, respectively.}, } @article {pmid39536754, year = {2024}, author = {Wang, T and Fan, Y and Tan, S and Wang, Z and Li, M and Guo, X and Yu, X and Lin, Q and Song, X and Xu, L and Li, L and Li, S and Gao, L and Liang, X and Li, C and Ma, C}, title = {Probiotics and their metabolite spermidine enhance IFN-γ[+]CD4[+] T cell immunity to inhibit hepatitis B virus.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {101822}, doi = {10.1016/j.xcrm.2024.101822}, pmid = {39536754}, issn = {2666-3791}, abstract = {The therapeutic potential of commensal microbes and their metabolites is promising in the functional cure of chronic hepatitis B virus (HBV) infection, which is defined as hepatitis B surface antigen (HBsAg) loss. Here, using both specific-pathogen-free and germ-free mice, we report that probiotics significantly promote the decline of HBsAg and inhibit HBV replication by enhancing intestinal homeostasis and provoking intrahepatic interferon (IFN)-γ[+]CD4[+] T cell immune response. Depletion of CD4[+] T cells or blockage of IFN-γ abolishes probiotics-mediated HBV inhibition. Specifically, probiotics-derived spermidine accumulates in the gut and transports to the liver, where it exhibits a similar anti-HBV effect. Mechanistically, spermidine enhances IFN-γ[+]CD4[+] T cell immunity by autophagy. Strikingly, administration of probiotics in HBV patients reveals a preliminary trend to accelerate the decline of serum HBsAg. In conclusion, probiotics and their derived spermidine promote HBV clearance via autophagy-enhanced IFN-γ[+]CD4[+] T cell immunity, highlighting the therapeutic potential of probiotics and spermidine for the functional cure of HBV patients.}, } @article {pmid39534584, year = {2024}, author = {Hrubesz, G and Leigh, J and Ng, TL}, title = {Understanding the relationship between breast cancer, immune checkpoint inhibitors, and gut microbiota: a narrative review.}, journal = {Translational breast cancer research : a journal focusing on translational research in breast cancer}, volume = {5}, number = {}, pages = {31}, pmid = {39534584}, issn = {2218-6778}, abstract = {BACKGROUND AND OBJECTIVE: The composition of gut microbiota plays an important role in predicting and influencing outcomes of cancer treated with immunotherapy. Our objective is to summarize the role of gut microbiota and immunotherapy in breast cancer.

METHODS: A systematic search from inception until July 2024 of key search terms including immunity, breast neoplasm, gastrointestinal microbiome/microbiota, fecal microbiota transplantation, pro- and prebiotics, antibiotics and immunotherapy using EMBASE, MEDLINE and CENTRAL was conducted. The results were screened by two reviewers independently and synthesized and presented descriptively.

KEY CONTENT AND FINDINGS: Thirteen studies (5 clinical, 8 pre-clinical) met the eligibility criteria and were published from 2020-2024. Clinical studies showed that the composition and diversity of gut microbiota was associated with patient response to immunotherapy. In pre-clinical studies, dysbiotic states induced by obesity, antibiotics, and diet were associated with immunosuppression and influenced response to programmed cell death-ligand 1 (PD-L1) inhibitors. Microbiota-modulating treatments such as probiotics showed the ability to enhance response to immunotherapy, indicating their potential use as adjunct therapies in breast cancer treatment.

CONCLUSIONS: The composition of gut microbiota could help predict the chance of response to immunotherapy, and modulating gut microbiota has the potential to enhance the efficacy of chemo-immunotherapy in breast cancer. However, the available data relating to breast cancer are limited. Larger prospective studies are required to further elucidate their role as a biomarker and treatment.}, } @article {pmid39534519, year = {2024}, author = {Jeyaraman, N and Jeyaraman, M and Mariappan, T and Muthu, S and Ramasubramanian, S and Sharma, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Insights of gut-liver axis in hepatic diseases: Mechanisms, clinical implications, and therapeutic potentials.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {15}, number = {6}, pages = {98146}, pmid = {39534519}, issn = {2150-5349}, abstract = {With the rising prevalence of chronic liver diseases worldwide, there exists a need to diversify our artillery to incorporate a plethora of diagnostic and therapeutic methods to combat this disease. Currently, the most common causes of liver disease are non-alcoholic fatty liver disease, hepatitis, and alcoholic liver disease. Some of these chronic diseases have the potential to transform into hepatocellular carcinoma with advancing fibrosis. In this review, we analyse the relationship between the gut and liver and their significance in liver disease. This two-way relationship has interesting effects on each other in liver diseases. The gut microbiota, through its metabolites, influences the metabolism in numerous ways. Careful manipulation of its composition can lead to the discovery of numerous therapeutic potentials that can be applied in the treatment of various liver diseases. Numerous cohort studies with a pan-omics approach are required to understand the association between the gut microbiome and hepatic disease progression through which we can identify effective ways to deal with this issue.}, } @article {pmid39534419, year = {2024}, author = {Wang, J and Meng, Y and Guo, ZG}, title = {Contribution of gut microbiota to the development of Crohn's disease: Insights gained from fecal microbiota transplantation studies in mice.}, journal = {World journal of gastroenterology}, volume = {30}, number = {41}, pages = {4514-4517}, pmid = {39534419}, issn = {2219-2840}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Crohn Disease/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Mice ; *Disease Models, Animal ; Humans ; Mesentery ; Feces/microbiology ; Intestines/microbiology/immunology ; Adipose Tissue/immunology ; }, abstract = {We would like to present some new thoughts on the publication in the journal published in August 2024 in World Journal of Gastroenterology. We specifically focused on the alterations in the intestinal tract, mesenteric adipose tissue (MAT), and systemic inflammatory changes in mice following fecal flora transplantation into a mouse model of Crohn's disease (CD). Accumulating evidence suggests that the occurrence of CD is influenced by environmental factors, host immune status, genetic susceptibility, and flora imbalance. One microbiota-based intervention, fecal microbiota transplantation, has emerged as a potential treatment option for CD. The MAT is considered a "second barrier" around the inflamed intestine. The interaction between gut microbes and inflammatory changes in MAT has attracted considerable interest. In the study under discussion, the authors transplanted fetal fecal microorganisms from patients with CD and clinically healthy donors, respectively, into 2,4,6-trinitrobenzene sulfonic acid-induced CD mice. The research explored the complex interplay between MAT, creeping fat, inflammation, and intestinal flora in CD by evaluating intestinal and mesenteric lesions, along with the systemic inflammatory state in the mice. This article provides several important insights. First, the transplantation of intestinal flora holds significant potential as a therapeutic strategy for CD, offering hope for patients with CD. Second, it presents a novel approach to the diagnosis and treatment of CD: The inflammatory response in CD could potentially be assessed through pathological or imaging changes in the MAT, and CD could be treated by targeting the inflammation of the MAT.}, } @article {pmid39533632, year = {2024}, author = {Philips, CA and Ahamed, R and Oommen, TT and Nahaz, N and Tharakan, A and Rajesh, S and Augustine, P}, title = {Clinical outcomes and associated bacterial and fungal microbiota changes after high dose probiotic therapy for severe alcohol-associated hepatitis: An observational study.}, journal = {Medicine}, volume = {103}, number = {45}, pages = {e40429}, pmid = {39533632}, issn = {1536-5964}, mesh = {Humans ; *Hepatitis, Alcoholic/therapy ; Male ; *Probiotics/administration & dosage/therapeutic use ; Middle Aged ; Female ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation/methods ; Adult ; Treatment Outcome ; Adrenal Cortex Hormones/administration & dosage/therapeutic use ; Mycobiome ; Dysbiosis/therapy/microbiology ; }, abstract = {Alcohol-associated hepatitis (AH) is a critical condition with high mortality rates and is worsened by infections. Organ failure is strongly associated with intestinal dysbiosis. Emerging research suggests that gut microbiota modulation with probiotics can improve AH outcomes. This study investigated the clinical and microbiome effects of high-dose probiotic infusion (HDPI) compared with corticosteroid therapy (CST) and fecal microbiota transplantation (FMT) in severe AH. Patients with biopsy-proven severe-AH were enrolled from March 2019 to June 2020 and matched for age and disease severity. The patients received HDPI (n = 20), FMT (n = 16), or CST (n = 14). HDPI consists of a potent probiotic mix delivered via a nasoduodenal tube for 6 days. The primary outcome was survival at 90-days. Stool samples were subjected to 16S and 18S rRNA sequencing to assess significant bacterial and fungal taxa and their interactions at baseline and post treatment. At 90-days, survival rates were 55%, 64.3%, and 87.5% (HDPI, CST, respectively). HDPI did not beneficially impact bacterial alpha-diversity but significantly altered beta-diversity. Notably, the number of pathogenic bacteria, such as Bilophila and Roseburia increased. Fungal analysis revealed no significant changes in alpha diversity, but significant dissimilarities in beta diversity post-HDPI. New fungal genera such as Basidiomycota and Phragmoplastophyta have emerged, with significant deleterious expansion in fungal communities and damaging modifications between fungal-bacterial interactions. HDPI failed to outperform CST in improving the clinical outcomes of patients with severe AH. While HDPI influenced both bacterial and fungal microbiomes, it also led to the persistence of pathogenic communities. FMT showed superior survival outcomes, highlighting the urgent need for further controlled trials.}, } @article {pmid39533343, year = {2024}, author = {Guo, X and Xu, J and Zhao, Y and Wang, J and Fu, T and Richard, ML and Sokol, H and Wang, M and Li, Y and Liu, Y and Wang, H and Wang, C and Wang, X and He, H and Wang, Y and Ma, B and Peng, S}, title = {Melatonin alleviates heat stress-induced spermatogenesis dysfunction in male dairy goats by regulating arachidonic acid metabolism mediated by remodeling the gut microbiota.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {233}, pmid = {39533343}, issn = {2049-2618}, support = {32072815//National Natural Science Foundation of China/ ; 2022YFD1300200//National Key Research and Development Program of China/ ; 2023-YBNY-140//General Project of the Key R & D Plan of Shaanxi Province/ ; TG20221184//Ningbo Second Hormone Factory/ ; }, mesh = {Animals ; *Melatonin/pharmacology ; Male ; *Spermatogenesis/drug effects ; *Goats ; *Gastrointestinal Microbiome/drug effects ; *Testis/drug effects/metabolism ; Mice ; *Heat-Shock Response/drug effects ; *Arachidonic Acid/metabolism ; Spermatozoa/drug effects ; Oxidative Stress/drug effects ; }, abstract = {BACKGROUND: Heat stress (HS) commonly occurring in summer has gradually become a factor threatening the reproductive performance of male dairy goats by reducing their fecundity. Despite the melatonin is applied to relieve HS, it is still unclear whether melatonin protects against reproductive damage induced by HS in dairy goats and how it works. The purpose of the present study is to evaluate the role of melatonin in alleviating HS-induced spermatogenesis dysfunction in male dairy goats and further explore its mechanism.

RESULTS: HS impaired spermatogenesis, sperm formation in the testes, and sperm maturation in the epididymis of dairy goats, resulting in decreased sperm quality. Melatonin rescued the decrease of sperm quality induced by HS via decreasing inflammatory and oxidative stress levels in testicular tissue and enhancing intercellular barrier function within the testes. Amplicon-based microbiota analysis revealed that despite gut microbiota differences between melatonin-treated dairy goats and NC dairy goats to some extent, melatonin administration tends to return the gut microbiota of male dairy goats under HS to the levels of natural control dairy goats. To explore whether the protective role of melatonin in sperm quality is mediated by regulating gut microbiota, fecal microbiota of HS dairy goats with or without melatonin treatment were transferred to HS mice, respectively. We found HS mice that had received fecal bacteria of HS dairy goats experienced serious testicular injury and dyszoospermia, while this phenomenon was ameliorated in HS mice that had received fecal bacteria of dairy goats treated with melatonin, indicating melatonin alleviates HS-induced spermatogenic damage in a microbiota dependent manner. We further found that the testicular tissue of both HS dairy goats and mice transplanted with HS dairy goat feces produced large amounts of arachidonic acid (AA)-related metabolites, which were closely associated with semen quality. Consistently, supplementation with AA has been shown to elevate the levels of inflammation and oxidative stress in the testicular tissue of mice, disrupting intercellular connections and ultimately leading to spermatogenic disorders.

CONCLUSION: This study has revealed that melatonin can effectively alleviate spermatogenic disorders in dairy goats caused by HS. This beneficial effect was primarily achieved through the modulation of gut microbiota, which subsequently inhibited the excessive synthesis of AA in testicular tissue. These discoveries are of great significance for preventing or improving the decline in male livestock reproductive performance caused by HS, enhancing the reproductive efficiency of elite male breeds, and ultimately improving the production efficiency of animal husbandry. Video Abstract.}, } @article {pmid39531305, year = {2024}, author = {Tursumetova, DR and Khan, Y and Tkacheva, LV and Rayevskii, KP}, title = {[The role and features of the gut microbiota in Alzheimer's disease.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {37}, number = {4}, pages = {442-452}, pmid = {39531305}, issn = {1561-9125}, mesh = {*Alzheimer Disease/microbiology/therapy/physiopathology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics/administration & dosage/therapeutic use ; Fecal Microbiota Transplantation/methods ; Prebiotics/administration & dosage ; Brain-Gut Axis/physiology ; Disease Progression ; }, abstract = {Alzheimer's disease causes gradual, persistent deterioration of cognitive function in the elderly, causing social and economic damage to society. Over the past decades, mankind has made significant progress in the study of Alzheimer's disease, but there are no methods to fully control the disease. The lack of effectiveness of existing treatment methods emphasizes the need to search for new approaches. The present review is devoted to the study of the latest data regarding the role of microbiota in the mechanisms of formation and progression of Alzheimer's disease, possible therapeutic ways to influence the processes of neurodegeneration through microbiota and taking into account identified relationships. The article considers the axis «gut microbiota-brain» as a link in the pathogenesis of neuroinflammation. New data on the influence of gut microbiota on neurodegenerative processes through metabolic, nervous, and immune mechanisms is analyzed. New data reveals correlations between microbiota specifics and the origin and/or progression of Alzheimer's disease, expanding the understanding of disease pathogenesis. The role of the oral microbiota in neurodegeneration processes is mentioned, emphasizing the diverse mechanisms of this disease. Available therapies for Alzheimer's disease are discussed, including probiotics and prebiotics, fecal microbiota transplantation, and dietary correction.}, } @article {pmid39529641, year = {2024}, author = {Kirsch, P and Rauch, J and Delau, O and Axelrad, J and Chang, S and Shaukat, A}, title = {Prevalence of Active Pouch Symptoms and Patient Perception of Symptom Control and Quality of Life in an Outpatient Practice.}, journal = {Gastro hep advances}, volume = {3}, number = {8}, pages = {1069-1078}, pmid = {39529641}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Pouchitis is an inflammatory condition affecting the ileal pouch in patients' status after ileal pouch anal anastomosis (IPAA). This affects a significant portion of IPAA patients. Our aim was to study the prevalence of active pouch symptoms among currently treated outpatients with endoscopic pouchitis and understand patients' perspective of disease control and quality of life.

METHODS: We cross-sectionally reviewed the medical charts of patients who had undergone pouchoscopy at NYU Langone Health from 2010 to 2022 and recorded demographic, clinical, and endoscopic data. Based on the most recent data in the medical record, we defined active pouch symptoms as 2 or more current clinical symptoms and "endoscopic pouchitis" as "moderate" or "severe" by pouchoscopy. We also administered surveys in March 2023 to 296 patients with an IPAA to understand symptom control, quality of life, and interest in fecal microbiota transplant.

RESULTS: We identified 282 unique patients. The median age of patients was 46 (interquartile range 33-59), with 54.3% males. Of these, 37.2% of patients currently had active pouch symptoms, 36.9% had endoscopic pouchitis, and 14.9% met the criteria for both. Of the 296 surveys sent to patients with IPAA, 74 (25%) responded. The median age of respondents was 49.5 (interquartile range 34-62). 59.5% were male. Average treatment satisfaction score (scale of 0-10) was 6.4 and quality of life score was 5.8. A majority (64.9%) expressed interest in fecal microbiota transplant.

CONCLUSION: Outpatients with active pouch symptoms or endoscopic pouchitis have high prevalence of active disease and report ongoing symptoms. The results underscore the inadequacy of current treatments and highlight the need for additional therapeutic options.}, } @article {pmid39524804, year = {2024}, author = {Zhang, Y and Wu, Y and Guan, Y and Lu, Y and Zhu, W and Ping, F and Wang, Y}, title = {Maidong Dishao Decoction mitigates submandibular gland injury in NOD mice through modulation of gut microbiota and restoration of Th17/Treg immune balance.}, journal = {Heliyon}, volume = {10}, number = {21}, pages = {e38421}, pmid = {39524804}, issn = {2405-8440}, abstract = {BACKGROUND: Primary Sjogren's syndrome (pSS) is a common chronic autoimmune disease that presents limited treatment options and poses significant challenges for patients. Maidong Dishao Decoction (MDDST), a traditional Chinese medicine compound, has demonstrated potential in alleviating dryness symptoms associated with pSS. Therefore, it is important to study the specific mechanism of its therapeutic effect.

OBJECTIVE: This study aims to investigate the effects of MDDST on gut microbiota, short-chain fatty acids (SCFAs), and the Th17/Treg immune balance in non-obese diabetes (NOD) mice.

METHODS: The study employed ultrahigh-performance liquid chromatography coupled with quadrupole-exactive mass spectrometry (UHPLC-QE-MS) to identify the primary components of MDDST. Subsequently, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assays (ELISA), and flow cytometry analyses were conducted to evaluate the therapeutic effects of MDDST in NOD mice. Additionally, 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS) were utilized to assess the influence of MDDST on gut microbiota and SCFAs. Finally, fecal microbiota transplantation (FMT) and SCFA-based interventions were performed to elucidate the mechanisms through which MDDST exerts its effects.

RESULTS: The research findings demonstrate that MDDST exerts therapeutic effects on NOD mice, primarily manifested as reduced inflammation, decreased water intake, ameliorated pathological changes and lowered levels of Sjogren's syndrome antigen A (SSA) and immunoglobulin G (IgG). Additionally, MDDST significantly decreased serum levels of interleukin-6 (IL-6) and interleukin-17 (IL-17), while enhancing levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), thereby regulating the Th17/Treg immune balance. Further investigations revealed that MDDST treatment induces alterations in gut microbiota composition and elevates SCFA levels in the gut. Subsequent FMT and SCFA intervention experiments demonstrated a downregulation of pSS-related phenotypes.

CONCLUSION: In summary, MDDST demonstrates protective effects against pSS by restoring the balance between Th17 and Treg cells. The therapeutic effects can be partially attributed to its regulation of gut microbiota and SCFAs. Our finding provides a new option for treating pSS.}, } @article {pmid39530534, year = {2024}, author = {Kao, D and Wong, K and Jijon, H and Moayyedi, P and Franz, R and McDougall, C and Hotte, N and Panaccione, R and Semlacher, E and Kroeker, KI and Peerani, F and MacDonald, KV and Xu, H and Narula, N and Turbide, C and Marshall, DA and Madsen, KL}, title = {Preliminary results from a multicenter, randomized trial using fecal microbial transplantation to induce remission in patients with mild to moderate Crohn's disease.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000003196}, pmid = {39530534}, issn = {1572-0241}, abstract = {INTRODUCTION: Fecal microbial transplantation (FMT) has shown promise at inducing remission in ulcerative colitis. This study is the first of its kind to evaluate the efficacy and safety of FMT at inducing remission in Crohn's disease (CD).

METHODS: This double-blind, placebo-controlled trial was conducted in three Canadian academic centers; randomized patients with mild to moderate CD received FMT or placebo. The first treatment was administered by colonoscopy followed by weekly fecal capsules for 7 weeks. Primary endpoint was clinical and endoscopic remission at week 8. Secondary outcomes included clinical and endoscopic response, adverse events, and health-related quality of life using generic and disease-specific instruments.

RESULTS: From July 2017 to June 2021, 21 and 13 patients were randomized to FMT and placebo groups, respectively. The trial terminated early due to futility. At week 8, 0% (0/15) of patients in the FMT group versus 8.3% (1/11) in the placebo group reached the primary endpoint of combined clinical and endoscopic remission as per protocol analysis. There were no differences between the groups in clinical or endoscopic responses. One participant in each group had worsening of CD. Although both groups experienced statistically significant improvements in health-related quality of life, only the FMT group had a significant decrease in activity impairment. Although there were no significant changes in microbial diversity or composition, participants who achieved clinical response became more similar to their donors in stool microbial composition.

DISCUSSION: FMT was not effective at inducing clinical and endoscopic remission in CD using the FMT regimen in this study. Future studies may use other strategies to enhance treatment response, including longer intervention, antibiotic pretreatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet, biologic or small molecule therapies.}, } @article {pmid39528920, year = {2024}, author = {Laperrousaz, B and Levast, B and Fontaine, M and Nancey, S and Dechelotte, P and Doré, J and Lehert, P}, title = {Safety comparison of single-donor and pooled fecal microbiota transfer product preparation in ulcerative colitis: systematic review and meta-analysis.}, journal = {BMC gastroenterology}, volume = {24}, number = {1}, pages = {402}, pmid = {39528920}, issn = {1471-230X}, mesh = {*Colitis, Ulcerative/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Multiple studies have evaluated fecal microbiota transfer (FMT) in patients with ulcerative colitis (UC) using single-donor (SDN) and multidonor (MDN) products. Systematic review and meta-analysis were performed to compare the safety of SDN and MDN products.

METHODS: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence to identify studies that compared FMT products manufactured using SDN or MDN strategies against control treatment in patients with UC. Fifteen controlled studies were selected for meta-analysis (11 randomized controlled trials and 4 controlled cohort trials). Safety of each treatment type was assessed using the counts of adverse events and serious adverse events using fixed- and random-effects models. Significance of the indirect difference between FMT preparations was assessed using a network approach. Benefit-risk ratios were calculated by multiplicative utility model, incorporating geometric mean of risk ratios (RRs) of efficacy and safety.

RESULTS: Safety data was collected for a total of 587 patients (193 exposed to SDN products, 114 exposed to MDN products and 280 exposed to control treatment). The 12 studies showed similar overall safety event counts for MDN and SDN versus placebo (RRs: 0.90 and 1.09, respectively [P = 0.206 and P = 0.420, respectively]). Results indicated similar risk of safety events for MDN compared to SDN (RR: 0.83, P = 0.159). Positive benefit-risk ratios were demonstrated for MDN and SDN versus placebo (RRs: 1.70 and 1.16, respectively [P = 0.003 and P = 0.173, respectively]). MDN had a greater benefit-risk ratio compared to SDN (RR: 1.46, P = 0.072).

CONCLUSION: Similar safety profiles were observed for MDN and SDN strategies. Alongside previously described superior efficacy, treatment with MDN has greater benefit-risk ratio than SDN in patients with UC. Further development of MDN FMT treatment for UC should be considered.}, } @article {pmid39526563, year = {2024}, author = {Tessier, MEM and Schraw, JM and Beer, S and Harpavat, S and Kyle Jensen, M and Magee, JC and Ng, V and Scheurer, ME and Taylor, SA and Shneider, BL}, title = {The association of human milk intake and outcomes in biliary atresia.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.12403}, pmid = {39526563}, issn = {1536-4801}, support = {5K23-DK119567//National Institute of Diabetes, Digestive and Kidney Diseases/ ; U01DK103140//University of Utah/ ; U01DK062453//Children's Hospital Colorado/ ; U01DK062456//The University of Michigan/ ; U01DK103149//Texas Children's Hospital/ ; U01DK103135//The Hospital for Sick Children/ ; U24DK062456//ChiLDReN's Scientific Data Coordinating Center, Ann Arbor, MI/ ; }, abstract = {OBJECTIVES: Human milk intake has many benefits which could influence outcomes in biliary atresia (BA). However, the role of human milk in BA has not been examined. We hypothesized that human milk intake would be associated with improved outcomes in BA.

METHODS: We assessed the impact of any human milk (AHM) as compared to formula only (FO) intake before Kasai portoenterostomy (KP) on outcomes in 447 infants with BA using the PROBE database (NCT00061828) post hoc. The primary outcome was clearance of jaundice (COJ = total bilirubin (TB) < 2 mg/dL by 3 months post-KP). Secondary outcomes included 2-year native liver survival (SNL), bilirubin levels, cholangitis, ascites, and growth. We assessed the fecal microbiome (n = 8) comparing AHM versus FO.

RESULTS: At baseline, 211 infants received AHM and 215 received FO. 53.9% of AHM and 50.5% of FO achieved COJ (p = NS). SNL was insignificantly increased in AHM (odds ratio = 1.47, 95% confidence interval: 1.00-2.12, p = 0.053). TB decreased in AHM from 4 weeks to 3 months post-KP [4.8-4.0 mg/dL (p = 0.01)] unlike the FO group (4.9-4.9 mg/dL, p = 0.4). At 3 months post-KP, AHM infants had greater weight gain (1.88 ± 0.66 vs. 1.57 ± 0.73 kg, p < 0.001) and mid-upper arm circumference (12.9 ± 1.4 vs. 12.2 ± 1.7 cm, p < 0.001). Other secondary outcomes were not different. Microbiome differences were seen between AHM and FO.

CONCLUSIONS: Human milk intake in infants with BA did not significantly improve COJ or SNL. However, growth parameters were improved, and TB 3 months post-KP was decreased. Thus, human milk intake should not be discouraged. Prospective studies with detailed assessment of human milk intake are needed.}, } @article {pmid39515099, year = {2024}, author = {Yu, ZQ and Du, HX and Gao, S and Liang, CZ}, title = {Eriocalyxin B ameliorated experimental autoimmune prostatitis via modulation of macrophage polarization through gut microbiota-mediated vitamin D3 alteration.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156191}, doi = {10.1016/j.phymed.2024.156191}, pmid = {39515099}, issn = {1618-095X}, abstract = {BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a often heterogeneous condition in urology. Accumulating evidence suggests that the autoimmune response against prostate antigens is related to CP/CPPS. The gut microbiota may be a possible cause of a number of autoimmune diseases. Eriocalyxin B (EriB) is used as an anti-inflammatory treatment for autoimmune disorders. The underlying mechanism of fecal metabolome involved in CP/CPPS treatment by EriB remains unclear.

METHODS: The experimental autoimmune prostatitis (EAP) mouse model was generated by subcutaneous immunization. Macrophages, inflammatory cytokines, intestinal microbiota, and fecal metabolome of the mice were analyzed. The alteration of the fecal metabolome was investigated in detail in EriB-treated EAP mice and confirmed by in vitro experiments.

RESULTS: EriB ameliorated significantly decreased prostate inflammation in EAP mice and promoted macrophage phenotype polarizing from M1 to M2. The gut microbiome was altered, and intestinal barrier damage was improved by EriB treatment. Furthermore, the enrichment of vitamin digestion and absorption pathways in the fecal metabolome revealed that vitamin D3 was altered by EriB. In vitro experiments confirmed that macrophage polarization from M1 to M2 was promoted by vitamin D3. Finally, fecal transplantation from EriB-treated mice markedly reduced inflammatory indicators and the macrophage M1/M2 ratio in pseudogerm-free EAP mice. In our study, the immune state of macrophage regulated by gut microbiota-mediated vitamin D3 alteration was first time revealed in EAP treatment.

CONCLUSIONS: EriB ameliorated in mice with EAP, the gut microbiota mediates vitamin D3 alterations to modulate macrophage phenotype polarizing from M1 to M2.}, } @article {pmid39515036, year = {2024}, author = {Sun, B and Hu, C and Li, J and Yang, Z and Chen, L}, title = {Interaction between young fecal transplantation and perfluorobutanesulfonate endocrine disrupting toxicity in aged recipients: An estrobolome perspective.}, journal = {Environment international}, volume = {193}, number = {}, pages = {109133}, doi = {10.1016/j.envint.2024.109133}, pmid = {39515036}, issn = {1873-6750}, abstract = {Transplanting young feces into the aged was found to effectively counteract the endocrine disrupting effects of perfluorobutanesulfonate (PFBS) pollutant, showing promise in the maintenance of healthy aging. However, the interactive mechanisms between young fecal transplantation and PFBS endocrine disruption during aging remain unclear. In this follow-up study, aged zebrafish were administered young donor feces and then exposed to environmentally relevant concentrations of PFBS (0 and 100 μg/L). Alterations in the holistic estrobolome along gut-liver axis were investigated. The results showed that PFBS singular exposure significantly increased blood estradiol concentration in the aged, inducing an estrogenic activity. Concentrations of other estrogen forms, including estrone and estriol, were also disrupted by PFBS. Interestingly, young fecal transplant effectively mitigated the estrogenic toxicity of PFBS and largely restored estrogen equilibrium. After PFBS exposure, the transcriptions of estrogen metabolic genes were consistently upregulated in aged livers, causing the accumulation of 2-methoxyestradiol-3-methylether metabolite. In contrast, aged livers coexposed to young fecal transplant and PFBS enhanced the glucuronidation process, successfully facilitating the elimination and detoxification of estrogen metabolites. In aged gut, PFBS exposure inhibited β-glucuronidase enzyme activity, implying the suppression of estrogen deconjugation and recycle. However, in the combined group, β-glucuronidase activity was significantly stimulated, thus reestablishing estrobolome dynamics. Overall, current findings provide mechanistic insights into the antagonistic interaction between young fecal transplant and PFBS on reproductive endocrinology. Gut microbiota manipulation appears appealing to maintain healthy aging progression albeit the interruption of environmental xenobiotics.}, } @article {pmid39513042, year = {2024}, author = {Park, KJ and Gao, Y}, title = {Gut-brain axis and neurodegeneration: mechanisms and therapeutic potentials.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1481390}, pmid = {39513042}, issn = {1662-4548}, abstract = {This paper reviews the effects of gut microbiota in regulating neurodegenerative diseases through controlling gut-brain axis. Specific microbial populations and their metabolites (short-chain fatty acids and tryptophan derivatives) regulate neuroinflammation, neurogenesis and neural barrier integrity. We then discuss ways by which these insights lead to possible interventions - probiotics, prebiotics, dietary modification, and fecal microbiota transplantation (FMT). We also describe what epidemiological and clinical studies have related certain microbiota profiles with the courses of neurodegenerative diseases and how these impact the establishment of microbiome-based diagnostics and individualized treatment options. We aim to guide microbial ecology research on this key link to neurodegenerative disorders and also to highlight collaborative approaches to manage neurological health by targeting microbiome-related factors.}, } @article {pmid39510500, year = {2024}, author = {Scull, CE and Hu, Y and Jennings, S and Wang, G}, title = {Normalization of CF Immune System Reverses Intestinal Neutrophilic Inflammation and Significantly Improves the Survival of CF Mice.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101424}, doi = {10.1016/j.jcmgh.2024.101424}, pmid = {39510500}, issn = {2352-345X}, abstract = {BACKGROUND & AIMS: Cystic fibrosis (CF) is an autosomal recessive genetic disorder, affecting multiple organ systems. CF intestinal disease develops early, manifesting as intestinal bacterial overgrowth/dysbiosis, neutrophilic inflammation and obstruction. As unresolvable infection and inflammation reflect host immune deficiency, we sought to determine if the CF-affected immune system plays any significant role in CF intestinal disease pathogenesis.

METHODS: CF and sibling wild-type (WT) mice underwent reciprocal bone marrow transplantation. After immune reconstitution, their mortality, intestinal transit, fecal inflammatory markers, and mucosal immune cell composition were assessed. Moreover, reciprocal neutrophil transfusion was conducted to determine if neutrophil function affects intestinal movement. Furthermore, expression of induced nitric oxide synthase (iNOS) and production of nitric oxide (NO) in CF and WT neutrophils were compared. Lastly, specific iNOS inhibitor 1400W was tested to prevent CF intestinal obstruction.

RESULTS: Immune restoration in CF mice reversed the intestinal neutrophilic inflammation, improved the intestinal dysmotility, and rescued the mice from mortality. Transfusion of WT neutrophils into CF mice ameliorated the retarded bowel movement. CF neutrophils expressed significantly more iNOS and produced significantly more NO. Pharmaceutical blocking of iNOS significantly improved intestinal transit and survival of CF mice.

CONCLUSION: CF immune defect plays a critical role in CF intestinal disease development. Activation of iNOS in inflammatory cells produces excessive NO, slows the bowel movement, and facilitates intestinal paralysis and obstruction in CF. Thus, normalization of the CF immune system may offer a novel therapy to treat CF intestinal disease.}, } @article {pmid39510376, year = {2024}, author = {Huang, Y and You, Y and Wang, W and Chen, YH and Zhang, H and Li, QP and Liu, L and Tong, K and Sun, N and Hao, JR and Gao, C}, title = {Adenosine regulates depressive behavior in mice with chronic social defeat stress through gut microbiota.}, journal = {Neuropharmacology}, volume = {262}, number = {}, pages = {110209}, doi = {10.1016/j.neuropharm.2024.110209}, pmid = {39510376}, issn = {1873-7064}, abstract = {Major depressive disorder (MDD) is recognized as the most prevalent affective disorder worldwide. Metagenomic studies increasingly support a critical role for dysbiosis of gut microbiota in the development of depression. Previous studies have demonstrated that adenosine alleviates gut dysbiosis, suggesting that elevating adenosine levels could be a novel intervention for MDD; however, the mechanisms underlying this effect remain unclear. This study utilized 16S rRNA gene sequencing, fecal microbiota transplantation (FMT) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to test the hypothesis that increased adenosine alleviates depressive behaviors in male mice subjected to chronic social defeat stress (CSDS) through alterations to gut microbiota. The data showed that depression-susceptible (SUS) mice exhibited gut dysbiosis, and FMT from SUS mice increased depression-like behaviors in healthy recipients. In SUS mice, adenosine supplementation ameliorated both depression-like behaviors and abnormalities in gut microbiota, and co-administration of probiotics and adenosine not only mitigated depression-like behaviors but also enhanced gut barrier integrity. By including 83 depressed adolescents and 67 healthy controls, this study found that the level of short-chain fatty acids (SCFAs) in the depression group was reduced, this finding parallels reductions seen in SUS mice and in recipient mice after FMT from SUS donors. Conversely, supplementation with either adenosine or probiotics led increased SCFAs concentrations in the serum of SUS mice. These findings suggest that adenosine may alleviate depression-like behaviors in CSDS mice by modulating the gut microbiota. This effect is likely associated with increased serum SCFAs, metabolites produced by the gut microbiota, following adenosine supplementation.}, } @article {pmid39510013, year = {2024}, author = {Yang, D and Lv, G and Wu, Y and Guo, W and Wang, Y and Hu, J and Li, N and Zheng, F and Dai, Y and Pi, Z and Yue, H}, title = {Licorice-regulated gut-joint axis for alleviating collagen-induced rheumatoid arthritis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156203}, doi = {10.1016/j.phymed.2024.156203}, pmid = {39510013}, issn = {1618-095X}, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is partially affected by the integrity of the intestinal barrier. Licorice (GC), a medicinal and food-related herb, exhibits potent anti-inflammatory activity; however, studies on its mechanisms of action in RA are limited.

METHOD: Using a bovine type-II collagen-induced arthritis rat model, this study examined how GC influences the gut-joint axis to decrease RA. The Th17/Treg cell ratios in the blood, colon, and joints were also measured. Metabolomics and 16S rRNA sequencing were applied to explore the effects of variations in gut flora and metabolites.

RESULTS: The arthropathological slices, inflammation markers, and joint inflammation index scores in the GC treatment group significantly differed from those in the CIA group. Studies on the effect of GC on the gut-joint axis showed changes in the levels of lipopolysaccharide and diamine oxidase, both directly associated with intestinal permeability. ZO-1, occludin, and claudin-1, three intestinal tight-junction proteins, may express themselves more when exposed to GC. By maintaining an appropriate Th17/Treg cell ratio in the blood, colon, and joints, GC may reduce impaired to the intestinal barrier. An imbalance in the intestinal microenvironment, caused by modifications in gut flora and endogenous substances, can damage the intestinal barrier. GC may modify the relative abundances of Papillibacter, Clostridium, Eubacterium, Helicobacter, Provotella, and Barnesiella during RA treatment by repairing the intestinal barrier. The metabolic differences were mainly related to primary bile acid biosynthesis, pyrimidine metabolism, steroid biosynthesis, biotin metabolism, and sphingolipid metabolism. A fecal microbiota transplantation experiment confirmed the involvement of the gut microbiota and its metabolites in GC-mediated RA therapy.

CONCLUSION: The results demonstrated that GC repairs the intestinal barrier and adjusts the gut-joint axis to manage immunological imbalance in RA.}, } @article {pmid39509684, year = {2024}, author = {L'Huillier, JC and Guo, WA}, title = {The always evolving diagnosis and management of Clostridioides difficile colitis: What you need to know.}, journal = {The journal of trauma and acute care surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/TA.0000000000004474}, pmid = {39509684}, issn = {2163-0763}, abstract = {The diagnosis, pharmacologic management, and surgical options for Clostridioides difficile infection (CDI) are rapidly evolving, which presents a challenge for the busy surgeon to remain up to date on the latest clinical guidelines. This review provides an evidence-based practical guide for CDI management tailored to the needs of surgeons and surgical intensivists. Historically, the diagnosis of CDI relied on slow cell culture cytotoxicity neutralization assays, but now, the rapidly resulting nucleic acid amplification tests and enzyme immunoassays have become mainstream. In terms of antibiotic therapy, metronidazole and oral vancomycin were the main "workhorse" antibiotics in the early 2000s, but large randomized controlled trials have now demonstrated that fidaxomicin produces superior results. Regarding surgical intervention, total abdominal colectomy was once the only procedure of choice; however, diverting loop ileostomy with colonic lavage is emerging as a viable alternative. Finally, novel adjuncts such as fecal microbiota transplantation and targeted therapy against toxin B (bezlotoxumab) are playing an increasingly important role in the management of CDI.}, } @article {pmid39507519, year = {2024}, author = {Claassen-Weitz, S and du Toit, E and Gardner-Lubbe, S and Kullin, B and Bellairs, G and Hilton, C and Chicken, A and Welp, K and Livingstone, H and Brink, A}, title = {Knowledge and perceptions of South African blood donors towards biobanking and stool donation.}, journal = {Southern African journal of infectious diseases}, volume = {39}, number = {1}, pages = {645}, pmid = {39507519}, issn = {2313-1810}, abstract = {BACKGROUND: The complexity of contexts and varied purposes for which biome donation are requested are unknown in South Africa.

OBJECTIVES: The aim of this study was to provide strategic data towards actualisation of whether a stool donor bank may be established as a collaborative between Western Cape Blood Services (WCBS) and the University of Cape Town (UCT).

METHOD: We designed a cross-sectional, questionnaire-based survey to determine willingness of WCBS blood donors to donate stool specimens for microbiome biobanking. The study was conducted between 01 June 2022 and 01 July 2022 at three WCBS donation centres in Cape Town, South Africa. Anonymous blood donors who met the inclusion criteria were enrolled. Anonymised demographic and interview data were analysed statistically.

RESULTS: Analysis of responses from 209/231 blood donors demonstrated in a logistic regression model that compensation (p < 0.001) and 'societal benefit outweighs inconvenience' beliefs (p = 7.751e-05) were covariates significantly associated with willingness to donate stool. Age was borderline significant at a 5% level (p = 0.0556). Most willing stool donors indicated that donating stool samples would not affect blood donations (140/157, 90%). Factors decreasing willingness to donate were stool collection being unpleasant or embarrassing.

CONCLUSION: The survey provides strategic data for the establishment of a stool bank and provided an understanding of the underlying determinants regarding becoming potential donors.

CONTRIBUTION: This is the first report on the perspectives of potential participants in donating samples towards a stool microbiome biobank in South Africa, a necessity for faecal microbiota transplantation (FMT).}, } @article {pmid39523344, year = {2024}, author = {You, X and Yan, J and Herzog, J and Nobakhti, S and Campbell, R and Hoke, A and Hammamieh, R and Sartor, RB and Shefelbine, S and Kacena, MA and Chakraborty, N and Charles, JF}, title = {Bone loss with aging is independent of gut microbiome in mice.}, journal = {Bone research}, volume = {12}, number = {1}, pages = {65}, pmid = {39523344}, issn = {2095-4700}, support = {R01-AG046257//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P30-AR070253//U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/ ; P40-OD010995//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30-DK034987//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 997397//Crohn's and Colitis Foundation (Crohn's & Colitis Foundation)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Aging/physiology ; Male ; Mice ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Bone Resorption/microbiology ; Germ-Free Life ; }, abstract = {Emerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice. The bone phenotype of 24-month-old germ-free (GF) mice was indistinguishable compared to their littermates colonized by fecal transplant at 1-month-old. Moreover, bone loss from 3 to 24-month-old was comparable between GF and specific pathogen-free (SPF) mice. Thus, GF mice were not protected from age-related bone loss. 16S rRNA gene sequencing of fecal samples from 3-month and 24-month-old SPF males indicated an age-dependent microbial shift with an alteration in energy and nutrient metabolism potential. An integrative analysis of 16S predicted metagenome function and LC-MS fecal metabolome revealed an enrichment of protein and amino acid biosynthesis pathways in aged mice. Microbial S-adenosyl methionine metabolism was increased in the aged mice, which has previously been associated with the host aging process. Collectively, aging caused microbial taxonomic and functional alteration in mice. To demonstrate the functional importance of young and old microbiome to bone, we colonized GF mice with fecal microbiome from 3-month or 24-month-old SPF donor mice for 1 and 8 months. The effect of microbial colonization on bone phenotypes was independent of the microbiome donors' age. In conclusion, our study indicates age-related bone loss occurs independent of gut microbiome.}, } @article {pmid39522895, year = {2024}, author = {Wan, J and Wang, F and Xiao, Y and Cheng, Y and Zhen, S and Jiang, Q and Tan, B and Li, X and Chen, J and Liao, S}, title = {Poria cocos polysaccharides alleviate dextran sulphate sodium-induced ulcerative colitis in mice by modulating intestinal inflammatory responses and microbial dysbiosis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {137450}, doi = {10.1016/j.ijbiomac.2024.137450}, pmid = {39522895}, issn = {1879-0003}, abstract = {Poria cocos polysaccharide (PCP), one of the main active components of P. cocos, is extensively used worldwide and exhibits strong pharmacological effects. However, whether PCP can attenuate inflammatory bowel disease remains unclear. In this study, we assessed the effects of PCP supplementation on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice. We found that PCP supplementation mitigated UC symptoms in DSS-treated mice, as evidenced by reductions in body weight loss, colon length shortening and disease activity index score. Importantly, PCP supplementation enhanced colonic barrier integrity by increasing tight junction protein abundance and exerted anti-inflammatory effects by suppressing nuclear factor-κB (NF-κB) activation in DSS-treated mice. Furthermore, PCP supplementation reversed DSS-induced dysbiosis in colonic microbiota by increasing the colonic abundance of beneficial bacteria (e.g. Akkermansiaceae) and decreasing the colonic abundance of harmful bacteria (e.g. Erysipelotrichaceae) in DSS-treated mice. Although PCP supplementation failed to ameliorate DSS-induced UC in antibiotic-treated mice, faecal microbiota transplantation from PCP-administered mice ameliorated DSS-induced UC in antibiotic-treated mice. In summary, PCP alleviates UC in mice by attenuating intestinal inflammation via the inhibition of NF-κB activation and modulating the intestinal microbiota.}, } @article {pmid39522254, year = {2024}, author = {Li, X and Khan, I and Han, R and Huang, G and Xia, W and Yin, L and Leong, WK and Su, L and Law, BY and Wong, VKW and Wu, Q and Guo, X and Hsiao, WLW}, title = {Gynostemma pentaphyllum saponins shield mice from peanut allergy by modulation of gut microbiota: A novel approach for peanut allergy management.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156101}, doi = {10.1016/j.phymed.2024.156101}, pmid = {39522254}, issn = {1618-095X}, abstract = {BACKGROUND: Food allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective.

PURPOSE: This study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments.

METHODS: To elucidate the role of GpS on peanut allergy, we first built a PN-sensitized C57BL/6J model mice. Through comprehensive sequencing analysis, we identified Parabacteroides distasonis as a key bacterium triggering PN sensitization. Employing the same mouse model, GpS was evaluated for its effects on anaphylactic symptoms, serum immunoglobulin levels, and allergy-related biomarkers. 16S rRNA sequencing and transcriptomic analysis were applied to investigate the impact of GpS on the host's gut epithelium and microbiome.

RESULTS: GpS treatment effectively reduced anaphylactic symptoms in PN-sensitized mice, as shown by decreased IgG1, total IgE, and PN-specific IgE levels. It also modulated the immune response by suppressing proinflammatory cytokines (IL-1β, IFN-γ, IL-21) and chemokines (CCL5, CCL12, CCL17, CCL22), while enhancing anti-inflammatory cytokines (IL-4, IL-10, IL-12, IL-13). Fecal microbial transplant from GpS-treated Model mice to PN-sensitized mice displayed anti-peanut allergy effects. Additionally, the administration of GpS-enhanced bacteria (Clostridium aldenese or Lactobacillus murinus), alleviated anaphylactic symptoms and reduced serum allergy markers in PN-sensitized mice.

CONCLUSION: To conclude, we revealed the intestinal environment, signaling molecules, mucosal cytokines, and commensal microbial profiles in the peanut-sensitized mouse model. We further presented evidence for the protective effect of GpS against PN allergen sensitization by downregulating a series of food-allergy-associated biomarkers and cytokines via the modulation of gut bacteria. More importantly, supported by both in vitro and in vivo experiments, we demonstrated that the protective effect of GpS against PN-allergy is through the enhancement of two commensal bacteria, Clostridium aldenese, and Lactobacillus murinus.}, } @article {pmid39521596, year = {2024}, author = {Hurtado-Lorenzo, A and Swantek, JL}, title = {The landscape of new therapeutic opportunities for IBD.}, journal = {Advances in pharmacology (San Diego, Calif.)}, volume = {101}, number = {}, pages = {1-83}, doi = {10.1016/bs.apha.2024.10.011}, pmid = {39521596}, issn = {1557-8925}, mesh = {Humans ; *Inflammatory Bowel Diseases/drug therapy/therapy/immunology ; Animals ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, abstract = {This chapter presents an overview of the emerging strategies to address the unmet needs in the management of inflammatory bowel diseases (IBD). IBD poses significant challenges, as over half of patients experience disease progression despite interventions, leading to irreversible complications, and a substantial proportion do not respond to existing therapies, such as biologics. To overcome these limitations, we describe a diverse array of novel therapeutic approaches. In the area of immune homeostasis restoration, the focus is on targeting cytokine networks, leukocyte trafficking, novel immune pathways, and cell therapies involving regulatory T cells and mesenchymal stem cells (MSC). Recognizing the critical role of impaired intestinal barrier integrity in IBD, we highlight therapies aimed at restoring barrier function and promoting mucosal healing, such as those targeting cell proliferation, tight junctions, and lipid mediators. Addressing the challenges posed by fibrosis and fistulas, we describe emerging targets for reversing fibrosis like kinase and cytokine inhibitors and nuclear receptor agonists, as well as the potential of MSC for fistulas. The restoration of a healthy gut microbiome, through strategies like fecal microbiota transplantation, rationally defined bacterial consortia, and targeted antimicrobials, is also highlighted. We also describe innovative approaches to gut-targeted drug delivery to enhance efficacy and minimize side effects. Reinforcing these advancements is the critical role of precision medicine, which emphasizes the use of multiomics analysis for the discovery of biomarkers to enable personalized IBD care. Overall, the emerging landscape of therapeutic opportunities for IBD holds great potential to surpass the therapeutic ceiling of current treatments.}, } @article {pmid39521225, year = {2024}, author = {Yang, X and Zhang, X and Ma, Y and Li, S and Wang, Q and Hong, JS and Yu, G and Qi, B and Wang, J and Liu, C and Shang, Q and Wu, X and Zhao, J}, title = {Fucoidan ameliorates rotenone-induced Parkinsonism in mice by regulating the microbiota-gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {137373}, doi = {10.1016/j.ijbiomac.2024.137373}, pmid = {39521225}, issn = {1879-0003}, abstract = {Microbiota-gut-brain axis, the bidirectional relationship between the gut microbiota and the brain, has been increasingly appreciated in the pathogenesis of Parkinson's disease (PD). Fucoidan, a sulphate-rich polysaccharide, has been shown to be neuroprotective by reducing oxidative stress in PD models. However, the role of microbiota-gut-brain axis in the neuroprotective activity of fucoidan has not been revealed. In this study, the therapeutic effects of fucoidan and involvement of microbiota-gut-brain axis in rotenone (ROT)-induced PD were investigated. The results showed that fucoidan gavage attenuated neuroinflammation, dopamine neuronal damage and motor dysfunction in ROT-induced PD mice. In addition, fucoidan treatment ameliorated gut dysfunction, intestinal inflammation and disruption of the intestinal barrier in PD mice. Fucoidan also affected the composition of gut microbiota in PD mice, indicated particularly by decreased abundance of Akkermansia muciniphila and Lactobacillus johnsonii and increased abundance of Lactobacillus murinus. Mechanistic studies showed that fecal microbiota transplantation (FMT) from the fucoidan-treated mice and probiotic Lactobacillus murinus supplement are as potent as fucoidan treatment in attenuating peripheral and central inflammation and ameliorating dopamine neuronal damage, which might be attributed to the downregulation of LPS/TLR4/NF-κB signaling pathway. Our study suggests that fucoidan might be potential candidates for the treatment of PD.}, } @article {pmid39519488, year = {2024}, author = {Pinto, C and Carrasco-Loncharic, T and González-Mienert, E and de Solminihac, J and Gálvez-Jirón, F and Cifuentes, F and Pino-Lagos, K}, title = {IL-33 Induces a Switch in Intestinal Metabolites Revealing the Tryptophan Pathway as a Target for Inducing Allograft Survival.}, journal = {Nutrients}, volume = {16}, number = {21}, pages = {}, doi = {10.3390/nu16213655}, pmid = {39519488}, issn = {2072-6643}, support = {1210654//Fondo Nacional de Desarrollo Científico y Tecnológico (Fondecyt)/ ; }, mesh = {Animals ; *Tryptophan/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Graft Survival/drug effects ; *Interleukin-33/metabolism ; *Skin Transplantation ; *T-Lymphocytes, Regulatory/metabolism ; Mice ; *Mice, Inbred C57BL ; Intestines/drug effects ; Allografts ; Mice, Inbred BALB C ; Male ; Kynurenic Acid/metabolism ; Dysbiosis ; }, abstract = {BACKGROUND: IL-33, a pleiotropic cytokine, has been associated with a plethora of immune-related processes, both inflammatory and anti-inflammatory. T regulatory (Treg) cells, the main leukocyte population involved in immune tolerance, can be induced by the administration of IL-33, the local microbiota, and its metabolites. Here, we demonstrate that IL-33 drastically induces the production of intestinal metabolites involved on tryptophan (Trp) metabolism.

METHODS: naïve mice were treated with IL-33 for 4 days and leukocyte populations were analyzed by flow cytometry, and feces were processed for microbiota and intestinal metabolites studies. Using a murine skin transplantation model, the effect of Kynurenic acid (KA) on allograft survival was tested.

RESULTS: Under homeostatic conditions, animals treated with IL-33 showed an increment in Treg cell frequencies. Intestinal bacterial abundance analysis indicates that IL-33 provokes dysbiosis, demonstrated by a reduction in Enterobacteria and an increment in Lactobacillus genera. Furthermore, metabolomics analysis showed a dramatic IL-33 effect on the abundance of intestinal metabolites related to amino acid synthesis pathways, highlighting molecules linked to Trp metabolism, such as kynurenic acid (KA), 5-Hydroxyindoleacetic acid (5-HIAA), and 6-Hydroxynicotinic acid (6-HNA), which was supported by an enhanced expression of Ido and Kat mRNA in MLN cells, which are two enzymes involved on KA synthesis. Interestingly, animals receiving KA in drinking water and subjected to skin transplantation showed allograft acceptance, which is associated with an increment in Treg cell frequencies.

CONCLUSIONS: Our study reveals a new property for IL-33 as a modulator of the intestinal microbiota and metabolites, especially those involved with Trp metabolism. In addition, we demonstrate that KA favors Tregs in vivo, positively affecting skin transplantation survival.}, } @article {pmid39519055, year = {2024}, author = {Misiąg, P and Molik, K and Kisielewska, M and Typek, P and Skowron, I and Karwowska, A and Kuźnicki, J and Wojno, A and Ekiert, M and Choromańska, A}, title = {Amelanotic Melanoma-Biochemical and Molecular Induction Pathways.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, doi = {10.3390/ijms252111502}, pmid = {39519055}, issn = {1422-0067}, mesh = {Humans ; *Melanoma, Amelanotic/metabolism/genetics/pathology ; Proto-Oncogene Proteins B-raf/genetics/metabolism/antagonists & inhibitors ; Biomarkers, Tumor/metabolism ; Proto-Oncogene Proteins c-kit/genetics/metabolism/antagonists & inhibitors ; Skin Neoplasms/metabolism/genetics/pathology/therapy ; Melanins/metabolism/biosynthesis ; Signal Transduction ; }, abstract = {Amelanotic melanoma (AM) is a subtype of hypomelanotic or completely amelanotic melanoma. AM is a rare subtype of melanoma that exhibits a higher recurrence rate and aggressiveness as well as worse surveillance than typical melanoma. AM shows a dysregulation of melanin production, cell cycle control, and apoptosis pathways. Knowing these pathways has an application in medicine due to targeted therapies based on the inhibiting elements of the abovementioned pathways. Therefore, we summarized and discussed AM biochemical and molecular induction pathways and personalized medicine approaches, clinical management, and future directions due to the fact that AM is relatively rare. AM is commonly misdiagnosed. Hence, the role of biomarkers is becoming significant. Nonetheless, there is a shortage of biomarkers specific to AM. BRAF, NRAS, and c-KIT genes are the main targets of therapy. However, the role of BRAF and KIT in AM varied among studies. BRAF inhibitors combined with MAK inhibitors demonstrate better results. Immune checkpoint inhibitors targeting CTLA-4 combined with a programmed death receptor 1 (PD-1) show better outcomes than separately. Fecal microbiota transplantation may overcome resistance to immune checkpoint therapy of AM. Immune-modulatory vaccines against indoleamine 2,3-dioxygenase (IDO) and PD ligand (PD-L1) combined with nivolumab may be efficient in melanoma treatment.}, } @article {pmid39518717, year = {2024}, author = {Brusnic, O and Onisor, D and Boicean, A and Hasegan, A and Ichim, C and Guzun, A and Chicea, R and Todor, SB and Vintila, BI and Anderco, P and Porr, C and Dura, H and Fleaca, SR and Cristian, AN}, title = {Fecal Microbiota Transplantation: Insights into Colon Carcinogenesis and Immune Regulation.}, journal = {Journal of clinical medicine}, volume = {13}, number = {21}, pages = {}, doi = {10.3390/jcm13216578}, pmid = {39518717}, issn = {2077-0383}, abstract = {Colorectal cancer (CRC) constitutes a significant global health challenge, with recent studies underscoring the pivotal role of the gut microbiome in its pathogenesis and progression. Fecal microbiota transplantation (FMT) has emerged as a compelling therapeutic approach, offering the potential to modulate microbial composition and optimize treatment outcomes. Research suggests that specific bacterial strains are closely linked to CRC, influencing both its clinical management and therapeutic interventions. Moreover, the gut microbiome's impact on immunotherapy responsiveness heralds new avenues for personalized medicine. Despite the promise of FMT, safety concerns, particularly in immunocompromised individuals, remain a critical issue. Clinical outcomes vary widely, influenced by genetic predispositions and the specific transplantation methodologies employed. Additionally, rigorous donor selection and screening protocols are paramount to minimize risks and maximize therapeutic efficacy. The current body of literature advocates for the establishment of standardized protocols and further clinical trials to substantiate FMT's role in CRC management. As our understanding of the microbiome deepens, FMT is poised to become a cornerstone in CRC treatment, underscoring the imperative for continued research and clinical validation.}, } @article {pmid39508236, year = {2024}, author = {Shen, H and Zhang, C and Zhang, Q and Lv, Q and Liu, H and Yuan, H and Wang, C and Meng, F and Guo, Y and Pei, J and Yu, C and Tie, J and Chen, X and Yu, H and Zhang, G and Wang, X}, title = {Gut microbiota modulates depressive-like behaviors induced by chronic ethanol exposure through short-chain fatty acids.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {290}, pmid = {39508236}, issn = {1742-2094}, support = {82271931//National Natural Science Foundation of China/ ; 82101979//National Natural Science Foundation of China/ ; 2022-MS-220//Natural Science Foundation of Liaoning Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Ethanol/toxicity/administration & dosage/pharmacology ; *Depression/chemically induced/metabolism ; *Fatty Acids, Volatile/metabolism ; Male ; *Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Anxiety/chemically induced ; Central Nervous System Depressants/pharmacology/toxicity ; }, abstract = {BACKGROUND: Chronic ethanol exposure (CEE) is recognized as an important risk factor for depression, and the gut-brain axis has emerged as a key mechanism underlying chronic ethanol exposure-induced anxiety and depression-like behaviors. Short-chain fatty acids (SCFAs), which are the key metabolites generated by gut microbiota from insoluble dietary fiber, exert protective roles on the central nervous system, including the reduction of neuroinflammation. However, the link between gut microbial disturbances caused by chronic ethanol exposure, production of SCFAs, and anxiety and depression-like behaviors remains unclear.

METHODS: Initially, a 90-day chronic ethanol exposure model was established, followed by fecal microbiota transplantation model, which was supplemented with SCFAs via gavage. Anxiety and depression-like behaviors were determined by open field test, forced swim test, and elevated plus-maze. Serum and intestinal SCFAs levels were quantified using GC-MS. Changes in related indicators, including the intestinal barrier, intestinal inflammation, neuroinflammation, neurotrophy, and nerve damage, were detected using Western blotting, immunofluorescence, and Nissl staining.

RESULTS: Chronic ethanol exposure disrupted with gut microbial homeostasis, reduced the production of SCFAs, and led to anxiety and depression-like behaviors. Recipient mice transplanted with fecal microbiota that had been affected by chronic ethanol exposure exhibited impaired intestinal structure and function, low levels of SCFAs, intestinal inflammation, activation of neuroinflammation, a compromised blood-brain barrier, neurotrophic defects, alterations in the GABA system, anxiety and depression-like behaviors. Notably, the negative effects observed in these recipient mice were significantly alleviated through the supplementation of SCFAs.

CONCLUSION: SCFAs not only mitigate damage to intestinal structure and function but also alleviate various lesions in the central nervous system, such as neuroinflammation, and reduce anxiety and depression-like behaviors, which were triggered by transplantation with fecal microbiota that had been affected by chronic ethanol exposure, adding more support that SCFAs serve as a bridge between the gut and the brain.}, } @article {pmid39502702, year = {2024}, author = {Han, YJ and Kim, S and Shin, H and Kim, HW and Park, JD}, title = {Protective effect of gut microbiota restored by fecal microbiota transplantation in a sepsis model in juvenile mice.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1451356}, pmid = {39502702}, issn = {1664-3224}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Sepsis/therapy/microbiology/immunology ; Mice ; *Disease Models, Animal ; Male ; Cytokines/metabolism/blood ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis/therapy ; Feces/microbiology ; Mice, Inbred C57BL ; }, abstract = {INTRODUCTION: Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice.

METHODS: Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP.

RESULTS: Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1β (IL-1β), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-α, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%).

CONCLUSION: FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children.}, } @article {pmid39502523, year = {2024}, author = {Anouti, A and Kerr, TA and Mitchell, MC and Cotter, TG}, title = {Advances in the management of alcohol-associated liver disease.}, journal = {Gastroenterology report}, volume = {12}, number = {}, pages = {goae097}, pmid = {39502523}, issn = {2052-0034}, abstract = {Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.}, } @article {pmid39500537, year = {2024}, author = {Slizovskiy, IB and Bonin, N and Bravo, JE and Ferm, PM and Singer, J and Boucher, C and Noyes, NR}, title = {Factors impacting target-enriched long-read sequencing of resistomes and mobilomes.}, journal = {Genome research}, volume = {}, number = {}, pages = {}, doi = {10.1101/gr.279226.124}, pmid = {39500537}, issn = {1549-5469}, abstract = {We investigated the efficiency of target-enriched long-read sequencing (TELSeq) for detecting antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) within complex matrices. We aimed to overcome limitations associated with traditional antimicrobial resistance (AMR) detection methods, including short-read shotgun metagenomics, which can lack sensitivity, specificity, and the ability to provide detailed genomic context. By combining biotinylated probe-based enrichment with long-read sequencing, we facilitated the amplification and sequencing of ARGs, eliminating the need for bioinformatic reconstruction. Our experimental design included replicates of human fecal microbiota transplant material, bovine feces, pristine prairie soil, and a mock human gut microbial community, allowing us to examine variables including genomic DNA input and probe set composition. Our findings demonstrated that TELSeq markedly improves the detection rates of ARGs and MGEs compared to traditional sequencing methods, underlining its potential for accurate AMR monitoring. A key insight from our research is the importance of incorporating mobilome profiles to better predict the transferability of ARGs within microbial communities, prompting a recommendation for the use of combined ARG-MGE probe sets for future studies. We also reveal limitations for ARG detection from low-input workflows, and describe the next steps for ongoing protocol refinement to minimize technical variability and expand utility in clinical and public health settings. This effort is part of our broader commitment to advancing methodologies that address the global challenge of AMR.}, } @article {pmid39500027, year = {2024}, author = {Hua, Y and Zhou, C and Fan, R and Benazzouz, S and Shen, J and Xiao, R and Ma, W}, title = {Altered intestinal microbiota induced by high-fat diets affect cognition differently in mice.}, journal = {Nutrition research (New York, N.Y.)}, volume = {132}, number = {}, pages = {67-84}, doi = {10.1016/j.nutres.2024.09.019}, pmid = {39500027}, issn = {1879-0739}, abstract = {The role of the gut microbiota in the association between high-fat diet and cognition is not clear. We hypothesized that a high-fat diet may influence cognition by altering the intestinal microbiota. Fecal microbiota isolated from male C57BL/6J mice feeding on various high-fat diets and a control basic diet were transplanted to antibiotic-treated recipient mice. The measurement of weight and plasma lipids, novel object recognition test, 16S rRNA gene sequencing of feces, and hematoxylin-eosin staining of the hippocampal cornu ammonis 1 and cornu ammonis 3 areas were performed for all mice. Compared with those in the control and n-3 polyunsaturated fatty acid (n-3 PUFA) groups, donor obese mice fed with diets high in long-chain saturated fatty acids, n-6 polyunsaturated fatty acids (n-6 PUFAs), and trans fatty acids exhibited significant cognitive impairment (all P < .05). There were fewer neurons in the hippocampal area in the n-6 PUFA group than in the n-3 PUFA group (P < .05). Similar effect on cognition and neurons in hippocampal area in corresponding recipient mice were revealed after fecal microbiota transplantation. In addition, the composition of intestinal microbiota differed among recipient mice after fecal microbiota transplantation from donor mice. According to these results, it was concluded that diets rich in long-chain saturated fatty acids, n-6 PUFAs, and trans fatty acids may lead to cognitive impairment by damaging the structure of the hippocampus through influencing the intestinal microbiota in mice, whereas a diet high in n-3 PUFAs may exhibit a beneficial effect.}, } @article {pmid39499189, year = {2024}, author = {Ghani, R and Chrysostomou, D and Roberts, LA and Pandiaraja, M and Marchesi, JR and Mullish, BH}, title = {Faecal (or intestinal) microbiota transplant: a tool for repairing the gut microbiome.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2423026}, pmid = {39499189}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy/microbiology ; Animals ; Feces/microbiology ; Clostridioides difficile/physiology ; Treatment Outcome ; Donor Selection ; }, abstract = {Faecal/intestinal microbiota transplant (FMT/IMT) is an efficacious treatment option for recurrent Clostridioides difficile infection, which has prompted substantial interest in FMT's potential role in the management of a much broader range of diseases associated with the gut microbiome. Despite its promise, the success rates of FMT in these other settings have been variable. This review critically evaluates the current evidence on the impact of clinical, biological, and procedural factors upon the therapeutic efficacy of FMT, and identifies areas that remain nebulous. Due to some of these factors, the optimal therapeutic approach remains unclear; for example, the preferred timing of FMT administration in a heavily antibiotic-exposed hematopoietic cell transplant recipient is not standardized, with arguments that can be made in alternate directions. We explore how these factors may impact upon more informed selection of donors, potential matching of donors to recipients, and aspects of clinical care of FMT recipients. This includes consideration of how gut microbiome composition and functionality may strategically inform donor selection criteria. Furthermore, we review how the most productive advances within the FMT space are those where clinical and translational outcomes are assessed together, and where this model has been used productively in recent years to better understand the contribution of the gut microbiome to human disease, and start the process toward development of more targeted microbiome therapeutics.}, } @article {pmid39495286, year = {2024}, author = {Zhang, H and Zhou, W and Gao, P and Li, Z and Li, C and Li, J and Bian, J and Gong, L and He, C and Han, L and Wang, M}, title = {Ellagic Acid Protects against Alcohol-Related Liver Disease by Modulating the Hepatic Circadian Rhythm Signaling through the Gut Microbiota-NPAS2 Axis.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {45}, pages = {25103-25117}, doi = {10.1021/acs.jafc.4c06992}, pmid = {39495286}, issn = {1520-5118}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Circadian Rhythm ; Animals ; *Basic Helix-Loop-Helix Transcription Factors/metabolism/genetics ; *Liver/metabolism/drug effects ; *Liver Diseases, Alcoholic/metabolism/prevention & control/microbiology/drug therapy ; Mice ; Male ; Humans ; *Ellagic Acid/pharmacology ; *Mice, Inbred C57BL ; Signal Transduction/drug effects ; Nerve Tissue Proteins/genetics/metabolism ; Bacteria/classification/genetics/metabolism/isolation & purification/drug effects ; Protective Agents/pharmacology/administration & dosage ; }, abstract = {Alcohol-related liver disease (ALD) encompasses a spectrum of hepatic disorders resulting from alcohol abuse, which constitutes the predominant etiology of morbidity and mortality associated with hepatic pathologies globally. Excessive alcohol consumption disrupts the integrity of the intestinal barrier and perturbs the balance of gut microbiota, thereby facilitating the progression of ALD. Ellagic acid (EA) has been extensively reported to be an effective intervention for alleviating liver symptoms. However, the target molecules of EA in improving ALD and its underlying mechanism remain elusive. First, our study indicates that EA ameliorated ALD through the hepatic circadian rhythm signaling by up-regulating neuronal PAS domain protein 2 (NPAS2). Furthermore, analysis of the intestinal microbiome showed that EA significantly enhanced the abundance of beneficial bacteria, which was positively correlated with NPAS2 expression and negatively correlated with liver injury. Finally, antibiotic treatment and fecal microbiota transplantation (FMT) experiments established a causal relationship between the reshaped microbiota and NPAS2 in the amelioration of ALD. In summary, our study demonstrates novel evidence that EA attenuated ALD by modulating the hepatic circadian rhythm signaling pathway via the gut microbiota-NPAS2 axis, providing valuable insights for EA and microbiome-targeted interventions against ALD.}, } @article {pmid39494101, year = {2024}, author = {Singh, AK and Durairajan, SSK and Iyaswamy, A and Williams, LL}, title = {Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout: Insights and therapeutic strategies.}, journal = {World journal of gastroenterology}, volume = {30}, number = {40}, pages = {4404-4410}, pmid = {39494101}, issn = {2219-2840}, mesh = {*Dysbiosis ; Humans ; *Gout/microbiology/therapy/complications ; *Gastrointestinal Microbiome/physiology ; *Hyperuricemia/microbiology/blood/therapy/diagnosis ; *Uric Acid/blood/metabolism ; *Probiotics/therapeutic use/administration & dosage ; *Prebiotics/administration & dosage ; Gout Suppressants/therapeutic use ; }, abstract = {Hyperuricemia (HUA) is a condition associated with a high concentration of uric acid (UA) in the bloodstream and can cause gout and chronic kidney disease. The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people. This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder. Some studies have suggested that changes in the composition, diversity, and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis. Therefore, we discussed how the gut microbiota contributes to HUA through purine metabolism, UA excretion, and intestinal inflammatory responses. We examined specific changes in the composition of the gut microbiota associated with gout and HUA, highlighting key bacterial taxa and the metabolic pathways involved. Additionally, we discussed the effect of conventional gout treatments on the gut microbiota composition, along with emerging therapeutic approaches that target the gut microbiome, such as the use of probiotics and prebiotics. We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.}, } @article {pmid39493843, year = {2024}, author = {Duan, X and Nie, Y and Xie, X and Zhang, Q and Zhu, C and Zhu, H and Chen, R and Xu, J and Zhang, J and Yang, C and Yu, Q and Cai, K and Wang, Y and Tian, W}, title = {Sex differences and testosterone interfere with the structure of the gut microbiota through the bile acid signaling pathway.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1421608}, pmid = {39493843}, issn = {1664-302X}, abstract = {BACKGROUND: The gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism.

METHODS: 16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues.

RESULTS: The composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP, FXR, CYP7A1, and ASBT) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway.

CONCLUSION: Sex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway.}, } @article {pmid39493719, year = {2024}, author = {Wang, L and Yu, L and Liu, Z and Che, C and Wang, Y and Zhao, Y and Zhu, M and Yang, G and Cao, A}, title = {FMT intervention decreases urine 5-HIAA levels: a randomized double-blind controlled study.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1411089}, pmid = {39493719}, issn = {2296-858X}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is often linked to gastrointestinal issues and altered serotonin metabolism. Emerging evidence suggests gut microbiota influence both, with fecal microbiota transplantation (FMT) offering a potential therapeutic approach. However, its impact on serotonin metabolism and ASD symptoms is not well understood. In this study, we aimed to evaluate the clinical effects of FMT and examine changes in specific urinary metabolites in children with ASD.

METHODS: A randomized double-blind controlled trial was performed to evaluate the clinical effects of FMT on GI and ASD-related symptoms. Gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and the ASD-related symptoms were assessed using the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and Social Responsiveness Scale (SRS) scores. Urinary metabolites were analyzed by homogeneous enzyme immunoassay using commercially available kits.

RESULTS: Significant improvements in GI and core ASD symptoms were observed following FMT intervention. The average GSRS scores decreased from 30.17 (before) to 19 (after; p < 0.0001), CARS scores decreased from 36.22 to 33.33 (p < 0.0001), SRS scores decreased from 151.17 to 137.5 (p = 0.0002), and the ABC scores decreased 76.39 to 53.17 (p < 0.0001) in the FMT group. However, in the placebo group, GSRS, CARS, and SRS scores showed no significant changes, while ABC scores decreased from 72 to 58.75 (p = 0.034). The FMT group also showed a significant reduction in urinary 5-hydroxyindoleacetic acid (5-HIAA) levels from 8.6 to 7.32 mg/L (p = 0.022), while other metabolites showed no significant changes.

CONCLUSION: FMT is a safe and effective treatment for improving GI and core symptoms in children with ASD, with 5-HIAA showing potential as a urinary biomarker for treatment response.}, } @article {pmid39492827, year = {2024}, author = {Jiang, L and Fan, JG}, title = {Gut microbiota in gastrointestinal diseases: Insights and therapeutic strategies.}, journal = {World journal of gastroenterology}, volume = {30}, number = {39}, pages = {4329-4332}, pmid = {39492827}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; Inflammatory Bowel Diseases/microbiology/therapy ; Hypertension, Portal/microbiology/therapy/diagnosis/etiology ; Liver/microbiology/metabolism ; Gastrointestinal Diseases/microbiology/therapy ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Considering the bidirectional crosstalk along the gut-liver axis, gut-derived microorganisms and metabolites can be released into the liver, potentially leading to liver injury. In this editorial, we comment on several studies published in the recent issue of the World Journal of Gastroenterology. We focus specifically on the roles of gut microbiota in selected gastrointestinal (GI) diseases that are prevalent, such as inflammatory bowel disease, metabolic dysfunction-associated steatotic liver disease, and hepatitis B virus-related portal hypertension. Over the past few decades, findings from both preclinical and clinical studies have indicated an association between compositional and metabolic changes in the gut microbiota and the pathogenesis of the aforementioned GI disorders. However, studies elucidating the mechanisms underlying the host-microbiota interactions remain limited. The purpose of this editorial is to summarize current findings and provide insights regarding the context-specific roles of gut microbiota. Ultimately, the discovery of microbiome-based biomarkers may facilitate disease diagnosis and the development of personalized medicine.}, } @article {pmid39492826, year = {2024}, author = {Kong, MW and Yu, Y and Wang, P and Wan, Y and Gao, Y and Zhang, CX}, title = {Advances in the research of intestinal fungi in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {39}, pages = {4318-4323}, pmid = {39492826}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology ; Humans ; *Gastrointestinal Microbiome ; Animals ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; *Fungi/pathogenicity ; *Disease Models, Animal ; Intestines/microbiology ; Mice ; Adipose Tissue/microbiology ; Mesentery/microbiology ; }, abstract = {This article reviews of the original research published by Wu et al in the World Journal of Gastroenterology, delving into the pivotal role of the gut microbiota in the pathogenesis of Crohn's disease (CD). Insights were gained from fecal microbiota transplantation (FMT) in mouse models, revealing the intricate interplay between the gut microbiota, mesenteric adipose tissue (MAT), and creeping fat. The study uncovered the characteristics of inflammation and fibrosis in the MAT and intestinal tissues of patients with CD; moreover, through the FMT mouse model, it observed the impact of samples from healthy patients and those with CD on symptoms. The pathogenesis of CD is complex, and its etiology remains unclear; however, it is widely believed that gut microbiota dysbiosis plays a significant role. Recently, with the development and application of next-generation sequencing technology, research on the role of fungi in the pathogenesis and chronicity of CD has deepened. This editorial serves as a supplement to the research by Wu et al who discussed advances related to the study of fungi in CD.}, } @article {pmid39491642, year = {2024}, author = {Shimokawa, C}, title = {The gut microbiome-helminth-immune axis in autoimmune diseases.}, journal = {Parasitology international}, volume = {104}, number = {}, pages = {102985}, doi = {10.1016/j.parint.2024.102985}, pmid = {39491642}, issn = {1873-0329}, abstract = {The global prevalence of autoimmune diseases has surged in recent decades. Consequently, environmental triggers have emerged as crucial contributors to autoimmune diseases, equally relevant to classical risk factors, such as genetic polymorphisms, infections, and smoking. Sequencing-based approaches have demonstrated distinct gut microbiota compositions in individuals with autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus (T1D), and systemic lupus erythematosus, compared to healthy controls. Furthermore, fecal microbiota transplantation and microbial inoculation experiments have supported the hypothesis that alterations in the gut microbiota can influence autoimmune responses and disease outcomes. Herein, we propose that intestinal helminths may serve as a critical factor in inducing alterations in the gut microbiota. The concept of helminth-mediated suppression of autoimmune diseases in humans is supported by substantial evidence, aligning with the long-standing "hygiene hypothesis." This review focused on T1D to explore the interactions between parasites, gut microbiota, and the immune system-a topic that remains a black box within this intricate triangular relationship.}, } @article {pmid39491609, year = {2024}, author = {Chen, D and Xie, J and Chen, X and Qin, B and Kong, D and Luo, J}, title = {Fecal microbiota transplantation alleviates neuronal Apoptosis, necroptosis and M1 polarization of microglia after ischemic stroke.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2024.10.053}, pmid = {39491609}, issn = {1873-7544}, abstract = {OBJECTIVE: This study aims to delve into the mechanisms underlying the improvement of neurological function in rats with ischemic stroke through fecal microbiota transplantation.

METHODS: A total of fifty male Sprague-Dawley rats were categorized into three groups: sham surgery, model, and fecal transplantation. We assessed behavioral and pathological alterations in the rats using modified neurological function scoring and TTC staining. Additionally, Western blot and immunofluorescence techniques were employed to examine the expression levels of RIP1, RIP3, MLKL, p-MLKL, Bcl-2, Bax, and cleaved caspase-3 in neurons of ischemic brain tissue, while iNOS and Arg1 were analyzed to evaluate microglial polarization.

RESULTS: The fecal transplantation group exhibited a decline in neurological function score compared to the model group, accompanied by a reduction in infarct volume (P < 0.05). Relative to the sham surgery group, the model group displayed a significant increase in the expression levels of necroptosis-related proteins RIP1, RIP3, p-MLKL, apoptotic proteins Bax and cleaved caspase-3, and the M1 microglial cell marker iNOS in ischemic brain tissue, while Bcl-2 expression was notably decreased (P < 0.05). Conversely, compared to the model group, the fecal transplantation group demonstrated decreased expression levels of RIP1, RIP3, p-MLKL, Bax, cleaved caspase-3, and iNOS, along with increased expression of Bcl-2.

CONCLUSION: Fecal microbiota transplantation presents a promising avenue for enhancing neurological function in rats with ischemic stroke by inhibiting neuronal apoptosis, necroptosis, and M1 polarization of microglial cells.}, } @article {pmid39491142, year = {2023}, author = {Zhao, T and Lv, J and Peng, M and Mi, J and Zhang, S and Liu, J and Chen, T and Sun, Z and Niu, R}, title = {Fecal microbiota transplantation and short-chain fatty acids improve learning and memory in fluorosis mice by BDNF-PI3K/AKT pathway.}, journal = {Chemico-biological interactions}, volume = {}, number = {}, pages = {110786}, doi = {10.1016/j.cbi.2023.110786}, pmid = {39491142}, issn = {1872-7786}, abstract = {Fluoride, an environmental toxicant, not only arouses intestinal microbiota dysbiosis, but also causes neuronal apoptosis and a decline in learning and memory ability. The purpose of this study was to explore whether fecal microbiota transplantation (FMT) from healthy mice and bacteria-derived metabolites short-chain fatty acids (SCFAs) supplement protect against fluoride-induced learning and memory impairment. Results showed that FMT reversed the elevated percentage of working memory errors (WME) and reference memory errors (RME) in fluorosis mice during the eight-arm maze test. Nissl and TUNEL staining presented that fluoride led to a decreased proportion of Nissl bodies area in the hippocampal CA3 region and an increased apoptotic ratio of nerve cells in CA1, CA3 and DG areas, whereas FMT alleviated those pathological damages. Moreover, the expressions of mRNA in hippocampal BDNF, PDK1, AKT, Bcl-2, and Bcl-xL were downregulated in mice exposed to fluoride, but the levels of PI3K, Bax, Bak, and Caspase-7 mRNA were upregulated. NaF treatment had an increase in PI3K and Caspase-3 protein levels and reduced the expressions of these four proteins, including BDNF, p-PI3K, AKT and p-AKT. By contrast, FMT enhanced the expression of BDNF and thus activated the PI3K/AKT pathway. Besides, the 16S rRNA sequencing revealed that fluoride caused a reduction in certain SCFA producers in the colon as evidenced by a decline in Erysipelatoclostridiaceae, and a downward trend in Akkermansia, Blautia and Alistipes. However, the disordered gut microbiome was restored via frequent FMT. Of note, SCFAs administration also increased BDNF levels and regulated its downstream pathways, which contributed to cell survival and learning and memory function recovery. In conclusion, FMT and SCFAs may activate the BDNF-PI3K/AKT pathway to play an anti-apoptotic role and ultimately improve learning and memory deficits in fluorosis mice.}, } @article {pmid39490563, year = {2024}, author = {Wu, J and Zhang, R and Yin, Z and Chen, X and Mao, R and Zheng, X and Yuan, M and Li, H and Lu, Y and Liu, S and Gao, X and Sun, Q}, title = {Gut microbiota-driven metabolic alterations reveal the distinct pathogenicity of chemotherapy-induced cachexia in gastric cancer.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107476}, doi = {10.1016/j.phrs.2024.107476}, pmid = {39490563}, issn = {1096-1186}, abstract = {Cachexia affects approximately 50-80% of advanced cancer patients, particularly those with gastric cancer (GC). Therefore, early detection of cachexia is essential to prevent its progression. Targeting the gut microbiota may be a promising approach for preventing and treating cachexia in patients with GC. Chemotherapy significantly reduced gut microbiota diversity in GC patients. Specifically, the abundance of bacterial genera such as Bacteroides, Streptococcus, and Prevotella was increased in the gut of patients postchemotherapy, which was closely associated with the development of cachexia. Serum metabolic analysis revealed a strong link between specific microbes and metabolite in patients with chemotherapy-induced GC cachexia. We further constructed a random forest model based on the top 6 genera in terms of abundance for the prediction of chemotherapy-related GC cachexia development; this model had an area under the receiver operating characteristic curve (AUC) of 93.5% [95% confidence interval (CI), 86.6%-100%], with a specificity and accuracy above 75%. Additionally, we identified Enterotoxin Bacteroides fragilis (ETBF) as a key factor in chemotherapy-induced GC cachexia. In an in vivo GC model, the colonization of ETBF in the intestines of mice significantly accelerated the muscle and adipose tissue consumption induced by chemotherapy, resulting in cachexia symptoms. Furthermore, ETBF damaged the intestinal mucosal barrier by disrupting cell connections and attracting M1 macrophages, which advances GC cachexia. In conclusion, our findings indicate that gut microbiota imbalance is crucial in GC cachexia development, suggesting potential biomarkers for early diagnosis. Clinical trial registration: http://www.chictr.org.cn, Identification No: ChiCTR2200064547.}, } @article {pmid39489477, year = {2024}, author = {Chen, W and Liu, Y and Pu, J and Gui, S and Wang, D and Zhong, X and Tao, W and Chen, X and Chen, X and Chen, Y and Zhao, L and Wu, Q and Chen, X and Zhang, Y and Xie, A and Xie, P}, title = {Comparative transcriptional analyses of the striatum in the chronic social defeat stress model in C57BL/6J male mice and the gut microbiota-dysbiosis model in Kumming mice.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2024.10.057}, pmid = {39489477}, issn = {1873-7544}, abstract = {Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression.}, } @article {pmid39487198, year = {2024}, author = {Chatthanathon, P and Leelahavanichkul, A and Cheibchalard, T and Wilantho, A and Hirankarn, N and Somboonna, N}, title = {Comparative time-series analyses of gut microbiome profiles in genetically and chemically induced lupus-prone mice and the impacts of fecal transplantation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26371}, pmid = {39487198}, issn = {2045-2322}, support = {CU_FRB65_hea(68)_131_23_61//Thailand Science Research and Innovation Fund Chulalongkorn University/ ; }, mesh = {Animals ; *Lupus Erythematosus, Systemic/microbiology/immunology/genetics ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Mice ; *Receptors, IgG/genetics ; *Dysbiosis/microbiology ; *Disease Models, Animal ; Female ; Feces/microbiology ; Mice, Knockout ; Terpenes ; Mice, Inbred C57BL ; }, abstract = {Although the association between gut dysbiosis (imbalance of the microbiota) in systemic lupus erythematosus (SLE) is well-known, the simultaneous exploration in gut dysbiosis in fecal and different intestinal sections before and after lupus onset (at 2, 4, 6, 8, and 10 months old) resulting from the loss of inhibitory Fc gamma receptor IIb (FcGIIb) and pristane induction have never been conducted. Anti-dsDNA (an important lupus autoantibody) and proteinuria developed as early as 6 months old in both models, with higher levels in FcGRIIb deficient (FcGRIIb-/-) mice. Compared to the healthy control at 2 and 4 months, the lupus mice (both FcGRRIIb-/- and pristane) and healthy mice at 6 months old demonstrated an alteration as indicated by the Shannon alpha diversity index, highlighting influences of lupus- and age-induced dysbiosis, respectively. Non-metric multidimensional scaling (NMDS) revealed that the fecal microbiota of FcGRIIb-/- mice were distinct from the age-matched healthy control at all timepoints (at 6 month, p < 0.05), while pristane mice showed divergence at only some timepoints. Analyses of different intestinal sections revealed similarity among microbiota in the cecum, colon, and feces, contrasting with those in the small intestines (duodenum, jejunum, and ileum). Subtle differences were found between FcGRIIb-/- and pristane mice in feces and the intestinal sections as assessed by several analyses, for examples, the similar or dissimilar distances (NMDS), the neighbor-joining clustering, and the potential metabolisms (KEGG pathway analysis). Due to the differences between the gut microbiota (feces and intestinal sections) in the lupus mice and the healthy control, rebalancing of the microbiota using rectal administration of feces from the healthy control (fecal transplantation; FMT) to 7-month-old FcGIIb-/- mice (the established lupus; positive anti-dsDNA and proteinuria) was performed. In comparison to FcGRIIb-/- mice without FMT, FMT mice (more effect on the female than the male mice) showed the lower anti-dsDNA levels with similar fecal microbiome diversity (16s DNA gene copy number) and microbiota patterns to the healthy control. In conclusion, gut microbiota (feces and intestinal sections) of lupus mice (FcGRIIb-/- and pristane) diverged from the control as early as 4-6 months old, correlating with lupus characteristics (anti-dsDNA and proteinuria). The different gut microbiota in FcGRIIb-/- and pristane suggested a possible different gut microbiota in lupus with various molecular causes. Furthermore, FMT appeared to mitigate gut dysbiosis and reduce anti-dsDNA, supporting the benefit of the rebalancing gut microbiota in lupus, with more studies are warranted.}, } @article {pmid39488230, year = {2024}, author = {Rubak, T and Baunwall, SMD and Gregersen, M and Paaske, SE and Asferg, M and Barat, I and Secher-Johnsen, J and Riis, MG and Rosenbæk, JB and Hansen, TK and Ørum, M and Steves, CJ and Veilbæk, H and Hvas, CL and Damsgaard, EMS}, title = {Early geriatric assessment and management in older patients with Clostridioides difficile infection in Denmark (CLODIfrail): a randomised trial.}, journal = {The lancet. Healthy longevity}, volume = {}, number = {}, pages = {100648}, doi = {10.1016/j.lanhl.2024.100648}, pmid = {39488230}, issn = {2666-7568}, abstract = {BACKGROUND: Clostridioides difficile infection causes diarrhoea and colitis. Older patients with C difficile infection are often frail and have comorbidities, leading to high mortality rates. The frailty burden in older people might restrict access to treatments, such as C difficile infection-specific antibiotics and faecal microbiota transplantation. We aimed to investigate the clinical effects of early comprehensive geriatric assessment (CGA) and frailty evaluation, including home visits and assessment for faecal microbiota transplantation, in older patients with C difficile infection.

METHODS: In this randomised, quality improvement trial with a pragmatic design, patients from the Central Denmark Region aged 70 years or older with a positive PCR test for C difficile toxin were randomly assigned (1:1) to CGA or standard care, both with equal access to faecal microbiota transplantation. Patients and investigators were unmasked to treatment. The primary outcome was 90-day mortality, and was compared in the study groups according to the intention-to-treat principle. The study is registered with ClinicalTrials.gov, NCT05447533.

FINDINGS: Between Sept 1, 2022, and May 3, 2023, we randomly assigned 217 patients to CGA (n=109) or standard care (n=108). The median patient age was 78 years (IQR 74-84). 116 (53%) of 217 patients were female and 101 (47%) were male. 16 (15%; 95% CI 9-23) of 109 patients in the CGA group and 22 (20%; 14-29) of 108 patients in the standard-care group died within 90 days (odds ratio 0·66, 95% CI 0·32-1·38. No serious adverse events or deaths related to patient assessment or faecal microbiota transplantation were recorded in either group. Deaths directly attributable to C difficile infection were lower in the CGA group (seven [44%] of 16 deaths vs 18 [82%] of 22 deaths in the standard-care group; p=0·020).

INTERPRETATION: Older patients who received CGA had a 90-day mortality rate similar to that of patients who received standard care, but with fewer deaths directly attributable to C difficile infection.

FUNDING: Innovation Fund Denmark, Novo Nordisk Foundation, and Helsefonden.}, } @article {pmid39484201, year = {2024}, author = {Cheng, X and Ren, C and Mei, X and Jiang, Y and Zhou, Y}, title = {Gut microbiota and irritable bowel syndrome: status and prospect.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1429133}, pmid = {39484201}, issn = {2296-858X}, abstract = {Irritable bowel syndrome (IBS) is a very common gastrointestinal disease that, although not as aggressive as tumors, affects patients' quality of life in different ways. The cause of IBS is still unclear, but more and more studies have shown that the characteristics of the gut microbiota, such as diversity, abundance, and composition, are altered in patients with IBS, compared to the healthy population, which confirms that the gut microbiota plays a crucial role in the development of IBS. This paper aims to identify the commonalities by reviewing a large body of literature. Changes in the characteristics of gut microbiota in patients with different types of IBS are discussed, relevant mechanisms are described, and the treatment modalities of gut microbiota in IBS are summarized. Although there are more clinical trials that have made good progress, more standardized, more generalized, larger-scale, multi-omics clinical studies are what is missing. Overall, gut microbiota plays a crucial role in the development of IBS, and there is even more potential for treating IBS by modulating gut microbiota.}, } @article {pmid39484168, year = {2024}, author = {Duo, H and Yang, Y and Zhang, G and Chen, Y and Cao, Y and Luo, L and Pan, H and Ye, Q}, title = {Comparative effectiveness of treatments for recurrent Clostridioides difficile infection: a network meta-analysis of randomized controlled trials.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1430724}, pmid = {39484168}, issn = {1663-9812}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infectious diarrhea. A major clinical challenge is recurrent CDI (rCDI) without effective standard drug-based therapy. Additionally, a comprehensive comparison of various therapy effectiveness in rCDI patients is still under investigation.

METHODS: A Bayesian network meta-analysis (NMA) of randomized control trials up to March 2024 was performed to investigate the efficacy of rCDI interventions.

RESULTS: Seventeen trials were included, comprising 4,148 CDI patients with ten interventions, including fecal microbiota transplantation (FMT) by lower gastrointestinal (LGI), FMT by upper gastrointestinal (UGI), Autologous FMT (AFMT), vancomycin + FMT, vancomycin, placebo, fidaxomicin, Vowst (SER109), Rebyota (RBX2660), and monoclonal antibody. NMA showed that FMT by LGI had the highest efficacy in treating rCDIs with an odds ratio (95% confidence interval) of 32.33 (4.03, 248.69) compared with placebo. FMT by UGI also showed high efficacy, whereas the efficacy comparison between FMT by LGI and UGI was not statistically significant (ORs) (95% CI), 1.72 (0.65, 5.21). The rankogram and surface under the cumulative ranking curve (SUCRA) also showed FMT by LGI ranked at the top and FMT by UGI ranked second in the curative effect.

CONCLUSION: NMA demonstrates FMT's significant efficacy in rCDI management, regardless of administration route (lower or upper gastrointestinal). Despite its significant benefits, FMT's safety is a concern due to the lack of standardized FDAcompliant manufacturing and oversight. Microbiota-based therapies also exhibit potential. However, limited research mandates further clinical exploration. Antibiotics, in contrast, display comparatively reduced efficacy in rCDI, potentially linked to disruptions in native gut microflora balance.

SYSTEMATIC REVIEW: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=368435, Identifier CRD42022368435.}, } @article {pmid39483608, year = {2024}, author = {Aslam, MR and Perala, A and Wishart, AV and Hamouda, RK and Elsaady, E and Khan, S}, title = {Therapeutic Potential of Fecal Microbiota Transplantation in Type 2 Diabetes Mellitus: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e70642}, pmid = {39483608}, issn = {2168-8184}, abstract = {Diabetes mellitus is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. It can cause various complications, which result in significant morbidity and mortality. There are multiple treatment options available to combat this disease; however, despite this, the incidence of type 2 diabetes mellitus is continuously increasing. Some promising results have shown that dysbiosis has a role in the pathogenesis of type 2 diabetes mellitus and fecal microbiota transplantation (FMT) in animals; however, the usage of FMT in humans needs further clarification and review. We explored PubMed, Popline, and Cochrane Library to identify relevant papers. Eight articles were then finalized after screening and applying eligibility criteria. These articles explored the role of the therapeutic efficacy of FMT in insulin resistance and hyperglycemia. The studies showed that the FMT had a positive impact on managing hyperglycemia and insulin resistance, which is evident in the decline of blood glucose and HBA1c levels and the rise of insulin and C-peptides. In addition, FMT also helped to control other risk factors such as hyperlipidemia and blood pressure; however, the impact on weight loss is not convincing. FMT also influenced the levels of some microbiota, which could be involved in controlling hyperglycemia and insulin resistance. Due to limited control trials and study periods and the small sample size of diabetic patients, more research is needed to explore the impact of FMT in controlling type 2 diabetes mellitus.}, } @article {pmid39482760, year = {2024}, author = {Nie, D and Wang, D and Wang, Z and Fang, Q and Wang, H and Xie, W and Li, C and Zhang, Y}, title = {The gut microbiome in patients with Cushing's disease affects depression- and anxiety-like behavior in mice.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {225}, pmid = {39482760}, issn = {2049-2618}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Pituitary ACTH Hypersecretion/microbiology/psychology/physiopathology ; *Depression/microbiology ; *Anxiety/microbiology ; Humans ; *Disease Models, Animal ; Male ; Behavior, Animal ; Feces/microbiology ; Female ; Corticosterone/blood ; Bacteria/classification/isolation & purification ; Adult ; Middle Aged ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Depression and anxiety significantly impact the quality of life in individuals with Cushing's disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology.

RESULTS: The gut bacterial phenotype of patients with Cushing's disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased. However, this effect can be alleviated by supplementing with 2-(14, 15-epoxyeicosatrienoyl) glycerol (2-14,15-EG) which was found at reduced levels in the peripheral blood of mice treated with coprofecal bacteria from Cushing's disease. In this process, the effects of hormone levels and immune factors were not significant. In addition, in an animal model, corticosterone has been observed to affect behavioral changes in mice through gut microbiota composition, clarifying the cause-and-effect relationship between hormones, microbiota, and behavior. Finally, there was no significant difference in gut microbiome composition and its effects on mouse behavior in patients with Cushing's disease with different levels of depression and anxiety.

CONCLUSIONS: In summary, this research enhances our current understanding of how gut microbes in patients with Cushing's disease contribute to depression and anxiety, offering novel insights for clinical treatment approaches. Video Abstract.}, } @article {pmid39486524, year = {2024}, author = {Kapoor, B and Biswas, P and Gulati, M and Rani, P and Gupta, R}, title = {Gut microbiome and Alzheimer's disease: what we know and what remains to be explored.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {102570}, doi = {10.1016/j.arr.2024.102570}, pmid = {39486524}, issn = {1872-9649}, abstract = {With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut-brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut-brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.}, } @article {pmid39486483, year = {2024}, author = {Lu, H and Xie, L and Guo, L and Gu, X and Zhu, R and Yang, Y and Tang, F and Li, M and Liu, C and Wang, D and Li, M and Tian, Y and Cai, S}, title = {EGCG protects intestines of mice and pelvic cancer patients against radiation injury via the gut microbiota/D-tagatose/AMPK axis.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {}, number = {}, pages = {110608}, doi = {10.1016/j.radonc.2024.110608}, pmid = {39486483}, issn = {1879-0887}, abstract = {BACKGROUND AND PURPOSE: Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII.

MATERIALS AND METHODS: We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing.

RESULTS: EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK.

CONCLUSION: Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.}, } @article {pmid39486191, year = {2024}, author = {Singh, R and Panganiban, K and Au, E and Ravikumar, R and Pereira, S and Prevot, TD and Mueller, DJ and Remington, G and Agarwal, SM and Verdu, EF and Bercik, P and De Palma, G and Hahn, MK}, title = {Human-fecal microbiota transplantation in relation to gut microbiome signatures in animal models for schizophrenia: A scoping review.}, journal = {Asian journal of psychiatry}, volume = {102}, number = {}, pages = {104285}, doi = {10.1016/j.ajp.2024.104285}, pmid = {39486191}, issn = {1876-2026}, abstract = {More recently, attention has turned to the putative role of gut microbiome (GMB) in pathogenesis, symptomatology, treatment response and/or resistance in schizophrenia (SCZ). It is foreseeable that fecal microbiota transplantation (FMT) from SCZ patients (SCZ-FMT) to germ-free mice could represent a suitable experimental framework for a better understanding of the relationship between GMB and SCZ. Thus, we set out to identify literature (i) characterizing the GMB in animal models of SCZ, and (ii) employing SCZ-FMT into rodents to model SCZ in relation to behavioral and molecular phenotypes. Five studies examining animal models of SCZ suggest distinct GMB composition compared to respective control groups, which was correlated with SCZ-like behavioral phenotypes. Four additional studies investigated SCZ-FMT into rodents in relation to behavioral phenotypes, including spontaneous hyperlocomotion, social deficits, exaggerated startle response, and cognitive impairments, resembling those observed in SCZ patients. Mice receiving SCZ-FMT showed altered neurochemical and metabolic pathways in the brain. Animal models of SCZ have shown altered GMB composition, whereas reported behavioral and neurochemical alterations following FMT from patients into rodents suggest early face and construct validity for SCZ-FMT animal models. However, the predictive validity of these models remains to be validated.}, } @article {pmid39485288, year = {2024}, author = {Minaya, DM and Kim, JS and Kirkland, R and Allen, J and Cullinan, S and Maclang, N and de Lartigue, G and de La Serre, C}, title = {Transfer of microbiota from lean donors in combination with prebiotics prevents excessive weight gain and improves gut-brain vagal signaling in obese rats.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2421581}, doi = {10.1080/19490976.2024.2421581}, pmid = {39485288}, issn = {1949-0984}, mesh = {Animals ; *Obesity/microbiology/metabolism ; Male ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Prebiotics/administration & dosage ; *Brain-Gut Axis/physiology ; *Diet, High-Fat/adverse effects ; *Vagus Nerve ; *Weight Gain/drug effects ; Dysbiosis/microbiology ; Rats, Sprague-Dawley ; Bacteria/classification/isolation & purification/genetics/metabolism ; Fecal Microbiota Transplantation ; Brain/metabolism ; Signal Transduction ; }, abstract = {Gastrointestinal (GI) microbiota plays an active role in regulating the host's immune system and metabolism, as well as certain pathophysiological processes. Diet is the main factor modulating GI microbiota composition and studies have shown that high fat (HF) diets induce detrimental changes (dysbiosis) in the GI bacterial makeup. HF diet induced dysbiosis has been associated with structural and functional changes in gut-brain vagally mediated signaling system, associated with overeating and obesity. Although HF-driven changes in microbiota composition are sufficient to alter vagal signaling, it is unknown if improving microbiota composition after diet-induced obesity has been established can ameliorate gut-brain signaling and metabolic outcomes. In this study, we evaluated the effect of lean gut microbiota transfer in obese, vagally compromised, rats on gut-brain communication, food intake, and body weight. Male rats were maintained on regular chow or 45% HF diet for nine weeks followed by three weeks of microbiota depletion using antibiotics. The animals were then divided into four groups (n = 10 each): LF - control fed regular chow, LF-LF - chow fed animals that received microbiota from chow fed donors, HF-LF - HF fed animals that received microbiota from chow fed donors, and HF-HF - HF fed animals that received microbiota from HF fed donors. HF-LF animals received inulin as a prebiotic to aid the establishment of the lean microbiome. We found that transferring a LF microbiota to HF fed animals (HF-LF) reduced caloric intake during the light phase when compared with HF-HF rats and prevented additional excessive weight gain. HF-LF animals displayed an increase in postprandial activation of both primary sensory neurons innervating the GI tract and brainstem secondary neurons. We concluded from these data that improving microbiota composition in obese rats is sufficient to ameliorate gut-brain communication and restore normal feeding patterns which was associated with a reduction in weight gain.}, } @article {pmid39484785, year = {2024}, author = {Li, Y and Song, X and Dai, L and Wang, Y and Luo, Q and Lei, L and Pu, Y}, title = {Mechanism of action of exercise regulating intestinal microflora to improve spontaneous hypertension in rats.}, journal = {Biomolecules & biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2024.11174}, pmid = {39484785}, issn = {2831-090X}, abstract = {Hypertension is a prevalent cardiovascular disease. Exercise is widely recognized as an effective treatment for hypertension, and it may also influence the composition of the intestinal microflora. However, it remains unclear whether exercise can specifically regulate the intestinal microflora in the context of hypertension treatment. In this study, tail blood pressure in spontaneously hypertensive rats (SHR) was measured using a blood pressure meter after exercise intervention and fecal bacteria transplantation following exercise. Blood lipid levels were assessed using an automatic biochemical analyzer, and 16S rRNA sequencing was employed to analyze the intestinal microflora. Histological examinations of ileal tissue were conducted using HE and Masson staining. Intestinal permeability, inflammatory status, and sympathetic activity were evaluated by measuring the levels of diamine oxidase, D-lactic acid, C-reactive protein, interleukin-6, tumor necrosis factor-α, lipopolysaccharide, norepinephrine, angiotensin II, cyclic adenosine monophosphate, and cyclic guanosine monophosphate. Exercise was found to reduce blood pressure and blood lipid levels in SHR. It also improved the composition of the intestinal microflora, as evidenced by a reduced Firmicutes/Bacteroidetes ratio, an increase in bacteria that produce acetic and butyric acid, and higher Chao 1 and Shannon diversity indices. Furthermore, exercise reduced the thickness of the fibrotic and muscular layers in the ileum, increased the goblet cell/villus ratio and villus length, and decreased intestinal permeability, inflammatory markers, and sympathetic nerve activity. The intestinal microbial flora regulated by exercise demonstrated similar effects on hypertension. In conclusion, exercise appears to regulate the intestinal microflora, and this exercise-induced change in flora may contribute to improvements in hypertension in rats.}, } @article {pmid39482823, year = {2024}, author = {Zhang, T and Li, X and Li, J and Sun, F and Duan, L}, title = {Gut microbiome-targeted therapies as adjuvant treatments in inflammatory bowel diseases: a systematic review and network meta-analysis.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16795}, pmid = {39482823}, issn = {1440-1746}, support = {2021YFA1301300//National Key Research and Development Program of China/ ; 82170557//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND AND AIM: Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD).

METHODS: We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values.

RESULTS: Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD.

CONCLUSIONS: FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.}, } @article {pmid38988278, year = {2024}, author = {Yan, M and Man, S and Ma, L and Guo, L and Huang, L and Gao, W}, title = {Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.}, journal = {Clinical and molecular hepatology}, volume = {30}, number = {4}, pages = {620-648}, doi = {10.3350/cmh.2024.0315}, pmid = {38988278}, issn = {2287-285X}, support = {82074069//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fatty Liver/complications/therapy/pathology ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Understanding the immunological mechanisms underlying SLD is crucial for advancing clinical therapeutic strategies.}, } @article {pmid38052097, year = {2024}, author = {Cooper, J and Markovinovic, A and Coward, S and Herauf, M and Shaheen, AA and Swain, M and Panaccione, R and Ma, C and Lu, C and Novak, K and Kroeker, KI and Ng, SC and Kaplan, GG}, title = {Incidence and Prevalence of Primary Sclerosing Cholangitis: A Meta-analysis of Population-based Studies.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {11}, pages = {2019-2026}, pmid = {38052097}, issn = {1536-4844}, support = {PJT-162393/CAPMC/CIHR/Canada ; G-2106-04697//Leona M. and Harry B. Helmsley Charitable Trust/ ; //Study of Inflammatory Bowel Disease/ ; PJT-162393/CAPMC/CIHR/Canada ; }, mesh = {*Cholangitis, Sclerosing/epidemiology ; Humans ; Incidence ; Prevalence ; Asia/epidemiology ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis is a chronic liver disease associated with significant morbidity, mortality, and healthcare utilization. We conducted a systematic review and meta-analysis of population-based studies of the incidence and prevalence of primary sclerosing cholangitis.

METHODS: Medline and Embase were systematically searched to identify population-based studies of a defined geographic area and reported the incidence or prevalence of primary sclerosing cholangitis in the general population. Meta-analyses, using random-effects, were performed to calculate overall and country-specific incidence (per 100 000 persons/year) and prevalence rates (per 100 000 persons) with 95% confidence intervals.

RESULTS: The 14 studies on incidence and the 12 for prevalence originated from North America, Asia, Europe, and Oceania. Incidence and prevalence rates of primary sclerosing cholangitis were 0.87 (95% confidence interval, 0.59-1.29) and 13.53 (95% confidence interval, 10.20-17.94) per 100 000 persons, respectively.

CONCLUSIONS: Both the prevalence and incidence of primary sclerosing cholangitis is low in the general population. Future studies on the incidence and prevalence of primary sclerosing cholangitis in the general population should be directed at Asia, Africa, and Latin America to allow for a more robust assessment of the global epidemiology of primary sclerosing cholangitis.}, } @article {pmid39481287, year = {2024}, author = {Gautam, R and Maan, P and Patel, AK and Vasudevan, S and Arora, T}, title = {Unveiling the complex interplay between gut microbiota and polycystic ovary syndrome: A narrative review.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {12}, pages = {199-208}, doi = {10.1016/j.clnu.2024.10.028}, pmid = {39481287}, issn = {1532-1983}, abstract = {BACKGROUND & AIM: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects women throughout their reproductive age and characterised via polycystic ovaries, hyperandrogenism, and irregular menstruation. There is rising evidence that the pathophysiology of PCOS is significantly affected via the gut microbiota and its metabolic products.

METHODS: This narrative review synthesizes current literature exploring the relationship between gut microbiota and PCOS. A comprehensive search of electronic databases was conducted to identify relevant studies. Further this review also analysed therapeutic options of probiotics, prebiotics, Fecal Microbiota Transplant (FMT), high fiber and poly phenol rich diet and novel therapeutic agents in treatment of PCOS.

RESULTS: Emerging evidence suggests alterations in the composition and diversity of gut microbiota in women with PCOS. The current literature showed a complex relationship of gut microbiota, short chain fatty acids (SCFAs) metabolism, intestinal permeability and LPS (Lipid Polysaccharide) metabolism, gut-brain axis and bile acid (BA) pathway within etiology and pathophysiology of PCOS. Additionally, the factors such as diet, lifestyle, genetics, and environmental influences may all contribute to alterations in gut microbiota that could potentially exacerbate or mitigate PCOS symptoms.

CONCLUSION: The review provides valuable insights into the intricate interplay between the gut and female reproductive health. The present evidence suggested that alterations in diversity and function of the gut microbiota may lead to specific pathogenic changes that lead to development of PCOS. A comprehensive understanding of these microbial dynamics may lead to new therapeutic approaches that target the gut micro biome.}, } @article {pmid39480487, year = {2024}, author = {Deda, O and Armitage, EG and Mouskeftara, T and Kachrimanidou, M and Zervos, I and Malousi, A and Loftus, NJ and Taitzoglou, I and Gika, H}, title = {Unraveling Cecal Alterations in Clostridioides difficile Colonized Mice through Comprehensive Metabolic Profiling.}, journal = {Journal of proteome research}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jproteome.4c00578}, pmid = {39480487}, issn = {1535-3907}, abstract = {The disruption of gut microbiota caused by antibiotics favors the intestinal colonization of Clostridioides difficile - a Gram-positive, spore-forming anaerobic bacterium that causes potentially fatal gastrointestinal infections. In an endeavor to elucidate the complexities of the gut-brain axis in the context of Clostridium difficile infection (CDI), a murine model has been used to investigate the potential effects of antibiotic administration and subsequent colonization by C. difficile, as well as the impact of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the cecal metabolome for the first time. This follows our previous research which highlighted the metabolic effect of CDI and these treatments in the brain and employs the same four different metabolomics-based methods (targeted GC-MS/MS, targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS and untargeted GC-MS). A total of 286 unique metabolites have been identified in the mouse cecal profiles and statistical analysis revealed that CDI, as well as the subsequent treatments, significantly alters cecal metabolites and lipids implicated in various biochemical pathways centered around amino acid metabolism, glycerophospholipid metabolism, and central carbon metabolism. To our knowledge, this study represents the first exploration of the effects of C. difficile-induced colitis and potential treatments on the cecal tissue metabolome.}, } @article {pmid39479215, year = {2024}, author = {Huang, J and Xu, T and Quan, G and Li, Y and Yang, X and Xie, W}, title = {Current progress on the microbial therapies for acute liver failure.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1452663}, pmid = {39479215}, issn = {1664-302X}, abstract = {Acute liver failure (ALF), associated with a clinical fatality rate exceeding 80%, is characterized by severe liver damage resulting from various factors in the absence of pre-existing liver disease. The role of microbiota in the progression of diverse liver diseases, including ALF, has been increasingly recognized, with the interactions between the microbiota and the host significantly influencing both disease onset and progression. Despite growing interest in the microbiological aspects of ALF, comprehensive reviews remain limited. This review critically examines the mechanisms and efficacy of microbiota-based treatments for ALF, focusing on their role in prevention, treatment, and prognosis over the past decade.}, } @article {pmid39473963, year = {2024}, author = {Wang, YN and Zhai, XY and Wang, Z and Gao, CL and Mi, SC and Tang, WL and Fu, XM and Li, HB and Yue, LF and Li, PF and Xi, SY}, title = {Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with H22 hepatocellular carcinoma.}, journal = {World journal of gastrointestinal oncology}, volume = {16}, number = {10}, pages = {4209-4231}, pmid = {39473963}, issn = {1948-5204}, abstract = {BACKGROUND: Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing & life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear.

AIM: To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC).

METHODS: Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1β, IL-6, IL-8, IL-10, IL-22, TNF-α, and TGF-β, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-κB, Occludin, MUC-2, Claudin-1, and IκB-α in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing.

RESULTS: TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-β, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-κB, IL-1β, IL-6, TNF-α, IL-22, IL-8, and IκB-α were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria, AF12, Adlercreutzia, Clostridium, Coriobacteriaceae, and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum, Odoribacter, RF32, YS2, and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora.

CONCLUSION: TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy.}, } @article {pmid39471749, year = {2024}, author = {Liu, X and Lu, B and Tang, H and Jia, X and Zhou, Q and Zeng, Y and Gao, X and Chen, M and Xu, Y and Wang, M and Tan, B and Li, J}, title = {Gut microbiome metabolites, molecular mimicry, and species-level variation drive long-term efficacy and adverse event outcomes in lung cancer survivors.}, journal = {EBioMedicine}, volume = {109}, number = {}, pages = {105427}, doi = {10.1016/j.ebiom.2024.105427}, pmid = {39471749}, issn = {2352-3964}, abstract = {BACKGROUND: The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms.

METHODS: We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts).

FINDINGS: The ICI benefit group was enriched for propionate (P = 0.01) and butyrate/isobutyrate (P = 0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P < 0.001, butyrate/isobutyrate P = 0.002). The acetyl-CoA pathway (P = 0.02) in beneficial species mainly mediated butyrate production. Microbiota sequences from irAE patients aligned with antigenic epitopes found in autoimmune diseases. Microbiotas of responsive patients contained more lung cancer-related antigens (P = 0.07), which was validated in the Routy cohort (P = 0.02). Escherichia coli and SGB15342 of Faecalibacterium prausnitzii showed strain-level variations corresponding to clinical phenotypes. Metabolome validation reviewed more abundant acetic acid (P = 0.03), propionic acid (P = 0.09), and butyric acid (P = 0.02) in the benefit group than the resistance group, and patients with higher acetic, propionic, and butyric acid levels had a longer progression-free survival and lower risk of tumor progression after adjusting for histopathological subtype and stage (P < 0.05).

INTERPRETATION: Long-term ICI survivors have coevolved a compact microbial community with high butyrate production, and molecular mimicry of autoimmune and tumor antigens by microbiota contribute to outcomes. These results not only characterize the gut microbiotas of patients who benefit long term from ICIs but pave the way for "smart" fecal microbiota transplantation. Registered in the Chinese Clinical Trial Registry (ChiCTR2000032088).

FUNDING: This work was supported by Beijing Natural Science Foundation (7232110), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-072, 2023-PUMCH-C-054), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-010).}, } @article {pmid39471538, year = {2024}, author = {Levitte, S and Nilkant, R and Jensen, AR and Zhang, KY}, title = {Unlocking the promise of mesenchymal stem cells and extracorporeal photopheresis to address rejection and graft failure in intestinal transplant recipients.}, journal = {Human immunology}, volume = {85}, number = {6}, pages = {111160}, doi = {10.1016/j.humimm.2024.111160}, pmid = {39471538}, issn = {1879-1166}, abstract = {INTRODUCTION: In patients with irreversible intestinal failure, intestinal transplant has become a standard treatment option. Graft failure secondary to acute or chronic cellular rejection continues to be a significant challenge following transplant. Even with optimal immune suppression, some patients continue to struggle with refractory rejection. Both extracorporeal photopheresis (ECP) and extracellular vesicles derived from mesenchymal stem cells (EVs) have been used to treat refractory rejection following intestinal transplantation, although their use remains limited and consistent treatment protocols are lacking.

METHODS: Intestinal transplant recipients who received ECP only or ECP and EVs as rescue therapy for acute cellular rejection or chronic inflammation between 2016 and 2022 were included in this single-center retrospective analysis. Baseline demographics, pre- and post-treatment histopathology, endoscopic and biochemical findings, and long-term transplant outcomes were analyzed.

RESULTS: Three patients (two pediatric and one adult) with acute steroid- and biologic-refractory rejection were treated with ECP and/or EVs, as was one patient (pediatric) with chronic graft rejection and inflammation. Patients received twice weekly ECP for 4 weeks and once weekly thereafter. EVs were administered in three doses each separated by 72 h. Immunosuppression at the time of treatment initiation included high-dose tacrolimus and sirolimus. Histologic resolution of rejection was achieved in all patients over 12-16 weeks. Steroids were weaned to low-dose or withdrawn in every patient within 4 weeks of ECP/EV treatment. C-reactive protein decreased from an average of 14.75 to 1.6 mg/dL post-treatment and fecal calprotectin decreased from average 800 mg/g to 31 mg/g. Donor-induced cytotoxic T cell populations were quantified for two of the patients with acute rejection, and in both cases decreased dramatically following treatment. There were no complications associated with either treatment.

CONCLUSION: Both ECP and EVs present novel opportunities to address graft rejection and inflammation in bowel transplant recipients. More work will be needed to define the optimal therapeutic parameters for each treatment modality.}, } @article {pmid39470619, year = {2024}, author = {Liu, X and Luo, Y and Chen, X and Wu, M and Xu, X and Tian, J and Gao, Y and Zhu, J and Wang, Z and Zhou, Y and Zhang, Y and Wang, X and Li, W and Lu, Q and Yao, X}, title = {Fecal microbiota transplantation against moderate-to-severe atopic dermatitis: A randomized, double-blind controlled explorer trial.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.16372}, pmid = {39470619}, issn = {1398-9995}, support = {//Nanjing Incubation Program for National Clinical Research Center/ ; //National Key Research and Development Program of China/ ; //CAMS Innovation Fund for Medical Sciences/ ; //Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; //National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate-to-severe atopic dermatitis (AD).

METHODS: In this randomized, double-blind, placebo-controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate-to-severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial.

RESULTS: Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo-treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF-α, and total IgE in serum. By contrast, the expression levels of IL-12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4-dihydroxy-6-naphthoate biosynthesis II.

CONCLUSION: FMT was a safe and effective therapy in moderate-to-severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.}, } @article {pmid39470206, year = {2024}, author = {Todd, CL and Johnson, EE and Stewart, F and Wallace, SA and Bryant, A and Woodward, S and Norton, C}, title = {Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.}, journal = {The Cochrane database of systematic reviews}, volume = {10}, number = {10}, pages = {CD002115}, pmid = {39470206}, issn = {1469-493X}, mesh = {Humans ; *Constipation/therapy/etiology ; *Fecal Incontinence/therapy/etiology ; *Randomized Controlled Trials as Topic ; Adult ; *Central Nervous System Diseases/complications ; Conservative Treatment/methods ; Quality of Life ; Bias ; }, abstract = {BACKGROUND: People with central neurological disease or injury have a much higher risk of both faecal incontinence (FI) and constipation than the general population. There is often a fine line between the two symptoms, with management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical, with a limited research base. The review is relevant to individuals with any disease directly and chronically affecting the central nervous system (post-traumatic, degenerative, ischaemic or neoplastic), such as multiple sclerosis, spinal cord injury, cerebrovascular disease, Parkinson's disease and Alzheimer's disease. This is an update of a Cochrane Review first published in 2001 and subsequently updated in 2003, 2006 and 2014.

OBJECTIVES: To assess the effects of conservative, physical and surgical interventions for managing FI and constipation in people with a neurological disease or injury affecting the central nervous system.

SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register (searched 27 March 2023), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP as well as handsearching of journals and conference proceedings; and all reference lists of relevant articles.

SELECTION CRITERIA: We included randomised, quasi-randomised (where allocation is not strictly random), cross-over and cluster-randomised trials evaluating any type of conservative, physical or surgical intervention against placebo, usual care or no intervention for the management of FI and constipation in people with central neurological disease or injury.

DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the risk of bias in eligible trials using Cochrane's 'Risk of bias' tool and independently extracted data from the included trials using a range of prespecified outcome measures. We produced summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE.

MAIN RESULTS: We included 25 studies with 1598 participants. The studies were generally at high risk of bias due to lack of blinding of participants and personnel to the intervention. Half of the included studies were also at high risk of bias in terms of selective reporting. Outcomes were often reported heterogeneously across studies, making it difficult to pool data. We did not find enough evidence to be able to analyse the effects of interventions on individual central neurological diseases. Additionally, very few studies reported on the primary outcomes of self-reported improvement in FI or constipation, or Neurogenic Bowel Dysfunction Score. Conservative interventions compared with usual care, no active treatment or placebo Thirteen studies assessed this comparison. The interventions included assessment-based nursing, holistic nursing, probiotics, psyllium, faecal microbiota transplantation, and a stepwise protocol of increasingly invasive evacuation methods. Conservative interventions may result in a large improvement in faecal incontinence (standardised mean difference (SMD) -1.85, 95% confidence interval (CI) -3.47 to -0.23; 3 studies; n = 410; low-certainty evidence). We interpreted SMD ≥ 0.80 as a large effect. It was not possible to pool all data from studies that assessed improvement in constipation, but the evidence suggested that conservative interventions may improve constipation symptoms (data not pooled; 8 studies; n = 612; low-certainty evidence). Conservative interventions may lead to a reduction in mean time taken on bowel care (data not pooled; 5 studies; n = 526; low-certainty evidence). The evidence is uncertain about the effects of conservative interventions on condition-specific quality of life and adverse events. Neurogenic Bowel Dysfunction Score was not reported. Physical therapy compared with usual care, no active treatment or placebo Twelve studies assessed this comparison. The interventions included massage therapy, standing, osteopathic manipulative treatment, electrical stimulation, transanal irrigation, and conventional physical therapy with visceral mobilisation. Physical therapies may make little to no difference to self-reported faecal continence assessed using the St Mark's Faecal Incontinence Score, where the minimally important difference is five, or the Cleveland Constipation Score (MD -2.60, 95% CI -4.91 to -0.29; 3 studies; n = 155; low-certainty evidence). Physical therapies may result in a moderate improvement in constipation symptoms (SMD -0.62, 95% CI -1.10 to -0.14; 9 studies; n = 431; low-certainty evidence). We interpreted SMD ≥ 0.5 as a moderate effect. However, physical therapies may make little to no difference in Neurogenic Bowel Dysfunction Score as the minimally important difference for this tool is 3 (MD -1.94, 95% CI -3.36 to -0.51; 7 studies; n = 358; low-certainty evidence). We are very uncertain about the effects of physical therapies on the time spent on bowel care, condition-specific quality of life and adverse effects (all very low-certainty evidence). Surgical interventions compared with usual care, no active treatment or placebo No studies were found for surgical interventions that met the inclusion criteria for this review.

AUTHORS' CONCLUSIONS: There remains little research on this common and, for patients, very significant issue of bowel management. The available evidence is almost uniformly of low methodological quality. The clinical significance of some of the research findings presented here is difficult to interpret, not least because each intervention has only been addressed in individual trials, against control rather than compared against each other, and the interventions are very different from each other. Understanding whether there is a clinically-meaningful difference from the results of available trials is largely hampered by the lack of uniform outcome measures. This is due to an absence of core outcome sets, and development of these needs to be a research priority to allow studies to be compared directly. Some studies used validated constipation, incontinence or condition-specific measures; however, others used unvalidated analogue scales to report effectiveness. Some studies did not use any patient-reported outcomes and focused on physiological outcome measures, which is of relatively limited significance in terms of clinical implementation. There was evidence in favour of some conservative interventions, but these findings need to be confirmed by larger, well-designed controlled trials, which should include evaluation of the acceptability of the intervention to patients and the effect on their quality of life.}, } @article {pmid39468666, year = {2024}, author = {Lian, J and Xia, L and Wang, G and Wu, W and Yi, P and Li, M and Su, X and Chen, Y and Li, X and Dou, F and Wang, Z}, title = {Multi-omics evaluation of clinical-grade human umbilical cord-derived mesenchymal stem cells in synergistic improvement of aging related disorders in a senescence-accelerated mouse model.}, journal = {Stem cell research & therapy}, volume = {15}, number = {1}, pages = {383}, pmid = {39468666}, issn = {1757-6512}, support = {3502220214001//Xiamen Cell Therapy Research Center/ ; 3502Z20234008//Key Healthcare Projects of Xiamen City/ ; 202212631066//Xiamen Medical College Undergraduate Innovation and Entrepreneurship Training Program/ ; 2022//Xiamen Medical College Undergraduate Innovation and Entrepreneurship Training Program/ ; 2023QNB003//Health science and technology project of Fujian Province/ ; 3502Z202372072//Natural Science Foundation of Xiamen/ ; 3502Z20244ZD1009//Natural Science Foundation of Xiamen/ ; }, mesh = {Animals ; Mice ; *Mesenchymal Stem Cells/metabolism/cytology ; Humans ; *Umbilical Cord/cytology/metabolism ; *Aging ; *Disease Models, Animal ; Mesenchymal Stem Cell Transplantation/methods ; Gastrointestinal Microbiome ; Male ; DNA Damage ; Multiomics ; }, abstract = {BACKGROUND: The prevalence of age-related disorders, particularly in neurological and cardiovascular systems, is an increasing global health concern. Mesenchymal stem cell (MSC) therapy, particularly using human umbilical cord-derived MSCs (HUCMSCs), has shown promise in mitigating these disorders. This study investigates the effects of HUCMSCs on aging-related conditions in a senescence-accelerated mouse model (SAMP8), with a focus on DNA damage, gut microbiota alterations, and metabolic changes.

METHODS: SAMP8 mice were treated with clinical-grade HUCMSCs via intraperitoneal injections. Behavioral and physical assessments were conducted to evaluate cognitive and motor functions. The Single-Strand Break Mapping at Nucleotide Genome Level (SSiNGLe) method was employed to assess DNA single-strand breaks (SSBs) across the genome, with particular attention to exonic regions and transcription start sites. Gut microbiota composition was analyzed using 16S rRNA sequencing, and carboxyl metabolomic profiling was performed to identify changes in circulating metabolites.

RESULTS: HUCMSC treatment significantly improved motor coordination and reduced anxiety in SAMP8 mice. SSiNGLe analysis revealed a notable reduction in DNA SSBs in MSC-treated mice, especially in critical genomic regions, suggesting that HUCMSCs may mitigate age-related DNA damage. The functional annotation of the DNA breaktome indicated a potential link between reduced DNA damage and altered metabolic pathways. Additionally, beneficial alterations in gut microbiota were observed, including an increase in short-chain fatty acid (SCFA)-producing bacteria, which correlated with improved metabolic profiles.

CONCLUSION: The administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism. The observed alterations in DNA break patterns, along with specific changes in microbiota and metabolic profiles, suggest that these could serve as potential biomarkers for evaluating the efficacy of HUCMSCs in treating age-related disorders. This highlights a promising avenue for the development of new therapeutic strategies that leverage these biomarkers, to enhance the effectiveness of HUCMSC-based treatments for aging-associated diseases.}, } @article {pmid39468065, year = {2024}, author = {Wang, G and Cao, L and Li, S and Zhang, M and Li, Y and Duan, J and Li, Y and Hu, Z and Wu, J and Ni, J and Lan, D and Li, T and Lu, J}, title = {Gut microbiota dysbiosis-mediated ceramides elevation contributes to corticosterone-induced depression by impairing mitochondrial function.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {111}, pmid = {39468065}, issn = {2055-5008}, support = {82371176//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81801331//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Mitochondria/metabolism ; *Corticosterone ; Mice ; *Depression ; *Ceramides/metabolism ; *Dysbiosis ; *Hippocampus/metabolism ; Fecal Microbiota Transplantation ; Male ; Disease Models, Animal ; Feces/microbiology ; Mice, Inbred C57BL ; Neurogenesis ; Behavior, Animal/drug effects ; }, abstract = {The role of gut microbiota (GM) dysbiosis in the pathogenesis of depression has received widespread attention, but the mechanism remains elusive. Corticosterone (CORT)-treated mice showed depression-like behaviors, reduced hippocampal neurogenesis, and altered composition of the GM. Fecal microbial transplantation from CORT-treated mice transferred depression-like phenotypes and their dominant GM to the recipients. Fecal metabolic profiling exposed remarkable increase of gut ceramides in CORT-treated and recipient mice. Oral gavage with Bifidobacterium pseudolongum and Lactobacillus reuteri could induce elevations of gut ceramides in mice. Ceramides-treated mice showed depressive-like phenotypes, significant downregulation of oxidative phosphorylation-associated genes, and hippocampal mitochondrial dysfunction. Our study demonstrated a link between chronic exposure to CORT and its impact on GM composition, which induces ceramides accumulation, ultimately leading to hippocampal mitochondrial dysfunction. This cascade of events plays a critical role in reducing adult hippocampal neurogenesis and is strongly associated with the development of depression-like behaviors.}, } @article {pmid39467697, year = {2024}, author = {Qu, J and Meng, F and Wang, Z and Xu, W}, title = {Unlocking Cardioprotective Potential of Gut Microbiome: Exploring Therapeutic Strategies.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {12}, pages = {1-12}, doi = {10.4014/jmb.2405.05019}, pmid = {39467697}, issn = {1738-8872}, abstract = {The microbial community inhabiting the human gut resembles a bustling metropolis, wherein beneficial bacteria play pivotal roles in regulating our bodily functions. These microorganisms adeptly break down resilient dietary fibers to fuel our energy, synthesize essential vitamins crucial for our well-being, and maintain the delicate balance of our immune system. Recent research indicates a potential correlation between alterations in the composition and activities of these gut microbes and the development of coronary artery disease (CAD). Consequently, scientists are delving into the intriguing realm of manipulating these gut inhabitants to potentially mitigate disease risks. Various promising strategies have emerged in this endeavor. Studies have evidenced that probiotics can mitigate inflammation and enhance the endothelial health of our blood vessels. Notably, strains such as Lactobacilli and Bifidobacteria have garnered substantial attention in both laboratory settings and clinical trials. Conversely, prebiotics exhibit anti-inflammatory properties and hold potential in managing conditions like hypertension and hypercholesterolemia. Synbiotics, which synergistically combine probiotics and prebiotics, show promise in regulating glucose metabolism and abnormal lipid profiles. However, uncertainties persist regarding postbiotics, while antibiotics are deemed unsuitable due to their potential adverse effects. On the other hand, TMAO blockers, such as 3,3-dimethyl-1-butanol, demonstrate encouraging outcomes in laboratory experiments owing to their anti-inflammatory and tissue-protective properties. Moreover, fecal transplantation, despite yielding mixed results, warrants further exploration and refinement. In this comprehensive review, we delve into the intricate interplay between the gut microbiota and CAD, shedding light on the multifaceted approaches researchers are employing to leverage this understanding for therapeutic advancements.}, } @article {pmid39466773, year = {2024}, author = {Partida-Rodríguez, O and Brown, EM and Woodward, SE and Cirstea, M and Reynolds, LA and Petersen, C and Vogt, SL and Peña-Díaz, J and Thorson, L and Arrieta, MC and Hernández, EG and Rojas-Velázquez, L and Moran, P and González Rivas, E and Serrano-Vázquez, A and Pérez-Juárez, H and Torres, J and Ximénez, C and Finlay, BB}, title = {Fecal microbiota transplantation from protozoa-exposed donors downregulates immune response in a germ-free mouse model, its role in immune response and physiology of the intestine.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0312775}, pmid = {39466773}, issn = {1932-6203}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; *Germ-Free Life ; Gastrointestinal Microbiome/immunology ; Cytokines/metabolism ; T-Lymphocytes, Regulatory/immunology ; Intestines/immunology/parasitology/microbiology ; Mice, Inbred C57BL ; Intestinal Mucosa/immunology/metabolism ; Down-Regulation ; Female ; Spleen/immunology/metabolism ; }, abstract = {Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP). We determined the production of intestinal cytokines, the lymphocyte populations in both the colon and the spleen, and the genetic expression of markers of intestinal epithelial integrity. We observed a general downregulation of the intestinal immune response in mice receiving FMT-P. We found significantly lower intestinal production of the cytokines IL-6, TNF, IFN-γ, MCP-1, IL-10, and IL-12 in the FMT-P. Furthermore, a significant decrease in the proportion of CD3+, CD4+, and Foxp3+ T regulatory cells (Treg) was observed in both, the colon and spleen with FMT-P in contrast to FMT-NP. We also found that in FMT-P mice there was a significant decrease in tjp1 expression in all three regions of the small intestine; ocln in the ileum; reg3γ in the duodenum and relmβ in both the duodenum and ileum. We also found an increase in colonic mucus layer thickness in mice colonized with FMT-P in contrast with FMT-NP. Finally, our results suggest that gut protozoa, such as Blastocystis hominis, Entamoeba coli, Endolimax nana, Entamoeba histolytica/E. dispar, Iodamoeba bütschlii, and Chilomastix mesnili consortia affect the immunoinflammatory state and induce functional changes in the intestine via the gut microbiota. Likewise, it allows us to establish an FMT model in germ-free mice as a viable alternative to explore the effects that exposure to intestinal parasites could have on the immune response in humans.}, } @article {pmid39463943, year = {2024}, author = {Dai, A and Adintori, PA and Funnell, T and Jogia, WP and Fei, T and Waters, NR and Rangesa, M and Ballweg, A and Gipson, B and Raj, S and Hayase, E and Markey, KA and Burgos da Silva, M and Miltiadous, O and Brambilla, CZ and Buchan, ML and Peets, T and Gradissimo, A and Smith, N and Katsamakis, Z and Warren, A and Amoretti, LA and Duan, C and Zhang, C and Matheis, F and Sullivan, AP and Slingerland, JB and Clurman, A and Brereton, DG and Giardina, PA and Gomes, ALC and Johnson, AJ and Knights, D and Jenq, RR and Perales, MA and Giralt, SA and Schluter, J and van den Brink, MRM and Peled, J}, title = {Sugar-rich foods exacerbate antibiotic-induced microbiome injury.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.10.14.617881}, pmid = {39463943}, issn = {2692-8205}, abstract = {Intestinal microbiota composition is implicated in several diseases; understanding the factors that influence it are key to elucidating host-commensal interactions and to designing microbiome-targeted therapies. We quantified how diet influences microbiome dynamics in hospitalized patients. We recorded 9,419 meals consumed by 173 patients undergoing hematopoietic cell transplantation and profiled the microbiome in 1,009 longitudinally collected stool samples from 158 of them. Caloric intake was correlated with fecal microbiota diversity. Bayesian inference revealed associations between intake of sweets or sugars during antibiotic exposure with microbiome disruption, as assessed by low diversity or expansion of the pathobiont Enterococcus. We validated this observation experimentally, finding that sucrose exacerbated antibiotic-induced Enterococcus expansion in mice. Taken together, our results suggest that avoiding sugar-rich foods during antibiotic treatment may reduce microbiome injury.}, } @article {pmid39462615, year = {2024}, author = {Ozaki, Y and Suzuki, Y and Suzuki, H}, title = {[Gut Microbiota as a Potential Biomarker for Immune Checkpoint Inhibitors].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {9}, pages = {862-864}, pmid = {39462615}, issn = {0385-0684}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use ; *Lung Neoplasms/drug therapy/immunology/microbiology ; Biomarkers, Tumor/immunology ; }, abstract = {Immune checkpoint inhibitors(ICIs)currently play a predominant role in the standard treatment of non-small cell lung cancer(NSCLC)across all stages. While PD-L1 positivity has traditionally been used as the sole effective biomarker, evidence suggests that certain efficacy exists even in PD-L1-negative lung cancers. Various investigations have been conducted to identify biomarkers predicting the therapeutic efficacy of ICIs, focusing on both tumor-local and host-related factors. Among indicators reflecting the host status, the gut microbiota has garnered attention, with its composition and diversity potentially influencing the efficacy of ICI therapy. The presence of specific gut microbiota has been frequently reported to enhance the effectiveness of ICI treatment. Furthermore, the use of antibiotics may diminish the effects of ICIs, while fecal microbiota transplantation has shown potential to enhance ICI therapy. In our department, analysis of the gut microbiota in patients receiving anti-PD-1 antibody treatment has been conducted, yielding promising results through the identification of specific bacterial species and the search for these species using real-time PCR, suggesting avenues for further research. Recently, attention has also been drawn to the lung microbiota and tumor microbiota in the context of lung cancer, with reports suggesting that increased diversity in these microbial communities may correlate with the efficacy of ICI therapy. However, none of these findings alone provide sufficient evidence as standalone biomarkers, necessitating future research to advance from both the host environment, including the gut microbiota, and the microenvironment of the tumor site, such as the lung and tumor microbiota.}, } @article {pmid39462312, year = {2024}, author = {Garcia-Martinez, Y and Alexandrova, E and Iebba, V and Ferravante, C and Spinelli, M and Franci, G and Amoresano, A and Weisz, A and Trepiccione, F and Borriello, M and Ingrosso, D and Perna, AF}, title = {Does gut microbiota dysbiosis impact the metabolic alterations of hydrogen sulfide and lanthionine in patients with chronic kidney disease?.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {436}, pmid = {39462312}, issn = {1471-2180}, support = {Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hydrogen Sulfide/metabolism ; *Renal Insufficiency, Chronic/microbiology/metabolism ; Male ; Female ; Middle Aged ; *Dysbiosis/microbiology ; *Feces/microbiology/chemistry ; Aged ; Sulfides/metabolism ; Adult ; Renal Dialysis ; Bacteria/classification/isolation & purification/metabolism/genetics ; Alanine/analogs & derivatives/metabolism ; Case-Control Studies ; }, abstract = {BACKGROUND: Chronic Kidney Disease (CKD) is characterized by a methionine-related metabolic disorder involving reduced plasma levels of hydrogen sulfide (H2S) and increased lanthionine. The gut microbiota influences methionine metabolism, potentially impacting sulfur metabolite dysfunctions in CKD. We evaluated whether gut microbiota dysbiosis contributes to H2S and lanthionine metabolic alterations in CKD.

METHODS: The gut microbiota of 88 CKD patients (non-dialysis, hemodialysis, and transplant patients) and 26 healthy controls were profiled using 16 S-amplicon sequencing. H2S and lanthionine concentrations were measured in serum and fecal samples using the methylene blue method and LC-MS/MS, respectively.

RESULTS: The CKD population exhibited a tenfold increase in serum lanthionine associated with kidney dysfunction. Despite lanthionine retention, hemodialysis and transplant patients had significantly lower serum H2S than healthy controls. Fecal H2S levels were not altered or related to bloodstream H2S concentrations. Conversely, fecal lanthionine was significantly increased in CKD compared to healthy controls and associated with kidney dysfunction. Microbiota composition varied among CKD groups and healthy controls, with the greatest dissimilarity observed between hemodialysis and transplant patients. Changes relative to the healthy group included uneven Ruminococcus gnavus distribution (higher in transplant patients and lower in non-dialysis CKD patients), reduced abundance of the short-chain fatty acid-producing bacteria Alistipes indistinctus and Coprococcus eutactus among transplant patients, and depleted Streptococcus salivarius in non-dialysis CKD patients. A higher abundance of Methanobrevibacter smithii, Christensenella minuta, and Negativibacillus massiliensis differentiated hemodialysis patients from controls. No correlation was found between differentially abundant species and the metabolic profile that could account for the H2S and lanthionine alterations observed.

CONCLUSIONS: The metabolic deregulation of H2S and lanthionine observed in the study was not associated with alterations in the gut microbiota composition in CKD patients. Further research on microbial sulfur pathways may provide a better understanding of the role of gut microbiota in maintaining H2S and lanthionine homeostasis.}, } @article {pmid39462039, year = {2024}, author = {Zhou, X and Shen, S and Wang, Z}, title = {Genetic evidence of bidirectional mendelian randomization study on the causality between gut microbiome and respiratory diseases contributes to gut-lung axis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {25550}, pmid = {39462039}, issn = {2045-2322}, support = {82174302//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/genetics ; *Genome-Wide Association Study ; Lung/microbiology/pathology ; Respiratory Tract Diseases/microbiology/genetics ; Risk Factors ; }, abstract = {Observational studies and clinical trials have suggested the relationship between the gut microbiome and respiratory diseases, but the causality between them remains unclear. Firstly, we selected eight respiratory diseases Genome-wide association study (GWAS) datasets mainly from the FinnGen collaboration as outcomes. The exposure was based on GWAS statistics about the gut microbiome, sourced from the MiBioGen consortium, including gut microbial taxa. The causal link between the gut microbiome and respiratory illnesses was then estimated using a Two-sample Mendelian randomization (MR) analysis, including the inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure reliability, F-statistics and sensitivity tests were conducted. Furthermore, we performed a reverse MR analysis of the pre-Mendelian positive findings to possible reverse causality. For the 196 gut microbe taxa, the IVW analysis suggested 88 potential associations with eight clinically prevalent respiratory diseases. Among them, 30 causal associations were found in more than one MR method. Multiple statistical corrections have confirmed three causal associations: genus Holdemanella was a risk factor for chronic obstructive pulmonary disease (COPD) (P = 1.3 × 10[-4], OR = 1.18), family FamilyXIII was a protective factor for COPD (P = 1.3 × 10[-3], OR = 0.75), and genus Oxalobacter was a risk factor for asthma (P = 2.1 × 10[-4], OR = 1.09). Our MR analysis results indicate that there would be a causal relationship between the gut microbiome and respiratory diseases, contributing to the gut-lung axis. This finding offers new insights into the gut microbiome's roles in respiratory diseases' clinical prevention, pathogenesis, and improvement of clinical symptoms. Further randomized controlled trials are necessary to clarify the protective effect of probiotics and fecal microbial transplantation on respiratory health.}, } @article {pmid39461299, year = {2024}, author = {Verbiest, A and Hvistendahl, MK and Bolognani, F and Li, C and Youssef, NN and Huh, S and Menys, A and Bhatnagar, G and Vanslembrouck, R and Peeters, R and Sartoris, R and Vermeersch, P and Wauters, L and Verbeke, K and Jeppesen, PB and Joly, F and Vanuytsel, T}, title = {Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity: A multicenter, open-label, metabolic balance study.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {12}, pages = {158-166}, doi = {10.1016/j.clnu.2024.10.011}, pmid = {39461299}, issn = {1532-1983}, abstract = {BACKGROUND: Apraglutide is a novel long-acting GLP-2 analog in development for short bowel syndrome with intestinal failure (SBS-IF). This multicenter, open-label, phase 2 study in SBS-IF and colon-in-continuity (CiC) investigates the safety and efficacy of apraglutide.

METHODS: This was a 52-week phase 2 metabolic balance study (MBS) in 9 adult patients with SBS-IF-CiC receiving once-weekly subcutaneous apraglutide injections. Safety was the primary endpoint. Secondary endpoints included changes in absorption parameters (MBS at baseline, after 4 weeks with stable parenteral support (PS), and 48 weeks), PS needs (48-week PS adjustment period based on monthly 48-h fluid balances) and intestinal morphology and motility (static and cine MRI at baseline and 4, 24 and 48 weeks).

RESULTS: PS volume decreased by -4702 mL/week (-52 %; p < 0.001) at week 52. Seven patients (78 %) achieved ≥1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253 g/day (p = 0.013). At 48 weeks, increases in wet weight absorption by 316 g/day (p = 0.039), energy absorption by 1134 kJ/day (p = 0.041) and carbohydrate absorption by 56.1 g/day (p = 0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7 cm (p = 0.012), duodenal wall thickness increased by 0.8 mm (p = 0.02) and motility in the proximal colon was reduced (p = 0.031). A total of 127 adverse events was reported, which were mostly mild to moderate.

CONCLUSION: Apraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC.

CLINICALTRIALS: gov, Number NCT04964986.}, } @article {pmid39460926, year = {2024}, author = {Magnusson, C and Ölfvingsson, E and Hjortswang, H and Östholm, Å and Serrander, L}, title = {Improved health-related quality of life in patients with recurrent Clostridioides difficile infection after treatment with faecal microbiota transplantation.}, journal = {Infectious diseases (London, England)}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/23744235.2024.2415694}, pmid = {39460926}, issn = {2374-4243}, abstract = {BACKGROUND: Clostridioides difficile is a major burden for both healthcare systems and the patients. Faecal microbiota transplantation (FMT) is becoming more common as a treatment since it reduces the risk of recurrent Clostridioides difficile infection (rCDI).

OBJECTIVES: To evaluate how treatment with FMT is affecting the health-related quality of life (HRQoL) in patients with rCDI.

METHODS: A prospective observational cohort study was conducted where patients who were offered FMT as a treatment for rCDI were asked to fill in a questionnaire based on the Short Health Scale (SHS) and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) about their HRQoL before and after treatment.

RESULTS: Patients with rCDI had poor HRQoL, which improved following FMT.

CONCLUSIONS: Since FMT cures, reduces the risk of new recurrences of CDI and improves the HRQoL of the patients, it should be offered as a treatment for patients with rCDI. Also, SHS is a useful and reliable instrument for measuring HRQoL in patients with rCDI.}, } @article {pmid39460538, year = {2024}, author = {Yang, J and Liang, J and Hu, N and He, N and Liu, B and Liu, G and Qin, Y}, title = {The Gut Microbiota Modulates Neuroinflammation in Alzheimer's Disease: Elucidating Crucial Factors and Mechanistic Underpinnings.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {10}, pages = {e70091}, pmid = {39460538}, issn = {1755-5949}, support = {2024yjscx013//Innovative Research Project for Postgraduate Students of Heilongjiang University of Traditional Chinese Medicine/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Alzheimer Disease/microbiology/metabolism/pathology ; Humans ; *Neuroinflammatory Diseases/microbiology/metabolism ; Animals ; Dysbiosis ; Blood-Brain Barrier/metabolism/microbiology ; Fecal Microbiota Transplantation ; Probiotics ; }, abstract = {BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuronal loss, commonly linked to amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Recent research highlights the gut microbiota as a key player in modulating neuroinflammation, a critical pathological feature of AD. Understanding the role of the gut microbiota in this process is essential for uncovering new therapeutic avenues and gaining deeper insights into AD pathogenesis.

METHODS: This review provides a comprehensive analysis of how gut microbiota influences neuroinflammation and glial cell function in AD. A systematic literature search was conducted, covering studies from 2014 to 2024, including reviews, clinical trials, and animal studies. Keywords such as "gut microbiota," "Alzheimer's disease," "neuroinflammation," and "blood-brain barrier" were used.

RESULTS: Dysbiosis, or the imbalance in gut microbiota composition, has been implicated in the modulation of key AD-related mechanisms, including neuroinflammation, blood-brain barrier integrity, and neurotransmitter regulation. These disruptions may accelerate the onset and progression of AD. Additionally, therapeutic strategies targeting gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, show promise in modulating AD pathology.

CONCLUSIONS: The gut microbiota is a pivotal factor in AD pathogenesis, influencing neuroinflammation and disease progression. Understanding the role of gut microbiota in AD opens avenues for innovative diagnostic, preventive, and therapeutic strategies.}, } @article {pmid39459579, year = {2024}, author = {Alswat, AS}, title = {The Influence of the Gut Microbiota on Host Health: A Focus on the Gut-Lung Axis and Therapeutic Approaches.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {39459579}, issn = {2075-1729}, abstract = {The human gut microbiota is a complex ecosystem harboring thousands of microbial strains that play a crucial role in maintaining the overall well-being of its host. The composition of the gut microbiota varies with age from infancy to adulthood and is influenced by dietary habits, environment, and genetic disposition. Recent advances in culture-independent techniques and nucleic acid sequencing have improved our understanding of the diversity of the gut microbiota. The microbial species present in the gut release short-chain fatty acids (SCFAs), which have anti-inflammatory properties. The gut microbiota also plays a substantial role in modulating the host's immune system, promoting immune tolerance, and maintaining homeostasis. The impact of the gut microbiota on the health of the host is quite evident, as gut dysbiosis has been linked to various diseases, including metabolic disorders, autoimmune diseases, allergies, and inflammatory bowel diseases. The gut microbiota has bidirectional communication with the respiratory system, creating the gut-lung axis, which has been associated with different respiratory diseases. Therapeutic approaches targeting the gut microbiota, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), aim to restore microbial balance and promote the growth of beneficial strains in the gut. Nonetheless, gaining knowledge of the complex interactions between the gut microbiota and the host is necessary to develop personalized medicine approaches and microbiota-based therapies for various conditions. This review summarizes studies related to the gut-lung axis with particular emphasis on the role of the microbiota. Future research directions are also discussed.}, } @article {pmid39458553, year = {2024}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {Nutritional and Microbial Strategies for Treating Acne, Alopecia, and Atopic Dermatitis.}, journal = {Nutrients}, volume = {16}, number = {20}, pages = {}, pmid = {39458553}, issn = {2072-6643}, mesh = {Humans ; *Dermatitis, Atopic/therapy/microbiology ; *Gastrointestinal Microbiome ; *Acne Vulgaris/therapy/microbiology ; *Probiotics/therapeutic use/administration & dosage ; *Alopecia/therapy/microbiology ; Synbiotics/administration & dosage ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Diet ; Skin/microbiology ; }, abstract = {BACKGROUND/OBJECTIVES: Diet is one of the major determinants of the composition and function of the gut microbiome, and diverse studies have established directional connections between gut microbiome dysbiosis and skin dyshomeostasis. Furthermore, a significant link between the gut and certain skin-related disorders has been reported. This work reviews the mechanisms underlying the relationship between nutritional factors, gut microbiome, and certain skin diseases such as acne vulgaris, alopecia, and atopic dermatitis. In addition, it explores how the modulation of the gut microbiome and human skin through diet and various microbial strategies, including probiotics, synbiotics, postbiotics, and fecal microbiota transplantation, may serve as future treatments for skin diseases, possibly replacing traditional methods such as antibiotic, topical corticosteroid, and laser therapies.

RESULTS: The adequate intake of certain foods can promote a balanced gut microbiome, potentially reducing skin inflammation and improving overall skin health, while poor dietary choices may lead to worse outcomes by disrupting gut homeostasis. In this regard, diets high in antioxidants, fiber, and phytonutrients appear to be beneficial for enhancing skin health and preventing associated comorbidities. In addition, the administration of probiotics, synbiotics, and postbiotics in the treatment of cutaneous diseases has been shown to restore skin dyshomeostasis and to improve the symptoms of the reviewed skin conditions.

CONCLUSIONS: Consuming a healthy, plant-based diet can reduce skin inflammation and enhance overall skin health. Although the application of probiotics, synbiotics, and postbiotics has demonstrated promise in modulating inflammation, enhancing tissue regeneration, and inhibiting pathogenic colonization, further research is required.}, } @article {pmid39458486, year = {2024}, author = {Gómez-Pérez, AM and Muñoz-Garach, A and Lasserrot-Cuadrado, A and Moreno-Indias, I and Tinahones, FJ}, title = {Microbiota Transplantation in Individuals with Type 2 Diabetes and a High Degree of Insulin Resistance.}, journal = {Nutrients}, volume = {16}, number = {20}, pages = {}, pmid = {39458486}, issn = {2072-6643}, support = {PI15/011114//Instituto de Salud Carlos III/ ; EPIGEN-MICROBIOTA NCT05076656, PI15/01114//CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Fondo de Investigación para la Salud/ ; CPII21/00013//Instituto de Salud Carlos III-FEDER: Miguel Servet II programm/ ; B-0033-2014//Servicio Andaluz de Salud/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/therapy/blood/microbiology ; Female ; Male ; *Insulin Resistance ; Middle Aged ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Aged ; *Blood Glucose/metabolism ; Single-Blind Method ; Glucose Tolerance Test ; Gastrointestinal Microbiome ; Insulin/blood ; Body Mass Index ; Lactobacillus delbrueckii ; Treatment Outcome ; Glycated Hemoglobin/metabolism ; }, abstract = {The objective of this study was to determine the results of fecal microbiota transplantation (FMT) from healthy lean subjects in patients with type 2 diabetes (T2D); Methods: We designed a phase II, randomized, single-blind, parallel-arm clinical trial. Twenty-one subjects (12 men [57.1%] and 9 women [42.9%]), who had previously signed an informed consent were randomized to FMT from lean donors, a probiotic (Lactobacillus delbrueckii spp. bulgaricus LB-14), or placebo. Mean age at baseline was 62.5 ± 5.8 years and mean body mass index (BMI) at baseline was approximately 32.4 ± 2.4 kg/m[2]. Anthropometric measures, biochemical variables, oral glucose tolerance test (OGTT), and a stool microbiota analysis were performed (baseline, 4 and 12 weeks). The trial was conducted following the Declaration of Helsinki, Good Clinical Practice Guides (CPMP/ICH/135/95) and the current Spanish legislation regarding clinical trials (RD 223/2004).; Results: FMT changes occurred at the expense of the species found in the donor. No differences in weight, body mass index, HbA1c, or the results of the OGTT for glucose and insulin were found between groups after the intervention, although a decrease in uric acid was observed in the probiotic group (-0.5 mg/dL; p = 0.037) and a mild increase in HbA1c in the FMT group (+0.25%; p = 0.041); Conclusions: In our sample, neither FMT from healthy and lean donors nor a probiotic were effective in improving insulin sensitivity and HbA1c in patients with T2D.}, } @article {pmid39458368, year = {2024}, author = {Marsiglia, R and Pane, S and Del Chierico, F and Russo, A and Vernocchi, P and Romani, L and Cardile, S and Diamanti, A and Galli, L and Tamborino, A and Terlizzi, V and De Angelis, P and Angelino, G and Putignani, L}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infections in a Cystic Fibrosis Child Previously Screen Positive, Inconclusive Diagnosis (CFSPID): A Case Report.}, journal = {Microorganisms}, volume = {12}, number = {10}, pages = {}, pmid = {39458368}, issn = {2076-2607}, support = {Current Research funds//Italian Ministry of Health/ ; }, abstract = {Clostridioides difficile infection (CDI) is generally treated with vancomycin, metronidazole or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults. In pediatric cystic fibrosis (CF) patients, CDIs are generally asymptomatic and respond to treatment. Here, we present the case of an 8-year-old female, initially diagnosed as "CFTR-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis" (CMRS/CFSPID), who then progressed to CF at 12 months. In the absence of CF-related symptoms, she presented multiple and disabling episodes of bloody diarrhoea with positive tests for C. difficile antigen and A/B toxin. After conventional treatments failed and several CDI relapses, FMT was proposed. Donor screening and GM donor-receiver matching identified her mother as a donor. Metataxonomy and targeted metabolomics provided, through a pre- and post-FMT time course, gut microbiota (GM) profiling to assess GM engraftment. At first, the GM map revealed severe dysbiosis, with a prevalence of Bacteroidetes and Proteobacteria (i.e., Klebsiella spp., Escherichia coli), a reduction in Firmicutes, a GM nearly entirely composed of Enterococcaceae (i.e., Enterococcus) and an almost complete depletion of Verrucomicrobia and Actinobacteria, mostly represented by Veillonella dispar. Post FMT, an increment in Bifidobacterium spp. and Collinsella spp. with a decrease in V. dispar restored intestinal eubiosis. Consistently, four weeks after FMT treatment, the child's gut symptoms cleared, without CDI recurrence.}, } @article {pmid39458032, year = {2024}, author = {Piccioni, A and Spagnuolo, F and Candelli, M and Voza, A and Covino, M and Gasbarrini, A and Franceschi, F}, title = {The Gut Microbiome in Sepsis: From Dysbiosis to Personalized Therapy.}, journal = {Journal of clinical medicine}, volume = {13}, number = {20}, pages = {}, pmid = {39458032}, issn = {2077-0383}, abstract = {Sepsis is a complex clinical syndrome characterized by an uncontrolled inflammatory response to an infection that may result in septic shock and death. Recent research has revealed a crucial link between sepsis and alterations in the gut microbiota, showing that the microbiome could serve an essential function in its pathogenesis and prognosis. In sepsis, the gut microbiota undergoes significant dysbiosis, transitioning from a beneficial commensal flora to a predominance of pathobionts. This transformation can lead to a dysfunction of the intestinal barrier, compromising the host's immune response, which contributes to the severity of the disease. The gut microbiota is an intricate system of protozoa, fungi, bacteria, and viruses that are essential for maintaining immunity and metabolic balance. In sepsis, there is a reduction in microbial heterogeneity and a predominance of pathogenic bacteria, such as proteobacteria, which can exacerbate inflammation and negatively influence clinical outcomes. Microbial compounds, such as short-chain fatty acids (SCFAs), perform a crucial task in modulating the inflammatory response and maintaining intestinal barrier function. However, the role of other microbiota components, such as viruses and fungi, in sepsis remains unclear. Innovative therapeutic strategies aim to modulate the gut microbiota to improve the management of sepsis. These include selective digestive decontamination (SDD), probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT), all of which have shown potential, although variable, results. The future of sepsis management could benefit greatly from personalized treatment based on the microbiota. Rapid and easy-to-implement tests to assess microbiome profiles and metabolites associated with sepsis could revolutionize the disease's diagnosis and management. These approaches could not only improve patient prognosis but also reduce dependence on antibiotic therapies and promote more targeted and sustainable treatment strategies. Nevertheless, there is still limited clarity regarding the ideal composition of the microbiota, which should be further characterized in the near future. Similarly, the benefits of therapeutic approaches should be validated through additional studies.}, } @article {pmid39457652, year = {2024}, author = {Zhang, J and Gan, H and Duan, X and Li, G}, title = {Targeting the Intestinal Microbiota: A Novel Direction in the Treatment of Inflammatory Bowel Disease.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457652}, issn = {2227-9059}, support = {82170617//National Natural Science Foundation of China/ ; }, abstract = {Over the past decade, there has been a rapid increase in the incidence of inflammatory bowel disease. It has been suggested that multifactorial interactions of environmental factors, genetic factors, immune response and intestinal microbiota are involved in the pathogenesis of inflammatory bowel disease. It is widely recognized that the intestinal microbiota are essential for human metabolism, the immune system and pathogen resistance, and are integral to human health. Therefore, the dysbiosis of the microbiota is a critical step leading to intestinal mucosal damage and a key factor in the pathogenesis of inflammatory bowel disease. Regulating the microbiota through interventions such as enteral nutrition, fecal microbiota transplantation, and probiotic supplementation has the potential to prevent or even reverse intestinal dysbiosis, opening up new perspectives for the treatment of inflammatory bowel disease.}, } @article {pmid39457040, year = {2024}, author = {Mousa, WK and Al Ali, A}, title = {The Gut Microbiome Advances Precision Medicine and Diagnostics for Inflammatory Bowel Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39457040}, issn = {1422-0067}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/diagnosis/genetics ; *Gastrointestinal Microbiome ; *Precision Medicine/methods ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Metabolomics/methods ; }, abstract = {The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.}, } @article {pmid39456641, year = {2024}, author = {Wu, M and Tian, C and Zou, Z and Jin, M and Liu, H}, title = {Gastrointestinal Microbiota in Gastric Cancer: Potential Mechanisms and Clinical Applications-A Literature Review.}, journal = {Cancers}, volume = {16}, number = {20}, pages = {}, pmid = {39456641}, issn = {2072-6694}, support = {WJ2023M92//Scientific research project of Hubei Provincial Health Commission/ ; 320.6750.2023-19-7 and 320.6750.2024-10-2//Clinical Research Special Fund of Wu Jieping Medical Foundation/ ; WX23A31//Medical Science Research Fundation of Wuhan/ ; }, abstract = {Emerging evidence highlights the crucial role of gastrointestinal microbiota in the pathogenesis of gastric cancer. Helicobacter pylori (H. pylori) infection stands out as a primary pathogenic factor. However, interventions such as anti-H. pylori therapy, gastric surgeries, immunotherapy, and chronic inflammation significantly remodel the gastric microbiome, implicating a broader spectrum of microorganisms in cancer development. These microbial populations can modulate gastric carcinogenesis through various mechanisms, including sustained chronic inflammation, bacterial genotoxins, alterations in short-chain fatty acids, elevated gastrointestinal bile acids, impaired mucus barrier function, and increased concentrations of N-nitrosamines and lactic acid. The dynamic changes in gut microbiota also critically influence the outcomes of anti-cancer therapies by modifying drug bioavailability and metabolism, thus affecting therapeutic efficacy and side effect profiles. Additionally, the effectiveness of radiotherapy can be significantly impacted by gut microbiota alterations. Novel therapeutic strategies targeting the microbiome, such as dietary interventions, probiotic and synbiotic supplementation, and fecal microbiota transplantation, are showing promise in cancer treatment. Understanding the intricate relationship between the gut microbiota and gastric cancer is essential for developing new, evidence-based approaches to the prevention and treatment of this malignancy.}, } @article {pmid39455910, year = {2024}, author = {Tang, BB and Su, CX and Wen, N and Zhang, Q and Chen, JH and Liu, BB and Wang, YQ and Huang, CQ and Hu, YL}, title = {FMT and TCM to treat diarrhoeal irritable bowel syndrome with induced spleen deficiency syndrome- microbiomic and metabolomic insights.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {433}, pmid = {39455910}, issn = {1471-2180}, support = {2023ZR004//TCM science and technology project of Zhejiang Province/ ; 2024KY869//Zhejiang Provincial Medical and Health Science and Technology Project/ ; 2022020801020508//Knowledge Innovation Program of Wuhan Shuguang Project/ ; 2022020801020584//Knowledge Innovation Program of Wuhan Shuguang Project/ ; 82374205//National Natural Science Foundation of China/ ; 2020020601012244//Wuhan Applied Foundational Frontier Project/ ; }, mesh = {Animals ; *Irritable Bowel Syndrome/therapy/microbiology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Fecal Microbiota Transplantation ; *Diarrhea/microbiology/therapy/drug therapy ; *Medicine, Chinese Traditional/methods ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Disease Models, Animal ; *Metabolomics ; Splenic Diseases/therapy/microbiology/drug therapy ; Male ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Spleen/microbiology/metabolism ; }, abstract = {BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D) is a functional bowel disease with diarrhea, and can be associated with common spleen deficiency syndrome of the prevelent traditional Chinese medicine (TCM) syndrome. Fecal microbiota transplantation (FMT) could help treating IBS-D, but may provide variable effects. Our study evaluated the efficacy of TCM- shenling Baizhu decoction and FMT in treating IBS-D with spleen deficiency syndrome, with significant implications on gut microbiome and serum metabolites.

METHODS: The new borne rats were procured from SPF facility and separated as healthy (1 group) and IBS-D model (3 groups) rats were prepared articially using mother's separation and senna leaf treatment. 2 groups of IBS-D models were further treated with TCM- shenling Baizhu decoction and FMT. The efficacy was evaluated by defecation frequency, bristol stool score, and intestinal tight junction proteins (occludin-1 and claudin-1) expression. Microbiomic analysis was conducted using 16 S rRNA sequencing and bioinformatics tools. Metabolomics were detected in sera of rats by LC-MS and annotated by using KEGG database.

RESULTS: Significant increment in occludin-1 and claudin-1 protein expression alleviated the diarrheal severity in IBS-D rats (P < 0.05) after treatment with FMT and TCM. FMT and TCM altered the gut microbiota and regulated the tryptophan metabolism, steroid hormone biosynthesis and glycerophospholipid metabolism of IBS-D rats with spleen deficiency syndrome.The microbial abundance were changed in each case e.g., Monoglobus, Dubosiella, and Akkermansia and othe metabolic profiles.

CONCLUSION: FMT and TCM treatment improved the intestinal barrier function by regulating gut microbiota and improved metabolic pathways in IBS-D with spleen deficiency syndrome.}, } @article {pmid39454127, year = {2024}, author = {Ran, X and Li, Y and Guo, W and Li, K and Guo, W and Wang, X and Liu, J and Bi, J and Fu, S}, title = {Angelica sinensis Polysaccharide Alleviates Staphylococcus aureus-Induced Mastitis by Regulating The Intestinal Flora and Gut Metabolites.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c06094}, pmid = {39454127}, issn = {1520-5118}, abstract = {The modulation of intestinal flora by various polysaccharides has been shown to mitigate disease progression. Recent research reveals a significant link between intestinal flora and the progression of mastitis. This study demonstrates that the oral administration of Angelica sinensis polysaccharide (ASP) reduces mammary inflammation and blood-milk barrier (BMB) damage induced by Staphylococcus aureus in mice, primarily through the modulation of intestinal flora. The beneficial effects of ASP were negated when antibiotics disrupted the gut microbiota in mice. Furthermore, fecal microbiota transplantation (FMT) from ASP-treated mice to recipients markedly alleviated symptoms of S. aureus-induced mastitis. Oral ASP not only enhances gut microbial diversity but also shifts its composition, increasing the abundance of Lachnospiraceae_NK4A136 while reducing Erysipelatoclostridium. Metabolomic analysis revealed that ASP alters intestinal metabolic pathways, elevating levels of metabolites, such as tabersonine and riboflavin. Notably, tabersonine was found to ameliorate S. aureus-induced mastitis. These results suggest that targeting intestinal flora and metabolism through polysaccharides could serve as a promising strategy for mastitis intervention and potentially for other infectious diseases, as well.}, } @article {pmid39452187, year = {2024}, author = {Niyazi, D and Vergiev, S and Markovska, R and Stoeva, T}, title = {Prevalence and Molecular Epidemiology of Intestinal Colonization by Multidrug-Resistant Bacteria among Hematopoietic Stem-Cell Transplantation Recipients: A Bulgarian Single-Center Study.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {10}, pages = {}, pmid = {39452187}, issn = {2079-6382}, support = {19019/2019//Medical University of Varna/ ; }, abstract = {Background/Objectives: Intestinal colonization by multidrug-resistant (MDR) bacteria is considered one of the main risk factors for invasive infections in the hematopoietic stem-cell transplant (HSCT) setting, associated with hard-to-eradicate microorganisms. The aim of this study was to assess the rate of intestinal colonization by MDR bacteria and their microbial spectrum in a group of post-HSCT patients to study the genetic determinants of beta-lactam and glycopeptide resistance in the recovered isolates, as well as to determine the epidemiological relation between them. Methods: The intestinal colonization status of 74 patients admitted to the transplantation center of University Hospital "St. Marina"-Varna in the period January 2019 to December 2021 was investigated. Stool samples/rectal swabs were screened for third-generation cephalosporin and/or carbapenem-resistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Stenotrophomonas maltophilia. Identification and antimicrobial susceptibility testing were performed by Phoenix (BD, Sparks, MD, USA) and MALDI Biotyper sirius (Bruker, Bremen, Germany). Molecular genetic methods (PCR, DNA sequencing) were used to study the mechanisms of beta-lactam and glycopeptide resistance in the collected isolates, as well as the epidemiological relationship between them. Results: A total of 28 patients (37.8%) were detected with intestinal colonization by MDR bacteria. Forty-eight non-duplicate MDR bacteria were isolated from their stool samples. Amongst them, the Gram-negative bacteria prevailed (68.8%), dominated by ESBL-producing Escherichia coli (30.3%), and followed by carbapenem-resistant Pseudomonas sp. (24.2%). The Gram-positive bacteria were represented exclusively by Enterococcus faecium (31.2%). The main beta-lactam resistance mechanisms were associated with CTX-M and VIM production. VanA was detected in all vancomycin-resistant enterococci. A clonal relationship was observed among Enterobacter cloacae complex and among E. faecium isolates. Conclusions: To the best of our knowledge, this is the first Bulgarian study that presents detailed information about the prevalence, resistance genetic determinants, and molecular epidemiology of MDR gut-colonizing bacteria in HSCT patients.}, } @article {pmid39449276, year = {2024}, author = {Zhang, H and Luo, M and Li, Y and Liu, L and Bian, J and Gong, L and He, C and Han, L and Wang, M}, title = {Ellagic acid ameliorates alcohol-induced cognitive and social dysfunction through the gut microbiota-mediated CCL21-CCR7 axis.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo03985h}, pmid = {39449276}, issn = {2042-650X}, abstract = {Chronic alcohol consumption disrupts the balance of the gut microbiome, resulting in alcohol-induced cognitive and social dysfunction (AICSD), and serves as a primary etiological factor for early-onset dementia. Ellagic acid (EA) is a polyphenolic compound belonging to the ellagitannin family, showing potential as a dietary intervention for alleviating cognitive impairments. Nonetheless, the protective effects and underlying mechanisms of EA on AICSD remain unclear. In our study, we employed a multi-omics approach to elucidate the microbiome-mediated mechanism underlying the beneficial effects of EA on AICSD. Firstly, our findings demonstrate that EA significantly ameliorated cognitive and social behavioral deficits as well as neuroinflammation induced by alcohol. Moreover, RNA-seq analysis of hippocampi indicates that EA regulated the KEGG pathway of cytokine-cytokine receptor interaction signaling by downregulating the CCL21-CCR7 axis. Furthermore, we observed that EA effectively restored the dysbiosis of gut microbiota and their derived metabolites induced by chronic alcohol consumption. Strong connections were observed between EA-regulated genes, microbiota and metabolites. Finally, the causal relationship between the microbiome and behavioral changes was further confirmed through antibiotic treatment and fecal microbiota transplantation experiments. Overall, our study provides innovative evidence supporting the role of EA in improving AICSD via regulation of the cytokine-cytokine receptor interaction signaling pathway through the microbiota-mediated CCl21-CCR7 axis. These findings offer valuable insights into both EA-based interventions as well as microbial interventions against AICSD.}, } @article {pmid39449261, year = {2024}, author = {Lee, JW and Kim, N}, title = {[Efficacy of Fecal Microbial Transplantation for Improving Symptoms of Irritable Bowel Syndrome - A Pilot Study for Voluntary Participants in Korea].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {84}, number = {4}, pages = {168-176}, doi = {10.4166/kjg.2024.107}, pmid = {39449261}, issn = {2233-6869}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/diagnosis ; *Fecal Microbiota Transplantation ; Male ; Female ; Adult ; Middle Aged ; Pilot Projects ; Surveys and Questionnaires ; Republic of Korea ; Severity of Illness Index ; Treatment Outcome ; Feces/microbiology ; }, abstract = {BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a chronic, intractable functional disease. It is inferred that fecal microbiota transplantation (FMT) may have favorable efficacy on IBS by gut microbial modification. The aim of this study was to investigate the efficacy of FMT for improving severity in patients with IBS.

METHODS: Patients who voluntarily wanted FMT were consecutively enrolled. The study subjects were classified by subtype of IBS by the ROME IV criteria. The IBS-symptom severity score (IBS-SSS) was used to evaluate the efficacy of FMT. The subjects completed a questionnaire at baseline week 0 and weeks 4, 12, and 24 after FMT. FMT was performed by esophagogastroduodenoscopy using frozen stock stool solution. If the follow-up IBS-SSS achieved less than 75 points, it was defined as remission. Adverse events were also gathered.

RESULTS: Twenty-one subjects were included from October 2023 until July 2024. There were 7 patients with IBS-C, 10 patients with IBS-D, 2 patients with IBS-M, and 2 patients with IBS-U type. The mean SSS of the IBS-D group was 244.0±64.2, which was higher than IBS-C group (192.9±85.4). Alleviations in IBS-SSS after FMT were observed in 19 subjects (19/21, 90.5%) at week 4. At week 12, 71.4% (5/7) in the IBS-C group and 20.0% (2/10) in the IBS-D group achieved remission. The remission states were maintained up to week 24 and no serious adverse events were reported.

CONCLUSIONS: FMT might be an effective treatment option for improving symptoms of mild to moderate IBS, especially IBS-C.}, } @article {pmid39449004, year = {2024}, author = {Munoz-Pinto, MF and Candeias, E and Melo-Marques, I and Esteves, AR and Maranha, A and Magalhães, JD and Carneiro, DR and Sant'Anna, M and Pereira-Santos, AR and Abreu, AE and Nunes-Costa, D and Alarico, S and Tiago, I and Morgadinho, A and Lemos, J and Figueiredo, PN and Januário, C and Empadinhas, N and Cardoso, SM}, title = {Gut-first Parkinson's disease is encoded by gut dysbiome.}, journal = {Molecular neurodegeneration}, volume = {19}, number = {1}, pages = {78}, pmid = {39449004}, issn = {1750-1326}, support = {SC01//Cure Parkinson's Trust/ ; PTDC/MED-NEU/3644/2020//Instituto Nacional de Ciência e Tecnologia de Ciência Animal/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Parkinson Disease/metabolism/microbiology/immunology ; Mice ; *Dysbiosis/immunology ; Male ; *Mice, Inbred C57BL ; Humans ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: In Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in the disease. Recent evidence suggests the gut microbiota may trigger body-first Parkinson Disease (PD), yet the underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through intestinal immune alterations triggers PD-related neurodegeneration.

METHODS: To determine the impact of gut dysbiosis on the development and progression of PD pathology, wild-type male C57BL/6 mice were transplanted with fecal material from PD patients and age-matched healthy donors to challenge the gut-immune-brain axis.

RESULTS: This study demonstrates that patient-derived intestinal microbiota caused midbrain tyrosine hydroxylase positive (TH +) cell loss and motor dysfunction. Ileum-associated microbiota remodeling correlates with a decrease in Th17 homeostatic cells. This event led to an increase in gut inflammation and intestinal barrier disruption. In this regard, we found a decrease in CD4 + cells and an increase in pro-inflammatory cytokines in the blood of PD transplanted mice that could contribute to an increase in the permeabilization of the blood-brain-barrier, observed by an increase in mesencephalic Ig-G-positive microvascular leaks and by an increase of mesencephalic IL-17 levels, compatible with systemic inflammation. Furthermore, alpha-synuclein aggregates can spread caudo-rostrally, causing fragmentation of neuronal mitochondria. This mitochondrial damage subsequently activates innate immune responses in neurons and triggers microglial activation.

CONCLUSIONS: We propose that the dysbiotic gut microbiome (dysbiome) in PD can disrupt a healthy microbiome and Th17 homeostatic immunity in the ileum mucosa, leading to a cascade effect that propagates to the brain, ultimately contributing to PD pathophysiology. Our landmark study has successfully identified new peripheral biomarkers that could be used to develop highly effective strategies to prevent the progression of PD into the brain.}, } @article {pmid39447641, year = {2024}, author = {Li, YL and Chen, BY and Feng, ZH and Zhou, LJ and Liu, T and Lin, WZ and Zhu, H and Xu, S and Bai, XB and Meng, XQ and Zhang, J and Liu, Y and Pu, J and Jiang, M and Duan, SZ}, title = {Roles of oral and gut microbiota in acute myocardial infarction.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.10.009}, pmid = {39447641}, issn = {2090-1224}, abstract = {INTRODUCTION: The significance of oral/gut microbiota in acute myocardial infarction (AMI) has been increasingly appreciated. However, correlations between oral/gut microbiota and AMI parameter, as well as the key microbiota that may have a crucial function in this process, remain unclear.

OBJECTIVES: To investigate the composition and structure of oral and gut microbiota associated with AMI and explore the roles of specific bacterial species in the progression of AMI.

METHODS: We conducted a case-control study with 37 AMI patients and 36 controls. Oral and gut sample were collected and sequenced. Using correlation analysis, we combined bioinformatics data with AMI clinical parameters and obtained heatmaps of correlation coefficients. Additionally, we used antibiotics to eliminate the gut microbiota of C57BL/6J mice, followed by the transplantation of selected bacteria to verify the gut colonization of oral bacteria and their impact on AMI.

RESULTS: The component of oral and gut microbiota of AMI group showed significant alterations when compared to the control group. 17 salivary genera, 21 subgingival genera, and 8 gut genera in AMI group substantially differed from those in control group. Additionally, 19 genera from saliva, 19 genera from subgingival plaque, and 11 genera from feces substantially correlated with AMI clinical parameters. Orally administrated S.o (Streptococcus oralis subsp. dentisani), S.p (Streptococcus parasanguinis), and S.s (Streptococcus salivarius) were able to colonize in the gut and exacerbate myocardial infarction.

CONCLUSION: There is a strong correlation between oral/gut microbiota and AMI. Streptococcus spp. is capable to transmit from oral to gut and exacerbate myocardial infarction in mice. Monitoring and control of specific oral microbiota may be an effective new strategy for improving the therapy of AMI.}, } @article {pmid39445550, year = {2024}, author = {Wu, Q and Li, P and Li, X and Ma, L and Chen, K and Man, S}, title = {Pueraria Extract Ameliorates Alcoholic Liver Disease via the Liver-Gut-Brain Axis: Focus on Restoring the Intestinal Barrier and Inhibiting Alcohol Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c05365}, pmid = {39445550}, issn = {1520-5118}, abstract = {Alcoholic liver disease (ALD) is one of the causes of hepatocellular carcinoma, accompanied by intestinal leakage and microbial changes. Pueraria has protective effects on liver injury. The aim of this study was to investigate the mechanism of pueraria in the treatment of ALD. UPLC-Q/TOF-MS was used to analyze the composition of the pueraria extract (PUE). Acute and chronic ALD models were established to evaluate the antialcoholic and hepatoprotective effects of PUE. As a result, PUE treatment reduced the serum levels of ALT, AST, TC, and TG and inflammatory factors and alleviated liver inflammation and drunk state. PUE decreased the gene expression of ADH1 and the serum level of acetaldehyde (ACH) to inhibit the generation of ACH from ethanol metabolism, increased the gene level of ALDH2 to accelerate the decomposition of ACH, and thereby alleviated liver inflammation and intestinal barrier damage. Meanwhile, 16 S rDNA revealed that PUE altered the microbiota composition, reduced the amount of Proteobacteria and Desulfobacterota, and thus inhibited the generation of lipopolysaccharide and its downstream-like TLR4/MyD88/NF-κB pathway. PUE also increased the abundance of Bacteroides, Ruminococcus, and Prevotella and producted short-chain fatty acids to protect the intestinal wall. Treatment with fecal microbiota transplantation further confirmed that PUE gut microbiota dependently alleviated ALD. Therefore, PUE regulated gut microbiota and inhibited ethanol metabolism to alleviate ALD through the liver-gut-brain axis. It has good prospects in the future.}, } @article {pmid39444759, year = {2024}, author = {Yaghmaei, H and Bahanesteh, A and Soltanipur, M and Takaloo, S and Rezaei, M and Siadat, SD}, title = {The Role of Gut Microbiota Modification in Nonalcoholic Fatty Liver Disease Treatment Strategies.}, journal = {International journal of hepatology}, volume = {2024}, number = {}, pages = {4183880}, pmid = {39444759}, issn = {2090-3448}, abstract = {One of the most common chronic liver diseases is nonalcoholic fatty liver disease (NAFLD), which affects many people around the world. Gut microbiota (GM) dysbiosis seems to be an influential factor in the pathophysiology of NAFLD because changes in GM lead to fundamental changes in host metabolism. Therefore, the study of the effect of dysbiosis on the pathogenicity of NAFLD is important. European clinical guidelines state that the best advice for people with NAFLD is to lose weight and improve their lifestyle, but only 40% of people can achieve this goal. Accordingly, it is necessary to provide new treatment approaches for prevention and treatment. In addition to dietary interventions and lifestyle modifications, GM modification-based therapies are of interest. These therapies include probiotics, synbiotics, fecal microbiota transplantation (FMT), and next-generation probiotics. All of these treatments have had promising results in animal studies, and it can be imagined that acceptable results will be obtained in human studies as well. However, further investigations are required to generalize the outcomes of animal studies to humans.}, } @article {pmid39442873, year = {2024}, author = {Wang, R and Chen, RL and Wu, C and Zhang, XC and Wu, WY and Dai, C and Wang, Y and Li, G}, title = {The gut microbiotas with metabolites regulate the protective role of miR-30a-5p in myocardial infarction.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.10.017}, pmid = {39442873}, issn = {2090-1224}, abstract = {INTRODUCTION: Gut microbial homeostasis is closely associated with myocardial infarction (MI). However, little is known about how gut microbiota influences miRNAs-regulated MI.

OBJECTIVES: This study aims to elucidate the connections between miR-30a-5p, MI, gut microbiota, and gut microbial metabolite-related pathways, to explore potential strategy for preventing and treating MI.

METHODS: We evaluated the effects of knocking out (KO) or overexpressing (OE) miR-30a-5p on MI by assessing cardiac structure and function, myocardial enzyme levels, and apoptosis. Then, we applied 16S rDNA sequencing and metabolomics to explore how intestinal microecology and its microorganisms affect miR-30a-5p-regulated MI.

RESULTS: The results showed that KO exacerbated MI, whereas OE improved MI damage, compared to the wild-type (WT) mice. KO exacerbated intestinal barrier structure deterioration and further downregulated the expression of Cloudin-1, Occludin, and ZO-1 in MI mice. 16S rDNA sequencing-analyzed gut microbiome of KO and WT mice found that KO mainly reduced g_Lactobacillus. Transplanting fecal microorganisms from KO mice aggravated MI damage in WT mice. However, administering probiotics (mainly containing lactobacilli) helped neutralize these damages. Intriguingly, fecal microbiota transplantation from OE mice reduced MI damage. Analysis of intestinal microbial metabolites in KO and WT mice found that KO may mainly affect ABC transporters. ABCC1 was identified as the target of KO-aggravated MI. Furthermore, fecal transplantation microorganisms of MI patients aggravated MI injury in mice and miR-30a-5p and ABCC1 were involved in the process.

CONCLUSIONS: Our findings demonstrate that miR-30a-5p regulates MI by affecting intestinal microbiota homeostasis and targeting ABCC1. This highlights the critical importance of maintaining a healthy gut microbiota homeostasis in MI management.}, } @article {pmid39442743, year = {2024}, author = {Bénard, MV and de Goffau, MC and Blonk, J and Hugenholtz, F and van Buuren, J and Paramsothy, S and Kaakoush, NO and D'Haens, GRAM and Borody, TJ and Kamm, MA and Ponsioen, CY}, title = {Fecal Microbiota Transplantation Outcome and Gut Microbiota Composition in Ulcerative Colitis: a Systematic Review and Meta-analysis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.10.001}, pmid = {39442743}, issn = {1542-7714}, abstract = {BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC), yet its efficacy needs improvement. We conducted a comprehensive evaluation of the current literature on microbial factors affecting outcome, as well as a meta-analysis on some of the largest datasets regarding composition.

METHODS: MEDLINE, Embase and Cochrane were systematically searched through August 2024 for relevant studies. The quality of studies was analyzed with Joanna Briggs tools and a composite critical appraisal-score. Additionally, species-level data from two landmark FMT-trials (TURN and FOCUS) were re-analyzed from a compositional perspective.

RESULTS: Out of 3755 citations identified, 56 met the inclusion criteria, of which 29 fulfilled quality standards. Higher microbial α-diversity, either in donors or recipients (at baseline or following FMT treatment), was associated with better clinical response rates. Engraftment of the donors' microbiota could not be clearly linked with clinical response, possibly because not every donor has an ideal microbiome. Butyrate producing species from the Lachnospiraceae and Oscillospiraceae families were often related with response, whereas the reverse was true for Fusobacteria, many Proteobacteria and Ruminococcus gnavus. Compositional analyses showed that clinical response is associated with a shift from a low-diversity, often Bacteroides dominant composition to one with higher diversity, either dominated by various butyrate producers, the Christensenellaceae-Methanobrevibacter trophic network, or a moderate/high diversity composition with abundant but not excessive levels of Prevotella copri.

CONCLUSION: This systematic review/meta-analysis yielded a coherent picture from a compositional perspective, which may help identify beneficial donor profiles and guide personalized FMT approaches.}, } @article {pmid39442742, year = {2024}, author = {Claytor, JD and Faith, JJ}, title = {Fecal Microbiota Transplantation (FMT) in Ulcerative Colitis: Holding Out for a Superdonor?.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.07.047}, pmid = {39442742}, issn = {1542-7714}, } @article {pmid39442279, year = {2024}, author = {Yang, X and Xin, Y and Gu, Y and Wang, Y and Hu, X and Ying, G and Zhang, Q and He, X}, title = {Total alkaloids of Aconitum carmichaelii Debx alleviate cisplatin-induced acute renal injury by inhibiting inflammation and oxidative stress related to gut microbiota metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156128}, doi = {10.1016/j.phymed.2024.156128}, pmid = {39442279}, issn = {1618-095X}, abstract = {BACKGROUND: Cisplatin-induced acute kidney injury (AKI) is a complex and serious clinical issue, representing a major cause of hospital-acquired AKI. Alkaloids are the main active constituents of Aconitum carmichaelii Debx, which exhibit protective effects in several kidney disease models and against other acute organ injuries. However, its activity and mechanism of action in AKI treatment remain unclear.

PURPOSE: This study aimed to elucidate the effect of Aconitum carmichaelii Debx (ACA) in a model of cisplain-induced AKI and comprehensively investigate its underlying mechanisms.

METHODS: The major alkaloids in ACA were analyzed using high-performance liquid chromatography. Blood urea nitrogen (BUN) and serum creatine levels were measured using automated biochemical instruments. 16S rRNA sequencing, short-chain fatty acid (SCFA) analysis, fecal microbiota transplantation (FMT), non-targeted metabolomics, and transcriptomics were performed to systematically identify prospective biomarkers after ACA treatment. Anti-inflammatory and anti-oxidative stress activities were monitored using ELISA and western blotting.

RESULTS: Four main compounds (fuziline, neoline, talatisamine, and songorine) were identified in ACA. ACA significantly alleviated cisplatin-induced AKI by reducing (BUN) and serum creatine levels and improving histopathological scores. Moreover, ACA balanced cisplatin-mediated confoundments in microbial composition and function, including decreasing the levels of Escherichia-Shigella, Clostridium, and Ruminococcus, as well as increasing Ligilactobacillus, Anaerotruncus, Bacteroides and Desulfovibrio levels, accompanied by uremic toxin reduction, and augmenting serum SCFAs. The FMT experiments further confirmed that ACA exerts anti-AKI effects by affecting gut microbiota. A multi-omics study has shown that ACA regulates glutathione and tryptophan metabolism and mediates pathways that trigger inflammatory responses. Finally, ACA reduced serum levels of inflammatory factors (IL-1β, IL-6, and TNF-α), restored enzymes of the antioxidative system (SOD and CAT) and GSH values, and decreased monoester diterpene alkaloid levels in the kidney by inhibiting the expression of NF-κB pathway-related proteins and increasing Nrf2/HO-1 pathway-related protein expression.

CONCLUSION: ACA protects against cisplatin-induced AKI through its anti-inflammatory and antioxidant functions, which may be associated with the restoration of gut microbiota metabolism. ACA is a potential drug for AKI and other forms of organ damage related to the disruption of the gut microbiota.}, } @article {pmid39439945, year = {2024}, author = {Chen, W and Zou, H and Xu, H and Cao, R and Zhang, H and Zhang, Y and Zhao, J}, title = {The potential influence and intervention measures of gut microbiota on sperm: it is time to focus on testis-gut microbiota axis.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1478082}, pmid = {39439945}, issn = {1664-302X}, abstract = {As the global male infertility rate continues to rise, there is an urgent imperative to investigate the underlying causes of sustained deterioration in sperm quality. The gut microbiota emerges as a pivotal factor in host health regulation, with mounting evidence highlighting its dual influence on semen. This review underscores the interplay between the Testis-Gut microbiota axis and its consequential effects on sperm. Potential mechanisms driving the dual impact of gut microbiota on sperm encompass immune modulation, inflammatory responses mediated by endotoxins, oxidative stress, antioxidant defenses, gut microbiota-derived metabolites, epigenetic modifications, regulatory sex hormone signaling. Interventions such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and Traditional natural herbal extracts are hypothesized to rectify dysbiosis, offering avenues to modulate gut microbiota and enhance Spermatogenesis and motility. Future investigations should delve into elucidating the mechanisms and foundational principles governing the interaction between gut microbiota and sperm within the Testis-Gut microbiota Axis. Understanding and modulating the Testis-Gut microbiota Axis may yield novel therapeutic strategies to enhance male fertility and combat the global decline in sperm quality.}, } @article {pmid39438902, year = {2024}, author = {Díaz-García, C and Moreno, E and Talavera-Rodríguez, A and Martín-Fernández, L and González-Bodí, S and Martín-Pedraza, L and Pérez-Molina, JA and Dronda, F and Gosalbes, MJ and Luna, L and Vivancos, MJ and Huerta-Cepas, J and Moreno, S and Serrano-Villar, S}, title = {Fecal microbiota transplantation alters the proteomic landscape of inflammation in HIV: identifying bacterial drivers.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {214}, pmid = {39438902}, issn = {2049-2618}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *HIV Infections/therapy ; *Gastrointestinal Microbiome ; *Inflammation ; Male ; Middle Aged ; Female ; *Proteomics/methods ; Adult ; *Feces/microbiology ; Pilot Projects ; Double-Blind Method ; Bacteria/classification/isolation & purification/metabolism ; }, abstract = {BACKGROUND: Despite effective antiretroviral therapy, people with HIV (PWH) experience persistent systemic inflammation and increased morbidity and mortality. Modulating the gut microbiome through fecal microbiota transplantation (FMT) represents a novel therapeutic strategy. We aimed to evaluate proteomic changes in inflammatory pathways following repeated, low-dose FMT versus placebo.

METHODS: This double-masked, placebo-controlled pilot study assessed the proteomic impacts of weekly FMT versus placebo treatment over 8 weeks on systemic inflammation in 29 PWH receiving stable antiretroviral therapy (ART). Three stool donors with high Faecalibacterium and butyrate profiles were selected, and their individual stools were used for FMT capsule preparation. Proteomic changes in 345 inflammatory proteins in plasma were quantified using the proximity extension assay, with samples collected at baseline and at weeks 1, 8, and 24. Concurrently, we characterized shifts in the gut microbiota composition and annotated functions through shotgun metagenomics. We fitted generalized additive models to evaluate the dynamics of protein expression. We selected the most relevant proteins to explore their correlations with microbiome composition and functionality over time using linear mixed models.

RESULTS: FMT significantly reduced the plasma levels of 45 inflammatory proteins, including established mortality predictors such as IL6 and TNF-α. We found notable reductions persisting up to 16 weeks after the final FMT procedure, including in the expression of proteins such as CCL20 and CD22. We identified changes in 46 proteins, including decreases in FT3LG, IL6, IL10RB, IL12B, and IL17A, which correlated with multiple bacterial species. We found that specific bacterial species within the Ruminococcaceae, Succinivibrionaceae, Prevotellaceae families, and the Clostridium genus, in addition to their associated genes and functions, were significantly correlated with changes in inflammatory markers.

CONCLUSIONS: Targeting the gut microbiome through FMT effectively decreased inflammatory proteins in PWH, with sustained effects. These findings suggest the potential of the microbiome as a therapeutic target to mitigate inflammation-related complications in this population, encouraging further research and development of microbiome-based interventions. Video Abstract.}, } @article {pmid39437686, year = {2024}, author = {Cao, Z and Wang, X and Liu, H and Yang, Z and Zeng, Z}, title = {Gut microbiota mediate the alleviation effect of Xiehuo-Guzheng granules on β cell dedifferentiation in type 2 diabetes mellitus.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156151}, doi = {10.1016/j.phymed.2024.156151}, pmid = {39437686}, issn = {1618-095X}, abstract = {BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide public health problem characterized by a progressive decline in β cell function. In traditional Chinese medicine (TCM) theory, 'fire' and 'healthy qi deficiency' are important pathogeneses of T2DM, and purging 'fire' and reinforcing the 'healthy qi' (Pinyin name: Xiehuo-Guzheng, XHGZ) are important method of treatment. Over the years, we have observed its benefit for diabetes. However, the underlying mechanisms remain unclear.

PURPOSE: To investigate the mechanism of XHGZ granules against β cell dedifferentiation in T2DM based on gut microbiota.

METHODS: Rats with T2DM, induced by intraperitoneal injection of streptozotocin after eight weeks of high-fat diet, were randomly allocated to receive XHGZ granules, metformin, or distilled water for eight consecutive weeks. Changes in metabolic parameters, β cell dedifferentiation, inflammatory cytokines, gut microbiota, and microbial metabolites (lipopolysaccharide (LPS) and short-chain fatty acids (SCFAs)), were detected. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the anti-diabetic effect of XHGZ granule-regulated gut microbiota in pseudo-germ-free T2DM rats.

RESULTS: XHGZ granules significantly ameliorated hyperglycaemia, improved islet function and pathology, and reduced β cell dedifferentiation and pro-inflammatory cytokines in T2DM rats. 16S rRNA sequencing revealed that XHGZ granules decreased the LPS-containing microbiota (e.g., Colidextribacter, Desulfovibrionaceae, and Morganella) and increased the SCFAs-producing bacteria (e.g., Prevotella, Alloprevotella, and Muribaculaceae) and Lactobacillus_intestinalis. Correspondingly, it strengthened intestinal barrier, lowered LPS, and elevated acetic and butyric acids. Tax4Fun analysis indicated that XHGZ granules restored abnormal metabolism, lipopolysaccharide biosynthesis, and pantothenate and CoA biosynthesis. Moreover, the XHGZ granule-regulated microbiota also exhibited the effects of anti-diabetes, anti-β cell dedifferentiation, and anti-inflammation along with the reduction of LPS and the increase of SCFAs in pseudo-germ-free T2DM rats.

CONCLUSION: Our results show that XHGZ granules alleviate β cell dedifferentiation via regulating gut microbiota and their metabolites in T2DM, suggesting its potential as a promising complementary treatment for T2DM. As far as we know, there are very few studies on the alleviation of β cell dedifferentiation by TCM, and investigations into the mechanism from the perspective of intestinal flora and microbial metabolites are yet to be reported.}, } @article {pmid39437444, year = {2024}, author = {Ciernikova, S and Sevcikova, A and Mego, M}, title = {Targeting the gut and tumor microbiome in cancer resistance.}, journal = {American journal of physiology. Cell physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpcell.00201.2024}, pmid = {39437444}, issn = {1522-1563}, support = {2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 1/0071/24//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, abstract = {Therapy resistance represents a significant challenge in oncology, occurring in various therapeutic approaches. Recently, animal models and an increasing set of clinical trials highlight the crucial impact of the gut and tumor microbiome on treatment response. The intestinal microbiome contributes to cancer initiation, progression, and formation of distant metastasis. In addition, tumor-associated microbiota is considered a critical player in influencing tumor microenvironment and regulating local immune processes. Intriguingly, numerous studies have successfully identified pathogens within the gut and tumor microbiome that might be linked to a poor response to different therapeutic modalities. The unfavorable microbial composition with the presence of specific microbes participates in cancer resistance and progression via several mechanisms, including upregulation of oncogenic pathways, macrophage polarization reprogramming, metabolism of chemotherapeutic compounds, autophagy pathway modulation, enhanced DNA damage repair, inactivation of a pro-apoptotic cascade, and bacterial secretion of extracellular vesicles, promoting the processes in the metastatic cascade. Targeted elimination of specific intratumoral bacteria appears to enhance treatment response. However, broad-spectrum antibiotic pre-treatment is mostly connected to reduced efficacy due to gut dysbiosis and lower diversity. Mounting evidence supports the potential of microbiota modulation by probiotics and fecal microbiota transplantation to improve intestinal dysbiosis and increase microbial diversity, leading to enhanced treatment efficacy while mitigating adverse effects. In this context, further research concerning the identification of clinically relevant microbiome signatures followed by microbiota-targeted strategies presents a promising approach to overcoming immunotherapy and chemotherapy resistance in refractory patients, improving their outcomes.}, } @article {pmid39435211, year = {2024}, author = {Koneru, HM and Sarwar, H and Bandi, VV and Sinha, M and Tarar, P and Bishara, R and Malasevskaia, I}, title = {A Systematic Review of Gut Microbiota Diversity: A Key Player in the Management and Prevention of Diabetes Mellitus.}, journal = {Cureus}, volume = {16}, number = {9}, pages = {e69687}, pmid = {39435211}, issn = {2168-8184}, abstract = {Diabetes mellitus represents a significant global health challenge, characterized by impaired insulin production and action, leading to elevated blood glucose levels. This systematic review investigates the association between gut microbiota composition and diversity, along with the structural and functional characteristics of the gut microbiome, and their implications for the risk, prevention, and management of both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a comprehensive search across multiple databases yielded 16 studies that met the inclusion criteria. The findings highlight the potential of gut microbiota interventions, such as fecal microbiota transplantation and probiotic supplementation, in improving metabolic parameters and glycemic control. Notably, the review underscores the importance of dietary interventions and the role of specific microbial populations in influencing diabetes outcomes. Despite the promising results, the variability in study designs, sample sizes, and methodologies poses challenges for generalizability and interpretation. This review emphasizes the need for further research to elucidate the mechanisms underlying these associations and to explore personalized microbiome-based therapies in diabetes management. The insights gained could pave the way for innovative therapeutic strategies aimed at harnessing gut health to mitigate the burden of diabetes mellitus.}, } @article {pmid39434180, year = {2024}, author = {Yan, S and Du, R and Yao, W and Zhang, H and Xue, Y and Teligun, and Li, Y and Bao, H and Zhao, Y and Cao, S and Cao, G and Li, X and Bao, S and Song, Y}, title = {Host-microbe interaction-mediated resistance to DSS-induced inflammatory enteritis in sheep.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {208}, pmid = {39434180}, issn = {2049-2618}, mesh = {Animals ; Sheep/microbiology ; Mice ; *Dextran Sulfate ; *Gastrointestinal Microbiome ; *Disease Models, Animal ; *Feces/microbiology ; *Colitis/microbiology/chemically induced ; Host Microbial Interactions ; Fecal Microbiota Transplantation ; Disease Resistance ; Enteritis/microbiology/veterinary ; Sheep Diseases/microbiology ; Bacteria/classification/isolation & purification/genetics ; }, abstract = {BACKGROUND: The disease resistance phenotype is closely related to immunomodulatory function and immune tolerance and has far-reaching implications in animal husbandry and human health. Microbes play an important role in the initiation, prevention, and treatment of diseases, but the mechanisms of host-microbiota interactions in disease-resistant phenotypes are poorly understood. In this study, we hope to uncover and explain the role of microbes in intestinal diseases and their mechanisms of action to identify new potential treatments.

METHODS: First, we established the colitis model of DSS in two breeds of sheep and then collected the samples for multi-omics testing including metagenes, metabolome, and transcriptome. Next, we made the fecal bacteria liquid from the four groups of sheep feces collected from H-CON, H-DSS, E-CON, and E-DSS to transplant the fecal bacteria into mice. H-CON feces were transplanted into mice named HH group and H-DSS feces were transplanted into mice named HD group and Roseburia bacteria treatment named HDR groups. E-CON feces were transplanted into mice named EH group and E-DSS feces were transplanted into mice in the ED group and Roseburia bacteria treatment named EDR groups. After successful modeling, samples were taken for multi-omics testing. Finally, colitis mice in HD group and ED group were administrated with Roseburia bacteria, and the treatment effect was evaluated by H&E, PAS, immunohistochemistry, and other experimental methods.

RESULTS: The difference in disease resistance of sheep to DSS-induced colitis disease is mainly due to the increase in the abundance of Roseburia bacteria and the increase of bile acid secretion in the intestinal tract of Hu sheep in addition to the accumulation of potentially harmful bacteria in the intestine when the disease occurs, which makes the disease resistance of Hu sheep stronger under the same disease conditions. However, the enrichment of harmful microorganisms in East Friesian sheep activated the TNFα signalling pathway, which aggravated the intestinal injury, and then the treatment of FMT mice by culturing Roseburia bacteria found that Roseburia bacteria had a good curative effect on colitis.

CONCLUSION: Our study showed that in H-DSS-treated sheep, the intestinal barrier is stabilized with an increase in the abundance of beneficial microorganisms. Our data also suggest that Roseburia bacteria have a protective effect on the intestinal barrier of Hu sheep. Accumulating evidence suggests that host-microbiota interactions are associated with IBD disease progression. Video Abstract.}, } @article {pmid39432486, year = {2024}, author = {Ebrahimi, R and Masouri, MM and Salehi Amniyeh Khozani, AA and Ramadhan Hussein, D and Nejadghaderi, SA}, title = {Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0311731}, pmid = {39432486}, issn = {1932-6203}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Virus Diseases/therapy ; COVID-19/therapy ; Gastrointestinal Microbiome ; Hepatitis B/therapy ; HIV Infections/therapy/microbiology ; Clinical Trials as Topic ; Treatment Outcome ; Clostridium Infections/therapy/microbiology ; SARS-CoV-2 ; }, abstract = {BACKGROUND: Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases.

METHODS: We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool.

RESULTS: Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities.

CONCLUSIONS: Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases.}, } @article {pmid39431286, year = {2024}, author = {Liu, T and Zhou, L and Dong, R and Qu, Y and Liu, Y and Song, W and Lv, J and Wu, S and Peng, W and Shi, L}, title = {Isomalto-Oligosaccharide Potentiates Alleviating Effects of Intermittent Fasting on Obesity-Related Cognitive Impairment during Weight Loss and the Rebound Weight Gain.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c07351}, pmid = {39431286}, issn = {1520-5118}, abstract = {Obesity-related cognitive dysfunction poses a significant threat to public health. The present study demonstrated mitigating effects of intermittent fasting (IF) and its combination with isomalto-oligosaccharides and IF (IF + IMO) on cognitive impairments induced by a high-fat-high-fructose (HFHF) diet in mice, with IF + IMO exhibiting superior effects. Transcriptomic analysis of the hippocampus revealed that the protective effects on cognition might be attributed to the suppression of toll-like receptor 4 (TLR4)/NFκB signaling, oxidative phosphorylation, and neuroinflammation. Moreover, both IF and IF + IMO modulated the gut microbiome and promoted the production of short-chain fatty acids, with IF + IMO displaying more pronounced effects. IF + IMO-modulated gut microbiota, metabolites, and molecular targets associated with cognitive impairments were further corroborated using human data from public databases Gmrepo and gutMgene. Furthermore, the fecal microbiome transplantation confirmed the direct impacts of IF + IMO-derived microbiota on improving cognition functions by suppressing TLR4/NFκB signaling and increasing BDNF levels. Notably, prior exposure to IF + IMO prevented weight-regain-induced cognitive decline, suppressed TLR4/NFκB signaling and inflammatory cytokines in the hippocampus, and mitigated weight regain-caused gut dysbacteriosis without altering body weight. Our study underscores that IMO-augmented alleviating effects of IF on obesity-related cognitive impairment particularly during weight-loss and weight-regain periods, presenting a novel nutritional strategy to tackle obesity-related neurodegenerative disorders.}, } @article {pmid39427741, year = {2024}, author = {Sun, Z and Zeng, Z and Chen, LX and Xu, JD and Zhou, J and Kong, M and Shen, H and Mao, Q and Wu, CY and Long, F and Zhou, SS and Li, SL}, title = {Integrated anti-fatigue effects of polysaccharides and small molecules coexisting in water extracts of ginseng: Gut microbiota-mediated mechanisms.}, journal = {Journal of ethnopharmacology}, volume = {337}, number = {Pt 3}, pages = {118958}, doi = {10.1016/j.jep.2024.118958}, pmid = {39427741}, issn = {1872-7573}, abstract = {Both clinical and animal studies have demonstrated that ginseng has curative effects on fatigue. Our previous study found that water extracts of ginseng (WEG) could significantly mitigate exercise-induced fatigue (EF). Notably, polysaccharides (GP) and small molecules (GS, mainly ginsenosides) coexist in WEG. Whether and how GP and GS contribute to the anti-EF effects of WEG remains unknown.

AIM OF THE STUDY: To evaluate the contribution of GP and GS to the anti-EF effects of WEG and clarify the potential gut microbiota-mediated mechanisms.

MATERIALS AND METHODS: Firstly, the anti-EF effects of WEG, GP and GS were comparatively investigated by determining fatigue phenotypes (energy metabolism and oxidative stress parameters), gut microbiota composition as well as exogenous and endogenous metabolites in EF modeling rats. Then, the gut microbiota mediated mechanisms were verified by antibiotics (ABX) intervention and fecal microbial transplantation (FMT).

RESULTS: GP, GS and WEG each exhibited distinct anti-EF effects in differentially improving EF-induced energy metabolism abnormality and oxidative stress, reshaping gut microbiota composition, and elevating systemic metabolites. Notably, WEG showed stronger anti-EF effects than both GP and GS, characterized by better alleviation of disturbances in energy metabolism (e.g. Glc) and oxidative stress parameters (e.g. SOD), regulation of gut microbiota homeostasis (e.g. enriching the genus Coprococcus and species Collinsella provencensis etc.), as well as increases in exogenous secondary ginsenosides (e.g. 20(S)-Rg3, 20(R)-Rg3, CK), endogenous bile acids (BAs) (e.g. CA, DCA, LCA), and short chain fatty acids (SCFAs) (e.g. butyric acid). The stronger anti-EF effects of WEG compared to GP and GS could be abolished by ABX intervention, and transferred by FMT.

CONCLUSION: GP and GS could collectively contribute to the anti-EF effects of WEG through integrated actions. Gut microbiota mediate the integrated anti-EF effects of GP and GS in WEG, potentially by regulating the levels of exogenous bioactive secondary ginsenosides, as well as endogenous BAs and SCFAs, thereby alleviating fatigue-related energy metabolic abnormalities and oxidative stress.}, } @article {pmid39426981, year = {2024}, author = {Lu, C and Liu, D and Wu, Q and Zeng, J and Xiong, Y and Luo, T}, title = {EphA2 blockage ALW-II-41-27 alleviates atherosclerosis by remodeling gut microbiota to regulate bile acid metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {108}, pmid = {39426981}, issn = {2055-5008}, support = {2023NSFSC1631//Department of Science and Technology of Sichuan Province (Sichuan Provincial Department of Science and Technology)/ ; 2023YFS0116//Department of Science and Technology of Sichuan Province (Sichuan Provincial Department of Science and Technology)/ ; 2022YFS0604//Department of Science and Technology of Sichuan Province (Sichuan Provincial Department of Science and Technology)/ ; Q22066//Education Department of Sichuan Province/ ; }, mesh = {Animals ; *Atherosclerosis/metabolism/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Bile Acids and Salts/metabolism ; Mice ; *Receptor, EphA2/metabolism ; *Diet, High-Fat/adverse effects ; Male ; Humans ; Disease Models, Animal ; Plaque, Atherosclerotic/etiology ; Mice, Inbred C57BL ; Bacteria/classification/isolation & purification/genetics/metabolism ; Dysbiosis ; }, abstract = {Coronary artery disease (CAD), a critical condition resulting from systemic inflammation, metabolic dysfunction, and gut microbiota dysbiosis, poses a global public health challenge. ALW-II-41-27, a specific inhibitor of the EphA2 receptor, has shown anti-inflammatory prosperities. However, the impact of ALW-II-41-27 on atherosclerosis has not been elucidated. This study aimed to examine the roles of pharmacologically inhibiting EphA2 and the underlying mechanism in ameliorating atherosclerosis. ALW-II-41-27 was administered to apoE[-/-] mice fed a high-fat diet via intraperitoneal injection. We first discovered that ALW-II-41-27 led to a significant reduction in atherosclerotic plaques, evidenced by reduced lipid and macrophage accumulation, alongside an increase in collagen and smooth muscle cell content. ALW-II-41-27 also significantly lowered plasma and hepatic cholesterol levels, as well as the colonic inflammation. Furthermore, gut microbiota was analyzed by metagenomics and plasma metabolites by untargeted metabolomics. ALW-II-41-27-treated mice enriched Enterococcus, Akkermansia, Eggerthella and Lactobaccilus, accompanied by enhanced secondary bile acids production. To explore the causal link between ALW-II-41-27-associated gut microbiota and atherosclerosis, fecal microbiota transplantation was employed. Mice that received ALW-II-41-27-treated mouse feces exhibited the attenuated atherosclerotic plaque. In clinical, lower plasma DCA and HDCA levels were determined in CAD patients using quantitative metabolomics and exhibited a negative correlation with higher monocytes EphA2 expression. Our findings underscore the potential of ALW-II-41-27 as a novel therapeutic agent for atherosclerosis, highlighting its capacity to modulate gut microbiota composition and bile acid metabolism, thereby offering a promising avenue for CAD.}, } @article {pmid39426255, year = {2024}, author = {Liu, SJ and Fu, JJ and Liao, ZY and Liu, YX and He, J and He, LY and Bai, J and Yang, JY and Niu, SQ and Guo, JL}, title = {Z-ligustilide alleviates atherosclerosis by reconstructing gut microbiota and sustaining gut barrier integrity through activation of cannabinoid receptor 2.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156117}, doi = {10.1016/j.phymed.2024.156117}, pmid = {39426255}, issn = {1618-095X}, abstract = {BACKGROUND: Z-Ligustilide (ZL) is an essential phthalide found in Ligusticum chuanxiong Hort, a commonly used traditional Chinese medicine for treating atherosclerosis (AS) clinically. ZL has been shown to be effective in treating AS. However, the underlying mechanism of ZL against AS and its potential targets remain elusive.

PURPOSE: The purpose of this research was to assess the influence of ZL on AS and explore the role of the gut microbiome in mediating this effect.

METHODS: A well-established AS mouse model, apolipoprotein E deficient (ApoE[-/-]) mice was used to examine the effects of ZL on AS, inflammation, and the intestinal barrier. To analyze the changes in gut microbial community, we employed the 16S rRNA gene sequencing. Antibiotic cocktail and fecal microbiota transplantation (FMT) were employed to clarify the contribution of the gut microbiota to the anti-AS effects of ZL. The mechanism through which ZL provided protective effects on AS and the intestinal barrier was explored by untargeted metabolomics, as well as by validating the involvement of cannabinoid receptor 2 (CB2R) in mice and Caco-2 cells.

RESULTS: Oral administration of ZL inhibited the development of atherosclerotic lesions, improved plaque stability, inhibited the increase in serum and atherosclerotic inflammation, and improved intestinal barrier function. Fecal bacteria from ZL-treated mice induced similar beneficial effects on AS and the intestinal barrier. We used 16S RNA gene sequencing to reveal a significant increase in Rikenella abundance in both ZL-treated mice and ZL-FMT mice, which was associated with the beneficial effects of ZL. Further function prediction analysis of the gut microbiota and CB2R antagonist intervention experiment in mice and Caco-2 cells showed that the activation of CB2R resulted in the enhancement of the intestinal barrier by ZL. Furthermore, the analysis of metabolomic profiling revealed the enrichment of capsaicin upon ZL treatment, which induced the activation of CB2R in human colon epithelial cells.

CONCLUSION: Our study is the first to demonstrate that oral treatment with ZL has the potential to alleviate AS by reducing inflammation levels and enhancing the intestinal barrier function. This mechanism relies on the gut microbiota in a CB2R-dependent manner, suggesting promising strategies and ideas for managing AS. This study provides insights into a novel mechanism for treating AS with ZL.}, } @article {pmid39425119, year = {2024}, author = {Qian, X and Lin, X and Hu, W and Zhang, L and Chen, W and Zhang, S and Ge, S and Xu, X and Luo, K}, title = {Intestinal homeostasis disrupted by Periodontitis exacerbates Alzheimer's Disease in APP/PS1 mice.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {263}, pmid = {39425119}, issn = {1742-2094}, support = {81860197//the National Natural Science Foundation of China/ ; 2020Y9032//the Joint Funds for the Innovation of Science and Technology/ ; JAT220078//the Educational Research Project for Young and Middle-aged Teachers of Fujian Provincial Department of Education/ ; 82301103//National Outstanding Youth Science Fund Project of National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Alzheimer Disease/pathology/metabolism ; Mice ; *Homeostasis/physiology ; *Mice, Transgenic ; *Periodontitis/pathology/complications/microbiology ; *Amyloid beta-Protein Precursor/genetics/metabolism ; *Gastrointestinal Microbiome/physiology ; *Presenilin-1/genetics ; Intestines/pathology ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Periodontitis exacerbates Alzheimer's disease (AD) through multiple pathways. Both periodontitis and AD are intricately correlated to intestinal homeostasis, yet there is still a lack of direct evidence regarding whether periodontitis can regulate the progression of AD by modulating intestinal homeostasis. The current study induced experimental periodontitis in AD mice by bilaterally ligating the maxillary second molars with silk and administering Pg-LPS injections in APP[swe]/PS1[ΔE9] (APP/PS1) mice. Behavioral tests and histological analyses of brain tissue were conducted after 8 weeks. Gut microbiota was analyzed and colon tissue were also evaluated. Then, fecal microbiota from mice with periodontitis was transplanted into antibiotic-treated mice to confirm the effects of periodontitis on AD and the potential mechanism was explored. The results indicated periodontitis exacerbated cognitive impairment and anxious behaviour in APP/PS1 mice, with increased Aβ deposition, microglial overactivation and neuroinflammation in brain. Moreover, the intestinal homeostasis of AD mice was altered by periodontitis, including affecting gut microbiota composition, causing colon inflammation and destroyed intestinal epithelial barrier. Furthermore, AD mice that underwent fecal transplantation from mice with periodontitis exhibited worsened AD progression and disrupted intestinal homeostasis. It also impaired intestinal barrier function, elevated peripheral inflammation, damaged blood-brain barrier (BBB) and caused neuroinflammation and synapses impairment. Taken together, the current study demonstrated that periodontitis could disrupt intestinal homeostasis to exacerbate AD progression potential via causing gut microbial dysbiosis, intestinal inflammation and intestinal barrier impairment to induce peripheral inflammation and damage BBB, ultimately leading to neuroinflammation and synapse impairment. It underscores the importance of maintaining both periodontal health and intestinal homeostasis to reduce the risk of AD.}, } @article {pmid39423571, year = {2024}, author = {Li, Y and Yan, M and Zhang, M and Zhang, B and Xu, B and Ding, X and Wang, J and Wang, Z}, title = {Scutellarin alleviated ulcerative colitis through gut microbiota-mediated cAMP/PKA/NF-κB pathway.}, journal = {Biochemical and biophysical research communications}, volume = {735}, number = {}, pages = {150837}, doi = {10.1016/j.bbrc.2024.150837}, pmid = {39423571}, issn = {1090-2104}, abstract = {PURPOSE: Ulcerative colitis (UC) is a chronic, non-specific inflammatory condition of the colon, characterized by recurrent episodes and a notable lack of effective pharmacological treatments. Scutellarin, a natural component, exhibits appreciable pharmacological effects and therapeutic potential for various diseases. However, its effects on UC are not fully understood, and the precise mechanisms remain to be deciphered. This study aimed to assess the therapeutic efficacy of scutellarin and elucidate its underlying mechanisms in treating UC.

METHODS: This study utilized dextran sulfate sodium (DSS)-induced mice to evaluate the therapeutic potential of scutellarin against UC and to elucidate the mechanisms involving the gut microbiota. An antibiotics cocktail (ABX) and fecal microbiota transplantation (FMT) were also used to determine the mechanistic role of the gut microbiota. An integrative approach combining fecal metabolomics and network pharmacology analysis was used to explore the gut microbiota-directed molecular mechanism.

RESULTS: The results showed that scutellarin provided various therapeutic benefits in UC management, including alleviating weight loss, slowing disease progression, and reducing inflammatory damage in colon structures. The improved gut microbiota after scutellarin administration contributed to these effects. Fecal metabolome revealed that scutellarin selectively mitigated DSS-induced dysregulation of gut microbiota-derived metabolites, including glycolic acid, γ-aminobutyric acid, glutamate, tryptophan, xanthine, and β-hydroxypyruvate. Network pharmacology analysis, along with in vivo experimental verification, implicated the cAMP/PKA/NF-κB pathway in the action of these metabolites in treating UC, which may be the mechanism responsible for scutellarin's curative effects on UC.

CONCLUSION: This study demonstrates the potential of scutellarin in alleviating UC by activating the cAMP/PKA/NF-κB pathway through gut microbiota-derived metabolites, highlighting scutellarin as a promising therapeutic agent for UC.}, } @article {pmid39423480, year = {2024}, author = {Xiao, Q and Luo, L and Zhu, X and Yan, Y and Li, S and Chen, L and Wang, X and Zhang, J and Liu, D and Liu, R and Zhong, Y}, title = {Formononetin alleviates ulcerative colitis via reshaping the balance of M1/M2 macrophage polarization in a gut microbiota-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156153}, doi = {10.1016/j.phymed.2024.156153}, pmid = {39423480}, issn = {1618-095X}, abstract = {BACKGROUND: Ulcerative colitis (UC), a type of inflammatory bowel disease, presents substantial challenges in clinical treatment due to the limitations of current medications. Formononetin (FN), a naturally compound with widespread availability, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties.

PURPOSE: This study aimed to investigate the efficacy of FN against UC and its potential regulatory mechanism.

METHODS: Here, dextran sulfate sodium (DSS) was employed to replicate experimental colitis in mice with concomitant FN treatment. The distribution and localisation of CD68 and F4/80 macrophages in colonic tissues were visualized by immunofluorescence, their chemokine and inflammatory cytokine concentrations were determined by ELISA, and macrophages and M1/M2 subpopulations were determined by flow cytometry. Additionally, 16 s rRNA and LC-MS techniques were used to detect the colonic intestinal microbiota and metabolite profiles, respectively. Correlation analyses was performed to clarify the interactions between differential bacteria, metabolites and M1/M2 macrophages, and pseudo sterile mice were constructed by depletion of gut flora with quadruple antibiotics, followed by faecal microbial transplantation to evaluate its effects on colitis and M1/M2 macrophage polarisation.

RESULTS: FN dose-dependently alleviated clinical symptoms and inflammatory injury in colonic tissues of colitis mice, with its high-dose efficacy comparable to that of 5-ASA. Concurrently, FN not only inhibited inflammatory infiltration of macrophages and their M1/M2 polarisation balance in colitis mice, but also improved the composition of colonic microbiota and metabolite profiles. However, FN lost its protective effects against DSS-induced colitis and failed to restore the equilibrium of M1/M2 macrophage differentiation following intestinal flora depletion through quadruple antibiotic treatment. Importantly, fecal microbiota transplantation from FN-treated mice restored FN's protective effects against DSS-induced colitis and reestablished its regulatory role in M1/M2 macrophage polarization.

CONCLUSION: Collectively, FN ameliorated UC through modulating the balance of M1/M2 macrophage polarization in a gut microbiota-dependent manner.}, } @article {pmid39421003, year = {2024}, author = {Hansen, MM and Rågård, N and Andreasen, PW and Paaske, SE and Dahlerup, JF and Mikkelsen, S and Erikstrup, C and Baunwall, SMD and Hvas, CL}, title = {Encapsulated donor faeces for faecal microbiota transplantation: the Glyprotect protocol.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241289065}, pmid = {39421003}, issn = {1756-283X}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection. Its use is backed by solid evidence, but application methods differ. Encapsulated FMT is a non-invasive, patient-friendly and scalable application method that may be preferred over colonoscopy or nasoduodenal tube application.

OBJECTIVES: We describe a detailed protocol, the Glyprotect protocol, for producing glycerol-based capsules to increase FMT accessibility.

DESIGN: Using iterative quality improvement methods, we developed and validated the Glyprotect protocol as a reproducible protocol for cryopreserving minimally processed donor faeces in a standard hospital laboratory setting.

METHODS: We describe detailed standard operating procedures for producing glycerol-based capsules, including all necessary materials and troubleshooting guidelines. Capsule integrity was tested at various temperatures and pH levels. Flow cytometry was used to measure microbiota counts and dose accuracy.

RESULTS: The Glyprotect protocol has been used for more than 2500 capsule-based FMT treatments and complies with European tissue and cell standards. The protocol is optimised to preserve microbes and minimise modulation of the donated microbiota by removing debris and water, which also reduces the number of capsules needed per FMT treatment. The intestinal microbiota is preserved in glycerol for cryoprotection and to prevent capsule leakage. Each capsule contains 650 µL microbe-glycerol mass, estimated to contain an average of 2.5 × 10[8] non-specified bacteria.

CONCLUSION: The Glyprotect protocol enables hospitals and tissue establishments to set up capsule production in a standard laboratory, improving patients' access to FMT. The protocol facilitates the scalability of FMT services because capsule FMT is less time-consuming and less expensive than liquid-suspension FMT applied by colonoscopy or nasojejunal tube.

TRIAL REGISTRATION: Not applicable.}, } @article {pmid39420836, year = {2024}, author = {Qu, W and Xu, Y and Yang, J and Shi, H and Wang, J and Yu, X and Chen, J and Wang, B and Zhuoga, D and Luo, M and Liu, R}, title = {Berberine alters the gut microbiota metabolism and impairs spermatogenesis.}, journal = {Acta biochimica et biophysica Sinica}, volume = {}, number = {}, pages = {}, doi = {10.3724/abbs.2024174}, pmid = {39420836}, issn = {1745-7270}, abstract = {Berberine (BBR) is used to treat diarrhea clinically. However, its reproductive toxicity is unclear. This study aims to investigate the impact of BBR on the male reproductive system. Intragastric BBR administration for 14 consecutive days results in a significant decrease in the serum testosterone concentration, epididymal sperm concentration, mating rate and fecundity of male mice. Testicular treatment with testosterone propionate (TP) partially reverses the damage caused by BBR to the male reproductive system. Mechanistically, the decrease in Muribaculaceae abundance in the gut microbiota of mice is the principal cause of the BBR-induced decrease in the sperm concentration. Both fecal microbiota transplantation (FMT) and polyethylene glycol (PEG) treatment demonstrate that Muribaculaceae is necessary for spermatogenesis. The intragastric administration of Muribaculaceae intestinale to BBR-treated mice restores the sperm concentration and testosterone levels. Metabolomic analysis reveals that BBR affects arginine and proline metabolism, of which ornithine level is downregulated. Combined analysis via 16S rRNA metagenomics sequencing and metabolomics shows that Muribaculaceae regulates ornithine level. The transcriptomic results of the testes indicate that the expressions of genes related to the low-density lipoprotein receptor (LDLR)-mediated testosterone synthesis pathway decrease after BBR administration. The transcriptional activity of the Ldlr gene in TM3 cells is increased with increased ornithine supplementation in the culture media, leading to increased testosterone synthesis. Overall, this study reveals an association between a BBR-induced decrease in Muribaculaceae abundance and defective spermatogenesis, providing a prospective therapeutic approach for addressing infertility-related decreases in serum testosterone triggered by changes in the gut microbiota composition.}, } @article {pmid39420603, year = {2024}, author = {Poupard, L and Page, G and Thoreau, V and Kaouah, Z}, title = {Relationships between Gut Microbiota and Autism Spectrum Disorders: Development and Treatment.}, journal = {Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology}, volume = {22}, number = {4}, pages = {554-564}, pmid = {39420603}, issn = {1738-1088}, abstract = {Many studies have demonstrated the impact of intestinal microbiota on normal brain development. Moreover, the gut microbiota (GM) is impacted by multiple endogenous and environmental factors that may promote gut dysbiosis (GD). An increasing number of studies are investigating the possible role of the GD in the development of neurological and behavioral disorders. For autism spectrum disorders (ASD), specific intestinal bacterial signatures have been identified, knowing that gastrointestinal symptoms are frequently found in ASD. In this review, the peri and post-natal factors modulating the GM are described and the specific gut bacterial signature of ASD children is detailed. Through bidirectional communication between the GM and the brain, several mechanisms are involved in the development of ASD, such as cytokine-mediated neuroinflammation and decreased production of neuroprotective factors such as short-chain fatty acids by the GM. Imbalance of certain neurotransmitters such as serotonin or gamma-aminobutyric acid could also play a role in these gut-brain interactions. Some studies show that this GD in ASD is partly reversible by treatment with pre- and probiotics, or fecal microbiota transplantation with promising results. However, certain limitations have been raised, in particular concerning the short duration of treatment, the small sample sizes and the diversity of protocols. The development of standardized therapeutics acting on GD in large cohort could rescue the gastrointestinal symptoms and behavioral impairments, as well as patient management.}, } @article {pmid39420082, year = {2024}, author = {Zhang, HJ and Wang, HW and Tian, FY and Yang, CZ and Zhao, M and Ding, YX and Wang, XY and Cui, XY}, title = {Decolonization strategies for ESBL-producing or carbapenem-resistant Enterobacterales carriage: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {24349}, pmid = {39420082}, issn = {2045-2322}, support = {2024L090//Shanxi Provincial Education Department/ ; 2017041037-2//Shanxi Provincial Science and Technology Department/ ; 202303021211121//Natural Science Foundation of Shanxi Province/ ; }, mesh = {Humans ; *beta-Lactamases/metabolism ; *Enterobacteriaceae Infections/drug therapy/microbiology ; *Carbapenem-Resistant Enterobacteriaceae/drug effects ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Carbapenems/therapeutic use/pharmacology ; Enterobacteriaceae/drug effects ; Carrier State/microbiology/drug therapy ; }, abstract = {The prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and carbapenem-resistant Enterobacterales (CRE) has become a global public health problem. ESBL-E/CRE colonization can increase the risk of infection in patients and lead to poor disease prognosis. We conducted a systematic review and meta-analysis to evaluate current decolonization strategies regarding ESBL-E/CRE and their efficacy. A literature search was conducted until August 2023 on the five databases to review decolonization strategies associated with ESBL-E/CRE. A meta-analysis was conducted using RevMan 5.4 to compare differences in the decolonization strategy with placebo controls. The primary outcome was decolonization rates, with secondary outcomes of attributable death and adverse events. Quality of identified studies was determined using the Newcastle-Ottawa scale and cochrane risk assessment tool. Random and fixed effects meta-analyses were performed to calculate pooled value. A total of 25 studies were included. In five randomized controlled trial (RCT) studies, the decolonization effect of selective digestive decontamination(SDD) on ESBL-E/CRE at the end of treatment was significantly better in the experimental group than the controls [risk radio (RR): 3.30; 95% CI 1.78-6.14]. In three n-RCT studies, the decolonization effect in the experimental group was still better than the controls one month after SDD therapy [odds ratio (OR): 4.01; 95% CI 1.88-8.56]. The combined decolonization rates reported by six single-arm trial studies of SDD therapy ranged from 53.8 to 68.0%. Additionally, TSA analysis confirmed the effectiveness of SDD therapy. In studies on Faecal microbiota transplantation (FMT) therapy, the decolonization effect of the experimental group was significantly better than the controls 1 month after treatment (OR: 2.57; 95% CI 1.07-6.16). In studies without a control group and with varying follow-up times, the decolonization rates varied widely but indicated the effectiveness trend of FMT therapy (61.3-81.2%). Currently, research on the decolonization effect of probiotic therapy on ESBL-E/CRE is insufficient, and only a systematic review was conducted. SDD and FMT strategies have short-term benefits for ESBL-E/CRE decolonization, but long-term effects are unclear. The effect of probiotic therapy on ESBL-E/CRE decolonization is an interesting topic that still requires further investigation.}, } @article {pmid39420033, year = {2024}, author = {Majzoub, ME and Paramsothy, S and Haifer, C and Parthasarathy, R and Borody, TJ and Leong, RW and Kamm, MA and Kaakoush, NO}, title = {The phageome of patients with ulcerative colitis treated with donor fecal microbiota reveals markers associated with disease remission.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8979}, pmid = {39420033}, issn = {2041-1723}, support = {988415//Crohn's and Colitis Foundation (Crohn's & Colitis Foundation)/ ; APP2011047//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Investigator grant//Department of Health | National Health and Medical Research Council (NHMRC)/ ; Scientia fellowship//University of New South Wales (UNSW Australia)/ ; }, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology/virology ; *Fecal Microbiota Transplantation ; *Bacteriophages/genetics/isolation & purification/physiology ; *Gastrointestinal Microbiome/genetics ; *Feces/microbiology/virology ; Double-Blind Method ; Male ; Female ; Metagenomics/methods ; Adult ; Dysbiosis/microbiology/therapy ; Middle Aged ; Virome/genetics ; Remission Induction ; Anti-Bacterial Agents/therapeutic use ; Biomarkers ; }, abstract = {Bacteriophages are influential within the human gut microbiota, yet they remain understudied relative to bacteria. This is a limitation of studies on fecal microbiota transplantation (FMT) where bacteriophages likely influence outcome. Here, using metagenomics, we profile phage populations - the phageome - in individuals recruited into two double-blind randomized trials of FMT in ulcerative colitis. We leverage the trial designs to observe that phage populations behave similarly to bacterial populations, showing temporal stability in health, dysbiosis in active disease, modulation by antibiotic treatment and by FMT. We identify a donor bacteriophage putatively associated with disease remission, which on genomic analysis was found integrated in a bacterium classified to Oscillospiraceae, previously isolated from a centenarian and predicted to produce vitamin B complex except B12. Our study provides an in-depth assessment of phage populations during different states and suggests that bacteriophage tracking has utility in identifying determinants of disease activity and resolution.}, } @article {pmid39419539, year = {2024}, author = {Scher, JU and Nayak, R and Clemente, JC}, title = {Microbiome research in autoimmune and immune-mediated inflammatory diseases: lessons, advances and unmet needs.}, journal = {Annals of the rheumatic diseases}, volume = {}, number = {}, pages = {}, doi = {10.1136/ard-2024-225735}, pmid = {39419539}, issn = {1468-2060}, abstract = {The increasing prevalence of autoimmune and immune-mediated diseases (AIMDs) underscores the need to understand environmental factors that contribute to their pathogenesis, with the microbiome emerging as a key player. Despite significant advancements in understanding how the microbiome influences physiological and inflammatory responses, translating these findings into clinical practice remains challenging. This viewpoint reviews the progress and obstacles in microbiome research related to AIMDs, examining molecular techniques that enhance our understanding of microbial contributions to disease. We discuss significant discoveries linking specific taxa and metabolites to diseases such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis, highlighting the role of gut dysbiosis and host-microbiome interactions. Furthermore, we explore the potential of microbiome-based therapeutics, including faecal microbiota transplantation and pharmacomicrobiomics, while addressing the challenges of identifying robust microbial targets. We advocate for integrative, transdisease studies and emphasise the need for diverse cohort research to generalise findings across populations. Understanding the microbiome's role in AIMDs will pave the way for personalised medicine and innovative therapeutic strategies.}, } @article {pmid39418776, year = {2024}, author = {Xie, Q and Sun, J and Sun, M and Wang, Q and Wang, M}, title = {Perturbed microbial ecology in neuromyelitis optica spectrum disorder: Evidence from the gut microbiome and fecal metabolome.}, journal = {Multiple sclerosis and related disorders}, volume = {92}, number = {}, pages = {105936}, doi = {10.1016/j.msard.2024.105936}, pmid = {39418776}, issn = {2211-0356}, abstract = {BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating immune-mediated ailment, which is influenced by genetic, epigenetic, and environmental elements. The escalating incidence of NMOSD in recent years implies alterations in environmental risk factors. Recent research has established a correlation between gut microbiomes and the development of NMOSD.

METHODS: Metagenomic shotgun sequencing and gas chromatography-mass spectrometry (GC-MS) were employed to assess alterations of the structure and function in the fecal microbiome, as well as levels of short-chain fatty acids (SCFAs) in fecal and blood samples, among individuals with neuromyelitis optica spectrum disorder (NMOSD) during the acute phase (n = 25), the remission phase (n = 11), and a group of healthy controls (HCs) (n = 24). We further explored the correlation between gut microbiota and the pathogenesis of NMOSD through fecal microbiota transplantation (FMT). The gut microbiome from human donors diagnosed with NMOSD or HCs was transplanted into germ-free mice, followed by an analysis of the alterations in the structure and functionality of the transplanted mice's gut microbiome. Additionally, the impact of microbiome transfer on the immunity and spinal cord of germ-free mice was assessed through various techniques, including ELISA, flow cytometry, western blot, histopathology, and transcriptome sequencing.

RESULTS: (1) At the taxonomic levels of genus and species, there were significant differences in the α-diversity of the microbiome between HCs and NMOSD patients in the acute phase, with NMOSD patients having higher species diversity. (2) In the acute phase, the gut microbiota of NMOSD patients was characterized by Ruminococcaceae_unclassified, Campylobacter, Parabacteroides, Lactobacillus, Akkermansia, Streptococcus oralis, Clostridium leptum, Clostridium asparagiforme, Firmicutes bacterium CAG 238, and Lactobacillus fermentum. (3) The relative abundances of Coprobacter, Turicimonas, Gemmiger, Enterobacter, Roseburia sp.CAG 471, Veillonella tobetsuensis, Proteobacteria bacterium CAG 139, Ruminococcus bicirculans, Lactococcus lactis, Flavonifractor plautii, and Streptococcus cristatus were notably lower in patients experiencing remission compared to NMOSD patients in the acute phase, On the other hand, the relative abundances of Flavonifractor (P = 0.049) and Clostridium aldenense (P = 0.049) were significantly higher. Following medication, the gut microbiome distribution in NMOSD patients during remission closely resembled that of healthy controls (HCs). (4) Compared with HCs, acetate levels in the feces of patients with NMOSD in the acute phase were significantly lower. (5) In addition, we transplanted feces from NMOSD patients into germ-free mice and revealed a significant increase in the levels of IL-6, IL-17A, and IL-23 in the blood of mice belonging to the NMOSD fecal transplantation (NFMT) group. Additionally, the IL-10 level exhibited a significant reduction. Moreover, the proportion of Th17 cells displayed a significant increase, while the proportion of Treg cells exhibited a significant decrease in the spleens of NFMT mice.

CONCLUSION: Patients in the acute phase of neuromyelitis optica spectrum disorder (NMOSD) exhibited imbalances in their gut microbiota and a deficiency in short-chain fatty acids (SCFAs). Following drug treatment, the composition of intestinal microbes in NMOSD patients during the remission phase closely resembled that of the healthy control population. The FMT experiment provided evidence of the significant association between intestinal flora and the pathogenesis of NMOSD. Consequently, investigating gut microbiota and identifying novel microbial markers hold promise for the diagnosis and treatment of NMOSD patients.}, } @article {pmid39412514, year = {2024}, author = {Han, M and Wang, X and Su, L and Pan, S and Liu, N and Li, D and Liu, L and Cui, J and Zhao, H and Yang, F}, title = {Intestinal microbiome dysbiosis increases Mycobacteria pulmonary colonization in mice by regulating the Nos2-associated pathways.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {39412514}, issn = {2050-084X}, support = {242102521045//Science and Technology Research Project of Henan Province/ ; 242102310202//Science and Technology Research Project of Henan Province/ ; LHGJ20230525//Project of Health Commission of Henan Province/ ; Open Project of the Institute of Tuberculosis XYJHB20210//Xinxiang Medical University/ ; Tuberculosis Capacity Improvement Project 2023-68//Henan Provincial Health Commission/ ; }, mesh = {Animals ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome/physiology ; Mice ; *Lung/microbiology ; *Nitric Oxide Synthase Type II/metabolism/genetics ; Mice, Inbred C57BL ; Mycobacterium tuberculosis ; Tuberculosis/microbiology ; }, abstract = {Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing Mycobacterium colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiota's effect on Mycobacterium's colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the 'gut-lung axis'. Nos2 high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of nitric oxide, decreasing the levels of reactive oxygen species and Defb1 in the cells, and promoting Mycobacteria colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of Mycobacteria infections and transmission by regulating the gut microbiome balance.}, } @article {pmid39410876, year = {2024}, author = {Wen, J and Feng, Y and Xue, L and Yuan, S and Chen, Q and Luo, A and Wang, S and Zhang, J}, title = {High-fat diet-induced L-saccharopine accumulation inhibits estradiol synthesis and damages oocyte quality by disturbing mitochondrial homeostasis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2412381}, pmid = {39410876}, issn = {1949-0984}, mesh = {Animals ; Female ; *Diet, High-Fat/adverse effects ; *Estradiol/metabolism/biosynthesis ; *Oocytes/metabolism/drug effects ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Mitochondria/metabolism/drug effects ; *Dysbiosis/microbiology ; *Homeostasis ; *Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Infertility, Female/microbiology/metabolism/etiology ; Ovary/metabolism/microbiology ; }, abstract = {High-fat diet (HFD) has been linked to female infertility. However, the specific age at which HFD impacts ovarian function and the underlying mechanisms remain poorly understood. Here, we administered a HFD to female mice at various developmental stages: pre-puberty (4 weeks old), post-puberty (6 weeks old), young adult (9 weeks old), and middle age (32 weeks old). Our observations indicated that ovarian function was most significantly compromised when HFD was initiated at post-puberty. Consequently, post-puberty mice were chosen for further investigation. Through transplantation of fecal bacteria from the HFD mice to the mice on a normal diet, we confirmed that gut microbiota dysbiosis contributed to HFD-induced deteriorated fertility and disrupted estradiol synthesis. Utilizing untargeted and targeted metabolomics analyses, we identified L-saccharopine as a key metabolite, which was enriched in the feces, serum, and ovaries of HFD and HFD-FMT mice. Subsequent in vitro and in vivo experiments demonstrated that L-saccharopine disrupted mitochondrial homeostasis by impeding AMPKα/MFF-mediated mitochondrial fission. This disruption ultimately hindered estradiol synthesis and compromised oocyte quality. AICAR, an activator of AMPKα, ameliorated L-saccharopine induced mitochondrial damage in granulosa cells and oocytes, thereby enhancing E2 synthesis and improving oocyte quality. Collectively, our findings indicate that the accumulation of L-saccharopine may play a pivotal role in mediating HFD-induced ovarian dysfunction. This highlights the potential therapeutic benefits of targeting the gut microbiota-metabolite-ovary axis to address HFD-induced ovarian dysfunction.}, } @article {pmid39409832, year = {2024}, author = {Kang, HJ and Kim, SW and Kim, SM and La, TM and Hyun, JE and Lee, SW and Kim, JH}, title = {Altered Gut Microbiome Composition in Dogs with Hyperadrenocorticism: Key Bacterial Genera Analysis.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {19}, pages = {}, pmid = {39409832}, issn = {2076-2615}, abstract = {Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, which is associated with diverse metabolic abnormalities. We hypothesized that elevated cortisol levels in dogs with HAC disrupt the gut microbiome (GM), and this disruption persists even after trilostane treatment. This study explored GM composition in dogs with HAC. We included 24 dogs, 15 with HAC and 9 healthy controls, and followed up with 5 dogs with HAC who received trilostane treatment. The GM analysis revealed significant compositional changes in dogs with HAC, including reduced microbiome diversity compared to healthy controls, particularly in rare taxa, as indicated by the Shannon index (p = 0.0148). Beta diversity analysis further showed a distinct clustering of microbiomes in dogs with HAC, separating them from healthy dogs (p < 0.003). Specifically, an overrepresentation of Proteobacteria (Pseudomonadota), Actinobacteria, Bacteroides, Enterococcus, Corynebacterium, Escherichia, and Proteus populations occurred alongside a decreased Firmicutes (Bacillota) population. Despite trilostane treatment, gut dysbiosis persisted in dogs with HAC at a median of 41 d post treatment, suggesting its potential role in ongoing metabolic issues. We identified GM dysbiosis in dogs with HAC by examining key bacterial genera, offering insights into potential interventions like probiotics or fecal microbiota transplants for better HAC management.}, } @article {pmid39408940, year = {2024}, author = {Luppi, S and Aldegheri, L and Azzalini, E and Pacetti, E and Barucca Sebastiani, G and Fabiani, C and Robino, A and Comar, M}, title = {Unravelling the Role of Gut and Oral Microbiota in the Pediatric Population with Type 1 Diabetes Mellitus.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, pmid = {39408940}, issn = {1422-0067}, support = {RC 26/22 (Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy)//Ministero della Salute/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 1/microbiology ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology ; Child ; Mouth/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; Microbiota ; }, abstract = {Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease that results in the destruction of pancreatic β cells, leading to hyperglycaemia and the need for lifelong insulin therapy. Although genetic predisposition and environmental factors are considered key contributors to T1DM, the exact causes of the disease remain partially unclear. Recent evidence has focused on the relationship between the gut, the oral cavity, immune regulation, and systemic inflammation. In individuals with T1DM, changes in the gut and oral microbial composition are commonly observed, indicating that dysbiosis may contribute to immune dysregulation. Gut dysbiosis can influence the immune system through increased intestinal permeability, altered production of short chain fatty acids (SCFAs), and interactions with the mucosal immune system, potentially triggering the autoimmune response. Similarly, oral dysbiosis may contribute to the development of systemic inflammation and thus influence the progression of T1DM. A comprehensive understanding of these relationships is essential for the identification of biomarkers for early diagnosis and monitoring, as well as for the development of therapies aimed at restoring microbial balance. This review presents a synthesis of current research on the connection between T1DM and microbiome dysbiosis, with a focus on the gut and oral microbiomes in pediatric populations. It explores potential mechanisms by which microbial dysbiosis contributes to the pathogenesis of T1DM and examines the potential of microbiome-based therapies, including probiotics, prebiotics, synbiotics, and faecal microbiota transplantation (FMT). This complex relationship highlights the need for longitudinal studies to monitor microbiome changes over time, investigate causal relationships between specific microbial species and T1DM, and develop personalised medicine approaches.}, } @article {pmid39408584, year = {2024}, author = {Guevara-Ramírez, P and Cadena-Ullauri, S and Paz-Cruz, E and Ruiz-Pozo, VA and Tamayo-Trujillo, R and Cabrera-Andrade, A and Zambrano, AK}, title = {Gut Microbiota Disruption in Hematologic Cancer Therapy: Molecular Insights and Implications for Treatment Efficacy.}, journal = {International journal of molecular sciences}, volume = {25}, number = {19}, pages = {}, pmid = {39408584}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hematologic Neoplasms/therapy/microbiology ; Probiotics/therapeutic use ; Treatment Outcome ; Antineoplastic Agents/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Hematologic malignancies (HMs), including leukemia, lymphoma, and multiple myeloma, involve the uncontrolled proliferation of abnormal blood cells, posing significant clinical challenges due to their heterogeneity and varied treatment responses. Despite recent advancements in therapies that have improved survival rates, particularly in chronic lymphocytic leukemia and acute lymphoblastic leukemia, treatments like chemotherapy and stem cell transplantation often disrupt gut microbiota, which can negatively impact treatment outcomes and increase infection risks. This review explores the complex, bidirectional interactions between gut microbiota and cancer treatments in patients with HMs. Gut microbiota can influence drug metabolism through mechanisms such as the production of enzymes like bacterial β-glucuronidases, which can alter drug efficacy and toxicity. Moreover, microbial metabolites like short-chain fatty acids can modulate the host immune response, enhancing treatment effectiveness. However, therapy often reduces the diversity of beneficial bacteria, such as Bifidobacterium and Faecalibacterium, while increasing pathogenic bacteria like Enterococcus and Escherichia coli. These findings highlight the critical need to preserve microbiota diversity during treatment. Future research should focus on personalized microbiome-based therapies, including probiotics, prebiotics, and fecal microbiota transplantation, to improve outcomes and quality of life for patients with hematologic malignancies.}, } @article {pmid39189787, year = {2024}, author = {Arcay, R and Barceló-Nicolau, M and Suárez, L and Martín, L and Reigada, R and Höring, M and Liebisch, G and Garrido, C and Cabot, G and Vílchez, H and Cortés-Lara, S and González de Herrero, E and López-Causapé, C and Oliver, A and Barceló-Coblijn, G and Mena, A}, title = {Gut microbiome and plasma lipidome analysis reveals a specific impact of Clostridioides difficile infection on intestinal bacterial communities and sterol metabolism.}, journal = {mBio}, volume = {15}, number = {10}, pages = {e0134724}, pmid = {39189787}, issn = {2150-7511}, support = {co-PI of the SYN17/12//Health Research Institute of the Balearic Islands (IdISBa)/ ; JUNIOR18/02//Health Research Institute of the Balearic Islands (IdISBa)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology/blood/therapy ; *Sterols/metabolism/blood ; *Lipid Metabolism ; *Clostridioides difficile/metabolism ; Bacteria/classification/metabolism/isolation & purification/genetics ; Male ; Lipidomics ; Female ; Middle Aged ; Aged ; Feces/microbiology ; Lipids/blood ; Adult ; Fecal Microbiota Transplantation ; }, abstract = {UNLABELLED: Clostridioides difficile infection (CDI) causes alterations in the intestinal microbiota, frequently associated with changes in the gut metabolism of bile acids and cholesterol. In addition to the impact on microbiome composition and given the metabolic changes occurring during CDI, our work focuses on the importance to know the effects at the local and systemic levels, both during the infection and its treatment, by paying particular attention to plasma lipid metabolism due to its relationship with CDI pathogenesis. Specific changes, characterized by a loss of microbial richness and diversity and related to a reduction in short-chain acid-producing bacteria and an increase in bile salt hydrolase-producing bacteria, were observed in the gut microbiota of CDI patients, especially in those suffering from recurrent CDI (RCDI). However, gut microbiota showed its ability to restore itself after treatment, resembling healthy individuals, in those patients treated by fecal microbiome transfer (FMT), in contrast with those treated with antibiotics, and displaying increased levels of Eubacterium coprostanoligenes, a cholesterol-reducing anaerobe. Interestingly, changes in plasma lipidome revealed a global depletion in circulating lipids in CDI, with the largest impact on cholesteryl esters. CDI patients also showed a specific and consistent decrease in the levels of lipid species containing linoleic acid-an essential fatty acid-which were only partially recovered after antibiotic treatment. Analysis of the plasma lipidome reflects CDI impact on the gut microbiota and its metabolism, evidencing changes in sterol and fatty acid metabolism that are possibly related to specific alterations observed in gut microbial communities of CDI patients.

IMPORTANCE: There is increasing evidence about the influence the changes in microbiota and its metabolism has on numerous diseases and infections such as Clostridioides difficile infection (CDI). The knowledge of these changes at local and systemic levels can help us manage this infection to avoid recurrences and apply the best therapies, such as fecal microbiota transfer (FMT). This study shows a better restoration of the gut in FMT-treated patients than in antibiotic-treated patients, resembling healthy controls and showing increased levels of cholesterol-reducing bacteria. Furthermore, it evidences the CDI impact on plasma lipidome. We observed in CDI patients a global depletion in circulating lipids, particularly cholesteryl esters, and a specific decrease in linoleic acid-containing lipids, an essential fatty acid. Our observations could impact CDI management because the lipid content was only partially recovered after treatment, suggesting that continued nutritional support, aiming to restore healthy lipid levels, could be essential for a full recovery.}, } @article {pmid39407442, year = {2024}, author = {Lamminpää, I and Niccolai, E and Amedei, A}, title = {Probiotics as adjuvants to mitigate adverse reactions and enhance effectiveness in Food Allergy Immunotherapy.}, journal = {Scandinavian journal of immunology}, volume = {}, number = {}, pages = {e13405}, doi = {10.1111/sji.13405}, pmid = {39407442}, issn = {1365-3083}, abstract = {In the past decades, food allergies became increasingly dominant since early childhood, leading to a lower quality of life and to increasing costs addressed by the health care system. Beside standard avoidance of specific allergens and drug treatments following allergen exposure, a great deal of research has lately focused on Food Allergy Allergen Immunotherapy (FA-AIT). SCIT and EPIT (Subcutaneous and Epicutaneous Immunotherapy), OIT (Oral Immunotherapy), and SLIT (Sublingual Immunotherapy) consist in gradual exposure to allergens to desensitize and achieve tolerance once therapy has ended. Although promising, FA-AIT may bring acute local and systemic adverse reactions. To enhance efficacy, safety and convenience of AIT, the quest of potential adjuvants to mitigate the adverse reactions becomes crucial. Immunomodulatory activities, such as that of increasing the regulatory T cells and decreasing the IgE, have been observed in specific probiotics' strains and multiple studies elucidated the role of gut microbiota as a major interplayer among the host and its immune system. In this review, the microbiome modulation is shown as potential AIT adjuvant, nevertheless the need of more clinical studies in the near future is pivotal to assess the efficacy of targeted bacterial therapies and faecal microbiota transplantation.}, } @article {pmid39407244, year = {2024}, author = {Huang, Y and Wang, Y and Huang, X and Yu, X}, title = {Unveiling the overlooked fungi: the vital of gut fungi in inflammatory bowel disease and colorectal cancer.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {59}, pmid = {39407244}, issn = {1757-4749}, support = {NSFC 32260024, 32060040//the National Natural Science Foundation of China/ ; 20232BAB216091, 20202BAB206062//The Jiangxi Natural Science Foundation/ ; jxsq2023201019//The Double-Thousand Talent Program of Jiangxi Province/ ; }, abstract = {The fungi of the human microbiota play important roles in the nutritional metabolism and immunological balance of the host. Recently, research has increasingly emphasised the role of fungi in modulating inflammation in intestinal diseases and maintaining health in this environment. It is therefore necessary to understand more clearly the interactions and mechanisms of the microbiota/pathogen/host relationship and the resulting inflammatory processes, as well as to offer new insights into the prevention, diagnosis and treatment of inflammatory bowel disease (IBD), colorectal cancer (CRC) and other intestinal pathologies. In this review, we comprehensively elucidate the fungal-associated pathogenic mechanisms of intestinal inflammation in IBD and related CRC, with an emphasis on three main aspects: the direct effects of fungi and their metabolites on the host, the indirect effects mediated by interactions with other intestinal microorganisms and the immune regulation of the host. Understanding these mechanisms will enable the development of innovative approaches based on the use of fungi from the resident human microbiota such as dietary interventions, fungal probiotics and faecal microbiota transplantation in the prevention, diagnosis and treatment of intestinal diseases.}, } @article {pmid39406549, year = {2024}, author = {Li, K and Guo, L and Yu, J and Yang, Y and Wei, L and Min, C and Xu, X and Li, F and Liu, J and Zhou, G and Zhang, J}, title = {Kui-Jie-Ling capsule inhibits ulcerative colitis by modulating inflammation and gut microbiota.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16758}, pmid = {39406549}, issn = {1440-1746}, support = {81202882//National Natural Science Foundation of China/ ; SNG2021022//Suzhou Science and Technology Planning Project in Jiangsu Province of China/ ; SYS2020079//Suzhou Science and Technology Planning Project in Jiangsu Province of China/ ; Z2020063//Jiangsu Health Commission Medical Research Projects, China/ ; JCZ21130//Science and Technology Bureau of Haian City, China/ ; SZWZYTD202205//Scientific and Technological Innovation Team Building Program of Suzhou Vocational Health College/ ; PAPD//Priority Academic Program Development of the Jiangsu Higher Education Institutes, China/ ; SZWZY202401//Science and Technology Planning Project of Suzhou Vocational Health College/ ; }, abstract = {BACKGROUND AND AIM: Kui-Jie-Ling capsule (Kui-Jie-Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS).

METHODS: Network pharmacology was combined with an animal experiment to reveal the targets of Kui-Jie-Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7 days. On the second day, the mice in the Kui-Jie-Ling group were orally administered with Kui-Jie-Ling (1.5 and 3.0 g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui-Jie-Ling (3.0 g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short-chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments.

RESULTS: The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui-Jie-Ling alleviated UC via multi-pathway. Kui-Jie-Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide-toll-like receptor 4/nuclear factor kappa B and interleukin-23-Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis.

CONCLUSION: These studies provided the experimental basis for the clinical administration of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab against UC.}, } @article {pmid39404715, year = {2024}, author = {Maev, IV and Velikolug, KA}, title = {[Cytomegalovirus infection in gastroenterology].}, journal = {Terapevticheskii arkhiv}, volume = {96}, number = {8}, pages = {723-731}, doi = {10.26442/00403660.2024.08.202814}, pmid = {39404715}, issn = {0040-3660}, mesh = {Humans ; *Cytomegalovirus Infections/diagnosis/drug therapy ; *Antiviral Agents/therapeutic use ; Cytomegalovirus/genetics/isolation & purification ; Gastrointestinal Diseases/virology/diagnosis/therapy/etiology ; Risk Factors ; Polymerase Chain Reaction/methods ; DNA, Viral/analysis ; }, abstract = {AIM: To highlight the relevance of gastrointestinal manifestations of cytomegalovirus infection (CMVI), to highlight the main risk factors for the development of this pathology, current trends in diagnosis and treatment.

KEY POINTS: CMVI is one of the most common opportunistic diseases, characterized by a variety of manifestations from asymptomatic to severe generalized forms affecting internal organs and body systems. The prevalence of CMVI worldwide ranges from 20 to 95%. Particular attention is paid to timely diagnosis, treatment and prevention of CMVI. The "gold standard" in the diagnosis of digestive diseases associated with CMVI is immunohistochemical examination and detection of cytomegalovirus (CMV) DNA in tissues using the polymerase chain reaction (PCR). Of undoubted interest in the diagnosis of CMV is the detection of CMV DNA in stool using digital PCR. Compared to quantitative PCR, digital PCR has higher accuracy and sensitivity. As first-line therapy, the drugs of choice are ganciclovir and valganciclovir. Maribavir has been successfully used to treat patients with CMV infection refractory to one or more previous therapies. One of the promising directions in the treatment of cytomegalovirus colitis in patients with ulcerative colitis is fecal microbiota transplantation.

CONCLUSION: Timely identification of risk factors for the development of CMV infection, the introduction of innovative methods and approaches in diagnosis, and the use of effective methods for treating diseases of the digestive system associated with CMV infection can improve the prognosis of the underlying disease and reduce the risk of developing urgent conditions in gastroenterology.}, } @article {pmid39403342, year = {2024}, author = {Bertin, L and Crepaldi, M and Zanconato, M and Lorenzon, G and Maniero, D and De Barba, C and Bonazzi, E and Facchin, S and Scarpa, M and Ruffolo, C and Angriman, I and Buda, A and Zingone, F and Savarino, EV and Barberio, B}, title = {Refractory Crohn's Disease: Perspectives, Unmet Needs and Innovations.}, journal = {Clinical and experimental gastroenterology}, volume = {17}, number = {}, pages = {261-315}, pmid = {39403342}, issn = {1178-7023}, abstract = {Crohn's disease (CD) is a complex, chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. Despite advances in treatment, CD remains a significant health burden, leading to substantial direct healthcare costs and out-of-pocket expenses for patients, especially in the first-year post-diagnosis. The impact of CD on patients' quality of life is profound, with significant reductions in physical, emotional, and social well-being. Despite advancements in therapeutic options, including biologics, immunomodulators, and small molecules, many patients struggle to achieve or maintain remission, leading to a considerable therapeutic ceiling. This has led to an increased focus on novel and emerging treatments. This context underscores the importance of exploring advanced and innovative treatment options for managing refractory CD. By examining the latest approaches, including immunomodulators, combination therapies, stem cell therapies, and emerging treatments like fecal microbiota transplantation and dietary interventions, there is an opportunity to gain a comprehensive understanding of how best to address and manage refractory cases of CD.}, } @article {pmid39403201, year = {2024}, author = {Napiórkowska-Baran, K and Biliński, J and Pujanek, M and Hałakuc, P and Pietryga, A and Szymczak, B and Deptuła, A and Rosada, T and Bartuzi, Z}, title = {Fecal microbiota transplantation in a patient with chronic diarrhea and primary and secondary immunodeficiency (common variable immunodeficiency and splenectomy).}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1456672}, pmid = {39403201}, issn = {2235-2988}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Diarrhea/microbiology/therapy ; Middle Aged ; *Splenectomy ; *Common Variable Immunodeficiency/complications/therapy ; *Gastrointestinal Microbiome ; Feces/microbiology/virology ; Cytomegalovirus Infections ; Male ; Treatment Outcome ; Valganciclovir/therapeutic use/administration & dosage ; Chronic Disease ; Immunocompromised Host ; Dysbiosis/therapy/microbiology ; Clostridioides difficile ; }, abstract = {The gut microbiota serves a crucial role in the development of host immunity. Immunocompromised patients are particularly vulnerable to dysbiosis not only by virtue of a defect in the immune system but also due to increased susceptibility to infection and multiple courses of antibiotic therapy. Fecal microbiota transplantation is by far the most effective option for restoring gastrointestinal homeostasis. However, it is contraindicated in patients with significant primary and secondary immunodeficiencies. This article presents the case of a 59-year-old patient with common variable immunodeficiency, after splenectomy at age 39 for primary immune thrombocytopenia, who manifested diarrhea of up to 10 stools per day accompanied by secondary malnutrition and cachexia. The patient was admitted to the hospital on multiple occasions due to this condition, with stool PCR tests confirming a HHV-5 (Cytomegalovirus, CMV) infection. Following the administration of valganciclovir, the patient's complaints diminished, although, upon cessation of the drug, the symptoms recurred. In addition, the patient had an intestinal infection with C. difficile etiology. Given that the patient's therapeutic options had been exhausted, after obtaining informed consent from the patient and approval from the bioethics committee to conduct a medical experiment, treatment of diarrhea was undertaken by fecal microbiota transplantation with the certified preparation Mbiotix HBI from the Human Biome Institute. The patient underwent two transplants, with a one-week interval between them. The initial procedure was performed using the endoscopic method, while the subsequent was conducted using the capsule method. Following the administration of the applied treatment, the patient's symptoms were successfully alleviated, and no adverse effects were observed. A microbiological analysis of the intestinal microbiota was conducted prior to and following transplantation via next-generation sequencing (NGS). No recurrence of symptoms was observed during the two-year follow-up period. To the best of our knowledge, this is the first fecal microbiota transplantation in an adult patient with primary and secondary immunodeficiency.}, } @article {pmid39403173, year = {2024}, author = {Huang, J and Wang, X and Zhang, J and Li, Q and Zhang, P and Wu, C and Jia, Y and Su, H and Sun, X}, title = {Fecal microbiota transplantation alleviates food allergy in neonatal mice via the PD-1/PD-L1 pathway and change of the microbiota composition.}, journal = {The World Allergy Organization journal}, volume = {17}, number = {10}, pages = {100969}, pmid = {39403173}, issn = {1939-4551}, abstract = {BACKGROUND: Food allergy (FA) is a common disorder in children and affects the health of children worldwide. The gut microbiota is closely related to the occurrence and development of FA. Fecal microbiota transplantation (FMT) is a way to treat diseases by reconstituting the microbiota; however, the role and mechanisms of FA have not been validated.

METHODS: In this study, we established an ovalbumin (OVA)-induced juvenile mouse model and used 16S RNA sequencing, pathological histological staining, molecular biology, and flow-through techniques to evaluate the protective effects of FMT treatment on FA and to explore the mechanisms.

RESULTS: OVA-induced dysregulation of the gut microbiota led to impaired intestinal function and immune dysregulation in FA mice. FMT treatment improved the structure, diversity, and composition of the gut microbiota and restored it to a near-donor state. FMT treatment reduced levels of Th2-associated inflammatory factors, decreased intestinal tissue inflammation, and reduced IgE production. In addition, FMT reduced the number of mast cells and eosinophils and suppressed OVA-specific antibodies. Further mechanistic studies revealed that FMT treatment induced immune tolerance by inducing the expression of CD103[+]DCs and programmed cell death ligand 1 (PD-L1) in mesenteric lymph nodes and promoting the production of Treg through the programmed cell death protein 1 (PD-1)/PD-L1 pathway. Meanwhile, Th2 cytokines, OVA-specific antibodies, and PD-1/PD-L1 showed a significant correlation with the gut microbiota.

CONCLUSIONS: FMT could regulate the gut microbiota and Th1/Th2 immune balance and might inhibit FA through the PD-1/PD-L1 pathway, which would provide a new idea for the treatment of FA.}, } @article {pmid39403057, year = {2024}, author = {Liang, C and Pereira, R and Zhang, Y and Rojas, OL}, title = {Gut Microbiome in Alzheimer's Disease: from Mice to Humans.}, journal = {Current neuropharmacology}, volume = {22}, number = {14}, pages = {2314-2329}, pmid = {39403057}, issn = {1875-6190}, mesh = {*Alzheimer Disease/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; Humans ; Animals ; *Brain-Gut Axis/physiology ; Mice ; Probiotics/therapeutic use ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; Prebiotics ; }, abstract = {Alzheimer's disease (AD) is the most prevalent type of dementia, but its etiopathogenesis is not yet fully understood. Recent preclinical studies and clinical evidence indicate that changes in the gut microbiome could potentially play a role in the accumulation of amyloid beta. However, the relationship between gut dysbiosis and AD is still elusive. In this review, the potential impact of the gut microbiome on AD development and progression is discussed. Pre-clinical and clinical literature exploring changes in gut microbiome composition is assessed, which can contribute to AD pathology including increased amyloid beta deposition and cognitive impairment. The gut-brain axis and the potential involvement of metabolites produced by the gut microbiome in AD are also highlighted. Furthermore, the potential of antibiotics, prebiotics, probiotics, fecal microbiota transplantation, and dietary interventions as complementary therapies for the management of AD is summarized. This review provides valuable insights into potential therapeutic strategies to modulate the gut microbiome in AD.}, } @article {pmid39401017, year = {2024}, author = {Yang, T and Liu, Y and Yin, J and Tian, Y and Zhou, F and Li, Y and Yang, L and Han, L and Huang, X}, title = {Transplantation of fecal microbiota from different breed improved intestinal barrier condition and modulated ileal microflora of recipient pigs.}, journal = {Journal of animal science}, volume = {}, number = {}, pages = {}, doi = {10.1093/jas/skae314}, pmid = {39401017}, issn = {1525-3163}, abstract = {In this study, we investigated the effects of transplanting Ningxiang pig fecal bacteria on ileum microflora and intestinal barrier of Duroc × Landrace × Large White (DLY) pigs. Thirty-two DLY pigs at 90-d-old were equally assigned to either control groups (fed the basal diet) or test group (fed the basal diet + 10ml fecal microbiota suspension from Ningxiang pig). Results showed that fecal microbiota transplantation (FMT) did not influence the growth performance, but increased the number of ileum goblet cells and the expression level of mucin-2. Additionally, the mucosal levels of anti-inflammatory cytokines interlukin-4 and interlukin-10 were upregulated, but the level of pro-inflammatory cytokine interferon-γ was downregulated by FMT. Moreover, FMT increased the expression level of porcine β defensin-114 in ileum mucus. 16S rRNA gene sequencing of ileal digesta showed that FMT modulated the diversity and composition of ileal microbiota of DLY pigs by increasing the relative abundances of beneficial bacteria, while decreasing the abundance of the pathogenic bacterium Streptococcus. Taken together, the study showed that FMT of Ningxiang pigs could improve intestinal barrier condition of DLY pigs by improving intestinal microflora and promoting intestinal health.}, } @article {pmid39400011, year = {2024}, author = {Lu, D and Ji, L and Liu, F and Liu, H and Sun, Z and Yan, J and Wu, H}, title = {Fecal Microbiota Transplantation Induced by Wumei Pills Improves Chemotherapy-Induced Intestinal Mucositis in BALB/c Mice by Modulating the TLR4/MyD88/NF-κB Signaling Pathway.}, journal = {Current drug delivery}, volume = {}, number = {}, pages = {}, doi = {10.2174/0115672018304338241003095955}, pmid = {39400011}, issn = {1875-5704}, abstract = {BACKGROUND: Our previous studies have found that Wumei Pills can regulate the intestinal flora to inhibit chemotherapy-induced intestinal mucositis (CIM). However, there is still insufficient evidence to confirm that intestinal flora is the main link in the regulation of CIM by Wumei Pills, and its downstream mechanism is still unclear.

METHOD: We first obtained the signal pathway of the intervention of Wumei Pill on CIM through network pharmacological analysis and then transplanted the bacterial solution into CIM mice, combined with Western Blot, HE, ELISA and other biological technology-related proteins and inflammatory factors.

RESULTS: It showed that 97 kinds of effective ingredients and 205 kinds of targets of Wumei pills were screened out and the potential mechanism of Wumei Pills on CIM may be the NF-κB signaling pathway. In contrast with the control group, the results displayed that the weight, food intake, and mice's colon length were apparently decreased in the 5-Fu group, while the diarrhea score was increased. However, FMT reversed this change, and the difference was statistically significant. Additionally, FMT could improve the pathological state of inflammatory cell infiltration in mice, reduce histopathological scores of colon and jejunum, decrease the expression levels of IL-1β, MPO, TNF-α, and IL-6, reverse the activation of signaling pathway named TLR4/Myd88/ NF-κB and down-regulate protein expression, thereby exerting its anti-inflammatory activities. Further experiments have found that FMT could reverse the decreasing of tight junction proteins and mucins caused by 5-Fu, thereby repairing the intestinal mucosal barrier, and FMT could also increase the content of acetic acid, propanoic acid, and butanoic acid in the feces of 5-Fu group.

CONCLUSION: FMT can defend the intestinal mucosal barrier integrality by increasing the content of exercise fatty acids, and its mechanism may be in connection with its inhibition of TLR4/My- D88/NF-κB signal pathway to relieve inflammation.}, } @article {pmid39399248, year = {2024}, author = {Scott, A and Khoruts, A and Freeman, ML and Beilman, G and Ramanathan, K and Bellin, MD and Trikudanathan, G}, title = {Successful Use of Fecal Microbiota Transplantation in Management of Nonobstructive Recurrent Cholangitis Following Total Pancreatectomy and Islet Autotransplant.}, journal = {ACG case reports journal}, volume = {11}, number = {10}, pages = {e01527}, pmid = {39399248}, issn = {2326-3253}, abstract = {Alterations in the gut microbiome have been implicated in various pathologies. Fecal microbiota transplantation (FMT) has been offered as a novel treatment for conditions implicated in the disruption of the gut-microbiota axis. This case report details the successful treatment of recurrent nonobstructive cholangitis following a single FMT application in a patient who had previously undergone a hepatobiliary tract surgical diversion. Cholangitis was suspected secondary to reflux of an altered microbiome into the surgically reanastomosed biliary tract, and FMT was justified based on the history of recurrent Clostridioides difficile infections. This case supports the further evaluation of the utility of FMT as one potential treatment of post hepatobiliary surgical diversion cholangitis.}, } @article {pmid39398388, year = {2024}, author = {Liu, T and Lei, C and Huang, Q and Song, W and Li, C and Sun, N and Liu, Z}, title = {Hesperidin and Fecal Microbiota Transplantation Modulate the Composition of the Gut Microbiota and Reduce Obesity in High Fat Diet Mice.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {17}, number = {}, pages = {3643-3656}, pmid = {39398388}, issn = {1178-7007}, abstract = {INTRODUCTION: Obesity, which is associated with gut microbiota dysbiosis, low-grade chronic inflammation and intestinal barrier dysfunction, can cause a variety of chronic metabolic diseases. Phytochemical flavonoids have a variety of biological activities, among which there may be safe and effective anti-obesity solutions.

METHODS: We tested a plant-derived flavonoid hesperidin and fecal microbiota transplantation (FMT) to alleviate diet-induced obesity. High-fat diet (HFD)-fed mice were treated with hesperidin (100 and 200 mg/kg BW) and FMT.

RESULTS: Results indicated that hesperidin had the effects of reducing obesity as indicated by reduction of body weight, fat accumulation and blood lipids, reducing inflammation as indicated by reduction of pro-inflammation factors including TNFα, IL-6, IL-1βand iNOS, and improving gut integrity as indicated by increasing colon length, reducing plasma gut permeability indicators iFABP and LBP, increased mRNA expression of mucus protein Muc2, tight junction p Claudin 2, Occludin and ZO-1 in the HFD-fed mice. The anti-obesity effects of hesperidin treatment have a dose-dependent manner. In addition, 16S rRNA-based gut microbiota analysis revealed that hesperidin selectively promoted the growth of Lactobacillus salivarius, Staphylococcus sciuri and Desulfovibrio C21_c20 while inhibiting Bifidobacterium pseudolongum, Mucispirillum schaedleri, Helicobacter ganmani and Helicobacter hepaticus in the HFD-fed mice. Horizontal feces transfer from the normal diet (ND)-fed mice to the HFD-fed mice conferred anti-obesity effects and transmitted some of the HFD-modulated microbes.

CONCLUSION: We concluded that hesperidin and FMT both affect the reduction of body weight and improve HFD-related disorders in the HFD-fed mice possibly through modulating the composition of the gut microbiota.}, } @article {pmid39397472, year = {2024}, author = {Ding, H and Wang, Q and Liao, G and Hao, Z}, title = {[Diagnosis and treatment of gastrointestinal bleeding after kidney transplantation].}, journal = {Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences}, volume = {56}, number = {5}, pages = {902-907}, pmid = {39397472}, issn = {1671-167X}, mesh = {Humans ; *Kidney Transplantation ; *Gastrointestinal Hemorrhage/etiology/diagnosis/therapy ; Retrospective Studies ; *Kidney Failure, Chronic/therapy/complications ; Gastroscopy ; Male ; Embolization, Therapeutic ; }, abstract = {OBJECTIVE: To analyze the clinical characteristics of acute and chronic gastrointestinal bleeding in patients with end-stage renal disease (ESRD) after kidney transplantation, to improve the understanding of the causes, diagnosis, treatment and prevention of this complication, and to improve the management of patients with gastrointestinal bleeding after kidney transplantation.

METHODS: The clinical, imaging and pathological data of patients with gastrointestinal bleeding after kidney transplantation in the Department of Urology of The First Affiliated Hospital of Anhui Medical University from August, 2015 to December, 2020 were collected. The etiology, early clinical manifestations, abnormal laboratory tests and examinations, treatment procedures, late prevention and treatment measures and outcomes of gastrointestinal bleeding were retrospectively studied, and the relevant literature was summarized and reviewed.

RESULTS: A total of 17 patients were included in this study. Nine patients had chronic small amount of bleeding, hemoglobin gradually decreased, melena and fecal occult blood positive in the early stage, and the general condition was good, vital signs were stable, and were cured by drug treatment. Gastroscopy showed small ulcers with active bleeding foci in 2 cases, and the bleeding was stopped by titanium clips, and the prognosis was good. Gastroscopy showed that the anterior wall longitudinal ulcer at the junction of gastric antrum body was not effective in 1 case, and the small branch of right gastroepithelial artery was embolized, and the patient recovered and discharged after 2 weeks. Gastroscopy showed deep pit ulcer at the lesser curvature of gastric antrum in 1 patient, who underwent distal gastroduodenal artery embolization and had a good prognosis. Gastroscopy showed huge multiple ulcers in the stomach and duodenal bulb in 2 patients, who underwent subtotal gastrectomy and partial duodenectomy, duodenal stump exclusion and remnant gastrojejunostomy. One patient recovered and was discharged, and the other patient died of rebleeding on the 12th day after surgery. Two cases of diverticulum underwent surgical resection of diverticulum, and the prognosis was good.

CONCLUSION: The onset of gastrointestinal hemorrhage in kidney transplant patients is insidious, and the condition is acute or slow, which can cause different degrees of damage to the patient and the transplanted kidney. Active prevention, early diagnosis, timely drug treatment, if the effect is not good, decisive endoscopic titanium clip hemostasis, transvascular interventional embolization, and even surgical treatment can minimize the harm of gastrointestinal bleeding.}, } @article {pmid39396842, year = {2024}, author = {González, A and Badiola, I and Fullaondo, A and Rodríguez, J and Odriozola, A}, title = {Personalised medicine based on host genetics and microbiota applied to colorectal cancer.}, journal = {Advances in genetics}, volume = {112}, number = {}, pages = {411-485}, doi = {10.1016/bs.adgen.2024.08.004}, pmid = {39396842}, issn = {0065-2660}, mesh = {Humans ; *Colorectal Neoplasms/genetics/microbiology ; *Precision Medicine/methods ; *Gastrointestinal Microbiome/genetics ; Biomarkers, Tumor/genetics ; Prognosis ; }, abstract = {Colorectal cancer (CRC) ranks second in incidence and third in cancer mortality worldwide. This situation, together with the understanding of the heterogeneity of the disease, has highlighted the need to develop a more individualised approach to its prevention, diagnosis and treatment through personalised medicine. This approach aims to stratify patients according to risk, predict disease progression and determine the most appropriate treatment. It is essential to identify patients who may respond adequately to treatment and those who may be resistant to treatment to avoid unnecessary therapies and minimise adverse side effects. Current research is focused on identifying biomarkers such as specific mutated genes, the type of mutations and molecular profiles critical for the individualisation of CRC diagnosis, prognosis and treatment guidance. In addition, the study of the intestinal microbiota as biomarkers is being incorporated due to the growing scientific evidence supporting its influence on this disease. This article comprehensively addresses the use of current and emerging diagnostic, prognostic and predictive biomarkers in precision medicine against CRC. The effects of host genetics and gut microbiota composition on new approaches to treating this disease are discussed. How the gut microbiota could mitigate the side effects of treatment is reviewed. In addition, strategies to modulate the gut microbiota, such as dietary interventions, antibiotics, and transplantation of faecal microbiota and phages, are discussed to improve CRC prevention and treatment. These findings provide a solid foundation for future research and improving the care of CRC patients.}, } @article {pmid39396755, year = {2024}, author = {Zhang, Y and Li, P and Chen, B and Zheng, R}, title = {Therapeutic Effects of Fecal Microbial Transplantation on Alcoholic Liver Injury in Rat models.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {}, number = {}, pages = {102478}, doi = {10.1016/j.clinre.2024.102478}, pmid = {39396755}, issn = {2210-741X}, abstract = {OBJECTIVE: Disruption of gut microbiota is closely related to the progression of alcoholic liver disease (ALD). This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) in ALD rats using a combination of microbiological and metabolomic techniques.

METHODS: Three liver injury rat models were constructed using alcohol, CCL4, and alcohol combined with CCL4, and administered an FMT treatment comprising the fecal microbiota of healthy rats via the gastric route for 12 consecutive weeks. We measured the therapeutic effect of FMT treatment on liver inflammation, intestinal mucosal barrier, and bacterial translocation in ALD rats using 16S rRNA and UPLC-Q/TOF-MS technology to detect the effects of FMT on the intestinal microbiota and metabolic patterns of ALD rats.

RESULTS: FMT treatment effectively improved liver function, prolonged survival time, improved the intestinal mucosal barrier, reduced bacterial translocation, alleviated liver inflammation, and delayed the progression of liver fibrosis in three types of liver injury models. The microbiome and metabolomic results showed that FMT can effectively improve gut microbiota disorder in ALD rats and improve metabolic patterns by regulating metabolic pathways such as the arachidonic acid and retinol pathways.

CONCLUSION: FMT treatment could reverse alcohol induced liver injury by improving gut microbiota and metabolic patterns in ALD rats, and oral FMT could be an effective therapeutic approach for ALD.}, } @article {pmid39396405, year = {2024}, author = {Luo, Z and Yang, L and Zhu, T and Fan, F and Wang, X and Liu, Y and Zhan, H and Luo, D and Guo, J}, title = {Aucubin ameliorates atherosclerosis by modulating tryptophan metabolism and inhibiting endothelial-mesenchymal transitions via gut microbiota regulation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156122}, doi = {10.1016/j.phymed.2024.156122}, pmid = {39396405}, issn = {1618-095X}, abstract = {BACKGROUND: The gut microbiota is believed to influence atherosclerosis (AS), and Aucubin (Au), a natural compound found in the traditional Chinese medicine Eucommia ulmoides Oliver, is being explored as a potential treatment for cardiovascular disease. Yet, the specific impact of Au on AS through the gut microbiota remains unclear.

PURPOSE: This study aimed to highlight the potential of Au in improving AS by influencing gut microbiota and investigating its potential mechanisms by which it and its metabolites of gut microbiota regulate lipid metabolism, inflammation and endothelial dysfunction.

METHODS: The impact of Au on AS in ApoE[-/-] mice was examined, followed by a fecal microbiota transplantation experiment to confirm the influence of Au on AS through gut microbiota. Subsequent analysis of fecal and serum samples using 16S rRNA gene sequencing and metabolomics revealed distinct features of gut microbiota and metabolites. Identified metabolites were then utilized in vivo experiments to investigate underlying mechanisms.

RESULTS: Au treatment effectively reduced dietary-induced dyslipidemia and endothelial dysfunction in a dose-dependent manner in atherosclerotic mice. It also improved vascular plaque accumulation and inflammation, increased aortic valve fibrous cap thickness, and decreased necrotic core and collagen fiber area. Subsequently, we observed a substantial increase in indole-3-acrylic acid (IAA), a microbe-derived metabolite, in cecal contents and serum, along with a significant rise in Lactobacillus abundance responsible for IAA production. Our findings demonstrated that IAA played a crucial role in alleviating AS. Furthermore, we discovered that IAA activated the Aryl hydrocarbon receptor (AhR) and suppressed the TGF-β/Smad pathway, potentially ameliorating endothelial-mesenchymal transitions in atherosclerotic mice.

CONCLUSION: These findings suggested that Au's anti-atherosclerotic effects were primarily due to elevated Lactobacillus-derived IAA, thereby potentially contributing to alleviating AS.}, } @article {pmid39395767, year = {2024}, author = {Qi, Z and Liu, J and Xu, Y and Hongguang, S and Qi, X and Cong, M and Zhang, X and Yan, Y and Liu, T}, title = {Protective effects of phenylethanol glycosides from Cistanche tubulosa against ALD through modulating gut microbiota homeostasis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {118925}, doi = {10.1016/j.jep.2024.118925}, pmid = {39395767}, issn = {1872-7573}, abstract = {Cistanche tubulosa (Schenk) Wight, a Chinese herbal medicine (Rou Cong Rong) with Xinjiang characteristics, was recorded in many medical books in ancient China and often used as a tonic medicine. Supported by the traditional Chinese medicine theory of "homology of liver and kidney," C. tubulosa (Schenk) Wight has many clinical applications in tonifying the kidney and protecting the liver. Modern pharmacological studies have also found that the protective effects of phenylethanol glycosides from C. tubulosa (Schenk) Wight (CPhGs) play an important role in ameliorating alcoholic liver injury.

AIM OF THE STUDY: We aimed to investigate whether CPhGs can enhance the therapeutic outcome of alcoholic liver disease (ALD) by targeting the "gut-liver axis," thus contributing to the knowledge of how Chinese herbs alleviate disease by influencing the gut microbiota.

MATERIALS AND METHODS: An ALD mouse model was established using the Lieber-DeCarli alcohol liquid diet, and the effects of CPhGs on the intestinal barrier and gut microbiota of ALD mice were investigated in a pseudo-sterile mouse model and fecal microbiota transplantation (FMT) mouse model. We fed female C57BL/6N mice with Lieber-DeCarli ethanol liquid diet, according to the NIAAA model. Animal experiment of long-term, ethanol diet intervention for 6W, and short-term for 11d. The FMT experiments were also performed.

RESULTS: CPhGs significantly improved ALD manifestations. ALD mice demonstrated significant gut microbiota dysbiosis and significantly abnormal proliferation of Allobaculum compared with the control diet group in long-term NIAAA mouse model (L-Pair). In mice that received the long-term intervention, the improvement in gut barrier function in the CPhGs-treated group was accompanied by a significant decrease in the abundance of Allobaculum and a significant increase in the abundance of Akkermansia. Furthermore, compared with the mouse were gavaged fecal microbiota from the long-term NIAAA mouse donors (FMT-EtOH), the number of goblet cells, abundance of Akkermansia, and the intestinal short-chain fatty acid concentrations were significantly increased in the mouse were gavaged fecal microbiota from high (700 mg/kg) doses of CPhGs orally in long-term NIAAA model donors (FMT-EtOH-H). Network analysis and species distribution results demonstrated that Akkermansia and Allobaculum were the genera with the highest abundances in the gut microbiota and that their interaction was related to propionic acid metabolism.

CONCLUSIONS: The results suggest that CPhGs exert a protective effect against ALD by modulating the abundance and composition of Akkermansia and Allobaculum in the intestine, maintaining the intestinal mucus balance, and safeguarding intestinal barrier integrity.}, } @article {pmid39395000, year = {2024}, author = {Sayol-Altarriba, A and Aira, A and Villasante, A and Albarracín, R and Faneca, J and Casals, G and Villanueva-Cañas, JL and Casals-Pascual, C}, title = {Normalization of short-chain fatty acid concentration by bacterial count of stool samples improves discrimination between eubiotic and dysbiotic gut microbiota caused by Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2415488}, doi = {10.1080/19490976.2024.2415488}, pmid = {39395000}, issn = {1949-0984}, mesh = {Humans ; *Fatty Acids, Volatile/metabolism/analysis ; *Feces/microbiology/chemistry ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology ; *Dysbiosis/microbiology ; *Clostridioides difficile/metabolism ; *Bacterial Load ; Male ; Female ; Middle Aged ; Adult ; Aged ; Butyrates/metabolism/analysis ; Bacteria/classification/isolation & purification/metabolism/genetics ; }, abstract = {Short-chain fatty acids (SCFAs) represent a cornerstone of gut health, serving as critical mediators of immune modulation and overall host homeostasis. Patients with dysbiosis caused by Clostridioides difficile infection (CDI) typically exhibit lower SCFAs levels compared to healthy stool donors and, thus, the concentration of SCFAs has been proposed as a proxy marker of a healthy microbiota. However, there is no consistency in the methods used to quantify SCFAs in stool samples and usually, the results are normalized by the weight of the stool samples, which does not address differences in water and fiber content and ignores bacterial counts in the sample (the main component of stool that contributes to the composition of these metabolites in the sample). Here, we show that normalized SCFAs concentrations by the bacterial count improve discrimination between healthy and dysbiotic samples (patients with CDI), particularly when using acetate and propionate levels. After normalization, butyrate is the metabolite that best discriminates eubiotic and dysbiotic samples according to the area under the receiver operating characteristic (ROC) curve (AUC-ROC = 0.860, [95% CI: 0.786-0.934], p < .0001).}, } @article {pmid39394819, year = {2024}, author = {Dong, L and Luo, P and Zhang, A}, title = {Intestinal microbiota dysbiosis contributes to the liver damage in subchronic arsenic-exposed mice.}, journal = {Acta biochimica et biophysica Sinica}, volume = {}, number = {}, pages = {}, doi = {10.3724/abbs.2024131}, pmid = {39394819}, issn = {1745-7270}, abstract = {There is an extensive amount of evidence that links changes in the intestinal microbiota structure to the progression and pathophysiology of many liver diseases. However, comprehensive analysis of gut flora dysbiosis in arsenic-induced hepatotoxicity is lacking. Herein, C57BL/6 mice are exposed to arsenic (1, 2, or 4 mg/kg) for 12 weeks, after which fecal microbiota transplantation (FMT) study is conducted to confirm the roles of the intestinal microbiome in pathology. Treatment with arsenic results in pathological and histological changes in the liver, such as inflammatory cell infiltration and decreased levels of TP and CHE but increased levels of ALP, GGT, TBA, AST, and ALT. Arsenic causes an increase in the relative abundance of Escherichia-Shigella, Klebsiella and Blautia, but a decrease in the relative abundance of Muribaculum and Lactobacillus. In arsenic-exposed mice, protein expressions of Occludin, ZO-1, and MUC2 are significantly decreased, but the level of FITC in serum is increased, and FITC fluorescence is extensively dispersed in the intestinal tract. Importantly, FMT experiments show that mice gavaged with stool from arsenic-treated mice exhibit severe inflammatory cell infiltration in liver tissues. Arsenic-manipulated gut microbiota transplantation markedly facilitates gut flora dysbiosis in the recipient mice, including an up-regulation in Escherichia-Shigella and Bacteroides, and a down-regulation in Lactobacillus and Desulfovibrio. In parallel with the intestinal microbiota wreck, protein expressions of Occludin, ZO-1, and MUC2 are decreased. Our findings suggest that subchronic exposure to arsenic can affect the homeostasis of the intestinal microbiota, induce intestinal barrier dysfunction, increase intestinal permeability, and cause damage to liver tissues in mice.}, } @article {pmid39394659, year = {2024}, author = {Hachem, Y and Djouadi, LN and Raddaoui, A and Boukli-Hacene, F and Boumerdassi, H and Achour, W and Nateche, F}, title = {Phenotypic and molecular characterization of vancomycin resistant Enterococci from wild birds: First detection of a plasmid-borne vanC1 in Enterococcus faecalis.}, journal = {Letters in applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/lambio/ovae098}, pmid = {39394659}, issn = {1472-765X}, abstract = {Vancomycin-resistant enterococci (VRE) are a public health concern as they lead to therapeutic impasses and play a pivotal role in the dissemination of vancomycin resistance genes. As recent evidence suggests that wildlife can play a role in the dissemination of bacterial resistomes, this study explored the potential role of Algerian wild birds as a reservoir of VRE. A total of 222 cloacal and fecal samples were collected from various wild bird species and screened for VRE using a selective medium. Of the 47 isolated strains, 22 were identified as Enterococcus casseliflavus with the vanC2/C3 gene, 24 as Enterococcus gallinarum (19 carrying vanC1 and five carrying vanC2/C3), and one strain as Enterococcus faecalis with the vanC1 gene. Twenty-four (24) strains were multidrug-resistant with 61.7% resistant to rifampicin while no resistance to teicoplanin, linezolid and gentamicin was found. Additionally, 53.20% of the strains exhibited at least one virulence factor. To our knowledge, this study represents the first documentation of the vanC1 gene in E. faecalis isolated from wild birds. Furthermore, this gene was found to be carried by a conjugative plasmid, highlighting its ability to spread among bacterial populations and lead to the emergence of novel resistance phenotypes.}, } @article {pmid39393983, year = {2024}, author = {Hamilton, AM and Krout, IN and White, AC and Sampson, TR}, title = {Microbiome-based therapeutics for Parkinson's disease.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {e00462}, doi = {10.1016/j.neurot.2024.e00462}, pmid = {39393983}, issn = {1878-7479}, abstract = {Recent experimental and clinical data demonstrate a significant dysregulation of the gut microbiome in individuals with Parkinson's disease (PD). With an immense influence on all aspects of physiology, this dysregulation has potential to directly or indirectly contribute to disease pathology. Experimental models have bridged these associations toward defined contributions, identifying various microbiome-dependent impacts to PD pathology. These studies have laid the foundation for human translation, examining whether certain members of the microbiome and/or whole restoration of the gut microbiome community can provide therapeutic benefit for people living with PD. Here, we review recent and ongoing clinically-focused studies that use microbiome-targeted therapies to limit the severity and progression of PD. Fecal microbiome transplants, prebiotic interventions, and probiotic supplementation are each emerging as viable methodologies to augment the gut microbiome and potentially limit PD symptoms. While still early, the data in the field to date support continued cross-talk between experimental systems and human studies to identify key microbial factors that contribute to PD pathologies.}, } @article {pmid39393976, year = {2024}, author = {Quera, R and Nuñez, P and von Muhlenbrock, C and Espinoza, R}, title = {Fecal microbiota transplantation through colonoscopy in the treatment of recurrent Clostridioides difficile: Experience at a university center.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.rgmxen.2024.03.004}, pmid = {39393976}, issn = {2255-534X}, abstract = {INTRODUCTION: The majority of cases of Clostridioides difficile infection (CDI) respond to antibiotic treatment. Fecal microbiota transplantation (FMT) has been accepted as an effective treatment in cases of recurrent CDI.

AIM: Our aim was to describe the clinical results of FMT performed for the treatment of recurrent CDI.

MATERIAL AND METHODS: The study was conducted on patients with recurrent CDI treated with FMT through colonoscopy, within the time frame of January 2021 and December 2023. Demographic and clinical data were collected, including pre-FMT treatment data, the FMT success rate, and clinical progression during follow-up. Telephone surveys were carried out to evaluate satisfaction.

RESULTS: Thirteen patients with a mean age of 55 years underwent FMT (including 7 patients above 65 years of age and one pregnant woman). Patients presented with a median of 3 previous episodes of CDI (range 2-4). The median time interval from first episode of CDI to FMT was 4 months (range 3-10). The effectiveness of a single FMT session was 100%. During post-FMT follow-up (median of 11 months, range 3-32), 3 patients have presented with a new CDI episode, and a successful second FMT was performed on 2 of them. No adverse events were registered, and all patients had a positive perception of FMT.

CONCLUSIONS: In the present study, despite its small size, FMT through colonoscopy was shown to be a safe, effective, and lasting therapy in cases of recurrent CDI, concurring with results from larger studies.}, } @article {pmid39393822, year = {2024}, author = {Liu, T and Fan, S and Meng, P and Ma, M and Wang, Y and Han, J and Wu, Y and Li, X and Su, X and Lu, C}, title = {Dietary Dihydroquercetin Alleviated Colitis via the Short-Chain Fatty Acids/miR-10a-5p/PI3K-Akt Signaling Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c03278}, pmid = {39393822}, issn = {1520-5118}, abstract = {Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3'-untranslated regions of gene pik3ca, inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.}, } @article {pmid39393557, year = {2024}, author = {Zhou, J and Yang, Q and Wei, W and Huo, J and Wang, W}, title = {Codonopsis pilosula polysaccharide alleviates ulcerative colitis by modulating gut microbiota and SCFA/GPR/NLRP3 pathway.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {118928}, doi = {10.1016/j.jep.2024.118928}, pmid = {39393557}, issn = {1872-7573}, abstract = {Codonopsis pilosula (Franch.) Nannf. (CP) is a Chinese herb commonly used in traditional Chinese medicine to treat ulcerative colitis (UC). C. pilosula polysaccharide (CPPS) is an important bioactive compound in CP. Polysaccharides are degraded by and interact with the gut microbiota, exerting therapeutic effects. However, the mechanism of action of CPPS in treating UC by regulating gut microbiota is unclear.

AIM OF THE STUDY: This study aimed to elucidate the therapeutic efficacy of CPPS on UC mice and its mechanism of action.

MATERIALS AND METHODS: Size-exclusion chromatography with multi-angle laser-light scattering and refractive index analysis was employed to ascertain the molecular weight of CPPS, while its monosaccharide composition was determined using ion chromatography. An experimental colitis mouse model was induced by administering 3% (dextran sulfate sodium) DSS in drinking water for five consecutive days. Three doses of CPPS were administered to evaluate their therapeutic effects on UC. CPPS was administered for seven days, and salicylazosulfapyridine was used as a positive control. Inflammatory cytokine secretion in the colon tissue was measured, and histopathological evaluation was performed on colon sections. Alterations in the abundance of the intestinal microbiota species were also analyzed. We then quantified short-chain fatty acids (SCFAs) in the cecal content and verified the G protein-coupled receptor (GPR)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathways using western blot. Furthermore, the ameliorative effect of gut microbiota on DSS-induced UC symptoms was verified using the fecal microbiota transplantation (FMT) experiment.

RESULTS: CPPS comprised of rhamnose, arabinose, galactose, glucose, and galacturonic acid. CPPS significantly alleviated DSS-induced UC. Compared to the DSS group, CPPS treatment significantly increased the ratio of the Firmicutes to the Bacteroidetes and upregulated the abundance of beneficial bacteria such as g__Ligilactobacillus, g_Akkermansia, g_Faecalibaculum, g_Odoribacter. The release of acetic acid and butyric acid were further promoted. CPPS can inhibit NLRP3 activation by binding SCFAs to GPR proteins, thereby reducing intestinal inflammation. FMT confirmed that the gut microbiota in the CPPS-trans group sufficiently mitigated DSS-induced UC symptoms.

CONCLUSIONS: CPPS ameliorates the symptoms of DSS-induced UC primarily through the gut microbiota modulation and SCFA/GPR/NLRP3 pathways, making it a promising candidate for UC treatment.}, } @article {pmid39391755, year = {2024}, author = {Fu, Y and Gu, Z and Cao, H and Zuo, C and Huang, Y and Song, Y and Jiang, Y and Wang, F}, title = {The role of the gut microbiota in neurodegenerative diseases targeting metabolism.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1432659}, pmid = {39391755}, issn = {1662-4548}, abstract = {In recent years, the incidence of neurodegenerative diseases (NDs) has gradually increased over the past decades due to the rapid aging of the global population. Traditional research has had difficulty explaining the relationship between its etiology and unhealthy lifestyle and diets. Emerging evidence had proved that the pathogenesis of neurodegenerative diseases may be related to changes of the gut microbiota's composition. Metabolism of gut microbiota has insidious and far-reaching effects on neurodegenerative diseases and provides new directions for disease intervention. Here, we delineated the basic relationship between gut microbiota and neurodegenerative diseases, highlighting the metabolism of gut microbiota in neurodegenerative diseases and also focusing on treatments for NDs based on gut microbiota. Our review may provide novel insights for neurodegeneration and approach a broadly applicable basis for the clinical therapies for neurodegenerative diseases.}, } @article {pmid39387234, year = {2024}, author = {Benech, N and Cassir, N and Alric, L and Barbut, F and Batista, R and Bleibtreu, A and Briot, T and Davido, B and Galperine, T and Joly, AC and Kapel, N and Melchior, C and Mosca, A and Nebbad, B and Pigneur, B and Schneider, SM and Wasiak, M and Scanzi, J and Sokol, H and , }, title = {Impact of Clinical and Pharmacological Parameters on Faecal Microbiota Transplantation Outcome in Clostridioides difficile Infections: Results of a 5-Year French National Survey.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.18330}, pmid = {39387234}, issn = {1365-2036}, abstract = {BACKGROUND: Detailed comparative assessment of procedure-related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited.

AIMS: We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure-related factors associated with FMT success in CDI.

METHODS: We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression.

RESULTS: Six hundred fifty-eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty-seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20-3.88]), non-severe refractory CDI (OR: 15.35, [1.94-318.2]), the use of ≥ 80% glycerol (OR: 2.52, [1.11-5.67]), insufficient bowel cleansing (OR: 5.47, [1.57-20.03]) and partial FMT retention (OR: 9.97, [2.62-48.49]) were associated with CDI recurrence within 8 weeks.

CONCLUSIONS: Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real-life practice, whereas it had lower efficacy in severe CDI and non-severe refractory CDI.}, } @article {pmid39391303, year = {2024}, author = {Karimi, M and Shirsalimi, N and Hashempour, Z and Salehi Omran, H and Sedighi, E and Beigi, F and Mortezazadeh, M}, title = {Safety and efficacy of fecal microbiota transplantation (FMT) as a modern adjuvant therapy in various diseases and disorders: a comprehensive literature review.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1439176}, pmid = {39391303}, issn = {1664-3224}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy ; Animals ; Treatment Outcome ; }, abstract = {The human gastrointestinal (GI) tract microbiome is a complex and all-encompassing ecological system of trillions of microorganisms. It plays a vital role in digestion, disease prevention, and overall health. When this delicate balance is disrupted, it can lead to various health issues. Fecal microbiota transplantation (FMT) is an emerging therapeutic intervention used as an adjuvant therapy for many diseases, particularly those with dysbiosis as their underlying cause. Its goal is to restore this balance by transferring fecal material from healthy donors to the recipients. FMT has an impressive reported cure rate between 80% and 90% and has become a favored treatment for many diseases. While FMT may have generally mild to moderate transient adverse effects, rare severe complications underscore the importance of rigorous donor screening and standardized administration. FMT has enormous potential as a practical therapeutic approach; however, additional research is required to further determine its potential for clinical utilization, as well as its safety and efficiency in different patient populations. This comprehensive literature review offers increased confidence in the safety and effectiveness of FMT for several diseases affecting the intestines and other systems, including diabetes, obesity, inflammatory and autoimmune illness, and other conditions.}, } @article {pmid39391251, year = {2024}, author = {Zheng, J and Chen, H}, title = {Effects of intratumoral microbiota on tumorigenesis, anti-tumor immunity, and microbe-based cancer therapy.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1429722}, pmid = {39391251}, issn = {2234-943X}, abstract = {Intratumoral microbiota (IM) has emerged as a significant component of the previously thought sterile tumor microenvironment (TME), exerting diverse functions in tumorigenesis and immune modulation. This review outlines the historical background, classification, and diversity of IM, elucidating its pivotal roles in oncogenicity, cancer development, and progression, alongside its influence on anti-tumor immunity. The signaling pathways through which IM impacts tumorigenesis and immunity, including reactive oxygen species (ROS), β-catenin, stimulator of interferon genes (STING), and other pathways [NF-κB, Toll-like receptor (TLR), complement, RhoA/ROCK, PKR-like ER kinase (PERK)], are discussed comprehensively. Furthermore, we briefly introduce the clinical implications of IM, emphasizing its potential as a target for novel cancer therapies, diagnostic biomarkers, and prognostic indicators. Notably, microbe-based therapeutic strategies such as fecal microbiome transplantation (FMT), probiotics regulation, bacteriotherapy, bacteriophage therapy, and oncolytic virotherapy are highlighted. These strategies hold promise for enhancing the efficacy of current cancer treatments and warrant further exploration in clinical settings.}, } @article {pmid39389400, year = {2024}, author = {Campagnoli, LIM and Marchesi, N and Varesi, A and Morozzi, M and Mascione, L and Ricevuti, G and Esposito, C and Galeotti, N and Pascale, A}, title = {New therapeutic avenues in multiple sclerosis: is there a place for gut microbiota-based treatments?.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107456}, doi = {10.1016/j.phrs.2024.107456}, pmid = {39389400}, issn = {1096-1186}, abstract = {The bidirectional interaction between the gut and the central nervous system (CNS), the so-called gut microbiota-brain axis, is reported to influence brain functions, thus having a potential impact on the development or the progression of several neurodegenerative disorders. Within this context, it has been documented that multiple sclerosis (MS), an autoimmune inflammatory, demyelinating, and neurodegenerative disease of the CNS, is associated with gastrointestinal symptoms, including constipation, dysphagia, and faecal incontinence. Moreover, some evidence suggests the existence of an altered gut microbiota (GM) composition in MS patients with respect to healthy individuals, as well as the potential influence of GM dysbiosis on typical MS features, including increased intestinal permeability, disruption of blood-brain barrier integrity, chronic inflammation, and altered T cells differentiation. Starting from these assumptions, the possible involvement of GM alteration in MS pathogenesis seems likely, and its restoration could represent a supplemental beneficial strategy against this disabling disease. In this regard, the present review will explore possible preventive approaches (including several dietary interventions, the administration of probiotics, prebiotics, synbiotics, and postbiotics, and the use of faecal microbiota transplantation) to be pursued as prophylaxis or in combination with pharmacological treatments with the aim of re-establishing a proper GM, thus helping to prevent the development of this disease or to manage it by alleviating symptoms or slowing down its progression.}, } @article {pmid39389184, year = {2024}, author = {Thomas, AS and Lu, Y and Campbell, M and Thompson, JA and Tan, D and Faleck, DM and Wang, Y}, title = {Immune checkpoint inhibitor induced colitis.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.09.034}, pmid = {39389184}, issn = {1528-0012}, } @article {pmid39387175, year = {2024}, author = {Zhang, K and Zhang, L and Jian, Y and Tang, X and Han, M and Pu, Z and Zhang, Y and Zhou, P}, title = {Early-Life Milk αS1-Casein Allergy Induces the Activation of Astrocytes in Mice and Leads to Stress Vulnerability in Adulthood.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c05425}, pmid = {39387175}, issn = {1520-5118}, abstract = {In recent years, the incidence of food allergies in children has been increasing annually, significantly affecting the quality of life for patients and their families. It has long been suspected that childhood allergies might potentially lead to behavioral and psychological issues in adulthood, but the specific connection remains unclear. In this study, we established a model of young mice allergic to milk αS1-casein, conducted behavioral tests, and employed transcriptomics, immunohistochemistry, Golgi staining, and fecal microbiota transplantation to explore the link between early life allergies and adult psychological problems. The results showed that early life milk protein allergy significantly increased intestinal epithelial permeability in mice, leading to the translocation of gut microbiota metabolites. This process subsequently activated astrocyte lysosomes via SLC15a3, making astrocytes more susceptible. This susceptibility caused mice with early life milk protein allergy to have more activated astrocytes and excessive dendritic spine phagocytosis (normal group: 5.4 ± 1.26 spines/10 μm, allergy group: 3.2 ± 0.92 spines/10 μm) under acute stress in adulthood, leading to anxiety and depressive behaviors.}, } @article {pmid39386168, year = {2024}, author = {Hao, L and Yan, Y and Huang, G and Li, H}, title = {From gut to bone: deciphering the impact of gut microbiota on osteoporosis pathogenesis and management.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1416739}, pmid = {39386168}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Osteoporosis/etiology/microbiology ; *Bone Density ; *Bone and Bones/microbiology ; Animals ; Risk Factors ; }, abstract = {Osteoporosis (OP) is characterized by decreased bone mineral density (BMD) and increased fracture risk, poses a significant global health burden. Recent research has shed light on the bidirectional relationship between gut microbiota (GM) and bone health, presenting a novel avenue for understanding OP pathogenesis and developing targeted therapeutic interventions. This review provides a comprehensive overview of the GM-bone axis, exploring the impact of GM on OP development and management. We elucidate established risk factors and pathogenesis of OP, delve into the diversity and functional changes of GM in OP. Furthermore, we examine experimental evidence and clinical observations linking alterations in GM composition or function with variations in BMD and fracture risk. Mechanistic insights into microbial mediators of bone health, such as microbial metabolites and products, are discussed. Therapeutic implications, including GM-targeted interventions and dietary strategies, are also explored. Finally, we identify future research directions and challenges in translating these findings into clinical practice.}, } @article {pmid39384730, year = {2024}, author = {Liang, Y and Li, Y and Lee, C and Yu, Z and Chen, C and Liang, C}, title = {Ulcerative colitis: molecular insights and intervention therapy.}, journal = {Molecular biomedicine}, volume = {5}, number = {1}, pages = {42}, pmid = {39384730}, issn = {2662-8651}, mesh = {Humans ; *Colitis, Ulcerative/therapy/immunology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by abdominal pain, diarrhea, rectal bleeding, and weight loss. The pathogenesis and treatment of UC remain key areas of research interest. Various factors, including genetic predisposition, immune dysregulation, and alterations in the gut microbiota, are believed to contribute to the pathogenesis of UC. Current treatments for UC include 5-aminosalicylic acids, corticosteroids, immunosuppressants, and biologics. However, study reported that the one-year clinical remission rate is only around 40%. It is necessary to prompt the exploration of new treatment modalities. Biologic therapies, such as anti-TNF-α monoclonal antibody and JAK inhibitor, primarily consist of small molecules targeting specific pathways, effectively inducing and maintaining remission. Given the significant role of the gut microbiota, research into intestinal microecologics, such as probiotics and prebiotics, and fecal microbiota transplantation (FMT) shows promising potential in UC treatment. Additionally, medicinal herbs, such as chili pepper and turmeric, used in complementary therapy have shown promising results in UC management. This article reviews recent findings on the mechanisms of UC, including genetic susceptibility, immune cell dynamics and cytokine regulation, and gut microbiota alterations. It also discusses current applications of biologic therapy, herbal therapy, microecologics, and FMT, along with their prospects and challenges.}, } @article {pmid39384149, year = {2024}, author = {Wang, H and Cai, Y and Wu, W and Zhang, M and Dai, Y and Wang, Q}, title = {Exploring the role of gut microbiome in autoimmune diseases: A comprehensive review.}, journal = {Autoimmunity reviews}, volume = {23}, number = {12}, pages = {103654}, doi = {10.1016/j.autrev.2024.103654}, pmid = {39384149}, issn = {1873-0183}, abstract = {As the industrialized society advances, there has been a gradual increase in the prevalence of autoimmune disorders. A probe into the fundamental causes has disclosed several factors in modern society that have an influence on the gut microbiome. These dramatic shifts in the gut microbiome are likely to be one of the reasons for the disarray in the immune system, and the relationship between the immune system and the gut microbiome emerging as a perennial hot topic of research. This review enumerates the findings from sequencing studies of gut microbiota on seven autoimmune diseases (ADs): Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Ankylosing Spondylitis (AS), Systemic Sclerosis (SSc), Sjögren's Syndrome (SjS), Juvenile Idiopathic Arthritis (JIA), and Behçet's Disease (BD). It aims to identify commonalities in changes in the gut microbiome within the autoimmune disease cohort and characteristics specific to each disease. The dysregulation of the gut microbiome involves a disruption of the internal balance and the balance between the external environment and the host. This dysregulation impacts the host's immune system, potentially playing a role in the development of ADs. Damage to the gut epithelial barrier allows potential pathogens to translocate to the mucosal layer, contacting epithelial cells, disrupting tight junctions, and being recognized by antigen-presenting cells, which triggers an immune response. Primed T-cells assist B-cells in producing antibodies against pathogens; if antigen mimicry occurs, an immune response is generated in extraintestinal organs during immune cell circulation, clinically manifesting as ADs. However, current research is limited; advancements in sequencing technology, large-scale cohort studies, and fecal microbiota transplantation (FMT) research are expected to propel this field to new peaks.}, } @article {pmid39382853, year = {2024}, author = {Khanna, S}, title = {Microbiota restoration for recurrent Clostridioides difficile infection.}, journal = {Panminerva medica}, volume = {}, number = {}, pages = {}, doi = {10.23736/S0031-0808.24.05111-5}, pmid = {39382853}, issn = {1827-1898}, abstract = {Since the publication of the recent North American and European guidelines on management of Clostridioides difficile infection (CDI), new evidence describing the epidemiology, testing and treatment of CDI has emerged. Despite all advances in infection control and antibiotic stewardship, the incidence and burden of CDI in the hospitals and the community remains at a stable high. Coupled with the incidence of primary CDI, there is a stable high incidence of recurrent CDI. Testing for primary and recurrent CDI remains a clinical challenge owing to high sensitivity of the PCR (leading to false positives) and somewhat limited sensitivity of EIA for toxin. The pathophysiology of recurrent CDI involves an ongoing disruption of the microbiota owing to the infection and the treatment of CDI employed. Broad spectrum antibiotics such as vancomycin leads to further disruption of microbiota compared to fidaxomicin which has a lower disruption of the microbiota and leads to fewer recurrences. Owing to these data fidaxomicin is considered as the first line antibiotic for recurrent CDI. Intravenous bezlotoxumab is a monoclonal antibody that reduces the risk of recurrence in high-risk patients but does not restore the microbiota. Experimental fecal microbiota transplantation (FMT) has been available for more than a decade. Owing to the success of FMT, two new non-invasive donor dependent Food and Drug Administration (FDA) approved therapies have been available since late 2022. This review summarizes all these conundrums regarding CDI and provides clinical pearls to use in day-to-day practice.}, } @article {pmid39381749, year = {2024}, author = {Fu, ZP and Ying, YG and Wang, RY and Wang, YQ}, title = {Aged gut microbiota promotes arrhythmia susceptibility via oxidative stress.}, journal = {iScience}, volume = {27}, number = {10}, pages = {110888}, pmid = {39381749}, issn = {2589-0042}, abstract = {Arrhythmias and sudden cardiac death (SCD) impose a significant burden. Their prevalence rises with age and is linked to gut dysbiosis. Our study aimed to determine whether aged gut microbiota affects arrhythmogenesis. Here, we demonstrated that arrhythmia susceptibility in aged mice could be transmitted to young mice using fecal microbiota transplantation (FMT). Mechanistically, increased intestinal reactive oxygen species (ROS) in aged mice reduced ion channel protein expression and promoted arrhythmias. Gut microbiota depletion by an antibiotic cocktail reduced ROS and arrhythmia in aged mice. Interestingly, oxidative stress in heart induced by hydrogen peroxide (H2O2) increased arrhythmia. Moreover, aged gut microbiota could induce oxidative stress in young mice colon by gut microbiota metabolites transplantation. Vitexin could reduce aging and arrhythmia through OLA1-Nrf2 signaling pathway. Overall, our study demonstrated that the gut microbiota of aged mice reduced cardiac ion channel protein expression through systemic oxidative stress, thereby increased the risk of arrhythmias.}, } @article {pmid39377587, year = {2024}, author = {McMillan, AS and Zhang, G and Dougherty, MK and McGill, SK and Gulati, AS and Baker, ES and Theriot, CM}, title = {Metagenomic, metabolomic, and lipidomic shifts associated with fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0070624}, doi = {10.1128/msphere.00706-24}, pmid = {39377587}, issn = {2379-5042}, abstract = {Recurrent C. difficile infection (rCDI) is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we use longitudinal stool samples collected from patients undergoing FMT to evaluate intra-individual changes in the microbiome, metabolome, and lipidome after successful FMTs relative to their baselines pre-FMT. We show changes in the abundance of many lipids, specifically a decrease in acylcarnitines post-FMT, and a shift from conjugated bile acids pre-FMT to deconjugated secondary bile acids post-FMT. These changes correlate with a decrease in Enterobacteriaceae, which encode carnitine metabolism genes, and an increase in Lachnospiraceae, which encode bile acid altering genes such as bile salt hydrolases (BSHs) and the bile acid-inducible (bai) operon, post-FMT. We also show changes in gut microbe-encoded amino acid biosynthesis genes, of which Enterobacteriaceae was the primary contributor to amino acids C. difficile is auxotrophic for. Liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT and generate hypotheses that require further experimental validation. This information is meant to help guide the development of new microbiota-focused therapeutics to treat rCDI.IMPORTANCERecurrent C. difficile infection is an urgent public health threat, for which the last resort and lifesaving treatment is a fecal microbiota transplant. However, the exact mechanisms that mediate a successful FMT are not well-understood. Here, we show changes in the abundance of many lipids, specifically acylcarnitines and bile acids, in response to FMT. These changes correlate with Enterobacteriaceae pre-FMT, which encodes carnitine metabolism genes, and Lachnospiraceae post-FMT, which encodes bile salt hydrolases and baiA genes. There was also a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here, we define the structural and functional changes associated with a successful FMT, which we hope will help aid in the development of new microbiota-focused therapeutics to treat rCDI.}, } @article {pmid39377303, year = {2024}, author = {Berrut, G and Baudron, CR and Paccalin, M and de Wazières, B and Gavazzi, G}, title = {[Clostridioides difficile infections: Update and therapeutic guidelines].}, journal = {Geriatrie et psychologie neuropsychiatrie du vieillissement}, volume = {22}, number = {3}, pages = {316-324}, doi = {10.1684/pnv.2024.1181}, pmid = {39377303}, issn = {2115-7863}, abstract = {Clostridioides difficile infection (CDI) represents a significant challenge due to its increasing incidence, severity, and treatment difficulty. Effective management requires a multifactorial approach that includes preventive strategies, prudent antibiotic use, and adapted therapeutic options. Ongoing research and innovation offer promising prospects for improving ICD management, making vigilance and informed practices essential among healthcare professionals. Two main complications of ICD are pseudomembranous colitis (PMC) and toxic megacolon. PMC involves severe colonic inflammation due to C. difficile toxins, leading to pseudomembrane formation. Diagnosis relies on clinical criteria, microbiological tests, and endoscopy. Toxic Megacolon is characterized by severe colonic dilation and systemic toxicity, requiring immediate medical intervention. ICD diagnosis combines clinical signs and microbiological tests. These tests include toxin tests, GDH antigen detection, PCR for toxin genes, and stool culture. Imaging techniques assess colonic inflammation and complications. Combined diagnostic criteria from the American Gastroenterological Association (AGA) and European guidelines emphasize integrating clinical and laboratory findings for accurate diagnosis. ICD treatment involves stopping the implicated antibiotics and starting specific antimicrobial therapy. Common treatments include mainly fidaxomicin and oral vancomycin. Fecal microbiota transplantation (TMF) is recommended for recurrent cases unresponsive to standard treatments. Bezlotoxumab, an antibody targeting C. difficile toxin B, is used to prevent recurrence in high-risk adults. ICD poses a major challenge due to its increasing incidence, severity, and difficulty in treatment. A multifactorial approach involving rigorous preventive strategies, prudent antibiotic management, and adapted therapeutic options is essential for controlling the infection. Ongoing research and innovations in treatment offer promising prospects for improving patient management. Healthcare professionals must remain vigilant and informed to ensure effective practices in combating this infection and utilizing available resources optimally.}, } @article {pmid39377231, year = {2024}, author = {Kim, DY and Lee, SY and Lee, JY and Whon, TW and Lee, JY and Jeon, CO and Bae, JW}, title = {Gut microbiome therapy: fecal microbiota transplantation vs live biotherapeutic products.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2412376}, doi = {10.1080/19490976.2024.2412376}, pmid = {39377231}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; Animals ; Clostridium Infections/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Biological Products/therapeutic use ; Gastrointestinal Diseases/therapy/microbiology ; }, abstract = {The human intestine hosts a complex ecosystem of various microorganisms, collectively known as the gut microbiome, which significantly impacts human health. Disruptions in the gut microbiome are linked to various disorders, including gastrointestinal diseases, such as Clostridioides difficile infection and inflammatory bowel disease, as well as metabolic, neurological, oncologic conditions. Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as prospective therapeutic procedures to restore microbial and metabolic balance in the gut. This review assesses the latest advancements, challenges, and therapeutic efficacy of FMT and LBPs, highlighting the need for standardization, safety, and long-term evaluation to optimize their clinical application.}, } @article {pmid39375173, year = {2024}, author = {Rognstad, ØB and Botteri, E and Hoff, G and Bretthauer, M and Gulichsen, E and Frigstad, SO and Holme, Ø and Randel, KR}, title = {Adverse events after colonoscopy in a randomised colorectal cancer screening trial.}, journal = {BMJ open gastroenterology}, volume = {11}, number = {1}, pages = {}, pmid = {39375173}, issn = {2054-4774}, mesh = {Humans ; Male ; Female ; *Colorectal Neoplasms/diagnosis ; *Colonoscopy/adverse effects/statistics & numerical data/methods ; Middle Aged ; *Early Detection of Cancer/methods ; Aged ; Norway/epidemiology ; Cross-Sectional Studies ; Risk Factors ; Sigmoidoscopy/adverse effects/methods/statistics & numerical data ; Occult Blood ; Gastrointestinal Hemorrhage/epidemiology/diagnosis ; Abdominal Pain/etiology ; }, abstract = {OBJECTIVE: Colonoscopy-related adverse events increase the burden of colorectal cancer (CRC) screening. This cross-sectional study evaluates adverse events during and after colonoscopy in a large, randomised CRC screening trial in Norway comparing sigmoidoscopy to immunochemical testing for faecal blood.

METHODS: We included all individuals who underwent colonoscopy at two screening centres between 2012 and 2020. From medical records, we retrieved data on adverse events during and within 30 days after colonoscopy and classified them according to the American Society for Gastrointestinal Endoscopy lexicon for endoscopic adverse events. Multivariable logistic regression models were fitted to identify risk factors for adverse events.

RESULTS: Of the 10 244 included individuals, 242 (2.4%) had at least one adverse event that was possibly, probably, or definitively related to the colonoscopy. 188 (1.8%) had mild adverse events, 50 (0.49%) had moderate, 3 (0.03%) had severe, and 1 had a fatal adverse event. The most frequent adverse events were lower gastrointestinal bleeding (0.86%), abdominal pain (0.48%), vasovagal reaction (0.39%), postpolypectomy syndrome (0.20%), and perforation (0.08%). 23 (0.22%) individuals had non-gastrointestinal adverse events. Risk factors associated with adverse events were older age, female sex, screening centre, anticoagulant therapy, number of polypectomies, size of lesion removed, presence of proximal lesion, and adenocarcinoma. Adverse event rates per endoscopist ranged from 0% to 4.9%.

CONCLUSION: Adverse events after colonoscopy of screening positives occurred in about 2 out of 100 procedures. Three-quarters of events were mild. Awareness of risk factors may help endoscopists to mitigate the risk.

TRIAL REGISTRATION NUMBER: NCT01538550.}, } @article {pmid39373714, year = {2024}, author = {Chen, Y and Yang, R and Qi, B and Shan, Z}, title = {Peptidoglycan-Chi3l1 interaction shapes gut microbiota in intestinal mucus layer.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {39373714}, issn = {2050-084X}, support = {2019YFA0803100//Ministry of Science and Technology of the People's Republic of China/ ; 32071129//National Natural Science Foundation of China/ ; 32170794//National Natural Science Foundation of China/ ; 202101AT070022//Yunnan Provincial Science and Technology Department/ ; 202201AT070196//Yunnan Provincial Science and Technology Department/ ; C619300A086//Science and Technological Talent Cultivation Plan of Yunnan Province/ ; K264202230211//Science and Technological Talent Cultivation Plan of Yunnan Province/ ; 202302AP370005//Yunnan Provincial Science and Technology Project at Southwest United Graduate School/ ; 2019YFA0802100//Ministry of Science and Technology of the People's Republic of China/ ; 202001AW070006//Yunnan Provincial Science and Technology Department/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Peptidoglycan/metabolism ; *Intestinal Mucosa/metabolism/microbiology ; *Chitinase-3-Like Protein 1/metabolism ; Colitis/microbiology/metabolism/chemically induced ; Mice, Inbred C57BL ; Humans ; Lactobacillus/metabolism ; }, abstract = {The balanced gut microbiota in intestinal mucus layer plays an instrumental role in the health of the host. However, the mechanisms by which the host regulates microbial communities in the mucus layer remain largely unknown. Here, we discovered that the host regulates bacterial colonization in the gut mucus layer by producing a protein called Chitinase 3-like protein 1 (Chi3l1). Intestinal epithelial cells are stimulated by the gut microbiota to express Chi3l1. Once expressed, Chi3l1 is secreted into the mucus layer where it interacts with the gut microbiota, specifically through a component of bacterial cell walls called peptidoglycan. This interaction between Chi3l1 and bacteria is beneficial for the colonization of bacteria in the mucus, particularly for Gram-positive bacteria like Lactobacillus. Moreover, a deficiency of Chi3l1 leads to an imbalance in the gut microbiota, which exacerbates colitis induced by dextran sodium sulfate. By performing fecal microbiota transplantation from Villin-cre mice or replenishing Lactobacillus in IEC[∆Chil1] mice, we were able to restore their colitis to the same level as that of Villin-cre mice. In summary, this study shows a 'scaffold model' for microbiota homeostasis by interaction between intestinal Chi3l1 and bacteria cell wall interaction, and it also highlights that an unbalanced gut microbiota in the intestinal mucus contributes to the development of colitis.}, } @article {pmid39373173, year = {2024}, author = {Randel, KR and Botteri, E and de Lange, T and Schult, AL and Eskeland, SL and El-Safadi, B and Norvard, ER and Bolstad, N and Bretthauer, M and Hoff, G and Holme, Ø}, title = {Performance of Faecal Immunochemical Testing for Colorectal Cancer Screening at Varying Positivity Thresholds.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.18314}, pmid = {39373173}, issn = {1365-2036}, support = {2015038//Helse Sør-Øst RHF/ ; //Norwegian Parliament/ ; }, abstract = {BACKGROUND: The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries.

AIMS: To explore the trade-off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial.

METHODS: We included first participation in biennial FIT screening for 47,265 individuals aged 50-74 years. Individuals with FIT > 15 μg Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen-detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150 μg/g.

RESULTS: At the 15 μg/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47 μg/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15 μg/g threshold. At 150 μg/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15 μg/g and 0.11% at 150 μg/g. Post-colonoscopy bleeding rates were 0.8% and 1.7%, respectively.

CONCLUSIONS: Increasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country-specific information on adverse events.

TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01538550.}, } @article {pmid39371609, year = {2024}, author = {Yuan, Y and Li, L and Wang, J and Myagmar, BO and Gao, Y and Wang, H and Wang, Z and Zhang, C and Zhang, X}, title = {Gut microbiota-derived acetate promotes long-term recovery through angiogenesis guided by lymphatic ingrowth in older adults with stroke.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1398913}, pmid = {39371609}, issn = {1662-4548}, abstract = {INTRODUCTION: Ischemic stroke is a leading cause of morbidity and mortality in older adults. Therefore, in this study, we sought to understand the interplay between the microbiota, gut, and brain in the context of stroke in older adults.

OBJECTIVE: To determine whether gut microbiota from younger individuals promotes recovery through angiogenesis in both elderly stroke patients and aged stroke mice, we explored the changes in gut microbiota and the correlation between short-chain fatty acids (SCFAs) and angiogenesis in the aged stroke population. Then, we altered the gut microbiome in aged mice by transplanting microbiota from younger donors before inducing experimental stroke to explore the mechanism by which gut microbiota-derived SCFAs promote angiogenesis.

METHODS: Part I: We conducted a single-center, double-blind trial to compare gut microbiota diversity and SCFA levels in fecal samples from older stroke patients with those from younger stroke patients. Additionally, we measured levels of vascular endothelial growth factor (VEGF) and VEGFC levels in plasma to assess their correlation with SCFA levels. Part II: We performed fecal microbiota transplantation (FMT) 3 days before inducing ischemic stroke in aged male mice (16-18) via distal middle cerebral artery occlusion (dMCAO). The FMT was conducted using gut microbiomes from either young donors (2-3 months) or aged donors (16-18 months).

RESULTS: In older stroke patients, gut microbiota diversity was significantly reduced compared to that in younger stroke patients. Furthermore, levels of acetate, a bacterially derived SCFA, were lower and positively correlated with angiogenesis markers (VEGF and VEGF-C). In aged stroke mice, transplantation of young microbiota improved stroke outcomes by promoting angiogenesis, which was facilitated by lymphatic ingrowth into the cortex. This protective effect was linked to gut microbiota-derived acetate, which enhanced lymphangiogenesis by replenishing acetyl coenzyme A.

CONCLUSIONS: (a) Gut microbiota-derived acetate promotes angiogenesis post-stroke and (b) lymphatic ingrowth into the cerebral cortex was observed in post-dMCAO mice. These findings suggest that selectively promoting SCFA-producing bacteria, particularly acetate-producers, could be a promising therapeutic strategy to reduce functional impairments in older stroke subjects.}, } @article {pmid39371270, year = {2024}, author = {Dong, H and Li, R and Zhao, N and Dadhania, DM and Suthanthiran, M and Lee, JR and Ling, W}, title = {Antibiotic subclasses differentially perturb the gut microbiota in kidney transplant recipients.}, journal = {Frontiers in transplantation}, volume = {3}, number = {}, pages = {1400067}, pmid = {39371270}, issn = {2813-2440}, abstract = {INTRODUCTION: The impact of antibiotics on the gut microbiota in kidney transplant recipients is not well characterized. In this study, we determine the impact of different subclasses of antibiotics on the gut microbiota in a cohort of 168 kidney transplant recipients.

METHODS: Gut microbiome profiling was performed on 510 fecal specimens using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We classified fecal specimens by antibiotic exposure into 5 categories: Beta-lactam, Fluoroquinolone (FQ), Beta-lactam & FQ Group, Other Antibiotics, and No Antibiotic (No Abx). Mixed-effects regression models were utilized to identify changes in microbial diversity and in the centered log-ratio (CLR) transformed abundance of genera while adjusting for important covariates.

RESULTS: Antibiotic administration was associated with a significant decrease in the Shannon alpha diversity index, a decreased abundance of 11 taxa including Eubacterium and Ruminococcus, and an increased abundance of 16 taxa including Enterococcus and Staphylococcus. Exposure to Beta-lactam antibiotics was associated with an increased abundance of 10 taxa including Enterococcus and a decreased abundance of 5 taxa including Eubacterium while exposure to FQ antibiotics was associated with an increased abundance of 3 taxa and a decreased abundance of 4 taxa including Ruminococcus.

CONCLUSIONS: Beta-lactam antibiotics and FQ antibiotics have a profound impact on the gut microbiota in kidney transplant recipients. Given the link of the gut microbiota to infectious complications, antibiotic associated changes in the microbiota may lead to an increased risk for further infections.}, } @article {pmid39371172, year = {2024}, author = {Akagbosu, CO and McCauley, KE and Namasivayam, S and Romero-Soto, HN and O'Brien, W and Bacorn, M and Bohrnsen, E and Schwarz, B and Mistry, S and Burns, AS and Perez-Chaparro, PJ and Chen, Q and LaPoint, P and Patel, A and Krausfeldt, LE and Subramanian, P and Sellers, BA and Cheung, F and Apps, R and Douagi, I and Levy, S and Nadler, EP and Hourigan, SK}, title = {Gut microbiome shifts in adolescents after sleeve gastrectomy with increased oral-associated taxa and pro-inflammatory potential.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.09.16.24313738}, pmid = {39371172}, abstract = {BACKGROUND: Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown.

OBJECTIVES: 1) To comprehensively examine gut microbiome and metabolome changes after laparoscopic vertical sleeve gastrectomy (VSG) in adolescents and 2) to assess whether the microbiome/metabolome changes observed with VSG influence phenotype using germ-free murine models.

DESIGN: 1) A longitudinal observational study in adolescents undergoing VSG with serial stool samples undergoing shotgun metagenomic microbiome sequencing and metabolomics (polar metabolites, bile acids and short chain fatty acids) and 2) a human-to-mouse fecal transplant study.

RESULTS: We show adolescents exhibit significant gut microbiome and metabolome shifts several months after VSG, with increased alpha diversity and notably with enrichment of oral-associated taxa. To assess causality of the microbiome/metabolome changes in phenotype, pre-VSG and post-VSG stool was transplanted into germ-free mice. Post-VSG stool was not associated with any beneficial outcomes such as adiposity reduction compared pre-VSG stool. However, post-VSG stool exhibited an inflammatory phenotype with increased intestinal Th17 and decreased regulatory T cells. Concomitantly, we found elevated fecal calprotectin and an enrichment of proinflammatory pathways in a subset of adolescents post-VSG.

CONCLUSION: We show that in some adolescents, microbiome changes post-VSG may have inflammatory potential, which may be of importance considering the increased incidence of inflammatory bowel disease post-VSG.

Bariatric surgery is highly effective in achieving weight loss in children and adolescents with severe obesity, however the underlying mechanisms are incompletely understood, and gut microbiome changes are unknown.

WHAT THIS STUDY ADDS: Significant gut microbiome and metabolome shifts were found several months after vertical sleeve gastrectomy in adolescents, notably with enrichment of oral-associated taxa. Using human to germ-free mice fecal transplant studies, the post-surgery changes in the gut microbiome/metabolome were shown to have inflammatory potential. Furthermore, raised fecal calprotectin and inflammatory systemic pathways were seen in a subset of adolescents post-surgery.

These findings may be of importance given the growing recognition of an increased incidence of inflammatory bowel disease after bariatric surgery and warrants further investigation.}, } @article {pmid39370012, year = {2024}, author = {Wang, J and Shen, Y and Li, L and Li, L and Zhang, J and Li, M and Qiu, F}, title = {Lycopene attenuates D-galactose-induced memory and behavioral deficits by mediating microbiota-SCFAs-gut-brain axis balance in female CD-1 mice.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109777}, doi = {10.1016/j.jnutbio.2024.109777}, pmid = {39370012}, issn = {1873-4847}, abstract = {Aging impairs cognitive function, whereas nutritional intervention can delay aging and age-related diseases. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, the effects of LYC on memory and behavioral deficits induced by D-galactose (D-gal) treatment and the relative contribution of LYC-derived gut microbiota in these process were investigated. Results demonstrated that LYC showed effective protection on D-gal induced cognitive deficit and neuronal damage. Moreover, LYC treatment has beneficial effects on gut barrier damage, microbiota dysbiosis and levels of SCFAs in D-gal-induced subacute aging mice. Next, fecal microbiota transplantation (FMT) experiment was performed and increased SCFAs were observed in mice received stools from D-gal+LYC group when compared with D-gal-FMT group. Thus, we added SCFAs treatment served as a control group in order to evaluated whether the alterations of gut-brain axis could be attributed to LYC-reshaped gut microbiota and SCFAs. Results showed that recipient mice received SCFAs and stools from D-gal+LYC group have similar beneficial effects in improving gut and brain function, demonstrated as: improved intestinal health via elevating antioxidant enzymes contents, increasing the expressions of tight junctions proteins and protecting gut barrier, enhanced mice working memory capacity via alleviating hippocampal neurons impairment, improving synaptic function and enhancing mitochondrial function in the intestinal pseudo-aseptic mice. In conclusion, our results demonstrated that LYC-derived microbiome played a pivotal role in the regulation of cognitive functions during aging and enhanced SCFAs formation might be an important signaling molecule connecting gut microbiome and brain.}, } @article {pmid39366468, year = {2024}, author = {Allegretti, JR and Kelly, CR and Louie, T and Fischer, M and Hota, S and Misra, B and Van Hise, NW and Yen, E and Bullock, JS and Silverman, M and Davis, I and McGill, SK and Pardi, DS and Orenstein, R and Grinspan, A and El-Nachef, N and Feuerstadt, P and Borody, TJ and Khanna S, S and Budree, S and Kassam, Z}, title = {Safety and Tolerability of CP101, a full spectrum, oral microbiome therapeutic for the prevention of recurrent C. difficile infection: A Phase 2 Randomized Controlled Trial.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.09.030}, pmid = {39366468}, issn = {1528-0012}, abstract = {BACKGROUND AND AIMS: Recurrent Clostridioides difficile infections (CDI) remain common. While novel microbiome therapeutics gain approval, the efficacy of a full spectrum, oral microbiome therapeutics is unknown. This study aimed to determine the safety and efficacy of CP101, an orally administered microbiome therapeutic, to restore a diverse microbiome and prevent recurrent CDI in a broad population.

METHODS: We conducted a multi-center, phase 2, double-blind, randomized, placebo-controlled trial in adults with recurrent CDI. Participants with one or more CDI recurrences and diagnosis by PCR or toxin EIA for the qualifying episode were included. Participants were randomized 1:1 to receive a single oral dose of either CP101 (∼ 6 x 10[11] CFU of lyophilized microbial cells) or placebo after standard-of-care (SOC) antibiotics. The primary efficacy endpoint was the proportion of participants without CDI recurrence through Week 8. Safety, efficacy and microbiome endpoints were evaluated through Week 8 and 24.

RESULTS: 198 participants were analyzed; CP101 (n=102) and placebo (n=96). Overall, 27.5% with a first recurrence and 62.7% diagnosed by PCR-based testing. The proportion without CDI recurrence through Week 8 was significantly higher in the CP101 group compared to placebo (74.5% [76/102] vs 61.5% [59/96], p=0.0488) with durable efficacy observed through Week 24 (73.5% [75/102] vs 59.4% [57/96], p=0.0347). Similar efficacy was observed regardless of diagnostic modality or number of CDI recurrences. Rapid and durable increase in microbiome diversity was observed in the CP101 group compared to placebo. The incidence of adverse events was similar between the two groups.

CONCLUSIONS: CP101 was superior to placebo in reducing recurrent CDI with a safety profile similar to placebo. https://clinicaltrials.gov/study/NCT03110133.}, } @article {pmid39364128, year = {2024}, author = {Guo, J and Yang, L}, title = {Regulation effect of the intestinal flora and intervention strategies targeting the intestinal flora in alleviation of pulmonary fibrosis development.}, journal = {Bioscience of microbiota, food and health}, volume = {43}, number = {4}, pages = {293-299}, pmid = {39364128}, issn = {2186-6953}, abstract = {Pulmonary fibrosis is an end-stage respiratory disease characterized by fibroblast proliferation and accumulation of extracellular matrix and collagen, which is accompanied by inflammatory damage. The disease is mainly based on pulmonary dysfunction and respiratory failure, the incidence of it is increasing year by year, and the current treatment methods for it are limited. In recent years, it has been found that gut microbes play a crucial role in the pathogenesis and development of pulmonary fibrosis. The microecological disturbance caused by changes in the composition of the intestinal flora can affect the course of pulmonary fibrosis. The regulatory network or information exchange system for gut-lung crosstalk is called the "gut-lung axis". This review focuses on the frontier research on entero-pulmonary regulation in pulmonary fibrosis and on intervention strategies for changing the gut microbiota to improve pulmonary fibrosis, including fecal microbiota transplantation, traditional Chinese medicine interventions, and supplementation with probiotics. In addition, the present problems in this field are also raised in order to provide strong theoretical and strategic support for the future exploration of regulatory mechanisms and therapeutic drug development. This paper reviews the interaction of the intestinal flora with pulmonary fibrosis, introduces the research progress for improving pulmonary fibrosis through interventions targeted at the intestinal flora, and provides new ideas for the treatment of pulmonary fibrosis.}, } @article {pmid39364121, year = {2024}, author = {Mao, Z and Zhang, J and Guo, L and Wang, X and Zhu, Z and Miao, M}, title = {Therapeutic approaches targeting the gut microbiota in ischemic stroke: current advances and future directions.}, journal = {Bioscience of microbiota, food and health}, volume = {43}, number = {4}, pages = {321-328}, pmid = {39364121}, issn = {2186-6953}, abstract = {Ischemic stroke (IS) is the predominant form of stroke pathology, and its clinical management remains constrained by therapeutic time frame. The gut microbiota (GM), comprising a multitude of bacterial and archaeal cells, surpasses the human cell count by approximately tenfold and significantly contributes to the human organism's growth, development, and overall well-being. The microbiota-gut-brain axis (MGBA) in recent years has established a strong association between gut microbes and the brain, demonstrating their intricate involvement in the progression of IS. The regulation of IS by the GM, encompassing changes in composition, abundance, and distribution, is multifaceted, involving neurological, endocrine, immunological, and metabolic mechanisms. This comprehensive understanding offers novel insights into the therapeutic approaches for IS. The objective of this paper is to examine the mechanisms of interaction between the GM and IS in recent years, assess the therapeutic effects of the GM on IS through various interventions, such as dietary modifications, probiotics, fecal microbiota transplantation, and antibiotics, and offer insights into the potential clinical application of the GM in stroke treatment.}, } @article {pmid39362719, year = {2024}, author = {Morgan, TR}, title = {Emerging Pharmacologic Treatments for Alcohol-Associated Hepatitis: Current Status and Future Landscape.}, journal = {Clinics in liver disease}, volume = {28}, number = {4}, pages = {747-760}, doi = {10.1016/j.cld.2024.06.014}, pmid = {39362719}, issn = {1557-8224}, mesh = {Humans ; *Hepatitis, Alcoholic/drug therapy/therapy ; Antioxidants/therapeutic use ; Interleukin-22 ; Acetylcysteine/therapeutic use ; Fecal Microbiota Transplantation ; Granulocyte Colony-Stimulating Factor/therapeutic use ; }, abstract = {Several treatments have shown efficacy in preliminary alcohol-associated hepatitis trials. Interleukin-22 improved Model of End-stage Liver Disease score and aminotransferases in a phase II trial. The endogenous cholesterol derivative, larsucosterol, improved outcomes in a multi-center United States or European phase II trial. The antioxidants N-acetylcysteine and metadoxine improved survival in large trials. Trials from India report improved survival with granulocyte-colony stimulating factor, as well as improved outcome among patients receiving fecal microbiota transfer. Translational studies suggest that phage treatment of cytolytic Enterococcus faecalis may reduce liver injury.}, } @article {pmid39362714, year = {2024}, author = {Yang, Y and Schnabl, B}, title = {Gut Bacteria in Alcohol-Associated Liver Disease.}, journal = {Clinics in liver disease}, volume = {28}, number = {4}, pages = {663-679}, pmid = {39362714}, issn = {1557-8224}, support = {I01 BX004594/BX/BLRD VA/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; R37 AA020703/AA/NIAAA NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Liver Diseases, Alcoholic/microbiology/therapy ; *Dysbiosis ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Bacteriophages ; }, abstract = {Alcohol-associated liver disease (ALD) poses a significant global public health challenge, with high patient mortality rates and economic burden. The gut microbiome plays an important role in the onset and progression of alcohol-associated liver disease. Excessive alcohol consumption disrupts the intestinal barrier, facilitating the entry of harmful microbes and their products into the liver, exacerbating liver damage. Dysbiosis, marked by imbalance in gut bacteria, correlates with ALD severity. Promising microbiota-centered therapies include probiotics, phages, and fecal microbiota transplantation. Clinical trials demonstrate the potential of these interventions to improve liver function and patient outcomes, offering a new frontier in ALD treatment.}, } @article {pmid39362281, year = {2024}, author = {Headley, SA and Chapman, DJ and Germain, MJ and Evans, EE and Madsen, KL and Miele, EM and Kirton, K and Loseke, J and Cornelius, A and Martin, B and Nindl, B and Park, H and Vaziri, ND and Ikizler, TA}, title = {Effects of high amylose resistant starch on gut microbiota and uremic toxin levels in patients with stage G3a-G4 chronic kidney disease: a randomized trial.}, journal = {Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.jrn.2024.09.005}, pmid = {39362281}, issn = {1532-8503}, abstract = {OBJECTIVE: This study was designed to determine the effect of 16 weeks of supplementation with Hi-maize 260 resistant starch on the gut microbiota, uremic toxins (indoxyl sulfate and p-cresyl sulfate), markers of inflammation and oxidative stress along with vascular function in patients with stage G3a-G4 chronic kidney disease (CKD).

DESIGN: & Methods: This was a double-blind, placebo-controlled, parallel-arm, randomized controlled trial. Sixty-eight patients with stage G3a-G4 CKD were randomized to either resistant starch with usual care or placebo and usual care. Patients attended four testing sessions: two baseline visits, and follow-up visits at 8 and 16 weeks. Fasting blood samples, resting brachial and central blood pressures, along with arterial stiffness, were collected at visits (1 or 2), and weeks 8 and 16. A stool sample was collected for analysis of microbial composition at baseline and week 16. Patients were randomized after the baseline visits.

RESULTS: Patients receiving the resistant starch had a reduction in p-cresyl sulfate at week 16. This reduction was associated with a decrease in microbial α-diversity between baseline and week 16 (Chao1 p=0.014, Shannon p=0.017, PD p= 0.046, and Simpson p=0.017) as well as increases in Subdoligranulum (p=0.03) and Oscillospiraceae UCG 002 (p=0.02) and decreases in Bacteroides (p=0.009).There were no changes in microbial beta diversity and other biomarkers or markers of vascular function following the 16-week period Conclusion: Sixteen weeks of supplementation of resistant starch in patients with stage G3a-G4 CKD led to changes in microbial composition that were associated with a significant reduction in p-cresyl sulfate.}, } @article {pmid39360770, year = {2024}, author = {Verma, N and Vinod, AP and Singal, AK}, title = {The pharmacological management of alcohol-related cirrhosis: what's new?.}, journal = {Expert opinion on pharmacotherapy}, volume = {}, number = {}, pages = {1-19}, doi = {10.1080/14656566.2024.2409941}, pmid = {39360770}, issn = {1744-7666}, abstract = {INTRODUCTION: Alcohol use disorder (AUD) is present in the majority of patients with alcohol-associated liver disease (ALD), which leads to about 50% of cirrhosis-related hospitalizations and over 25% of deaths worldwide. Patients with ALD often present at an advanced stage, like cirrhosis with its complications and alcohol-associated hepatitis (AH), which has high short-term mortality. Current treatments are limited, with the limited benefit of glucocorticoids only in the short-term among patients with AH, highlighting an urgent need for novel therapies.

AREAS COVERED: This review applies the PIRO (Predisposition, Injury, Response, Organ dysfunction) concept to ALD, understanding an ongoing process of liver damage, and opportunities to address and halt the progression. We also highlight the significance of treating AUD to improve long-term outcomes in ALD.

EXPERT OPINION: Personalized therapies targeting specific genetic profiles and multiple pathogenic pathways are crucial in managing ALD. Emerging therapies like gut-liver-brain axis modulators like fecal microbiota transplant and probiotics, interleukin-22, granulocyte-colony stimulating factor (G-CSF) and stem cells, epigenetic regulators of inflammation and regeneration are encouraging with the potential of efficacy in patients with ALD. Liver transplantation (LT) is a definitive therapy for advanced cirrhosis with increasing impetus on early LT select patients with active alcohol use.}, } @article {pmid39360586, year = {2024}, author = {Cibulková, I and Řehořová, V and Wilhelm, M and Soukupová, H and Hajer, J and Duška, F and Daňková, H and Cahová, M}, title = {Evaluating Bacterial Viability in Faecal Microbiota Transplantation: A Comparative Analysis of In Vitro Cultivation and Membrane Integrity Methods.}, journal = {Journal of clinical laboratory analysis}, volume = {}, number = {}, pages = {e25105}, doi = {10.1002/jcla.25105}, pmid = {39360586}, issn = {1098-2825}, support = {IN 00023001//Institute for Clinical and Experimental medicine - IKEM/ ; //Institutional Support of FNKV University Hospital/ ; VAT No 0907206//Donatio Intensivistam Endowement fund/ ; //Cooperation Intensive Care Medicine Programme of Charles University/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a developing therapy for disorders related to gut dysbiosis. Despite its growing application, standardised protocols for FMT filtrate preparation and quality assessment remain undeveloped. The viability of bacteria in the filtrate is crucial for FMT's efficacy and for validating protocol execution. We compared two methods-in vitro cultivation and membrane integrity assessment-for their accuracy, reproducibility and clinical applicability in measuring bacterial viability in frozen FMT stool filtrate.

METHODS: Bacterial viability in stool filtrate was evaluated using (i) membrane integrity through fluorescent DNA staining with SYTO9 and propidium iodide, followed by flow cytometry and (ii) culturable bacteria counts (colony-forming units, CFU) under aerobic or anaerobic conditions.

RESULTS: Using different types of samples (pure bacterial culture, stool of germ-free and conventionally bred mice, native and heat-treated human stool), we refined the bacterial DNA staining protocol integrated with flow cytometry for assessment of bacterial viability in frozen human stool samples. Both the membrane integrity-based and cultivation-based methods exhibited significant variability in bacterial viability across different FMT filtrates, without correlation. The cultivation-based method showed a mean coefficient of variance of 30.3%, ranging from 7.4% to 60.1%. Conversely, the membrane integrity approach yielded more reproducible results, with a mean coefficient of variance for viable cells of 6.4% ranging from 0.2% to 18.2%.

CONCLUSION: Bacterial viability assessment in stool filtrate using the membrane integrity method offers robust and precise data, making it a suitable option for faecal material evaluation in FMT. In contrast, the cultivation-dependent methods produce inconsistent outcomes.}, } @article {pmid39360560, year = {2024}, author = {Arzamendi, MJ and Habibyan, YB and Defaye, M and Shute, A and Baggio, CH and Chan, R and Ohland, C and Bihan, DG and Lewis, IA and Sharkey, KA and McCoy, KD and Altier, C and Geuking, MB and Nasser, Y}, title = {Sex-specific post-inflammatory dysbiosis mediates chronic visceral pain in colitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2409207}, pmid = {39360560}, issn = {1949-0984}, mesh = {Male ; Female ; Animals ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; *Visceral Pain/microbiology/physiopathology/metabolism ; *Colitis/microbiology ; Mice ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Sex Factors ; Bacteria/classification/isolation & purification/genetics/metabolism ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Dextran Sulfate ; Disease Models, Animal ; Fatty Acids, Volatile/metabolism/analysis ; Chronic Pain/microbiology/physiopathology ; Inflammation/microbiology ; Hyperalgesia/microbiology ; }, abstract = {BACKGROUND: Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. Visceral pain and the microbiome exhibit sex-dependent interactions, while visceral pain in IBD shows a sex bias. Our aim was to evaluate whether post-inflammatory microbial perturbations contribute to visceral hypersensitivity in a sex-dependent manner.

METHODS: Males, cycling females, ovariectomized, and sham-operated females were given dextran sodium sulfate to induce colitis and allowed to recover. Germ-free recipients received sex-appropriate and cross-sex fecal microbial transplants (FMT) from post-inflammatory donor mice. Visceral sensitivity was assessed by recording visceromotor responses to colorectal distention. The composition of the microbiota was evaluated via 16S rRNA gene V4 amplicon sequencing, while the metabolome was assessed using targeted (short chain fatty acids - SCFA) and semi-targeted mass spectrometry.

RESULTS: Post-inflammatory cycling females developed visceral hyperalgesia when compared to males. This effect was reversed by ovariectomy. Both post-inflammatory males and females exhibited increased SCFA-producing species, but only males had elevated fecal SCFA content. FMT from post-inflammatory females transferred visceral hyperalgesia to both males and females, while FMT from post-inflammatory males could only transfer visceral hyperalgesia to males.

CONCLUSIONS: Female sex, hormonal status as well as the gut microbiota play a role in pain modulation. Our data highlight the importance of considering biological sex in the evaluation of visceral pain.}, } @article {pmid39358432, year = {2024}, author = {Zhi, W and Li, A and Wang, Q and Yuan, X and Qing, J and Zhang, C and Wang, Y and Li, Y}, title = {Safety and efficacy assessment of fecal microbiota transplantation as an adjunctive treatment for IgA nephropathy: an exploratory clinical trial.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {22935}, pmid = {39358432}, issn = {2045-2322}, support = {82170716//National Science Foundation of China/ ; }, mesh = {Humans ; *Glomerulonephritis, IGA/therapy ; Male ; Female ; Adult ; *Fecal Microbiota Transplantation/methods/adverse effects ; *Gastrointestinal Microbiome ; Middle Aged ; Treatment Outcome ; Cytokines/blood/metabolism ; }, abstract = {To assess the safety and efficacy of fecal microbiota transplantation (FMT) as an adjunctive therapeutic intervention for IgA nephropathy (IgAN). Fifteen patients with IgA nephropathy were recruited based on inclusion and exclusion criteria and underwent FMT using enteric microbial capsules. Clinical indicators, intestinal microbiota and metabolomic profiles, as well as changes in serum immune cells and cytokines, were monitored before and after FMT. No severe adverse reactions were observed in the subjects. After FMT, there was a reduction in the 24-h urinary protein quantification in subjects. The relative abundances of Phocaeicola_vulgatus, Bacteroides_uniformis, Prevotella_copri, Phocaeicola_dorei, Bacteroides_ovatus, Bacteroides_xylanisolvens, Parabacteroides _distasonis, Bifidobacterium_pseudocatenulatum, Bacteroides_sp._HF-162, and Bifidobacterium_longum changed after FMT. In terms of intestinal metabolites, the levels of acylcarnitine18:0 (ACar.18:0), cotinine, N-arachidonoyl-L-serine, phosphatidylcholine (PC. (18:3e/22:6)), serotonin, and fumagillin showed significant changes. Flow cytometry analysis showed the absolute count of plasma B cells decreased in subjects, and this change correlated with alterations in the intestinal microbiota and metabolites. This study preliminarily evaluates the safety and efficacy of FMT in patients with IgAN. No significant adverse reactions were observed, and the administration of FMT alongside ACEI/ARB therapy was effective in reducing urinary protein levels in patients with IgAN, a process that may be associated with B-cell immunity.}, } @article {pmid39358252, year = {2024}, author = {Tanigawa, H and Kohara, K and Onizuka, M and Otsuka, A and Suzuki, Y and Hirohara, M}, title = {[Survey of Preventing Exposure Regarding Sweat in Patients Receiving Antineoplastic Agents at Base Hospitals for Promoting Hematopoietic Stem Cell].}, journal = {Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan}, volume = {144}, number = {10}, pages = {957-962}, doi = {10.1248/yakushi.24-00098}, pmid = {39358252}, issn = {1347-5231}, mesh = {Humans ; *Antineoplastic Agents/adverse effects ; *Occupational Exposure/prevention & control ; *Hematopoietic Stem Cell Transplantation ; Surveys and Questionnaires ; *Sweat/chemistry ; Personal Protective Equipment ; Gloves, Protective ; Guideline Adherence ; Clothing ; Practice Guidelines as Topic ; }, abstract = {This survey aimed to reveal the actual preventing exposure for handling of clothing and sweat of patients treated with anticancer drugs, following the publication of "Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 Edition" (Guideline 2019). A survey was conducted among nurses working at 95 hematopoietic stem cell transplantation promotion base hospitals from September 1, 2023 to October 31, 2023. The response rate was 84.2% (80 facilities). Of the respondents, 45% wore gloves when touching patients' skin to administer anticancer drugs. Almost the nurses identified "urine" and "feces" as fluids on contaminated linen, while 14.1% also identified "sweat." For new staff, the results for preventing exposure education on "if touching the patients' skin" and "if handling clothing and linen" were 23.8% and 34.9%, respectively. This survey shows that nurses may not be following the Guideline 2019 for use of personal protective equipment and handling of clothes. Medical institutions handling anticancer drugs need to educate their staff for preventing occupational exposure.}, } @article {pmid39355844, year = {2024}, author = {Ning, S and Zhang, Z and Zhou, C and Wang, B and Liu, Z and Feng, B}, title = {Cross-talk between macrophages and gut microbiota in inflammatory bowel disease: a dynamic interplay influencing pathogenesis and therapy.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1457218}, pmid = {39355844}, issn = {2296-858X}, abstract = {Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic immune-mediated gastrointestinal disorders. The etiology of IBD is multifactorial, involving genetic susceptibility, environmental factors, and a complex interplay between the gut microbiota and the host's immune system. Intestinal resident macrophages play an important role in the pathogenesis and progress of IBD, as well as in maintaining intestinal homeostasis and facilitating tissue repair. This review delves into the intricate relationship between intestinal macrophages and gut microbiota, highlighting their pivotal roles in IBD pathogenesis. We discuss the impact of macrophage dysregulation and the consequent polarization of different phenotypes on intestinal inflammation. Furthermore, we explore the compositional and functional alterations in gut microbiota associated with IBD, including the emerging significance of fungal and viral components. This review also examines the effects of current therapeutic strategies, such as 5-aminosalicylic acid (5-ASA), antibiotics, steroids, immunomodulators, and biologics, on gut microbiota and macrophage function. We underscore the potential of fecal microbiota transplantation (FMT) and probiotics as innovative approaches to modulate the gut microbiome in IBD. The aim is to provide insights into the development of novel therapies targeting the gut microbiota and macrophages to improve IBD management.}, } @article {pmid39355779, year = {2024}, author = {Zhang, S and Lu, J and Jin, Z and Xu, H and Zhang, D and Chen, J and Wang, J}, title = {Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1459655}, pmid = {39355779}, issn = {1663-9812}, abstract = {BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective in preventing or mitigating the progression of AD. An increasing number of recent studies support the hypothesis that the gut microbiome and its metabolites may be associated with upstream regulators of AD pathology.

METHODS: In this review, we comprehensively explore the potential mechanisms and currently available interventions targeting the microbiome for the improvement of AD. Our discussion is structured around modern research advancements in AD, the bidirectional communication between the gut and brain, the multi-target regulatory effects of microbial metabolites on AD, and therapeutic strategies aimed at modulating gut microbiota to manage AD.

RESULTS: The gut microbiota plays a crucial role in the pathogenesis of AD through continuous bidirectional communication via the microbiota-gut-brain axis. Among these, microbial metabolites such as lipids, amino acids, bile acids and neurotransmitters, especially sphingolipids and phospholipids, may serve as central components of the gut-brain axis, regulating AD-related pathogenic mechanisms including β-amyloid metabolism, Tau protein phosphorylation, and neuroinflammation. Additionally, interventions such as probiotic administration, fecal microbiota transplantation, and antibiotic use have also provided evidence supporting the association between gut microbiota and AD. At the same time, we propose an innovative strategy for treating AD: a healthy lifestyle combined with targeted probiotics and other potential therapeutic interventions, aiming to restore intestinal ecology and microbiota balance.

CONCLUSION: Despite previous efforts, the molecular mechanisms by which gut microbes act on AD have yet to be fully described. However, intestinal microorganisms may become an essential target for connecting the gut-brain axis and improving the symptoms of AD. At the same time, it requires joint exploration by multiple centers and multiple disciplines.}, } @article {pmid39353099, year = {2024}, author = {Loman, BR and Alzoubi, Z and Lynch, AJ and Jaggers, RM and Jordan, K and Grant, CV and Rogers, LK and Pyter, LM and Bailey, MT}, title = {Paclitaxel chemotherapy disrupts microbiota-enterohepatic bile acid metabolism in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2410475}, pmid = {39353099}, issn = {1949-0984}, mesh = {Animals ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Mice, Inbred C57BL ; *Liver/metabolism/drug effects ; Male ; Hepatocytes/metabolism/drug effects ; Lipopolysaccharides/metabolism ; Colon/microbiology/metabolism/drug effects/pathology ; Bacteria/classification/metabolism/genetics/isolation & purification/drug effects ; }, abstract = {Balanced interactions between the enteric microbiota and enterohepatic organs are essential to bile acid homeostasis, and thus normal gastrointestinal function. Disruption of these interactions by cancer treatment instigates bile acid malabsorption, leading to treatment delays, malnutrition, and decreased quality of life. However, the nature of chemotherapy-induced bile acid malabsorption remains poorly characterized with limited treatment options. Therefore, this study sought to characterize changes in hepatic, enteric, and microbial bile acid metabolism in a mouse model of chemotherapy-induced toxicity. Consistent with clinical bile acid malabsorption, chemotherapy increased fecal excretion of primary bile acids and water, while diminishing microbiome diversity, secondary bile acid formation, and small intestinal bile acid signaling. We identified new contributors to pathology of bile acid malabsorption in the forms of lipopolysaccharide-induced cholestasis and colonic crypt hyperplasia from reduced secondary bile acid signaling. Chemotherapy reduced markers of hepatic bile flow and bile acid synthesis, elevated markers of fibrosis and endotoxemia, and altered transcription of genes at all stages of bile acid metabolism. Primary hepatocytes exposed to lipopolysaccharide (but not chemotherapy) replicated chemotherapy-induced transcriptional differences, while gut microbial transplant into germ-free mice replicated very few differences. In the colon, chemotherapy-altered bile acid profiles (particularly higher tauromuricholic acid and lower hyodeoxycholic acid) coincided with crypt hyperplasia. Exposing primary colonoids to hyodeoxycholic acid reduced proliferation, while gut microbiota transplant enhanced proliferation. Together, these investigations reveal complex involvement of the entire microbiota-enterohepatic axis in chemotherapy-induced bile acid malabsorption. Interventions to reduce hepatic lipopolysaccharide exposure and enhance microbial bile acid metabolism represent promising co-therapies to cancer treatment.}, } @article {pmid39351254, year = {2024}, author = {Zhang, ZN and Sang, LX}, title = {Dual-targeted treatment for inflammatory bowel disease: Whether fecal microbiota transplantation can be an important part of it.}, journal = {World journal of gastroenterology}, volume = {30}, number = {36}, pages = {4025-4030}, pmid = {39351254}, issn = {2219-2840}, mesh = {*Fecal Microbiota Transplantation/methods/adverse effects ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Inflammatory Bowel Diseases/therapy/microbiology/immunology ; Treatment Outcome ; Combined Modality Therapy/methods ; Feces/microbiology ; Biological Products/therapeutic use ; Gastrointestinal Agents/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease. With the emergence of biologics and other therapeutic methods, two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD. Although treatment strategies for IBD are being optimized, their efficacy and risks still warrant further consideration. This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation (FMT) may have for use in combination therapy for IBD. We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment. In this new therapy regimen, FMT represents a promising combination therapy.}, } @article {pmid39351201, year = {2024}, author = {Frith, ME and Kashyap, PC and Linden, DR and Theriault, B and Chang, EB}, title = {Microbiota-dependent early-life programming of gastrointestinal motility.}, journal = {iScience}, volume = {27}, number = {10}, pages = {110895}, pmid = {39351201}, issn = {2589-0042}, abstract = {Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNA sequencing (RNA-seq) of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later-or not at all-showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early-life microbiome in later-life dysmotility.}, } @article {pmid39350740, year = {2024}, author = {Jochumsen, EA and Kragsnaes, MS and Nilsson, AC and Rasmussen, KF and Ellingsen, T and Juul, MA and Kjeldsen, J and Holm, DK}, title = {'Does this fecal microbiota transplant work?' Quality assurance of capsule based fecal microbiota transplant production.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/00365521.2024.2401460}, pmid = {39350740}, issn = {1502-7708}, abstract = {BACKGROUND: Fecal Microbiota Transplant (FMT) is an effective treatment for recurring Clostridioides Difficile Infections (rCDI). FMT administered via oral capsules (caFMT) offers several practical advantages to conventional liquid FMT. We began using caFMT in 2021 imported from an external institution. Based on similar production methods, we began our own caFMT production in 2022. We aimed to evaluate the quality of our caFMT.

STUDY DESIGN AND METHODS: We created a database of all FMT treatments (n = 180) provided by our institution. Quality of all FMT was evaluated by treatment success rates. We compared our caFMT to the imported caFMT.

RESULTS: Our caFMT yielded similar success rates compared to that of the imported caFMT, 65% (CI 95% 58-72%) and 72% (CI 95% 66-79%) respectively. FMT administered via colonoscopy had a significantly higher success rate, 79% (CI 95% 73-85%) than own our caFMT and other routes of administration. The combined success rate of treatments increased notably for all routes of administration when repeating FMT after prior failure.

DISCUSSION: The fact that our caFMT compared similarly to the imported caFMT was viewed as a success in terms of quality assurance. Our caFMT had a slightly lower success rates compared to data from other studies, but could be affected by several other factors than our FMT-production methods. A lower success rate of caFMT compared to FMT via colonoscopy is acceptable due to the practical advantages offed by caFMT. Our study serves as a practical example, proving that of the standardization of caFMT production is indeed viable.}, } @article {pmid39349020, year = {2024}, author = {Dutta, R and Stothers, L and Ackerman, AL}, title = {Manipulating the Gut Microbiome in Urinary Tract Infection-Prone Patients.}, journal = {The Urologic clinics of North America}, volume = {51}, number = {4}, pages = {525-536}, doi = {10.1016/j.ucl.2024.07.016}, pmid = {39349020}, issn = {1558-318X}, mesh = {Humans ; *Urinary Tract Infections/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Female ; Anti-Bacterial Agents/therapeutic use ; Vaccinium macrocarpon ; }, abstract = {Although antibiotics remain the mainstay of urinary tract infection treatment, many affected women can be caught in a vicious cycle in which antibiotics given to eradicate one infection predispose them to develop another. This effect is primarily mediated by disturbances in the gut microbiome that both directly enrich for uropathogenic overgrowth and induce systemic alterations in inflammation, tissue permeability, and metabolism that also decrease host resistance to infection recurrences. Here, we discuss nonantibiotic approaches to manipulating the gut microbiome to reverse the systemic consequences of antibiotics, including cranberry supplementation and other dietary approaches, probiotic administration, and fecal microbiota transplantation.}, } @article {pmid39349017, year = {2024}, author = {Werneburg, GT and Hsieh, MH}, title = {Clinical Microbiome Testing for Urology.}, journal = {The Urologic clinics of North America}, volume = {51}, number = {4}, pages = {493-504}, doi = {10.1016/j.ucl.2024.06.007}, pmid = {39349017}, issn = {1558-318X}, mesh = {Humans ; *Microbiota ; *Urinary Tract Infections/diagnosis/microbiology ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {The urine culture is imperfect, and a series of alternative approaches are in development to assist in diagnosis, treatment, and prevention of urinary tract infection (UTI). Culture-independent approaches typically do not distinguish between viable and nonviable bacteria, and are generally not included in current clinical guidance. Next-generation sequencing may play an important future role in precise targeting of antibiotic treatment of asymptomatic bacteriuria prior to endourologic surgery or in pregnancy. Future studies are needed to determine whether microbiota modulation could prevent UTI. Possible modulation mechanisms may include fecal microbiota transplant, application of topical vaginal estrogen or probiotics, and bacteriophage therapy.}, } @article {pmid39348436, year = {2024}, author = {Liu, C and Cyphert, EL and Stephen, SJ and Wang, B and Morales, AL and Nixon, JC and Natsoulas, NR and Garcia, M and Carmona, PB and Vill, AC and Donnelly, E and Brito, IL and Vashishth, D and Hernandez, CJ}, title = {Microbiome-induced Increases and Decreases in Bone Matrix Strength can be Initiated After Skeletal Maturity.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {}, number = {}, pages = {}, doi = {10.1093/jbmr/zjae157}, pmid = {39348436}, issn = {1523-4681}, abstract = {Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n = 143 total, n = 12-17/group/sex) were allocated into five study groups:1) Unaltered, 2) Continuous (dosing 4-24 weeks of age), 3) Delayed (dosing only 16-24 weeks of age), 4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and 5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25-35% less than expected by geometry in mice from the Continuous (P=.001), Delayed (P=.005), and Initial (P=.040) groups as compared to Unaltered. Reconstitution of the gut microbiota led to a bone matrix strength similar to Unaltered animals (P=.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating a sex-dependent response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed with Raman spectroscopy. Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) was small; suggesting that microbiome-induced changes in bone matrix occurred without osteoblast/osteoclast turnover through a yet unidentified mechanism. These findings provide evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.}, } @article {pmid39347394, year = {2024}, author = {Zhao, Y and Guo, K and Yan, Y and Jiang, B}, title = {Cucurbitacin IIb alleviates colitis via regulating gut microbial composition and metabolites.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e38051}, pmid = {39347394}, issn = {2405-8440}, abstract = {Cucurbitacin IIb, a member of the triterpenoid family, exerts beneficial effects on intestinal diseases, including enteritis and bacillary dysentery. However, its effects and mechanisms of action on colitis have not yet been explored. In this study, we used a mouse model of dextran sulfate sodium (DSS)-induced colitis and explored the effects of cucurbitacin IIb on colitis symptoms, inflammatory responses, microbiota, and metabolite profiles. The results showed that cucurbitacin IIb alleviated colitis symptoms including body weight loss, an increase in the disease activity index, and elevated levels of myeloperoxidase and eosinophil peroxidase content. Additionally, it ameliorated intestinal morphology impairment, reduced the phosphorylation of NFκB protein, and mitigated accumulation of pro-inflammatory cytokines IL-6 and IL-1β. Furthermore, cucurbitacin IIb alleviated alterations in gut microbial composition and metabolites in DSS-treated mice. However, antibiotic treatment diminishes the beneficial effects of cucurbitacin IIb on colitis. We further found that transplantation of fresh feces or heat-inactivated feces from mice treated with cucurbitacin IIb to DSS-treated mice alleviated colitis, similar to the effects of cucurbitacin IIb. Collectively, our results suggest that cucurbitacin IIb exerted anti-inflammatory effects in colitis by regulating the microbiota composition and metabolites, thereby alleviating colitis symptoms.}, } @article {pmid39346901, year = {2024}, author = {Alatan, H and Liang, S and Shimodaira, Y and Wu, X and Hu, X and Wang, T and Luo, J and Iijima, K and Jin, F}, title = {Supplementation with Lactobacillus helveticus NS8 alleviated behavioral, neural, endocrine, and microbiota abnormalities in an endogenous rat model of depression.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1407620}, pmid = {39346901}, issn = {1664-3224}, mesh = {Animals ; Rats ; *Gastrointestinal Microbiome/drug effects ; *Lactobacillus helveticus ; *Probiotics/administration & dosage/therapeutic use ; *Disease Models, Animal ; *Rats, Inbred WKY ; *Depression/immunology/metabolism ; Male ; *Brain-Gut Axis ; Behavior, Animal ; Rats, Wistar ; }, abstract = {INTRODUCTION: Major depressive disorder is a condition involving microbiota-gut-brain axis dysfunction. Increasing research aims to improve depression through gut microbiota regulation, including interventions such as probiotics, prebiotics, and fecal microbiota transplants. However, most research focuses on exogenous depression induced by chronic stress or drugs, with less attention given to endogenous depression. Additionally, research on gut mycobiota in depression is significantly less than that on gut bacteria.

METHODS: In the present study, Wistar-Kyoto rats were used as an endogenous depression and treatment-resistant depression model, while Wistar rats served as controls. Differences between the two rat strains in behavior, gut bacteria, gut mycobiota, nervous system, endocrine system, immune system, and gut barrier were evaluated. Additionally, the effects of Lactobacillus helveticus NS8 supplementation were investigated.

RESULTS: Wistar-Kyoto rats demonstrated increased depressive-like behaviors in the forced swimming test, reduced sucrose preference in the sucrose preference test, and decreased locomotor activity in the open field test. They also exhibited abnormal gut bacteria and mycobiota, characterized by higher bacterial α-diversity but lower fungal α-diversity, along with increased butyrate, L-tyrosine, and L-phenylalanine biosynthesis from bacteria. Furthermore, these rats showed dysfunction in the microbiota-gut-brain axis, evidenced by a hypo-serotonergic system, hyper-noradrenergic system, defective hypothalamic-pituitary-adrenal axis, compromised gut barrier integrity, heightened serum inflammation, and diminished gut immunity. A 1-month L. helveticus NS8 intervention increased the fecal abundance of L. helveticus; reduced the abundance of Bilophila and Debaryomycetaceae; decreased immobility time but increased climbing time in the forced swimming test; reduced hippocampal corticotropin-releasing hormone levels; decreased hypothalamic norepinephrine levels; increased hippocampal glucocorticoid receptor, brain-derived neurotrophic factor dopamine, and 5-hydroxyindoleacetic acid content; and improved the gut microbiota, serotonergic, and noradrenergic system.

CONCLUSION: The depressive phenotype of Wistar-Kyoto rats is not only attributed to their genetic context but also closely related to their gut microbiota. Abnormal gut microbiota and a dysfunctional microbiota-gut-brain axis play important roles in endogenous depression, just as they do in exogenous depression. Supplementing with probiotics such as L. helveticus NS8 is likely a promising approach to improve endogenous depression and treatment-resistant depression.}, } @article {pmid39345742, year = {2024}, author = {Liu, X and Wang, Z and Teng, C and Wang, Z}, title = {Changes in gut microbiota and metabolites of mice with intravenous graphene oxide-induced embryo toxicity.}, journal = {Toxicological research}, volume = {40}, number = {4}, pages = {571-584}, pmid = {39345742}, issn = {1976-8257}, abstract = {UNLABELLED: The expanding applications of graphene oxide (GO) nanomaterials have attracted interest in understanding their potential adverse effects on embryonic and fetal development. Numerous studies have revealed the importance of the maternal gut microbiota in pregnancy. In this study, we established a mouse GO exposure model to evaluate embryo toxicity induced by intravenous administration of GO during pregnancy. We also explored the roles of gut microbiota and fecal metabolites using a fecal microbiota transplantation (FMT) intervention model. We found that administration of GO at doses up to 1.25 mg/kg caused embryo toxicity, characterized by significantly increased incidences of fetal resorption, stillbirths, and decreased birth weight. In pregnant mice with embryo toxicity, the richness of the maternal gut microbiota was dramatically decreased, and components of the microbial community were disturbed. FMT alleviated the decrease in birth weight by remodeling the gut microbiota, especially via upregulation of the Firmicutes/Bacteroidetes ratio. We subsequently used untargeted metabolomics to identify characteristic fecal metabolites associated with GO exposure. These metabolites were closely correlated with the phyla Actinobacteria, Proteobacteria, and Cyanobacteria. Our findings offer new insights into the embryo toxic effects of GO exposure during pregnancy; they emphasize the roles of gut microbiota-metabolite interactions in adverse pregnancy outcomes induced by GO or other external exposures, as demonstrated through FMT intervention.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43188-024-00242-3.}, } @article {pmid39338992, year = {2024}, author = {Lim, X and Ooi, L and Ding, U and Wu, HHL and Chinnadurai, R}, title = {Gut Microbiota in Patients Receiving Dialysis: A Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {39338992}, issn = {2076-0817}, abstract = {The human gut microbiota constitutes a complex community of microorganisms residing within the gastrointestinal tract, encompassing a vast array of species that play crucial roles in health and disease. The disease processes involved in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are now increasingly established to result in dysregulation of gut microbiota composition and function. Gut microbiota dysbiosis has been associated with poor clinical outcomes and all-cause mortality in patients with ESKD, particularly individuals receiving dialysis. Prior studies highlighted various factors that affect gut microbiota dysbiosis in CKD and ESKD. These include, but are not limited to, uraemic toxin accumulation, chronic inflammation, immune dysfunction, medications, and dietary restrictions and nutritional status. There is a lack of studies at present that focus on the evaluation of gut microbiota dysbiosis in the context of dialysis. Knowledge on gut microbiota changes in this context is important for determining their impact on dialysis-specific and overall outcomes for this patient cohort. More importantly, evaluating gut microbiota composition can provide information into potential targets for therapeutic intervention. Identification of specific microbial signatures may result in further development of personalised treatments to improve patient outcomes and mitigate complications during dialysis. Optimising gut microbiota through various therapeutic approaches, including dietary adjustments, probiotics, prebiotics, medications, and faecal transplantation, have previously demonstrated potential in multiple medical conditions. It remains to be seen whether these therapeutic approaches are effective within the dialysis setting. Our review aims to evaluate evidence relating to alterations in the gut microbiota of patients undergoing dialysis. A growing body of evidence pointing to the complex yet significant relationship which surrounds gut microbiota and kidney health emphasises the importance of gut microbial balance to improve outcomes for individuals receiving dialysis.}, } @article {pmid39338430, year = {2024}, author = {Fanizzi, F and D'Amico, F and Zanotelli Bombassaro, I and Zilli, A and Furfaro, F and Parigi, TL and Cicerone, C and Fiorino, G and Peyrin-Biroulet, L and Danese, S and Allocca, M}, title = {The Role of Fecal Microbiota Transplantation in IBD.}, journal = {Microorganisms}, volume = {12}, number = {9}, pages = {}, pmid = {39338430}, issn = {2076-2607}, abstract = {Gut microbiota dysbiosis has a critical role in the pathogenesis of inflammatory bowel diseases, prompting the exploration of novel therapeutic approaches like fecal microbiota transplantation, which involves the transfer of fecal microbiota from a healthy donor to a recipient with the aim of restoring a balanced microbial community and attenuating inflammation. Fecal microbiota transplantation may exert beneficial effects in inflammatory bowel disease through modulation of immune responses, restoration of mucosal barrier integrity, and alteration of microbial metabolites. It could alter disease course and prevent flares, although long-term durability and safety data are lacking. This review provides a summary of current evidence on fecal microbiota transplantation in inflammatory bowel disease management, focusing on its challenges, such as variability in donor selection criteria, standardization of transplant protocols, and long-term outcomes post-transplantation.}, } @article {pmid39338312, year = {2024}, author = {Qi, X and Sun, H and Liu, J and Cong, M and Zhang, X and Yan, Y and Xia, Z and Liu, T and Zhao, J}, title = {Phenylethanol Glycoside from Cistanche tubulosa Attenuates BSA-Induced Liver Fibrosis in Rats by Modulating the Gut Microbiota-Liver Axis.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {9}, pages = {}, pmid = {39338312}, issn = {1424-8247}, support = {2022D01D36//This work was financially supported by the Key project of Natural Science Foundation of Xinjiang Uygur Autonomous Region in China/ ; }, abstract = {This study aimed to investigate the effect of phenylethanol glycoside from Cistanche tubulosa (CPhGs) on the prevention of bovine serum albumin (BSA)-induced hepatic fibrosis in rats. Investigation of the mechanisms of the anti-hepatic fibrosis effect was focused on CPhGs' influence on the "gut-liver" regulation, including the gut microbiota, intestinal barrier, systemic lipopolysaccharide (LPS) concentration, and LPS-related signaling pathway. The results show that CPhGs restored the diversity of gut microbiota, increased the relative abundance of Bacteroidetes, and decreased the relative abundance of Firmicutes and Proteobacteria in the fibrotic rats. In addition, CPhGs promoted the enrichment of probiotics such as Blautia, Oscillospira, Ruminococcus, Odoribacter, Bacteroides, and Parabacteroides in intestines of these rats. Furthermore, CPhGs reduced histopathological injury in the intestine and restored the tight junctions of the intestine by increasing the expression of ZO-1, occludin, and E-cadherin. CPhGs efficiently reduced serum LPS and liver lipopolysaccharide-binding protein (LBP) levels and inhibited the LPS-TLR4/MyD88/NF-κB pathway, which is related to protein expression in the liver. Correlation analysis confirmed that these beneficial bacteria were negatively associated with pathological damage, while LPS and harmful bacteria were positively associated with liver injury. Our fecal microbiota transplantation (FMT) experiment confirmed that gut microbiota is an important part of disease progression and that CPhGs is useful for the prevention and treatment of hepatic fibrosis. Our data demonstrate that the anti-hepatic fibrosis mechanism of CPhGs was mediated by regulation of the "gut-liver" axis. These results can stimulate consideration for its use in clinical practices.}, } @article {pmid39186389, year = {2024}, author = {Cotto, C and Baker, K and Fallon, E and Rimon, S}, title = {Fecal Microbiota, Live-jslm (RBL; REBYOTA ®) for Prevention of Recurrent Clostridioides difficile Infection: What Gastroenterology Nurses Need to Know.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {47}, number = {5}, pages = {378-382}, pmid = {39186389}, issn = {1538-9766}, mesh = {Humans ; *Clostridium Infections/prevention & control ; *Clostridioides difficile ; *Fecal Microbiota Transplantation ; Gastroenterology ; Feces/microbiology ; Recurrence ; Secondary Prevention/methods ; }, } @article {pmid39337526, year = {2024}, author = {Missiego-Beltrán, J and Beltrán-Velasco, AI}, title = {The Role of Microbial Metabolites in the Progression of Neurodegenerative Diseases-Therapeutic Approaches: A Comprehensive Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337526}, issn = {1422-0067}, mesh = {Humans ; *Neurodegenerative Diseases/metabolism/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; *Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; Disease Progression ; Blood-Brain Barrier/metabolism ; Oxidative Stress ; Fatty Acids, Volatile/metabolism ; }, abstract = {The objective of this review is to provide a comprehensive examination of the role of microbial metabolites in the progression of neurodegenerative diseases, as well as to investigate potential therapeutic interventions targeting the microbiota. A comprehensive literature search was conducted across the following databases: PubMed, Scopus, Web of Science, ScienceDirect, and Wiley. Key terms related to the gut microbiota, microbial metabolites, neurodegenerative diseases, and specific metabolic products were used. The review included both preclinical and clinical research articles published between 2000 and 2024. Short-chain fatty acids have been demonstrated to play a crucial role in modulating neuroinflammation, preserving the integrity of the blood-brain barrier, and influencing neuronal plasticity and protection. Furthermore, amino acids and their derivatives have been demonstrated to exert a significant influence on CNS function. These microbial metabolites impact CNS health by regulating intestinal permeability, modulating immune responses, and directly influencing neuroinflammation and oxidative stress, which are integral to neurodegenerative diseases. Therapeutic strategies, including prebiotics, probiotics, dietary modifications, and fecal microbiota transplantation have confirmed the potential to restore microbial balance and enhance the production of neuroprotective metabolites. Furthermore, novel drug developments based on microbial metabolites present promising therapeutic avenues. The gut microbiota and its metabolites represent a promising field of research with the potential to advance our understanding of and develop treatments for neurodegenerative diseases.}, } @article {pmid39337098, year = {2024}, author = {Tîrziu, AT and Susan, M and Susan, R and Sonia, T and Harich, OO and Tudora, A and Varga, NI and Tiberiu-Liviu, D and Avram, CR and Boru, C and Munteanu, M and Horhat, FG}, title = {From Gut to Eye: Exploring the Role of Microbiome Imbalance in Ocular Diseases.}, journal = {Journal of clinical medicine}, volume = {13}, number = {18}, pages = {}, pmid = {39337098}, issn = {2077-0383}, abstract = {Background: The gut microbiome plays a crucial role in human health, and recent research has highlighted its potential impact on ocular health through the gut-eye axis. Dysbiosis, or an imbalance in the gut microbiota, has been implicated in various ocular diseases. Methods: A comprehensive literature search was conducted using relevant keywords in major electronic databases, prioritizing recent peer-reviewed articles published in English. Results: The gut microbiota influences ocular health through immune modulation, maintenance of the blood-retinal barrier, and production of beneficial metabolites. Dysbiosis can disrupt these mechanisms, contributing to ocular inflammation, tissue damage, and disease progression in conditions such as uveitis, age-related macular degeneration, diabetic retinopathy, dry eye disease, and glaucoma. Therapeutic modulation of the gut microbiome through probiotics, prebiotics, synbiotics, and fecal microbiota transplantation shows promise in preclinical and preliminary human studies. Conclusions: The gut-eye axis represents a dynamic and complex interplay between the gut microbiome and ocular health. Targeting the gut microbiome through innovative therapeutic strategies holds potential for improving the prevention and management of various ocular diseases.}, } @article {pmid39334498, year = {2024}, author = {De Filippo, C and Chioccioli, S and Meriggi, N and Troise, AD and Vitali, F and Mejia Monroy, M and Özsezen, S and Tortora, K and Balvay, A and Maudet, C and Naud, N and Fouché, E and Buisson, C and Dupuy, J and Bézirard, V and Chevolleau, S and Tondereau, V and Theodorou, V and Maslo, C and Aubry, P and Etienne, C and Giovannelli, L and Longo, V and Scaloni, A and Cavalieri, D and Bouwman, J and Pierre, F and Gérard, P and Guéraud, F and Caderni, G}, title = {Gut microbiota drives colon cancer risk associated with diet: a comparative analysis of meat-based and pesco-vegetarian diets.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {180}, pmid = {39334498}, issn = {2049-2618}, support = {JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; JTC-2017-7//Joint Programming Initiative a Healthy Diet for a Healthy Life-Intestinal Microbiomics (JPI HDHL-INTIMIC) Call for Joint Transnational Research Proposals on "Interrelation of the Intestinal Microbiome, Diet and Health"/ ; Expression of interest # 895//HDHL INTIMIC-Knowledge Platform on food, diet, intestinal microbiomics and human health/ ; Expression of interest # 895//HDHL INTIMIC-Knowledge Platform on food, diet, intestinal microbiomics and human health/ ; PE00000003//National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 - Call for tender No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union - NextGenerationEU; Project title "ON Foods - Research and innovation network on food and nutrition Sustainability, Safety and Security - Working ON Foods"/ ; PE00000003//National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 - Call for tender No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union - NextGenerationEU; Project title "ON Foods - Research and innovation network on food and nutrition Sustainability, Safety and Security - Working ON Foods"/ ; PE00000003//National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 - Call for tender No. 341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union - NextGenerationEU; Project title "ON Foods - Research and innovation network on food and nutrition Sustainability, Safety and Security - Working ON Foods"/ ; ECS00000017//European Union - NextGenerationEU - National Recovery and Resilience Plan, Mission 4 Component 2 - Investment 1.5 - THE - Tuscany Health Ecosystem/ ; ECS00000017//European Union - NextGenerationEU - National Recovery and Resilience Plan, Mission 4 Component 2 - Investment 1.5 - THE - Tuscany Health Ecosystem/ ; G. Caderni//University of Florence (Fondo ex-60%), Italy/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Rats ; *Colonic Neoplasms/microbiology/etiology ; *Diet, Vegetarian/adverse effects ; *Feces/microbiology ; *Fecal Microbiota Transplantation ; *RNA, Ribosomal, 16S/genetics ; Male ; Bacteria/classification/isolation & purification/genetics/metabolism ; Diet/adverse effects ; Azoxymethane ; Meat/adverse effects/microbiology ; Colorectal Neoplasms/microbiology/etiology ; Disease Models, Animal ; Humans ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) risk is strongly affected by dietary habits with red and processed meat increasing risk, and foods rich in dietary fibres considered protective. Dietary habits also shape gut microbiota, but the role of the combination between diet, the gut microbiota, and the metabolite profile on CRC risk is still missing an unequivocal characterisation.

METHODS: To investigate how gut microbiota affects diet-associated CRC risk, we fed Apc-mutated PIRC rats and azoxymethane (AOM)-induced rats the following diets: a high-risk red/processed meat-based diet (MBD), a normalised risk diet (MBD with α-tocopherol, MBDT), a low-risk pesco-vegetarian diet (PVD), and control diet. We then conducted faecal microbiota transplantation (FMT) from PIRC rats to germ-free rats treated with AOM and fed a standard diet for 3 months. We analysed multiple tumour markers and assessed the variations in the faecal microbiota using 16S rRNA gene sequencing together with targeted- and untargeted-metabolomics analyses.

RESULTS: In both animal models, the PVD group exhibited significantly lower colon tumorigenesis than the MBD ones, consistent with various CRC biomarkers. Faecal microbiota and its metabolites also revealed significant diet-dependent profiles. Intriguingly, when faeces from PIRC rats fed these diets were transplanted into germ-free rats, those transplanted with MBD faeces developed a higher number of preneoplastic lesions together with distinctive diet-related bacterial and metabolic profiles. PVD determines a selection of nine taxonomic markers mainly belonging to Lachnospiraceae and Prevotellaceae families exclusively associated with at least two different animal models, and within these, four taxonomic markers were shared across all the three animal models. An inverse correlation between nonconjugated bile acids and bacterial genera mainly belonging to the Lachnospiraceae and Prevotellaceae families (representative of the PVD group) was present, suggesting a potential mechanism of action for the protective effect of these genera against CRC.

CONCLUSIONS: These results highlight the protective effects of PVD while reaffirming the carcinogenic properties of MBD diets. In germ-free rats, FMT induced changes reminiscent of dietary effects, including heightened preneoplastic lesions in MBD rats and the transmission of specific diet-related bacterial and metabolic profiles. Importantly, to the best of our knowledge, this is the first study showing that diet-associated cancer risk can be transferred with faeces, establishing gut microbiota as a determinant of diet-associated CRC risk. Therefore, this study marks the pioneering demonstration of faecal transfer as a means of conveying diet-related cancer risk, firmly establishing the gut microbiota as a pivotal factor in diet-associated CRC susceptibility. Video Abstract.}, } @article {pmid39333864, year = {2024}, author = {Huang, F and Deng, Y and Zhou, M and Tang, R and Zhang, P and Chen, R}, title = {Fecal microbiota transplantation from patients with polycystic ovary syndrome induces metabolic disorders and ovarian dysfunction in germ-free mice.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {364}, pmid = {39333864}, issn = {1471-2180}, support = {82201781//National Natural Science Foundation of China/ ; 81871141//National Natural Science Foundation of China/ ; 2022-PUMCH-B-123//National High-Level Hospital Clinical Research Funding/ ; 2018YFC1004801//National Key Research and Development Program/ ; 2020-I2M-CT-B-040//CAMS Innovation Fund for Medical Sciences (CIFMS)/ ; }, mesh = {*Polycystic Ovary Syndrome/microbiology/therapy ; Animals ; *Fecal Microbiota Transplantation ; Female ; Mice ; *Gastrointestinal Microbiome ; Humans ; *Dysbiosis/microbiology ; Feces/microbiology ; Metabolic Diseases/microbiology/etiology/therapy ; Bacteria/classification/isolation & purification/genetics ; Insulin Resistance ; Ovary/microbiology ; Germ-Free Life ; Disease Models, Animal ; Adult ; }, abstract = {BACKGROUND: Dysbiosis of the microbiome is a key hallmark of polycystic ovary syndrome (PCOS). However, the interaction between the host and microbiome and its relevance to the pathogenesis of PCOS remain unclear.

METHODS: To evaluate the role of the commensal gut microbiome in PCOS, we gavaged germ-free mice with the fecal microbiota from patients with PCOS or healthy individuals and evaluated the reproductive endocrine features of the recipient mice.

RESULTS: Mice transplanted with fecal microbiota from PCOS patients and those transplanted from healthy controls presented different bacterial profiles and reproductive endocrine features. The fecal microbiota of the mice in the PCOS group was enriched in Phocaeicola, Mediterraneibacter, Oscillospiraceae, Lawsonibacter and Rikenellaceae. Fecal microbiota transplantation (FMT) from PCOS patients induced increased disruption of ovarian functions, lipo-metabolic disturbance, insulin resistance and an obese-like phenotype in recipient mice.

CONCLUSION: Our findings suggest that the microbiome may govern the set point of PCOS-bearing individuals and that gut ecosystem manipulation may be a useful marker and target for the management of PCOS.}, } @article {pmid39333064, year = {2024}, author = {Chen, X and Chen, X and Yan, D and Zhang, N and Fu, W and Wu, M and Ge, F and Wang, J and Li, X and Geng, M and Wang, J and Tang, D and Liu, J}, title = {GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8278}, pmid = {39333064}, issn = {2041-1723}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Male ; Mice ; *Pancreatitis/immunology/microbiology/metabolism ; *Mice, Inbred C57BL ; *Disease Models, Animal ; Macrophages/immunology/metabolism ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Humans ; Metabolomics ; }, abstract = {Despite recent advances, severe acute pancreatitis (SAP) remains a lethal inflammation with limited treatment options. Here, we provide compelling evidence of GV-971 (sodium oligomannate), an anti-Alzheimer's medication, as being a protective agent in various male mouse SAP models. Microbiome sequencing, along with intestinal microbiota transplantation and mass cytometry technology, unveil that GV-971 reshapes the gut microbiota, increasing Faecalibacterium populations and modulating both peripheral and intestinal immune systems. A metabolomics analysis of cecal contents from GV-971-treated SAP mice further identifies short-chain fatty acids, including propionate and butyrate, as key metabolites in inhibiting macrophage M1 polarization and subsequent lethal inflammation by blocking the MAPK pathway. These findings suggest GV-971 as a promising therapeutic for SAP by targeting the microbiota metabolic immune axis.}, } @article {pmid39331938, year = {2024}, author = {Zhao, Y and Qiu, P and Shen, T}, title = {Gut microbiota and eye diseases: A review.}, journal = {Medicine}, volume = {103}, number = {39}, pages = {e39866}, pmid = {39331938}, issn = {1536-5964}, support = {NO.2023C03089//the Research and Development Plan of Zhejiang Science and Technology Department/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Eye Diseases/microbiology/therapy/immunology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Recent studies reveal that alterations in gut microbiota play a significant role in the progression of various diseases, including those affecting the eyes. The association between gut microbiota and eye health is an emerging focus of research. This review seeks to summarize the connection between the gut microbiome and specific eye conditions, such as ocular surface diseases, funduscopic disorders and immune-mediated eye diseases. Gut microbiota may influence these conditions by regulating the immune system or altering metabolites, thereby contributing to disease development. Strategies like probiotics, antibiotics, dietary modifications, and fecal transplants show promise in addressing these issues. This review examines how the gut microbiome may be linked to the pathogenesis of eye diseases, providing fresh therapeutic perspectives for ophthalmology.}, } @article {pmid39330818, year = {2024}, author = {Hanifeh, M and Scarsella, E and Rojas, CA and Ganz, HH and Huhtinen, M and Laine, T and Spillmann, T}, title = {Oral Fecal Microbiota Transplantation in Dogs with Tylosin-Responsive Enteropathy-A Proof-of-Concept Study.}, journal = {Veterinary sciences}, volume = {11}, number = {9}, pages = {}, pmid = {39330818}, issn = {2306-7381}, support = {V3130001//Orion Corporation (Finland)/ ; }, abstract = {A clinical trial was conducted to evaluate the effect of fecal microbiota transplantation (FMT) on the canine chronic enteropathy clinical activity index (CCECAI), fecal consistency, and microbiome of dogs with tylosin-responsive enteropathy (TRE). The trial consisted of four phases: (1) screening with discontinuation of tylosin for 4 weeks, (2) inclusion with re-introduction of tylosin for 3-7 days, (3) treatment with FMT/placebo for 4 weeks, and (4) post-treatment with follow-up for 4 weeks after treatment cessation. The study found that the treatment efficacy of FMT (71.4%) was slightly higher than that of placebo (50%), but this difference was not statistically significant due to underpowering. The most abundant bacterial species detected in the fecal microbiomes of dogs with TRE before FMT or placebo treatment were Blautia hansenii, Ruminococcus gnavus, Escherichia coli, Clostridium dakarense, Clostridium perfringens, Bacteroides vulgatus, and Faecalimonas umbilicata. After FMT, the microbiomes exhibited increases in Clostridium dakarense, Clostridium paraputrificum, and Butyricicoccus pullicaecorum. The microbiome alpha diversity of TRE dogs was lower when on tylosin treatment compared to healthy dogs, but it increased after treatment in both the FMT and placebo groups. Comparisons with the stool donor showed that, on average, 30.4% of donor strains were engrafted in FMT recipients, with the most common strains being several Blautia sp., Ruminococcus gnavus, unclassified Lachnoclostridium, Collinsella intestinalis, and Fournierella massiliensis.}, } @article {pmid39329364, year = {2024}, author = {Rani, M and Akhilesh, and Chouhan, D and Uniyal, A and Tiwari, V}, title = {Fecal Microbiota Transplantation-Mediated Rebalancing of the Gut-Brain Axis Alleviates Cisplatin-Induced Neuropathic Pain.}, journal = {ACS chemical neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1021/acschemneuro.4c00267}, pmid = {39329364}, issn = {1948-7193}, abstract = {Chemotherapy-induced neuropathic pain (CINP) presents a significant challenge in cancer treatment, necessitating novel therapeutic approaches. The intricate relationship between CINP and the gut-brain axis indicates a crucial role for the gut microbiota in pain modulation during cancer therapy. In this study, we investigated the effect of gut microbiota and their modulation on CINP in rats. Cisplatin administration (20 mg/kg, ip) disrupted the integrity of the blood-spinal cord barrier, as evidenced by reduced expression of tight junction proteins occludin and claudin-5 and increased leakage of pro-inflammatory cytokines into the spinal cord. Fecal microbiota transplantation (FMT, 0.5 mL of P.O.) from healthy rats over 21 days restored barrier integrity, as confirmed by Evan's blue assay. FMT intervention halted the progression of cisplatin-induced pain, demonstrated through a battery of pain assays assessing mechanical, thermal, and cold allodynia alongside hyperalgesia measurements. Additionally, FMT treatment reduced oxidative stress and modulated neuro-inflammatory markers, resulting in a rebalanced cytokine profile with decreased levels of neuro-inflammatory cytokines (IL-6 and TNFα) and increased expression of the anti-inflammatory cytokine IL-10. Gut microbiota-mediated IL-1β/NF-κB signaling emerged as a critical factor in leukocyte recruitment and microglial activation, highlighting the gut-brain axis as a key regulatory nexus in managing cisplatin-induced neuropathic pain. These findings underscore the therapeutic potential of targeting gut microbiota modulation as a promising strategy for alleviating CINP and improving the well-being of cancer patients undergoing chemotherapy.}, } @article {pmid39326141, year = {2024}, author = {Hu, T and Zhu, Y and Zhou, X and Ye, M and Wang, X and Lu, C and Wang, Y}, title = {Baicalein ameliorates SEB-induced acute respiratory distress syndrome in a microbiota-dependent manner.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156049}, doi = {10.1016/j.phymed.2024.156049}, pmid = {39326141}, issn = {1618-095X}, abstract = {BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by sudden and extensive pulmonary inflammation, with a mortality rate of approximately 40 %. Presently, there is no effective treatment to prevent or reverse its severe consequences. Baicalein (BAI) is a natural vicinal trihydroxyflavone and has been identified as the core quality marker of Scutellariae baicalensis for its effect on lung inflammation. However, its oral bioavailability is limited. The majority of studies that investigate BAI's in vivo mechanisms use injection techniques. Currently, there is no clear understanding of the mechanisms by which low-bioavailable BAI functions orally.

PURPOSE: This study aimed to evaluate the efficiency of BAI in ARDS mice and its underlying mechanisms.

STUDY DESIGN AND METHODS: Behavioral experiments, histological analysis, immunofluorescence staining, flow cytometry of immune cells, qRT-PCR, and ELISA analysis were performed to evaluate the efficiency of BAI in ARDS mice. Lung tissues transcriptomic-based analyses were performed to detect the differentially expressed genes and biological pathways. Fecal samples were subjected to microbial 16S rRNA analysis and untargeted metabolomics analysis in order to identify the specific flora and metabolites associated with BAI. Furthermore, antibiotic cocktail treatment and fecal microbiota transplantation were used to elucidate the gut microbiota-mediated effects on ARDS.

RESULTS: In our study, we first find that oral administration of BAI effectively mitigates staphylococcal enterotoxin B-induced ARDS. BAI can alleviate gut dysbiosis and regulate the Toll-like signaling pathway and amino acid metabolism. The protective effects of BAI against ARDS are gut microbiota dependent. Modulation of gut microbiota increases the production of short-chain fatty acids and enhances lung barrier function, which is consistent with the therapeutic interventions with BAI. Notably, BAI greatly enriches the abundance of Prevotellaceae, a butyrate-producing bacterial family, exhibiting a positive correlation with key differentially expressed genes in the TLR4/MyD88 signaling cascades.

CONCLUSION: BAI emerges as a potential prebiotic agent to attenuate ARDS, and targeting specific microbial species may offer an innovative therapeutic approach to investigate other flavonoids with limited bioavailability.}, } @article {pmid39276368, year = {2024}, author = {Čížková, D and Payne, P and Bryjová, A and Ďureje, Ľ and Piálek, J and Kreisinger, J}, title = {Convergence of gut phage communities but not bacterial communities following wild mouse bacteriophage transplantation into captive house mice.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {39276368}, issn = {1751-7370}, support = {19-19307S//Czech Science Foundation/ ; e-INFRA CZ LM2018140//Ministry of Education, Youth, and Sports of the Czech Republic/ ; }, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Bacteriophages/isolation & purification/genetics/physiology ; Bacteria/classification/virology/genetics/isolation & purification ; Animals, Wild/microbiology ; Specific Pathogen-Free Organisms ; Feces/microbiology/virology ; Female ; Virome ; }, abstract = {Bacteriophages are abundant components of vertebrate gut microbial communities, impacting bacteriome dynamics, evolution, and directly interacting with the superhost. However, knowledge about gut phageomes and their interaction with bacteriomes in vertebrates under natural conditions is limited to humans and non-human primates. Widely used specific-pathogen-free (SPF) mouse models of host-microbiota interactions have altered gut bacteriomes compared to wild mice, and data on phageomes from wild or other non-SPF mice are lacking. We demonstrate divergent gut phageomes and bacteriomes in wild and captive non-SPF mice, with wild mice phageomes exhibiting higher alpha-diversity and interindividual variability. In both groups, phageome and bacteriome structuring mirrored each other, correlating at the individual level. Re-analysis of previous data from phageomes of SPF mice revealed their enrichment in Suoliviridae crAss-like phages compared to our non-SPF mice. Disrupted bacteriomes in mouse models can be treated by transplanting healthy phageomes, but the effects of phageome transplants on healthy adult gut microbiota are still unknown. We show that experimental transplantation of phageomes from wild to captive mice did not cause major shifts in recipient phageomes. However, the convergence of recipient-to-donor phageomes confirmed that wild phages can integrate into recipient communities. The differences in the subset of integrated phages between the two recipient mouse strains illustrate the context-dependent effects of phage transplantation. The transplantation did not impact recipient gut bacteriomes. This resilience of healthy adult gut microbiomes to the intervention has implications for phage allotransplantation safety.}, } @article {pmid39324491, year = {2024}, author = {Pu, D and Yao, Y and Zhou, C and Liu, R and Wang, Z and Liu, Y and Wang, D and Wang, B and Wang, Y and Liu, Z and Zhang, Z and Feng, B}, title = {FMT rescues mice from DSS-induced colitis in a STING-dependent manner.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2397879}, doi = {10.1080/19490976.2024.2397879}, pmid = {39324491}, issn = {1949-0984}, mesh = {Animals ; *Colitis/therapy/chemically induced/immunology ; *Membrane Proteins/genetics/metabolism ; Mice ; *Dextran Sulfate/adverse effects ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Mice, Inbred C57BL ; Th17 Cells/immunology ; Disease Models, Animal ; Th1 Cells/immunology ; Colon/microbiology/immunology/pathology ; Macrophages/immunology ; Humans ; Th2 Cells/immunology ; }, abstract = {Fecal microbiota transplantation (FMT) is currently a promising therapy for inflammatory bowel disease (IBD). However, clinical studies have shown that there is an obvious individual difference in the efficacy of FMT. Therefore, it is a pressing issue to identify the factors that influence the efficacy of FMT and find ways to screen the most suitable patients for this therapy. In this work, we targeted the stimulator of interferon genes (STING), a DNA-sensing protein that regulates host-defense. By comparing the differential efficacy of FMT in mice with different expression level of STING, it is revealed that FMT therapy provides treatment for DSS-induced colitis in a STING-dependent manner. Mechanistically, FMT exerts a regulatory effect on the differentiation of intestinal Th17 cells and macrophages, splenic Th1 and Th2 cells, as well as Th1 cells of the mesenteric lymph nodes via STING, down-regulating the colonic M1/M2 and splenic Th1/Th2 cell ratios, thereby improving the imbalanced immune homeostasis in the inflamed intestine. Meanwhile, based on the 16SrDNA sequencing of mice fecal samples, STING was found to facilitate the donor strain colonization in recipients' gut, mainly Lactobacillales, thereby reshaping the gut microbiota disturbed by colitis. Consequently, we proposed that STING, as a key target of FMT therapy, is potentially a biomarker for screening the most suitable individuals for FMT to optimize treatment regimens and enhance clinical benefit.}, } @article {pmid39323880, year = {2024}, author = {Deng, L and Guo, X and Chen, J and Li, B and Liu, N and Xia, J and Ou, M and Hong, Z}, title = {Effect of intestinal microbiota transplantation on chronic hepatitis B virus infection associated liver disease.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1458754}, pmid = {39323880}, issn = {1664-302X}, abstract = {BACKGROUND: Research on the effects of intestinal microbiota transplantation (IMT) on chronic HBV infection (CHB) progression associated liver disease (HBV-CLD) and alterations in the microbiota post-IMT are quite limited for the moment.

METHODS: By integrating microbiome with metabolome analyses, we aimed to the function of IMT and the alterations of gut microbiota in patients with HBV-CLD. First, this study included 20 patients with HBV-CLD and ten healthy controls. Then, 16 patients with CHB were given IMT with donor feces (heterologous) via oral capsule. Fecal samples from CHB patients were obtained before and after IMT, as well as healthy controls, for 16S rDNA sequencing and untargeted metabolomics analysis.

RESULTS: The proalbuminemia were significantly increased after IMT, and the HBsAg and TBA showed a significant decrease after IMT in the HBV-CLD patients. There was statistical difference in the Chaol indexes between between CHB patients and healthy controls, suggesting a lower abundance of the gut microbiota in HBV-CLD patients. In addition, there was statistical difference in the Shannon and Simpson indexes between prior to IMT and post-IMT, indicating that the impaired abundance of the gut microbiota had been improved after IMT. The host-microbiota-metabolite interplay, amino acid metabolism, nicotinate and nicotinamide metabolism, starch and sucrose metabolism, steroid biosynthesis, and vitamins metabolism, were significantly lower in HBV-CLD patients than healthy controls.

CONCLUSION: IMT may improve the therapeutic effects on patients HBV-CLD. Furthermore, IMT appears to improve amino acid metabolism by impaired abundance of the gut microbiota and therefore improve liver prealbumin synthesis.}, } @article {pmid39323631, year = {2024}, author = {Zhang, D and Cheng, H and Wu, J and Zhou, Y and Tang, F and Liu, J and Feng, W and Peng, C}, title = {The energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1392385}, pmid = {39323631}, issn = {1663-9812}, abstract = {INTRODUCTION: As a widely used traditional Chinese medicine with hot property, aconite can significantly promote energy metabolism. However, it is unclear whether the gut microbiota and bile acids contribute to the energy metabolism-promoting properties of aconite. The aim of this experiment was to verify whether the energy metabolism-promoting effect of aconite aqueous extract (AA) is related to gut microbiota and bile acid (BA) metabolism.

METHODS: The effect of AA on energy metabolism in rats was detected based on body weight, body temperature, and adipose tissue by HE staining and immunohistochemistry. In addition, 16S rRNA high-throughput sequencing and targeted metabolomics were used to detect changes in gut microbiota and BA concentrations, respectively. Antibiotic treatment and fecal microbiota transplantation (FMT) were also performed to demonstrate the importance of gut microbiota.

RESULTS: Rats given AA experienced an increase in body temperature, a decrease in body weight, and an increase in BAT (brown adipose tissue) activity and browning of WAT (white adipose tissue). Sequencing analysis and targeted metabolomics indicated that AA modulated gut microbiota and BA metabolism. The energy metabolism promotion of AA was found to be mediated by gut microbiota, as demonstrated through antibiotic treatment and FMT. Moreover, the energy metabolism-promoting effect of aconite is associated with the bile acid receptor TGR5 (Takeda G-protein-coupled receptor 5)-UCP1 (uncoupling protein 1) signaling pathway.

CONCLUSION: The energy metabolism-promoting effect of aconite is associated with gut microbiota and bile acid receptor TGR5-UCP1 signaling.}, } @article {pmid39322832, year = {2024}, author = {Zeng, X and Ma, C and Fu, W and Xu, Y and Wang, R and Liu, D and Zhang, L and Hu, N and Li, D and Li, W}, title = {Changes in Type 1 Diabetes-Associated Gut Microbiota Aggravate Brain Ischemia Injury by Affecting Microglial Polarization Via the Butyrate-MyD88 Pathway in Mice.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39322832}, issn = {1559-1182}, support = {81701288//National Natural Science Foundation of China/ ; YQJH2023028//Program for Young Talents of Basic Research in Universities of Heilongjiang Province/ ; }, abstract = {People with type 1 diabetes (T1D) have a significantly elevated risk of stroke, but the mechanism through which T1D worsens ischemic stroke remains unclear. This study was aimed at investigating the roles of T1D-associated changes in the gut microbiota in aggravating ischemic stroke and the underlying mechanism. Fecal 16SrRNA sequencing indicated that T1D mice and mice with transplantation of T1D mouse gut microbiota had lower relative abundance of butyric acid producers, f_Erysipelotrichaceae and g_Allobaculum, and lower content of butyric acid in feces. After middle cerebral artery occlusion (MCAO), these mice had poorer neurological outcomes and more severe inflammation, but higher expression of myeloid differentiation factor 88 (MyD88) in the ischemic penumbra; moreover, the microglia were inclined to polarize toward the pro-inflammatory type. Administration of butyrate to T1D mice in the drinking water alleviated the neurological damage after MCAO. Butyrate influenced the response and polarization of BV2 and decreased the production of inflammatory cytokines via MyD88 after oxygen-glucose deprivation/reoxygenation. Knocking down MyD88 in the brain alleviated neurological outcomes and decreased the concentrations of inflammatory cytokines in the brain after stroke in mice with transplantation of T1D mouse gut microbiota. Poor neurological outcomes and aggravated inflammatory responses of T1D mice after ischemic stroke may be partly due to differences in microglial polarization mediated by the gut microbiota-butyrate-MyD88 pathway. These findings provide new ideas and potential intervention targets for alleviating neurological damage after ischemic stroke in T1D.}, } @article {pmid39322747, year = {2024}, author = {Zhang, SL and Wang, X and Cai, QQ and Chen, C and Zhang, ZY and Xu, YY and Yang, MX and Jia, QA and Wang, Y and Wang, ZM}, title = {Acarbose enhances the efficacy of immunotherapy against solid tumours by modulating the gut microbiota.}, journal = {Nature metabolism}, volume = {}, number = {}, pages = {}, pmid = {39322747}, issn = {2522-5812}, support = {82203048//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8[+] T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8[+] T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8[+] T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.}, } @article {pmid39322314, year = {2024}, author = {Van Hul, M and Cani, PD and Petifils, C and De Vos, WM and Tilg, H and El Omar, EM}, title = {What defines a healthy gut microbiome?.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-333378}, pmid = {39322314}, issn = {1468-3288}, abstract = {The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition and vice versa, yet there is a problematic issue with the term 'dysbiosis', which broadly links microbial imbalances to various chronic illnesses without precision or definition. Another significant issue in microbiome discussions is defining 'healthy individuals' to ascertain what characterises a healthy microbiome. This involves questioning who represents the healthiest segment of our population-whether it is those free from illnesses, athletes at peak performance, individuals living healthily through regular exercise and good nutrition or even elderly adults or centenarians who have been tested by time and achieved remarkable healthy longevity.This review advocates for delineating 'what defines a healthy microbiome?' by considering a broader range of factors related to human health and environmental influences on the microbiota. A healthy microbiome is undoubtedly linked to gut health. Nevertheless, it is very difficult to pinpoint a universally accepted definition of 'gut health' due to the complexities of measuring gut functionality besides the microbiota composition. We must take into account individual variabilities, the influence of diet, lifestyle, host and environmental factors. Moreover, the challenge in distinguishing causation from correlation between gut microbiome and overall health is presented.The review also highlights the resource-heavy nature of comprehensive gut health assessments, which hinders their practicality and broad application. Finally, we call for continued research and a nuanced approach to better understand the intricate and evolving concept of gut health, emphasising the need for more precise and inclusive definitions and methodologies in studying the microbiome.}, } @article {pmid39321881, year = {2024}, author = {Bano, N and Khan, S and Ahamad, S and Kanshana, JS and Dar, NJ and Khan, S and Nazir, A and Bhat, SA}, title = {Microglia and Gut Microbiota: A Double-Edged Sword in Alzheimer's Disease.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {102515}, doi = {10.1016/j.arr.2024.102515}, pmid = {39321881}, issn = {1872-9649}, abstract = {The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration.}, } @article {pmid39321863, year = {2024}, author = {Liang, J and Xiong, Z and Lei, Q and Jiang, Z and Wei, J and Ouyang, F and Chen, Y and Zeng, J}, title = {Sleep dysfunction and gut dysbiosis related amino acids metabolism disorders in cynomolgus monkeys after middle cerebral artery occlusion.}, journal = {Experimental neurology}, volume = {}, number = {}, pages = {114970}, doi = {10.1016/j.expneurol.2024.114970}, pmid = {39321863}, issn = {1090-2430}, abstract = {INTRODUCTION: This study aimed to explore the characteristics of post-stroke sleep dysfunction and verify their association with gut dysbiosis and the related amino acid metabolism disorders. This was achieved by using fecal microbiota transplantation (FMT) in a non-human primate stroke model.

METHODS: Twenty adult male cynomolgus monkeys were divided into the sham (n = 4), middle cerebral artery occlusion (MCAO, n = 5), MCAO + FMT (n = 3), and donor (n = 8) groups. The MCAO+FMT group received FMT at post-MCAO week 4. Sleep parameters, gut microbiota, gamma-aminobutyric acid (GABA), and glutamine (Gln) in the cerebrospinal fluid (CSF) were measured at baseline and postoperative weeks 4, 8, and 12.

RESULTS: At postoperative weeks 4, 8, and 12, the MCAO group showed decreased sleep efficiency, measured as the percentage of sleep during the whole night (82.3 ± 3.2 % vs 91.3 ± 2.5 %, 79.0 ± 3.75 % vs 90.8 ± 3.2 %, and 69.5 ± 4.8 % vs 90.5 ± 2.7 %; all P < 0.05), lower relative abundance of Lactobacillus (all P < 0.05), and reduced GABA concentrations in the CSF (317.3 ± 30.6 nmol/L vs 437.7 ± 25.6 nmol/L, 303.1 ± 48.9 nmol/L vs 4 40.9 ± 37.8 nmol/L, and 337.9 ± 49.4 nmol/L vs 457.4 ± 39.2 nmol/L; all P < 0.05) compared with the sham group. Sleep efficiency at post-FMT weeks 4 and 8 (84.7 ± 1.1 % vs 79.0 ± 3.75 %, and 84.1 ± 2.0 % vs 69.5 ± 4.8 %; both P < 0.05) and GABA concentration in the CSF at post-FMT week 4 (403.1 ± 25.4 nmol/L vs 303.1 ± 48.9 nmol/L, P < 0.05) was higher in the MCAO+FMT group than in the MCAO group.

CONCLUSIONS: Post-stroke sleep dysfunction in monkeys is characterized by impaired sleep coherence, associated with decreased levels of probiotics such as Lactobacillus, GABA, and Gln in the CSF and can be ameliorated using FMT.}, } @article {pmid39321508, year = {2024}, author = {Phanchana, M and Pipatthana, M and Phetruen, T and Konpetch, P and Prangthip, P and Harnvoravongchai, P and Sripong, C and Singhakaew, S and Wongphayak, S and Chankhamhaengdecha, S and Janvilisri, T}, title = {Identification and preclinical evaluation of MMV676558 as a promising therapeutic candidate against Clostridioides difficile.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {180}, number = {}, pages = {117469}, doi = {10.1016/j.biopha.2024.117469}, pmid = {39321508}, issn = {1950-6007}, abstract = {Clostridioides difficile, a gram-positive, toxin-producing, spore-forming anaerobe, is a major cause of antibiotic-associated diarrhoea. The bacterium's intrinsic drug resistance limits current treatment options to fidaxomicin and vancomycin for initial episodes, with anti-toxin B monoclonal antibody or faecal microbiota transplantation recommended for complicated or recurrent cases. This underscores the urgent need for novel therapeutics. In this study, we screened the MMV Pathogen Box at a 10 µM concentration against C. difficile R20291. Primary hits were evaluated for minimum inhibitory concentrations (MIC), killing kinetics, and biofilm inhibition. Bacterial cytological profiling (BCP) and transmission electron microscopy (TEM) were employed to study the mode of action. MMV676558 was further tested in a mouse model to assess survival, histopathology, and gut microbiota effects. We identified nineteen hits that inhibited over 50 % of C. difficile growth. MIC assays revealed three hits with MICs below 16 µg/mL: MMV676558, MMV688755, and MMV690027. These hits were effective against various C. difficile ribotypes. Killing kinetics were comparable or superior to vancomycin and fidaxomicin, and biofilm assays showed inhibitory effects. BCP and TEM analyses suggested membrane function disruption as the mode of action. Furthermore, MMV676558 demonstrated a protective effect in mice, with favourable histopathology and gut microbiota profiles. Given the urgent threat posed by C. difficile antibiotic resistance, discovering new treatments is a top priority. Our study identified three promising hits from the MMV Pathogen Box, with MMV676558 showing significant in vivo potential for further evaluation.}, } @article {pmid39320321, year = {2024}, author = {Berry, P and Khanna, S}, title = {Fecal microbiota spores, live-brpk (VOWST™/VOS) for prevention of recurrent Clostridioides difficile infection.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/17460913.2024.2403892}, pmid = {39320321}, issn = {1746-0921}, abstract = {Clostridioides difficile infection (CDI) is a health crisis comprising a majority of healthcare-associated infections and is now being seen in the community. Persistent dysbiosis despite treatment with standard-of-care antibiotics increases risk of recurrent infections. Fecal microbiota transplantation has been an effective way of addressing dysbiosis, but the studies have lacked standardization, which makes outcome and safety data difficult to interpret. Standardized microbiome therapies have demonstrated efficacy and safety for recurrent CDI and have been approved to prevent recurrent infection. In this review, we discuss the data behind and the practice use of fecal microbiota spores, live-brpk (VOWST™ / VOS), a US FDA approved live biotherapeutic for the prevention of recurrent CDI.}, } @article {pmid39320101, year = {2024}, author = {Xue, H and Wang, Y and Mei, C and Han, L and Lu, M and Li, X and Chen, T and Wang, F and Tang, X}, title = {Gut microbiome and serum metabolome alterations associated with lactose intolerance (LI): a case‒control study and paired-sample study based on the American Gut Project (AGP).}, journal = {mSystems}, volume = {}, number = {}, pages = {e0083924}, doi = {10.1128/msystems.00839-24}, pmid = {39320101}, issn = {2379-5077}, abstract = {UNLABELLED: Lactose intolerance (LI) is a prevalent condition characterized by gastrointestinal symptoms that arise following lactose consumption. Recent evidence suggests that the gut microbiome may influence lactose levels in the gut. However, there is limited understanding regarding the alterations in microbiota and metabolism between individuals with LI and non-LI. This study conducted a paired-sample investigation utilizing data from the American Gut Project (AGP) and performed metagenomic and untargeted metabolomic analyses in a Chinese cohort to explore the interaction between the gut microbiome and serum metabolites. In addition, fecal microbiota transplantation (FMT) experiments were conducted to further examine the impact of the LI-associated gut microbiome on inflammatory outcomes. We identified 14 microbial genera that significantly differed between LI and controls from AGP data. Using a machine learning approach, group separation was predicted based on seven species and nine metabolites in the Chinese cohort. Notably, increased levels of Escherichia coli in the LI group were negatively correlated with several metabolites, including PC (22:6/0:0), indole, and Lyso PC, while reduced levels of Faecalibacterium prausnitzii and Eubacterium rectale were positively correlated with indole and furazolidone. FMT-LI rats displayed visceral hypersensitivity and an altered gut microbiota composition compared to FMT-HC rats. Metagenomic and metabolomic analyses revealed an enrichment of MAPK signaling in LI, which was confirmed by FMT-LI rats showing higher expression of ERK and RAS, along with increased concentrations of proinflammatory cytokines. This study provides valuable insights into the disrupted microbial and metabolic traits associated with LI, emphasizing potential microbiome-based approaches for its prevention and treatment.

IMPORTANCE: Lactose intolerance (LI) is a prevalent condition characterized by gastrointestinal symptoms after lactose consumption due to a deficiency of lactase. There is limited understanding regarding the microbiota and metabolic alterations between individuals with LI and non-LI. This study represents the first exploration to investigate metagenomic and metabolomic signatures among subjects with lactose intolerance as far as our knowledge. We identified 14 microbial genera in the Western cohort and 7 microbial species, along with 9 circulating metabolites in the Chinese cohort, which significantly differed in LI patients. Metagenomic and metabolomic analyses revealed an enrichment of MAPK signaling in LI patients. This finding was confirmed by FMT-LI rats, exhibiting increased expression of ERK and RAS, along with higher concentrations of pro-inflammatory cytokines. Our study provides insights into the disrupted functional and metabolic traits of the gut microbiome in LI, highlighting potential microbiome-based approaches for preventing and treating LI.}, } @article {pmid39318889, year = {2024}, author = {McGrath, E and Herson, MR and Kuehnert, MJ and Moniz, K and Szczepiorkowski, ZM and Pruett, TL}, title = {A WHO remit to improve global standards for medical products of human origin.}, journal = {Bulletin of the World Health Organization}, volume = {102}, number = {10}, pages = {707-714}, pmid = {39318889}, issn = {1564-0604}, mesh = {Humans ; *World Health Organization ; Global Health ; International Cooperation ; Biological Products/standards ; }, abstract = {In recent decades, considerable advances have been made in assuring the safety of blood transfusion and organ transplantation. However, with the increasing movement of medical products of human origin across international boundaries, there is a need to enhance global norms and governance. These products, which include blood, organs, tissues, cells, human milk and faecal microbiota, are today crucial for health care but they also pose unique risks due to their human origin, such as disease transmission and graft failure. Moreover, the demand for medical products of human origin often exceeds supply, leading to dependence on international supply chains, and emerging technologies like cell and gene therapy present further challenges because of their unproven efficacy and long-term risks. Current regulatory mechanisms, especially in low- and middle-income countries, are insufficient. The World Health Organization (WHO) has both the mandate and experience to lead the development of international quality and safety standards, consistent product nomenclature, and robust traceability and biovigilance systems. An international, multistakeholder approach is critical for addressing the complexities of how medical products of human origin are used globally and for ensuring their safety. This approach will require promoting uniform product descriptions, enhancing digital communication systems and leveraging existing resources to support countries in establishing regulations for these products. As illustrated by World Health Assembly resolution WHA77.4 on transplantation in 2024, WHO's ongoing efforts to ensure the safe, efficient and ethical use of medical products of human origin worldwide provide the opportunity to galvanize international cooperation on establishing norms.}, } @article {pmid39317918, year = {2024}, author = {Ahmadi, S and Hasani, A and Khabbaz, A and Poortahmasbe, V and Hosseini, S and Yasdchi, M and Mehdizadehfar, E and Mousavi, Z and Hasani, R and Nabizadeh, E and Nezhadi, J}, title = {Dysbiosis and fecal microbiota transplant: Contemplating progress in health, neurodegeneration and longevity.}, journal = {Biogerontology}, volume = {}, number = {}, pages = {}, pmid = {39317918}, issn = {1573-6768}, abstract = {The gut-brain axis plays an important role in mental health. The intestinal epithelial surface is colonized by billions of commensal and transitory bacteria, known as the Gut Microbiota (GM). However, potential pathogens continuously stimulate intestinal immunity when they find the place. The last two decades have witnessed several studies revealing intestinal bacteria as a key factor in the health-disease balance of the gut, as well as disease-emergent in other parts of the body. Various neurological processes, such as cognition, learning, and memory, could be affected by dysbiosis in GM. Additionally, the aging process and longevity are related to systemic inflammation caused by dysbiosis. Commensal GM affects brain development, behavior, and healthy aging suggesting that building changes in GM might be a potential therapeutic method. The innovation in GM dysbiosis is intervention by Fecal Microbiota Transplantation (FMT), which has been confirmed as a therapy for recurrent Clostridium difficile infections and is promising for other clinical disorders, such as Parkinson's disease, Multiple Sclerosis (MS), Alzheimer's disease, and depression. Additionally, FMT may be possible to promote healthy aging, and extend longevity. This review aims to connect dysbiosis, neurological disorders, and aging and the potential of FMT as a therapeutic strategy to treat these disorders, and to enhance the quality of life in the elderly.}, } @article {pmid39316685, year = {2024}, author = {Ke, S and Gálvez, JAV and Sun, Z and Cao, Y and Pollock, NR and Chen, X and Kelly, CP and Liu, YY}, title = {Rational Design of Live Biotherapeutic Products for the Prevention of Clostridioides difficile Infection.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiae470}, pmid = {39316685}, issn = {1537-6613}, abstract = {Clostridioides difficile infection (CDI) is a major cause of healthcare- and antibiotic-associated diarrhea. While fecal microbiota transplantation (FMT) shows promise for recurrent CDI, its mechanisms and long-term safety are not fully understood. Live biotherapeutic products (LBPs) using pre-defined bacterial consortia offer an alternative option, but the rational designing LBPs remains challenging. Here, we employ a computational pipeline and three metagenomic datasets to identify microbial strains for LBPs targeting CDI. We constructed the CDI-related microbial genome catalog, comprising 3,741 non-redundant metagenome-assembled genomes (nrMAGs) and identified multiple potential protective nrMAGs, including strains from Dorea formicigenerans, Oscillibacter welbionis, and Faecalibacterium prausnitzii. Importantly, some of these protective nrMAGs were found to play an important role in FMT success, and most top protective nrMAGs can be validated by various previous findings. Our results demonstrate a framework for selecting microbial strains targeting CDI, paving the way for the computational design of LBPs against other enteric infections.}, } @article {pmid39315788, year = {2024}, author = {Wang, Y and Bing, H and Jiang, C and Wang, J and Wang, X and Xia, Z and Chu, Q}, title = {Gut microbiota dysbiosis and neurological function recovery after intracerebral hemorrhage: an analysis of clinical samples.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0117824}, doi = {10.1128/spectrum.01178-24}, pmid = {39315788}, issn = {2165-0497}, abstract = {We aimed to investigate the microbial community composition in patients with intracerebral hemorrhage (ICH) and its effect on prognosis. We designed two clinical cohort studies to explore the gut dysbiosis after ICH and their relationship with neurological function prognosis. First, fecal samples from patients with ICH at three time points: T1 (within 24 h of admission), T2 (3 days after surgery), and T3 (7 days after surgery), and healthy volunteers were subjected to 16S rRNA sequencing using Illumina high-throughput sequencing technology. When differential gut microbiota was identified, the correlation between clinical indicators and microbiotas was analyzed. Subsequently, the patients with ICH were categorized into GOOD and POOR groups based on their Glasgow Outcome Scale Extended (GOS-E) score, and the disparities in gut microbiota between the two groups were assessed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The composition and diversity of the gut microbiota in patients with ICH were different from those in the control group and changed dynamically with the extension of the course of cerebral hemorrhage. The abundances of Enterococcaceae, Clostridiales incertae sedis XI, and Peptoniphilaceae were significantly increased in patients with ICH, whereas Bacteroidaceae, Ruminococcaceae, Lachnospiraceae, and Veillonellaceae were significantly reduced. The relative abundance of Enterococcus gradually increased with the extension of the duration of ICH after surgery, and the abundance of Bacteroides gradually decreased. The abundance of Enterococcus before surgery was found to be negatively associated with patient neurological function prognosis. The original ICH score and Lachnospiraceae status were independent risk factors for predicting the prognosis of neurological function in patients with ICH (P < 0.05). Changes in the gut microbiota diversity in patients with ICH were related to prognosis. Lachnospiraceae may have a protective effect on prognosis.IMPORTANCEAcute central nervous system injuries like hemorrhagic stroke are major global health issues. While surgical hematoma removal can alleviate brain damage, severe cases still have a high 1-month mortality rate of up to 40%. Gut microbiota significantly impacts health, and treatments like fecal microbiota transplantation (FMT) and probiotics can improve brain damage by correcting gut microbiota imbalances caused by ischemic stroke. However, few clinical studies have explored this relationship in hemorrhagic stroke. This study investigated the impact of cerebral hemorrhage on the composition of gut microbiota, and we found that Lachnospiraceae were the independent risk factors for poor prognosis in intracerebral hemorrhage (ICH). The findings offer potential insights for the application of FMT in patients with ICH, and it may improve the prognosis of patients.}, } @article {pmid38925098, year = {2024}, author = {Barron, M and Fernando, DG and Atkinson, SN and Kirby, J and Kindel, TL}, title = {Sleeve Gastrectomy Protects Against Hypertension in Rats due to Changes in the Gut Microbiome.}, journal = {The Journal of surgical research}, volume = {301}, number = {}, pages = {118-126}, doi = {10.1016/j.jss.2024.05.044}, pmid = {38925098}, issn = {1095-8673}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Gastrectomy/adverse effects ; Male ; *Hypertension/microbiology/etiology/therapy ; *Rats, Zucker ; *Fecal Microbiota Transplantation ; Rats ; *Obesity/microbiology/surgery ; Blood Pressure ; Disease Models, Animal ; Feces/microbiology ; }, abstract = {INTRODUCTION: Sleeve gastrectomy (SG), results in improvement in hypertension. We have previously published that rodent SG improves hypertension independent of weight loss associated with unique shifts in the gut microbiome. We tested if the gut microbiome directly improves blood pressure by performing fecal material transfer (FMT) from post-SG rats to surgery-naïve animals.

METHODS: We performed SG or Sham surgery in male, Zucker rats (n = 6-7) with obesity. Stool was collected postop from surgical donors for treatment of recipient rats. Three nonsurgical groups received daily, oral consumption of SG stool, sham stool, or vehicle alone (Nutella) for 10 wk (n = 7-8). FMT treatment was assessed for effects on body weight, food intake, oral glucose tolerance, and blood pressure. Genomic deoxyribonucleic acid of stool from donor and recipient groups were sequenced by 16S ribosomal ribonucleic acid and analyzed for diversity, abundance, and importance.

RESULTS: Ten weeks of SG-FMT treatment significantly lowered systolic blood pressures in surgery-naïve, recipient rats compared to vehicle treatment alone (126.8 ± 13.3 mmHg versus 151.8 ± 12.2 mmHg, P = 0.001). SG-FMT treatment also significantly altered beta diversity metrics compared to Sham-FMT and vehicle treatment. In random forest analysis, amplicon sequence variant level significantly predicted FMT group, P = 0.01.

CONCLUSIONS: We have found a direct link between gut microbial changes after SG and regulation of blood pressure. Future mechanistic studies are required to learn what specific gut microbial changes are required to induce improvements in obesity-associated hypertension and translation to clinical, metabolic surgery.}, } @article {pmid39315776, year = {2024}, author = {Li, S and Liu, M and Han, Y and Liu, C and Cao, S and Cui, Y and Zhu, X and Wang, Z and Liu, B and Shi, Y}, title = {Gut microbiota-derived gamma-aminobutyric acid improves host appetite by inhibiting satiety hormone secretion.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0101524}, doi = {10.1128/msystems.01015-24}, pmid = {39315776}, issn = {2379-5077}, abstract = {Globally, appetite disorders have become an increasingly prominent public health issue. While short-term appetite loss may seem relatively harmless, prolonged instances can lead to serious physical and mental damage. In recent years, numerous studies have highlighted the significant role of the "microbiota-gut-brain" axis in the regulation of feeding behavior in organisms, suggesting that targeting the gut microbiota may be a novel therapeutic strategy for appetite disorders. However, the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between the two remain unclear. Based on this, we conducted 16S rRNA sequencing to analyze the gut microbiota of rabbits with high and low feed intake, followed by fecal microbiota transplantation (FMT) and metabolite gavage experiments to elucidate the underlying mechanisms. Our research indicates that the high feed intake group exhibited significant enrichment of the g__Bacteroides and gamma-aminobutyric acid (GABA), and intragastric administration of GABA effectively promoted the host's feeding behavior. The underlying mechanism involves GABA derived from the gut microbiota inhibiting the secretion of satiety hormones to enhance the host's feeding behavior. Furthermore, the results of FMT suggest that differences in gut microbiota composition may be a contributing factor to varying levels of feed intake in the host. In conclusion, these findings emphasize the role of the gut microbiota-derived GABA, in increasing host feed intake, offering a new target for the treatment of appetite disorders from the perspective of gut microbiota.IMPORTANCEThe incidence of anorexia is rapidly increasing and has become a global burden. Gut microbiota can participate in the regulation of host feeding behavior, yet the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between them remain unclear. In this study, we utilized 16S rRNA sequencing to investigate the composition of the gut microbiota in rabbits with varying levels of feed intake and employed fecal microbiota transplantation and gastric infusion experiments with gamma-aminobutyric acid (GABA) to elucidate the potential mechanisms involved. GABA derived from the gut microbiota can effectively enhance the host's feeding behavior by inhibiting the secretion of satiety hormones. This discovery underscores the pivotal role of the gut microbiota in modulating host appetite, offering novel research avenues and therapeutic targets for appetite disorders.}, } @article {pmid39315595, year = {2024}, author = {Sun, B and Wang, Y and Bai, J and Li, X and Ma, L and Man, S}, title = {Litchi Procyanidins Ameliorate DSS-Induced Colitis through Gut Microbiota-Dependent Regulation of Treg/Th17 Balance.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c05577}, pmid = {39315595}, issn = {1520-5118}, abstract = {Ulcerative colitis (UC) is a common chronic, relapsing inflammatory bowel condition. Procyanidins (PC) are known for their antiangiogenic, anti-inflammatory, antioxidant, and antimetastatic properties. However, there is comparatively limited information on how PC interacts with UC. In this study, 5 mg/10 mL/kg body weight of PC was administered to mice with dextran sulfate sodium (DSS)-induced colitis mice. PC treatment prolonged the survival period of mice, ameliorated UC symptoms, reduced damage to the intestinal mucosal barrier, and increased the protein expression of ZO-1 and occludin in the DSS-treated mice. Importantly, PC treatment significantly reduced gene expression related to Th17 cell differentiation, including STAT3, SMAD3, TGF-β, and JAK1. The results of the flow cytometry analysis indicated significant increase in the number of Treg cells and a concomitant decrease in the proportion of Th17 cells in the colon following PC treatment. Additionally, PC increased the abundance of gut microbiota such as Bacteroidota, Oscillospiraceae, Muribaculaceae, and Desulfovibrionaceae, as well as the concentrations of acetate acid, propionate acid, and butyrate acid in the feces. PC also activated short-chain fatty acid receptors, such as G-protein coupled receptor 43 in the colon, which promoted the proliferation of Treg cells. The depletion of gut microbiota and subsequent transplantation of fecal microbiota demonstrated that PC's effects on gut microbiota were effective in improving UC and restoring intestinal Th17/Treg homeostasis in a microbiota-dependent manner. This suggests that PC could be a promising functional food for the prevention and treatment of UC in the future.}, } @article {pmid39315196, year = {2024}, author = {Luo, C and Yang, Y and Jiang, C and Lv, A and Zuo, W and Ye, Y and Ke, J}, title = {Influenza and the gut microbiota: A hidden therapeutic link.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37661}, pmid = {39315196}, issn = {2405-8440}, abstract = {BACKGROUND: The extensive community of gut microbiota significantly influences various biological functions throughout the body, making its characterization a focal point in biomedicine research. Over the past few decades, studies have revealed a potential link between specific gut bacteria, their associated metabolic pathways, and influenza. Bacterial metabolites can communicate directly or indirectly with organs beyond the gut via the intestinal barrier, thereby impacting the physiological functions of the host. As the microbiota increasingly emerges as a 'gut signature' in influenza, gaining a deeper understanding of its role may offer new insights into its pathophysiological relevance and open avenues for novel therapeutic targets. In this Review, we explore the differences in gut microbiota between healthy individuals and those with influenza, the relationship between gut microbiota metabolites and influenza, and potential strategies for preventing and treating influenza through the regulation of gut microbiota and its metabolites, including fecal microbiota transplantation and microecological preparations.

METHODS: We utilized PubMed and Web of Science as our search databases, employing keywords such as "influenza," "gut microbiota," "traditional Chinese medicine," "metabolites," "prebiotics," "probiotics," and "machine learning" to retrieve studies examining the potential therapeutic connections between the modulation of gut microbiota and its metabolites in the treatment of influenza. The search encompassed literature from the inception of the databases up to December 2023.

RESULTS: Fecal microbiota transplantation (FMT), microbial preparations (probiotics and prebiotics), and traditional Chinese medicine have unique advantages in regulating intestinal microbiota and its metabolites to improve influenza outcomes. The primary mechanism involves increasing beneficial intestinal bacteria such as Bacteroidetes and Bifidobacterium while reducing harmful bacteria such as Proteobacteria. These interventions act directly or indirectly on metabolites such as short-chain fatty acids (SCFAs), amino acids (AAs), bile acids, and monoamines to alleviate lung inflammation, reduce viral load, and exert anti-influenza virus effects.

CONCLUSION: The gut microbiota and its metabolites have direct or indirect therapeutic effects on influenza, presenting broad research potential for providing new directions in influenza research and offering references for clinical prevention and treatment. Future research should focus on identifying key strains, specific metabolites, and immune regulation mechanisms within the gut microbiota to accurately target microbiota interventions and prevent respiratory viral infections such as influenza.}, } @article {pmid39314882, year = {2024}, author = {Larsen, OFA and Brummer, RJM}, title = {Perspective: on the future of fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1449133}, pmid = {39314882}, issn = {1664-302X}, abstract = {Fecal Microbiota Transplantation (FMT) has shown to possess impressive potential benefit for a wide range of clinical indications. Due to its inherent safety issues and efficacy constraints, the use of personalized FMT analogs could be a promising avenue. The development of such analogs will require a detailed understanding of their functionality, encompassing not only microbe-host interactions of the microbial taxa that are involved, but also of the ecological dimensions of the analogs and an overview of the gastrointestinal sites where these relevant microbial interactions take place. Moreover, characterization of taxa that have been lost due to diminished exposure to beneficial microbes, as a consequence of Western lifestyle, may lead to creation of future FMT analogs with the capacity to restore functionalities that we have lost.}, } @article {pmid39314425, year = {2024}, author = {de Araujo, A and Sree Kumar, H and Yang, T and Plata, AA and Dirr, EW and Bearss, N and Baekey, DM and Miller, DS and Donertas-Ayaz, B and Ahmari, N and Singh, A and Kalinoski, AL and Garrett, TJ and Martyniuk, CJ and de Lartigue, G and Zubcevic, J}, title = {Intestinal serotonergic vagal signaling as a mediator of microbiota-induced hypertension.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.07.17.603451}, pmid = {39314425}, issn = {2692-8205}, abstract = {Hypertension is a pervasive global health challenge, impacting over a billion individuals worldwide. Despite strides in therapeutic strategies, a significant proportion of patients remain resistant to the currently available therapies. While conventional treatments predominantly focus on cardiac, renal, and cerebral targets, emerging research underscores the pivotal role of the gut and its microbiota. Yet, the precise mechanisms governing interactions between the gut microbiota and the host blood pressure remain unclear. Here we describe a neural host-microbiota interaction that is mediated by the intestinal serotonin (5-HT) signaling via vagal 5HT3a receptors and which is crucial for maintenance of blood pressure homeostasis. Notably, a marked decrease in both intestinal 5-HT and vagal 5HT3aR signaling is observed in hypertensive rats, and in rats subjected to fecal microbiota transplantation from hypertensive rats. Leveraging an intersectional genetic strategy in a Cre rat line, we demonstrate that intestinal 5HT3aR vagal signaling is a crucial link between the gut microbiota and blood pressure homeostasis and that recovery of 5-HT signaling in colon innervating vagal neurons can alleviate hypertension. This paradigm-shifting finding enhances our comprehension of hypertensive pathophysiology and unveils a promising new therapeutic target for combating resistant hypertension associated with gut dysbiosis.}, } @article {pmid39311394, year = {2024}, author = {Ben Salem, I and Khemiri, H and Drechsel, O and Arbi, M and Böttcher, S and Mekki, N and Ben Fraj, I and Souiai, O and Yahyaoui, M and Ben Farhat, E and Meddeb, Z and Touzi, H and Ben Mustapha, I and BenKahla, A and Ouederni, M and Barbouche, MR and Diedrich, S and Triki, H and Haddad-Boubaker, S}, title = {Reversion of neurovirulent mutations, recombination and high intra-host diversity in vaccine-derived poliovirus excreted by patients with primary immune deficiency.}, journal = {Journal of medical virology}, volume = {96}, number = {9}, pages = {e29918}, doi = {10.1002/jmv.29918}, pmid = {39311394}, issn = {1096-9071}, support = {811034//European project PHINDaccess: Strengthening Omics data analysis capacities in pathogen-host interaction/ ; LR20IPT10//Tunisian Ministry of Higher Education and Scientifc Research/ ; }, mesh = {Humans ; *Poliovirus/genetics/classification/isolation & purification/immunology ; *Poliovirus Vaccine, Oral/genetics/adverse effects ; *Recombination, Genetic ; *Mutation ; *Poliomyelitis/virology/prevention & control ; *Feces/virology ; Male ; Female ; *Virus Shedding ; Genome, Viral/genetics ; Genetic Variation ; Primary Immunodeficiency Diseases/genetics ; Child, Preschool ; Evolution, Molecular ; Child ; Infant ; Virulence/genetics ; Phylogeny ; }, abstract = {Patients with Primary immunodeficiency (PIDs) may be infected by Polioviruses (PVs), especially when vaccinated with live Oral Polio Vaccine before diagnosis. They may establish long-term shedding of divergent strains and may act as reservoirs of PV transmission. This study delved into the effect of the genetic evolution of complete PV genomes, from MHC class II-deficient patients, on the excretion duration and clinical outcomes. Stool samples from three PID patients underwent analysis for PV detection through inoculation on cell culture and real-time PCR, followed by VP1 partial sequencing and full genome sequencing using the Illumina technology. Our findings revealed a low number of mutations for one patient who cleared the virus, while two exhibited a high intra-host diversity favoring the establishment of severe outcomes. Neurovirulence-reverse mutations were detected in two patients, possibly leading to paralysis development. Furthermore, a recombination event, between type 3 Vaccine-Derived Poliovirus and Sabin-like1 (VDPV3/SL1), occurred in one patient. Our findings have suggested an association between intra-host diversity, recombination, prolonged excretion of the virus, and emergence of highly pathogenic strains. Further studies on intra-host diversity are crucial for a better understanding of the virus evolution as well as for the success of the Global Polio Eradication Initiative.}, } @article {pmid39309854, year = {2024}, author = {Wu, M and Chen, X and Lu, Q and Yao, X}, title = {Fecal microbiota transplantation for the treatment of chronic inflammatory skin diseases.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37432}, pmid = {39309854}, issn = {2405-8440}, abstract = {The regulation of immune functions and the maintenance of homeostasis in the internal environment are both integral to human gut microbiota (GM). If GM is disturbed, it can result in a range of autoimmune diseases, including chronic inflammatory skin conditions. Chronic inflammatory skin diseases driven by T or B-cell-mediated immune reactions are complex, including the most prevalent diseases and some rare diseases. Expanding knowledge of GM dysbiosis in chronic inflammatory skin diseases has emerged. The GM has some causal roles in the pathogenesis of these skin conditions. Targeting microbiota treatment, particularly fecal microbiota transplantation (FMT), is considered to be a promising strategy. FMT was commonly used in intestinal diseases by reshaping and balancing GM, serving as a reasonable administration in these skin inflammatory diseases. This paper summarizes the existing knowledge of GM dysbiosis in chronic inflammatory skin diseases and the research data on FMT treatment for such conditions.}, } @article {pmid39306158, year = {2024}, author = {Peng, G and Wang, S and Zhang, H and Xie, F and Jiao, L and Yuan, Y and Ma, C and Wu, H and Meng, Z}, title = {Tremella aurantialba polysaccharides alleviates ulcerative colitis in mice by improving intestinal barrier via modulating gut microbiota and inhibiting ferroptosis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {135835}, doi = {10.1016/j.ijbiomac.2024.135835}, pmid = {39306158}, issn = {1879-0003}, abstract = {We aimed to investigate the effect of a polysaccharide from Tremella aurantialba on ulcerative colitis (UC), which targets ferroptosis in epithelial cells. TA 2-1 (127 kDa) was isolated from T. aurantialba and consisted of Man, Xyl, GlcA, Glc, Fuc and Rha with a molar ratio of 59.2: 23.2: 13.9: 1.6: 1.7: 0.4, exhibited a 1, 3-Man structure with branch chains of T-Xylp, 1,3-Xylp, 1,4-GlcAp, and T-Manp at its O-2 position. TA 2-1 (100 mg/mL) inhibited the cell viability of ferroptosis (19.8 %) in RLS3-induced Caco2 cells and significantly ameliorated symptoms in the colons of mice with dextran sodium sulfate (DSS)-induced UC. TA 2-1 remarkably repaired the intestinal barrier by upregulating claudin-1 and zonula occludens-1 levels. Further analysis found TA 2-1 significantly suppressed lipid peroxidation by regulating ferroptosis-related proteins in UC mice, suggesting that its protective effects are partially mediated by inhibiting ferroptosis. Further analysis of the gut microbiota and fecal microbiota transplantation revealed TA 2-1 might relieve UC symptoms or inhibit ferroptosis by modulating the gut microbiota's composition or metabolites. Results suggest the protective effects of TA 2-1 on the intestinal barrier by inhibiting ferroptosis of epithelial cells, at least by regulating the gut microbiota, highlighting the potential of TA 2-1 in UC treatment.}, } @article {pmid39306049, year = {2024}, author = {Shan, L and Fan, H and Guo, J and Zhou, H and Li, F and Jiang, Z and Wu, D and Feng, X and Mo, R and Liu, Y and Zhang, T and Zhou, Y}, title = {Impairment of oocyte quality caused by gut microbiota dysbiosis in obesity.}, journal = {Genomics}, volume = {116}, number = {5}, pages = {110941}, doi = {10.1016/j.ygeno.2024.110941}, pmid = {39306049}, issn = {1089-8646}, abstract = {Obesity poses risks to oocyte maturation and embryonic development in mice and humans, linked to gut microbiota dysbiosis and altered host metabolomes. However, it is unclear whether symbiotic gut microbes have a pivotal role in oocyte quality. In mouse models of fecal microbiota transplantation, we demonstrated aberrant meiotic apparatus and impaired maternal mRNA in oocytes, which is coincident with the poor developmental competence of embryos. Using metabolomics profiling, we discovered that the cytosine and cytidine metabolism was disturbed, which could account for the fertility defects observed in the high-fat diet (HFD) recipient mice. Additionally, cytosine and cytidine are closely related with gut microbiota dysbiosis, which is accompanied by a notable reduction of abundance of Christensenellaceae R-7 group in the HFD mice. In summary, our findings provided evidence that modifying the gut microbiota may be of value in the treatment of infertile female individuals with obesity.}, } @article {pmid38367140, year = {2024}, author = {Tao, Y and Luo, CJ and Zhang, BH and Shen, XY and Zhao, RK and Ma, BY and Shen, N and Luo, CY and Wang, JM and Xia, YJ and Xie, L and Chen, J and Mo, X}, title = {Diagnostic performance of a multiplexed gastrointestinal PCR panel for identifying diarrheal pathogens in children undergoing hematopoietic stem cell transplant.}, journal = {World journal of pediatrics : WJP}, volume = {20}, number = {9}, pages = {966-975}, pmid = {38367140}, issn = {1867-0687}, support = {20dz2260900//Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics/ ; 20dz2261100//Shanghai Key Laboratory of Emergency Prevention Diagnosis and Treatment of Respiratory Infectious Diseases/ ; 22ZR1440300//Natural Science Foundation of Shanghai/ ; 81971890//National Natural Science Foundation of China/ ; PKJ2020-Y01//Science and Technology Innovation Plan Of Shanghai Science and Technology CommissionScience and Technology Development Fund of Shanghai Pudong New Area/ ; 20Y11903600//Scientific and Technology Commission of Shanghai Municipality/ ; 2022XD054//Shanghai Municipal Health Commission/ ; 22SG13//Shanghai Municipal Education Commission/ ; }, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; *Diarrhea/microbiology/diagnosis/etiology ; Child ; Child, Preschool ; Prospective Studies ; Adolescent ; Multiplex Polymerase Chain Reaction ; Feces/microbiology/virology ; Infant ; Graft vs Host Disease/diagnosis ; }, abstract = {BACKGROUND: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection.

METHODS: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28 ± 7 days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays.

RESULTS: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P < 0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%).

CONCLUSIONS: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed.}, } @article {pmid39305117, year = {2024}, author = {Walrath, T and Najarro, KM and Giesy, LE and Khair, S and Orlicky, DJ and McMahan, RH and Kovacs, EJ}, title = {Reducing the excessive inflammation after burn injury in aged mice by maintaining a healthier intestinal microbiome.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {38}, number = {18}, pages = {e70065}, doi = {10.1096/fj.202401020R}, pmid = {39305117}, issn = {1530-6860}, support = {R01 AG018859/AG/NIA NIH HHS/United States ; R35 GM131831/GM/NIGMS NIH HHS/United States ; T32 GM136444/GM/NIGMS NIH HHS/United States ; T32 AG000279/AG/NIA NIH HHS/United States ; F32 AG082443/AG/NIA NIH HHS/United States ; I01BX004335//U.S. Department of Veterans Affairs (VA)/ ; }, mesh = {Animals ; *Burns/microbiology ; *Gastrointestinal Microbiome ; Mice ; *Inflammation/microbiology ; Mice, Inbred C57BL ; Male ; Aging ; Feces/microbiology ; Lung/microbiology/metabolism/pathology ; Fecal Microbiota Transplantation ; Bacteroidetes ; Ileum/microbiology/metabolism ; }, abstract = {One in six people are projected to be 65 years or older by 2050. As the population ages, better treatments for injuries that disproportionately impact the aged population will be needed. Clinical studies show that people aged 65 and older experience higher rates of morbidity and mortality after burn injury, including a greater incidence of pulmonary complications when compared to younger burn injured adults, which we and others believe is mediated, in part, by inflammation originating in the intestines. Herein, we use our clinically relevant model of scald burn injury in young and aged mice to determine whether cohousing aged mice with young mice or giving aged mice oral gavage of fecal material from young mice is sufficient to alter the microbiome of the aged mice and protect them from inflammation in the ileum and the lungs. Aged burn injured mice have less DNA expression of Bacteroidetes in the feces and an unhealthy Firmicutes/Bacteroidetes ratio. Both Bacteroidetes and the ratio of these two phyla are restored in aged burn injured by prior cohousing for a month with younger mice but not fecal transfer from young mice. This shift in the microbiome coincides with heightened expression of danger-associated molecular patterns (DAMP), and pro-inflammatory cytokine interleukin-6 (il6) in the ileum and lung of aged, burn injured mice, and heightened antimicrobial peptide camp in the lung. Cohousing reverses DAMP expression in the ileum and lung, and cathelicidin-related antimicrobial peptide protein (camp) in the lung, while fecal transfer heightened DAMPs while reducing camp in the lung, and also increased IL-6 protein in the lungs. These results highlight the importance of the intestinal microbiome in mediating inflammation within the gut-lung axis, giving insights into potential future treatments in the clinic.}, } @article {pmid39303815, year = {2024}, author = {Xie, X and Li, W and Xiong, Z and Xu, J and Liao, T and Sun, L and Xu, H and Zhang, M and Zhou, J and Xiong, W and Fu, Z and Li, Z and Han, Q and Cui, D and Anthony, DC}, title = {Metformin reprograms tryptophan metabolism via gut Microbiome-Derived bile acid metabolites to ameliorate Depression-Like behaviors in mice.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2024.09.014}, pmid = {39303815}, issn = {1090-2139}, abstract = {As an adjunct therapy, metformin enhances the efficacy of conventional antidepressant medications. However, its mode of action remains unclear. Here, metformin was found to ameliorate depression-like behaviors in mice exposed to chronic restraint stress (CRS) by normalizing the dysbiotic gut microbiome. Fecal transplants from metformin-treated mice ameliorated depressive behaviors in stressed mice. Microbiome profiling revealed that Akkermansia muciniphila (A. muciniphila), in particular, was markedly increased in the gut by metformin and that oral administration of this species alone was sufficient to reverse CRS-induced depressive behaviors and normalize aberrant stress-induced 5-hydroxytryptamine (5-HT) metabolism in the brain and gut. Untargeted metabolomic profiling further identified the bile acid metabolites taurocholate and deoxycholic acid as direct A. muciniphila-derived molecules that are, individually, sufficient to rescue the CRS-induced impaired 5-HT metabolism and depression-like behaviors. Thus, we report metformin reprograms 5-HT metabolism via microbiome-brain interactions to mitigate depressive syndromes, providing novel insights into gut microbiota-derived bile acids as potential therapeutic candidates for depressive mood disorders from bench to bedside.}, } @article {pmid39303724, year = {2024}, author = {Wang, X and Fang, Y and Liang, W and Wong, CC and Qin, H and Gao, Y and Liang, M and Song, L and Zhang, Y and Fan, M and Liu, C and Lau, HC and Xu, L and Li, X and Song, W and Wang, J and Wang, N and Yang, T and Mo, M and Zhang, X and Fang, J and Liao, B and Sung, JJY and Yu, J}, title = {Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer.}, journal = {Cancer cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ccell.2024.08.019}, pmid = {39303724}, issn = {1878-3686}, abstract = {Microsatellite stable (MSS) colorectal cancers (CRCs) are often resistant to anti-programmed death-1 (PD-1) therapy. Here, we show that a CRC pathogen, Fusobacterium nucleatum (Fn), paradoxically sensitizes MSS CRC to anti-PD-1. Fecal microbiota transplantation (FMT) from patients with Fn-high MSS CRC to germ-free mice bearing MSS CRC confers sensitivity to anti-PD-1 compared to FMT from Fn-low counterparts. Single Fn administration also potentiates anti-PD-1 efficacy in murine allografts and CD34[+]-humanized mice bearing MSS CRC. Mechanistically, we demonstrate that intratumoral Fn generates abundant butyric acid, which inhibits histone deacetylase (HDAC) 3/8 in CD8[+] T cells, inducing Tbx21 promoter H3K27 acetylation and expression. TBX21 transcriptionally represses PD-1, alleviating CD8[+] T cell exhaustion and promoting effector function. Supporting this notion, knockout of a butyric acid-producing gene in Fn abolishes its anti-PD-1 boosting effect. In patients with MSS CRC, high intratumoral Fn predicts favorable response to anti-PD-1 therapy, indicating Fn as a potential biomarker of immunotherapy response in MSS CRC.}, } @article {pmid39303605, year = {2024}, author = {Zhao, Y and Sokol, H and Cao, Q and Zhang, H and Yan, Y and Xie, L and Wang, H}, title = {Systemic inflammatory response to daily exposure to microcystin-LR and the underlying gut microbial mechanisms.}, journal = {Journal of hazardous materials}, volume = {480}, number = {}, pages = {135855}, doi = {10.1016/j.jhazmat.2024.135855}, pmid = {39303605}, issn = {1873-3336}, abstract = {Cyanobacterial toxins have raised global concerns due to potential chronic disease implications from daily drinking water exposure, which remain largely unknown despite extensive research on their acute effects. To understand the mechanisms underlying microcystin-LR (MC-LR)-induced inflammation-associated diseases. Mice were exposed to MC-LR for one year at concentrations comparable to human environmental exposure levels. Comprehensive pathological observation and multi-omics approaches based on 16S rRNA gene sequencing, untargeted metabolomics, transcriptomics and proteomics were conducted across various organs. Daily exposure to MC-LR induced intestinal microbial dysbiosis and colitis-like changes. It also caused systemic chronic inflammation marked by elevated serum levels of inflammatory cytokines, inflammation-associated pathological changes, and identification of infection-related genes/proteins within the gut-brain-spleen-liver axis. Furthermore, multi-omics analysis across organs suggested that Muribaculaceae may promote a systemic infection-inflammatory response, relying on kynurenine metabolites signaling in peripheral tissues. In contrast, Lachnospiraceae may act an opposing role, dependent on intestinal indole derivatives via the neuroimmunomodulation pathway. A fecal microbiota transplantation experiment confirmed that alterations in Muribaculaceae and Lachnospiraceae resulting from exposure to MC-LR triggered the local and systemic chronic inflammation in mice. This study light on the potential strategies employed by gut microbial community in regulating MC-induced inflammation-associated chronic diseases under repeated exposure through drinking water.}, } @article {pmid39301964, year = {2024}, author = {Bohm, MS and Ramesh, AV and Pierre, JF and Cook, KL and Murphy, EA and Makowski, L}, title = {Fecal microbiome transfer an investigative tool and treatment strategy in cancer.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00171.2024}, pmid = {39301964}, issn = {1522-1547}, support = {R01CA253329//HHS | NIH | National Cancer Institute (NCI)/ ; U01CA272541//HHS | NIH | National Cancer Institute (NCI)/ ; U01CA272977//HHS | NIH | National Cancer Institute (NCI)/ ; R01CA246809//HHS | NIH | National Cancer Institute (NCI)/ ; BC210715//U.S. Department of Defense (DOD)/ ; }, abstract = {The gut microbiome plays a critical role in the development, progression, and treatment of cancer. As interest in microbiome-immune-cancer interactions expands, the prevalence of fecal microbial transplant (FMT) models has increased proportionally. However, current literature does not provide adequate details or consistent approaches to allow for necessary rigor and experimental reproducibility. In this review, we evaluate key studies utilizing FMT to investigate the relationship between the gut microbiome and various types of cancer. Additionally, we will discuss the common pitfalls of these experiments and methods for improved standardization and validation as the field utilizes FMT with greater frequency. Last, this review focuses on the impacts of the gut and extra-intestinal microbes, pre-biotics, pro-biotics, and post-biotics in cancer risk and response to therapy across a variety of tumor types.}, } @article {pmid39301264, year = {2024}, author = {Zhao, Y and Ma, S and Liang, L and Cao, S and Fan, Z and He, D and Shi, X and Zhang, Y and Liu, B and Zhai, M and Wu, S and Kuang, F and Zhang, H}, title = {Gut Microbiota-Metabolite-Brain Axis Reconstitution Reverses Sevoflurane-Induced Social and Synaptic Deficits in Neonatal Mice.}, journal = {Research (Washington, D.C.)}, volume = {7}, number = {}, pages = {0482}, pmid = {39301264}, issn = {2639-5274}, abstract = {Background: The mechanisms underlying social dysfunction caused by repeated sevoflurane in early life remain unclear. Whether the gut microbiota-metabolite-brain axis is involved in the mechanism of sevoflurane developmental neurotoxicity still lacks report. Methods: Mice received 3% sevoflurane at postnatal day (PND) 6, 7, and 8 for 2 h per day. Metagenomic sequencing and untargeted metabolomic analysis were applied to investigate the effects of sevoflurane on gut microbiota and metabolism. The animal social behavior and the synaptic development were analyzed during PND 35. Subsequently, fecal microbiota transplantation (FMT) from the control group and bile acid administration were performed to see the expected rescuing effect on socially related behaviors that were impaired by repeated sevoflurane exposure in the mice. Results: In the 3-chamber test, sevoflurane-exposed mice spent less time with stranger mice compared with the control group. The density of both the apical and basal spine decreased in mice exposed to sevoflurane. In addition, repeated sevoflurane exposure led to a notable alteration in the gut microbiota and metabolite synthesis, particularly bile acid. FMT reduced the production of intestinal bile acid and attenuated the effect of sevoflurane exposure on social function and synaptic development. Cholestyramine treatment mimics the protective effects of FMT. Conclusions: The gut microbiota-metabolite-brain axis underlies social dysfunction caused by sevoflurane exposure in early age, and bile acid regulation may be a promising intervention to this impairment.}, } @article {pmid39302074, year = {2024}, author = {Duan, T and Alim, A and Tian, H and Li, T}, title = {Roundup-Induced Gut Dysbiosis, Irrelevant to Aromatic Amino Acid Deficiency, Impairs the Gut Function in Rats.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c04045}, pmid = {39302074}, issn = {1520-5118}, abstract = {Glyphosate, the most popular herbicide globally, has long been considered safe for mammals. However, whether glyphosate can disturb gut microbiota via inhibiting aromatic amino acid (AAA) synthesis has been under debate recently. Here, we evaluated the impacts of chronic exposure to Roundup on gut health with the addition of AAA and explored the mechanism behind Roundup-induced gut dysfunction by performing fecal microbiota transplantation. 500 mg/kg·bw of Roundup, independent of AAA deficiency, caused severe damage to gut function, as characterized by gut microbial dysbiosis, oxidative stress damage, intestinal inflammation, and histopathological injury, particularly in female rats. Notably, similar to Roundup, Roundup-shaped gut microbiome evidently damaged serum, cecum, and colon profiling of oxidative stress biomarkers (malonaldehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione (GSH), and H2O2). Moreover, it induced 0.65-, 3.29-, and 2.36-fold increases in colonic IL-1β, IL-6, and TNF-α levels, and 0.34-fold decreases in the IL-10 level. Upon transplanting healthy fecal microbiota to Roundup-treated rats, they exhibited a healthier gut microenvironment with mitigated inflammation, oxidative damage, and intestinal injury. Overall, our findings provide new insights into the safety of Roundup, highlight the crucial role of gut microbiota in Roundup-induced gut dysfunction, and pave the way for developing gut-microbiota-based strategies to address Roundup-related safety issues.}, } @article {pmid39300177, year = {2024}, author = {Hunthai, S and Usawachintachit, M and Taweevisit, M and Srisa-Art, M and Anegkamol, W and Tosukhowong, P and Rattanachaisit, P and Chuaypen, N and Dissayabutra, T}, title = {Unraveling the role of gut microbiota by fecal microbiota transplantation in rat model of kidney stone disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {21924}, pmid = {39300177}, issn = {2045-2322}, support = {B36G660010//the Program Management Unit for Human Resources and Institutional Development, Research, and Innovation (PMU-B)/ ; RA65/045//Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University, grant number/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Kidney Calculi/microbiology/metabolism/therapy ; Humans ; Rats ; Male ; *Rats, Wistar ; Dysbiosis/microbiology ; Disease Models, Animal ; Feces/microbiology ; Female ; Adult ; Middle Aged ; }, abstract = {Emerging research on the microbiome highlights the significant role of gut health in the development of kidney stones, indicating that an imbalance in gut bacteria or dysbiosis can influence the formation of stones by altering oxalate metabolism and urinary metabolite profiles. In particular, the overabundance of specific bacteria such as Enterococcus and Oxalobacter spp., which are known to affect oxalate absorption, is observed in patients with urolithiasis. This study investigates the effects of gut dysbiosis on urolithiasis through fecal microbiota transplantation (FMT) from patients to rats and its impact on urinary mineral excretion and stone formation. Fecal samples from eight patients with calcium oxalate stones and ten healthy volunteers were collected to assess the gut microbiome. These samples were then transplanted to antibiotic-pretreated Wistar rats for a duration of four weeks. After transplantation, we evaluated changes in the fecal gut microbiome profile, urinary mineral excretion rates, and expression levels of intestinal zonula occluden-1 (ZO-1), SLC26A6 and renal NF-κB. In humans, patients with urolithiasis exhibited increased urinary calcium and oxalate levels, along with decreased citrate excretion and increased urinary supersaturation index. The fecal microbiota showed a notable abundance of Bacteroidota. In rodents, urolithiasis-FMT rats showed urinary disturbances similar to patients, including elevated pH, oxalate level, and supersaturation index, despite negative renal pathology. In addition, a slight elevation in the expression of renal NF-κB, a significant intestinal SLC26A6, and a reduction in ZO-1 expression were observed. The gut microbiome of urolithiasis-FMT rats showed an increased abundance of Bacteroidota, particularly Muribaculaceae, compared to their healthy FMT counterparts. In conclusion, the consistent overabundance of Bacteroidota in both urolithiasis patients and urolithiasis-FMT rats is related to altered intestinal barrier function, hyperoxaluria, and renal inflammation. These findings suggest that gut dysbiosis, characterized by an overgrowth of Bacteroidota, plays a crucial role in the pathogenesis of calcium oxalate urolithiasis, underscoring the potential of targeting the gut microbiota as a therapeutic strategy.}, } @article {pmid39300146, year = {2024}, author = {Juhász, B and Horváth, K and Kuti, D and Shen, J and Feuchtinger, A and Zhang, C and Bata-Vidács, I and Nagy, I and Kukolya, J and Witting, M and Baranyi, M and Ferenczi, S and Walch, A and Sun, N and Kovács, KJ}, title = {Dipeptide metabolite, glutamyl-glutamate mediates microbe-host interaction to boost spermatogenesis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {21864}, pmid = {39300146}, issn = {2045-2322}, support = {SFB 824 C04//Deutsche Forschungsgemeinschaft/ ; 124424//Hungarian National Research, Development and Innovation Office/ ; -1.2.1-NKP-2017-00002//National Brain Research Program 2017/ ; RRF-2.3.1-21-2022-00011//National Laboratory of Translational Neuroscience/ ; }, mesh = {Animals ; Male ; Mice ; *Spermatogenesis ; *Dipeptides/metabolism ; *Testis/metabolism/microbiology ; Sperm Count ; Fecal Microbiota Transplantation ; Testosterone/metabolism ; Host Microbial Interactions ; Metabolomics/methods ; Gastrointestinal Microbiome ; Fertility ; }, abstract = {The decrease in sperm count and infertility is a global issue that remains unresolved. By screening environmental bacterial isolates, we have found that a novel lactic acid bacterium, Lactiplantibacillus plantarum SNI3, increased testis size, testosterone levels, sperm count, sexual activity and fertility in mice that have consumed the bacteria for four weeks. The abundance of L. plantarum in the colon microbiome was positively associated with sperm count. Fecal microbiota transplantation (FMT) from L. plantarum SNI3-dosed mice improved testicular functions in microbiome-attenuated recipient animals. To identify mediators that confer pro-reproductive effects on the host, untargeted in situ mass spectrometry metabolomics was performed on testis samples of L. plantarum SNI3-treated and control mice. Enrichment pathway analysis revealed several perturbed metabolic pathways in the testis of treated mice. Within the testis, a dipeptide, glutamyl-glutamate (GluGlu) was the most upregulated metabolite following L. plantarum SNI3 administration. To validate the pro-reproductive feature of GluGlu, systemic and local injections of the dipeptide have been performed. γ-GluGlu increased sperm count but had no effect on testosterone. These findings highlight the role of γ-GluGlu in mediating spermatogenetic effects of L. plantarum on the male mouse host and -following relevant human clinical trials- may provide future tools for treating certain forms of male infertility.}, } @article {pmid39299827, year = {2024}, author = {Sanabani, SS}, title = {Impact of Gut Microbiota on Lymphoma: New Frontiers in Cancer Research.}, journal = {Clinical lymphoma, myeloma & leukemia}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clml.2024.08.008}, pmid = {39299827}, issn = {2152-2669}, abstract = {The gut microbiome (GMB), which is made up of various microorganisms, plays a crucial role in maintaining the health of the host. Disruptions in this delicate ecosystem, known as microbial dysbiosis, have been linked to various diseases, including hematologic malignancies such as lymphoma. This review article explores the complex relationship between the GMB and the development of lymphoma and highlights its implications for diagnostic and therapeutic approaches. It discusses how GMB influences lymphoma development directly through the presence of certain microorganisms and indirectly through changes in the immune system. The clinical relevance of GMB is highlighted and its potential utility for diagnosis, predicting treatment outcomes and developing personalized therapeutic strategies for lymphoma patients is demonstrated. The review also looks at microbiome-targeted interventions such as fecal microbiome transplantation and dietary modification, which have shown promise for treating microbial dysbiosis and improving patient outcomes. In addition, it highlights the analytical challenges and the need for further research to fully elucidate the mechanistic functions of the GMB in the context of lymphoma. This review emphasizes the critical role of GMB in lymphomagenesis and its potential for the development of diagnostic and therapeutic strategies.}, } @article {pmid37204182, year = {2024}, author = {Wu, X and Tian, X and Cao, G and Wang, Z and Wu, X and Gu, Y and Yan, T}, title = {Distinct profiles of bile acid metabolism caused by gut microbiota in kidney transplantation recipients revealed by 16S rRNA gene sequencing.}, journal = {Archives of physiology and biochemistry}, volume = {130}, number = {5}, pages = {581-590}, doi = {10.1080/13813455.2023.2212331}, pmid = {37204182}, issn = {1744-4160}, mesh = {*Kidney Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; *Bile Acids and Salts/metabolism ; *RNA, Ribosomal, 16S/genetics ; Male ; Female ; Adult ; Middle Aged ; Phylogeny ; Feces/microbiology ; }, abstract = {The present study sought to characterise the gut microbiota of subjects with kidney transplantation and healthy control to identify the distinct gut microbiota and analyse their potential function. We found that gut microbiota abundance had significant differences in subjects between the two groups. Line Discriminant Analysis (LDA) Effect Size (LEfSe) analysis showed that the bacterial taxa were differentially represented between the two groups, and the potential biomarkers at different taxonomic levels in kidney transplant recipients were Streptococcus, Enterococcaceae, and Ruminococcus. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) Functional Inference analyses suggested that the difference in gut microbiota between the two groups was correlated with bile acid metabolism. In conclusion, gut microbiota abundance is different between the two groups, which is related to bile acid metabolism, and may influence the metabolic homeostasis of allograft recipients.}, } @article {pmid39299249, year = {2024}, author = {Aubert, O and Irvine, WFE and Aminoff, D and de Blaauw, I and Cascio, S and Cretolle, C and Iacobelli, BD and Mantzios, K and Midrio, P and Miserez, M and Sarnacki, S and Schmiedeke, E and Schwarzer, N and Sloots, C and Stenström, P and Lacher, M and Gosemann, JH}, title = {European Reference Network eUROGEN Guidelines on the Management of Anorectal Malformations, Part II: Treatment.}, journal = {European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie}, volume = {}, number = {}, pages = {}, doi = {10.1055/s-0044-1791257}, pmid = {39299249}, issn = {1439-359X}, abstract = {INTRODUCTION: Anorectal malformations (ARMs) are rare birth defects affecting the anorectum and oftentimes the genitourinary region. The management of ARM patients is complex and requires highly specialized surgical and medical care. The European Reference Network eUROGEN for rare and complex urogenital conditions aimed to develop comprehensive guidelines for the management of ARM applicable on a European level.

METHODS:  The Dutch Quality Standard for ARM served as the basis for the development of guidelines. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from seven European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering the current evidence, expert opinion, and the European context.

RESULTS:  Surgical and medical treatment of ARM, postoperative instructions, toilet training, and management of fecal and urinary incontinence were addressed. Seven new studies were identified. The panel adapted 23 recommendations, adopted 3, and developed 8 de novo. The overall level of newly found evidence was considered low.

CONCLUSION:  Treatment of ARM patients requires a multidisciplinary team and expertise about anatomical and surgical aspects of the disease, as well as long-term follow-up. This guideline offers recommendations for surgical and medical treatment of ARM and associated complications, according to the best available evidence and applicable on a European level.}, } @article {pmid39298907, year = {2024}, author = {Kaul, R and Paul, P and Harfouche, M and Ayyan, M and Laws, S and Chaari, A}, title = {The effect of microbiome-modulating therapeutics on glucose homeostasis in metabolic syndrome: A systematic review, meta-analysis, and meta-regression of clinical trials.}, journal = {Diabetes & metabolic syndrome}, volume = {18}, number = {8}, pages = {103118}, doi = {10.1016/j.dsx.2024.103118}, pmid = {39298907}, issn = {1878-0334}, abstract = {BACKGROUND: Metabolic syndrome (MetS) is a chronic disorder featuring overweight/obesity, high blood pressure, and dysfunction of lipid and carbohydrate metabolism. Microbiome-modulating probiotics, prebiotics, synbiotics and fecal microbiota transplant (FMT) are promising adjunct therapies for improving parameters of glucose homeostasis and insulinemia.

METHODS: We conducted a comprehensive systematic review, meta-analyses, and meta-regressions to investigate the effect of the abovementioned microbiome therapies on various biomarkers after screening clinical trials published through April 2023. We pooled data using random effects meta-analyses, reporting them as mean differences (MDs) with 95 % confidence intervals (CIs), and conducting univariate linear model meta-regressions.

RESULTS: Data from 21 trial comparisons across 19 studies (n = 911) revealed that, compared to placebo/control, microbiome-modulating therapies were associated with statistically significant changes in fasting plasma glucose (MD: 4.03 mg/dL [95%CI: 6.93; -1.13]; p effect = 0.006, I[2] = 89.8 %), and fasting insulin (MD: 2.56 μU/mL [95%CI: 4.28; -0.84]; p effect = 0.004, I[2] = 87.9 %), but not insulin resistance or sensitivity indices and HbA1c. Age, baseline BMI, baseline biomarker value, pro/synbiotic dosage, trial duration, nutraceutical type, and WHO region were factors affecting the efficacy of these interventions at producing changes in biomarkers, signaling the potential role of personalized precision medicine adjunct therapy for deranged glucose homeostasis in patients with MetS. Nevertheless, presence of heterogeneity calls for further investigation before their clinical application.

CONCLUSIONS: Probiotics, prebiotics, synbiotics and FMT supplementation improved fasting glucose and insulin in patients with MetS. Further large-scale and high-quality trials are required before potential clinical applications.}, } @article {pmid39298815, year = {2024}, author = {Wang, XZ and Huang, JL and Zhang, J and Li, QH and Zhang, PP and Wu, C and Jia, YY and Su, H and Sun, X}, title = {Fecal microbiota transplantation as a new way for OVA-induced atopic dermatitis of juvenile mice.}, journal = {International immunopharmacology}, volume = {142}, number = {Pt B}, pages = {113183}, doi = {10.1016/j.intimp.2024.113183}, pmid = {39298815}, issn = {1878-1705}, abstract = {Children all over the world suffer from atopic dermatitis (AD), a prevalent condition that impairs their health. Corticosteroids, which have long-term negative effects, are frequently used to treat AD. There has been a growing body of research on the gut microbiota's function in AD. Nevertheless, the function and underlying mechanisms of fecal microbiota transplantation (FMT) in AD children remain to be established. Therefore, in order to assess the preventive effects of FMT treatment on AD and investigate the mechanisms, we constructed an ovalbumin (OVA)-induced juvenile mouse AD model in this investigation. This study explored the role and mechanism of FMT treatment in AD through 16S RNA sequencing, pathological histological staining, molecular biology, and Flow cytometry. Results demonstrated that the FMT treatment improved the gut microbiota's diversity and composition, bringing it back to a level similar to that of a close donor. Following FMT treatment, OVA-specific antibodies were inhibited, immunoglobulin (Ig) E production was decreased, the quantity of mast cells and eosinophils was decreased, and specific inflammatory markers in the skin and serum were decreased. Further mechanistic studies revealed that FMT treatment induced CD103[+] DCs and programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression in skin-draining lymph nodes and promoted Treg production to induce immune tolerance and suppress skin inflammation. Meanwhile, changes in the gut microbiota were substantially correlated with Th2 cytokines, OVA-specific antibodies, and PD-L1/PD-1. In conclusion, FMT regulates the Th1/Th2 immunological balance and the gut microbiota. It may also inhibit AD-induced allergy responses through the PD-L1/PD-1 pathway, and providing a unique idea and possibly a fresh approach to the treatment of AD.}, } @article {pmid39295732, year = {2024}, author = {Wang, S and Yuan, Z and Gao, X and Wu, J and Ren, Y and Yu, X and Li, J and Wei, W}, title = {Global research trends on the links between gut microbiota and radiotherapy: a bibliometric analysis (2004-2023).}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1414196}, pmid = {39295732}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; *Bibliometrics ; Humans ; *Radiotherapy ; China ; }, abstract = {BACKGROUND: There is a crosstalk between gut microbiota and radiotherapy. The aim of this study is to use bibliometric analysis to explore the research status and development trends of research on gut microbiota and radiotherapy.

METHODS: A literature search regarding publications on gut microbiota and radiotherapy from 2004 to 2023 was retrieved. CiteSpace and VOSviewer were used to conduct the bibliometric analysis. The growth rate of publications, leading countries and institutions, preferred journals, top authors and co-cited authors, top co-cited references, keywords and citation were analyzed in this study.

RESULTS: A total of 2821 papers were extracted. The number of papers has increased rapidly over the past decade, especially after 2017. The USA and China had the most publications and made great contributions to this field. The Chinese Academy of Sciences stood out as the institution with the highest number of publications, followed by the Chinese Academy of Medical Sciences & Peking Union Medical College. The most influential authors were Fan Saijun and Li Yuan. PLoS One had the most publications and the most total citations. Highly cited papers and high-frequency keywords illustrated the current status and trends. Furthermore, analysis of keyword with burst revealed that immunotherapy, acid, intestinal barrier, therapy, immunotherapy, fecal microbiota transplantation, etc, are at the forefront of research in this area.

CONCLUSION: This study provides an overview of research on gut microbiota and radiotherapy, highlighting influential contributors, impactful publications, and emerging trends. Our finding suggests avenues for further exploration to improve clinical outcomes.}, } @article {pmid39295910, year = {2023}, author = {Sehn Hilgert, S and Dias, DPM}, title = {The intestinal microbiota as an ally in the treatment of Alzheimer's disease.}, journal = {Gut microbiome (Cambridge, England)}, volume = {4}, number = {}, pages = {e9}, pmid = {39295910}, issn = {2632-2897}, abstract = {The evolution of the understanding of the intestinal microbiota and its influence on our organism leverages it as a potential protagonist in therapies aimed at diseases that affect not only the intestine but also neural pathways and the central nervous system itself. This study, developed from a thorough systematic review, sought to demonstrate the influence of the intervention on the intestinal microbiota in subjects with Alzheimer's disease. Clinical trials using different classes of probiotics have depicted noteworthy remission of symptoms, whose measurement was performed based on screenings and scores applied before, during, and after the period of probiotics use, allowing the observation of changes in functionality and symptomatology of patients. On the other hand, faecal microbiota transplantation requires further validation through clinical trials, even though it has already been reported in case studies as promising from the symptomatology point of view. The current compilation of studies made it possible to demonstrate the potential influence of the intestinal microbiota on Alzheimer's pathology. However, new clinical studies with a larger number of participants are needed to obtain further clarification on pathophysiological correlations.}, } @article {pmid39295774, year = {2022}, author = {Iribarren, C and Maasfeh, L and Öhman, L and Simrén, M}, title = {Modulating the gut microenvironment as a treatment strategy for irritable bowel syndrome: a narrative review.}, journal = {Gut microbiome (Cambridge, England)}, volume = {3}, number = {}, pages = {e7}, pmid = {39295774}, issn = {2632-2897}, abstract = {Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with a complex pathophysiology. Growing evidence suggests that alterations of the gut microenvironment, including microbiota composition and function, may be involved in symptom generation. Therefore, attempts to modulate the gut microenvironment have provided promising results as an indirect approach for IBS management. Antibiotics, probiotics, prebiotics, food and faecal microbiota transplantation are the main strategies for alleviating IBS symptom severity by modulating gut microbiota composition and function (eg. metabolism), gut barrier integrity and immune activity, although with varying efficacy. In this narrative review, we aim to provide an overview of the current approaches targeting the gut microenvironment in order to indirectly manage IBS symptoms.}, } @article {pmid39293564, year = {2024}, author = {Zhang, M and Yin, YS and May, KS and Wang, S and Purcell, H and Zhang, XS and Blaser, MJ and den Hartigh, LJ}, title = {The role of intestinal microbiota in physiologic and body compositional changes that accompany CLA-mediated weight loss in obese mice.}, journal = {Molecular metabolism}, volume = {}, number = {}, pages = {102029}, doi = {10.1016/j.molmet.2024.102029}, pmid = {39293564}, issn = {2212-8778}, abstract = {BACKGROUND: Obesity continues to be a major problem, despite known treatment strategies such as lifestyle modifications, pharmaceuticals, and surgical options, necessitating the development of novel weight loss approaches. The naturally occurring fatty acid, 10,12 conjugated linoleic acid (10,12 CLA), promotes weight loss by increasing fat oxidation and browning of white adipose tissue, leading to increased energy expenditure in obese mice. Coincident with weight loss, 10,12 CLA also alters the murine gut microbiota by enriching for microbes that produce short chain fatty acids (SCFAs), with concurrent elevations in fecal butyrate and plasma acetate.

METHODS: To determine if the observed microbiota changes are required for 10,12 CLA-mediated weight loss, adult male mice with diet-induced obesity were given broad-spectrum antibiotics (ABX) to perturb the microbiota prior to and during 10,12 CLA-mediated weight loss. Conversely, to determine whether gut microbes were sufficient to induce weight loss, conventionally-raised and germ-free mice were transplanted with cecal contents from mice that had undergone weight loss by 10,12 CLA supplementation.

RESULTS/CONCLUSION: While body weight was minimally modulated by ABX-mediated perturbation of gut bacterial populations, adult male mice given ABX were more resistant to the increased energy expenditure and fat loss that are induced by 10,12 CLA supplementation. Transplanting cecal contents from donor mice losing weight due to oral 10,12 CLA consumption into conventional or germ-free mice led to improved glucose metabolism with increased butyrate production. These data suggest a critical role for the microbiota in diet-modulated changes in energy balance and glucose metabolism, and distinguish the metabolic effects of orally delivered 10,12 CLA from cecal transplantation of the resulting microbiota.}, } @article {pmid39293366, year = {2024}, author = {Chen, S and Xue, X and Zhang, H and Huang, X and Lin, X and He, J and Chen, L and Luo, S and Gao, J}, title = {Jianwei Shoutai Pills alleviates miscarriage by modulating gut microbial production of BAs and NLRP3-inflammasome at the maternal-fetal interface of rats.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156000}, doi = {10.1016/j.phymed.2024.156000}, pmid = {39293366}, issn = {1618-095X}, abstract = {BACKGROUND: Miscarriage has the characteristics of recurrent attacks and complex etiology, so it is gradually attracted the wide attention of scholars in the fields of reproduction. Potential association between gut microbiome (GM) and pregnancy disorders has been investigated. Jianwei Shoutai pills (JWP), as a representative formula, have been proven to have protective effect in both clinical and experimental research in miscarriage. However, the specific mechanism of JWP in miscarriage through GM remains unclear.

PURPOSE: To investigate the underlying mechanism of JWP against miscarriage through the gut-uterus axis.

METHODS: The effects of JWP on an RU486-induced rat model of miscarriage were evaluated by embryo resorption rate, vaginal bleeding rate, and appearance of the uterus and embryo. We used 16S rRNA sequencing to measure the extent of the effect of JWP on GM of rats with miscarriage. Bile acid (BA) content of the feces of rats treated with JWP was evaluated by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS). The activation of bile acid-associated receptor, Farnesoid X receptor (FXR), was evaluated by immunofluorescence. The expression level of NLRP3 inflammasome-associated protein was detected by Western blot or Elisa. Fecal microbiota transplantation (FMT) was used to confirm that GM was essential for the therapeutic effect of JWP in miscarriage.

RESULTS: JWP significantly ameliorated miscarriage symptoms and embryo resorption rate caused by RU486-induced miscarriage as well as restored the abnormal activation of NLRP3-inflammasome at the maternal-fetal interface. Furthermore, JWP can significantly regulated GM dysbiosis and closely associated with BA metabolism by KEGG pathway prediction analysis. Several BA content were significantly restored by HPLC-MS. The expression of NLRP3 inflammasome-associated protein at maternal-fetal interface was reversed by JWP. Combined with FMT, JWP could regulate activation of NLRP3 at the maternal-fetal interface by BAs produced by GM.

CONCLUSION: JWP restored abnormal activation of the NLRP3-inflammasome in an RU486-induced miscarriage rat model, and corrected the BA disorder by regulating imbalance of the GM.}, } @article {pmid39292598, year = {2024}, author = {Goldsmith, J and Tomkovich, S and Auniņš, JG and McGovern, BH and Mahoney, JC and Hasson, BR and McChalicher, CWJ and Ege, DS}, title = {End-to-end donor screening and manufacturing controls: complementary quality-based strategies to minimize patient risk for donor-derived microbiome therapeutics.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2402550}, doi = {10.1080/19490976.2024.2402550}, pmid = {39292598}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; *Feces/microbiology ; *Donor Selection ; Enema ; }, abstract = {Advances in microbiome therapeutics have been motivated by a deeper understanding of the role that the gastrointestinal microbiome plays in human health and disease. The FDA approval of two stool-derived live biotherapeutic products (LBPs), REBYOTA® 150 mL enema (fecal microbiota, live-jslm; formerly RBX2660) and VOWST® oral capsules (fecal microbiota spores, live-brpk; formerly SER-109), for the prevention of recurrent CDI in adults following antibiotic treatment for recurrent CDI provides promise and insights for the development of LBPs for other diseases associated with microbiome dysfunction. Donor-derived products carry risk of disease transmission that must be mitigated through a robust donor screening program and downstream manufacturing controls. Most published recommendations for donor screening practices are prescriptive and do not include a systematic, risk-based approach for donor stool-derived products. A general framework for an end-to-end donor screening program is needed using risk management strategies for donor-derived microbiome therapeutic using a matrixed approach, combining the elements of donor screening with manufacturing controls that are designed to minimize risk to patients. A donor screening paradigm that incorporates medical history, physical examination, laboratory testing, and donor sample inspection are only the first steps in reducing risk of transmission of infectious agents. Manufacturing controls are the cornerstone of risk mitigation when screening unwittingly fails. Failure Mode and Effects Analysis (FMEA) can be used as a tool to assess for residual risk that requires further donor or manufacturing controls. Together, a well-reasoned donor program and manufacturing controls are complementary strategies that must be revisited and reexamined frequently with constant vigilance to mitigate risk to patients. In the spirit of full disclosure and informed consent, physicians should discuss any limitations in the donor screening and manufacturing processes with their patients prior to treatment with microbiome-based therapeutics.}, } @article {pmid39290901, year = {2024}, author = {Polak, K and Muszyński, T and Frątczak, A and Meznerics, F and Bánvölgyi, A and Kiss, N and Miziołek, B and Bergler-Czop, B}, title = {Study of gut microbiome alterations in plaque psoriasis patients compared to healthy individuals.}, journal = {Postepy dermatologii i alergologii}, volume = {41}, number = {4}, pages = {378-387}, pmid = {39290901}, issn = {1642-395X}, abstract = {INTRODUCTION: Many studies have shown significant alterations in the gut microbiome of patients with psoriasis compared to healthy controls.

AIM: The primary objective of the current research was to explore the impact of gut microbiome composition on the progression and severity of plaque psoriasis.

MATERIAL AND METHODS: A total of 20 patients with moderate-to-severe psoriasis and 20 healthy individuals were recruited and provided a stool sample to assess the gut microbiome. After the samples were prepared according to the NGS library preparation workflow, they were sequenced using the Illumina platform and the report was generated that underwent statistical analysis.

RESULTS: The microbiome profiles of psoriasis patients exhibited significant differences compared to healthy controls as evidenced by the statistical analysis of various bacterial genera, with the median abundance significantly lower in psoriasis patients compared to healthy controls (p = 0.033). The analysis of the Firmicutes-to-Bacteroidetes ratio, a commonly evaluated marker of dysbiosis, did not reach statistical significance (p = 0.239). However, there was a noticeable trend towards a higher median ratio in psoriasis patients compared to healthy controls. The ratio did not show significant associations with PASI or BSA but trends towards significance with DLQI (B = -12.11, p = 0.095).

CONCLUSIONS: Overall, the above findings underscore the importance of the gut microbiome in psoriasis and suggest that modulation of specific bacterial genera, especially that with significant differences, could be a potential strategy for therapeutic intervention. Targeting these depleted genera through microbiome-based interventions, such as probiotic supplementation or faecal microbiota transplantation, could potentially help to restore gut homeostasis and alleviate the inflammatory burden in psoriasis.}, } @article {pmid39289768, year = {2024}, author = {Lo, SW and Hung, TH and Lin, YT and Lee, CS and Chen, CY and Fang, CJ and Lai, PC}, title = {Clinical efficacy and safety of faecal microbiota transplantation in the treatment of irritable bowel syndrome: a systematic review, meta-analysis and trial sequential analysis.}, journal = {European journal of medical research}, volume = {29}, number = {1}, pages = {464}, pmid = {39289768}, issn = {2047-783X}, support = {NCKUH-11304017//National Cheng Kung University Hospital/ ; }, mesh = {*Irritable Bowel Syndrome/therapy ; Humans ; *Fecal Microbiota Transplantation/methods ; Treatment Outcome ; Quality of Life ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: The aim of this study is to evaluate the efficacy and safety of faecal microbiota transplantation (FMT) for the treatment of irritable bowel syndrome (IBS).

METHODS: We searched four databases for randomised controlled trials (RCTs) that compared FMT with a control intervention in patients with IBS. The revised Cochrane risk-of-bias (RoB) tool was chosen for appraisal. Meta-analysis with trial sequential analysis (TSA) was conducted. Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence (CoE).

RESULTS: We included 12 RCTs with a total of 615 participants. Meta-analyses showed no significant difference between the FMT and control groups in terms of clinical responses (relative risk [RR] = 1.44, 95% confidence interval [CI] 0.88-2.33) and changes in IBS Severity Scoring System (IBS-SSS) scores (standardised mean difference [SMD] =  - 0.31, 95% CI  - 0.72 to 0.09) and IBS Quality of Life (IBS-QOL) scores (SMD = 0.30, 95% CI  - 0.09 to 0.69). Subgroup analysis revealed that in studies with low RoB and using endoscopy, nasojejunal tube and rectal enema delivery, FMT led to a significant improvement in clinical responses and changes in IBS-SSS and IBS-QOL scores. TSA suggested that the current evidence is inconclusive and that the CoE is very low.

CONCLUSION: This study suggests that patients with IBS may benefit from FMT especially when it is administered via endoscopy, nasojejunal tube or rectal enema. However, the certainty of evidence is very low. Further research is needed to confirm the efficacy and safety of FMT for IBS treatment.

TRIAL REGISTRATION: PROSPERO registration number CRD42020211002.}, } @article {pmid39288846, year = {2024}, author = {Chen, Q and Cheng, W and Zhang, J and Chi, C and Lin, M and He, C and Liao, Z and Gong, F}, title = {Fibroblast Growth Factor 21 Improves Insulin Sensitivity by Modulating the Bile Acid-Gut Microbiota Axis in Type Ⅱ Diabetic Mice.}, journal = {Free radical biology & medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.freeradbiomed.2024.09.017}, pmid = {39288846}, issn = {1873-4596}, abstract = {BACKGROUND: Fibroblast growth factor 21 (FGF21) is an important regulator of glycolipid metabolism. However, whether the gut microbiota is related to the anti-diabetic and obesity effects of FGF21 remains unclear.

METHODS: Our research used KO/KO db/db male mice and streptozotocin (STZ)-induced to simulate the construction of two type II diabetic mellitus (T2DM) models, and detected impaired glucose tolerance in the model by using the ipGTT and ITT assays, and collected feces from the model mice for sequencing of the intestinal flora and the content of short-chain fatty acids. H＆E staining was used to detect changes in intestinal tissue, the serum levels of LPS and GLP-1 were detected by ELISA.

RESULTS: In this study, we found that FGF21 significantly improved insulin sensitivity, attenuated intestinal lesions, and decreased serum lipopolysaccharide (LPS) concentrations in T2DM mice. Moreover, FGF21 reshaped the gut microbiota and altered their metabolic pathways in T2DM mice, promoting the production of short-chain fatty acids (SCFAs) and the secretion of glucagon-like peptide 1 (GLP-1). Fecal transplantation experiments further confirmed that feces from FGF21-treated diabetic mice demonstrated similar effects as FGF21 in terms of anti-diabetic activity and regulation of gut microbiota dysbiosis. Additionally, the antibiotic depletion of gut microbiota abolished the beneficial effects of FGF21, including increased GLP-1 secretion and fecal SCFA concentration. Additionally, the FGF21 effects of ameliorating intestinal damage and suppressing plasma LPS secretion were suppressed. All these findings suggest that FGF21 prevents intestinal lesions by modifying the gut microbiota composition. Furthermore, FGF21 affected bile acid synthesis by inhibiting CYP7A1, the key enzyme of bile acid synthesis.

CONCLUSSION: Therefore, FGF21 enriched beneficial bacteria by preventing bile acid synthesis and stimulating the secretion of the intestinal hormone GLP-1 via the increased production of gut microbiota metabolites, thereby exerting its anti-diabetic effects.}, } @article {pmid39287858, year = {2024}, author = {Engin, ED}, title = {Microbiota and Lipotoxicity.}, journal = {Advances in experimental medicine and biology}, volume = {1460}, number = {}, pages = {357-372}, pmid = {39287858}, issn = {0065-2598}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis ; *Metabolic Syndrome/microbiology/metabolism ; *Obesity/microbiology/metabolism ; Animals ; Lipid Metabolism ; Inflammation/metabolism/microbiology ; Adipose Tissue/metabolism/immunology ; }, abstract = {Gut microbiota is an indispensable commensal partner of human superorganism. The wealth of genetic repertoire provided by these microorganisms extends host's substrate processing capability. Energy and nutrient harvesting machinery primarily depends on the proper function of these organisms. However, the dynamic composition of microbiota changes with age, lifestyle, stress factors, infections, medications, and host pathophysiological conditions. Host immune system is primarily responsible for shaping up the microbial community and sustaining the symbiotic state. This involves controlling the delicate balance between agility toward pathobionts and tolerance toward symbionts. When things go wrong with this crosstalk, dysbiosis may arise.Metabolic syndrome is a multisystemic, low-grade chronic inflammatory disease that involves dyslipidemia, glucose intolerance, insulin resistance, and central obesity. Excess caloric intake with high-sugar and high-fat diet promote high energy harvesting and lipogenesis. The secretion of adipokines accompanies lipid spillover from fat cells, which contribute to insulin resistance and the expansion of adipose tissue in ectopic sites. Proinflammatory cytokines from adipose tissue macrophages increase the extent of adipose dysfunction.The inflammatory nature of obesity and metabolic syndrome recall the connection between dysbiosis and immune dysfunction. A remarkable association exits between obesity, inflammatory bowel disease, gluten-sensitive enteropathy, and dysbiosis. These conditions compromise the gut mucosa barrier and allow lipopolysaccharide to enter circulation. Unresolved chronic inflammation caused by one condition may overlap or trigger the other(s). Experimental studies and therapeutic trials of fecal microbiota transplantation promise limited improvement in some of these conditions.Typically, metabolic syndrome is considered as a consequence of overnutrition and the vicious cycle of lipogenesis, lipid accumulation, and chronic low-level inflammation. Because of the complex nature of this disorder, it remains inconclusive whether dysbiosis is a cause or consequence of obesity and metabolic syndrome.}, } @article {pmid39287045, year = {2024}, author = {Li, N and Han, X and Ruan, M and Huang, F and Yang, L and Xu, T and Wang, H and Wu, H and Shi, S and Wang, Y and Wu, X and Wang, S}, title = {Prebiotic inulin controls Th17 cells mediated central nervous system autoimmunity through modulating the gut microbiota and short chain fatty acids.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2402547}, pmid = {39287045}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Inulin/administration & dosage/pharmacology ; *Encephalomyelitis, Autoimmune, Experimental/immunology/drug therapy/microbiology ; *Th17 Cells/immunology ; Mice ; *Prebiotics/administration & dosage ; *Mice, Inbred C57BL ; Female ; *Fatty Acids, Volatile/metabolism ; *Autoimmunity/drug effects ; *Multiple Sclerosis/immunology/drug therapy/microbiology ; Central Nervous System/immunology ; Bacteria/classification/isolation & purification ; }, abstract = {Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination occurring in the central nervous system (CNS). Inulin is a common prebiotic that can improve metabolic disorders by modulating the gut microbiota. However, its capacity to affect CNS autoimmunity is poorly recognized. Experimental autoimmune encephalomyelitis (EAE) is a classical mouse model of MS. Herein, we found that oral administration of inulin ameliorated the severity EAE in mice, accompanied by reductions in inflammatory cell infiltration and demyelination in the CNS. These reductions were associated with decreased proportion and numbers of Th17 cells in brain and spleen. Consistent with the findings, the serum concentrations of IL-17, IL-6, and TNF-α were reduced in inulin treated EAE mice. Moreover, the proliferation of auto-reactive lymphocytes, against MOG35-55 antigen, was attenuated ex vivo. Mechanistically, inulin treatment altered the composition of gut microbiota. It increased Lactobacillus and Dubosiella whereas decreased g_Prevotellaceae_NK3B31_group at the genus level, alongside with elevated concentration of butyric acid in fecal content and serum. In vitro, butyrate, but not inulin, could inhibit the activation of MOG35-55 stimulated lymphocytes. Furthermore, fecal microbiota transplantation assay confirmed that fecal contents of inulin-treated normal mice had an ameliorative effect on EAE mice. In contrast, antibiotic cocktail (ABX) treatment diminished the therapeutic effect of inulin in EAE mice as well as the reduction of Th17 cells, while supplementation with Lactobacillus reuteri restored the amelioration effect. These results confirmed that the attenuation of inulin on Th17 cells and inflammatory demyelination in EAE mice was dependent on its modulation on gut microbiota and metabolites. Our findings provide a potential therapeutic regimen for prebiotic inulin supplementation in patients with multiple sclerosis.}, } @article {pmid39285046, year = {2024}, author = {Wang, Z and Gong, M and Fang, Y and Yuan, H and Zhang, C}, title = {Reconstruction characteristics of gut microbiota from patients with type 1 diabetes affect the phenotypic reproducibility of glucose metabolism in mice.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {39285046}, issn = {1869-1889}, abstract = {The human microbiota-associated (HMA) mice model, especially the germ-free (GF)-humanized mice, has been widely used to probe the causal relationships between gut microbiota and human diseases such as type 1 diabetes (T1D). However, most studies have not clarified the extent to which the reconstruction of the human donor microbiota in recipient mice correlates with corresponding phenotypic reproducibility. In this study, we transplanted fecal microbiota from five patients with T1D and four healthy people into GF mice, and microbiota from each donor were transplanted into 10 mice. Mice with similar microbiota structure to the donor exhibited better phenotypic reproducibility. The characteristics of the microbial community assembly of donors also influenced the phenotypic reproducibility in mice, and individuals with a higher proportion of stochastic processes showed more severe disorders. Microbes enriched in patients with T1D had a stronger colonization potential in mice with impaired glucose metabolism, and microbiota functional features related to T1D were better reproduced in these mice. This indicates that assembly traits and colonization efficacy of microbiota influence phenotypic reproducibility in GF-humanized mice. Our findings provide important insights for using HMA mice models to explore links between gut microbiota and human diseases.}, } @article {pmid39283061, year = {2024}, author = {McBurney, MI and Cho, CE}, title = {Understanding the role of the human gut microbiome in overweight and obesity.}, journal = {Annals of the New York Academy of Sciences}, volume = {}, number = {}, pages = {}, doi = {10.1111/nyas.15215}, pmid = {39283061}, issn = {1749-6632}, abstract = {The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet. Host-microbiota interactions are bidirectional. We propose three pathways whereby these interactions may modulate the gut microbiome and obesity: (1) ingested compounds or derivatives affecting small intestinal transit, endogenous secretions, digestion, absorption, microbiome balance, and gut barrier function directly affect host metabolism; (2) substrate availability affecting colonic microbial composition and contact with the gut barrier; and (3) microbial end products affecting host metabolism. The quantity/concentration, duration, and/or frequency (circadian rhythm) of changes in these pathways can alter the gut microbiome, disrupt the gut barrier, alter host immunity, and increase the risk of and progression to overweight and obesity. Host-specific characteristics (e.g., genetic variations) may further affect individual sensitivity and/or resilience to diet- and microbiome-associated perturbations in the colonic environment. In this narrative review, the effects of selected interventions, including fecal microbiota transplantation, dietary calorie restriction, dietary fibers and prebiotics, probiotics and synbiotics, vitamins, minerals, and fatty acids, on the gut microbiome, body weight, and/or adiposity are summarized to help identify mechanisms of action and research opportunities.}, } @article {pmid39282548, year = {2024}, author = {Salvati, F and Catania, F and Murri, R and Fantoni, M and Torti, C}, title = {Clostridioides difficile infection: an update.}, journal = {Le infezioni in medicina}, volume = {32}, number = {3}, pages = {280-291}, pmid = {39282548}, issn = {2532-8689}, abstract = {Clostridioides difficile (C. difficile) is a Gram-positive, spore-forming anaerobic bacterium emerged as a leading cause of diarrhea globally. CDI's (Clostridioides difficile infection) impact on healthcare systems is concerning due to high treatment cost and increased hospitalisation time. The incidence of CDI has been influenced by hypervirulent strains such as the 027 ribotype, responsible for significant outbreaks in North America and Europe. CDI's epidemiology has evolved, showing increased community-acquired cases alongside traditional hospital-acquired infections. Mortality rates remain high, with recurrent infections further elevating the risk. Transmission of C. difficile primarily occurs via spores, which survive in healthcare settings and play a pivotal role in transmission. Not only health workers, but also the food chain could have a significant impact on the transmission of infection, although no confirmed foodborne cases have been documented. Pathogenicity of C. difficile involves spore germination and toxin production. Toxins A and B can cause cellular damage and inflammatory responses in the host, leading to colitis. Clinical picture can range from mild diarrhea to fulminant colitis with toxic megacolon, and bowel perforation. Risk factors for CDI include antibiotic exposure, advanced age, hospitalization, and use of proton pump inhibitors. Patients who experience abdominal surgery or patients with inflammatory bowel disease (IBD) are particularly susceptible due to their compromised gut microbiota. Management of CDI has evolved, with fidaxomicin emerging as a superior treatment option over vancomycin for initial and recurrent infections due to its reduction of recurrence rate. Faecal microbiota transplantation (FMT) is effective for recurrent CDI, restoring gut eubiosis. Bezlotoxumab, a monoclonal antibody against C. difficile toxin B, has shown promise in reducing recurrence rates. Severe cases of CDI may require surgical intervention, particularly in instances of toxic megacolon or bowel perforation. In conclusion, CDI remains a significant clinical entity. Further research are needed to improve patients' outcome and reduce the burden on healthcare systems.}, } @article {pmid39282183, year = {2024}, author = {Mishra, V and Mishra, Y}, title = {Role of Gut Microbiome in Cancer Treatment.}, journal = {Indian journal of microbiology}, volume = {64}, number = {3}, pages = {1310-1325}, pmid = {39282183}, issn = {0046-8991}, abstract = {The gut microbiota influences the effectiveness and side effects of cancer treatments, particularly immunotherapy and associated immune-related complications. This important involvement of the microbiome is supported by the patients receiving antibiotics responding poorly to immunotherapy. Relatively few research has examined the underlying processes, and until recently, data regarding the detection of the microbial organisms that trigger these effects were inconsistent. Since then, a deeper comprehension of the processes of action and taxonomic classification of the relevant species has been attained. It's been demonstrated that certain bacterial species can enhance the body's reaction to immune checkpoint inhibitors through the release of distinct metabolites or products. Nonetheless, in certain patients who are not responding, Gram-negative bacteria may have a dominating suppressive impact. Patients' propensity to react to immunotherapy can be somewhat accurately predicted by machine learning techniques based on their microbiome makeup. Consequently, there has been an increase in interest in modifying the microbiome makeup to enhance patient reaction to medication. Clinical proof-of-concept studies demonstrate that dietary modifications or fecal microbiota transplantation (FMT) might be used therapeutically to increase the efficacy of immunotherapy in cancer patients. Current developments and new approaches for microbiota-based cancer treatments have been emphasized. In conclusion, preclinical research on animals and human clinical trials has made tremendous progress in our understanding of the function of the gut microbiome in health and illness. These investigations have shed light on the effects of food, FMT, probiotics, prebiotics, and microbiome-disease connections. However, there are still a lot of issues and restrictions that must be resolved before this research can be used in real-world clinical settings.}, } @article {pmid39282181, year = {2024}, author = {Kamath, HS and Shukla, R and Shah, U and Patel, S and Das, S and Chordia, A and Satish, P and Ghosh, D}, title = {Role of Gut Microbiota in Predisposition to Colon Cancer: A Narrative Review.}, journal = {Indian journal of microbiology}, volume = {64}, number = {3}, pages = {1-13}, pmid = {39282181}, issn = {0046-8991}, abstract = {Globally, colorectal cancer (CRC) is a leading cause of cancer-related mortality. Dietary habits, inflammation, hereditary characteristics, and gut microbiota are some of its causes. The gut microbiota, a diverse population of bacteria living in the digestive system, has an impact on a variety of parameters, including inflammation, DNA damage, and immune response. The gut microbiome has a significant role in colon cancer susceptibility. Many studies have highlighted dysbiosis, an imbalance in the gut microbiota's makeup, as a major factor in colon cancer susceptibility. Dysbiosis has the potential to produce toxic metabolites and pro-inflammatory substances, which can hasten the growth of tumours. The ability of the gut microbiota to affect the host's immune system can also influence whether cancer develops or not. By better comprehending these complex interactions between colon cancer predisposition and gut flora, new preventive and therapeutic techniques might be developed. Targeting the gut microbiome with dietary modifications, probiotics, or faecal microbiota transplantation may offer cutting-edge approaches to reducing the risk of colon cancer and improving patient outcomes. The complex connection between the makeup of the gut microbiota and the emergence of colorectal cancer is explored in this narrative review.}, } @article {pmid39281978, year = {2024}, author = {Zhang, S and Lu, G and Wang, W and Li, Q and Wang, R and Zhang, Z and Wu, X and Liang, C and Liu, Y and Li, P and Wen, Q and Cui, B and Zhang, F}, title = {A predictive machine-learning model for clinical decision-making in washed microbiota transplantation on ulcerative colitis.}, journal = {Computational and structural biotechnology journal}, volume = {24}, number = {}, pages = {583-592}, pmid = {39281978}, issn = {2001-0370}, abstract = {Machine learning based on clinical data and treatment protocols for better clinical decision-making is a current research hotspot. This study aimed to build a machine learning model on washed microbiota transplantation (WMT) for ulcerative colitis (UC), providing patients and clinicians with a new evaluation system to optimize clinical decision-making. Methods Patients with UC who underwent WMT via mid-gut or colonic delivery route at an affiliated hospital of Nanjing Medical University from April 2013 to June 2022 were recruited. Model ensembles based on the clinical indicators were constructed by machine-learning to predict the clinical response of WMT after one month. Results A total of 366 patients were enrolled in this study, with 210 patients allocated for training and internal validation, and 156 patients for external validation. The low level of indirect bilirubin, activated antithrombin III, defecation frequency and cholinesterase and the elderly and high level of creatine kinase, HCO3 [-] and thrombin time were related to the clinical response of WMT at one month. Besides, the voting ensembles exhibited an area under curve (AUC) of 0.769 ± 0.019 [accuracy, 0.754; F1-score, 0.845] in the internal validation; the AUC of the external validation was 0.614 ± 0.017 [accuracy, 0.801; F1-score, 0.887]. Additionally, the model was available at https://wmtpredict.streamlit.app. Conclusions This study pioneered the development of a machine learning model to predict the one-month clinical response of WMT on UC. The findings demonstrate the potential value of machine learning applications in the field of WMT, opening new avenues for personalized treatment strategies in gastrointestinal disorders. Trial registration clinical trials, NCT01790061. Registered 09 February 2013 - Retrospectively registered, https://clinicaltrials.gov/study/NCT01790061.}, } @article {pmid39281262, year = {2024}, author = {Nagesh, VK and Tran, HH and Elias, D and Kianifar Aguilar, I and Sethi, T and Menon, A and Mansour, C and Furman, F and Tsotsos, K and Subar, T and Auda, A and Sidiqui, A and Lamar, J and Wadhwani, N and Dey, S and Lo, A and Atoot, A and Weissman, S and Sifuentes, H and Bangolo, AI}, title = {Therapeutics involved in managing initial and recurrent Clostridium difficile infection: An updated literature review.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {15}, number = {5}, pages = {95467}, pmid = {39281262}, issn = {2150-5349}, abstract = {Clostridium difficile infection (CDI) has been increasing due to the effect of recurrent hospitalizations. The use of antibiotics has been shown to alter the gut microbiome and lead to CDIs. The treatment is limited to three major antibiotics; however, the incidence of recurrent CDIs has been increasing and drug resistance is a major concern. This aspect is a growing concern in modern medicine especially in the elderly population, critical care patients, and immunocompromised individuals who are at high risk of developing CDIs. Clostridium difficile can lead to various complications including septic shock and fulminant colitis that could prove to be lethal in these patients. Newer modalities of treatment have been developed including bezlotoxumab, a monoclonal antibody and fecal microbiota transplant. There have been studies showing asymptomatic carriers and drug resistance posing a major threat to the healthcare system. Newer treatment options are being studied to treat and prevent CDIs. This review will provide an insight into the current treatment modalities, prevention and newer modalities of treatment and challenges faced in the treatment of CDIs.}, } @article {pmid39280427, year = {2024}, author = {Lima Barrientos, J and Rojas Huerta, A and Perez Mendoza, A and Abreu Lopez, BA and Salolin Vargas, VP and Garcia Gonzalez, OY and Saldaña Ruiz, MA and Diarte, E and Torijano Sarria, AJ}, title = {The Relationship Between Gut Microbiome and Ophthalmologic Diseases: A Comprehensive Review.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66808}, pmid = {39280427}, issn = {2168-8184}, abstract = {The gut microbiome has been studied in recent years due to its association with various pathological pathways involved in different diseases, caused by its structure, function, and diversity alteration. The knowledge of this mechanism has generated interest in the investigation of its relationship with ophthalmologic diseases. Recent studies infer the existence of a gut-eye microbiota axis, influenced by the intestinal barrier, the blood-retina barrier, and the immune privilege of the eye. A common denominator among ophthalmologic diseases that have been related to this axis is inflammation, which is perpetuated by dysbiosis, causing an alteration of the intestinal barrier leading to increased permeability and, in turn, the release of components such as lipopolysaccharides (LPS), trimethylamine oxide (TMAO), and bacterial translocation. Some theories explain that depending on how the microbiome is composed, a different type of T cells will be activated, while others say that some bacteria can pre-activate T cells that mimic ocular structures and intestinal permeability that allow leakage of metabolites into the circulation. In addition, therapies such as probiotics, diet, and fecal microbiota transplantation (FMT) have been shown to favor the presence of a balanced population of microorganisms that limit inflammation and, in turn, generate a beneficial effect in these eye pathologies. This review aims to analyze how the intestinal microbiome influences various ocular pathologies based on microbial composition and pathological mechanisms, which may provide a better understanding of the diseases and their therapeutic potential.}, } @article {pmid39280360, year = {2024}, author = {Patibandla, S and Bhatt, N and Lief, S and Beauti, SM and Ansari, AZ}, title = {Gut Microbiota Modulation in the Management of Chronic Obstructive Pulmonary Disease: A Literature Review.}, journal = {Cureus}, volume = {16}, number = {8}, pages = {e66875}, pmid = {39280360}, issn = {2168-8184}, abstract = {Chronic obstructive pulmonary disease (COPD) represents a significant global health burden, characterized by progressive airflow limitation and exacerbations that significantly impact patient morbidity and mortality. Recent research has investigated the interplay between the gut and the lungs, known as the gut-lung axis, highlighting the role of the gut microbiome in COPD pathogenesis. Dysbiosis, characterized by microbial imbalance, has implications for COPD, influencing disease progression and susceptibility to exacerbations. This comprehensive review integrates current scientific literature on gut microbiota modulation as a therapeutic avenue for COPD management. Through a thorough discussion of studies investigating probiotics, prebiotics, synbiotics, antibiotics, dietary fiber, and fecal microbiota transplantation, this review summarizes the influence of these interventions on COPD via the gut-lung axis through the modulation of systemic inflammation, mucosal immunity, and metabolic processes. The interventions highlighted here show potential in preventing COPD exacerbations, preserving lung function, and improving patient quality of life. By compiling the latest scientific evidence, this review provides a comprehensive framework for physicians and researchers to deduce the effectiveness of gut microbiome modulation as an adjunctive therapeutic strategy in COPD management.}, } @article {pmid39280189, year = {2024}, author = {Jeyaraman, M and Mariappan, T and Jeyaraman, N and Muthu, S and Ramasubramanian, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Gut microbiome: A revolution in type II diabetes mellitus.}, journal = {World journal of diabetes}, volume = {15}, number = {9}, pages = {1874-1888}, pmid = {39280189}, issn = {1948-9358}, abstract = {Type II diabetes mellitus (T2DM) has experienced a dramatic increase globally across countries of various income levels over the past three decades. The persistent prevalence of T2DM is attributed to a complex interplay of genetic and environmental factors. While numerous pharmaceutical therapies have been developed, there remains an urgent need for innovative treatment approaches that offer effectiveness without significant adverse effects. In this context, the exploration of the gut microbiome presents a promising avenue. Research has increasingly shown that the gut microbiome of individuals with T2DM exhibits distinct differences compared to healthy individuals, suggesting its potential role in the disease's pathogenesis and progression. This emerging field offers diverse applications, particularly in modifying the gut environment through the administration of prebiotics, probiotics, and fecal microbiome transfer. These inter-ventions aim to restore a healthy microbiome balance, which could potentially alleviate or even reverse the metabolic dysfunctions associated with T2DM. Although current results from clinical trials have not yet shown dramatic effects on diabetes management, the groundwork has been laid for deeper investigation. Ongoing and future clinical trials are critical to advancing our understanding of the microbiome's impact on diabetes. By further elucidating the mechanisms through which microbiome alterations influence insulin resistance and glucose metabolism, researchers can develop more targeted interventions. The potential to harness the gut microbiome in developing new therapeutic strategies offers a compelling prospect to transform the treatment landscape of T2DM, potentially reducing the disease's burden significantly with approaches that are less reliant on traditional pharmaceuticals and more focused on holistic, systemic health improvements.}, } @article {pmid39278946, year = {2024}, author = {Messaoudene, M and Ferreira, S and Saint-Lu, N and Ponce, M and Truntzer, C and Boidot, R and Le Bescop, C and Loppinet, T and Corbel, T and Féger, C and Bertrand, K and Elkrief, A and Isaksen, M and Vitry, F and Sablier-Gallis, F and Andremont, A and Bod, L and Ghiringhelli, F and de Gunzburg, J and Routy, B}, title = {The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteers.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8083}, pmid = {39278946}, issn = {2041-1723}, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology/administration & dosage/adverse effects ; *Healthy Volunteers ; Animals ; *Dysbiosis/microbiology/chemically induced ; Female ; Mice ; Adult ; Male ; *Gastrointestinal Microbiome/drug effects ; *Colon/microbiology/drug effects ; *Feces/microbiology/chemistry ; Middle Aged ; Fecal Microbiota Transplantation ; Young Adult ; Immune Checkpoint Inhibitors ; }, abstract = {The deleterious impact of antibiotics (ATB) on the microbiome negatively influences immune checkpoint inhibitors (ICI) response in patients with cancer. We conducted a randomized phase I study (EudraCT:2019-A00240-57) with 148 healthy volunteers (HV) to test two doses of DAV132, a colon-targeted adsorbent, alongside intravenous ceftazidime-avibactam (CZA), piperacillin-tazobactam (PTZ) or ceftriaxone (CRO) and a group without ATB. The primary objective of the study was to assess the effect of DAV132 on ATB plasma concentrations and both doses of DAV132 did not alter ATB levels. Secondary objectives included safety, darkening of the feces, and fecal ATB concentrations. DAV132 was well tolerated, with no severe toxicity and similar darkening at both DAV132 doses. DAV132 led to significant decrease in CZA or PTZ feces concentration. When co-administered with CZA or PTZ, DAV132 preserved microbiome diversity, accelerated recovery to baseline composition and protected key commensals. Fecal microbiota transplantation (FMT) in preclinical cancer models in female mice from HV treated with CZA or PTZ alone inhibited anti-PD-1 response, while transplanted samples from HV treated with ATB + DAV132 circumvented resistance to anti-PD-1. This effect was linked to activated CD8[+] T cell populations in the tumor microenvironment. DAV132 represents a promising strategy for overcoming ATB-related dysbiosis and further studies are warranted to evaluate its efficacy in cancer patients.}, } @article {pmid39277768, year = {2024}, author = {Ma, X and Park, HS and Shin, YJ and Kim, JK and Hong, JK and Han, SW and Yoon, IY and Kim, DH}, title = {The extracellular vesicle of depressive patient-derived Escherichia fergusonii induces vagus nerve-mediated neuroinflammation in mice.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {224}, pmid = {39277768}, issn = {1742-2094}, support = {RS-2024-00344277//the Korea Dementia Research Project/ ; 2017R1A5A2014768//National Research Foundation of Korea/ ; }, mesh = {Animals ; Mice ; *Vagus Nerve/metabolism ; *Extracellular Vesicles/metabolism ; Humans ; Male ; *Neuroinflammatory Diseases/metabolism ; *Depression/metabolism/etiology ; Mice, Inbred C57BL ; Vagotomy ; }, abstract = {BACKGROUND: Gut microbiota dysbiosis is closely associated with psychiatric disorders such as depression and anxiety (DA). In our preliminary study, fecal microbiota transplantation from volunteers with psychological stress and subclinical symptoms of depression (Vsd) induced DA-like behaviors in mice. Escherichia fergusonii (Esf) was found to be more abundant in the feces of Vsd compared to healthy volunteers. Therefore, we investigated the effect of Esf on DA-like behavior and neuroinflammation in mice with and without celiac vagotomy.

METHODS AND RESULTS: Orally gavaged Esf increased DA-like behaviors, tumor necrosis factor (TNF)-α, and toll-like receptor-4 (TLR4) expression, and NF-κB[+]Iba1[+] and lipopolysaccharide (LPS)[+]Iba1[+] cell populations, while decreasing serotonin, 5-HT1A receptor, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex. However, celiac vagotomy attenuated Esf-induced DA-like behavior and neuroinflammation. Orally gavaged extracellular vesicle (EV) from Vsd feces (vfEV) or Esf culture (esEV) induced DA-like behavior and inflammation in hippocampus, prefrontal cortex and colon. However, celiac vagotomy attenuated vfEV- or esEV-induced DA-like behaviors and inflammation in the brain alone, while vfEV- or esEV-induced blood LPS and TNF-α levels, colonic TNF-α expression and NF-κB-positive cell number, and fecal LPS level were not. Although orally gavaged fluorescence isothiocyanate-labeled esEV was translocated into the blood and hippocampus, celiac vagotomy decreased its translocation into the hippocampus alone.

CONCLUSIONS: esEVs may be translocated into the brain via the vagus nerve and bloodstream, subsequently inducing TNF-α expression and suppressing serotonin, its receptor, and BDNF expression through the activation of TLR4-mediated NF-κB signaling, thereby contributing to DA pathogenesis.}, } @article {pmid39277177, year = {2024}, author = {Meng, Q and Zhang, S and Zhang, C and Liu, B and Zhu, W and Wu, L and Zhang, Q and Li, Y and Wang, X and Bian, H}, title = {Disordered gut microbiota in postmenopausal stage amplifies intestinal tight junction damage to accelerate atherosclerosis.}, journal = {Beneficial microbes}, volume = {}, number = {}, pages = {1-23}, doi = {10.1163/18762891-bja00036}, pmid = {39277177}, issn = {1876-2891}, abstract = {The causes and characteristics of gut microbiota abnormalities and whether microbiota manipulation can prevent atherosclerosis in the postmenopausal stage remain to be determined. Aortic oestrogen receptor expression, histological changes and gut microbiota in women before and after menopause were detected. Serum oestrogen levels, systemic inflammation, intestinal oestrogen receptor expression and histological changes, atherosclerosis, and gut microbiota in low density lipoprotein deletion (LDLR-∕-) female mice before and after ovariectomy were tested. This study examined aortic oestrogen receptor expression, histological changes, and gut microbiota in women before and after menopause, and tested serum oestrogen levels, systemic inflammation, intestinal oestrogen receptor expression, histological changes, atherosclerosis, and gut microbiota in low-density lipoprotein receptor knockout (LDLR-∕-) female mice before and after ovariectomy. We demonstrated that the downregulation of oestrogen and oestrogen receptors after menopause promotes gut microbiota disturbance in both women and female mice. We found that gut microbiota disturbance amplifies the intestinal barrier damage and aggravates systemic inflammation, thereby promoting atherosclerosis in female mice. Faecal microbiota transplantation and antibiotics inhibit the proinflammatory properties of gut microbiota and prevent atherosclerosis by reducing intestinal barrier damage in postmenopausal mice. Together, our study highlights the causes of gut microbiota disturbances and the role of microbiota manipulation in preventing atherosclerosis in postmenopausal stage.}, } @article {pmid39276451, year = {2024}, author = {Tian, Y and Tian, R and He, J and Guo, Y and Yan, P and Chen, Y and Li, R and Wang, B}, title = {Toralactone alleviates cisplatin-induced acute kidney injury by modulating the gut microbiota-renal axis.}, journal = {International immunopharmacology}, volume = {142}, number = {Pt A}, pages = {113115}, doi = {10.1016/j.intimp.2024.113115}, pmid = {39276451}, issn = {1878-1705}, abstract = {BACKGROUND: Gut microbiota has been reported to be perturbed by cisplatin and to modulate the nephrotoxicity of chemotherapeutic agents. However, the critical role of toralactone, a bioactive components of Cassia obtusifolia L. seeds, in modulating the gut microbiota in the pathogenesis of cisplatin-induced nephrotoxicity remains to be elucidated.

METHODS: In this study, we verified the reno-protective effects of toralactone and compared the composition and function of the gut microbiota in the normal, cisplatin-treated and low or high dose of toralactone-treated mice using 16S rDNA gene sequencing. We also investigated the gut microbiota related LPS/TLR4/NF-κB/TNF-α pathway in renal tissue. To elucidate the causal relationship between gut dysbiosis and cisplatin nephrotoxicity, an antibiotic cocktail was administered to deplete the gut microbiota and fecal microbiota transplantation (FMT) was performed prior to cisplatin treatment.

RESULTS: The renal histopathology showed that toralactone significantly alleviated cisplatin-induced renal injury. 16S rDNA gene sequencing analysis demonstrated that toralactone treatment effectively reversed cisplatin-induced gut microbiota dysbiosis in mice. FMT from toralactone-treated mice to cisplatin-induced kidney injury mice was observed to have the reno-protective effects, and deletion of gut microbiota by antibiotics was found to negate the reno-protective effect of toralactone. Interestingly, the renal tissue of cisplatin-associated kidney injury mice showed activation of the LPS/TLR4/NF-κB pathway and increase in TNF-α within the renal tissue, whereas toralactone treatment was observed to inhibit the LPS/TLR4/NF-κB/TNF-α pathway.

CONCLUSION: This study elucidated the reno-protective effects for the first time, demonstrating that it exerts its beneficial effects through the gut microbiota, which mediate the LPS/TLR4/NF-κB/TNF-α inflammatory pathway. It may help to develop therapeutic approaches using toralactone and targeted restoration of the gut microbiota.}, } @article {pmid39273662, year = {2024}, author = {Acevedo-Román, A and Pagán-Zayas, N and Velázquez-Rivera, LI and Torres-Ventura, AC and Godoy-Vitorino, F}, title = {Insights into Gut Dysbiosis: Inflammatory Diseases, Obesity, and Restoration Approaches.}, journal = {International journal of molecular sciences}, volume = {25}, number = {17}, pages = {}, pmid = {39273662}, issn = {1422-0067}, support = {P20 GM103475/GM/NIGMS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; U54 MD007600//MD/NIMHD NIH HHS/United States ; S21 MD001830/MD/NIMHD NIH HHS/United States ; T32 GM148406/GM/NIGMS NIH HHS/United States ; U54 MD007600/MD/NIMHD NIH HHS/United States ; }, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *Gastrointestinal Microbiome ; *Obesity/microbiology ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Animals ; Inflammation/microbiology ; Prebiotics/administration & dosage ; }, abstract = {The gut microbiota is one of the most critical factors in human health. It involves numerous physiological processes impacting host health, mainly via immune system modulation. A balanced microbiome contributes to the gut's barrier function, preventing the invasion of pathogens and maintaining the integrity of the gut lining. Dysbiosis, or an imbalance in the gut microbiome's composition and function, disrupts essential processes and contributes to various diseases. This narrative review summarizes key findings related to the gut microbiota in modern multifactorial inflammatory conditions such as ulcerative colitis or Crohn's disease. It addresses the challenges posed by antibiotic-driven dysbiosis, particularly in the context of C. difficile infections, and the development of novel therapies like fecal microbiota transplantation and biotherapeutic drugs to combat these infections. An emphasis is given to restoration of the healthy gut microbiome through dietary interventions, probiotics, prebiotics, and novel approaches for managing gut-related diseases.}, } @article {pmid39272235, year = {2024}, author = {Li, H and Han, L and Zhou, F and Wu, Z and Zhang, L and Xie, R and Jiang, F and Tian, Q and Huang, X}, title = {Ningxiang Pig-Derived Microbiota Affects the Growth Performance, Gut Microbiota, and Serum Metabolome of Nursery Pigs.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {17}, pages = {}, pmid = {39272235}, issn = {2076-2615}, support = {U20A2055//National Natural Science Foundation of China/ ; }, abstract = {The gut microbiota is crucial for maintaining the host's intestinal homeostasis and metabolism. This study investigated the effects of fecal microbiota transplantation (FMT) from Ningxiang pigs on the growth performance, fecal microbiota, and serum metabolites of the same-old DLY pigs. The results indicated that the average daily gain of FMT pigs was significantly greater than that of the control (CON) group. Compared to the CON group, the FMT group significantly improved the apparent digestibility of crude fiber, crude ash, gross energy, and calcium of the pigs. The analysis of serum antioxidant status revealed that the activities of total superoxide dismutase and catalase in the serum of pigs in the FMT group were significantly elevated, whereas the level of malondialdehyde was significantly reduced. Furthermore, 16S rRNA sequencing analysis revealed that the Ningxiang pig-derived microbiota altered the fecal microbiota structure and modulated the diversity of the gut microbiota in the DLY pigs. Untargeted LC-MS metabolomics demonstrated that pigs in the FMT group exhibited distinct metabolomic profiles compared to those in the CON group. Significant changes were observed in key metabolites involved in amino acid, lipid, and carbohydrate metabolism. Additionally, a correlation analysis between serum differential metabolites and the gut microbiota revealed that the relative abundance of Lachnospiraceae_NK4A136_group and Corynebacterium was highly correlated with lipid compounds. In conclusion, Ningxiang pig-derived microbiota can alleviate oxidative stress and enhance growth performance in DLY pigs by modulating their gut microbiota and metabolic features.}, } @article {pmid39271443, year = {2024}, author = {López Zúñiga, MÁ and Sánchez Cabello, A and López Ruz, MÁ}, title = {Diagnostic and therapeutic management of Clostridioides difficile infection.}, journal = {Medicina clinica}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.medcli.2024.06.004}, pmid = {39271443}, issn = {1578-8989}, abstract = {A review of the diagnostic and therapeutic management algorithm of the pathogen Clostridioides difficile for daily practice is presented. Its diagnosis, in any unformed stool sample sent to the laboratory, is based on a two-step algorithm, with demonstration of the pathogen by means of its enzyme glutamate dehydrogenase by immunoassay and subsequent PCR (polymerase chain reaction) of its toxin. The mainstay of step therapy, reserved for symptomatic patients, is fidaxomicin, over vancomycin. Metronidazole is not an adequate treatment. Emerging therapies, such as faecal microbiota transplantation or the antibody bezlotoxumab, are gaining importance in patients with risk factors or relapses. Surgery is indicated in patients with worse prognosis and complications. Prevention is essential, based on vigilance and contact precautions, in addition to the elimination of spores from the environment.}, } @article {pmid39271107, year = {2024}, author = {Drekonja, DM and Shaukat, A and Huang, Y and Zhang, JH and Reinink, AR and Nugent, S and Dominitz, JA and Davis-Karim, A and Gerding, DN and Kyriakides, TC}, title = {A randomized controlled trial of efficacy and safety of Fecal Microbiota Transplant for preventing recurrent Clostridioides difficile infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciae467}, pmid = {39271107}, issn = {1537-6591}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infections in US hospitals with 15%-30% of patients experiencing recurrence. The aim of our randomized, double-blind clinical trial was to assess the efficacy of capsule-delivered fecal microbiota transplantation (FMT) versus placebo in reducing recurrent diarrhea and CDI recurrence. The secondary aim was FMT safety assessment.

METHODS: Between 2018 and 2022, Veterans across the Veterans Health Administration system with recurrent CDI who responded to antibiotic treatment were randomized in a 1:1 ratio to oral FMT or placebo capsules. Randomization was stratified by number of prior CDI recurrences (1 or ≥2). The primary endpoint was clinical recurrence by day 56, defined as >3 unformed stools daily for ≥2 days with or without laboratory confirmation of C. difficile, or death within 56 days.

RESULTS: The study was stopped due to futility after meeting pre-specified criteria. Of 153 participants (76 FMT, 77 placebo) with an average age of 66.5 years, 25 participants (32.9%) in the FMT arm and 23 (29.9%) in the placebo arm experienced the primary endpoint of diarrhea and possible or definite CDI recurrence or death within 56 days of capsule administration (absolute difference 3.0%; 95% CI [-11.7%, 17.7%]). Stratification by number of recurrences revealed no statistically significant differences. There were no clinically important differences in adverse events.

CONCLUSIONS: FMT therapy vs. placebo did not reduce CDI recurrence or death at 56 days. There were no meaningful differences in adverse events between treatment groups.}, } @article {pmid39270883, year = {2024}, author = {Li, F and Han, Q and Cai, Y and Li, Y and Yang, Y and Li, J and Wu, R and Chen, R and Liu, R}, title = {Si-Ni-San ameliorates cholestatic liver injury by favoring P. goldsteinii colonization.}, journal = {Journal of ethnopharmacology}, volume = {337}, number = {Pt 1}, pages = {118804}, doi = {10.1016/j.jep.2024.118804}, pmid = {39270883}, issn = {1872-7573}, abstract = {Current treatment options for cholestatic liver diseases are limited, and addressing impaired intestinal barrier has emerged as a promising therapeutic approach. Si-Ni-San (SNS) is a Traditional Chinese Medicine (TCM) formula commonly utilized in the management of chronic liver diseases. Our previous studies have indicated that SNS effectively enhanced intestinal barrier function through the modulation of gut microbiota.

AIM OF THE STUDY: This study aims to verify the therapeutic effects of SNS on cholestatic liver injury, focusing on elucidating the underlying mechanism involving the gut-liver axis.

MATERIALS AND METHODS: The 16s RNA gene sequencing, non-targeted metabolomics were used to investigate the effects of SNS on the gut microbiota dysbiosis. Fecal microbiota transplantation (FMT) was conducted to identify potential beneficial probiotics underlying the therapeutic effects of SNS.

RESULTS: Our results demonstrated that SNS significantly ameliorated cholestatic liver injury induced by partial bile duct ligation (pBDL). Additionally, SNS effectively suppressed cholestasis-induced inflammation and barrier dysfunction in both the small intestine and colon. While SNS did not impact the intestinal FXR-FGF15-hepatic CYP7A1 axis, it notably improved gut microbiota dysbiosis and modulated the profile of microbial metabolites, including beneficial secondary bile acids and tryptophan derivatives. Furthermore, gut microbiota depletion experiments and FMT confirmed that the therapeutic benefits of SNS in cholestatic liver disease are dependent on gut microbiota modulation, particularly through the promotion of the growth of potential probiotic P. goldsteinii. Moreover, a synergistic improvement in cholestatic liver injury was observed with the co-administration of P. goldsteinii and SNS.

CONCLUSION: Our study underscores that SNS effectively alleviates cholestatic liver injury by addressing gut microbiota dysbiosis and enhancing intestinal barrier function, supporting its rational clinical utilization. Furthermore, we highlight P. goldsteinii as a promising probiotic candidate for the management of cholestatic liver diseases.}, } @article {pmid39270730, year = {2024}, author = {Poutanen, SM and Hota, SS}, title = {Déjà vu: Unanswered Questions about Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciae468}, pmid = {39270730}, issn = {1537-6591}, } @article {pmid39269473, year = {2024}, author = {Singh, V and Choi, SD and Mahra, K and Son, H and Lee, H and Lee, YJ and Kim, ES and Shin, JH}, title = {Cultured fecal microbial community and its impact as fecal microbiota transplantation treatment in mice gut inflammation.}, journal = {Applied microbiology and biotechnology}, volume = {108}, number = {1}, pages = {463}, pmid = {39269473}, issn = {1432-0614}, support = {2021R1A6C101A416//Korea Basic Science Institute/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Animals ; *Feces/microbiology ; Mice ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy/microbiology ; *Disease Models, Animal ; *Cytokines/metabolism ; *RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; Dextran Sulfate ; Male ; Culture Media/chemistry ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {The fecal microbiome is identical to the gut microbial communities and provides an easy access to the gut microbiome. Therefore, fecal microbial transplantation (FMT) strategies have been used to alter dysbiotic gut microbiomes with healthy fecal microbiota, successfully alleviating various metabolic disorders, such as obesity, type 2 diabetes, and inflammatory bowel disease (IBD). However, the success of FMT treatment is donor-dependent and variations in gut microbes cannot be avoided. This problem may be overcome by using a cultured fecal microbiome. In this study, a human fecal microbiome was cultured using five different media; growth in brain heart infusion (BHI) media resulted in the highest microbial community cell count. The microbiome (16S rRNA) data demonstrated that the cultured microbial communities were similar to that of the original fecal sample. Therefore, the BHI-cultured fecal microbiome was selected for cultured FMT (cFMT). Furthermore, a dextran sodium sulfate (DSS)-induced mice-IBD model was used to confirm the impact of cFMT. Results showed that cFMT effectively alleviated IBD-associated symptoms, including improved gut permeability, restoration of the inflamed gut epithelium, decreased expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6, IL-12, and IL-17), and increased expression of anti-inflammatory cytokines (IL-4 and IL-10). Thus, study's findings suggest that cFMT can be a potential alternative to nFMT. KEY POINTS: • In vitro fecal microbial communities were grown in a batch culture using five different media. • Fecal microbial transplantation was performed on DSS-treated mice using cultured and normal fecal microbes. • Cultured fecal microbes effectively alleviated IBD-associated symptoms.}, } @article {pmid39267518, year = {2024}, author = {Gan, Y and Wu, ZH and Li, QL and Lu, ZX and Chen, LL}, title = {[Advances in the treatment of Clostridium difficile infection in children].}, journal = {Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics}, volume = {26}, number = {9}, pages = {995-1001}, pmid = {39267518}, issn = {1008-8830}, mesh = {Humans ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Child ; Clostridioides difficile ; Risk Factors ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Clostridium difficile infection (CDI) is a major cause of hospital-acquired gastrointestinal infections in children. Current treatment for pediatric CDI primarily involves antibiotics; however, some children experience recurrence after antibiotic treatment, and those with initial recurrence remain at risk for further recurrences following subsequent antibiotic therapy. In such cases, careful consideration of treatment options is necessary. Fecal microbiota transplantation has been shown to be effective for recurrent CDI and has a high safety profile. This article reviews the latest research on the pathogenesis, risk factors, diagnosis, and treatment of pediatric CDI domestically and internationally, with a particular focus on fecal microbiota transplantation therapy.}, } @article {pmid39267235, year = {2024}, author = {}, title = {Correction to "Long-Term Effects of Fecal Microbiota Transplantation on Gut Microbiota After Helicobacter pylori Eradication With Bismuth Quadruple Therapy: A Randomized Controlled Trial".}, journal = {Helicobacter}, volume = {29}, number = {5}, pages = {e13127}, doi = {10.1111/hel.13127}, pmid = {39267235}, issn = {1523-5378}, } @article {pmid39267080, year = {2024}, author = {Wei, X and Xing, F and Xu, Y and Zhang, F and Cheng, D and Zhou, Y and Zheng, F and Zhang, W}, title = {Preoperative gut microbiota of POCD patients induces pre- and postoperative cognitive impairment and systemic inflammation in rats.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {221}, pmid = {39267080}, issn = {1742-2094}, support = {82002086//National Natural Science Foundation of China/ ; 82001187//National Natural Science Foundation of China/ ; 82071240//National Natural Science Foundation of China/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Rats ; *Postoperative Cognitive Complications/etiology ; Male ; Humans ; Female ; Aged ; *Inflammation ; Rats, Sprague-Dawley ; Middle Aged ; Retrospective Studies ; Cognitive Dysfunction/etiology/microbiology ; }, abstract = {BACKGROUND: Postoperative cognitive dysfunction (POCD) is common following surgery in elderly patients. The role of the preoperative gut microbiota in POCD has attracted increasing attention, but the potential underlying mechanisms remain unclear. This research aimed to investigate the impact of the preoperative gut microbiota on POCD.

METHODS: Herein, we analyzed the preoperative gut microbiota of POCD patients through a prospective specimen collection and retrospective blinded evaluation study. Then, we transferred the preoperative gut microbiota of POCD patients to antibiotic-treated rats and established POCD model by abdominal surgery to explore the impact of the preoperative gut microbiota on pre- and postoperative cognitive function and systemic inflammation. The gut microbiota was analyzed using 16S rRNA sequencing analysis. The Morris water maze test was performed to evaluate learning and memory abilities. The inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1.

RESULTS: Based on the decrease in the postoperative MMSE score, 24 patients were identified as having POCD and were matched with 24 control patients. Compared with control patients, POCD patients exhibited higher BMI and lower preoperative MMSE score. The preoperative gut microbiota of POCD patients had lower bacterial richness but a larger distribution, decreased abundance of Firmicutes and increased abundance of Proteobacteria than did that of control patients. Compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-α and IL-1β in the serum, increased levels of TNF-α and greater microglial activation in the hippocampus. Additionally, correlation analysis revealed a positive association between the abundance of Desulfobacterota and the level of serum TNF-α in rats. Then, we performed abdominal surgery to investigate the impact of the preoperative gut microbiota on postoperative conditions, and the surgery did indeed cause POCD and inflammatory response. Notably, compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-α, IL-1β and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus.

CONCLUSIONS: Our findings suggest that the preoperative gut microbiota of POCD patients can induce preoperative and aggravate postoperative cognitive impairment and systemic inflammation in rats. Modulating inflammation by targeting the gut microbiota might be a promising approach for preventing POCD.}, } @article {pmid39266472, year = {2024}, author = {Bell, J and Radial, SL and Cuming, RS and Trope, G and Hughes, KJ}, title = {Effects of fecal microbiota transplantation on clinical outcomes and fecal microbiota of foals with diarrhea.}, journal = {Journal of veterinary internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1111/jvim.17185}, pmid = {39266472}, issn = {1939-1676}, support = {//Agrifutures Australia/ ; }, abstract = {BACKGROUND: Diarrhea in foals can be associated with disruption of the intestinal microbiota (dysbiosis). Effective management of intestinal dysbiosis in foals has not been demonstrated.

HYPOTHESIS/OBJECTIVES: Fecal microbiota transplantation (FMT) in foals with diarrhea influences the intestinal microbiota and improves clinical and clinicopathological outcomes.

ANIMALS: Twenty-five foals <6 months of age with diarrhea and systemic inflammatory response syndrome at 3 veterinary hospitals.

METHODS: A prospective randomized placebo-controlled cohort study. Foals in the FMT group (n = 19) or control group (n = 9) received FMT or electrolyte solution once daily for 3 days. Fecal samples were obtained on Day 0 (D0), D1, D2, D3, and D7. Within group and between group data analyses were performed for clinical, clinicopathological, and microbiota variables.

RESULTS: Treatment had no effect on survival (FMT 79%; control 100%, P = .3) or resolution of diarrhea (FMT 68%; control 55%, P = .4). On D3, the white blood cell count of the FMT group was lower than the control group (D3 FMT group median 6.4 g/L [5-8.3 g/L]; D3 control group median 14.3 g/L [6.7-18.9 g/L] P = .04). Heart rate reduced over time in the FMT group (D0 median 80 bpm [60-150 bpm]; D2 median 70 bpm [52-110 bpm] [P = .005]; and D3 median 64, [54-102 bpm] [P < .001]). Phylum Verrucomicrobiota, genus Akkermansia, and family Prevotellaceae were enriched in the FMT group on D1 (linear discriminate analysis > 4).

In foals with diarrhea, FMT appears safe and can be associated with some clinical and microbiota changes suggestive of beneficial effect.}, } @article {pmid39263354, year = {2024}, author = {Zhang, C and Wang, G and Yin, X and Gou, L and Guo, M and Suo, F and Zhuang, T and Yuan, Z and Liu, Y and Gu, M and Yao, R}, title = {Hepatic protein phosphatase 1 regulatory subunit 3G alleviates obesity and liver steatosis by regulating the gut microbiota and bile acid metabolism.}, journal = {Journal of pharmaceutical analysis}, volume = {14}, number = {8}, pages = {100976}, pmid = {39263354}, issn = {2214-0883}, abstract = {Intestinal dysbiosis and disrupted bile acid (BA) homeostasis are associated with obesity, but the precise mechanisms remain insufficiently explored. Hepatic protein phosphatase 1 regulatory subunit 3G (PPP1R3G) plays a pivotal role in regulating glycolipid metabolism; nevertheless, its obesity-combatting potency remains unclear. In this study, a substantial reduction was observed in serum PPP1R3G levels in high-body mass index (BMI) and high-fat diet (HFD)-exposed mice, establishing a positive correlation between PPP1R3G and non-12α-hydroxylated (non-12-OH) BA content. Additionally, hepatocyte-specific overexpression of Ppp1r3g (PPP1R3G HOE) mitigated HFD-induced obesity as evidenced by reduced weight, fat mass, and an improved serum lipid profile; hepatic steatosis alleviation was confirmed by normalized liver enzymes and histology. PPP1R3G HOE considerably impacted systemic BA homeostasis, which notably increased the non-12-OH BAs ratio, particularly lithocholic acid (LCA). 16S ribosomal DNA (16S rDNA) sequencing assay indicated that PPP1R3G HOE reversed HFD-induced gut dysbiosis by reducing the Firmicutes/Bacteroidetes ratio and Lactobacillus population, and elevating the relative abundance of Blautia, which exhibited a positive correlation with serum LCA levels. A fecal microbiome transplantation test confirmed that the anti-obesity effect of hepatic PPP1R3G was gut microbiota-dependent. Mechanistically, PPP1R3G HOE markedly suppressed hepatic cholesterol 7α-hydroxylase (CYP7A1) and sterol-12α-hydroxylase (CYP8B1), and concurrently upregulated oxysterol 7-α hydroxylase and G protein-coupled BA receptor 5 (TGR5) expression under HFD conditions. Furthermore, LCA administration significantly mitigated the HFD-induced obesity phenotype and elevated non-12-OH BA levels. These findings emphasize the significance of hepatic PPP1R3G in ameliorating diet-induced adiposity and hepatic steatosis through the gut microbiota-BA axis, which may serve as potential therapeutic targets for obesity-related disorders.}, } @article {pmid39262376, year = {2024}, author = {Wang, T and Hao, L and Yang, K and Feng, W and Guo, Z and Liu, M and Xiao, R}, title = {Fecal microbiota transplantation derived from mild cognitive impairment individuals impairs cerebral glucose uptake and cognitive function in wild-type mice: Bacteroidetes and TXNIP-GLUT signaling pathway.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2395907}, doi = {10.1080/19490976.2024.2395907}, pmid = {39262376}, issn = {1949-0984}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Cognitive Dysfunction/metabolism/microbiology ; Mice ; *Gastrointestinal Microbiome ; *Glucose/metabolism ; *Brain/metabolism ; *Bacteroidetes/metabolism ; *Signal Transduction ; *Dysbiosis/microbiology/metabolism ; Male ; Humans ; *Cognition ; Mice, Inbred C57BL ; Carrier Proteins/metabolism/genetics ; Glucose Transport Proteins, Facilitative/metabolism/genetics ; Thioredoxins ; }, abstract = {Gut microbiome dysbiosis has been widely implicated in cognitive impairment, but the identity of the specific bacterial taxa and mechanisms are not fully elucidated. Brain glucose hypometabolism coincides with the cognitive decline. This study explored the link among cognition, gut microbiota and glucose uptake based on the fecal microbiota transplantation from mild cognitive impairment individuals (MCI-FMT) and investigated whether similar mechanisms were involved in 27-hydroxycholesterol (27-OHC)-induced cognitive decline. Our results showed that the MCI-FMT mice exhibited learning and memory decline and morphological lesions in the brain and colon tissues. There were reduced [18]F-fluorodeoxyglucose uptake, downregulated expression of glucose transporters (GLUT1,3,4) and upregulated negative regulator of glucose uptake (TXNIP) in the brain. MCI-FMT altered the bacterial composition and diversity of the recipient mice, and the microbial signatures highlighted by the increased abundance of Bacteroides recapitulated the negative effects of MCI bacterial colonization. However, inhibiting Bacteroidetes or TXNIP increased the expression of GLUT1 and GLUT4, significantly improving brain glucose uptake and cognitive performance in 27-OHC-treated mice. Our study verified that cognitive decline and abnormal cerebral glucose uptake were associated with gut microbiota dysbiosis; we also revealed the involvement of Bacteroidetes and molecular mechanisms of TXNIP-related glucose uptake in cognitive deficits caused by 27-OHC.}, } @article {pmid39262248, year = {2024}, author = {Mu, X and Zhang, J and Li, H and Li, H and Mu, Z and Ye, F and Li, J and Ye, F}, title = {Effects of intestinal flora on cerebral hemorrhage area and brain tissue inflammation in acute hemorrhagic stroke.}, journal = {Cellular and molecular biology (Noisy-le-Grand, France)}, volume = {70}, number = {8}, pages = {153-157}, doi = {10.14715/cmb/2024.70.8.21}, pmid = {39262248}, issn = {1165-158X}, mesh = {Animals ; Male ; *Cerebral Hemorrhage/complications/pathology/microbiology/metabolism ; *Mice, Inbred C57BL ; *Gastrointestinal Microbiome ; *Hemorrhagic Stroke/pathology/metabolism ; *Brain/pathology/metabolism ; Inflammation/pathology/metabolism ; Disease Models, Animal ; Mice ; Brain Edema/pathology/metabolism ; Hematoma/pathology/metabolism/complications ; }, abstract = {To explore the impacts of intestinal flora on cerebral hemorrhage area and brain tissue inflammation in acute hemorrhagic stroke, seventy-two male C57BL/6 mice were randomly separated into 6 groups (n=12), the experimental group (EG, day 1, day 3 and day 7) and the control group (CG, day 1, day 3 and day 7). The mouse cerebral hemorrhage model was established by collagenase injection, and the EG received 0.4 mL fecal filtrate of healthy mice once a day, and the CG received the same amount of normal saline transplantation. The mNSS score, hematoma volume and cerebral edema content were used to evaluate nerve function injury and brain injury degree at each time point after operation. The expressions of inflammatory factors were detected by western blot. We found that at each time point after operation, compared with the CG, nerve function deficit scores of mice in the EG declined (P<0.05), the water content of mice brain tissue in the EG declined (P<0.05), and the protein expressions of inflammatory factors in the EG were decreased (P<0.05). Relative to the CG, the volume of hematoma in the EG declined on day 3 along with day 7 after operation (P<0.05). In conclusion, intestinal flora can reduce cerebral hemorrhage area and brain tissue inflammation, and then improve the performance of nerve function deficit in acute hemorrhagic stroke.}, } @article {pmid39261424, year = {2024}, author = {Evrensel, A}, title = {Probiotics and Fecal Microbiota Transplantation in Major Depression: Doxa or Episteme?.}, journal = {Advances in experimental medicine and biology}, volume = {1456}, number = {}, pages = {67-83}, pmid = {39261424}, issn = {0065-2598}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; *Depressive Disorder, Major/therapy/microbiology ; Antidepressive Agents/therapeutic use ; Animals ; }, abstract = {In the human body, eukaryotic somatic cells and prokaryotic microorganisms live together. In this state, the body can be viewed as a "superorganism." Symbiotic life with commensal microorganisms can be observed in almost every part of the body. Intestinal microbiota plays an important role in health and disease, and in shaping and regulating neuronal functions from the intrauterine period to the end of life. Microbiota-based treatment opportunities are becoming more evident in both understanding the etiopathogenesis and treatment of neuropsychiatric disorders, especially depression. Antidepressant drugs, which are the first choice in the treatment of depression, also have antimicrobial and immunomodulatory mechanisms of action. From these perspectives, direct probiotics and fecal microbiota transplantation are treatment options to modulate microbiota composition. There are few preclinical and clinical studies on the effectiveness and safety of these applications in depression. The information obtained from these studies may still be at a doxa level. However, the probability that this information will become episteme in the future seems to be increasing.}, } @article {pmid39259805, year = {2024}, author = {Sawaed, J and Zelik, L and Levin, Y and Feeney, R and Naama, M and Gordon, A and Zigdon, M and Rubin, E and Telpaz, S and Modilevsky, S and Ben-Simon, S and Awad, A and Harshuk-Shabso, S and Nuriel-Ohayon, M and Werbner, M and Schroeder, BO and Erez, A and Bel, S}, title = {Antibiotics damage the colonic mucus barrier in a microbiota-independent manner.}, journal = {Science advances}, volume = {10}, number = {37}, pages = {eadp4119}, pmid = {39259805}, issn = {2375-2548}, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology/adverse effects ; Mice ; *Intestinal Mucosa/metabolism/microbiology/drug effects/pathology ; *Gastrointestinal Microbiome/drug effects ; *Colon/metabolism/drug effects/pathology/microbiology ; *Mucus/metabolism ; Inflammatory Bowel Diseases/chemically induced/metabolism/pathology/microbiology ; Endoplasmic Reticulum Stress/drug effects ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Humans ; }, abstract = {Antibiotic use is a risk factor for development of inflammatory bowel diseases (IBDs). IBDs are characterized by a damaged mucus layer, which does not separate the intestinal epithelium from the microbiota. Here, we hypothesized that antibiotics affect the integrity of the mucus barrier, which allows bacterial penetrance and predisposes to intestinal inflammation. We found that antibiotic treatment led to breakdown of the colonic mucus barrier and penetration of bacteria into the mucus layer. Using fecal microbiota transplant, RNA sequencing followed by machine learning, ex vivo mucus secretion measurements, and antibiotic treatment of germ-free mice, we determined that antibiotics induce endoplasmic reticulum stress in the colon that inhibits colonic mucus secretion in a microbiota-independent manner. This antibiotic-induced mucus secretion flaw led to penetration of bacteria into the colonic mucus layer, translocation of microbial antigens into circulation, and exacerbation of ulcerations in a mouse model of IBD. Thus, antibiotic use might predispose to intestinal inflammation by impeding mucus production.}, } @article {pmid39256134, year = {2024}, author = {Sono, M and Iimori, K and Nagao, M and Ogawa, S and Maruno, T and Nakanishi, Y and Anazawa, T and Nagai, K and Masui, T and Mori, H and Hosomi, K and Kunisawa, J and Yokota, H and Tanaka, Y and Ohno, H and Hatano, E and Fukuda, A and Seno, H}, title = {Reduction of butyrate-producing bacteria in the gut microbiome of Japanese patients with pancreatic cancer.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pan.2024.09.002}, pmid = {39256134}, issn = {1424-3911}, abstract = {BACKGROUND: The incidence of pancreatic cancer is on the rise, and its prognosis remains poor. Recent reports have established a link between the gut and oral microbiome and pancreatic cancer. However, the intricacies of this association within the Japanese population remain unclear. In this study, we investigated the gut and oral microbiomes of Japanese patients with pancreatic cancer, comparing them with those of healthy individuals.

METHODS: We recruited 30 patients with untreated pancreatic cancer and 18 healthy controls at Kyoto University Hospital (2018-2022). We performed a comprehensive 16S rRNA gene sequencing to analyze their gut and oral microbiomes.

RESULTS: Analysis revealed that the diversity of the gut and oral microbiomes of patients with pancreatic cancer was reduced compared to that of the healthy controls. Specifically, we observed an increase in the genus Streptococcus in both the gut and oral microbiomes and a significant decrease in several butyrate-producing bacteria in fecal samples. Moreover, bacteria such as Streptococcus mitis and Holdemanella biformis were present in pancreatic cancer tissues, suggesting that they might influence the carcinogenesis and progression of pancreatic cancer.

CONCLUSIONS: The gut and oral microbiome differed between patients with pancreatic cancer and healthy controls, with a notable decrease in butyrate-producing bacteria in the gut microbiome of the patients. This suggests that there may be a distinct microbial signature associated with pancreatic cancer in the Japanese population. Further studies are required to elucidate the microbiome's causal role in this cancer and help develop prognostic markers or targeted therapies.}, } @article {pmid39253878, year = {2024}, author = {Jangi, S and Hecht, G}, title = {Microbiome 2.0: lessons from the 2024 Gut Microbiota for Health World Summit.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2400579}, doi = {10.1080/19490976.2024.2400579}, pmid = {39253878}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Fecal Microbiota Transplantation ; *Probiotics/administration & dosage ; Congresses as Topic ; }, abstract = {This Meeting Summary highlights the key insights from the 12th meeting of the Gut Microbiota for Health World Summit, held in Washington, DC, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM). Through a 2-day series of plenary sessions, workshops, a poster session, and live discussions involving thought leaders, physicians, researchers, and representatives from the Food and Drug Administration and the pharmaceutical industry, the conference attendees focused on the strategies and challenges in developing microbiome-based therapies to prevent and treat human disease. The conference highlighted progress in the field, including the recently successful introduction of 2 new fecal microbial transplantation-based products into the clinical setting, and the continuing development of next-generation probiotics. However, to continue to advance microbiome-directed treatments, three key themes emerged during the meeting, including (1) better methods to identify actionable targets in the microbiome (2) developing effective strategies to manipulate the microbiome (3) aligning microbiome-based therapies with existing treatment paradigms in the real world.}, } @article {pmid39252488, year = {2024}, author = {Park, J and Hong, SN and Lee, HS and Shin, J and Oh, EH and Nam, K and Seong, G and Kim, HG and Kim, JO and Jeon, SR and , }, title = {Perception of fecal microbiota transplantation in patients with ulcerative colitis in Korea: a KASID multicenter study.}, journal = {The Korean journal of internal medicine}, volume = {39}, number = {5}, pages = {783-792}, pmid = {39252488}, issn = {2005-6648}, support = {//Soonchunhyang University/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Colitis, Ulcerative/therapy/microbiology/diagnosis ; Male ; Female ; Adult ; Republic of Korea ; Middle Aged ; Prospective Studies ; *Health Knowledge, Attitudes, Practice ; Patient Education as Topic ; Patient Preference ; Treatment Outcome ; Patient Acceptance of Health Care ; Young Adult ; Aged ; Perception ; }, abstract = {BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) is a promising therapy for inducing and maintaining remission in patients with ulcerative colitis (UC). However, FMT has not been approved for UC treatment in Korea. Our study aimed to investigate patient perceptions of FMT under the national medical policy.

METHODS: This was a prospective, multicenter study. Patients with UC ≥ 19 years of age were included. Patients were surveyed using 22 questions on FMT. Changes in perceptions of FMT before and after education were also compared.

RESULTS: A total of 210 patients with UC were enrolled. We found that 51.4% of the patients were unaware that FMT was an alternative treatment option for UC. After reading the educational materials on FMT, more patients were willing to undergo this procedure (27.1% vs. 46.7%; p < 0.001). The preferred fecal donor was the one recommended by a physician (41.0%), and the preferred transplantation method was the oral capsule (30.4%). A large proportion of patients (50.0%) reported that the national medical policy influenced their choice of FMT treatment. When patients felt severe disease activity, their willingness to undergo FMT increased (92.3% vs. 43.1%; p = 0.001).

CONCLUSION: Education can increase preference for FMT in patients with UC. When patients have severe disease symptoms or their quality of life decreases their willingness to undergo FMT increases. Moreover, national medical policies may influence patient choices regarding FMT.}, } @article {pmid39252487, year = {2024}, author = {Kim, YC and Sohn, KH and Kang, HR}, title = {Gut microbiota dysbiosis and its impact on asthma and other lung diseases: potential therapeutic approaches.}, journal = {The Korean journal of internal medicine}, volume = {39}, number = {5}, pages = {746-758}, pmid = {39252487}, issn = {2005-6648}, support = {RS-2023-00217157//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; }, mesh = {Humans ; *Dysbiosis ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Asthma/microbiology/immunology/therapy ; *Fecal Microbiota Transplantation ; *Prebiotics ; Animals ; Lung/microbiology/immunology/metabolism ; Lung Diseases/microbiology/therapy/immunology ; }, abstract = {The emerging field of gut-lung axis research has revealed a complex interplay between the gut microbiota and respiratory health, particularly in asthma. This review comprehensively explored the intricate relationship between these two systems, focusing on their influence on immune responses, inflammation, and the pathogenesis of respiratory diseases. Recent studies have demonstrated that gut microbiota dysbiosis can contribute to asthma onset and exacerbation, prompting investigations into therapeutic strategies to correct this imbalance. Probiotics and prebiotics, known for their ability to modulate gut microbial compositions, were discussed as potential interventions to restore immune homeostasis. The impact of antibiotics and metabolites, including short-chain fatty acids produced by the gut microbiota, on immune regulation was examined. Fecal microbiota transplantation has shown promise in various diseases, but its role in respiratory disorders is not established. Innovative approaches, including mucus transplants, inhaled probiotics, and microencapsulation strategies, have been proposed as novel therapeutic avenues. Despite challenges, including the sophisticated adaptability of microbial communities and the need for mechanistic clarity, the potential for microbiota-based interventions is considerable. Collaboration between researchers, clinicians, and other experts is essential to unravel the complexities of the gut-lung axis, paving a way for innovative strategies that could transform the management of respiratory diseases.}, } @article {pmid39252485, year = {2024}, author = {Seo, J and Choi, CH}, title = {Seeking acceptance: how education shifts views on fecal microbiota transplants for ulcerative colitis in Korea.}, journal = {The Korean journal of internal medicine}, volume = {39}, number = {5}, pages = {697-699}, pmid = {39252485}, issn = {2005-6648}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Colitis, Ulcerative/microbiology/therapy/diagnosis ; Republic of Korea ; Health Knowledge, Attitudes, Practice ; Patient Acceptance of Health Care ; Gastrointestinal Microbiome ; }, } @article {pmid39251400, year = {2024}, author = {Patel, SK and Gooya, M and Guo, Q and Noel, S and Rabb, H}, title = {The microbiome and acute organ injury: focus on kidneys.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {}, number = {}, pages = {}, doi = {10.1093/ndt/gfae196}, pmid = {39251400}, issn = {1460-2385}, abstract = {The microbiome of critically ill patients is significantly altered by both effects of the illnesses and clinical interventions provided during intensive care. Studies have shown that manipulating the microbiome can prevent or modulate complications of critical illness in experimental models and preliminary clinical trials. This review aims to discuss general concepts about the microbiome, including mechanisms of modifying acute organ dysfunction. The focus will be on the effects of microbiome modulation during experimental acute kidney injury (excluding septic AKI) and comparison with other experimental acute organ injuries commonly seen in critically ill patients.}, } @article {pmid39249130, year = {2024}, author = {Ju, T and Song, Z and Qin, D and Cheng, J and Li, T and Hu, G and Fu, S}, title = {Neohesperidin Attenuates DSS-Induced Ulcerative Colitis by Inhibiting Inflammation, Reducing Intestinal Barrier Damage, and Modulating Intestinal Flora Composition.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c04433}, pmid = {39249130}, issn = {1520-5118}, abstract = {Flavonoid natural products are emerging as a promising approach for treating Ulcerative Colitis (UC) due to their natural origin and minimal toxicity. This study investigates the effects of Neohesperidin (NEO), a natural flavonoid, on Dextran Sodium Sulfate (DSS)-induced UC in mice, focusing on the underlying molecular mechanisms. Early intervention with NEO (25 and 50 mg/kg) mitigated colon shortening, restored damaged barrier proteins, and significantly reduced the inflammatory cytokine levels. Moreover, NEO inhibited the MAPK/NF-κB signaling pathway and enhanced the levels of intestinal barrier proteins (Claudin-3 and ZO-1). Additionally, NEO increased beneficial intestinal probiotics (S24-7 and Lactobacillaceae) while reducing harmful bacteria (Erysipelotrichi, Enterobacteriaceae). Fecal microbial transplantation (FMT) results demonstrated that NEO (50 mg/kg) markedly improved UC symptoms. In conclusion, early NEO intervention may alleviate DSS-induced UC by inhibiting inflammatory responses, preserving intestinal barrier integrity and modulating gut microbiota.}, } @article {pmid39247802, year = {2024}, author = {Naji, A and Siskin, D and Woodworth, MH and Lee, JR and Kraft, CS and Mehta, N}, title = {The Role of the Gut, Urine, and Vaginal Microbiomes in the Pathogenesis of Urinary Tract Infection in Women and Consideration of Microbiome Therapeutics.}, journal = {Open forum infectious diseases}, volume = {11}, number = {9}, pages = {ofae471}, pmid = {39247802}, issn = {2328-8957}, abstract = {The gut, urine, and vaginal microbiomes play significant roles in the pathogenesis of recurrent urinary tract infections (rUTIs). Analysis of these microbiota has shown distinct associations with urinary tract infections. Encouraging data indicate that rUTIs may be responsive to microbiome treatments such as fecal microbiota transplantation, expanding potential treatments beyond antibiotics, hydration, and behavioral interventions. If successful, these nonantibiotic therapies have the potential to increase time between rUTI episodes and reduce the prevalence of multidrug-resistant organisms. In this review, we discuss the role of the 3 microbiomes in the pathogenesis of rUTI and utilization of live biotherapeutic products as therapy for rUTI.}, } @article {pmid39247190, year = {2024}, author = {Strzępa, A and Marcińska, K and Kiecka, A and Majewska-Szczepanik, M and Szczepanik, M}, title = {Proton pump inhibitor alters Th17/Treg balance and induces gut dysbiosis suppressing contact hypersensitivity reaction in mice.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1390025}, pmid = {39247190}, issn = {1664-3224}, mesh = {Animals ; *Proton Pump Inhibitors/adverse effects/pharmacology ; *Gastrointestinal Microbiome/drug effects/immunology ; *Th17 Cells/immunology/metabolism ; Mice ; *T-Lymphocytes, Regulatory/immunology ; *Dysbiosis ; *Omeprazole/pharmacology ; Disease Models, Animal ; Cytokines/metabolism ; Female ; Mice, Inbred C57BL ; Dermatitis, Contact/immunology/etiology ; }, abstract = {Proton pump inhibitors (PPIs), such as omeprazole, are the most commonly prescribed drugs. Treatment with PPIs alters gut microbiota composition and reduces the production of reactive oxygen (ROS) and proinflammatory IL-1β, IL-6, and TNF-α cytokines. Here, using the T cell-dependent contact hypersensitivity (CHS) response, an animal model of allergic contact dermatitis (ACD) that affects up to 30% of the population, we demonstrated that a two-week omeprazole treatment suppresses the development of CHS. Omeprazole treatment before CHS induction, reduced inflammatory response in ears measured by ear swelling, ear biopsy weight, MPO activity, and proinflammatory cytokine production. These changes were associated with reduced frequency of TCRαβ[+] CD4[+] IL-17A[+] and TCRαβ[+] CD8[+] IL-17A[+] T cells and increased frequency of TCRαβ[+] CD4[+] CD25[+] FoxP3[+] Treg, and TCRαβ[+] CD4+ IL-10+ Tr1 cells in peripheral lymphoid organs. Omeprazole treatment decreased the production of ROS, TNF-α, and IL-6, which supported Th17 cell induction, and increased the frequency of Clostridium cluster XIVab and Lactobacillus, implicated in Treg cell induction. The fecal microbiota transplantation (FMT) experiment confirmed the role of omeprazole-induced changes in gut microbiota profile in CHS suppression. Our data suggests that omeprazole ameliorates inflammatory response mediated by T-cells.}, } @article {pmid39245800, year = {2024}, author = {Ge, P and Xie, H and Guo, Y and Jin, H and Chen, L and Chen, Z and Liu, Y}, title = {Linoleyl acetate and mandenol alleviate HUA-induced ED via NLRP3 inflammasome and JAK2/STAT3 signalling conduction in rats.}, journal = {Journal of cellular and molecular medicine}, volume = {28}, number = {17}, pages = {e70075}, pmid = {39245800}, issn = {1582-4934}, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Janus Kinase 2/metabolism ; Male ; *Inflammasomes/metabolism ; *STAT3 Transcription Factor/metabolism ; *Signal Transduction/drug effects ; Rats ; *Rats, Sprague-Dawley ; *Erectile Dysfunction/drug therapy/etiology/metabolism ; *Hyperuricemia/drug therapy/complications ; Apoptosis/drug effects ; Disease Models, Animal ; }, abstract = {Hyperuricemia (HUA) is characterized by elevated blood uric acid levels, which can increase the risk of erectile dysfunction (ED). Clinical studies have demonstrated satisfactory efficacy of a traditional Chinese medicine formula QYHT decoction in improving ED. Furthermore, the main monomeric components of this formula, linoleyl acetate and mandenol, demonstrate promise in the treatment of ED. This study established an ED rat model induced by HUA and the animals were administered with linoleyl acetate and mandenol. HE and TUNEL were performed to detect tissue changes, ELISA to measure the levels of serum testosterone (T), MDA, NO, CRP, and TNF-α and qPCR and WB to assess the expression levels of NLRP3, ASC, Caspase-1, JAK2, and STAT3 in whole blood. The findings showed that linoleyl acetate and mandenol improved kidney tissue morphology, reduced cell apoptosis in penile tissue, significantly increased T and NO levels, while substantially decreasing levels of MDA, CRP, and TNF-α. Meanwhile, the expression of NLRP3, ASC, and Caspase-1 mRNAs and proteins was markedly reduced, and the phosphorylation of JAK2 and STAT3 was inhibited. These findings were further validated through faecal microbiota transplantation results. Taken together, linoleyl acetate and mandenol could inhibit NLRP3 inflammasome activation, reduce inflammatory and oxidative stress responses, suppress the activity of JAK-STAT signalling pathway, ultimately providing a potential treatment for HUA-induced ED.}, } @article {pmid38834146, year = {2024}, author = {Dafnis, G}, title = {Transsphincteric Repair of Rectourethral Fistulas in Combination With Dartos Muscle Flap Interposition Following Radical Prostatectomy.}, journal = {Urology}, volume = {191}, number = {}, pages = {130-135}, doi = {10.1016/j.urology.2024.05.041}, pmid = {38834146}, issn = {1527-9995}, mesh = {Humans ; Male ; *Rectal Fistula/surgery/etiology ; *Prostatectomy/methods/adverse effects ; *Urinary Fistula/surgery/etiology ; *Urethral Diseases/surgery/etiology ; *Surgical Flaps/transplantation ; Middle Aged ; Aged ; Scrotum/surgery ; Urologic Surgical Procedures, Male/methods ; Postoperative Complications/etiology/surgery ; Retrospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: To present our experience with a novel technique that combines the York-Mason transsphincteric approach with dartos muscle flap interposition to treat rectourethral fistulas.

METHODS: We extracted records from our prospectively kept database of 35 procedures conducted for treating rectourethral fistulas during 2002-2023; the York-Mason approach was combined with dartos muscle flap interposition in 5 cases, performed for treating rectourethral fistulas due to radical prostatectomy, all of which were referral cases.

RESULTS: All 5 patients were successfully treated and followed up for a median of 70.0 months without recurrence. Before the fistula repair, all had a diverting stoma. In all cases, the first voiding cystourethrogram revealed a healed fistula. The posterior and the scrotal incisions healed uneventfully. All patients reported normal voiding and no urinary incontinence. To date, the stoma has closed in 3 patients, all of whom had intact fecal continence and no postoperative anal stenosis.

CONCLUSION: The transsphincteric modified York-Mason approach combined with dartos muscle flap interposition resulted in complete healing of rectourethral fistulas.}, } @article {pmid39245217, year = {2024}, author = {Banerjee, A and Chatterji, U}, title = {Prevalence of perturbed gut microbiota in pathophysiology of arsenic-induced anxiety- and depression-like behaviour in mice.}, journal = {Chemosphere}, volume = {364}, number = {}, pages = {143293}, doi = {10.1016/j.chemosphere.2024.143293}, pmid = {39245217}, issn = {1879-1298}, abstract = {Severe toxic effects of arsenic on human physiology have been of immense concern worldwide. Arsenic causes irrevocable structural and functional disruption of tissues, leading to major diseases in chronically exposed individuals. However, it is yet to be resolved whether the effects result from direct deposition and persistence of arsenic in tissues, or via activation of indirect signaling components. Emerging evidences suggest that gut inhabitants play an active role in orchestrating various aspects of brain physiology, as the gut-brain axis maintains cognitive health, emotions, learning and memory skills. Arsenic-induced dysbiosis may consequentially evoke neurotoxicity, eventually leading to anxiety and depression. To delineate the mechanism of action, mice were exposed to different concentrations of arsenic. Enrichment of Gram-negative bacteria and compromised barrier integrity of the gut enhanced lipopolysaccharide (LPS) level in the bloodstream, which in turn elicited systemic inflammation. Subsequent alterations in neurotransmitter levels, microglial activation and histoarchitectural disruption in brain triggered onset of anxiety- and depression-like behaviour in a dose-dependent manner. Finally, to confirm whether the neurotoxic effects are specifically a consequence of modulation of gut microbiota (GM) by arsenic and not arsenic accumulation in the brain, fecal microbiota transplantations (FMT) were performed from arsenic-exposed mice to healthy recipients. 16S rRNA gene sequencing indicated major alterations in GM population in FMT mice, leading to severe structural, functional and behavioural alterations. Moreover, suppression of Toll-like receptor 4 (TLR4) using vivo-morpholino oligomers (VMO) indicated restoration of the altered parameters towards normalcy in FMT mice, confirming direct involvement of the GM in inducing neurotoxicity through the arsenic-gut-brain axis. This study accentuates the potential role of the gut microbiota in promoting neurotoxicity in arsenic-exposed mice, and has immense relevance in predicting neurotoxicity under altered conditions of the gut for designing therapeutic interventions that will target gut dysbiosis to attenuate arsenic-mediated neurotoxicity.}, } @article {pmid39240145, year = {2024}, author = {Moutsoglou, D and Syal, A and Lopez, S and Nelson, EC and Chen, L and Kabage, AJ and Fischer, M and Khoruts, A and Vaughn, BP and Staley, C}, title = {Novel Microbial Engraftment Trajectories following Microbiota Transplantation Therapy in Ulcerative Colitis.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjae142}, pmid = {39240145}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: Microbiota transplant therapy is an emerging treatment for ulcerative colitis. One proposed mechanism for the benefit of microbiota transplant therapy is through engraftment of donor microbiota. However, the kinetics of engraftment are unknown. We identified SourceTracker as an efficient method both to determine engraftment and for the kinetic study of engrafting donor taxa to aid in determining the mechanism of how this therapy may treat ulcerative colitis.

METHODS: Ulcerative colitis patients were treated with either encapsulated (drug name MTP-101C) or placebo capsules daily for eight weeks followed by a four-week washout period. Amplicon sequence data from donors and patients were analyzed using the Bayesian algorithm SourceTracker.

RESULTS: Twenty-seven patients were enrolled, 14 to the placebo group and 13 to the microbiota transplant therapy group. Baseline Shannon and Chao1 indices negatively correlated with week 12 donor engraftment for patients treated with active drug capsules but not for placebo patients. SourceTracker engraftment positively correlated with the week 12 distance from donors measured using the Bray-Curtis similarity metric in treated patients but not with placebo. We identified engrafting taxa from donors in our patients as well as quantified the proportion of donor similarity or engraftment during weeks one through eight (active treatment) and week 12, four weeks after the last dose.

CONCLUSION: SourceTracker can be used as a simple and reliable method to quantify donor microbial community engraftment and donor taxa contribution in patients with ulcerative colitis and other inflammatory conditions treated with microbiota transplant therapy.}, } @article {pmid39239516, year = {2024}, author = {Wang, M and Sun, P and Chai, X and Liu, YX and Li, L and Zheng, W and Chen, S and Zhu, X and Zhao, S}, title = {Reconstituting gut microbiota-colonocyte interactions reverses diet-induced cognitive deficits: The beneficial of eucommiae cortex polysaccharides.}, journal = {Theranostics}, volume = {14}, number = {12}, pages = {4622-4642}, pmid = {39239516}, issn = {1838-7640}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Diet, High-Fat/adverse effects ; Mice ; *Cognitive Dysfunction/therapy ; *Polysaccharides/pharmacology ; *Fecal Microbiota Transplantation ; *Mice, Inbred C57BL ; Male ; *Dysbiosis/therapy ; Colon/microbiology ; Escherichia coli ; Butyrates/metabolism ; Proteobacteria/isolation & purification/drug effects ; Disease Models, Animal ; }, abstract = {Rationale: Consumption of a high-fat diet (HFD) has been implicated in cognitive deficits and gastrointestinal dysfunction in humans, with the gut microbiota emerging as a pivotal mediator of these diet-associated pathologies. The introduction of plant-based polysaccharides into the diet as a therapeutic strategy to alleviate such conditions is gaining attention. Nevertheless, the mechanistic paradigm by which polysaccharides modulate the gut microbiota remains largely undefined. This study investigated the mechanisms of action of Eucommiae cortex polysaccharides (EPs) in mitigating gut dysbiosis and examined their contribution to rectifying diet-related cognitive decline. Methods: Initially, we employed fecal microbiota transplantation (FMT) and gut microbiota depletion to verify the causative role of changes in the gut microbiota induced by HFD in synapse engulfment-dependent cognitive impairments. Subsequently, colonization of the gut of chow-fed mice with Escherichia coli (E. coli) from HFD mice confirmed that inhibition of Proteobacteria by EPs was a necessary prerequisite for alleviating HFD-induced cognitive impairments. Finally, supplementation of HFD mice with butyrate and treatment of EPs mice with GW9662 demonstrated that EPs inhibited the expansion of Proteobacteria in the colon of HFD mice by reshaping the interactions between the gut microbiota and colonocytes. Results: Findings from FMT and antibiotic treatments demonstrated that HFD-induced cognitive impairments pertaining to neuronal spine loss were contingent on gut microbial composition. Association analysis revealed strong associations between bacterial taxa belonging to the phylum Proteobacteria and cognitive performance in mice. Further, introducing E. coli from HFD-fed mice into standard diet-fed mice underscored the integral role of Proteobacteria proliferation in triggering excessive synaptic engulfment-related cognitive deficits in HFD mice. Crucially, EPs effectively counteracted the bloom of Proteobacteria and subsequent neuroinflammatory responses mediated by microglia, essential for cognitive improvement in HFD-fed mice. Mechanistic insights revealed that EPs promoted the production of bacteria-derived butyrate, thereby ameliorating HFD-induced colonic mitochondrial dysfunction and reshaping colonocyte metabolism. This adjustment curtailed the availability of growth substrates for facultative anaerobes, which in turn limited the uncontrolled expansion of Proteobacteria. Conclusions: Our study elucidates that colonocyte metabolic disturbances, which promote Proteobacteria overgrowth, are a likely cause of HFD-induced cognitive deficits. Furthermore, dietary supplementation with EPs can rectify behavioral dysfunctions associated with HFD by modifying gut microbiota-colonocyte interactions. These insights contribute to the broader understanding of the modulatory effects of plant prebiotics on the microbiota-gut-brain axis and suggest a potential therapeutic avenue for diet-associated cognitive dysfunction.}, } @article {pmid39238062, year = {2024}, author = {Lv, Y and Ge, C and Wu, L and Hu, Z and Luo, X and Huang, W and Zhan, S and Shen, X and Yu, D and Liu, B}, title = {Hepatoprotective effects of magnolol in fatty liver hemorrhagic syndrome hens through shaping gut microbiota and tryptophan metabolic profile.}, journal = {Journal of animal science and biotechnology}, volume = {15}, number = {1}, pages = {120}, pmid = {39238062}, issn = {1674-9782}, abstract = {BACKGROUND: Magnolol (MAG) exhibits hepatoprotective activity, however, whether and how MAG regulates the gut microbiota to alleviate fatty liver hemorrhagic syndrome (FLHS) remains unclear. Therefore, we investigated the mechanism of MAG in FLHS laying hens with an emphasis on alterations in the gut-liver axis. We randomly divided 540 56-week-old Hy-line white laying hens with FLSH into 4 groups. The birds were fed a high-fat low-protein (HFLP) diet (CON) or HELP diets supplemented with 200, 400, and 600 mg/kg of MAG (M1, M2, and M3, respectively) for 9 weeks.

RESULTS: Magnolol supplementation increased the laying rate and ameliorated hepatic damage and dysfunction by regulating lipid metabolism, improving intestinal barrier function, and shaping the gut microbiota and tryptophan metabolic profiles. Dietary MAG supplementation downregulated the expression of lipid synthesis genes and upregulated the expression of lipid transport genes at varying degrees. The intestinal barrier function was improved by 200 and 400 mg/kg of MAG supplementation, as evidenced by the increased villus height and mRNA expression of tight junction related genes. Microbiological profile information revealed that MAG changed the gut microbiota, especially by elevating the abundances of Lactobacillus, Faecalibacterium, and Butyricicoccus. Moreover, non-targeted metabolomic analysis showed that MAG significantly promoted tryptophan metabolites, which was positively correlated with the MAG-enriched gut microbiota. The increased tryptophan metabolites could activate aryl hydrocarbon receptor (AhR) and relieved hepatic inflammation and immune response evidenced by the downregulated the gene expression levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the liver. The fecal microbiota transplantation (FMT) experiments further confirmed that the hepatoprotective effect is likely mediated by MAG-altered gut microbiota and their metabolites.

CONCLUSIONS: Magnolol can be an outstanding supplement for the prevention and mitigation of FLHS in laying hens by positively regulating lipid synthesis and transport metabolism, improving the intestinal barrier function, and relieving hepatic inflammation by reshaping the gut microbiota and metabolite profiles through gut microbiota-indole metabolite-hepatic AhR crosstalk. These findings elucidate the mechanisms by which MAG alleviates FLHS and provide a promising method for preventing liver diseases by modulating gut microbiota and their metabolites.}, } @article {pmid39235561, year = {2024}, author = {Jiang, SS and Kang, ZR and Chen, YX and Fang, JY}, title = {The gut microbiome modulate response to immunotherapy in cancer.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {39235561}, issn = {1869-1889}, abstract = {Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors. Currently, clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of cancers. Preclinical investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy. Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells. Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies. Fecal microbial transplants, probiotics, dietary interventions, and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy. Ongoing clinical trials are evaluating these approaches. This review presents the recent advancements in understanding the dynamic interplay among the host immunity, the microbiome, and cancer immunotherapy, as well as strategies for modulating the microbiome, with a view to translating into clinical applications.}, } @article {pmid39235366, year = {2024}, author = {Liu, L and Ma, L and Liu, H and Zhao, F and Li, P and Zhang, J and Lü, X and Zhao, X and Yi, Y}, title = {Targeted discovery of gut microbiome-remodeling compounds for the treatment of systemic inflammatory response syndrome.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0078824}, doi = {10.1128/msystems.00788-24}, pmid = {39235366}, issn = {2379-5077}, abstract = {Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted in vitro experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, in vitro experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD's therapeutic potential in SIRS and highlights the importance of innovative treatment approaches for this disease by targeting the gut microbiota.IMPORTANCEDeveloping effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition.}, } @article {pmid39234553, year = {2024}, author = {Xu, J and Zou, Z and Li, X and Sun, X and Wang, X and Qin, F and Abulizi, A and Chen, Q and Pan, Z and Shen, H and Lv, Y and Yan, R}, title = {Effect of Gegen Qinlian Decoction on the regulation of gut microbiota and metabolites in type II diabetic rats.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1429360}, pmid = {39234553}, issn = {1664-302X}, abstract = {Gegen Qinlian Decoction (GGQLT) is a traditional Chinese herbal medicine that has been reported to have a significant therapeutic effect in the management of type II diabetes mellitus (T2DM). In this study, we constructed a T2DM rat model by feeding a high-fat diet and injecting streptozotocin (STZ) and tested the effects of feeding GGQLT and fecal transplantation on the physiological indices, microbiota, and metabolism of rats. The results showed that the administration of GGQLT can significantly improve the growth performance of rats and has a remarkable antihyperlipidemic effect. In addition, GGQLT altered the composition of gut microbiota by increasing beneficial bacteria such as Coprococcus, Bifidobacterium, Blautia, and Akkermansia. In addition, GGQLT elevated levels of specific bile acids by metabolomic analysis, potentially contributing to improvements in lipid metabolism. These findings suggest that GGQLT may have beneficial effects on T2DM by influencing lipid metabolism and gut microbiota. However, further studies are needed to elucidate its mechanisms and assess clinical applications.}, } @article {pmid39230353, year = {2024}, author = {Bland, CM and Love, BL and Jones, BM}, title = {Human microbiome: Impact of newly approved treatments on C. difficile infection.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {}, number = {}, pages = {}, doi = {10.1093/ajhp/zxae249}, pmid = {39230353}, issn = {1535-2900}, abstract = {DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice.

SUMMARY: The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies.

CONCLUSION: Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement.}, } @article {pmid39226363, year = {2024}, author = {Zhang, N and Zhang, R and Jiang, L and Gao, Z and Xia, W and Ma, X and Qin, Y and Zhang, D and Li, J and Tian, P and Zhang, Q and Wang, W and Zhang, K and Xu, S and Zhao, N and Xu, S}, title = {Inhibition of colorectal cancer in Alzheimer's disease is mediated by gut microbiota via induction of inflammatory tolerance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {37}, pages = {e2314337121}, doi = {10.1073/pnas.2314337121}, pmid = {39226363}, issn = {1091-6490}, support = {82100863//MOST | National Natural Science Foundation of China (NSFC)/ ; H2020206105//Hebei Natural Science Foundation/ ; H2018206358//Hebei Natural Science Foundation/ ; C20210346//Funding project for introducing overseas students of Hebei Province/ ; 20211628//Medical Science Research Project of Hebei Province/ ; ZF2023029//Hebei Province Government-funded Excellent Talents Project in Clinical Medicine/ ; 20377707D//The Science and Technology project of the People's Livelihood in Hebei Province/ ; 206Z7701G//Special Funding for Local Science and Technology Development Guided by the Central Government/ ; 2019-I2M-5-055//CAMS Innovation Fund for Medical Sciences/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Alzheimer Disease/microbiology ; *Colorectal Neoplasms/microbiology/immunology/pathology ; Mice ; Humans ; *Fecal Microbiota Transplantation ; Male ; Inflammation ; Cognitive Dysfunction ; Female ; Prevotella ; Disease Models, Animal ; Lipopolysaccharides ; Carcinogenesis ; Dextran Sulfate ; }, abstract = {Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer's disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT). AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane-dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella, were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella-derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI. These data reveal that intestinal Prevotella-derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.}, } @article {pmid39226184, year = {2024}, author = {Zhai, Z and Yang, Y and Chen, S and Wu, Z}, title = {Long-Term Exposure to Polystyrene Microspheres and High-Fat Diet-Induced Obesity in Mice: Evaluating a Role for Microbiota Dysbiosis.}, journal = {Environmental health perspectives}, volume = {132}, number = {9}, pages = {97002}, pmid = {39226184}, issn = {1552-9924}, mesh = {Animals ; *Dysbiosis/microbiology ; Mice ; *Obesity/microbiology ; *Diet, High-Fat ; *Mice, Inbred C57BL ; *Microspheres ; *Polystyrenes/toxicity ; *Gastrointestinal Microbiome/drug effects ; Male ; Microplastics/toxicity ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Microplastics (MPs) have become a global environmental problem, emerging as contaminants with potentially alarming consequences. However, long-term exposure to polystyrene microspheres (PS-MS) and its effects on diet-induced obesity are not yet fully understood.

OBJECTIVES: We aimed to investigate the effect of PS-MS exposure on high-fat diet (HFD)-induced obesity and underlying mechanisms.

METHODS: In the present study, C57BL/6J mice were fed a normal diet (ND) or a HFD in the absence or presence of PS-MS via oral administration for 8 wk. Antibiotic depletion of the microbiota and fecal microbiota transplantation (FMT) were performed to assess the influence of PS-MS on intestinal microbial ecology. We performed 16S rRNA sequencing to dissect microbial discrepancies and investigated the dysbiosis-associated intestinal integrity and inflammation in serum.

RESULTS: Compared with HFD mice, mice fed the HFD with PS-MS exhibited higher body weight, liver weight, metabolic dysfunction-associated steatotic liver disease (MASLD) activity scores, and mass of white adipose tissue, as well as higher blood glucose and serum lipid concentrations. Furthermore, 16S rRNA sequencing of the fecal microbiota revealed that mice fed the HFD with PS-MS had greater α-diversity and greater relative abundances of Lachnospiraceae, Oscillospiraceae, Bacteroidaceae, Akkermansiaceae, Marinifilaceae, Deferribacteres, and Desulfovibrio, but lower relative abundances of Atopobiaceae, Bifidobacterium, and Parabacteroides. Mice fed the HFD with PS-MS exhibited lower expression of MUC2 mucin and higher levels of lipopolysaccharide and inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-17A] in serum. Correlation analyses revealed that differences in the microbial flora of mice exposed to PS-MS were associated with obesity. Interestingly, microbiota-depleted mice did not show the same PS-MS-associated differences in Muc2 and Tjp1 expression in the distal colon, expression of inflammatory cytokines in serum, or obesity outcomes between HFD and HFD + PS-MS. Importantly, transplantation of feces from HFD + PS-MS mice to microbiota-depleted HFD-fed mice resulted in a lower expression of mucus proteins, higher expression of inflammatory cytokines, and obesity outcomes, similar to the findings in HFD + PS-MS mice.

CONCLUSIONS: Our findings provide a new gut microbiota-driven mechanism for PS-MS-induced obesity in HFD-fed mice, suggesting the need to reevaluate the adverse health effects of MPs commonly found in daily life, particularly in susceptible populations. https://doi.org/10.1289/EHP13913.}, } @article {pmid39225491, year = {2024}, author = {Huang, H and Zhou, T and He, F and Wen, B and Yang, Y and Zhong, W and Wang, Q and Li, J}, title = {The gut microbiota improves reproductive dysfunction in obese mice by suppressing the NLRP3/ASC/caspase-1 axis.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/17460913.2024.2386867}, pmid = {39225491}, issn = {1746-0921}, abstract = {Aim: To explore the complex relationship between gut microbiota, obesity-related male reproductive impairments, and the NLRP3 inflammasome.Methods: A high-fat diet was administered to induce obesity in a mouse model, fecal microbiota transplantation or a high-dietary fiber diet (HDFD) was administered for 5 weeks to evaluate changes in parameters related to reproductive capacity, NLRP3, gut microbiota composition and metabolites in mice.Results: A high-fat diet induces obesity and decreases reproductive capacity in male mice. Fecal microbiota transplantation and HDFD can improve reproductive capacity in obese mice by adjusting the gut microbiota population to suppress the NLRP3/ASC/caspase-1 axis, thereby reducing IL-1β levels.Conclusion: This study offers a potential treatment for obesity-induced reproductive dysfunction by targeting the gut microbiota and the NLRP3 inflammasome pathway.}, } @article {pmid38182136, year = {2024}, author = {Frishman, S and Nuriel-Ohayon, M and Turjeman, S and Pinto, Y and Yariv, O and Tenenbaum-Gavish, K and Peled, Y and Poran, E and Pardo, J and Chen, R and Muller, E and Borenstein, E and Hod, M and Louzoun, Y and Schwartz, B and Hadar, E and Collado, MC and Koren, O}, title = {Positive effects of diet-induced microbiome modification on GDM in mice following human faecal transfer.}, journal = {Gut}, volume = {73}, number = {10}, pages = {e17}, doi = {10.1136/gutjnl-2023-331456}, pmid = {38182136}, issn = {1468-3288}, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Mice ; Humans ; Female ; *Gastrointestinal Microbiome/physiology ; Pregnancy ; Diet ; Feces/microbiology ; Disease Models, Animal ; }, } @article {pmid39225490, year = {2024}, author = {Pinto, S and Šajbenová, D and Benincà, E and Nooij, S and Terveer, EM and Keller, JJ and van der Meulen-de Jong, AE and Bogaards, JA and Steyerberg, E}, title = {Dynamics of Gut Microbiota after Fecal Microbiota Transplantation in Ulcerative Colitis: Success Linked to Control of Prevotellaceae.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjae137}, pmid = {39225490}, issn = {1876-4479}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an experimental treatment for ulcerative colitis (UC). We aimed to study microbial families associated with FMT treatment success.

METHODS: We analyzed stools from 24 UC patients treated with four FMTs weekly after randomization for pretreatment during three weeks with budesonide (n = 12) or placebo (n = 12). Stool samples were collected nine times pre-, during, and post FMT. Clinical and endoscopic response was assessed 14 weeks after initiation of the study using the full Mayo score. Early withdrawal due to worsening of UC symptoms was classified as non-response.

RESULTS: Nine patients (38%) reached remission at week 14, and 15 patients had a partial response or non-response at or before week 14. With a Dirichlet Multinomial Mixture model we identified five distinct clusters based on the microbiota composition of 180 longitudinally collected patient samples and 27 donor samples. A Prevotellaceae-dominant cluster was associated with poor response to FMT treatment. Conversely, the families Ruminococcaceae and Lachnospiraceae were associated with a successful clinical response. These associations were already visible at the start of the treatment for a subgroup of patients and were retained in repeated measures analyses of family-specific abundance over time. Responders were also characterized by a significantly lower Simpson dominance compared to non-responders.

CONCLUSIONS: The success of FMT treatment of UC patients appears to be associated with specific gut microbiota families, such as control of Prevotellaceae. Monitoring the dynamics of these microbial families could potentially be used to inform treatment success early during FMT.}, } @article {pmid39224820, year = {2024}, author = {Lin, M and Wang, P and Lu, B and Jin, M and Tan, J and Liu, W and Yuan, J and Peng, X and Chen, Y}, title = {Development and evaluation of a rapid visual loop-mediated isothermal amplification assay for the tcdA gene in Clostridioides difficile detection.}, journal = {PeerJ}, volume = {12}, number = {}, pages = {e17776}, pmid = {39224820}, issn = {2167-8359}, mesh = {*Clostridioides difficile/genetics/isolation & purification ; *Nucleic Acid Amplification Techniques/methods ; Humans ; *Bacterial Toxins/genetics ; *Sensitivity and Specificity ; *Clostridium Infections/diagnosis/microbiology ; *Feces/microbiology/chemistry ; *Enterotoxins/genetics ; DNA Primers/genetics ; Molecular Diagnostic Techniques/methods ; Polymerase Chain Reaction/methods ; Adult ; Middle Aged ; }, abstract = {BACKGROUND: The tcdA gene codes for an important toxin produced by Clostridioides difficile (C. difficile), but there is currently no simple and cost-effective method of detecting it. This article establishes and validates a rapid and visual loop-mediated isothermal amplification (LAMP) assay for the detection of the tcdA gene.

METHODS: Three sets of primers were designed and optimized to amplify the tcdA gene in C. difficile using a LAMP assay. To evaluate the specificity of the LAMP assay, C. difficile VPI10463 was used as a positive control, while 26 pathogenic bacterial strains lacking the tcdA gene and distilled water were utilized as negative controls. For sensitivity analysis, the LAMP assay was compared to PCR using ten-fold serial dilutions of DNA from C. difficile VPI10463, ranging from 207 ng/µl to 0.000207 pg/µl. The tcdA gene of C.difficile was detected in 164 stool specimens using both LAMP and polymerase chain reaction (PCR). Positive and negative results were distinguished using real-time monitoring of turbidity and chromogenic reaction.

RESULTS: At a temperature of 66 °C, the target DNA was successfully amplified with a set of primers designated, and visualized within 60 min. Under the same conditions, the target DNA was not amplified with the tcdA12 primers for 26 pathogenic bacterial strains that do not carry the tcdA gene. The detection limit of LAMP was 20.700 pg/µl, which was 10 times more sensitive than that of conventional PCR. The detection rate of tcdA in 164 stool specimens using the LAMP method was 17% (28/164), significantly higher than the 10% (16/164) detection rate of the PCR method (X[2] = 47, p < 0.01).

CONCLUSION: LAMP method is an effective technique for the rapid and visual detection of the tcdA gene of C. difficile, and shows potential advantages over PCR in terms of speed, simplicity, and sensitivity. The tcdA-LAMP assay is particularly suitable for medical diagnostic environments with limited resources and is a promising diagnostic strategy for the screening and detection of C. difficile infection in populations at high risk.}, } @article {pmid39224076, year = {2024}, author = {McMillan, AS and Theriot, CM}, title = {Bile acids impact the microbiota, host, and C. difficile dynamics providing insight into mechanisms of efficacy of FMTs and microbiota-focused therapeutics.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2393766}, pmid = {39224076}, issn = {1949-0984}, mesh = {*Bile Acids and Salts/metabolism ; Humans ; *Fecal Microbiota Transplantation ; *Clostridioides difficile/physiology ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy/microbiology ; Animals ; }, abstract = {Clostridioides difficile is a major nosocomial pathogen, causing significant morbidity and mortality worldwide. Antibiotic usage, a major risk factor for Clostridioides difficile infection (CDI), disrupts the gut microbiota, allowing C. difficile to proliferate and cause infection, and can often lead to recurrent CDI (rCDI). Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as effective treatments for rCDI and aim to restore colonization resistance provided by a healthy gut microbiota. However, much is still unknown about the mechanisms mediating their success. Bile acids, extensively modified by gut microbes, affect C. difficile's germination, growth, and toxin production while also shaping the gut microbiota and influencing host immune responses. Additionally, microbial interactions, such as nutrient competition and cross-feeding, contribute to colonization resistance against C. difficile and may contribute to the success of microbiota-focused therapeutics. Bile acids as well as other microbial mediated interactions could have implications for other diseases being treated with microbiota-focused therapeutics. This review focuses on the intricate interplay between bile acid modifications, microbial ecology, and host responses with a focus on C. difficile, hoping to shed light on how to move forward with the development of new microbiota mediated therapeutic strategies to combat rCDI and other intestinal diseases.}, } @article {pmid39222063, year = {2024}, author = {Shiroma, H and Darzi, Y and Terajima, E and Nakagawa, Z and Tsuchikura, H and Tsukuda, N and Moriya, Y and Okuda, S and Goto, S and Yamada, T}, title = {Enteropathway: the metabolic pathway database for the human gut microbiota.}, journal = {Briefings in bioinformatics}, volume = {25}, number = {5}, pages = {}, pmid = {39222063}, issn = {1477-4054}, support = {JPMJCR19U3//JST AIP Acceleration Research/ ; JP16H06279//Japan Society for the Promotion of Science/ ; JP21ck0106546h0002//Japan Agency for Medical Research and Development/ ; 2020-A-7//National Cancer Center Research and Development Fund/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Metabolic Networks and Pathways ; *Databases, Factual ; Software ; Computational Biology/methods ; }, abstract = {The human gut microbiota produces diverse, extensive metabolites that have the potential to affect host physiology. Despite significant efforts to identify metabolic pathways for producing these microbial metabolites, a comprehensive metabolic pathway database for the human gut microbiota is still lacking. Here, we present Enteropathway, a metabolic pathway database that integrates 3269 compounds, 3677 reactions, and 876 modules that were obtained from 1012 manually curated scientific literature. Notably, 698 modules of these modules are new entries and cannot be found in any other databases. The database is accessible from a web application (https://enteropathway.org) that offers a metabolic diagram for graphical visualization of metabolic pathways, a customization interface, and an enrichment analysis feature for highlighting enriched modules on the metabolic diagram. Overall, Enteropathway is a comprehensive reference database that can complement widely used databases, and a tool for visual and statistical analysis in human gut microbiota studies and was designed to help researchers pinpoint new insights into the complex interplay between microbiota and host metabolism.}, } @article {pmid39218555, year = {2024}, author = {Zhang, M and Cui, Y and Liu, P and Mo, R and Wang, H and Li, Y and Wu, Y}, title = {Oat β-(1 → 3, 1 → 4)-d-glucan alleviates food allergy-induced colonic injury in mice by increasing Lachnospiraceae abundance and butyrate production.}, journal = {Carbohydrate polymers}, volume = {344}, number = {}, pages = {122535}, doi = {10.1016/j.carbpol.2024.122535}, pmid = {39218555}, issn = {1879-1344}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Colon/pathology/drug effects/metabolism ; *Butyrates/metabolism ; *Food Hypersensitivity ; *Avena/chemistry ; Clostridiales ; beta-Glucans/pharmacology/chemistry ; Mice, Inbred BALB C ; Male ; Glucans/pharmacology/chemistry ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Oat β-(1 → 3, 1 → 4)-d-glucan (OBG), a linear polysaccharide primarily found in oat bran, has been demonstrated to possess immunomodulatory properties and regulate gut microbiota. This study aimed to investigate the impact of low molecular weight (Mw) OBG (155.2 kDa) on colonic injury and allergic symptoms induced by food allergy (FA), and to explore its potential mechanism. In Experiment 1, results indicated that oral OBG improved colonic inflammation and epithelial barrier, and significantly relieved allergy symptoms. Importantly, the OBG supplement altered the gut microbiota composition, particularly increasing the abundance of Lachnospiraceae and its genera, and promoted the production of short-chain fatty acids, especially butyrate. However, in Experiment 2, the gut microbial depletion eliminated these protective effects of OBG on the colon in allergic mice. Further, in Experiment 3, fecal microbiota transplantation and sterile fecal filtrate transfer directly validated the role of OBG-mediated gut microbiota and its metabolites in relieving FA and its induced colonic injury. Our findings suggest that low Mw OBG can alleviate FA-induced colonic damage by increasing Lachnospiraceae abundance and butyrate production, and provide novel insights into the health benefits and mechanisms of dietary polysaccharide intervention for FA.}, } @article {pmid39217880, year = {2024}, author = {Jin, Z and Liu, Z and Pan, J and Wang, S and Cui, M and He, C and Lin, M and Liu, X and Yu, X and Gong, F}, title = {FGF20 modulates gut microbiota to mitigate dextran sodium sulfate-induced ulcerative colitis in mouse models.}, journal = {International immunopharmacology}, volume = {142}, number = {Pt A}, pages = {113044}, doi = {10.1016/j.intimp.2024.113044}, pmid = {39217880}, issn = {1878-1705}, abstract = {Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), presents a significant clinical challenge due to the lack of optimal therapeutic strategies. Emerging evidence suggests that fibroblast growth factor 20 (FGF20) may play a crucial role in mitigating UC symptoms, though the mechanistic underpinnings remain elusive. In this study, a mouse model of UC was established using dextran sodium sulfate (DSS) to investigate the potential role of FGF20. Our findings revealed a marked reduction in FGF20 expression in the serum and colonic tissues of DSS-treated mice. Furthermore, FGF20 knockout did not exacerbate colonic damage in these mice. Conversely, overexpression of FGF20 via adeno-associated virus (AAV) significantly alleviated UC-associated symptoms. This alleviation was evidenced by attenuated intestinal shortening, mitigated weight loss, increased colonic goblet cell density and crypt formation, reduced inflammation severity and inflammatory cell infiltration, and enhanced expression of tight junction and mucin proteins. Moreover, FGF20 significantly ameliorated the dysbiosis of gut microbiota in DSS-treated mice by increasing the abundance of beneficial bacteria and decreasing the abundance of harmful bacteria. The beneficial effects of FGF20 were notably attenuated following gut microbiota depletion with an antibiotic regimen. Fecal microbiota transplantation experiments further supported the critical role of gut microbiota in mediating the effects of FGF20 on DSS-treated mice. In conclusion, these findings highlight the potential involvement of gut microbiota in the therapeutic effects of FGF20 in UC.}, } @article {pmid39217582, year = {2024}, author = {Yang, Q and Wang, Z and Liu, M and Gan, L}, title = {Causal Relationship Between Gut Microbiota and Leukemia: Future Perspectives.}, journal = {Oncology and therapy}, volume = {}, number = {}, pages = {}, pmid = {39217582}, issn = {2366-1089}, abstract = {The gut microbiota plays a crucial role in maintaining homeostasis in the human gastrointestinal tract. Numerous studies have shown a strong association between the gut microbiota and the emergence and progression of various diseases. Leukemia is one of the most common hematologic malignancies. Although standardized protocols and expert consensus have been developed for routine diagnosis and treatment, limitations remain due to individual differences. Nevertheless, a large number of studies have established a link between the gut microbiota and leukemia, with disturbances in the gut microbiota directly or indirectly affecting the development of leukemia. However, the causal relationship between the two remains unclear, and studying and exploring the causal relationship may open up entirely new avenues and protocols for use in the prevention and/or treatment of leukemia, offering new insights into diagnosis and treatment. In this review, the intricate relationship between the gut microbiota and leukemia is explored in depth, including causal associations, metabolite effects, therapeutic applications, and complications. Based on the characteristics of the gut microbiota, the future applications and prospects of gut microbiota are discussed to provide useful information for clinical treatment of leukemia.}, } @article {pmid39217051, year = {2024}, author = {Akhmedov, M and Espinoza, JL}, title = {Addressing the surge of infections by multidrug-resistant Enterobacterales in hematopoietic cell transplantation.}, journal = {Blood reviews}, volume = {}, number = {}, pages = {101229}, doi = {10.1016/j.blre.2024.101229}, pmid = {39217051}, issn = {1532-1681}, abstract = {Patients undergoing hematopoietic cell transplantation (HCT) have an increased risk of developing severe infections. In recent years, bloodstream infections caused by Gram-negative bacteria have been increasingly reported among HCT recipients, and many of these infections are caused by bacterial strains of the Enterobacterales order. Among these pathogens, particularly concerning are the multidrug-resistant Enterobacterales (MDRE), such as Extended Spectrum β-lactamase-producing Enterobacterales and Carbapenem-resistant Enterobacterales, since infections caused by these pathogens are difficult to treat due to the limited antimicrobial options and are associated with worse transplant outcomes. We summarized the evidence from studies published in PubMed and Scopus on the burden of MDRE infections in HCT recipients, and strategies for the management and prevention of these infections, including strict adherence to recommended infection control practices and multidisciplinary antimicrobial stewardship, the use of probiotics, and fecal microbiota transplantation, are also discussed.}, } @article {pmid39214188, year = {2024}, author = {Hensen, ADO and Vehreschild, MJGT and Gerding, DN and Krut, O and Chen, W and Young, VB and Tzipori, S and Solbach, P and Gibani, MM and Chiu, C and de Keersmaecker, SCJ and Dasyam, D and Morel, S and Devaster, JM and Corti, N and Kuijper, EJ and Roestenberg, M and Smits, WK}, title = {How to develop a Controlled Human Infection Model for Clostridioides difficile.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2024.08.025}, pmid = {39214188}, issn = {1469-0691}, abstract = {BACKGROUND: Clostridioides difficile (C. difficile) remains the leading cause of healthcare-associated diarrhoea, posing treatment challenges due to antibiotic resistance and high relapse rates. Fecal microbiota transplantation (FMT) is a novel treatment strategy to prevent relapses of C. difficile infection (CDI), however the exact components conferring colonisation resistance are unknown, hampering its translation to a medicinal product. Development of novel products independent of antibiotics, which increase colonisation resistance or induce protective immune mechanisms are urgently needed.

OBJECTIVES: To establish a framework for a Controlled Human Infection Model (CHIM) for C. difficile, in which healthy volunteers are exposed to toxigenic C. difficile spores, offering the possibility to test novel approaches and identify microbiota and immunological targets. Whereas experimental exposure to non-toxigenic C. difficile (NTCD) has been done before, a toxigenic C. difficile CHIM faces ethical, scientific, logistical and biosafety challenges.

SOURCES: Specific challenges in developing a C. difficile CHIM were discussed by a group of international experts during a workshop organized by Inno4Vac, an IHI-funded consortium.

CONTENT: The experts agreed that the main challenges are: developing a clinically relevant CHIM which induces mild to moderate CDI symptoms but no severe CDI, determining optimal C. difficile inoculum dose and understanding the timing and duration of antibiotic pre-treatment in inducing susceptibility to CDI in healthy volunteers.

IMPLICATIONS: Should these challenges be tackled, a C. difficile CHIM not only provides a way forward for the testing of novel products but also offers a framework for better understanding of the pathophysiology, pathogenesis and immunology of C. difficile colonisation and infection.}, } @article {pmid39212186, year = {2024}, author = {Junker Mentzel, CM and Hui, Y and Hammerich, TMS and Klug-Dambmann, M and Liu, Y and Zachariassen, LF and Hansen, LH and Aslampaloglou, A and Kiersgaard, M and Nielsen, DS and Hansen, AK and Krych, L}, title = {Low-gainer diet-induced obese microbiota transplanted mice exhibit increased fighting.}, journal = {Clinical and translational science}, volume = {17}, number = {9}, pages = {e13906}, pmid = {39212186}, issn = {1752-8062}, support = {//LIFEPHARM/ ; //Novo Nordisk A/S/ ; //Center for Applied Laboratory Animal Research/ ; }, mesh = {Animals ; Male ; *Obesity/microbiology/etiology ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Mice, Inbred C57BL ; *Diet, High-Fat/adverse effects ; *Weight Gain ; Mice ; Disease Models, Animal ; Leptin/blood/metabolism ; Feces/microbiology ; }, abstract = {Weight gain variation is a great challenge in diet-induced obesity studies since low-gainer animals are of limited experimental value. The inbred C57BL/6 (B6) mice are frequently used models due to their genetic homogeneity and susceptibility to diet-induced obesity (DIO). The aim of this study is to investigate if the gut microbiota (GM) influences the fraction of low weight gainers in DIO studies. A total of 100 male B6 mice (donor population) were fed a high-fat diet for 14 weeks and divided into the study groups high gainer (HG) and low gainer (LG) based on their weight gain. Subsequently, fecal matter transplantation (FMT) was done on germ-free B6 mice with GM from HG and LG donors (FMT population). LG (13.35 ± 2.5 g) and HG (25.52 ± 2.0 g) animals were identified by the weight gain from week 1 to week 12. Interestingly, the start weight of the LG (20.36 ± 1.4 g) and HG (21.59 ± 0.7 g) groups differed significantly. Transplanting LG or HG fecal matter to germ-free mice resulted in significant differences in weight gain between HG and LG, as well as differences in serum leptin levels and epididymal fat pad weight. A clear LG-specific GM composition could not be distinguished by 16S rRNA gene amplicon sequencing. Surprisingly, significantly more fighting was recorded in LG groups of both donor populations and when transplanted to germ-free mice. The HG and LG phenotypes could be transferred to germ-free mice. The increased fighting in the LG group in both studies suggests not only that the tendency to fight can be transferred by FMT in these mice, but also that fighting should be prevented in DIO studies to minimize the number of LG animals.}, } @article {pmid39214085, year = {2024}, author = {Hayase, E and Hayase, T and Mukherjee, A and Stinson, SC and Jamal, MA and Ortega, MR and Sanchez, CA and Ahmed, SS and Karmouch, JL and Chang, CC and Flores, II and McDaniel, LK and Brown, AN and El-Himri, RK and Chapa, VA and Tan, L and Tran, BQ and Xiao, Y and Fan, C and Pham, D and Halsey, TM and Jin, Y and Tsai, WB and Prasad, R and Glover, IK and Enkhbayar, A and Mohammed, A and Schmiester, M and King, KY and Britton, RA and Reddy, P and Wong, MC and Ajami, NJ and Wargo, JA and Shelburne, S and Okhuysen, PC and Liu, C and Fowler, SW and Conner, ME and Katsamakis, Z and Smith, N and Burgos da Silva, M and Ponce, DM and Peled, JU and van den Brink, MRM and Peterson, CB and Rondon, G and Molldrem, JJ and Champlin, RE and Shpall, EJ and Lorenzi, PL and Mehta, RS and Martens, EC and Alousi, AM and Jenq, RR}, title = {Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2024.08.004}, pmid = {39214085}, issn = {1934-6069}, abstract = {Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.}, } @article {pmid39213702, year = {2024}, author = {Su, Y and Fan, X and Cai, X and Ning, J and Shen, M}, title = {Effects of fecal microbiota transplantation combined with selenium on intestinal microbiota in mice with colorectal cancer.}, journal = {Biochemical and biophysical research communications}, volume = {733}, number = {}, pages = {150580}, doi = {10.1016/j.bbrc.2024.150580}, pmid = {39213702}, issn = {1090-2104}, abstract = {Colorectal cancer (CRC) is the third most common cancer in the world. With the development of high-throughput gene sequencing technology, homeostasis imbalance of the intestinal microbiota has been proven to play a key role in the pathogenesis of CRC. Furthermore, fecal bacteria transplantation (FMT) has been shown to alter the intestinal microecology, and is potentially an effective treatment for CRC. Sodium selenite plays an important role in anticancer adjuvant therapy due to its high pro-oxidation characteristics. In this study, a murine CRC tumor model was induced by AOM/DSS, and CRC mice were treated by FMT, sodium selenite, and FMT combined with sodium selenite. The results showed that FMT, sodium selenite, and FMT combined with sodium selenite inhibited the occurrence of CRC in mice, increased the abundance of beneficial intestinal bacteria, produced different microorganisms, and changed the metabolic pathways of the intestinal microbiota. In summary, FMT, sodium selenite, and FMT combined with sodium selenite can inhibit the occurrence of CRC by increasing the abundance of beneficial bacteria and regulating phenotypes and metabolic pathways. Notably, the effect of FMT combined with sodium selenite in reducing the number of tumors, protecting intestinal tissues, and restoring the diversity and richness of the intestinal microbiota is superior to that of FMT alone or sodium selenite alone. The results of this study provide new ideas for the application of FMT and selenium in the treatment of CRC.}, } @article {pmid39212377, year = {2024}, author = {Pan, L and Yin, N and Duan, M and Mei, Q and Zeng, Y}, title = {The role of gut microbiome and its metabolites in pancreatitis.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0066524}, doi = {10.1128/msystems.00665-24}, pmid = {39212377}, issn = {2379-5077}, abstract = {Gut microbiome plays a vital role in the intestinal ecosystem and has close association with metabolites. Due to the development of metabolomics and microbiomics, recent studies have observed that alteration of either the gut microbiome or metabolites may have effects on the progression of pancreatitis. Several new treatments based on the gut microbiome or metabolites have been studied extensively in recent years. Gut microbes, such as Bifidobacterium, Akkermansia, and Lactobacillus, and metabolites, such as short-chain fatty acids, bile acids, vitamin, hydrogen sulfide, and alcohol, have different effects on pancreatitis. Some preliminary studies about new intervention measures were based on the gut microbiome and metabolites such as diet, prebiotic, herbal medicine, and fecal microbiota transplantation. This review aims to summarize the recent advances about the gut microbiome, metabolites, and pancreatitis in order to determine the potential beneficial role of the gut microbiome and metabolites in pancreatitis.}, } @article {pmid39212113, year = {2024}, author = {Liu, Z and Wang, M and Hu, Y and Li, J and Gong, W and Guo, X and Song, S and Zhu, B}, title = {Ulva lactuca polysaccharides combined with fecal microbiota transplantation ameliorated dextran sodium sulfate-induced colitis in C57BL/6J mice.}, journal = {Journal of the science of food and agriculture}, volume = {}, number = {}, pages = {}, doi = {10.1002/jsfa.13839}, pmid = {39212113}, issn = {1097-0010}, support = {2023YFD2100200//National Key Research and Development Program of China/ ; 32302148//National Natural Science Foundation of China/ ; ZDSYS20220117155800001//Shenzhen Science and Technology Program/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) of healthy donors improves ulcerative colitis (UC) patients by restoring the balance of the gut microbiota. However, donors vary in microbial diversity and composition, often resulting in weak or even ineffective FMT. Improving the efficacy of FMT through combination treatment has become a promising strategy. Ulva lactuca polysaccharides (ULP) have been found to benefit host health by regulating gut microbiota. The effect of the combination of ULP and FMT in ameliorating UC has not yet been evaluated.

RESULTS: The present study found that supplementation with ULP combined with FMT showed better effects in ameliorating UC than supplementation with FMT alone. Results suggested that FMT or ULP combined with FMT alleviated the symptoms of UC in mice, as evidenced by prevention of body weight loss, improvement of disease activity index and protection of the intestinal mucus. Notably, ULP in combination with FMT was more effective than FMT in reducing levels of cytokines and related inflammatory enzymes. In addition, ULP combined with FMT effectively restored the dysbiosis induced by dextran sulfate sodium (DSS) and further enriched probiotics (such as Bifidobacterium). The production of short-chain fatty acids, especially acetic acid, was also significantly enriched by ULP combined with FMT.

CONCLUSION: Supplementation of ULP combined with FMT could significantly ameliorate DSS-induced colitis in mice by inhibiting inflammation and restoring dysbiosis of gut microbiota. These results suggested that ULP combined with FMT has potential application in ameliorating UC. © 2024 Society of Chemical Industry.}, } @article {pmid39211181, year = {2024}, author = {Kennedy, MS and Freiburger, A and Cooper, M and Beilsmith, K and St George, ML and Kalski, M and Cham, C and Guzzetta, A and Ng, SC and Chan, FK and Rubin, D and Henry, CS and Bergelson, J and Chang, EB}, title = {Diet outperforms microbial transplant to drive microbiome recovery post-antibiotics.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.08.01.606245}, pmid = {39211181}, issn = {2692-8205}, abstract = {High-fat, low-fiber Western-style diets (WD) induce microbiome dysbiosis characterized by reduced taxonomic diversity and metabolic breadth, which in turn increases risk for a wide array of metabolic, immune and systemic pathologies. Recent work has established that WD can impair microbiome resilience to acute perturbations like antibiotic treatment, although we know little about the mechanism of impairment and the specific host consequences of prolonged post-antibiotic dysbiosis. Here, we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) and WD, and find that only mice on RC undergo a rapid successional process of recovery. Metabolic modeling indicates that RC diet promotes the development of syntrophic cross-feeding interactions, while on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither. Furthermore, prolonged post-antibiotic dysbiosis in mice on WD renders them susceptible to infection by the intestinal pathogen Salmonella enterica serovar Typhimurium. Our data challenge widespread enthusiasm for fecal microbiota transplant (FMT) as a strategy to address dysbiosis and demonstrate that specific dietary interventions are, at minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural, and less invasive alternative to FMT.}, } @article {pmid39210613, year = {2024}, author = {Xu, Y and Wu, X and Li, Y and Liu, X and Fang, L and Jiang, Z}, title = {Probiotics and the Role of Dietary Substrates in Maintaining the Gut Health: Use of Live Microbes and Their Products for Anticancer Effects against Colorectal Cancer.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {9}, pages = {1-14}, doi = {10.4014/jmb.2403.03056}, pmid = {39210613}, issn = {1738-8872}, abstract = {The gut microbiome is an important and the largest endocrine organ linked to the microbes of the GI tract. The bacterial, viral and fungal communities are key regulators of the health and disease status in a host at hormonal, neurological, immunological, and metabolic levels. The useful microbes can compete with microbes exhibiting pathogenic behavior by maintaining resistance against their colonization, thereby maintaining eubiosis. As diagnostic tools, metagenomic, proteomic and genomic approaches can determine various microbial markers in clinic for early diagnosis of colorectal cancer (CRC). Probiotics are live non-pathogenic microorganisms such as lactic acid bacteria, Bifidobacteria, Firmicutes and Saccharomyces that can help maintain eubiosis when administered in appropriate amounts. In addition, the type of dietary intake contributes substantially to the composition of gut microbiome. The use of probiotics has been found to exert antitumor effects at preclinical levels and promote the antitumor effects of immunotherapeutic drugs at clinical levels. Also, modifying the composition of gut microbiota by Fecal Microbiota Transplantation (FMT), and using live lactic acid producing bacteria such as Lactobacillus, Bifidobacteria and their metabolites (termed postbiotics) can contribute to immunomodulation of the tumor microenvironment. This can lead to tumor-preventive effects at early stages and antitumor effects after diagnosis of CRC. To conclude, probiotics are presumably found to be safe to use in humans and are to be studied further to promote their appliance at clinical levels for management of CRC.}, } @article {pmid39206530, year = {2024}, author = {Gupta, CL and Jaganathasamy, N and Madkaikar, M}, title = {Microbiome in sickle cell disease: Pathophysiology and therapeutic insights.}, journal = {British journal of haematology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bjh.19736}, pmid = {39206530}, issn = {1365-2141}, abstract = {Sickle cell disease (SCD) is a complex genetic blood disorder characterized by abnormal haemoglobin, resulting in sickle-shaped red blood cells. While extensive research has concentrated on the genetic and physiological aspects of SCD, recent studies suggest a potential role of the human microbiome in SCD pathophysiology, adding new dimensions to its understanding. This review synthesizes current knowledge on the microbiome's involvement in SCD, focusing on alterations in the gut microbiome composition and diversity compared to healthy individuals, and their implications for disease pathogenesis. We explore how microbiome changes may contribute to vaso-occlusive crises and other complications, along with the possible associations of specific microbial taxa or markers with disease crises and clinical outcomes. Additionally, we discuss the potential of microbiome-targeted interventions, including probiotics, dietary modifications, and faecal microbiota transplantation, in managing SCD complications and improving patient outcomes. Understanding the intricate relationship between the microbiome and SCD could lead to innovative therapeutic strategies and personalized interventions for better managing the disease. This review underscores the importance of further microbiome research and its integration into holistic SCD care.}, } @article {pmid39205822, year = {2024}, author = {Hosseini-Asl, SMK and Mehrabani, G and Masoumi, SJ}, title = {Key Focus Areas in Pouchitis Therapeutic Status: A Narrative Review.}, journal = {Iranian journal of medical sciences}, volume = {49}, number = {8}, pages = {472-486}, pmid = {39205822}, issn = {1735-3688}, mesh = {Humans ; *Pouchitis/therapy/etiology/drug therapy ; Fecal Microbiota Transplantation/methods ; Probiotics/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Pouchitis, as the most common complication after ileal pouch-anal anastomosis (IPAA), has an incidence from 7% to 46%. Pouchitis treatment still represents one of the biggest gaps of knowledge in the treatment of diseases. This review has focused on achievements and challenges in the treatment of pouchitis. A combined assessment of symptoms, endoscopic findings, histologic results, quick biomarkers, and fecal calprotectin test were determined to be valuable diagnostic criteria. Conventional therapy was described as a modification of bacterial flora, mainly with antibiotics and more recently with probiotics such as bifidobacteria, lactobacilli, and streptococci. Other therapeutic approaches such as anti-tumor necrosis factor, infliximab, adalimumab, vedolizumab, ustekinumab, tacrolimus, tofacitinib, thiopurines, corticosteroids, prolyl hydroxylase-containing enzymes, povidone-iodine, dextrose spray, fecal microbiota transplantation, herbal medicines, and leukocyte apheresis have been discussed. Changes in dietary components, and administration of complementary and alternative medicine, probiotics, and fecal transplantation in addition to conventional therapies were also shown to affect the outcome of disease. Due to the potential significant impairment in quality of life caused by pouchitis, it is essential to address the gaps in knowledge for both patients and physicians in its treatment. Therefore, well-designed and adequately powered studies should assess the optimal treatment for pouchitis.}, } @article {pmid39205654, year = {2024}, author = {Wu, L and Zhou, J and Zhou, A and Lei, Y and Tang, L and Hu, S and Wang, S and Xiao, X and Chen, Q and Tu, D and Lu, C and Lai, Y and Li, Y and Zhang, X and Tang, B and Yang, S}, title = {Lactobacillus acidophilus ameliorates cholestatic liver injury through inhibiting bile acid synthesis and promoting bile acid excretion.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2390176}, doi = {10.1080/19490976.2024.2390176}, pmid = {39205654}, issn = {1949-0984}, mesh = {*Lactobacillus acidophilus ; *Bile Acids and Salts/metabolism ; Animals ; *Gastrointestinal Microbiome ; *Cholestasis/metabolism/microbiology ; Mice ; Humans ; Male ; *Probiotics/pharmacology/administration & dosage ; *Liver/metabolism ; *Mice, Inbred C57BL ; Feces/microbiology ; Cholesterol 7-alpha-Hydroxylase/metabolism/genetics ; Female ; Fibroblast Growth Factors/metabolism/genetics ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology/therapy ; RNA, Ribosomal, 16S/genetics ; Middle Aged ; Adult ; Disease Models, Animal ; Ileum/microbiology/metabolism ; }, abstract = {Gut microbiota dysbiosis is involved in cholestatic liver diseases. However, the mechanisms remain to be elucidated. The purpose of this study was to examine the effects and mechanisms of Lactobacillus acidophilus (L. acidophilus) on cholestatic liver injury in both animals and humans. Bile duct ligation (BDL) was performed to mimic cholestatic liver injury in mice and serum liver function was tested. Gut microbiota were analyzed by 16S rRNA sequencing. Fecal bacteria transplantation (FMT) was used to evaluate the role of gut microbiota in cholestasis. Bile acids (BAs) profiles were analyzed by targeted metabolomics. Effects of L. acidophilus in cholestatic patients were evaluated by a randomized controlled clinical trial (NO: ChiCTR2200063330). BDL induced different severity of liver injury, which was associated with gut microbiota. 16S rRNA sequencing of feces confirmed the gut flora differences between groups, of which L. acidophilus was the most distinguished genus. Administration of L. acidophilus after BDL significantly attenuated hepatic injury in mice, decreased liver total BAs and increased fecal total BAs. Furthermore, after L. acidophilus treatment, inhibition of hepatic Cholesterol 7α-hydroxylase (CYP7α1), restored ileum Fibroblast growth factor 15 (FGF15) and Small heterodimer partner (SHP) accounted for BAs synthesis decrease, whereas enhanced BAs excretion was attributed to the increase of unconjugated BAs by enriched bile salt hydrolase (BSH) enzymes in feces. Similarly, in cholestasis patients, supplementation of L. acidophilus promoted the recovery of liver function and negatively correlated with liver function indicators, possibly in relationship with the changes in BAs profiles and gut microbiota composition. L. acidophilus treatment ameliorates cholestatic liver injury through inhibited hepatic BAs synthesis and enhances fecal BAs excretion.}, } @article {pmid39204246, year = {2024}, author = {Spigaglia, P}, title = {Clostridioides difficile and Gut Microbiota: From Colonization to Infection and Treatment.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, pmid = {39204246}, issn = {2076-0817}, abstract = {Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea (AAD) in hospitals in the developed world. Both infected patients and asymptomatic colonized individuals represent important transmission sources of C. difficile. C. difficile infection (CDI) shows a large range of symptoms, from mild diarrhea to severe manifestations such as pseudomembranous colitis. Epidemiological changes in CDIs have been observed in the last two decades, with the emergence of highly virulent types and more numerous and severe CDI cases in the community. C. difficile interacts with the gut microbiota throughout its entire life cycle, and the C. difficile's role as colonizer or invader largely depends on alterations in the gut microbiota, which C. difficile itself can promote and maintain. The restoration of the gut microbiota to a healthy state is considered potentially effective for the prevention and treatment of CDI. Besides a fecal microbiota transplantation (FMT), many other approaches to re-establishing intestinal eubiosis are currently under investigation. This review aims to explore current data on C. difficile and gut microbiota changes in colonized individuals and infected patients with a consideration of the recent emergence of highly virulent C. difficile types, with an overview of the microbial interventions used to restore the human gut microbiota.}, } @article {pmid39203805, year = {2024}, author = {Deleu, S and Jacobs, I and Vazquez Castellanos, JF and Verstockt, S and Trindade de Carvalho, B and Subotić, A and Verstockt, B and Arnauts, K and Deprez, L and Vissers, E and Lenfant, M and Vandermeulen, G and De Hertogh, G and Verbeke, K and Matteoli, G and Huys, GRB and Thevelein, JM and Raes, J and Vermeire, S}, title = {Effect of Mutant and Engineered High-Acetate-Producing Saccharomyces cerevisiae var. boulardii Strains in Dextran Sodium Sulphate-Induced Colitis.}, journal = {Nutrients}, volume = {16}, number = {16}, pages = {}, doi = {10.3390/nu16162668}, pmid = {39203805}, issn = {2072-6643}, support = {VR 2021 1712 DOC. 1492/4//Grand Challenges Program of VIB/ ; }, mesh = {Animals ; *Dextran Sulfate ; Female ; *Acetates ; Mice ; *Saccharomyces cerevisiae/genetics ; *Colitis/chemically induced/therapy ; *Probiotics ; Disease Models, Animal ; Colon/metabolism/microbiology/pathology ; Saccharomyces boulardii ; Colitis, Ulcerative/chemically induced/therapy/microbiology ; Mutation ; Gastrointestinal Microbiome ; Feces/microbiology ; Mice, Inbred C57BL ; }, abstract = {Acetate-producing Saccharomyces cerevisiae var. boulardii strains could exert improved effects on ulcerative colitis, which here, was preclinically evaluated in an acute dextran sodium sulphate induced model of colitis. Nine-week-old female mice were divided into 12 groups, receiving either drinking water or 2.75% dextran sodium sulphate for 7 days, combined with a daily gavage of various treatments with different levels of acetate accumulation: sham control (phosphate buffered saline, no acetate), non-probiotic control (Baker's yeast, no acetate), probiotic control (Enterol[®], transient acetate), and additionally several Saccharomyces cerevisiae var. boulardii strains with respectively no, high, and extra-high acetate accumulation. Disease activity was monitored daily, and feces samples were collected at different timepoints. On day 14, the mice were sacrificed, upon which blood and colonic tissue were collected for analysis. Disease activity in inflamed mice was lower when treated with the high-acetate-producing strain compared to sham and non-probiotic controls. The non-acetate-producing strain showed higher disease activity compared to the acetate-producing strains. Accordingly, higher histologic inflammation was observed in non- or transient-acetate-producing strains compared to the sham control, whereas this increase was not observed for high- and extra-high-acetate-producing strains upon induction of inflammation. These anti-inflammatory findings were confirmed by transcriptomic analysis of differentially expressed genes. Moreover, only the strain with the highest acetate production was superior in maintaining a stable gut microbial alpha-diversity upon inflammation. These findings support new possibilities for acetate-mediated management of inflammation in inflammatory bowel disease by administrating high-acetate-producing Saccharomyces cerevisae var. boulardii strains.}, } @article {pmid39203583, year = {2024}, author = {Yamada, CH and Ortis, GB and Buso, GM and Martins, TC and Zequinao, T and Telles, JP and Wollmann, LC and Montenegro, CO and Dantas, LR and Cruz, JW and Tuon, FF}, title = {Validation of Lyophilized Human Fecal Microbiota for the Treatment of Clostridioides difficile Infection: A Pilot Study with Pharmacoeconomic Analysis of a Middle-Income Country-Promicrobioma Project.}, journal = {Microorganisms}, volume = {12}, number = {8}, pages = {}, doi = {10.3390/microorganisms12081741}, pmid = {39203583}, issn = {2076-2607}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) represents a prevalent and potentially severe health concern linked to the usage of broad-spectrum antibiotics. The aim of this study was to evaluate a new lyophilized product based on human fecal microbiota for transplant, including cost-benefit analysis in the treatment of recurrent or refractory CDI.

METHODS: The product for fecal microbiota transplant was obtained from two donors. Microbiological, viability, and genomic analysis were evaluated. After validation, a clinical pilot study including recurrent or refractory CDI with 24 patients was performed. Clinical response and 4-week recurrence were the outcome. Cost-benefit analysis compared the fecal microbiota transplant with conventional retreatment with vancomycin or metronidazole.

RESULTS: The microbiota for transplant presented significant bacterial viability, with and adequate balance of Firmicutes and Bacteroidetes. The clinical response with the microbiota transplant was 92%. In financial terms, estimated expenditure for CDI solely related to recurrence, based on stochastic modeling, totals USD 222.8 million per year in Brazil.

CONCLUSIONS: The lyophilized human fecal microbiota for transplant is safe and can be an important step for a new product with low cost, even with genomic sequencing. Fecal microbiota transplantation emerges as a more cost-effective alternative compared to antimicrobials in the retreatment of CDI.}, } @article {pmid39200335, year = {2024}, author = {Zikou, E and Koliaki, C and Makrilakis, K}, title = {The Role of Fecal Microbiota Transplantation (FMT) in the Management of Metabolic Diseases in Humans: A Narrative Review.}, journal = {Biomedicines}, volume = {12}, number = {8}, pages = {}, doi = {10.3390/biomedicines12081871}, pmid = {39200335}, issn = {2227-9059}, abstract = {The gut microbiota represents a complex ecosystem of trillions of microorganisms residing in the human gastrointestinal tract, which is known to interact with the host physiology and regulate multiple functions. Alterations in gut microbial composition, diversity, and function are referred to as dysbiosis. Dysbiosis has been associated with a variety of chronic diseases, including Clostridioides difficile infections, but also cardiometabolic diseases, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). The implication of gut microbiota dysbiosis in the pathogenesis of both obesity and T2DM has paved the way to implementing novel therapeutic approaches for metabolic diseases through gut microbial reconfiguration. These interventions include probiotics, prebiotics, and synbiotics, while a more innovative approach has been fecal microbiota transplantation (FMT). FMT is a procedure that delivers healthy human donor stool to another individual through the gastrointestinal tract, aiming to restore gut microbiota balance. Several studies have investigated this approach as a potential tool to mitigate the adverse metabolic effects of gut microbiota aberrations associated with obesity and T2DM. The aim of the present review was to critically summarize the existing evidence regarding the clinical applications of FMT in the management of obesity and T2DM and provide an update on the potential of this method to remodel the entire host microbiota, leading thus to weight loss and sustained metabolic benefits. Safety issues, long-term efficacy, limitations, and pitfalls associated with FMT studies are further discussed, emphasizing the need for further research and standardization in certain methodological aspects in order to optimize metabolic outcomes.}, } @article {pmid39200203, year = {2024}, author = {Kerstens, R and Joyce, P}, title = {The Gut Microbiome as a Catalyst and Emerging Therapeutic Target for Parkinson's Disease: A Comprehensive Update.}, journal = {Biomedicines}, volume = {12}, number = {8}, pages = {}, doi = {10.3390/biomedicines12081738}, pmid = {39200203}, issn = {2227-9059}, support = {2022-CF-EMCR-004-25314//Hospital Research Foundation/ ; }, abstract = {Parkinson's Disease is the second most prevalent neurological disorder globally, and its cause is still largely unknown. Likewise, there is no cure, and existing treatments do little more than subdue symptoms before becoming ineffective. It is increasingly important to understand the factors contributing to Parkinson's Disease aetiology so that new and more effective pharmacotherapies can be established. In recent years, there has been an emergence of research linking gut dysbiosis to Parkinson's Disease via the gut-brain axis. Advancements in microbial profiling have led to characterisation of a Parkinson's-specific microbial signature, where novel treatments that leverage and correct gut dysbiosis are beginning to emerge for the safe and effective treatment of Parkinson's Disease. Preliminary clinical studies investigating microbiome-targeted therapeutics for Parkinson's Disease have revealed promising outcomes, and as such, the aim of this review is to provide a timely and comprehensive update of the most recent advances in this field. Faecal microbiota transplantation has emerged as a novel and potential frontrunner for microbial-based therapies due to their efficacy in alleviating Parkinson's Disease symptomology through modulation of the gut-brain axis. However, more rigorous clinical investigation, along with technological advancements in diagnostic and in vitro testing tools, are critically required to facilitate the widespread clinical translation of microbiome-targeting Parkinson's Disease therapeutics.}, } @article {pmid39199404, year = {2024}, author = {Fu, Y and Cheng, HW}, title = {The Influence of Cecal Microbiota Transplantation on Chicken Injurious Behavior: Perspective in Human Neuropsychiatric Research.}, journal = {Biomolecules}, volume = {14}, number = {8}, pages = {}, doi = {10.3390/biom14081017}, pmid = {39199404}, issn = {2218-273X}, support = {2017-67015-26567//NIFA-AFRI, USDA/ ; }, mesh = {Animals ; *Chickens ; Humans ; *Gastrointestinal Microbiome ; Brain-Gut Axis ; Behavior, Animal ; Fecal Microbiota Transplantation ; Aggression ; Cecum/microbiology ; Mental Disorders/etiology/microbiology ; Stress, Psychological/microbiology ; Dysbiosis/microbiology ; }, abstract = {Numerous studies have evidenced that neuropsychiatric disorders (mental illness and emotional disturbances) with aggression (or violence) pose a significant challenge to public health and contribute to a substantial economic burden worldwide. Especially, social disorganization (or social inequality) associated with childhood adversity has long-lasting effects on mental health, increasing the risk of developing neuropsychiatric disorders. Intestinal bacteria, functionally as an endocrine organ and a second brain, release various immunomodulators and bioactive compounds directly or indirectly regulating a host's physiological and behavioral homeostasis. Under various social challenges, stress-induced dysbiosis increases gut permeability causes serial reactions: releasing neurotoxic compounds, leading to neuroinflammation and neuronal injury, and eventually neuropsychiatric disorders associated with aggressive, violent, or impulsive behavior in humans and various animals via a complex bidirectional communication of the microbiota-gut-brain (MGB) axis. The dysregulation of the MGB axis has also been recognized as one of the reasons for the prevalence of social stress-induced injurious behaviors (feather pecking, aggression, and cannibalistic pecking) in chickens. However, existing knowledge of preventing and treating these disorders in both humans and chickens is not well understood. In previous studies, we developed a non-mammal model in an abnormal behavioral investigation by rationalizing the effects of gut microbiota on injurious behaviors in chickens. Based on our earlier success, the perspective article outlines the possibility of reducing stress-induced injurious behaviors in chickens through modifying gut microbiota via cecal microbiota transplantation, with the potential for providing a biotherapeutic rationale for preventing injurious behaviors among individuals with mental disorders via restoring gut microbiota diversity and function.}, } @article {pmid39199231, year = {2024}, author = {Mostafavi Abdolmaleky, H and Zhou, JR}, title = {Gut Microbiota Dysbiosis, Oxidative Stress, Inflammation, and Epigenetic Alterations in Metabolic Diseases.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {8}, pages = {}, doi = {10.3390/antiox13080985}, pmid = {39199231}, issn = {2076-3921}, abstract = {Gut dysbiosis, resulting from an imbalance in the gut microbiome, can induce excessive production of reactive oxygen species (ROS), leading to inflammation, DNA damage, activation of the immune system, and epigenetic alterations of critical genes involved in the metabolic pathways. Gut dysbiosis-induced inflammation can also disrupt the gut barrier integrity and increase intestinal permeability, which allows gut-derived toxic products to enter the liver and systemic circulation, further triggering oxidative stress, inflammation, and epigenetic alterations associated with metabolic diseases. However, specific gut-derived metabolites, such as short-chain fatty acids (SCFAs), lactate, and vitamins, can modulate oxidative stress and the immune system through epigenetic mechanisms, thereby improving metabolic function. Gut microbiota and diet-induced metabolic diseases, such as obesity, insulin resistance, dyslipidemia, and hypertension, can transfer to the next generation, involving epigenetic mechanisms. In this review, we will introduce the key epigenetic alterations that, along with gut dysbiosis and ROS, are engaged in developing metabolic diseases. Finally, we will discuss potential therapeutic interventions such as dietary modifications, prebiotics, probiotics, postbiotics, and fecal microbiota transplantation, which may reduce oxidative stress and inflammation associated with metabolic syndrome by altering gut microbiota and epigenetic alterations. In summary, this review highlights the crucial role of gut microbiota dysbiosis, oxidative stress, and inflammation in the pathogenesis of metabolic diseases, with a particular focus on epigenetic alterations (including histone modifications, DNA methylomics, and RNA interference) and potential interventions that may prevent or improve metabolic diseases.}, } @article {pmid39197065, year = {2024}, author = {Xu, W and Liu, AX and Liu, KH and Zhang, S and Gong, ZH and Xiao, WJ}, title = {l-Theanine Alleviates Ulcerative Colitis by Regulating Colon Immunity via the Gut Microbiota in an MHC-II-Dependent Manner.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c04379}, pmid = {39197065}, issn = {1520-5118}, abstract = {Alterations to the gut microbiota are associated with ulcerative colitis (UC), whereas restoration of normobiosis can effectively alleviate UC. l-Theanine has been shown to reshape the gut microbiota and regulate gut immunity. To investigate the mechanisms by which l-theanine alleviates UC, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice. In this study, we used l-theanine and l-theanine fecal microbiota solution to treat UC mice to explore the mechanism by which l-theanine alleviates UC. By reducing inflammation in the colon, we demonstrated that l-theanine alleviates symptoms of UC. Meanwhile, l-theanine can improve the abundance of microbiota related to short-chain fatty acid, bile acid, and tryptophan production. Single-cell sequencing results indicated that l-theanine-mediated suppression of UC was associated with immune cell changes, especially regarding macrophages and T and B cells, and validated the immune cell responses to the gut microbiota. Further, flow cytometry results showed that the ability of dendritic cells, macrophages, and monocytes to present microbiota antigens to colonic T cells in an MHC-II-dependent manner was reduced after treating normal mouse fecal donors with l-theanine. These results demonstrate that l-theanine modulates colon adaptive and innate immunity by regulating the gut microbiota in an MHC-II-dependent manner, thereby alleviating UC.}, } @article {pmid39198444, year = {2024}, author = {Chang, D and Gupta, VK and Hur, B and Cobo-López, S and Cunningham, KY and Han, NS and Lee, I and Kronzer, VL and Teigen, LM and Karnatovskaia, LV and Longbrake, EE and Davis, JM and Nelson, H and Sung, J}, title = {Gut Microbiome Wellness Index 2 enhances health status prediction from gut microbiome taxonomic profiles.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {7447}, pmid = {39198444}, issn = {2041-1723}, support = {UL1TR002377//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, mesh = {*Gastrointestinal Microbiome/genetics ; Humans ; *Feces/microbiology ; *Health Status ; Metagenome ; Bacteria/classification/genetics/isolation & purification ; Female ; }, abstract = {Recent advancements in translational gut microbiome research have revealed its crucial role in shaping predictive healthcare applications. Herein, we introduce the Gut Microbiome Wellness Index 2 (GMWI2), an enhanced version of our original GMWI prototype, designed as a standardized disease-agnostic health status indicator based on gut microbiome taxonomic profiles. Our analysis involves pooling existing 8069 stool shotgun metagenomes from 54 published studies across a global demographic landscape (spanning 26 countries and six continents) to identify gut taxonomic signals linked to disease presence or absence. GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence (i.e., outside the "reject option"). This performance exceeds that of the original GMWI model and traditional species-level α-diversity indices, indicating a more robust gut microbiome signature for differentiating between healthy and non-healthy phenotypes across multiple diseases. When assessed through inter-study validation and external validation cohorts, GMWI2 maintains an average accuracy of nearly 75%. Furthermore, by reevaluating previously published datasets, GMWI2 offers new insights into the effects of diet, antibiotic exposure, and fecal microbiota transplantation on gut health. Available as an open-source command-line tool, GMWI2 represents a timely, pivotal resource for evaluating health using an individual's unique gut microbial composition.}, } @article {pmid39197710, year = {2024}, author = {Vashishth, S and Ambasta, RK and Kumar, P}, title = {Deciphering the Microbial Map and its implications in the therapeutics of Neurodegenerative Disorder.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {102466}, doi = {10.1016/j.arr.2024.102466}, pmid = {39197710}, issn = {1872-9649}, abstract = {Every facet of biological anthropology, including development, ageing, diseases, and even health maintenance, is influenced by gut microbiota's significant genetic and metabolic capabilities. With current advancements in sequencing technology and with new culture-independent approaches, researchers can surpass older correlative studies and develop mechanism-based studies on microbiome-host interactions. The microbiota-gut-brain axis (MGBA) regulates glial functioning, making it a possible target for the improvement of development and advancement of treatments for neurodegenerative diseases (NDDs). The gut-brain axis (GBA) is accountable for the reciprocal communication between the gastrointestinal and central nervous system, which plays an essential role in the regulation of physiological processes like controlling hunger, metabolism, and various gastrointestinal functions. Lately, studies have discovered the function of the gut microbiome for brain health-different microbiota through different pathways such as immunological, neurological and metabolic pathways. Additionally, we review the involvement of the neurotransmitters and the gut hormones related to gut microbiota. We also explore the MGBA in neurodegenerative disorders by focusing on metabolites. Further, targeting the blood-brain barrier (BBB), intestinal barrier, meninges, and peripheral immune system is investigated. Lastly, we discuss the therapeutics approach and evaluate the pre-clinical and clinical trial data regarding using prebiotics, probiotics, paraprobiotics, fecal microbiota transplantation, personalised medicine, and natural food bioactive in NDDs. A comprehensive study of the GBA will felicitate the creation of efficient therapeutic approaches for treating different NDDs.}, } @article {pmid39194379, year = {2024}, author = {Noguera-Fernández, N and Candela-González, J and Orenes-Piñero, E}, title = {Probiotics, Prebiotics, Fecal Microbiota Transplantation, and Dietary Patterns in Inflammatory Bowel Disease.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2400429}, doi = {10.1002/mnfr.202400429}, pmid = {39194379}, issn = {1613-4133}, support = {//Instituto Murciano de Investigaciones Biosanitarias Pascual Parrilla/ ; }, abstract = {SCOPE: Inflammatory bowel disease (IBD) is one of the most common chronic and debilitating functional bowel disorders affecting around 11% of the population across the world. IBD is associated with 3.6 million physician visits per year, being the most common reason visiting a gastroenterologist and the second most common reason to be absent from work, sharply increasing the health care costs.

METHODS AND RESULTS: Several treatments seem to be effective in IBD symptoms relief, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary patterns. Probiotics (living microorganisms that can be supplemented) can protect against pathogenic bacteria due to their antimicrobial qualities. Prebiotics (nondigestible food ingredients) promote the growth of beneficial microbial strains in the gut, giving a health benefit to the host. FMT is supposed to directly change the recipient's microbial composition when a transfer of gastrointestinal microbiota from a healthy donor is carried out. And finally, dietary patterns are in the spotlight, due to the presence of certain nutrients in the gastrointestinal tract affecting gastrointestinal motility, sensitivity, barrier function, and gut microbiota.

CONCLUSION: It is particularly important to know what treatment options are available and which are the most efficient in relieving IBD symptoms and improving IBD patient's quality of life.}, } @article {pmid39194187, year = {2024}, author = {Wang, L and Xu, Y and Li, L and Yang, B and Zhao, D and Ye, C and Lin, Z and Cui, J and Liu, Y and Zhu, W and Li, N and Tian, H and Chen, Q}, title = {The impact of small intestinal bacterial overgrowth on the efficacy of fecal microbiota transplantation in patients with chronic constipation.}, journal = {mBio}, volume = {}, number = {}, pages = {e0202324}, doi = {10.1128/mbio.02023-24}, pmid = {39194187}, issn = {2150-7511}, abstract = {UNLABELLED: To investigate the impact of Small Intestinal Bacterial Overgrowth (SIBO) on the efficacy of Fecal Microbiota Transplantation (FMT) in patients with chronic constipation, our research team included 218 patients with chronic constipation treated with FMT. Based on the results of the SIBO breath test, the patients were divided into two groups: the constipation with SIBO group (SIBO) and the constipation without SIBO group (non-SIBO). The efficacy of the two groups was evaluated using constipation-related scoring scales. At the same time, feces and small intestinal fluid samples were collected from both groups before and after FMT to compare the changes in the intestinal microbiota through 16S rRNA sequencing. In this study, it was found that the clinical efficacy of FMT in the SIBO group was superior to that in the non-SIBO group. After FMT treatment, both groups showed a significant increase in bowel frequency and improvement in stool characteristics. Abdominal symptoms, rectal symptoms, and defecation symptoms were significantly alleviated (P < 0.05), and patients' quality of life was significantly enhanced (P < 0.05). After FMT, except for the Constipation Assessment Scale scores, other scale scores showed significant differences between the two groups, the SIBO group scoring significantly better than the non-SIBO group (P < 0.05). After FMT, there were minor changes in the colonic microbiota but more substantial changes in the small intestinal microbiota. At baseline, the SIBO group had a higher abundance of Veillonella, and lower abundances of Escherichia-Shigella and Acinetobacter compared to the non-SIBO group. Chronic constipation patients with SIBO have a better response to FMT than those without SIBO.

IMPORTANCE: Existing studies have rarely considered the impact of the small intestine's microbial state on the efficacy of fecal microbiota transplantation (FMT), nor have they extensively explored the effect of the small intestine's microbial state on the recovery of colonic motility. Therefore, this study investigates the influence of small intestinal bacterial overgrowth (SIBO) on the efficacy of FMT in treating constipation, specifically the impact of the microbial state of the small intestine on the restoration of colonic homeostasis, and consequently on the recovery of colonic motility.}, } @article {pmid39193826, year = {2024}, author = {Jelveh Moghaddam, E and Pourmand, G and Ahmadi Badi, S and Yarmohammadi, H and Soltanipur, M and Mahalleh, M and Rezaei, M and Mirhosseini, SM and Siadat, SD}, title = {Gut microbiota alterations in renal transplant recipients and the risk of urinary tract infection and delayed graft function: A preliminary prospective study.}, journal = {Urologia}, volume = {}, number = {}, pages = {3915603241276742}, doi = {10.1177/03915603241276742}, pmid = {39193826}, issn = {1724-6075}, abstract = {BACKGROUND: The implication of gut microbiota in the gut-kidney axis affects the pathophysiology of chronic kidney disease (CKD). Gut microbiota composition changes during CKD. We aimed to determine the relative frequency of important gut microbiota members in end-stage renal disease (ERSD) patients before and after renal transplantation compared to healthy subjects.

METHODS: Fifteen kidney transplant patients and 10 healthy subjects were recruited in this case-control prospective study. Fecal samples were taken sequentially from all patients before kidney transplantation, 1 week, and 1 month after it. The relative frequency of Lactobacillus spp., Bifidobacterium spp., Akkermansia muciniphila, Bacteroides fragilis, Escherichia coli, and Faecalibacterium pruasnitzii were determined through quantitative PCR. The obtained data was statistically analyzed by Stata software (Stata Corporation, USA).

RESULTS: The mean log number of all bacteria was significantly higher in healthy individuals than kidney transplant recipients (p < 0.001) except for Lactobacillus where the mean levels were almost identical in the two groups (p = 0.67). Moreover, 20% (3) of patients developed a urinary tract infection. Besides, 2 (13.33%) patients were diagnosed with delayed graft function. There were no statistically significant differences regarding changing trends in bacteria log number of Akkermansia muciniphila (p = 0.12), Bacteroid fragilis (p = 0.75), Bifidobacterium (p = 0.99), Escherichia coli (p = 0.5), Faecalibacterium (p = 0.98), and Lactobacilli (p = 0.93) between patients with and without delayed graft function (DGF).

CONCLUSION: Gut microbiota composition in patients with ESRD was significantly different from those without it. However, the microbiota profile did not significantly differ in patients with and without DGF.}, } @article {pmid39193000, year = {2024}, author = {Wu, Q and Yuan, LW and Yang, LC and Zhang, YW and Yao, HC and Peng, LX and Yao, BJ and Jiang, ZX}, title = {Role of gut microbiota in Crohn's disease pathogenesis: Insights from fecal microbiota transplantation in mouse model.}, journal = {World journal of gastroenterology}, volume = {30}, number = {31}, pages = {3689-3704}, pmid = {39193000}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/therapy/pathology/metabolism ; Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Disease Models, Animal ; Mice ; Female ; Male ; Adult ; Feces/microbiology ; Trinitrobenzenesulfonic Acid ; Colon/microbiology/pathology/immunology ; Fibrosis ; Mesentery ; Intestinal Mucosa/microbiology/pathology ; Middle Aged ; Mice, Inbred C57BL ; Case-Control Studies ; Young Adult ; Permeability ; Adipose Tissue ; Adipokines/metabolism ; }, abstract = {BACKGROUND: Inflammatory bowel disease, particularly Crohn's disease (CD), has been associated with alterations in mesenteric adipose tissue (MAT) and the phenomenon termed "creeping fat". Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD, with these tissues characterized by inflammation and fibrosis.

AIM: To evaluate the complex interplay among MAT, creeping fat, inflammation, and gut microbiota in CD.

METHODS: Intestinal tissue and MAT were collected from 12 patients with CD. Histological manifestations and protein expression levels were analyzed to determine lesion characteristics. Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice. The intestinal and mesenteric lesions in these mice, as well as their systemic inflammatory status, were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects.

RESULTS: Pathological examination of MAT showed significant differences between CD-affected and unaffected colons, including significant differences in gut microbiota structure. Fetal microbiota transplantation (FMT) from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD ameliorated CD symptoms, whereas FMT from CD patients into these mice exacerbated CD symptoms. Notably, FMT influenced intestinal permeability, barrier function, and levels of proinflammatory factors and adipokines. Furthermore, FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD.

CONCLUSION: Gut microbiota play a critical role in the histopathology of CD. Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.}, } @article {pmid39192045, year = {2024}, author = {Nikdasti, A and Khodadadi, ES and Ferdosi, F and Dadgostar, E and Yahyazadeh, S and Heidari, P and Ehtiati, S and Vakili, O and Khatami, SH}, title = {Nutritional Strategies in Major Depression Disorder: From Ketogenic Diet to Modulation of the Microbiota-Gut-Brain Axis.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39192045}, issn = {1559-1182}, abstract = {Major depressive disorder (MDD) is a leading cause of disability worldwide. While traditional pharmacological treatments are effective for many cases, a significant proportion of patients do not achieve full remission or experience side effects. Nutritional interventions hold promise as an alternative or adjunctive approach, especially for treatment-resistant depression. This review examines the potential role of nutrition in managing MDD through addressing biological deficits and modulating pathways relevant to its pathophysiology. Specifically, it explores the ketogenic diet and gut microbiome modulation through various methods, including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Numerous studies link dietary inadequacies to increased MDD risk and deficiencies in nutrients like omega-3 s, vitamins D and B, magnesium, and zinc. These deficiencies impact neurotransmitters, inflammation, and other biological factors in MDD. The gut-brain axis also regulates mood, stress response, and immunity, and disruptions are implicated in MDD. While medications aid acute symptoms, nutritional strategies may improve long-term outcomes by preventing relapse and promoting sustained remission. This comprehensive review aims to provide insights into nutrition's multifaceted relationship with MDD and its potential for developing more effective integrated treatment approaches.}, } @article {pmid39191760, year = {2024}, author = {Hartikainen, AK and Jalanka, J and Lahtinen, P and Ponsero, AJ and Mertsalmi, T and Finnegan, L and Crispie, F and Cotter, PD and Arkkila, P and Satokari, R}, title = {Fecal microbiota transplantation influences microbiota without connection to symptom relief in irritable bowel syndrome patients.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {73}, pmid = {39191760}, issn = {2055-5008}, support = {316338//Academy of Finland (Suomen Akatemia)/ ; 323156//Academy of Finland (Suomen Akatemia)/ ; }, mesh = {*Irritable Bowel Syndrome/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; *RNA, Ribosomal, 16S/genetics ; Female ; Male ; Adult ; Treatment Outcome ; *Gastrointestinal Microbiome ; Middle Aged ; Feces/microbiology ; Metagenomics/methods ; Bacteria/classification/genetics/isolation & purification ; }, abstract = {Imbalanced microbiota may contribute to the pathophysiology of irritable bowel syndrome (IBS), thus fecal microbiota transplantation (FMT) has been suggested as a potential treatment. Previous studies on the relationship between clinical improvement and microbiota after FMT have been inconclusive. In this study, we used 16S rRNA gene amplicon and shotgun metagenomics data from a randomized, placebo controlled FMT trial on 49 IBS patients to analyze changes after FMT in microbiota composition and its functional potential, and to identify connections between microbiota and patients' clinical outcome. As a result, we found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of symptoms in IBS patients. Notably, a donor derived strain of Prevotella copri dominated the microbiota in those patients in the FMT group who had a low relative abundance of P. copri pre-FMT. The results highlight the multifactorial nature of IBS and the role of recipient's microbiota in the colonization of donor's strains.}, } @article {pmid39189608, year = {2024}, author = {Tejada, JN and Walters, WA and Wang, Y and Kordahi, M and Chassaing, B and Pickard, J and Nunez, G and Ley, R and Gewirtz, AT}, title = {Prevention and cure of murine C. difficile infection by a Lachnospiraceae strain.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2392872}, pmid = {39189608}, issn = {1949-0984}, support = {R01 DK083890/DK/NIDDK NIH HHS/United States ; R01 DK095782/DK/NIDDK NIH HHS/United States ; R01 DK099071/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Clostridioides difficile/genetics/growth & development/physiology/pathogenicity ; *Clostridium Infections/microbiology/prevention & control ; *Gastrointestinal Microbiome/drug effects ; *Germ-Free Life ; *Clostridiales/genetics/growth & development ; Mice, Inbred C57BL ; Disease Models, Animal ; Feces/microbiology ; Female ; Anti-Bacterial Agents/pharmacology ; }, abstract = {We sought to better understand how intestinal microbiota confer protection against Clostridioides difficile (C. difficile) infection (CDI). We utilized gnotobiotic altered Schaedler flora (ASF) mice, which lack the abnormalities of germfree (GF) mice as well as the complexity and heterogeneity of antibiotic-treated mice. Like GF mice, ASF mice were highly prone to rapid lethal CDI, without antibiotics, while very low infectious doses resulted in chronic CDI. Administering such chronic CDI mice an undefined preparation of Clostridia lowered C. difficile levels by several logs. Importantly, such resolution of CDI was associated with colonization of Lachnospiraceae. Fractionation of the Clostridia population to enrich for Lachnospiraceae led to the appreciation that its CDI-impeding property strongly associated with a specific Lachnospiraceae strain, namely uncultured bacteria and archaea (UBA) 3401. UBA3401 was recalcitrant to being propagated as a pure culture but could be maintained in ASF mice, wherein it comprised up to about 50% of the intestinal microbiota, which was sufficient to generate a high-quality genomic sequence of this bacterium. Sequence analysis and ex vivo study of UBA3401 indicated that it had the ability to secrete substance(s) that directly impeded C. difficile growth. Moreover, in vivo administration of UBA3401/ASF feces provided strong protection to C. difficile challenge. Thus, UBA3401 may contribute to and/or provide a means to study microbiota-mediated CDI resistance.}, } @article {pmid39189041, year = {2024}, author = {Haussmann, AJ and McMahan, ZH and Volkmann, ER}, title = {Understanding the gastrointestinal microbiome in systemic sclerosis: methodological advancements and emerging research.}, journal = {Current opinion in rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/BOR.0000000000001048}, pmid = {39189041}, issn = {1531-6963}, abstract = {PURPOSE OF REVIEW: This review highlights the role of the gastrointestinal (GI) microbiome in systemic sclerosis (SSc). We describe techniques for evaluating the GI microbiome in humans, and emerging research linking GI microbiome alterations (i.e., dysbiosis) and distinct SSc clinical manifestations. We also address the evolving treatment landscape targeting dysbiosis in SSc.

RECENT FINDINGS: Recent literature brings into focus the complex relationship between the GI microbiome and SSc pathogenesis. Advanced techniques (e.g., shotgun metagenomics, meta-transcriptomics) provide deeper insights into microbial taxonomy and active gene expression, exposing dysbiosis as a potential driver of SSc. New studies demonstrate that SSc patients who possess specific SSc clinical features, (e.g., interstitial lung disease), have unique GI microbiome profiles.

SUMMARY: Dysbiosis is associated with specific clinical features in patients with SSc. New tools for studying the GI microbiome have furthered our understanding of the relationship between dysbiosis and SSc complications. Therapeutic avenues such as dietary adjustments, probiotics, antibiotics, mindfulness practices, and fecal transplants offer potential for managing SSc and preventing its progression through GI microbiome modulation. By clarifying what is known about the relationship between the GI dysbiosis, GI dysfunction, and SSc, this review enhances our understanding of SSc pathogenesis and proposes targeted interventions.}, } @article {pmid39188602, year = {2024}, author = {Soldera, J}, title = {Navigating treatment resistance: Janus kinase inhibitors for ulcerative colitis.}, journal = {World journal of clinical cases}, volume = {12}, number = {24}, pages = {5468-5472}, pmid = {39188602}, issn = {2307-8960}, abstract = {The management of refractory ulcerative colitis (UC) and acute severe UC (ASUC) is challenging due to the lack of standardized approaches in cases resistant to multiple treatments. In this editorial, I investigate the efficacy and safety of Janus kinase inhibitors, particularly upadacitinib and tofacitinib, in controlling severe and refractory disease. I highlight a notable case report by Xu et al, which explores the case of a patient with primary nonresponse to two classes of biologics and two fecal microbiota transplants who exhibited a remarkable response to upadacitinib. Furthermore, I discuss the use of tofacitinib in refractory UC and ASUC, either as monotherapy or in combination with biologics, which has shown promising response rates. Additionally, emerging evidence of upadacitinib efficacy in ASUC is presented. Overall, these cases emphasize the complex nature of managing refractory ASUC and the potential of small-molecule therapies to achieve remission. Further research is needed to refine treatment strategies for patients with treatment-resistant UC.}, } @article {pmid39188104, year = {2024}, author = {Naik, A and Godbole, MS}, title = {Elucidating the Intricate Roles of Gut and Breast Microbiomes in Breast Cancer Metastasis to the Bone.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {7}, number = {8}, pages = {e70005}, pmid = {39188104}, issn = {2573-8348}, mesh = {Humans ; *Breast Neoplasms/pathology/microbiology/therapy ; Female ; *Gastrointestinal Microbiome ; *Bone Neoplasms/secondary/microbiology/therapy ; *Tumor Microenvironment/immunology ; Breast/pathology/microbiology ; Microbiota ; Animals ; }, abstract = {BACKGROUND: Breast cancer is the most predominant and heterogeneous cancer in women. Moreover, breast cancer has a high prevalence to metastasize to distant organs, such as the brain, lungs, and bones. Patients with breast cancer metastasis to the bones have poor overall and relapse-free survival. Moreover, treatment using chemotherapy and immunotherapy is ineffective in preventing or reducing cancer metastasis.

RECENT FINDINGS: Microorganisms residing in the gut and breast, termed as the resident microbiome, have a significant influence on the formation and progression of breast cancer. Recent studies have identified some microorganisms that induce breast cancer metastasis to the bone. These organisms utilize multiple mechanisms, including induction of epithelial-mesenchymal transition, steroid hormone metabolism, immune modification, bone remodeling, and secretion of microbial products that alter tumor microenvironment, and enhance propensity of breast cancer cells to metastasize. However, their involvement makes these microorganisms suitable as novel therapeutic targets. Thus, studies are underway to prevent and reduce breast cancer metastasis to distant organs, including the bone, using chemotherapeutic or immunotherapeutic drugs, along with probiotics, antibiotics or fecal microbiota transplantation.

CONCLUSIONS: The present review describes association of gut and breast microbiomes with bone metastases. We have elaborated on the mechanisms utilized by breast and gut microbiomes that induce breast cancer metastasis, especially to the bone. The review also highlights the current treatment options that may target both the microbiomes for preventing or reducing breast cancer metastases. Finally, we have specified the necessity of maintaining a diverse gut microbiome to prevent dysbiosis, which otherwise may induce breast carcinogenesis and metastasis especially to the bone. The review may facilitate more detailed investigations of the causal associations between these microbiomes and bone metastases. Moreover, the potential treatment options described in the review may promote discussions and research on the modes to improve survival of patients with breast cancer by targeting the gut and breast microbiomes.}, } @article {pmid39187939, year = {2024}, author = {Wan, L and Wang, H and Liang, Y and Zhang, X and Yao, X and Zhu, G and Cai, J and Liu, G and Liu, X and Niu, Q and Li, S and Zhang, B and Gao, J and Wang, J and Shi, X and Hu, L and Liu, X and Zou, Z and Yang, G}, title = {Effect of oral faecal microbiota transplantation intervention for children with autism spectrum disorder: A randomised, double-blind, placebo-controlled trial.}, journal = {Clinical and translational medicine}, volume = {14}, number = {9}, pages = {e70006}, pmid = {39187939}, issn = {2001-1326}, support = {2023YFC2706405//National Key Research and Development Program of China/ ; 2022YFC2705301//National Key Research and Development Program of China/ ; 7222187//Beijing Natural Science Foundation/ ; qzx-2023-1//Seventh Medical Center of Chinese PLA General Hospital/ ; 22JSZ20//Seventh Medical Center of Chinese PLA General Hospital/ ; 82170302//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Autism Spectrum Disorder/therapy ; Double-Blind Method ; Child ; Male ; Female ; Treatment Outcome ; Child, Preschool ; Placebos ; }, } @article {pmid39187483, year = {2024}, author = {Li, H and Du, Y and Cheng, K and Chen, Y and Wei, L and Pei, Y and Wang, X and Wang, L and Zhang, Y and Hu, X and Lu, Y and Zhu, X}, title = {Gut microbiota-derived indole-3-acetic acid suppresses high myopia progression by promoting type I collagen synthesis.}, journal = {Cell discovery}, volume = {10}, number = {1}, pages = {89}, pmid = {39187483}, issn = {2056-5968}, support = {82122017//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82271069//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81870642//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81470613//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81670835//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {High myopia (HM) is a leading cause of blindness worldwide with currently no effective interventions available. A major hurdle lies in its often isolated perception as a purely ocular morbidity, disregarding potential systemic implications. Recent evidence suggests the existence of a gut-eye axis; however, the role of gut microbiota in the pathogenesis of HM remains largely unexplored. Herein, we provide a potential crosstalk among HM's gut dysbiosis, microbial metabolites, and scleral remodeling. Utilizing 16S rRNA gene sequencing, we observed an altered gut microbiota profile in HM patients with a significant reduction in probiotic abundance compared with healthy controls. Subsequent targeted metabolic profiling revealed a notable decrease in plasma levels of the gut microbiota-derived metabolite indole-3-acetic acid (3-IAA) among HM patients, which is closely associated with the reduced probiotics, both negatively correlated with HM severity. Genetic analyses determined that gut microbiota are causally associated with myopia risk. Importantly, when mice subjected to HM modeling receive fecal microbiota transplantation from healthy donors, there is an increase in 3-IAA plasma levels and simultaneous retardation of HM progression along with better maintenance of collagen type I alpha 1 (COL1A1) expression in the sclera. Furthermore, 3-IAA gavage achieves similar effects. Mechanistic investigations confirm the transcriptional activation of COL1A1 by 3-IAA via promoting the enrichment of SP1 to its promoter. Together, our findings provide novel insights into the gut microbiota-eye axis in the pathogenesis of HM and propose new strategies for HM intervention by remodeling the gut microbiota and indole supplementation.}, } @article {pmid39187454, year = {2024}, author = {Lu, M and Xie, L and Yin, S and Zhou, J and Yi, L and Ye, L}, title = {The Gut Microbial Lipid Metabolite 14(15)- EpETE Inhibits Substance P Release by Targeting GCG/PKA Signaling to Relieve Cisplatin-Induced Nausea and Vomiting in Rats.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {9}, pages = {1-9}, doi = {10.4014/jmb.2403.03044}, pmid = {39187454}, issn = {1738-8872}, abstract = {Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect related to activation of substance P (SP). SP activation can result from dysregulation of the gut-brain axis, and also from activation of protein kinase A signaling (PKA) signaling. In this study, we connected these factors in an attempt to unveil the mechanisms underlying CINV and develop new therapeutic strategies. Female rats were injected with cisplatin to induce pica. Fecal samples were collected before/after injection, and subjected to lipid metabolomics analysis. In another portion of pica rats, the PKA inhibitor KT5720 was applied to investigate the involvement of PKA signaling in CINV, while fecal microbiota transplantation (FMT) was implemented to verify the therapeutic effect of the lipid metabolite 14(15)-EpETE. Pica symptoms were recorded, followed by ileal histological examination. The targeting relationship between 14(15)-EpETE and glucagon was determined by bioinformatics. SP and glucagon/PKA signaling in rat ileum, serum, and/or brain substantia nigra were detected by immunohistochemistry, enzyme-linked immunosorbent assay, and/or western blot. The results showed a significantly lower level of 14(15)-EpETE in rat feces after cisplatin injection. KT5720 treatment alleviated cisplatin-induced pica symptoms, ileal injury, SP content increase in the ileum, serum, and brain substantia nigra, and ileal PKA activation in rats. The ileal level of glucagon was elevated by cisplatin in rats. FMT exerted an effect similar to that of KT5720 treatment, relieving the cisplatin-induced changes, including ileal glucagon/PKA activation in rats. Our findings demonstrate that FMT restores 14(15)-EpETE production, which inhibits SP release by targeting GCG/PKA signaling, ultimately mitigating CINV.}, } @article {pmid39187187, year = {2024}, author = {Zhang, H and Wei, H and Qin, X and Song, H and Yang, M and Zhang, L and Liu, Y and Wang, Z and Zhang, Y and Lai, Y and Yang, J and Chen, Y and Chen, Z and Zeng, J and Wang, X and Liu, R}, title = {Is anxiety and depression transmissible? - Depressed mother rats transmit anxiety- and depression-like phenotypes to cohabited rat pups through gut microbiota assimilation.}, journal = {Journal of affective disorders}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jad.2024.08.164}, pmid = {39187187}, issn = {1573-2517}, abstract = {OBJECTIVE: This study is to investigate the role of gut microbiota transmission in the development of anxiety/depression in offspring exposed to maternal depression.

METHOD: Offspring rats were cohabitated with their depressed mother or father rats (which exposed to chronic unpredictable mild stress (CUMS)) for 2, 4, and 6 months, the anxiety- and depression-like behaviors, and interaction/caring activities between mother/father and their pups were detected. The gut microbiota composition and its relationship with behaviors were analyzed. Fecal microbiota transplantation (FMT) was performed to establish the gut microbiota of depressed/normal mother rats in the offspring rats to further confirm the role of "depressive gut microbiota" transmission in mediating the anxiety/depression in the pups.

RESULTS: Anxiety and depression phenotypes can be transmitted from depressed mother rats to their cohabited offspring. Frequent interaction and gut microbiota assimilation were observed between rat mothers and pups. Remodeling of the gut microbiota in pups by FMT could induce or attenuate anxiety- and depression-like phenotypes depending on the origin of the fecal microbiota. By comparison, the pups cohabitated with depressed father rats showed slighter anxiety and depression.

CONCLUSIONS: These data together support that depressed mother can transmit anxiety/depression to their pups through gut microbiota assimilation, which is related to frequent interaction. Our study reinforces the importance of mental health of mothers in preventing the occurrence of childhood anxiety and depression, and pointing out the possibility of remodeling intestinal microbiota as an effective therapy for treating anxiety/depression in children.}, } @article {pmid39184689, year = {2024}, author = {Smith, B and Smith, H and Machini, M}, title = {Novel Pharmaceuticals and Therapeutics for Tumor Necrosis Factor-Alpha-Resistant Crohn's Disease: A Narrative Review.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e65357}, pmid = {39184689}, issn = {2168-8184}, abstract = {Inflammatory bowel disease (IBD) is a medical condition that causes persistent, relapsing inflammation of the gastrointestinal tract. It is an umbrella term encompassing two different conditions: ulcerative colitis (UC) and Crohn's disease (CD). The standard treatment for patients with moderate to severe CD is tumor necrosis factor-α (TNF-α) inhibitors; however, a subset of CD patients face challenges in regard to this disease's treatment. Certain populations of patients with CD may exhibit resistance or develop tolerance to TNF-α inhibitor therapy over time. The recurrent gastrointestinal inflammation associated with CD can severely impact the quality of life and lead to complications for those suffering from this condition. The symptomatic flare-ups these subpopulations continue to experience underscores why such a need for alternative therapies is desperately needed. These alternative therapies not only offer potential benefits for those with TNF-α resistance, but CD may also serve as a superior therapy option for those trying to avoid the adverse effects of CD treatments available today. This review aims to explore and investigate the novel drugs and therapies that are being investigated for the treatment of TNF-α resistant CD, such as upadacitinib, risankizumab, vedolizumab, synbiotics, fecal microbiota transplantation (FMT), and stem cell therapy. Upadacitinib is a Janus kinase inhibitor, Risankizumab is a monoclonal antibody targeting interleukin-23, and Vedolizumab is an integrin receptor antagonist. The latest advancements in CD management have shown encouraging results. Some of these novel drugs and therapies not only offer a potential solution for CD patients exhibiting resistance to TNF-α inhibitors but may also provide a superior alternative for individuals prone to opportunistic infections.}, } @article {pmid39184030, year = {2024}, author = {Shera, S and Katzka, W and Yang, JC and Chang, C and Arias-Jayo, N and Lagishetty, V and Balioukova, A and Chen, Y and Dutson, E and Li, Z and Mayer, EA and Pisegna, JR and Sanmiguel, C and Pawar, S and Zhang, D and Leitman, M and Hernandez, L and Jacobs, JP and Dong, TS}, title = {Bariatric-induced microbiome changes alter MASLD development in association with changes in the innate immune system.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1407555}, pmid = {39184030}, issn = {1664-302X}, abstract = {INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects nearly 25% of the population and is the leading cause for liver-related mortality. Bariatric surgery is a well-known treatment for MASLD and obesity. Understanding the fundamental mechanisms by which bariatric surgery can alter MASLD can lead to new avenues of therapy and research. Previous studies have identified the microbiome's role in bariatric surgery and in inflammatory immune cell populations. The host innate immune system modulates hepatic inflammation and fibrosis, and thus the progression of MASLD. The precise role of immune cell types in the pathogenesis of MASLD remains an active area of investigation. The aim of this study was to understand the interplay between microbiota composition post-bariatric surgery and the immune system in MASLD.

METHODS: Eighteen morbidly obese females undergoing sleeve gastrectomy were followed pre-and post-surgery. Stool from four patients, showing resolved MASLD post-surgery with sustained weight loss, was transplanted into antibiotic treated mice. Mice received pre-or post-surgery stool and were fed a standard or high-fat diet. Bodyweight, food intake, and physiological parameters were tracked weekly. Metabolic parameters were measured post-study termination.

RESULTS: The human study revealed that bariatric surgery led to significant weight loss (p > 0.05), decreased inflammatory markers, and improved glucose levels six months post-surgery. Patients with weight loss of 20% or more showed distinct changes in blood metabolites and gut microbiome composition, notably an increase in Bacteroides. The mouse model confirmed surgery-induced microbiome changes to be a major factor in the reduction of markers and attenuation of MASLD progression. Mice receiving post-surgery fecal transplants had significantly less weight gain and liver steatosis compared to pre-surgery recipients. There was also a significant decrease in inflammatory cytokines interferon gamma, interleukin 2, interleukin 15, and mig. This was accompanied by alterations in liver immunophenotype, including an increase in natural killer T cells and reduction of Kupfer cells in the post-surgery transplant group.

DISCUSSION: Our findings suggest surgery induced microbial changes significantly reduce inflammatory markers and fatty liver progression. The results indicate a potential causal link between the microbiome and the host immune system, possibly mediated through modulation of liver NKT and Kupffer cells.}, } @article {pmid39183943, year = {2024}, author = {Fitzjerrells, RL and Ollberding, NJ and Mangalam, AK}, title = {Looking at the full picture, using topic modeling to observe microbiome communities associated with disease.}, journal = {Gut microbes reports}, volume = {1}, number = {1}, pages = {1-11}, pmid = {39183943}, issn = {2993-3935}, abstract = {The microbiome, a complex micro-ecosystem, helps the host with various vital physiological processes. Alterations of the microbiome (dysbiosis) have been linked with several diseases, and generally, differential abundance testing between the healthy and patient groups is performed to identify important bacteria. However, providing a singular species of bacteria to an individual as treatment has not been as successful as fecal microbiota transplant therapy, where the entire microbiome of a healthy individual is transferred. These observations suggest that a combination of bacteria might be crucial for the beneficial effects. Here we provide the framework to utilize topic modeling, an unsupervised machine learning approach, to identify a community of bacteria related to health or disease. Specifically, we used our previously published gut microbiome data of patients with multiple sclerosis (MS), a neurodegenerative disease linked to a dysbiotic gut microbiome. We identified communities of bacteria associated with MS, including genera previously discovered, but also others that would have been overlooked by differential abundance testing. This method can be a useful tool for analyzing the microbiome, and it should be considered along with the commonly utilized differential abundance tests to better understand the role of the gut microbiome in health and disease.}, } @article {pmid39182245, year = {2024}, author = {Luo, X and Yang, X and Tan, S and Zhang, Y and Liu, Y and Tian, X and Huang, Y and Zhou, Y and He, C and Yin, K and Xu, D and Li, X and Sun, F and Tang, R and Cao, J and Zheng, K and Yu, Y and Pan, W}, title = {Gut microbiota mediates anxiety-like behaviors induced by chronic infection of Toxoplasma gondii in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2391535}, pmid = {39182245}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Anxiety/microbiology ; *Mice, Inbred C57BL ; *Toxoplasma/physiology ; Male ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology ; Amygdala/metabolism ; Behavior, Animal ; Toxoplasmosis/physiopathology/psychology/parasitology/microbiology ; Chronic Disease ; Brain-Gut Axis/physiology ; Disease Models, Animal ; Colon/microbiology/parasitology ; }, abstract = {BACKGROUND: Chronic infection with the neurotropic parasite Toxoplasma gondii (T. gondii) can cause anxiety and gut microbiota dysbiosis in hosts. However, the potential role of gut microbiota in anxiety induced by the parasite remains unclear.

METHODS: C57BL/6J mice were infected with 10 cysts of T. gondii. Antibiotic depletion of gut microbiota and fecal microbiota transplantation experiments were utilized to investigate the causal relationship between gut microbiota and anxiety. Anxiety-like behaviors were examined by the elevated plus maze test and the open field test; blood, feces, colon and amygdala were collected to evaluate the profiles of serum endotoxin (Lipopolysaccharide, LPS) and serotonin (5-hydroxytryptamine, 5-HT), gut microbiota composition, metabolomics, global transcriptome and neuroinflammation in the amygdala. Furthermore, the effects of Diethyl butylmalonate (DBM, an inhibitor of mitochondrial succinate transporter, which causes the accumulation of endogenous succinate) on the disorders of the gut-brain axis were evaluated.

RESULTS: Here, we found that T. gondii chronic infection induced anxiety-like behaviors and disturbed the composition of the gut microbiota in mice. In the amygdala, T. gondii infection triggered the microglial activation and neuroinflammation. In the colon, T. gondii infection caused the intestinal dyshomeostasis including elevated colonic inflammation, enhanced bacterial endotoxin translocation to blood and compromised intestinal barrier. In the serum, T. gondii infection increased the LPS levels and decreased the 5-HT levels. Interestingly, antibiotics ablation of gut microbiota alleviated the anxiety-like behaviors induced by T. gondii infection. More importantly, transplantation of the fecal microbiota from T. gondii-infected mice resulted in anxiety and the transcriptomic alteration in the amygdala of the antibiotic-pretreated mice. Notably, the decreased abundance of succinate-producing bacteria and the decreased production of succinate were observed in the feces of the T. gondii-infected mice. Moreover, DBM administration ameliorated the anxiety and gut barrier impairment induced by T. gondii infection.

CONCLUSIONS: The present study uncovers a novel role of gut microbiota in mediating the anxiety-like behaviors induced by chronic T. gondii infection. Moreover, we show that DBM supplementation has a beneficial effect on anxiety. Overall, these findings provide new insights into the treatment of T. gondii-related mental disorders.}, } @article {pmid39182099, year = {2024}, author = {Zheng, H and Zhang, X and Li, C and Wang, D and Shen, Y and Lu, J and Zhao, L and Li, X and Gao, H}, title = {BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {157}, pmid = {39182099}, issn = {2049-2618}, support = {22074106//National Natural Science Foundation of China/ ; 21974096//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Fibroblast Growth Factors/metabolism ; Mice ; *Gastrointestinal Microbiome ; *Diabetic Cardiomyopathies/metabolism/microbiology ; *Liver/metabolism ; *Amino Acids, Branched-Chain/metabolism ; Signal Transduction ; Diabetes Mellitus, Type 1/microbiology/metabolism ; Male ; Myocardium/metabolism/pathology ; PPAR alpha/metabolism ; Mice, Inbred C57BL ; Diabetes Mellitus, Experimental/metabolism/microbiology ; }, abstract = {BACKGROUND: Diabetic cardiomyopathy (DCM) is one of leading causes of diabetes-associated mortality. The gut microbiota-derived branched-chain amino acids (BCAA) have been reported to play a central role in the onset and progression of DCM, but the potential mechanisms remain elusive.

RESULTS: We found the type 1 diabetes (T1D) mice had higher circulating BCAA levels due to a reduced BCAA degradation ability of the gut microbiota. Excess BCAA decreased hepatic FGF21 production by inhibiting PPARα signaling pathway and thereby resulted in a higher expression level of cardiac LAT1 via transcription factor Zbtb7c. High cardiac LAT1 increased the levels of BCAA in the heart and then caused mitochondrial damage and myocardial apoptosis through mTOR signaling pathway, leading to cardiac fibrosis and dysfunction in T1D mice. Additionally, transplant of faecal microbiota from healthy mice alleviated cardiac dysfunction in T1D mice, but this effect was abolished by FGF21 knockdown.

CONCLUSIONS: Our study sheds light on BCAA-mediated crosstalk among the gut microbiota, liver and heart to promote DCM and FGF21 serves as a key mediator. Video Abstract.}, } @article {pmid39180723, year = {2024}, author = {Jiang, L and Hao, Y and Han, D and Dong, W and Yang, A and Sun, Z and Ge, Y and Duan, S and Zhang, X and Dai, Z}, title = {Gut microbiota dysbiosis deteriorates immunoregulatory effects of tryptophan via colonic indole and LBP/HTR2B-mediated macrophage function.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrae166}, pmid = {39180723}, issn = {1751-7370}, abstract = {Tryptophan (Trp) has been shown to regulate immune function by modulating gut serotonin (5-HT) metabolism and signaling. However, the mechanisms underlying the microbial modulation of gut 5-HT signaling in gut inflammation with gut microbiota dysbiosis require further investigation. Here, we investigated the effects of Trp supplementation on the composition and metabolism of the gut microbiome and 5-HT signaling-related gut immune function using a dextran sodium sulfate (DSS)-induced colitis mouse model coupled with antibiotic exposure. The results showed that antibiotic treatment before but not during DSS treatment decreased the immunoregulatory effects of Trp and aggravated gut inflammation and body weight loss in mice. Metagenomic analysis revealed that the fecal microbiota transplantation (FMT) of Trp-enriched gut microbiota to recipient mice subject to antibiotic preexposure and DSS treatment aggravated inflammation by increasing the relative abundances of Lactobacillus and Parabacteroides and the microbial production of indole coupled with the activation of the 5-HT receptor HTR2B in the colon. Transcriptomic analysis showed that HTR2B agonist administration strengthened the beneficial effects of Trp in DSS-induced colitis mice with antibiotic exposure by reducing gut lipopolysaccharide-binding protein (LBP) production, IκB-α/nuclear factor-κB signaling, and M1 macrophage polarization. Indole treatment reduced LBP production and M1 macrophage polarization both in mice with DSS-induced colitis and in lipopolysaccharide-treated mouse macrophages; however, the HTR2B antagonist reversed the effects of indole. Our findings provide the basis for developing new dietary and therapeutic interventions to improve gut microbiota dysbiosis-associated inflammatory gut disorders and diseases.}, } @article {pmid39180442, year = {2024}, author = {Wang, Z and Yang, L and Feng, Y and Duan, B and Zhang, H and Tang, Y and Zhang, C and Yang, J}, title = {Isoorientin Alleviates DSS-Treated Acute Colitis in Mice by Regulating Intestinal Epithelial P-Glycoprotein (P-gp) Expression.}, journal = {DNA and cell biology}, volume = {}, number = {}, pages = {}, doi = {10.1089/dna.2024.0101}, pmid = {39180442}, issn = {1557-7430}, abstract = {Isoorientin (ISO) is a naturally occurring flavonoid with diverse functional properties that mitigate the risk of diseases stemming from oxidation, inflammation, and cancer cell proliferation. P-glycoprotein (P-gp) is a vital component of the intestinal epithelium and may play a role in the onset of intestinal inflammatory conditions, such as inflammatory bowel disease (IBD). Recent studies have suggested that short-chain fatty acids (SCFAs) and secondary bile acids (SBAs) produced by the gut microbiota stimulate the increase of P-gp expression, alleviating excessive inflammation and thereby preservation of intestinal homeostasis. ISO has been shown to improve colon health and modulate the gut microbiota. In this study, we aimed to explore whether ISO can modulate the microbes and their metabolites to influence P-gp expression to alleviate IBD. First, the impact of ISO on dextran sulfate sodium (DSS)-treated colitis in mice was investigated. Second, 16S rRNA gene sequencing was conducted. The present study indicated that ISO mitigated the symptoms and pathological damage associated with DSS-treated colitis in mice. Western blot analysis revealed ISO upregulated P-gp in colon tissues, suggesting the critical role of P-gp protein in intestinal epithelial cells. 16S microbial diversity sequencing revealed ISO restored the richness and variety of intestinal microorganisms in colitis-bearing mice and enriched SCFA-producing bacteria, such as Lachnospiraceae_NK4A136_group. The experiments also revealed that the ISO fecal microbiota transplantation (FMT) inoculation of DSS-treated mice had similarly beneficial results. FMT mice showed a reduction in colitis symptoms, which was more pronounced in ISO-FMT than in CON-FMT mice. Meanwhile, ISO-FMT expanded the abundance of beneficial microorganisms, increased the expression of metabolites, such as SCFAs and total SBAs, and significantly upregulated the expression of P-gp protein. In addition, Spearman's correlation analysis demonstrated a positive correlation between the production of SCFAs and SBAs and the expression of P-gp. The present study identified that ISO increases the expression of P-gp in the intestinal epithelium by regulating intestinal microorganisms and their metabolites, which maintains colonic homeostasis, improves the integrity of the colonic epithelium, and alleviates colitis.}, } @article {pmid39180286, year = {2024}, author = {Jin, X and Sheng, W and Liu, X and Zhu, D}, title = {Optimizing Colonoscopy Preparation in Autistic Children: A Comparative Study of Hypertonic Sugar Saline and Normal Saline Enemas.}, journal = {Clinical pediatrics}, volume = {}, number = {}, pages = {99228241275054}, doi = {10.1177/00099228241275054}, pmid = {39180286}, issn = {1938-2707}, abstract = {OBJECTIVE: This study evaluates the effectiveness of combining oral polyethylene glycol electrolyte solution with hypertonic sugar saline enema for colonoscopy preparation in autistic children.

METHODS: Clinical data of 58 children with autism who underwent fecal bacteria transplantation and transendoscopic enteral tubing (TET) catheterization at the hospital were retrospectively analyzed. Participants were allocated into 2 groups: a control group (26 children) and an observation group (32 children), differentiated by their intestinal preparation protocols. The control group was administered oral polyethylene glycol combined with normal saline enema, whereas the observation group was given oral polyethylene glycol combined with hypertonic sugar saline enema. The Boston Bowel Preparation Scale (BBPS) was used to score intestinal cleanliness. Differences in intestinal cleanliness and colonoscopy duration between the 2 groups were compared.

RESULTS: The group treated with hypertonic sugar saline enema exhibited significantly higher BBPS scores (6.78 ± 0.83) and an intestinal passage rate of 96.86%, which were statistically significant compared with the control group (P < 0.05). In addition, the colonoscopy duration was notably shorter in the observation group (14.03 ± 4.86 minutes) compared with the control group (P < 0.05).

CONCLUSION: Our findings suggest that an oral polyethylene glycol electrolyte solution combined with a hypertonic sugar saline enema is a more effective preparation method for colonoscopy in autistic children.}, } @article {pmid39179176, year = {2024}, author = {Ngo, VL and Wang, Y and Wang, Y and Shi, Z and Britton, R and Zou, J and Ramani, S and Jiang, B and Gewirtz, AT}, title = {Select gut microbiota impede rotavirus vaccine efficacy.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101393}, doi = {10.1016/j.jcmgh.2024.101393}, pmid = {39179176}, issn = {2352-345X}, abstract = {BACKGROUND& AIMS: The protection provided by rotavirus (RV) vaccines is highly heterogeneous amongst individuals. We hypothesized that microbiota composition might influence RV vaccine efficacy.

METHODS: First, we examined the potential of segmented filamentous bacteria (SFB) colonization to influence RV vaccine efficacy in mice. Next, we probed the Influence of human microbiomes on RV vaccination via administering mice fecal microbial transplants (FMT) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to RV vaccination followed by RV challenge.

RESULTS: SFB colonization induced a phenotype that was reminiscent of RV vaccine failure, i.e. failure to generate RV antigens and, consequently, anti-RV antibodies following RV vaccination resulting in proneness to RV challenge after SFB levels diminished. FMT from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMT from high-responsive vaccinees copiously shed RV antigens and robustly generated anti-RV antibodies following RV vaccination. Concomitantly, such mice were impervious to RV challenge. In contrast, mice receiving FMT from children who had not responded to RV vaccination exhibited only modest responses to RV vaccination and, concomitantly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested involvement of Clostridium perfringens. Oral administration of cultured C. perfringens to gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of published microbiome data found C. perfringens abundance in children modestly associated with RV vaccine failure.

CONCLUSION: Microbiota composition influences RV vaccine efficacy with C. perfringens being one, perhaps of many, potential contributing taxa.}, } @article {pmid39178987, year = {2024}, author = {Shukla, V and Singh, S and Verma, S and Verma, S and Rizvi, AA and Abbas, M}, title = {Targeting the Microbiome to Improve Human Health with the Approach of Personalized Medicine: Latest Aspects and Current Updates.}, journal = {Clinical nutrition ESPEN}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clnesp.2024.08.005}, pmid = {39178987}, issn = {2405-4577}, abstract = {The intricate ecosystem of microorganisms residing within and on the human body, collectively known as the microbiome, significantly influences human health. Imbalances in this microbiome, referred to as dysbiosis, have been associated with various diseases, prompting the exploration of novel therapeutic approaches. Personalized medicine, Tailors treatments to individual patient characteristics, offers a promising avenue for addressing microbiome-related health issues. This review highlights recent developments in utilizing personalized medicine to target the microbiome, aiming to enhance health outcomes. Noteworthy strategies include fecal microbiota transplantation (FMT), where healthy donor microbes are transferred to patients, showing promise in treating conditions such as recurrent Clostridium difficile infection. Additionally, probiotics, which are live microorganisms similar to beneficial gut inhabitants, and prebiotics, non-digestible compounds promoting microbial growth, are emerging as tools to restore microbiome balance. The integration of these approaches, known as synbiotics, enhances microbial colonization and therapeutic effects. Advances in metagenomics and sequencing technologies provide the means to understand individual microbiome profiles, enabling tailored interventions. This paper aims to present the latest insights in leveraging personalized medicine to address microbiome-related health concerns, envisioning a future where microbiome-based therapies reshape disease management and promote human health.}, } @article {pmid39176325, year = {2024}, author = {Nilofar, F and Babu, N and Kumar, M and Palanisamy, S and T, G}, title = {From Hemorrhage to Diarrhea: The Comprehensive Clinical Journey of a Patient With Pseudomembranous Colitis.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e65176}, pmid = {39176325}, issn = {2168-8184}, abstract = {Pseudomembranous colitis (PC) is an inflammation of the colon primarily caused by the bacterium Clostridium difficile (C. difficile), often following antibiotic use. This case report describes the intricate clinical course of a 48-year-old male farmer with a history of chronic alcoholism, tobacco use, and seizure disorder, who presented with acute onset of left-sided weakness. CT brain revealed an intra-axial hemorrhage in the right gangliocapsular region with significant edema and midline shift. The patient's condition necessitated mechanical ventilation due to a low Glasgow Coma Scale (GCS) score. Complications ensued with the onset of ventilator-associated pneumonia (VAP) on day six, attributed to multi-drug resistant Acinetobacter baumannii, which was managed with meropenem and polymyxin. Following successful weaning from the ventilator, he experienced severe watery diarrhea, high-grade fever, and diffuse abdominal pain on day 13. Subsequent stool tests confirmed PC caused by C. difficile, characterized by diffuse colonic wall-thickening with a water target sign on contrast-enhanced CT (CECT) abdomen. Initial treatment with oral vancomycin and metronidazole was followed by symptomatic treatment. Two weeks later, the patient had a relapse of PC, presenting with multiple episodes of loose stools, which was managed with oral metronidazole alone. Colonoscopy and biopsy confirmed the relapse, showing inflamed colonic mucosa with pseudomembranes. This case highlights the importance of strict infection control, prudent antibiotic use, and close monitoring for these patients. It also suggests the potential role of fecal microbiota transplantation (FMT) for recurrent cases. The patient's recovery demonstrates the effectiveness of meticulous medical management and adherence to infection control protocols in achieving optimal outcomes.}, } @article {pmid39173982, year = {2024}, author = {Ding, FF and Zhou, NN and Wang, T and Bao, MY and Qiao, F and Du, ZY and Zhang, ML}, title = {Fish gut-derived probiotic Pediococcus pentosaceus alleviates gossypol-induced intestinal inflammation by inhibiting NLRC3/NF-κB/IL-1β signal pathway in Nile tilapia.}, journal = {Fish & shellfish immunology}, volume = {153}, number = {}, pages = {109852}, doi = {10.1016/j.fsi.2024.109852}, pmid = {39173982}, issn = {1095-9947}, abstract = {Cottonseed meal (CSM) and cottonseed protein concentrate (CPC) serve as protein alternatives to fish meal and soybean meal in the feed industry. However, the presence of gossypol residue in CSM and CPC can potentially trigger severe intestinal inflammation, thereby restricting the widespread utilization of these two protein sources. Probiotics are widely used to prevent or alleviate intestinal inflammation, but their efficacy in protecting fish against gossypol-induced enteritis remains uncertain. Here, the protective effect of Pediococcus pentosaceus, a strain isolated from the gut of Nile tilapia (Oreochromis niloticus), was evaluated. Three diets, control diet (CON), gossypol diet (GOS) and GOS supplemented with P. pentosaceus YC diet (GP), were used to feed Nile tilapia for 10 weeks. After the feeding trial, P. pentosaceus YC reduced the activity of myeloperoxidase (MPO) in the proximal intestine (PI) and distal intestine (DI). Following a 7-day exposure to Aeromonas hydrophila, the addition of P. pentosaceus YC was found to increase the survival rate of the fish. P. pentosaceus YC significantly inhibited the oxidative stress caused by gossypol, which was evidenced by lower reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in PI and DI. Addition of P. pentosaceus YC significantly inhibited enteritis, with the lower expression of pro-inflammatory cytokines (il-1β, il-6, il-8) and higher expression of anti-inflammatory cytokines tgf-β. RNA-seq analysis indicated that P. pentosaceus YC supplementation significantly inhibited nlrc3 and promoted nf-κb expression in PI and DI, and the siRNA interference experiment in vivo demonstrated that intestinal inflammation was mediated by NLRC3/NF-κB/IL-1β signaling pathway. Fecal bacteria transplantation experiment demonstrated that gut microbiota mediated the protective effect of P. pentosaceus YC. These findings offer valuable insights into the application of P. pentosaceus YC for alleviating gossypol-induced intestinal inflammation in fish.}, } @article {pmid39173885, year = {2024}, author = {MacGibeny, MA and Adjei, S and Pyle, H and Bunick, CG and Ghannoum, M and Grada, A and Harris-Tryon, T and Tyring, SK and Kong, HH}, title = {Alterations in the Skin Microbiome in Dermatologic Diseases and with External Exposures: CME Part 2.}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2024.07.1499}, pmid = {39173885}, issn = {1097-6787}, abstract = {In Part I of our CME we reviewed the skin microbiome in healthy individuals. Part II reviews the evolving understanding of alterations in the skin microbiome in specific human diseases. We also discuss how the skin microbiome can change with environmental exposures and medications such as antibiotics as well as ongoing research on microbiome-based interventions.}, } @article {pmid39173756, year = {2024}, author = {Liu, J and Zhang, Z and Zhong, S and Zhang, X and Yang, J and Zhou, Q and Wang, D and Chang, X and Wang, H}, title = {Fecal microbiome transplantation alleviates manganese-induced neurotoxicity by altering the composition and function of the gut microbiota via the cGAS-STING/NLRP3 pathway.}, journal = {The Science of the total environment}, volume = {951}, number = {}, pages = {175681}, doi = {10.1016/j.scitotenv.2024.175681}, pmid = {39173756}, issn = {1879-1026}, abstract = {Manganese (Mn) is an environmental pollutant, and overexposure can cause neurodegenerative disorders similar to Alzheimer's disease and Parkinson's disease that are characterized by β-amyloid (Aβ) overexpression, Tau hyperphosphorylation and neuroinflammation. However, the mechanisms of Mn neurotoxicity are not clearly defined. In our study, a knockout mouse model of Mn exposure combined with gut flora-induced neurotoxicity was constructed to investigate the effect of gut flora on Mn neurotoxicity. The results showed that the levels of Tau, p-Tau and Aβ in the hippocampus of C57BL/6 mice were greater than those in the hippocampus of control mice after 5 weeks of continuous exposure to manganese chloride (Mn content of 200 mg/L). Transplanted normal and healthy fecal microbiota from mice significantly downregulated Tau, p-Tau and Aβ expression and ameliorated brain pathology. Moreover, Mn exposure activated the cGAS-STING pathway and altered the cecal microbiota profile, characterized by an increase in Clostridiales, Pseudoflavonifractor, Ligilactobacillus and Desulfovibrio, and a decrease in Anaerotruncus, Eubacterium_ruminantium_group, Fusimonas and Firmicutes, While fecal microbiome transplantation (FMT) treatment inhibited this pathway and restored the microbiota profile. FMT alleviated Mn exposure-induced neurotoxicity by inhibiting activation of the NLRP3 inflammasome triggered by overactivation of the cGAS-STING pathway. Deletion of the cGAS and STING genes and FMT altered the gut microbiota composition and its predictive function. Phenotypic prediction revealed that FMT markedly decreased the abundances of anaerobic and stress-tolerant bacteria and significantly increased the abundances of facultative anaerobic bacteria and biofilm-forming bacteria after blocking the cGAS-STING pathway compared to the Mn-exposed group. FMT from normal and healthy mice ameliorated the neurotoxicity of Mn exposure, possibly through alterations in the composition and function of the microbiome associated with the cGAS-STING/NLRP3 pathway. This study provides a prospective direction for future research on the mechanism of Mn neurotoxicity.}, } @article {pmid39172643, year = {2024}, author = {Offersen, SM and Mao, X and Spiegelhauer, MR and Larsen, F and Li, VR and Sandris Nielsen, D and Aunsholt, L and Thymann, T and Brunse, A}, title = {Fecal virus-like particles are sufficient to reduce necrotizing enterocolitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2392876}, doi = {10.1080/19490976.2024.2392876}, pmid = {39172643}, issn = {1949-0984}, mesh = {*Enterocolitis, Necrotizing/prevention & control/therapy ; Animals ; *Feces/virology/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; Swine ; Humans ; Bacteria/classification/isolation & purification/genetics ; Animals, Newborn ; Disease Models, Animal ; Virome ; Clostridium perfringens ; Bacteriophages/genetics/physiology ; Diarrhea/therapy/virology/prevention & control/microbiology ; }, abstract = {Fecal filtrate transfer (FFT) is emerging as a safer alternative to traditional fecal microbiota transplantation (FMT) - particularly in the context of necrotizing enterocolitis (NEC), a severe gastrointestinal condition affecting preterm infants. Using a preterm piglet model, FFT has demonstrated superiority over FMT in safety and NEC prevention. Since FFT is virtually devoid of bacteria, prokaryotic viruses (bacteriophages) are assumed to mediate the beneficial effects. However, this assumption remains unproven. To address this gap, we separated virus-like particles (30 kDa to 0.45 µm) of donor feces from the residual postbiotic fluid. We then compared clinical and gut microbiota responses to these fractions with the parent FFT solution after transferring them to NEC-susceptible preterm piglets. Virome transfer was equally effective as FFT in reducing the severity of NEC-like pathology. The bacterial compositional data corroborated clinical findings as virome transfer reduced the relative abundance of several NEC-associated pathogens e.g. Klebsiella pneumoniae and Clostridium perfringens. Virome transfer diversified gut viral communities with concomitant constraining effects on the bacterial composition. Unexpectedly, virome transfer, but not residual postbiotic fluid, led to earlier diarrhea. While diarrhea may be a minor concern in human infants, future work should identify ways of eliminating this side effect without losing treatment efficacy.}, } @article {pmid39172216, year = {2024}, author = {Xu, X and Jin, H and Li, X and Yan, C and Zhang, Q and Yu, X and Liu, Z and Liu, S and Zhu, F}, title = {Fecal Microbiota Transplantation Regulates Blood Pressure by Altering Gut Microbiota Composition and Intestinal Mucosal Barrier Function in Spontaneously Hypertensive Rats.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39172216}, issn = {1867-1314}, abstract = {Hypertension is accompanied by gut microbiota imbalance, but the role of bacteria in the pathogenesis of hypertension requires further study. In this study, we used fecal microbiota transplantation to determine the impact of microbiota composition on blood pressure in spontaneous hypertensive rats (SHRs), using normotensive Wistar Kyoto (WKY) rats as controls. SHRs were randomly divided into two groups (n = 10/group), SHR and SHR-T (SHR plus fecal transplantation) and WKY into WKY and WKY-T (WKY plus fecal transplantation). SHR-T received fecal transplantation from WKY, while WKY-T received fecal transplantation from SHR. Blood pressure was measured from the tail artery in conscious rats. 16S rDNA gene amplicon sequencing was used to analyze bacterial composition. Circulating levels of diamine oxidase, D-lactate, FITC-Dextrans, and lipopolysaccharide were determined. Hematoxylin and eosin (H&E) staining was used to observe structural changes in the intestinal mucosa. Immunofluorescence, Western blot, and RT-PCR were utilized to determine changes in the expression of tight junction proteins. Following cross fecal transplantation, blood pressure decreased in SHR and increased in WKY. Significant differences in gut microbial composition were found between hypertensive and normotensive rats, specifically regarding the relative abundance of lactic and butyric acid-producing bacteria. Changes in gut microbiota composition also impacted the intestinal mucosal barrier integrity. Moreover, fecal transplantation affected the expression of tight junction proteins that may impact intestinal mucosal permeability and structural integrity. Blood pressure may be associated with butyric acid-producing intestinal microbiota and its function in regulating the integrity of intestinal mucosal barrier.}, } @article {pmid39170992, year = {2024}, author = {Sanchez Cruz, C and Rojas Huerta, A and Lima Barrientos, J and Rodriguez, C and Devani, A and Boosahda, V and Rasagna Mareddy, NS and Briceno Silva, G and Del Castillo Miranda, JC and Reyes Gochi, KA and Reyes Gochi, MD and Alvarez, S and Ghattas Hasbun, PE}, title = {Inflammatory Bowel Disease and Cardiovascular Disease: An Integrative Review With a Focus on the Gut Microbiome.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e65136}, pmid = {39170992}, issn = {2168-8184}, abstract = {Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory condition of the gastrointestinal tract. Recent research indicates a significant link between IBD and cardiovascular disease (CVD), the leading cause of global morbidity and mortality. This review examines the association between IBD and CVD, emphasizing the role of the gut microbiome in this relationship. IBD patients have a higher risk of cardiovascular events, such as coronary artery disease, heart failure, and cerebrovascular incidents, primarily due to chronic systemic inflammation, genetic factors, and gut microbiota imbalance (dysbiosis). Dysbiosis in IBD increases intestinal permeability, allowing bacterial products to enter the bloodstream, which promotes inflammation and endothelial dysfunction, contributing to CVD. Understanding the gut microbiome's role in IBD and CVD suggests new therapeutic interventions. Modulating the microbiome through diet, probiotics, and fecal microbiota transplantation (FMT) are promising research avenues. These interventions aim to restore a healthy gut microbiota balance, potentially reducing inflammation and improving cardiovascular outcomes. Additionally, the review emphasizes the importance of regular cardiovascular risk assessments and personalized preventive measures in managing IBD patients. Such measures include routine monitoring of cardiovascular health, tailored lifestyle modifications, and early intervention strategies to mitigate cardiovascular risk. By integrating current knowledge, this review aims to improve understanding and management of the interconnected pathophysiology of IBD and CVD. This approach will ultimately enhance patient outcomes and provide a foundation for future research and clinical practice guidelines in this area.}, } @article {pmid39170985, year = {2024}, author = {Zou, X and Zou, X and Gao, L and Zhao, H}, title = {Gut microbiota and psoriasis: pathogenesis, targeted therapy, and future directions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1430586}, pmid = {39170985}, issn = {2235-2988}, mesh = {*Psoriasis/therapy/microbiology/drug therapy ; Humans ; *Gastrointestinal Microbiome ; *Medicine, Chinese Traditional ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Prebiotics ; Cytokines/metabolism ; Interleukin-17/metabolism ; }, abstract = {BACKGROUND: Psoriasis is one of the most common autoimmune skin diseases. Increasing evidence shows that alterations in the diversity and function of microbiota can participate in the pathogenesis of psoriasis through various pathways and mechanisms.

OBJECTIVE: To review the connection between microbial changes and psoriasis, how microbial-targeted therapy can be used to treat psoriasis, as well as the potential of prebiotics, probiotics, synbiotics, fecal microbiota transplantation, diet, and Traditional Chinese Medicine as supplementary and adjunctive therapies.

METHODS: Literature related to the relationship between psoriasis and gut microbiota was searched in PubMed and CNKI.

RESULTS: Adjunct therapies such as dietary interventions, traditional Chinese medicine, and probiotics can enhance gut microbiota abundance and diversity in patients with psoriasis. These therapies stimulate immune mediators including IL-23, IL-17, IL-22, and modulate gamma interferon (IFN-γ) along with the NF-kB pathway, thereby suppressing the release of pro-inflammatory cytokines and ameliorating systemic inflammatory conditions.

CONCLUSION: This article discusses the direction of future research and clinical treatment of psoriasis from the perspective of intestinal microbiota and the mechanism of traditional Chinese medicine, so as to provide clinicians with more comprehensive diagnosis and treatment options and bring greater hope to patients with psoriasis.}, } @article {pmid39166878, year = {2024}, author = {Lu, Q and Zhu, R and Zhou, L and Zhang, R and Li, Z and Xu, P and Wang, Z and Wu, G and Ren, J and Jiao, D and Song, Y and Li, J and Wang, W and Liang, R and Ma, X and Sun, Y}, title = {Gut dysbiosis contributes to the development of Budd-Chiari syndrome through immune imbalance.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0079424}, doi = {10.1128/msystems.00794-24}, pmid = {39166878}, issn = {2379-5077}, abstract = {UNLABELLED: Budd-Chiari syndrome (B-CS) is a rare and lethal condition characterized by hepatic venous outflow tract blockage. Gut microbiota has been linked to numerous hepatic disorders, but its significance in B-CS pathogenesis is uncertain. First, we performed a case-control study (Ncase = 140, Ncontrol = 63) to compare the fecal microbiota of B-CS and healthy individuals by metagenomics sequencing. B-CS patients' gut microbial composition and activity changed significantly, with a different metagenomic makeup, increased potentially pathogenic bacteria, including Prevotella, and disease-linked microbial function. Imbalanced cytokines in patients were demonstrated to be associated with gut dysbiosis, which led us to suspect that B-CS is associated with gut microbiota and immune dysregulation. Next, 16S ribosomal DNA sequencing on fecal microbiota transplantation (FMT) mice models examined the link between gut dysbiosis and B-CS. FMT models showed damaged liver tissues, posterior inferior vena cava, and increased Prevotella in the disturbed gut microbiota of FMT mice. Notably, B-CS-FMT impaired the morphological structure of colonic tissues and increased intestinal permeability. Furthermore, a significant increase of the same cytokines (IL-5, IL-6, IL-9, IL-10, IL-17A, IL-17F, and IL-13) and endotoxin levels in B-CS-FMT mice were observed. Our study suggested that gut microbial dysbiosis may cause B-CS through immunological dysregulation.

IMPORTANCE: This study revealed that gut microbial dysbiosis may cause Budd-Chiari syndrome (B-CS). Gut dysbiosis enhanced intestinal permeability, and toxic metabolites and imbalanced cytokines activated the immune system. Consequently, the escalation of causative factors led to their concentration in the portal vein, thereby compromising both the liver parenchyma and outflow tract. Therefore, we proposed that gut microbial dysbiosis induced immune imbalance by chronic systemic inflammation, which contributed to the B-CS development. Furthermore, Prevotella may mediate inflammation development and immune imbalance, showing potential in B-CS pathogenesis.}, } @article {pmid39166867, year = {2024}, author = {Sintes, R and McLellan, P and Navelli, G and Landman, C and Delage, S and Truong, S and Benech, N and Kapel, N and Moreino Sabater, A and Schnuriger, A and Eckert, C and Bleibtreu, A and Joly, A-C and Sokol, H}, title = {Use of frozen native feces for fecal microbiota transplantation in recurrent Clostridioides difficile infection: a simple way to improve the efficiency of donor feces preparation.}, journal = {Antimicrobial agents and chemotherapy}, volume = {}, number = {}, pages = {e0073424}, doi = {10.1128/aac.00734-24}, pmid = {39166867}, issn = {1098-6596}, abstract = {Preparing fecal microbiota transplants immediately after donation is resource-intensive, and a proportion are destroyed following abnormal screening results. We retrospectively compared two processes, frozen fecal preparation (FFP) and fresh native frozen preparation (FNFP), for clinical efficacy in the treatment of recurrent Clostridioides difficile infection (rCDI). FFP and FNFP were similarly effective with clinical success rates of 76.7% and 86.7% (P = 0.32), respectively. FNFP is an efficient procedure that saves resources while maintaining clinical efficacy in rCDI.}, } @article {pmid39165355, year = {2024}, author = {Huang, J and Zhang, J and Wang, F and Tang, X}, title = {Modified Gegen Qinlian Decoction modulated the gut microbiome and bile acid metabolism and restored the function of goblet cells in a mouse model of ulcerative colitis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1445838}, pmid = {39165355}, issn = {1664-3224}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Colitis, Ulcerative/microbiology/drug therapy/metabolism/therapy ; Mice ; *Disease Models, Animal ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Goblet Cells/drug effects/metabolism ; *Bile Acids and Salts/metabolism ; Male ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; Colon/pathology/metabolism/drug effects/microbiology ; }, abstract = {OBJECTIVE: Modified Gegen Qinlian Decoction (MGQD) has been shown to effectively relieve ulcerative colitis (UC) without a known pharmacological mechanism. In this study, the anti-colitis efficaciousness of MGQD and its underlying mechanisms in UC were evaluated.

METHODS: Mice with colitis were administered MGQD for 7 days. Following the evaluation of clinical symptoms, gut microbiota in the feces of UC mice was examined using 16S rRNA sequencing and bile acids (BAs) were examined using LC/MS. Gut microbiota consumption and fecal microbiota transplantation (FMT) were used to explore the involvement of gut microbiota in the anti-UC action of MGQD.

RESULTS: MGQD relieved colitis as shown by weight loss protection, a lower disease activity index (DAI), restoration of intestinal length reduction, and lower histopathologic scores. MGQD also restored crypt stem cell proliferation and function of colonic goblet cells, and promoted MUC2 protein secretion. Interestingly, investigations using gut bacterial depletion and FMT showed that MGQD attenuated colonic damage in a gut-dependent way. The modulation of the gut microbiota by MGQD might be attributed to a decrease in Odoribacter and an increase in norank_f_Muribaculaceae. In addition, MGQD modulated the metabolism of BAs while restoring the structure of the gut microbiota.

CONCLUSION: MGQD significantly alleviated colitis in mice, which may be associated with the modulation of gut microbiota and BA metabolism and restoration of function of goblet cells. However, factors other than the gut microbiota may also be involved in the amelioration of UC by MGQD.}, } @article {pmid39165756, year = {2023}, author = {Hosseini, PSK and Wang, B and Luan, Y and Sun, F and Michail, S}, title = {Gut metabolomic profiles in paediatric ulcerative colitis patients prior to and after receiving faecal microbiota transplants.}, journal = {Gut microbiome (Cambridge, England)}, volume = {4}, number = {}, pages = {}, pmid = {39165756}, issn = {2632-2897}, support = {R01 HD081197/HD/NICHD NIH HHS/United States ; UL1 TR000130/TR/NCATS NIH HHS/United States ; UL1 TR001855/TR/NCATS NIH HHS/United States ; }, abstract = {Ulcerative colitis (UC) is an immune-mediated inflammation of the colonic mucosa. Gut microbiota dysbiosis may play a significant role in disease pathogenesis by causing shifts in metabolomic profiles within the gut. To identify differences and trends in the metabolomic profile of paediatric UC patients pre- and post-faecal microbiota transplants (FMT). Forty-six paediatric patients with mild-to-moderate UC and 30 healthy paediatric patients were enrolled in this study. Baseline stool samples were collected prior to FMT initiation and at months 1, 3, 6, and 12 post-FMT. Pediatric Ulcerative Colitis Activity Index (PUCAI) scores were calculated at baseline and months 1, 3, 6, and 12 after FMT. The average Bray-Curtis dissimilarities to healthy subjects decreased after FMT. In principal coordinate analysis plots, UC patients' centroids drew nearer to healthy individuals. The variance explained by phenotype (Healthy versus UC) reduced and remained significant. From 1 to 3 months after FMT, PUCAI trends were statistically significant and decreasing. PUCAI scores remain flat starting 6 months after FMT. This study concludes that paediatric UC patients have a significantly different baseline metabolite profile than healthy controls. Although being time limited, FMT significantly altered these metabolite profiles and shifted them towards that of healthy controls.}, } @article {pmid39163753, year = {2024}, author = {Wang, Z and Wang, X and Fu, L and Xu, S and Wang, X and Liao, Q and Zhuang, T and Liu, L and Zhang, H and Li, W and Xiong, A and Gu, L and Wang, Z and Wang, R and Tao, F and Yang, L and Ding, L}, title = {Shengmai San formula alleviates high-fat diet-induced obesity in mice through gut microbiota-derived bile acid promotion of M2 macrophage polarization and thermogenesis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {133}, number = {}, pages = {155938}, doi = {10.1016/j.phymed.2024.155938}, pmid = {39163753}, issn = {1618-095X}, abstract = {BACKGROUND: Shengmai San Formula (SMS) is a traditional Chinese medicine (TCM) that has been used to treat wasting-thirst regarded as diabetes mellitus, which occurs disproportionately in obese patients. Therefore, we investigated whether SMS could be used to treat obesity, and explored possible mechanisms by which it might improve glucose and fat metabolism.

METHODS: To investigate the effects of SMS on a high-fat diet (HFD)-induced obesity (DIO) model, we studied glucose metabolism via glucose tolerance testing (GTT) and insulin tolerance testing (ITT). Browning of white adipose tissue (WAT) was evaluated using H&E staining, along with browning-related gene and protein expression. Changes in bile acid (BA) levels in serum, liver, ileum, and inguinal white adipose tissue were detected by Ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In addition, antimicrobial mixture (ABX) and fecal microbial transplantation (FMT) experiments were used to verify the role of gut flora in the effects produced by SMS on HFD-induced obesity model.

RESULTS: SMS ameliorated diet-induced dyslipidemia in a dose-dependent manner and reduced glucose intolerance and insulin resistance in DIO mice, helping to restore energy metabolism homeostasis. SMS significantly altered the structure of intestinal microbiome composition, decreasing the abundance of Lactobacillus carrying bile salt hydrolase (BSH) enzymes and thereby increasing the level of conjugated BAs in the blood, ileum, and iWAT. Increased TCA content promoted the secretion of Slit3 from M2 macrophages in iWAT, which activates the protein kinase A/calmodulin-dependent protein kinase II (PKA/CaMKII) signaling pathway in sympathetic neurons via the roundabouts receptor 1(ROBO1). This pathway promotes the synthesis and release of norepinephrine (NE), inducing cyclic adenosine monophosphate (cAMP) release in adipose tissue that activates the cyclic adenosine monophosphate/protein kinase A/phosphorylated hormone-sensitive lipase (cAMP/PKA/pHSL) pathway and enhances WAT browning. ABX treatment eliminated SMS effects on glucose and lipid metabolism in DIO mice, whereas glucose and lipid metabolism in obese mice improved following SMS-FMT and increased the level of serum bile acids.

CONCLUSION: SMS affects intestinal flora and bile acid composition in vivo and increased TCA promotes M2 macrophage polarization and Slit3 release in adipose tissue. This induces NE release and increases WAT browning in obese mice, which may be a mechanism by which SMS could be used to treat obesity.}, } @article {pmid39163678, year = {2024}, author = {Wang, X and Peng, J and Cai, P and Xia, Y and Yi, C and Shang, A and Akanyibah, FA and Mao, F}, title = {The emerging role of the gut microbiota and its application in inflammatory bowel disease.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {179}, number = {}, pages = {117302}, doi = {10.1016/j.biopha.2024.117302}, pmid = {39163678}, issn = {1950-6007}, abstract = {Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex disorder with an unknown cause. However, the dysbiosis of the gut microbiome has been found to play a role in IBD etiology, including exacerbated immune responses and defective intestinal barrier integrity. The gut microbiome can also be a potential biomarker for several diseases, including IBD. Currently, conventional treatments targeting pro-inflammatory cytokines and pathways in IBD-associated dysbiosis do not yield effective results. Other therapies that directly target the dysbiotic microbiome for effective outcomes are emerging. We review the role of the gut microbiome in health and IBD and its potential as a diagnostic, prognostic, and therapeutic target for IBD. This review also explores emerging therapeutic advancements that target gut microbiome-associated alterations in IBD, such as nanoparticle or encapsulation delivery, fecal microbiota transplantation, nutritional therapies, microbiome/probiotic engineering, phage therapy, mesenchymal stem cells (MSCs), gut proteins, and herbal formulas.}, } @article {pmid39163526, year = {2024}, author = {van der Vossen, EWJ and Davids, M and Voermans, B and Wortelboer, K and Hartstra, AV and Koopen, AM and de Groot, P and Levin, E and Nieuwdorp, M}, title = {Disentangle beneficial effects of strain engraftment after fecal microbiota transplantation in subjects with MetSyn.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2388295}, pmid = {39163526}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; Male ; Middle Aged ; *Metabolic Syndrome/therapy/microbiology ; Female ; Feces/microbiology ; Bacteria/classification/isolation & purification/metabolism/genetics ; Adult ; Blood Pressure ; Treatment Outcome ; }, abstract = {Fecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strain associations through canonical correlation analysis. Integrating the metabolomics profile shows that engraftment of Collinsella aerofaciens and Fusocatenibacter saccharovorans was related to a reduction in 2-oxoarginine in plasma, which was subsequently correlated to a reduction in diastolic blood pressure. In conclusion, we applied a novel framework to elucidate on the complex and heterogenous FMT intervention, establishing a connection between engrafted microbiota and clinical outcome parameters. Our findings underscore the potential therapeutic efficacy of FMT in ameliorating MetSyn, demonstrating a potential contribution of microbial strain engraftment to the improvement of MetSyn via modulation of circulating metabolites.}, } @article {pmid39163273, year = {2024}, author = {Zhu, X and Dai, X and Zhao, L and Li, J and Zhu, Y and He, W and Guan, X and Wu, T and Liu, L and Song, H and Lei, L}, title = {Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2390136}, pmid = {39163273}, issn = {1949-0984}, mesh = {*Quercetin/pharmacology ; Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Energy Metabolism/drug effects ; *Metabolic Syndrome/metabolism/microbiology/drug therapy ; Male ; *Bile Acids and Salts/metabolism ; *Mice, Inbred C57BL ; *Thermogenesis/drug effects ; *Adipose Tissue, Brown/metabolism/drug effects ; Adipose Tissue, White/metabolism/drug effects ; Receptors, G-Protein-Coupled/metabolism/genetics ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.}, } @article {pmid39163019, year = {2024}, author = {Manithody, C and Denton, C and Mehta, S and Carter, J and Kurashima, K and Bagwe, A and Syn, M and Guzman, M and Besmer, S and Jain, S and McHale, M and Qureshi, K and Nazzal, M and Caliskan, Y and Long, J and Lin, CJ and Hutchinson, C and Ericsson, AC and Jain, AK}, title = {Intraduodenal Fecal Microbiota Transplantation Ameliorates Gut Atrophy and Cholestasis in a Novel Parenteral Nutrition Piglet Model.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00012.2024}, pmid = {39163019}, issn = {1522-1547}, support = {NIH-1R01DK131136-01//HHS | National Institutes of Health (NIH)/ ; NIH-R21AI169487-01//HHS | National Institutes of Health (NIH)/ ; NIH-1R03 DK121046-01//HHS | National Institutes of Health (NIH)/ ; NIH-P01AG078106-01//HHS | National Institutes of Health (NIH)/ ; NIH-1U01 AI163064-01//HHS | National Institutes of Health (NIH)/ ; }, abstract = {BACKGROUND: Total parenteral nutrition (TPN) provides lifesaving nutritional support intravenously; however it is associated with significant side effects. Given gut microbial alterations noted with TPN, we hypothesized that transferring fecal microbiota from healthy controls would restore gut-systemic signaling in TPN and mitigate injury.

METHODS: Using our novel ambulatory model (US Patent: US 63/136,165), 31 piglets were randomly allocated to enteral nutrition (EN), TPN only, TPN + antibiotics (TPN-A) or TPN + intraduodenal fecal microbiota transplant (TPN-FMT) for 14 days. Gut, liver, and serum were assessed through histology, biochemistry, and qPCR. Stool samples underwent 16s rRNA sequencing. PERMANOVA, Jaccard and Bray-Curtis metrics were performed.

RESULTS: Significant bilirubin elevation in TPN and TPN-A vs EN (p<0.0001) was prevented with FMT. IFN-G, TNF-alpha, IL-beta, IL-8 and LPS were significantly higher in TPN (p=0.009/0.001/0.043/0.011/<0.0001), with preservation upon FMT. Significant gut-atrophy by villous/crypt ratio in TPN (p<0.0001) and TPN-A (p=0.0001) vs EN was prevented by FMT (p=0.426 vs EN). Microbiota profiles using Principal Coordinate Analysis demonstrated significant FMT and EN overlap, with the largest separation in TPN-A followed by TPN, driven primarily by Firmicutes and Fusobacteria. TPN altered gut barrier was preserved upon FMT. Upregulated CYP7A1 and BSEP in TPN and TPN-A, and downregulatedFGFR4, EGF, FXR and TGR5 vs EN was prevented by FMT.

CONCLUSION: This study provides novel evidence of prevention of gut atrophy, liver injury and microbial dysbiosis with intraduodenal FMT, challenging current paradigms into TPN injury mechanisms and underscores importance of gut microbes as prime targets for therapeutics and drug discovery.}, } @article {pmid39162553, year = {2024}, author = {Yang, S and Tong, L and Li, X and Zhang, Y and Chen, H and Zhang, W and Zhang, H and Chen, Y and Chen, R}, title = {A novel clinically relevant human fecal microbial transplantation model in humanized mice.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0043624}, doi = {10.1128/spectrum.00436-24}, pmid = {39162553}, issn = {2165-0497}, abstract = {The intact immune system of mice exhibits resistance to colonization by exogenous microorganisms, but the gut microbiota profiles of the humanized mice and the patterns of human fecal microbiota colonization remain unexplored. Humanized NCG (huNCG) mice were constructed by injected CD34 +stem cells. 16S rRNA sequencing and fecal microbiota transplantation (FMT) technologies were used to detect the differences in microbiota and selective colonization ability for exogenous community colonization among three mice cohorts (C57BL/6J, NCG, and huNCG). Flow cytometry analysis showed that all huNCG mice had over 25% hCD45 +in peripheral blood. 16S rRNA gene sequence analysis showed that compared with NCG mice, the gut microbiota of huNCG mice were significantly altered. After FMT, the principal coordinates analysis (PCoA) showed that the gut microbial composition of huNCG mice (huNCG-D9) was similar to that of donors. The relative abundance of Firmicutes and Bacteroidetes were significantly increased in huNCG mice compared to NCG mice. Further comparison of ASV sequences revealed that Bacteroides plebeius, Bacteroides finegoldii, Escherichia fergusonii, Escherichia albertii, Klebsiella pneumoniae, and Klebsiella variicola exhibited higher abundance and stability in huNCG mice after FMT. Furthermore, PICRUSt2 analysis showed that huNCG mice had significantly enhanced metabolism and immunity. This study demonstrated that humanized mice are more conducive to colonization within the human gut microbiota, which provides a good method for studying the association between human diseases and microbiota.IMPORTANCEThe gut microbiota and biomarkers of humanized mice are systematically revealed for the first time. The finding that human fecal microbiota colonize humanized mice more stably provides new insights into the study of interactions between immune responses and gut microbiota.}, } @article {pmid39162211, year = {2024}, author = {Zhang, H and Xiao, Y and Wen, Q and Zhang, S and Li, P and Marcella, C and Hu, B and Liu, H and Zhang, F and Cui, B}, title = {Washed microbiota transplantation improved the level of serum vitamin D in ulcerative colitis.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16717}, pmid = {39162211}, issn = {1440-1746}, support = {81600417//National Natural Science Foundation of China/ ; BK20211384//Natural Science Foundation of Jiangsu Province/ ; YKK23284//Nanjing Health Technology Development Project/ ; //Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; }, abstract = {BACKGROUND AND AIM: Vitamin D (VD) deficiency was reported to correlate with ulcerative colitis (UC) activity, which might be closely related to gut microbiota dysbiosis. This study aims to investigate the effects of washed microbiota transplantation (WMT) on VD metabolism in UC.

METHODS: The serum levels of 25-hdroxyvitamin D [25(OH)D] in 121 patients with UC and 53 healthy controls (HC) were detected. Subsequently, a non-randomized control trial (non-RCT) was conducted. Patients with UC were non-randomly assigned to undergo WMT (n = 28) vs. conventional treatment (5-aminosalicylic acid, 5-ASA, n = 10). Serum levels of 25(OH)D, fecal microbiota, and the expression of vitamin D receptor (VDR) in patients with UC were evaluated with a 3-month follow-up.

RESULTS: Serum VD levels collected in the clinic practice indicated that patients with UC had significantly lower VD levels than HC (P < 0.001). In the non-RCT, serum 25(OH)D level and VDR expression significantly increased (P = 0.011, 0.026, respectively) in the WMT group, while no noticeable changes were observed in the non-WMT group. Microbiome profiling revealed that the increase in VD levels after WMT was positively associated with the abundances of Adlercreutzia_equolifaciens, Ruminococcus_obeum, and Dorea but negatively correlated with Escherichia.

CONCLUSIONS: The study suggested that WMT increases the levels of VD with characteristic changes of specific microbiota, which indicated the association between the VD and the activity of UC might be regulated by gut microbiota.}, } @article {pmid39161885, year = {2024}, author = {Wang, J and Yuan, ZY and Wang, XY and Zhu, JX and Huang, WF and Xu, GH and Yi, LT}, title = {Anthocyanins-rich cranberry extract attenuates DSS-induced IBD in an intestinal flora independent manner.}, journal = {Current research in food science}, volume = {9}, number = {}, pages = {100815}, pmid = {39161885}, issn = {2665-9271}, abstract = {Cranberry is abundantly rich in anthocyanins, a type of flavonoid with potent antioxidant properties and the resistance against certain diseases. In this study, anthocyanin-rich cranberry extract was extracted, purified, and its components were analyzed. 92.18 % of anthocyanins was obtained and the total content of anthocyanins was 302.62 mg/g after AB-8 resin purification. Quantification analysis showed that the extract mainly contained cyanidin-3-galactoside, procyanidin B2 and procyanidin B4. Then we explored its effects on dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice. The supplementation of cranberry extract resulted in an alleviation of IBD symptoms, evidenced by improvements in the disease activity index (DAI), restoration of colon length and colonic morphology. Cranberry extract reversed the elevated iron and malondialdehyde (MDA) levels and restored glutathione (GSH) levels in IBD mice. Further analysis revealed that cranberry modulated ferroptosis-associated genes and reduced expression of pro-inflammatory cytokines. Although cranberry influenced the intestinal flora balance by reducing Proteobacteria and Escherichia-Shigella, and increasing Lactobacillus, as well as enhancing SCFAs content, these effects were not entirely dependent on intestinal flora modulation, as indicated by antibiotic intervention and fecal microbiota transplantation (FMT) experiments. In conclusion, our findings suggest that the beneficial impact of cranberry extract on IBD may primarily involve the regulation of colonic ferroptosis, independent of significant alterations in intestinal flora.}, } @article {pmid39096665, year = {2024}, author = {Garg, P and Bhasin, SL and Malhotra, P and Rana, SS and Singh, S and Sethi, J and Sehgal, R and Khurana, S and Datta, P}, title = {Multiplex PCR for gastrointestinal parasites in stool: Benchmarking against direct microscopy and simplex PCR.}, journal = {Diagnostic microbiology and infectious disease}, volume = {110}, number = {2}, pages = {116475}, doi = {10.1016/j.diagmicrobio.2024.116475}, pmid = {39096665}, issn = {1879-0070}, mesh = {Humans ; *Feces/parasitology ; *Multiplex Polymerase Chain Reaction/methods ; *Sensitivity and Specificity ; *Microscopy/methods ; *Giardia lamblia/genetics/isolation & purification ; Adult ; *Entamoeba histolytica/genetics/isolation & purification ; Female ; Male ; Middle Aged ; Cryptosporidium/genetics/isolation & purification ; Child ; Young Adult ; Child, Preschool ; Intestinal Diseases, Parasitic/diagnosis/parasitology ; Adolescent ; Benchmarking ; Coinfection/parasitology/diagnosis ; Aged ; Diarrhea/parasitology/diagnosis ; Giardiasis/diagnosis/parasitology ; Molecular Diagnostic Techniques/methods ; Infant ; }, abstract = {PURPOSE: To develop and validate a multiplex conventional PCR assay to simultaneously detect Cryptosporidium spp., Entamoeba histolytica, and Giardia lamblia in diarrheal samples as a rapid, cost-effective, and sensitive diagnostic tool for prevalent co-infections for improved diagnostic accuracy and efficiency in resource-limited settings.

METHODS: Stool samples collected from patients with gastrointestinal symptoms after taking written consent, processed via wet mount, iodine mount, and PCR assays. Cohen's kappa statistical analysis was done to test agreement.

RESULT: Among 240 patients, 28.75% showed intestinal protozoa via Microscopy; Single-plex and multiplex PCR demonstrated 100% concordance, detecting 27.9%; confirmed by sequencing. Highest parasite positivity was observed in transplant and immunocompromised patients, with moderate to almost perfect agreement between microscopy and molecular methods.

CONCLUSION: Multiplex-conventional PCR offers superior sensitivity and specificity over microscopy and 100% concordance with single-plex PCR, enabling rapid, cost-effective diagnosis of multiple parasites from single stool sample. Its adoption could revolutionize parasitic infection management in routine diagnostics.}, } @article {pmid39161797, year = {2024}, author = {Taha, AM and Abouelmagd, K and Nada, SA and Mahmoud, AM and Nguyen, D and Sharma, S and Elewa, M}, title = {Impact of fecal microbiota transplantation in severe alcoholic hepatitis: A systematic review and meta-analysis.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {8}, number = {8}, pages = {e70007}, pmid = {39161797}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: Severe alcoholic hepatitis (SAH) is a serious condition with few treatments. By modifying the gut-liver axis, fecal microbiota transplantation (FMT) was proposed as a treatment for SAH. The purpose of this meta-analysis was to evaluate the efficacy of FMT versus the standard of care (SOC) in improving SAH patient survival rates.

METHODS: A thorough search of electronic databases was conducted till September 2023. The survival rates of SAH patients undergoing FMT versus SOC were compared. Using Review Manager 5.4, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

RESULTS: The meta-analysis consisted of six studies with a total of 371 patients with SAH. Patients who received FMT had significantly higher survival rates at 1 and 3 months compared to those who received SOC, with pooled OR of 2.91 (95% CI: 1.56-5.42, P = 0.0008) and 3.07 (95% CI: 1.81-5.20, P < 0.0001), respectively. However, the survival advantage disappeared after 6 months (OR: 2.96, 95% CI: 0.99-8.85, P = 0.05) and 1 year of follow-up (OR: 1.81, 95% CI: 0.44-7.46, P = 0.41).

CONCLUSION: This meta-analysis highlights the potential of FMT to significantly improve short-term survival rates in SAH patients. However, the survival benefit did not last 6-12 months. These findings call for additional research into the effectiveness of FMT over the long term, along with strategies for extending the survival benefit.}, } @article {pmid39161161, year = {2024}, author = {Yang, H and Shao, Y and Hu, Y and Qian, J and Wang, P and Tian, L and Ni, Y and Li, S and Al-Nusaif, M and Liu, C and Le, W}, title = {Fecal microbiota from patients with Parkinson's disease intensifies inflammation and neurodegeneration in A53T mice.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {8}, pages = {e70003}, pmid = {39161161}, issn = {1755-5949}, support = {YDZX20213100001002//Shanghai Municipal Central Government Funds for Guiding Local Scientific and Technological Development/ ; 32220103006//National Nature Science Foundation of China/ ; 82271524//National Nature Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Parkinson Disease/microbiology/metabolism ; Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Male ; Inflammation/metabolism/microbiology ; Feces/microbiology ; Mice, Transgenic ; Mice, Inbred C57BL ; Female ; alpha-Synuclein/metabolism ; Brain/metabolism/pathology ; }, abstract = {AIMS: We evaluated the potential of Parkinson's disease (PD) fecal microbiota transplantation to initiate or exacerbate PD pathologies and investigated the underlying mechanisms.

METHODS: We transplanted the fecal microbiota from PD patients into mice by oral gavage and assessed the motor and intestinal functions, as well as the inflammatory and pathological changes in the colon and brain. Furthermore, 16S rRNA gene sequencing combined with metabolomics analysis was conducted to assess the impacts of fecal delivery on the fecal microbiota and metabolism in recipient mice.

RESULTS: The fecal microbiota from PD patients increased intestinal inflammation, deteriorated intestinal barrier function, intensified microglia and astrocyte activation, abnormal deposition of α-Synuclein, and dopaminergic neuronal loss in the brains of A53T mice. A mechanistic study revealed that the fecal microbiota of PD patients stimulated the TLR4/NF-κB/NLRP3 pathway in both the brain and colon. Additionally, multiomics analysis found that transplantation of fecal microbiota from PD patients not only altered the composition of the gut microbiota but also influenced the fecal metabolic profile of the recipient mice.

CONCLUSION: The fecal microbiota from PD patients intensifies inflammation and neurodegeneration in A53T mice. Our findings demonstrate that imbalance and dysfunction in the gut microbiome play significant roles in the development and advancement of PD.}, } @article {pmid39161102, year = {2024}, author = {Fasano, A and Chassaing, B and Haller, D and Flores Ventura, E and Carmen-Collado, M and Pastor, N and Koren, O and Berni Canani, R}, title = {Microbiota during pregnancy and early life: role in maternal-neonatal outcomes based on human evidence.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2392009}, doi = {10.1080/19490976.2024.2392009}, pmid = {39161102}, issn = {1949-0984}, mesh = {Humans ; Pregnancy ; Female ; Infant, Newborn ; *Gastrointestinal Microbiome ; Milk, Human/microbiology ; Fecal Microbiota Transplantation ; Infant ; Host Microbial Interactions ; }, abstract = {Here, we explored the vast potential of microbiome-based interventions in preventing and managing non-communicable diseases including obesity, diabetes, allergies, celiac disease, inflammatory bowel diseases, malnutrition, and cardiovascular diseases across different life stages. We discuss the intricate relationship between microbiome and non-communicable diseases, emphasizing on the "window of opportunity" for microbe-host interactions during the first years after birth. Specific biotics and also live biotherapeutics including fecal microbiota transplantation emerge as pivotal tools for precision medicine, acknowledging the "one size doesn't' fit all" aspect. Challenges in implementation underscore the need for advanced technologies, scientific transparency, and public engagement. Future perspectives advocate for understanding maternal-neonatal microbiome, exploring the maternal exposome and delving into human milk's role in the establishment and restoration of the infant microbiome and its influence over health and disease. An integrated scientific approach, employing multi-omics and accounting for inter-individual variance in microbiome composition and function appears central to unleash the full potential of early-life microbiome interventions in revolutionizing healthcare.}, } @article {pmid39159270, year = {2024}, author = {Romaní-Pérez, M and Líebana-García, R and Flor-Duro, A and Bonillo-Jiménez, D and Bullich-Vilarrubias, C and Olivares, M and Sanz, Y}, title = {Obesity and the gut microbiota: implications of neuroendocrine and immune signaling.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.17249}, pmid = {39159270}, issn = {1742-4658}, support = {//The European Commission - NextGeneration EU/ ; CEX2021-001189-S//Spanish Ministry of Science and Innovation/ ; PID2020-119536RB-I00//Spanish Ministry of Science and Innovation/ ; }, abstract = {Obesity is a major health challenge due to its high prevalence and associated comorbidities. The excessive intake of a diet rich in fat and sugars leads to a persistent imbalance between energy intake and energy expenditure, which increases adiposity. Here, we provide an update on relevant diet-microbe-host interactions contributing to or protecting from obesity. In particular, we focus on how unhealthy diets shape the gut microbiota and thus impact crucial intestinal neuroendocrine and immune system functions. We describe how these interactions promote dysfunction in gut-to-brain neuroendocrine pathways involved in food intake control and postprandial metabolism and elevate the intestinal proinflammatory tone, promoting obesity and metabolic complications. In addition, we provide examples of how this knowledge may inspire microbiome-based interventions, such as fecal microbiota transplants, probiotics, and biotherapeutics, to effectively combat obesity-related disorders. We also discuss the current limitations and gaps in knowledge of gut microbiota research in obesity.}, } @article {pmid39158846, year = {2024}, author = {Chen, J and Song, YU and Zeng, W and Wang, L and Qin, J and Fang, L and Ding, Y}, title = {Research progress on the role of gut microbiota and its metabolites in the occurrence and development of septic-associated liver injury.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000002441}, pmid = {39158846}, issn = {1540-0514}, abstract = {Sepsis is a life-threatening organ dysfunction that occurs due to a dysregulated host response to infection. Septic-associated liver injury (SALI) has been closely linked to the prognosis and mortality of sepsis. Recent investigations have delved into the gut-liver axis and its association with SALI, identifying its pivotal role in the gut microbiota. Bacterial translocation and the onset of SALI can occur due to an imbalance in the gut microbiota, impairing the function of the gut barrier. Moreover, their metabolites might exacerbate or initiate SALI by modulating immune responses. Nevertheless, interventions to restore the balance of the gut microbiota, such as the administration of probiotics, fecal microbiota transplantation, or dietary adjustments, may ameliorate SALI and enhance the prognosis and survival rates of septic patients. This review aimed to elucidate the function of the gut microbiota in the genesis and procession of SALI and its potential therapeutic value, offering a deeper understanding of the pathogenesis and therapeutic avenues for SALI.}, } @article {pmid39158277, year = {2024}, author = {Cabirol, A and Chhun, A and Liberti, J and Kesner, L and Neuschwander, N and Schaerli, Y and Engel, P}, title = {Fecal transplant allows transmission of the gut microbiota in honey bees.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0026224}, doi = {10.1128/msphere.00262-24}, pmid = {39158277}, issn = {2379-5042}, abstract = {UNLABELLED: The study of the fecal microbiota is crucial for unraveling the pathways through which gut symbionts are acquired and transmitted. While stable gut microbial communities are essential for honey bee health, their modes of acquisition and transmission are yet to be confirmed. The gut of honey bees is colonized by symbiotic bacteria within 5 days after emergence from their wax cells as adults. Few studies have suggested that bees could be colonized in part via contact with fecal matter in the hive. However, the composition of the fecal microbiota is still unknown. It is particularly unclear whether all bacterial species can be found viable in the feces and can therefore be transmitted to newborn nestmates. Using 16S rRNA gene amplicon sequencing, we revealed that the composition of the honey bee fecal microbiota is strikingly similar to the microbiota of entire guts. We found that fecal transplantation resulted in gut microbial communities similar to those obtained from feeding gut homogenates. Our study shows that fecal sampling and transplantation are viable tools for the non-invasive analysis of bacterial community composition and host-microbe interactions. It also implies that contact of young bees with fecal matter in the hive is a plausible route for gut microbiota acquisition.

IMPORTANCE: Honey bees are crucial pollinators for many crops and wildflowers. They are also powerful models for studying microbiome-host interactions. However, current methods rely on gut tissue disruption to analyze microbiota composition and use gut homogenates to inoculate microbiota-deprived bees. Here, we provide two new and non-invasive approaches that will open doors to longitudinal studies: fecal sampling and transplantation. Furthermore, our findings provide insights into gut microbiota transmission in social insects by showing that ingestion of fecal matter can result in gut microbiota acquisition.}, } @article {pmid39157730, year = {2024}, author = {Ceccon, M and Kantsjö, JB and Ronchi, F}, title = {Personalized Paths: Unlocking Alzheimer's via the Gut-Brain Axis.}, journal = {Visceral medicine}, volume = {40}, number = {4}, pages = {194-209}, pmid = {39157730}, issn = {2297-4725}, abstract = {BACKGROUND: Alzheimer's disease (AD) is characterised by abnormal protein aggregates in the brain that lead to cognitive decline. While current therapies only treat symptoms, disease-modifying treatments are urgently needed. Studies suggest that the composition of the microbiota is altered in people with AD, suggesting a link between gut bacteria and AD-related brain changes.

SUMMARY: In our narrative review, we explore various microbial interventions, such as faecal microbiota transplantation, probiotics, and diet, as powerful potential treatments. Studies suggest changes in microbiota composition following these interventions, with some beneficial effects on cognitive function. However, the mechanism of action of these microbial interventions is still unknown.

KEY MESSAGE: Our aim was to highlight the importance of personalised approaches, taking into account individual metabolic and microbiome profiles. We try to address gaps in current research and emphasise the need for microbiota analysis at different stages of the disease and its integration with clinical parameters and lifestyle information for a comprehensive understanding of AD progression (summarised in online suppl. Fig. 1; for all online suppl. material, see https://doi.org/10.1159/000535869).}, } @article {pmid39155775, year = {2024}, author = {Jarasvaraparn, C and Rodrigo, M and Hartley, C and Karnsakul, W}, title = {Exploring Odevixibat's efficacy in alagille syndrome: insights from recent clinical trials and IBAT Inhibitor Experiences.}, journal = {Expert opinion on pharmacotherapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14656566.2024.2392873}, pmid = {39155775}, issn = {1744-7666}, abstract = {INTRODUCTION: Alagille syndrome (ALGS) is a rare, genetic, multisystem disorder commonly associated with cholestatic liver disease; patients with ALGS may experience elevated serum bile acids and severe pruritus with associated impaired sleep. The ileal bile acid transporter (IBAT) is located on the luminal surface of enterocytes in the terminal ileum; this transport protein mediates resorption of conjugated bile acids for recirculation back to the liver. Inhibition of IBAT disrupts the enterohepatic circulation and leads to fecal elimination of bile acids.

AREAS COVERED: Here, the role of odevixibat as a novel, nonsurgical approach to interrupting the enterohepatic circulation from the intestine by inhibition of IBAT is reviewed, specifically in reference to currently available data on pharmacologic IBAT inhibition. IBAT inhibition has been shown to reduce serum bile acids and pruritus in trials of cholestatic liver diseases in children including ALGS.

EXPERT OPINION: Odevixibat or IBAT inhibitor should be considered as a first-line treatment for ALGS to improve pruritis, quality of life and liver-related outcomes including absence of liver transplant, surgical biliary diversion, hepatic decompensation, and death.}, } @article {pmid39154362, year = {2024}, author = {Feng, R and Yang, W and Feng, W and Huang, X and Cen, M and Peng, G and Wu, W and Wang, Z and Jing, Y and Long, T and Liu, Y and Li, Z and Chang, G and Huang, K}, title = {Time-restricted feeding ameliorates non-alcoholic fatty liver disease through modulating hepatic nicotinamide metabolism via gut microbiota remodeling.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2390164}, pmid = {39154362}, issn = {1949-0984}, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/metabolism/microbiology ; *Gastrointestinal Microbiome ; Mice ; *Liver/metabolism ; *Diet, High-Fat/adverse effects ; Male ; *Niacinamide/metabolism ; *Mice, Inbred C57BL ; Disease Models, Animal ; Lipid Metabolism ; Aldehyde Oxidase/metabolism ; Lipogenesis ; Hepatocytes/metabolism ; Humans ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health concern, lacking specific therapeutic strategies. Time-restricted feeding (TRF) regimen demonstrated beneficial effects in NAFLD; however, the underlying mechanisms remain unclear. In this study, we established a NAFLD mouse model through a high-fat diet (HFD) and implemented the 16:8 TRF regimen for a duration of 6 weeks. We demonstrated that TRF remarkably alleviated hepatic steatosis in HFD mice. Of note, aldehyde oxidase 1 (AOX1), a key enzyme in hepatic nicotinamide (NAM) catabolism, exhibited apparent upregulation in response to HFD, leading to abnormal accumulation of N-Methyl-6-pyridone-3-carboxamide (N-Me-6-PY, also known as 2PY) and N-Methyl-4-pyridone-5-carboxamide (N-Me-4-PY, also known as 4PY), whereas it was almost restored by TRF. Both N-Me-6-PY and N-Me-4-PY promoted de novo lipogenesis and fatty acid uptake capacities in hepatocyte, and aggravated hepatic steatosis in mice either fed chow diet or HFD. In contrast, pharmacological inhibition of AOX1 was sufficient to ameliorate the hepatic steatosis and lipid metabolic dysregulation induced by HFD. Moreover, transplantation of fecal microbiota efficiently mimicked the modulatory effect of TRF on NAM metabolism, thus mitigating hepatic steatosis and lipid metabolic disturbance, suggesting a gut microbiota-dependent manner. In conclusion, our study reveals the intricate relationship between host NAM metabolic modification and gut microbiota remodeling during the amelioration of NAFLD by TRF, providing promising insights into the prevention and treatment of NAFLD.}, } @article {pmid39153277, year = {2024}, author = {Huang, Y and Chen, H and Chen, J and Wu, Q and Zhang, W and Li, D and Lu, Y and Chen, Y}, title = {Yellow tea polysaccharides protect against non-alcoholic fatty liver disease via regulation of gut microbiota and bile acid metabolism in mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {133}, number = {}, pages = {155919}, doi = {10.1016/j.phymed.2024.155919}, pmid = {39153277}, issn = {1618-095X}, abstract = {BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major clinical and global public health issue, with no specific pharmacological treatment available. Currently, there is a lack of approved drugs for the clinical treatment of NAFLD. Large-leaf yellow tea polysaccharides (YTP) is a natural biomacromolecule with excellent prebiotic properties and significant therapeutic effects on multiple metabolic diseases. However, the specific mechanisms by which YTP regulates NAFLD remain unclear.

PURPOSE: This study aims to explore the prebiotic effects of YTP and the potential mechanisms by which it inhibits hepatic cholesterol accumulation in NAFLD mice.

METHODS: The effects of YTP on lipid accumulation were evaluated in NAFLD mice through obesity trait analysis and bile acids (BAs) metabolism assessment. Additionally, fecal microbiota transplantation (FMT) was performed, and high-throughput sequencing was employed to investigate the mechanisms underlying YTP's regulatory effects on gut microbiota and BA metabolism.

RESULTS: Our study demonstrated that YTP altered the constitution of colonic BA, particularly increasing the levels of conjugated BA and non-12OH BA, which suppressed ileum FXR receptors and hepatic BA reabsorption, facilitated BA synthesis, and fecal BA excretion. The modifications were characterized by a decrease in the levels of FXR, FGF15, FGFR4, and ASBT proteins, and an increase in the levels of Cyp7a1 and Cyp27a1 proteins. YTP might affect enterohepatic circulation and by the activated the hepatic FXR-SHP pathway. Meanwhile, YTP reshaped the intestinal microbiome structure by decreasing BSH-producing genera and increasing taurine metabolism genera. The correlation analysis implied that Muribaculaceae, Pseudomonas, acterium_coprostanoligenes_group, Clostridiales, Lachnospiraceae_NK4A136_group, Delftia, Dubosiella, and Romboutsia were strongly correlated with specific BA monomers.

CONCLUSIONS: YTP modulates bile salt hydrolase-related microbial genera to activate alternative bile acid synthesis pathways, thereby inhibiting NAFLD progression. These results suggest that YTP may serve as a potential probiotic formulation, offering a feasible dietary intervention for NAFLD.}, } @article {pmid39152200, year = {2024}, author = {Han, Z and Sun, J and Jiang, B and Chen, K and Ge, L and Sun, Z and Wang, A}, title = {Fecal microbiota transplantation accelerates restoration of florfenicol-disturbed intestinal microbiota in a fish model.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {1006}, pmid = {39152200}, issn = {2399-3642}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Thiamphenicol/analogs & derivatives/pharmacology ; *Fecal Microbiota Transplantation ; *Dysbiosis/therapy/microbiology ; *Anti-Bacterial Agents/pharmacology/adverse effects ; Carps/microbiology ; Bacteria/metabolism/drug effects ; }, abstract = {Antibiotic-induced dysbiosis in the fish gut causes significant adverse effects. We use fecal microbiota transplantation (FMT) to accelerate the restoration of florfenicol-perturbed intestinal microbiota in koi carp, identifying key bacterial populations and metabolites involved in the recovery process through microbiome and metabolome analyses. We demonstrate that florfenicol disrupts intestinal microbiota, reducing beneficial genera such as Lactobacillus, Bifidobacterium, Bacteroides, Romboutsia, and Faecalibacterium, and causing mucosal injuries. Key metabolites, including aromatic amino acids and glutathione-related compounds, are diminished. We show that FMT effectively restores microbial populations, repairs intestinal damage, and normalizes critical metabolites, while natural recovery is less effective. Spearman correlation analyses reveal strong associations between the identified bacterial genera and the levels of aromatic amino acids and glutathione-related metabolites. This study underscores the potential of FMT to counteract antibiotic-induced dysbiosis and maintain fish intestinal health. The restored microbiota and normalized metabolites provide a basis for developing personalized probiotic therapies for fish.}, } @article {pmid39150086, year = {2024}, author = {Di Stefano, M}, title = {Fecal Microbiota Transplantation in the Treatment of Severe Constipation in Children: Is It the Future?.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {39150086}, issn = {1572-0241}, } @article {pmid39147234, year = {2024}, author = {Li, Z and Sun, T and He, Z and Li, Z and Xiong, J and Xiang, H}, title = {Intestinal dysbacteriosis contributes to persistent cognitive impairment after resolution of acute liver failure.}, journal = {The American journal of pathology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajpath.2024.07.014}, pmid = {39147234}, issn = {1525-2191}, abstract = {Regulating the gut microbiota alleviates hepatic encephalopathy (HE). It remains unclear whether it is imperative to withhold treatment for microbial imbalance after liver functional recovery. This work aims to elucidate the alterations in cognitive behavior, liver function, synaptic transmission, and brain metabolites in acute liver failure(ALF) mice before and after hepatic function recovery. Here, thioacetamide was injected intraperitoneally to establish an ALF mouse model, which induced HE. By performing hierarchical clustering analysis, we found that the liver functions normalized, but cognitive dysfunction and intestinal dysbacteriosis were found in the ALF mice 14 days after thioacetamide injection. Additionally, fecal microbiota transplant from the ALF mice with liver function recovery could induce liver injury and cognitive impairment. Moreover, we found alterations in synaptic transmission in the ALF mice with liver function improvement, and the correlations between the gut bacteria and synaptic transmission in the cortex were significant. Finally, we detected apparent alterations in the brain metabolic profiles of the ALF mice after liver function improvement by performing [1]H nuclear magnetic resonance spectroscopy, suggesting a risk of HE. These results showed that intestinal dysbacteriosis in ALF mice with liver function recovery is sufficient to induce liver injury and cognitive impairment. These results indicated continuous care may be necessary for monitoring microbial imbalance even in ALF-induced HE patients whose liver function has recovered significantly.}, } @article {pmid39146793, year = {2024}, author = {Sartor, RB}, title = {Microbiome modification for personalized treatment of dysbiotic diseases.}, journal = {Cell host & microbe}, volume = {32}, number = {8}, pages = {1219-1224}, doi = {10.1016/j.chom.2024.07.023}, pmid = {39146793}, issn = {1934-6069}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Dysbiosis/therapy ; *Precision Medicine/methods ; *Gastrointestinal Microbiome ; Clostridium Infections/therapy/microbiology ; Inflammation ; Clostridioides difficile ; Biomarkers ; }, abstract = {Fecal microbial transplantation (FMT) for inflammatory diseases or refractory immune checkpoint inhibitor therapy is less effective than for preventing recurrent Clostridioides difficile infection. This commentary outlines strategies to use biomarkers of successful FMT to guide newer approaches to restore microbial homeostasis in individuals with dysbiosis-mediated inflammation.}, } @article {pmid39146792, year = {2024}, author = {Chambers, L and Grencewicz, D and Spakowicz, D}, title = {From poo to promise: Fecal microbiota transplants support immunotherapy re-sensitization in solid tumors.}, journal = {Cell host & microbe}, volume = {32}, number = {8}, pages = {1217-1218}, doi = {10.1016/j.chom.2024.07.015}, pmid = {39146792}, issn = {1934-6069}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use ; Gastrointestinal Microbiome/immunology ; Melanoma/therapy/immunology ; Neoplasms/therapy/immunology ; Esophageal Neoplasms/therapy/immunology/microbiology ; Carcinoma, Hepatocellular/therapy/immunology/microbiology ; Liver Neoplasms/therapy/immunology ; Animals ; Feces/microbiology ; }, abstract = {Fecal microbiota transplants (FMTs) recently entered the cancer therapeutics field as a method to resensitize treatment-resistant melanoma patients to immune checkpoint inhibitors (ICIs). In this issue of Cell Host & Microbe, Kim and colleagues extend its utility to other solid tumors, including esophageal and hepatocellular carcinomas.[1].}, } @article {pmid39141079, year = {2024}, author = {Suárez-Carantoña, C and Corbacho-Loarte, MD and Del Campo Albendea, L and Kamel-Rey, S and Halperin, AV and Escudero-Sánchez, R and Ponce-Alonso, M and Moreno, S and Cobo, J}, title = {Is advanced age still a risk factor for recurrence of C. difficile infection in the era of new treatments?.}, journal = {Age and ageing}, volume = {53}, number = {8}, pages = {}, doi = {10.1093/ageing/afae182}, pmid = {39141079}, issn = {1468-2834}, mesh = {Humans ; Male ; Aged, 80 and over ; *Clostridium Infections/epidemiology/mortality/microbiology/therapy/diagnosis/drug therapy ; Female ; Retrospective Studies ; Risk Factors ; *Recurrence ; Aged ; Age Factors ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; Middle Aged ; Fidaxomicin/therapeutic use ; Broadly Neutralizing Antibodies/therapeutic use ; Antibodies, Monoclonal ; }, abstract = {BACKGROUND: Advanced age has been widely identified as a risk factor for recurrent Clostridioides difficile infection (CDI), but most related studies were performed before the introduction of novel therapies. The aim of this study was to compare CDI characteristics and outcomes in patients over and under 80 years old with CDI and their outcomes in the era of new treatments.

METHODS: This was a retrospective cohort study of patients diagnosed with CDI from January 2021 to December 2022 in an academic hospital. We compared recurrence and mortality at 12 weeks after the end of treatment. An extension of the Fine and Grey model adjusted for competing events was used to assess the effect of age on recurrence.

RESULTS: Four hundred seventy-six patients were considered to have CDI (320 in patients <80 years and 156 in ≥80 years). CDI in older patients was more frequently healthcare-associated and was more severe. Although the Charlson index was almost identical between populations, comorbidities clearly differed. New treatments (bezlotoxumab, fidaxomicin and faecal microbiota transplantation) were more frequently used in older patients without statistical significance (41.3% vs. 33.4%, P = .053). There were 69 (14.5%) recurrences, with no differences by age group after adjusting for competing events. Mortality was greater in the oldest (35.3%) than in the youngest (13.1%); P < .001.

CONCLUSIONS: No differences in CDI recurrence rates were found between age groups. However, there was a high mortality rate in patients ≥80 years old, which emphasises the urgent need to improve the prevention and treatment of CDI in this group.}, } @article {pmid39141021, year = {2024}, author = {Mirzababaei, M and Babaei, F and Ghafghazi, S and Rahimi, Z and Asadi, S and Dargahi, L and Nassiri-Asl, M and Haghnazari, L}, title = {Saccharomyces Boulardii alleviates neuroinflammation and oxidative stress in PTZ-kindled seizure rat model.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {39141021}, issn = {1432-1912}, support = {50000886//Kermanshah University of Medical Sciences/ ; }, abstract = {Previous research have reported that modulating the gut microbiome composition by fecal microbiota transplantation and probiotic administration can alleviate seizure occurrence and severity. Saccharomyces boulardii (SB) is a yeast probiotic that has demonstrated ameliorating effects on anxiety, memory and cognitive deficit, and brain amyloidogenesis. In this research, our goal was to examine the anti-seizure effects of SB on the pentylenetetrazole (PTZ)-kindled male Wistar rats. The animals were randomly categorized into four test groups. The rats were orally administered with saline (control and PTZ groups) or S. boulardii (SB + PTZ and SB groups) for 57 days. From the 29th day of the experiment, the animals received intraperitoneally saline (control and SB groups) or PTZ (PTZ and SB + PTZ groups) on alternate days for 30 days. The administration dose of SB and PTZ was 10[10] CFU/ml/day and 35 mg/kg, respectively. We assessed animal seizure behavior, neuroinflammation, oxidative stress, and the levels of matrix metalloproteinase-9 (MMP-9) and brain-derived neurotrophic factor (BDNF) in the hippocampus tissue. S. boulardii hindered the PTZ-induced kindling development. SB treatment elevated glutathione (GSH) and total antioxidant capacity (TAC) and reduced malondialdehyde (MDA) levels. SB also lessened the hippocampal levels of BDNF and MMP-9. Following SB supplementation, proinflammatory cytokines interleukin-1 beta (IL-1β) and IL-6 were lowered, and anti-inflammatory cytokine IL-10 was enhanced. Overall, our data indicated, for the first time, the positive impact of SB on the PTZ-kindled seizure rat model. The anti-seizure activity of SB was mediated by modulating oxidative stress, neuroinflammation, and MMP-9 and BDNF levels.}, } @article {pmid39140343, year = {2024}, author = {Wang, R and Huang, G and Li, S and Huang, H and Zhu, G and Wang, L and Yang, J and Yang, S and Jiang, Z and Zhang, W}, title = {Blueberry extract for the treatment of ischaemic stroke through regulating the gut microbiota and kynurenine metabolism.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8300}, pmid = {39140343}, issn = {1099-1573}, support = {0001/2023/AKP//Science and Technology Development Fund, Macau SAR/ ; 006/2023/SKL//Science and Technology Development Fund, Macau SAR/ ; }, abstract = {Although the gut microbiota and kynurenine (KYN) metabolism have significant protective effects against ischaemic stroke (IS), the exact mechanism has yet to be fully elucidated. Combined serum metabolomics and 16S rRNA gene sequencing were used to reveal the differences between the gut microbiota and metabolites in rats treated with or without blueberry extract. Faecal microbiota transplantation (FMT) was employed to validate the protective role of the gut microbiota in IS. Furthermore, the interaction between Prevotella and IS was also confirmed in patients. Rats with IS experienced neurological impairments accompanied by an impaired intestinal barrier and disturbed intestinal flora, which further contributed to heightened inflammatory responses. Furthermore, Prevotella played a critical role in IS pathophysiology, and a positive correlation between Prevotella and KYN was detected. The role of KYN metabolism in IS was further demonstrated by the finding that IDO was significantly upregulated and that the use of the IDO inhibitor, attenuated KYN metabolic pathway activity and ameliorated neurological damage in rats with IS. Prevotella intervention also significantly improved stroke symptoms and decreasing KYN levels in rats with IS. FMT showed that the beneficial effects of blueberry extract on IS involve gut bacteria, especially Prevotella, which were confirmed by microbiological analyses conducted on IS patients. Moreover, blueberry extract led to significant changes in kynurenic acid levels and tryptophan and IDO levels through interactions with Prevotella. Our study demonstrates for the first time that blueberry extract could modulate "intestinal microecology-KYN metabolism" to improve IS.}, } @article {pmid39139438, year = {2024}, author = {Jing, L and Zhang, H and Xiang, Q and Hu, H and Zhai, C and Xu, S and Tian, H}, title = {Role of Trimethylamine N-Oxide in Heart Failure.}, journal = {Reviews in cardiovascular medicine}, volume = {25}, number = {7}, pages = {240}, pmid = {39139438}, issn = {2153-8174}, abstract = {Heart failure (HF) is a clinical syndrome characterizing by typical physical signs and symptomatology resulting from reduced cardiac output and/or intracardiac pressure at rest or under stress due to structural and/or functional abnormalities of the heart. HF is often the final stage of all cardiovascular diseases and a significant risk factor for sudden cardiac arrest, death, and liver or kidney failure. Current pharmacological treatments can only slow the progression and recurrence of HF. With advancing research into the gut microbiome and its metabolites, one such trimethylamine N-oxide (TMAO)-has been implicated in the advancement of HF and is correlated with poor prognosis in patients with HF. However, the precise role of TMAO in HF has not yet been clarified. This review highlights and concludes the available evidence and potential mechanisms associated with HF, with the hope of contributing new insights into the diagnosis and prevention of HF.}, } @article {pmid39138075, year = {2024}, author = {Yeom, M and Ahn, S and Hahm, DH and Jang, SY and Jang, SH and Park, SY and Jang, JH and Park, J and Oh, JY and Lee, IS and Kim, K and Kwon, SK and Park, HJ}, title = {Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice.}, journal = {Journal of integrative medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.joim.2024.07.004}, pmid = {39138075}, issn = {2095-4964}, abstract = {OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome. Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events, but its underlying mechanism is not completely understood. The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent.

METHODS: AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse. Acupuncture was done at the Gok-Ji (LI11) acupoints. AD-like symptoms were assessed by lesion scores, scratching behavior, and histopathological changes; intestinal barrier function was measured by fecal output, serum lipopolysaccharide levels, histopathological changes, and mRNA expression of markers involved in intestinal permeability and inflammation. Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples.

RESULTS: Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening, and also significantly altered gut microbiota structure as revealed by β-diversity indices and analysis of similarities. These beneficial effects were eliminated by antibiotic depletion of gut microbiota, but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice. Interestingly, AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability, atrophy of the mucosal structure (reduced villus height and crypt depth), decreased expression of tight junctions and mucus synthesis genes, and increased expression of inflammatory mediators in the ileum. Acupuncture attenuated these abnormalities, which was gut microbiota-dependent.

CONCLUSION: Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier, providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD. Please cite this article as: Yeom M, Ahn S, Hahm DH, Jang SY, Jang SH, Park SY, Jang JH, Park J, Oh JY, Lee IS, Kim K, Kwon SK, Park HJ. Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice. J Integr Med. 2024; Epub ahead of print.}, } @article {pmid39137736, year = {2024}, author = {Cui, S and Huang, Q and Li, T and Shen, W and Chen, X and Sun, X}, title = {Reduction in renal interstitial fibrosis in aged male mice by intestinal microbiota rejuvenation.}, journal = {Gerontology}, volume = {}, number = {}, pages = {}, doi = {10.1159/000540839}, pmid = {39137736}, issn = {1423-0003}, abstract = {INTRODUCTION: Renal interstitial fibrosis is an important pathological basis for kidney ageing and the progression of ageing nephropathy. In the present research, we established an aged mouse model of faecal microbiota transplantation (FMT), identified the rejuvenation features of the kidney in aged male mice, and preliminarily analysed the possible mechanism by which the rejuvenation of the intestinal microbiota reduces renal interstitial fibrosis and delays senescence in aged male mice.

METHODS: We established an aged male mice model that was treated with FMT (FMT-Old) and a normal aged male mice control group (Old). Differentially expressed cytokines were identified using a cytokine array, and changes in protein expression related to signal transduction pathways in renal tissues were detected using a signalling pathway array. Senescence-associated β-galactosidase and Masson staining were performed to observe the degrees of renal senescence and tubule interstitial fibrosis. Immunohistochemistry was utilized to detect changes in the expression of the ageing markers p53 and p21 and the inflammation-related protein nuclear factor (NF) κB p65 subunit (RelA/p65).

RESULTS: The pathological features of renal senescence in the FMT-Old group were significantly alleviated, and the levels of the ageing indicators p53 and p21 were decreased (P < 0.05). Integrated predictive analysis revealed that six differentially expressed cytokines, macrophage inflammatory protein-3 beta (MIP-3β or CCL-19), E-selectin, Fas ligand, C-X-C motif chemokine 11 (CXCL-11 or I-TAC), CXCL-1 (keratinocyte-derived chemokine), and CCL-3 (MIP-1α) were related to a common upstream regulatory protein, RelA/p65, and the expression of this protein was significantly different between groups according to the signalling pathway array.

CONCLUSION: Our findings suggest that the intestinal microbiota regulates the renal microenvironment by reducing immune inflammatory responses through the inhibition of the NF-κB signalling pathway, thereby delaying renal senescence in aged male mice.}, } @article {pmid39135690, year = {2024}, author = {Li, J and Wang, SY and Yan, KX and Wang, P and Jiao, J and Wang, YD and Chen, ML and Dong, Y and Zhong, JC}, title = {Intestinal microbiota by angiotensin receptor blocker therapy exerts protective effects against hypertensive damages.}, journal = {iMeta}, volume = {3}, number = {4}, pages = {e222}, pmid = {39135690}, issn = {2770-596X}, abstract = {Dysbiosis of the gut microbiota has been implicated in hypertension, and drug-host-microbiome interactions have drawn considerable attention. However, the influence of angiotensin receptor blocker (ARB)-shaped gut microbiota on the host is not fully understood. In this work, we assessed the alterations of blood pressure (BP), vasculatures, and intestines following ARB-modified gut microbiome treatment and evaluated the changes in the intestinal transcriptome and serum metabolome in hypertensive rats. Hypertensive patients with well-controlled BP under ARB therapy were recruited as human donors, spontaneously hypertensive rats (SHRs) receiving normal saline or valsartan were considered animal donors, and SHRs were regarded as recipients. Histological and immunofluorescence staining was used to assess the aorta and small intestine, and 16S rRNA amplicon sequencing was performed to examine gut bacteria. Transcriptome and metabonomic analyses were conducted to determine the intestinal transcriptome and serum metabolome, respectively. Notably, ARB-modified fecal microbiota transplantation (FMT), results in marked decreases in systolic BP levels, collagen deposition and reactive oxygen species accumulation in the vasculature, and alleviated intestinal structure impairments in SHRs. These changes were linked with the reconstruction of the gut microbiota in SHR recipients post-FMT, especially with a decreased abundance of Lactobacillus, Aggregatibacter, and Desulfovibrio. Moreover, ARB-treated microbes contributed to increased intestinal Ciart, Per1, Per2, Per3, and Cipc gene levels and decreased Nfil3 and Arntl expression were detected in response to ARB-treated microbes. More importantly, circulating metabolites were dramatically reduced in ARB-FMT rats, including 6beta-Hydroxytestosterone and Thromboxane B2. In conclusion, ARB-modified gut microbiota exerts protective roles in vascular remodeling and injury, metabolic abnormality and intestinal dysfunctions, suggesting a pivotal role in mitigating hypertension and providing insights into the cross-talk between antihypertensive medicines and the gut microbiome.}, } @article {pmid39135376, year = {2024}, author = {Wang, J and Jiang, M and Li, X and Ye, Y and Xie, Y and Wu, T and Chen, Y and Yu, H and Wu, H and Yang, Z and Zhou, E}, title = {Inulin Supplementation Alleviates Ochratoxin A-Induced Kidney Injury through Modulating Intestinal Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c04382}, pmid = {39135376}, issn = {1520-5118}, abstract = {Ochratoxin A (OTA) is a prevalent mycotoxin found in feed that causes significant kidney injury in animals. Further investigation was needed to devise strategies for treating OTA-induced kidney damage through the gut-kidney axis. Evidence indicates the crucial role of intestinal microbiota in kidney damage development. Inulin, a dietary fiber, protects kidneys by modulating intestinal microbiota and promoting short-chain fatty acid (SCFA) production. However, its precise mechanism in OTA-induced kidney damage remained unclear. In this study, chickens were orally administered OTA and inulin for 2 weeks to investigate inulin's effects on OTA-induced kidney damage and underlying mechanisms. The alteration of intestinal microbiota, SCFAs contents, and SCFA receptors was further analyzed. Results demonstrated that inulin supplementation influenced intestinal microbiota, increased SCFAs production, and mitigated OTA-induced kidney damage in chickens. The importance of microbiota in mediating inulin's renal protection was further confirmed by antibiotic and fecal microbiota transplantation experiments. Additionally, inulin exhibited antioxidant and anti-inflammatory properties, alleviating NLRP3 inflammasome activation and pyroptosis. In summary, inulin protected chickens from OTA-induced kidney damage, which might provide a potential strategy to mitigate the harmful effects of mycotoxins through prebiotics and safeguard renal health.}, } @article {pmid39135306, year = {2024}, author = {Zuo, S and Huang, Y and Zou, J}, title = {The role of the gut microbiome in modulating immunotherapy efficacy in colorectal cancer.}, journal = {IUBMB life}, volume = {}, number = {}, pages = {}, doi = {10.1002/iub.2908}, pmid = {39135306}, issn = {1521-6551}, support = {2023AH051777//Key Project in Natural Science Research in Higher Education Institutions of Anhui Province/ ; WK2022ZF29//Key Project of Natural Science Foundation of Wannan Medical College/ ; WHWJ2023z007//Key Research Project of Wuhu Municipal Health Commission/ ; DFJH2022018//Climbing Scientific Peak Project for Talents, the Second Affiliated Hospital of Wannan Medical College/ ; }, abstract = {This systematic literature review and meta-analysis provide an overview of the critical role of gut microbiota in modulating the efficacy of immunotherapy for colorectal cancer. Gut microbes influence host immune responses through multiple mechanisms including modulation of immune cell activity, metabolite action, and immune tolerance. The ability of specific gut microbes to improve the efficacy of immune checkpoint inhibitors has been linked to their ability to improve gut barrier function, modulate immune cell activity, and produce key immunomodulatory metabolites such as short-chain fatty acids. In addition, the composition and diversity of the gut microbiota are strongly associated with the efficacy of immunotherapies, demonstrating the potential to improve therapeutic response by modifying the gut microbiota. This paper also discusses the prospect of manipulating the gut microbiota through strategies such as fecal microbial transplantation, probiotic supplementation, and dietary modifications to optimize the efficacy of immunotherapy.}, } @article {pmid39134825, year = {2024}, author = {Ni, Y and Tong, Q and Xu, M and Gu, J and Ye, H}, title = {Gut Microbiota-Induced Modulation of the Central Nervous System Function in Parkinson's Disease Through the Gut-Brain Axis and Short-Chain Fatty Acids.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39134825}, issn = {1559-1182}, support = {Y20170064//Wenzhou Science and Technology Bureau Project/ ; }, abstract = {Recent insights into Parkinson's disease (PD), a progressive neurodegenerative disorder, suggest a significant influence of the gut microbiome on its pathogenesis and progression through the gut-brain axis. This study integrates 16S rRNA sequencing, high-throughput transcriptomic sequencing, and animal model experiments to explore the molecular mechanisms underpinning the role of gut-brain axis in PD, with a focus on short-chain fatty acids (SCFAs) mediated by the SCFA receptors FFAR2 and FFAR3. Our findings highlighted prominent differences in the gut microbiota composition between PD patients and healthy individuals, particularly in taxa such as Escherichia_Shigella and Bacteroidetes, which potentially impact SCFA levels through secondary metabolite biosynthesis. Notably, fecal microbiota transplantation (FMT) from healthy to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models significantly improved motor function, enhanced dopamine and serotonin levels in the striatum, and increased the number of dopaminergic neurons in the substantia nigra while reducing glial cell activation. This therapeutic effect was associated with increased levels of SCFAs such as acetate, propionate, and butyrate in the gut of MPTP-lesioned mice. Moreover, transcriptomic analyses revealed upregulated expression of FFAR2 and FFAR3 in MPTP-lesioned mice, indicating their crucial role in mediating the benefits of FMT on the central nervous system. These results provide compelling evidence that gut microbiota and SCFAs play a critical role in modulating the gut-brain axis, offering new insights into PD's etiology and potential targets for therapeutic intervention.}, } @article {pmid38019088, year = {2024}, author = {Feuerstadt, P and Crawford, CV and Tan, X and Pokhilko, V and Bancke, L and Ng, S and Guthmueller, B and Bidell, MR and Tillotson, G and Johnson, S and Skinner, AM}, title = {Fecal Microbiota, Live-jslm for the Prevention of Recurrent Clostridioides difficile Infection : Subgroup Analysis of PUNCH CD2 and PUNCH CD3.}, journal = {Journal of clinical gastroenterology}, volume = {58}, number = {8}, pages = {818-824}, pmid = {38019088}, issn = {1539-2031}, support = {IK2 BX005609/BX/BLRD VA/United States ; }, mesh = {Humans ; *Clostridium Infections/prevention & control/microbiology ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Male ; Female ; Middle Aged ; *Anti-Bacterial Agents/administration & dosage/adverse effects ; Adult ; *Clostridioides difficile/isolation & purification ; Aged ; Feces/microbiology ; Recurrence ; Bayes Theorem ; Treatment Outcome ; Gastrointestinal Microbiome ; Vancomycin/administration & dosage/therapeutic use ; Risk Factors ; Secondary Prevention/methods ; }, abstract = {GOALS: To assess fecal microbiota, live-jslm (REBYOTA, abbreviated as RBL, formerly RBX2660) efficacy and safety in participants grouped by recurrent Clostridioides difficile infection (rCDI) risk factors and treatment-related variables.

BACKGROUND: RBL is the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration for the prevention of rCDI in adults after antibiotic treatment for rCDI.

STUDY: Treatment success rates across subgroups for PUNCH CD3 (NCT03244644) were estimated using a Bayesian hierarchical model, borrowing data from PUNCH CD2 (NCT02299570). Treatment-emergent adverse events were summarized for the double-blind treatment period within 8 weeks.

RESULTS: Treatment differences between RBL and placebo at 8 weeks were similar to the total population for most subgroups. Treatment effect sizes were similar between CDI tests, higher for oral vancomycin courses >14 days versus ≤14 days and higher for antibiotic washout periods of 3 days versus ≤2 days. The largest reductions in the rate of rCDI with RBL versus placebo were observed for participants with a 3-day CDI antibiotic washout period and participants with ≥4 previous CDI episodes. Most RBL-treated participants experienced TEAEs that were mild or moderate in severity and related to preexisting conditions.

CONCLUSION: This analysis provides further evidence of RBL efficacy and safety across subgroups, including those at high risk for rCDI.}, } @article {pmid39130120, year = {2023}, author = {Kahan, T and Chandan, S and Khan, SR and Deliwala, S and Chang, S and Axelrad, J and Shaukat, A}, title = {Safety and Efficacy of Fecal Microbiota Transplant in Chronic Pouchitis-A Systematic Review With Meta-Analysis.}, journal = {Gastro hep advances}, volume = {2}, number = {6}, pages = {843-852}, pmid = {39130120}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Pouchitis is the most common long-term complication after ileal-pouch anal anastomosis in patients with ulcerative colitis. We conducted a systematic review and meta-analysis evaluating the safety and efficacy of fecal microbiota transplant (FMT) in chronic antibiotic dependent and refractory pouchitis.

METHODS: Multiple databases were searched through April 2022 for studies that reported the efficacy and safety of FMT in patients with chronic pouchitis. Meta-analysis using random effects model was performed to calculate pooled rates.

RESULTS: Eight studies with a total of 89 patients were included in our review, with 74 patients having received FMT and 15 patients having received placebo. The mean age ranged from 32.6 to 51.5 years. In patients that received FMT, the pooled rates of overall remission was (Pouchitis Disease Activity Index score < 7) 22% (95% CI, 9%-43%; I[2], 29%), clinical remission was 20% (95% CI, 6%-49%; I[2], 25%), clinical response rate was 42% (95% CI, 30%-54%; I[2], 7%), and the relapse rate 60% (95% CI, 40%-77%, I[2] 16%) over the mean follow up of 4.67 months (range 1-12 months). The pooled proportion of patients with adverse events was 54% (95% CI, 21%-84%; I[2], 73%). There were no serious adverse events or deaths.

CONCLUSION: In patients with chronic pouchitis, FMT is safe though there are mixed results in terms of its long-term efficacy. Future Randomized Controlled Trials with larger sample sizes and greater standardization in terms of preparation, delivery, and length of treatment of FMT are needed to determine efficacy.}, } @article {pmid39131119, year = {2022}, author = {Watts, AE and Sninsky, JA and Richey, MM and Donovan, K and Dougherty, MK and McGill, SK}, title = {Family Stool Donation Predicts Failure of Fecal Microbiota Transplant for Clostridioides difficile Infection.}, journal = {Gastro hep advances}, volume = {1}, number = {2}, pages = {141-146}, pmid = {39131119}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplant (FMT) via colonoscopy is highly effective treatment for Clostridioides difficile infection (CDI). We aimed to determine baseline patient characteristics that predict failure to respond to colonoscopy-based FMT.

METHODS: We evaluated adult patients who received FMT for CDI not responding to standard therapies at a single tertiary center between 2014 and 2018 in this retrospective cohort study. We defined clinical success as formed stool or C difficile-negative diarrhea at 2 months after FMT. If patients required a second FMT, follow-up was extended 2 months after repeat infusion. We performed multivariate logistic regression and a random forest model to identify variables predictive of response to FMT.

RESULTS: Clinical success was attained in 87.3% of 103 patients who underwent FMT for CDI. In the multivariate model, the odds of FMT failure for family donation compared with stool bank were odds ratio 4.13 (1.00-7.01 P = .049). Diarrhea while taking anti-CDI antibiotics was common (37.8% of patients) and did not predict failure (odds ratio 0.64, 0.19-2.11 P = .46) in the univariate model. A machine learning model to predict response using clinical factors only achieved a sensitivity of 70%, specificity of 77%, and negative predictive value of 96%.

CONCLUSION: Colonoscopy-based FMT was highly effective for CDI, even in a population where immunosuppression and proton pump inhibitor use were common. Family stool donation was associated with FMT failure, compared with the use of a stool bank. The study suggests that the use of a stool bank may not only improve access to FMT but also its efficacy.}, } @article {pmid39128572, year = {2024}, author = {Uzan-Yulzari, A and Turjeman, S and Moadi, L and Getselter, D and Rautava, S and Isolauri, E and Khatib, S and Elliott, E and Koren, O}, title = {A gut reaction? The role of the microbiome in aggression.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2024.08.011}, pmid = {39128572}, issn = {1090-2139}, abstract = {Recent research has unveiled conflicting evidence regarding the link between aggression and the gut microbiome. Here, we compared behavior profiles of control, germ-free (GF) and antibiotic-treated mice, as well as re-colonized GF mice to understand the impact of gut microbiome on aggression using the resident-intruder paradigm. Our findings revealed a link between gut microbiome depletion and higher aggression, accompanied by notable changes in urine metabolite profiles and brain gene expression. Our study extends beyond classical murine models to humanized mice to reveal the clinical relevance of early-life antibiotic use on aggression. Fecal microbiome transplant from infants exposed to antibiotics in early life (and sampled one month later) into mice led to increased aggression compared to mice receiving transplants from unexposed infants. This study sheds light on the role of the gut microbiome in modulating aggression and highlights its potential avenues of action, offering insights for development of therapeutic strategies for aggression-related disorders.}, } @article {pmid39126667, year = {2024}, author = {Yang, L and Gao, Y and Gong, J and Su, Q and Guo, Z and Farag, MA and Xiao, J}, title = {Myricetin ameliorates prediabetes through gut microbiota-SCFAs-Gpr43 axis.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/10408398.2024.2386450}, pmid = {39126667}, issn = {1549-7852}, } @article {pmid39126020, year = {2024}, author = {Alexandrescu, L and Nicoara, AD and Tofolean, DE and Herlo, A and Nelson Twakor, A and Tocia, C and Trandafir, A and Dumitru, A and Dumitru, E and Aftenie, CF and Preotesoiu, I and Dina, E and Tofolean, IT}, title = {Healing from Within: How Gut Microbiota Predicts IBD Treatment Success-A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39126020}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Inflammatory Bowel Diseases/microbiology/therapy ; *Fecal Microbiota Transplantation/methods ; Treatment Outcome ; Probiotics/therapeutic use ; Antibodies, Monoclonal, Humanized ; }, abstract = {Recent research indicates that the microbiome has a significant impact on the progression of inflammatory bowel disease (IBD) and that creating therapies that change its composition could positively impact the outcomes of IBD treatment. This review summarizes the results of extensive studies that examined IBD patients undergoing several therapies, including anti-TNF medication, vedolizumab, ustekinumab, probiotics, and fecal microbiota transplantation (FMT), and the alterations in their gut microbiota's composition and function. The objective was to investigate the variety and effectiveness of microbial species in order to discover new biomarkers or therapeutic targets that could improve the outcome of treatment for these patients. This research aimed to offer useful insights into personalized medicine techniques for managing IBD. Beneficial bacteria such as Faecalibacterium prausnitzii and Roseburia have been consistently linked to favorable clinical outcomes, whereas pathogenic bacteria such as Escherichia coli and Clostridioides difficile are associated with worsening disease conditions. Although many studies have examined the role of gut microbiota in IBD, there is still a need for more targeted research on the connection between specific microbial communities and treatment outcomes. This study sought to address this gap by exploring the intricate relationship between the gut microbiota composition and the effectiveness of IBD medications.}, } @article {pmid39122767, year = {2024}, author = {Zhang, B and Magnaye, KM and Stryker, E and Moltzau-Anderson, J and Porsche, CE and Hertz, S and McCauley, KE and Smith, BJ and Zydek, M and Pollard, KS and Ma, A and El-Nachef, N and Lynch, SV}, title = {Sustained mucosal colonization and fecal metabolic dysfunction by Bacteroides associates with fecal microbial transplant failure in ulcerative colitis patients.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {18558}, pmid = {39122767}, issn = {2045-2322}, support = {T32 DK007007/DK/NIDDK NIH HHS/United States ; K12 GM081266-11/GM/NIGMS NIH HHS/United States ; 1563159//National Science Foundation/ ; }, mesh = {Humans ; *Colitis, Ulcerative/microbiology/therapy/metabolism ; *Fecal Microbiota Transplantation ; Male ; Female ; *Feces/microbiology ; *Bacteroides/genetics ; Adult ; *Intestinal Mucosa/microbiology/metabolism ; Middle Aged ; Gastrointestinal Microbiome ; Treatment Failure ; RNA, Ribosomal, 16S/genetics ; Metabolome ; }, abstract = {Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure.}, } @article {pmid39121607, year = {2024}, author = {Qiu, L and Yan, C and Yang, Y and Liu, K and Yin, Y and Zhang, Y and Lei, Y and Jia, X and Li, G}, title = {Morin alleviates DSS-induced ulcerative colitis in mice via inhibition of inflammation and modulation of intestinal microbiota.}, journal = {International immunopharmacology}, volume = {140}, number = {}, pages = {112846}, doi = {10.1016/j.intimp.2024.112846}, pmid = {39121607}, issn = {1878-1705}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory condition with recurrent and challenging symptoms. Effective treatments are lacking, making UC management a critical research area. Morin (MO), a flavonoid from the Moraceae family, shows potential as an anti-UC agent, but its mechanisms are not fully understood. Using a dextran sulfate sodium (DSS)-induced UC mouse model, we employed network pharmacology to predict MO's therapeutic effects. Assessments included changes in body weight, disease activity index (DAI), and colon length. Immunofluorescence, hematoxylin and eosin (H&E), and PAS staining evaluated colon damage. ELISA and western blot analyzed inflammatory factors, tight junction (TJ)-associated proteins (Claudin-3, Occludin, ZO-1), and Mitogen-Activated Protein Kinase (MAPK)/ Nuclear Factor kappa B (NF-κB) pathways. 16S rRNA sequencing assessed gut microbiota diversity, confirmed by MO's modulation via Fecal Microbial Transplantation (FMT). Early MO intervention reduced UC severity by improving weight, DAI scores, and colon length, increasing goblet cells, enhancing barrier function, and inhibiting MAPK/NF-κB pathways. MO enriched gut microbiota, favoring beneficial bacteria like Muribaculaceae and Erysipelotrichaceae while reducing harmful Erysipelotrichaceae and Muribaculaceae. This study highlights MO's potential in UC management through inflammation control, mucosal integrity maintenance, and gut flora modulation.}, } @article {pmid39118149, year = {2024}, author = {Li, DH and Li, ZW and Sun, Q and Wang, L and Ning, SB}, title = {Lower fecal microbiota transplantation ameliorates ulcerative colitis by eliminating oral-derived Fusobacterium nucleatum and virulence factor.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {42}, pmid = {39118149}, issn = {1757-4749}, abstract = {BACKGROUND: Recently, the oral oncobacterium Fusobacterium nucleatum (F. nucleatum), has been linked with ulcerative colitis (UC). Here, we aim to investigate whether Fecal Microbiota Transplantation (FMT) can alleviate UC by restoring gut microbiota and eliminating oral-derived F. nucleatum and virulence factor fadA.

METHOD: C57BL/6J mice were randomly divided into a healthy control group (HC), Dextran Sulfate Sodium group (DSS), oral inoculation group (OR), upper FMT group (UFMT), and lower FMT group (LFMT). Disease activity index, body weight, survival rate, and histopathological scores were used to measure the severity of colitis. The function of the intestinal mucosal barrier was evaluated by performing immunohistochemical staining of the tight junction protein Occludin. Real-time PCR was used to assess the relative abundance of the nusG gene and the virulence gene fadA. Cytokine levels were detected by ELISA. Full-length sequencing of 16S rRNA was used to analyze the changes and composition of gut microbiota.

FINDINGS: Oral incubation of F. nucleatum further exacerbated the severity of colitis and gut dysbiosis. Peptostreptococcaceae, Enterococcaceae, and Escherichia coli were significantly enriched in OR mice. However, LFMT mice showed an obvious decrease in disease activity and were more effective in restoring gut microbiota and eliminating F. nucleatum than UFMT mice. Bacteroidota, Lachnospiraceae, and Prevotellaceae were mainly enriched bacteria in LFMT mice. In addition, Genera such as Lactobacillus, Allobaculum, and Bacteroidales were found negative correlation with TNF-α, IL-1β, and IL-6. Genera like Romboutsia, Escherichia Shigella, Enterococcus, and Clostridium were found positively correlated with TNF-α, IL-1β, and IL-6.

CONCLUSIONS: Oral incubation of F. nucleatum further exacerbates the severity and dysbiosis in DSS-induced colitis mice. Besides, lower tract FMT can ameliorate colitis by restoring the gut microbiota diversity and eliminating F. nucleatum and virulence factor fadA.}, } @article {pmid39117173, year = {2024}, author = {Bell, J and Raidal, S and Peters, A and Hughes, KJ}, title = {Storage of equine faecal microbiota transplantation solution has minimal impact on major bacterial communities and structure.}, journal = {Veterinary journal (London, England : 1997)}, volume = {}, number = {}, pages = {106220}, doi = {10.1016/j.tvjl.2024.106220}, pmid = {39117173}, issn = {1532-2971}, abstract = {Management of diarrhoea in horses is usually non-specific and supportive. Faecal microbiota transplantations (FMT) are used to manage dysbiosis in horses with diarrhoea. There are few studies investigating the effects of storage on prepared FMT solutions. This study was an in vitro non-randomised controlled experiment that investigated the effects of FMT solution preparation and storage on the faecal microbiota. Fresh faeces were collected from five healthy adult horses and used for DNA extraction and preparation of FMT. From each FMT, seven aliquots were collected and DNA was extracted immediately after FMT preparation (0hr), after storage at 4[o]C for 24, 48 or 72hours, and after storage at -20°C for 7 days, 14 days or 28 days. The extracted DNA was used for 16S rRNA gene sequencing. The relative abundance, alpha diversity and beta diversity between fresh faeces and FMT 0hr showed no differences (P ≥ 0.05). There were minimal changes in the microbiota of FMT stored at 4°C for up to 72hours and -20°C for up to 28 days. The results of this study indicate that preparation of equine FMT solution has minimal effect on the microbiota in comparison to fresh faeces. FMT solution can be stored at 4°C for up to 3 days and -20°C for 28 days without major change in microbiota.}, } @article {pmid39113144, year = {2024}, author = {Han, L and Sun, X and Kong, J and Li, J and Feng, K and Bai, Y and Wang, X and Zhu, Z and Yang, F and Chen, Q and Zhang, M and Yue, B and Wang, X and Fu, L and Chen, Y and Yang, Q and Wang, S and Xin, Q and Sun, N and Zhang, D and Zhou, Y and Gao, Y and Zhao, J and Jiang, Y and Guo, R}, title = {Multi-omics analysis reveals a feedback loop amplifying immune responses in acute graft-versus-host disease due to imbalanced gut microbiota and bile acid metabolism.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {746}, pmid = {39113144}, issn = {1479-5876}, support = {82100240//National Natural Science Foundation of China/ ; }, mesh = {*Bile Acids and Salts/metabolism ; Humans ; *Graft vs Host Disease/immunology/microbiology ; *Gastrointestinal Microbiome/immunology ; Female ; Male ; *Feces/microbiology ; Middle Aged ; Acute Disease ; Adult ; Feedback, Physiological ; Immunity ; Metabolomics ; Hematopoietic Stem Cell Transplantation ; Multiomics ; }, abstract = {Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving "immune cell-gut microbes-bile acid metabolites" contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD.}, } @article {pmid39113097, year = {2024}, author = {Gray, SM and Moss, AD and Herzog, JW and Kashiwagi, S and Liu, B and Young, JB and Sun, S and Bhatt, AP and Fodor, AA and Balfour Sartor, R}, title = {Mouse adaptation of human inflammatory bowel diseases microbiota enhances colonization efficiency and alters microbiome aggressiveness depending on the recipient colonic inflammatory environment.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {147}, pmid = {39113097}, issn = {2049-2618}, support = {T32 DK007737/DK/NIDDK NIH HHS/United States ; T32DK007737//NIH/NIDDK/ ; NSF Cooperative Agreement No. EEC-2133504//The Engineering Research Centers Program of the National Science Foundation/ ; }, mesh = {Animals ; Humans ; Mice ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/microbiology ; *Disease Models, Animal ; *Dysbiosis/microbiology ; *Interleukin-10/genetics ; Colitis/microbiology ; Feces/microbiology ; Colon/microbiology ; Mice, Knockout ; Mice, Inbred C57BL ; Female ; Bacteria/classification/genetics/isolation & purification ; Inflammation ; Male ; }, abstract = {BACKGROUND: Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis.

RESULTS: Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota-associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10[-/-] mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10[-/-] mice. Engraftment of human-to-mouse FMT stochastically varied with individual transplantation events more than mouse-adapted FMT. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10[-/-] host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10[-/-] mice than the distinct microbiota reassembled in non-inflamed WT hosts.

CONCLUSIONS: Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated by gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer. Video Abstract.}, } @article {pmid39111080, year = {2024}, author = {Zhu, J and Li, B and Fang, W and Zhou, X and Li, D and Jin, J and Li, W and Su, Y and Yuan, R and Ye, JM and Wu, R}, title = {Oral matrine alleviates CCl4-induced liver fibrosis via preserved HSP72 from modulated gut microbiota.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {178}, number = {}, pages = {117262}, doi = {10.1016/j.biopha.2024.117262}, pmid = {39111080}, issn = {1950-6007}, abstract = {Hepatic fibrosis is intricately associated with dysregulation of gut microbiota and host metabolomes. Our previous studies have demonstrated that matrine can effectively reduce hepatosteatosis and associated disorders. However, it is poorly understood whether the gut microbiota involved in the attenuation of liver fibrosis by matrine. Herein we explored a novel mechanism of how oral administration of matrine alleviates liver fibrosis by modulating gut microbiota. Administration of matrine not only potently ameliorated liver fibrosis in carbon tetrachloride (CCl4)-induced mice, but also significantly preserved hepatic heat shock protein 72 (HSP72) in vivo and in vitro. Matrine was failed to reduce liver fibrosis when HSP72 upregulation was blocked by the HSP72 antagonist VER-155008. Also, consumption of matrine significantly alleviated gut dysbiosis and fecal metabonomic changes in CCl4-treated mice. Transplanted the faces of matrine-treated mice induced a remarkable upregulation of HSP72 and remission of fibrosis in liver in CCl4-exposed mice and inhibition of TGF-β1-induced inflammatory response and epithelial-mesenchymal transition (EMT) in AML-12 cells. Furthermore, deficiency of HSP72 partly reversed the intestinal microbial composition that prevented matrine from reducing CCl4-induced liver fibrosis in mice. This study reveals the "gut microbiota-hepatic HSP72" axis as a key mechanism of matrine in reducing liver fibrosis and suggest that this axis may be targeted for developing other new therapies for liver fibrosis.}, } @article {pmid39110590, year = {2024}, author = {He, Y and Zhao, C and Su, N and Yang, W and Yang, H and Yuan, C and Zhang, N and Hu, X and Fu, Y}, title = {Disturbances of the gut microbiota-derived tryptophan metabolites as key actors in vagotomy-induced mastitis in mice.}, journal = {Cell reports}, volume = {43}, number = {8}, pages = {114585}, doi = {10.1016/j.celrep.2024.114585}, pmid = {39110590}, issn = {2211-1247}, abstract = {Previous studies have demonstrated that gut microbiota dysbiosis promotes the development of mastitis. The interaction of the vagus nerve and gut microbiota endows host homeostasis and regulates disease development, but whether the vagus nerve participates in the pathogenesis of mastitis is unclear. Here, vagotomized mice exhibit disruption of the blood-milk barrier and mammary gland inflammation. Notably, mastitis and barrier damage caused by vagotomy are dependent on the gut microbiota, as evidenced by antibiotic treatment and fecal microbiota transplantation. Vagotomy significantly alters the gut microbial composition and tryptophan metabolism and reduces the 5-hydroxyindole acetic acid (5-HIAA) level. Supplementation with 5-HIAA alleviates vagotomy-induced mastitis, which is associated with the activation of the aryl hydrocarbon receptor (AhR) and subsequent inhibition of the NF-κB pathway. Collectively, our findings indicate the important role of the vagus-mediated gut-mammary axis in the pathogenesis of mastitis and imply a potential strategy for the treatment of mastitis by targeting the vagus-gut microbiota interaction.}, } @article {pmid39109266, year = {2024}, author = {Li, Q and Liu, Y and Zhang, Z and Zhang, S and Ding, X and Zhang, F}, title = {Washed Microbiota Transplantation Improves the Sleep Quality in Patients with Inflammatory Bowel Disease.}, journal = {Nature and science of sleep}, volume = {16}, number = {}, pages = {1141-1152}, pmid = {39109266}, issn = {1179-1608}, abstract = {PURPOSE: There is scarce evidence to support the effectiveness of faecal microbiota transplantation (FMT) in improving sleep among individuals with inflammatory bowel disease (IBD). Our study aimed to evaluate the effect of washed microbiota transplantation (WMT) (the new method of FMT) on the sleep of patients with IBD in short term.

PATIENTS AND METHODS: This prospective study was conducted as part of two interventional clinical trials (starting on February 2013 and expected to end on December 2025) and placed significant emphasis on evaluating sleep quality in patients with IBD. To measure subjective sleep, we used the Pittsburgh sleep quality index (PSQI). The primary endpoint was the PSQI score one month after WMT.

RESULTS: This stage study included 52 eligible patients evaluated by PSQI questionnaire who underwent WMT from January 2020 to March 2021 and 47 patients were enrolled for analysis. The age of the patients ranged from 13 to 60 years, with a mean of 33.4 years, and 57.4% (25/47) of the patients were male. The PSQI scores for all 47 patients one month after undergoing WMT were significantly lower (Cohen d = 0.59, p < 0.001) compared to the baseline. Moreover, baseline PSQI score was correlated with the difference value of the PSQI score before and after WMT (post-PSQI minus pre-PSQI) (r = 0.61, p < 0.05).

CONCLUSION: The study suggests that WMT might be a helpful intervention for improving the sleep quality of patients with IBD, encouraging clinicians to consider its use in clinical practice for addressing poor sleep in IBD patients.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; ID: NCT01793831, NCT01790061.}, } @article {pmid39109116, year = {2024}, author = {Khalil, Z and Maher, S}, title = {The Impact of Microbiome Dysbiosis on Hematopoietic Stem Cell Transplantation Outcomes: A Review Article.}, journal = {Cureus}, volume = {16}, number = {7}, pages = {e63995}, pmid = {39109116}, issn = {2168-8184}, abstract = {Microbiome dysbiosis has emerged as a critical factor influencing the outcomes of hematopoietic stem cell transplantation (HSCT). This comprehensive review delves into the intricate relationship between microbiome composition and HSCT outcomes, highlighting the mechanisms through which dysbiosis impacts engraftment, graft-versus-host disease (GVHD), infection rates, and overall survival. The gut microbiome plays a pivotal role in modulating immune responses and maintaining intestinal homeostasis, both of which are crucial for the success of HSCT. This review aims to elucidate the underlying pathways and potential therapeutic strategies to mitigate adverse outcomes associated with microbiome imbalances in HSCT patients. Integrating microbiome modulation strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and antibiotic stewardship into clinical practice can significantly improve patient outcomes and quality of life post-transplantation.}, } @article {pmid39107366, year = {2024}, author = {Zhang, YJ and Bousvaros, A and Docktor, M and Kaplan, AL and Rufo, PA and Leier, M and Weatherly, M and Zimmerman, L and Nguyen, LTT and Barton, B and Russell, G and Alm, EJ and Kahn, SA}, title = {Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after fecal microbiota transplant in inflammatory bowel disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {18188}, pmid = {39107366}, issn = {2045-2322}, support = {K12 HD052896/HD/NICHD NIH HHS/United States ; 5K12HD052896//National Institute of Child Health and Human Development/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Adult ; Adolescent ; Female ; Male ; Young Adult ; *Lactobacillus ; Double-Blind Method ; Inflammatory Bowel Diseases/therapy/microbiology ; Gastrointestinal Microbiome ; Pilot Projects ; Feces/microbiology ; Treatment Outcome ; Crohn Disease/therapy/microbiology ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Colitis, Ulcerative/therapy/microbiology ; }, abstract = {Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.}, } @article {pmid39106569, year = {2024}, author = {Chen, Y and Zeng, Q and Luo, Y and Song, M and He, X and Sheng, H and Gao, X and Zhu, Z and Sun, J and Cao, C}, title = {Polystyrene microplastics aggravate radiation-induced intestinal injury in mice.}, journal = {Ecotoxicology and environmental safety}, volume = {283}, number = {}, pages = {116834}, doi = {10.1016/j.ecoenv.2024.116834}, pmid = {39106569}, issn = {1090-2414}, abstract = {Radiotherapy is a common treatment for abdominal and pelvic tumors, while the radiation-induced intestinal injury (RIII) is one of the major side-effects of radiotherapy, which reduces the life quality and impedes the treatment completion of cancer patients. Previous studies have demonstrated that environmental pollutant microplastics led to various kinds of injury in the gut, but its effects on RIII are still uncovered. In this study, we fed the C57BL/6J mice with distilled water or 50 μg/d polystyrene microplastics (PSMPs) for 17 days and exposed the mice to total abdominal irradiation (TAI) at day 14. Then the severity of RIII was examined by performing histopathological analysis and microbial community analysis. The results demonstrated that PSMPs significantly aggravated RIII in small intestine rather than colon of mice upon TAI. PSMPs increased levels of the histopathological damage and the microbial community disturbance in mice small intestine, shown by the overabundance of Akkermansiaceae and the decrease of microflora including Lactobacillaceae, Muribaculaceae and Bifidobacteriaceae. In conclusion, our results suggested that more microplastics exposure might led to more severe RIII, which should be considered in patients' daily diet adjustment and clinical radiotherapy plan evaluation. Furthermore, this study also called for the further researches to uncover the underlying mechanism and develop novel strategies to attenuate RIII in mice intestine.}, } @article {pmid39105259, year = {2024}, author = {Jiang, H and Yu, Y and Hu, X and Du, B and Shao, Y and Wang, F and Chen, L and Yan, R and Li, L and Lv, L}, title = {The fecal microbiota of patients with primary biliary cholangitis (PBC) causes PBC-like liver lesions in mice and exacerbates liver damage in a mouse model of PBC.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2383353}, pmid = {39105259}, issn = {1949-0984}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Mice ; *Liver Cirrhosis, Biliary/microbiology/pathology/metabolism ; *Disease Models, Animal ; *Liver/pathology/metabolism/microbiology ; *Feces/microbiology ; Female ; Bacteria/classification/isolation & purification/genetics ; Fecal Microbiota Transplantation ; Male ; Bile Acids and Salts/metabolism ; Transcriptome ; Mice, Inbred C57BL ; }, abstract = {The role of the gut microbiota in the occurrence and progression of primary biliary cholangitis (PBC) is not fully understood. First, the fecal microbiota of patients with PBC (n = 4) (PBC-FMT) or healthy individuals (n = 3) (HC-FMT) was transplanted into pseudo germ-free mice or 2OA-BSA-induced PBC models. The functions, histology and transcriptome of the liver, and microbiota and metabolome of the feces were analyzed. Second, the liver transcriptomes of PBC patients (n = 7) and normal individuals (n = 7) were analyzed. Third, the liver transcriptomes of patients with other liver diseases were collected from online databases and compared with our human and mouse data. Our results showed that PBC-FMT increased the serum ALP concentration, total bile acid content, liver injury and number of disease-related pathways enriched with upregulated liver genes in pseudo germ-free mice and increased the serum glycylproline dipeptidyl aminopeptidase level and liver damage in a 2OA-BSA-induced PBC model. The gut microbiota and metabolome differed between PBC-FMT and HC-FMT mice and reflected those of their donors. PBC-FMT tended to upregulate hepatic immune and signal transduction pathways but downregulate metabolic pathways, as in some PBC patients. The hematopoietic cell lineage, Toll-like receptor, and PPAR signaling pathway were not affected in patients with alcoholic hepatitis, HBV, HCV, HCV cirrhosis, or NASH, indicating their potential roles in the gut microbiota affecting PBC. In conclusion, the altered gut microbiota of PBC patients plays an important role in the occurrence and progression of PBC. The improvement of the gut microbiota is worthy of in-depth research and promotion as a critical aspect of PBC prevention and treatment.}, } @article {pmid39105129, year = {2024}, author = {Aslam, R and Herrles, L and Aoun, R and Pioskowik, A and Pietrzyk, A}, title = {Link between gut microbiota dysbiosis and childhood asthma: Insights from a systematic review.}, journal = {The journal of allergy and clinical immunology. Global}, volume = {3}, number = {3}, pages = {100289}, pmid = {39105129}, issn = {2772-8293}, abstract = {Asthma, a chronic inflammatory disorder of the airways, is a prevalent childhood chronic disease with a substantial global health burden. The complex etiology and pathogenesis of asthma involve genetic and environmental factors, posing challenges in diagnosis, severity prediction, and therapeutic strategies. Recent studies have highlighted the significant role of the gut microbiota and its interaction with the immune system in the development of asthma. Dysbiosis, an imbalance in microbial composition, has been associated with respiratory diseases through the gut-lung axis. This axis is an interaction between the gut and lungs, allowing microbial metabolites to influence the host immune system. This systematic review examines the association between gut microbiota composition, measured using 16S rRNA sequencing, during infancy and childhood, and the subsequent development of atopic wheeze and asthma. The results suggest that higher alpha diversity of bacteria such as Bifidobacterium, Faecalibacterium, and Roseburia may have protective effects against asthmatic outcomes. Conversely, lower relative abundances of bacteria like Bacteroides and certain fungi, including Malassezia, were associated with asthma. These findings highlight the potential of early screening and risk assessment of gut microbiota to identify individuals at risk of asthma. Furthermore, investigations targeting gut microbiota, such as dietary modifications and probiotic supplementation, may hold promise for asthma prevention and management. Future research should focus on identifying specific microbial signatures associated with asthma susceptibility and further investigate approaches like fecal microbiota transplantation. Understanding the role of gut microbiota in asthma pathogenesis can contribute to early detection and development of interventions to mitigate the risk of asthmatic pathogenesis in childhood.}, } @article {pmid39104728, year = {2024}, author = {Webster, CI and Withycombe, JS and Bhutada, JS and Bai, J}, title = {Review of the microbiome and metabolic pathways associated with psychoneurological symptoms in children with cancer.}, journal = {Asia-Pacific journal of oncology nursing}, volume = {11}, number = {8}, pages = {100535}, pmid = {39104728}, issn = {2347-5625}, abstract = {Children with cancer often endure a range of psychoneurological symptoms (PNS), including pain, fatigue, cognitive impairment, anxiety, depressive symptoms, and sleep disturbance. Despite their prevalence, the underlying pathophysiology of PNS remains unclear. Hypotheses suggest an interplay between the gut microbiome and the functional metabolome, given the immune, neurological, and inflammatory influences these processes exert. This mini-review aims to provide a synopsis of the literature that examines the relationship between microbiome-metabolome pathways and PNS in children with cancer, drawing insights from the adult population when applicable. While there is limited microbiome research in the pediatric population, promising results in adult cancer patients include an association between lower microbial diversity and compositional changes, including decreased abundance of the beneficial microbes Fusicatenibacter, Ruminococcus, and Odoribacter, and more PNS. In pediatric patients, associations between peptide, tryptophan, carnitine shuttle, and gut microbial metabolism pathways and PNS outcomes were found. Utilizing multi-omics methods that combine microbiome and metabolome analyses provide insights into the functional capacity of microbiomes and their associated microbial metabolites. In children with cancer receiving chemotherapy, increased abundances of Intestinibacter and Megasphaera correlated with six metabolic pathways, notably carnitine shuttle and tryptophan metabolism. Interventions that target the underlying microbiome-metabolome pathway may be effective in reducing PNS, including the use of pre- and probiotics, fecal microbiome transplantation, dietary modifications, and increased physical activity. Future multi-omics research is needed to corroborate the associations between the microbiome, metabolome, and PNS outcomes in the pediatric oncology population.}, } @article {pmid39104406, year = {2024}, author = {Adamberg, S and Rasmussen, TS and Larsen, SB and Mao, X and Nielsen, DS and Adamberg, K}, title = {Reproducible chemostat cultures to minimize eukaryotic viruses from fecal transplant material.}, journal = {iScience}, volume = {27}, number = {8}, pages = {110460}, pmid = {39104406}, issn = {2589-0042}, abstract = {Recent studies indicate an important role of bacteriophages for successful fecal microbiota transplantation (FMT). However, wider clinical applications of FMT are hampered by to donor variability and concerns of infection risks by bacteria and human viruses. To overcome these challenges, mouse cecal and human fecal material were propagated in a chemostat fermentation setup supporting multiplication of bacteria, and phages, while propagation of eukaryotic viruses will be prevented in the absence of eukaryotic host cells. The results showed decrease of the median relative abundance of viral contigs of classified eukaryotic viruses below 0.01%. The corresponding virome profiles showed dilution rate dependency, a reproducibility between biological replicates, and maintained high diversity regarding both the human and mouse inocula. This proof-of-concept cultivation approach may constitute the first step of developing novel therapeutic tools with high reproducibility and with low risk of infection from the donor material to target gut-related diseases.}, } @article {pmid39097746, year = {2024}, author = {Mo, C and Lou, X and Xue, J and Shi, Z and Zhao, Y and Wang, F and Chen, G}, title = {The influence of Akkermansia muciniphila on intestinal barrier function.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {41}, pmid = {39097746}, issn = {1757-4749}, support = {82160366//National Natural Science Foundation of China/ ; 2021LCZXXFHX03//Yunnan Clinical Medical Center Open Project/ ; 202205AC160060//Yunnan Young and Middle-aged Academic and Technical Leaders Reserve Talent Project/ ; 2022YNKQ004//Yunnan Key Laboratory of Stomatology Open Project/ ; }, abstract = {Intestinal barriers play a crucial role in human physiology, both in homeostatic and pathological conditions. Disruption of the intestinal barrier is a significant factor in the pathogenesis of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. The profound influence of the gut microbiota on intestinal diseases has sparked considerable interest in manipulating it through dietary interventions, probiotics, and fecal microbiota transplantation as potential approaches to enhance the integrity of the intestinal barrier. Numerous studies have underscored the protective effects of specific microbiota and their associated metabolites. In recent years, an increasing body of research has demonstrated that Akkermansia muciniphila (A. muciniphila, Am) plays a beneficial role in various diseases, including diabetes, obesity, aging, cancer, and metabolic syndrome. It is gaining popularity as a regulator that influences the intestinal flora and intestinal barrier and is recognized as a 'new generation of probiotics'. Consequently, it may represent a potential target and promising therapy option for intestinal diseases. This article systematically summarizes the role of Am in the gut. Specifically, we carefully discuss key scientific issues that need resolution in the future regarding beneficial bacteria represented by Am, which may provide insights for the application of drugs targeting Am in clinical treatment.}, } @article {pmid39096912, year = {2024}, author = {Feng, Y and Zheng, H and Yin, C and Liang, D and Zhang, S and Chen, J and Mai, F and Lan, Z and Zhu, M and Mai, Z and Shen, S and Jayawardana, T and Wu, R and Tang, W and Zhang, R and He, X and Zheng, S and Hu, Q and Han, Y and Yang, Y and Gong, S and Wang, Z and El-Omar, EM and Luo, W and Chen, X and Chen, G and Li, P and Chen, X}, title = {β-resorcylic acid released by Limosilactobacillusreuteri protects against cisplatin-induced ovarian toxicity and infertility.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {101678}, doi = {10.1016/j.xcrm.2024.101678}, pmid = {39096912}, issn = {2666-3791}, abstract = {Chemotherapy-induced premature ovarian insufficiency (CIPOI) triggers gonadotoxicity in women undergoing cancer treatment, leading to loss of ovarian reserves and subfertility, with no effective therapies available. In our study, fecal microbiota transplantation in a cisplatin-induced POI mouse model reveals that a dysbiotic gut microbiome negatively impacts ovarian health in CIPOI. Multi-omics analyses show a significant decrease in Limosilactobacillus reuteri and its catabolite, β-resorcylic acid , in the CIPOI group in comparison to healthy controls. Supplementation with L. reuteri or β-RA mitigates cisplatin-induced hormonal disruptions, morphological damages, and reductions in follicular reserve. Most importantly, β-RA pre-treatment effectively preserves oocyte function, embryonic development, and fetus health, thereby protecting against chemotherapy-induced subfertility. Our results provide evidence that β-RA suppresses the nuclear accumulation of sex-determining region Y-box 7, which in turn reduces Bcl-2-associated X activation and inhibits granulosa cell apoptosis. These findings highlight the therapeutic potential of targeting the gut-ovary axis for fertility preservation in CIPOI.}, } @article {pmid39095306, year = {2024}, author = {Zugman, M and Wong, M and Jaime-Casas, S and Pal, SK}, title = {The gut microbiome and dietary metabolites in the treatment of renal cell carcinoma.}, journal = {Urologic oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.urolonc.2024.07.003}, pmid = {39095306}, issn = {1873-2496}, abstract = {The gut microbiome is interlinked with renal cell carcinoma (RCC) and its response to systemic treatment. Mounting data suggests that certain elements of the gut microbiome may correlate with improved outcomes. New generation sequencing techniques and advanced bioinformatic data curation are accelerating the investigation of specific markers and metabolites that could predict treatment response. A variety of new therapeutic strategies, such as fecal microbiota transplantation, probiotic supplements, and dietary interventions, are currently being developed to modify the gut microbiome and improve anticancer therapies in patients with RCC. This review discusses the preliminary evidence indicating the role of the microbiome in cancer treatment, the techniques and tools necessary for its proper study and some of the current forms with which the microbiome can be modulated to improve patient outcomes.}, } @article {pmid39094622, year = {2024}, author = {Reisinger, A and Stübing, H and Suchodolski, JS and Pilla, R and Unterer, S and Busch, K}, title = {Comparing treatment effects on dogs with acute hemorrhagic diarrhea syndrome: fecal microbiota transplantation, symptomatic therapy, or antibiotic treatment.}, journal = {Journal of the American Veterinary Medical Association}, volume = {}, number = {}, pages = {1-9}, doi = {10.2460/javma.24.03.0153}, pmid = {39094622}, issn = {1943-569X}, abstract = {OBJECTIVE: Dogs with acute hemorrhagic diarrhea syndrome (AHDS) present with similar clinical signs and histopathological findings as dogs with parvovirosis, in which fecal microbiota transplantation (FMT) has led to a significantly faster resolution of diarrhea and shorter hospitalization times. We investigated whether FMT results in faster clinical improvement and normalization of the intestinal microbiome compared to standard treatment.

ANIMALS: 32 client-owned dogs with AHDS.

METHODS: A prospective, double-anonymized clinical trial included 3 groups: symptomatic treatment (n = 12), FMT treatment (FMTT; 12), and antibiotic treatment (AT; 8). Clinical improvement was determined on the basis of AHDS index, changes in the microbiome based on the dysbiosis index, and PCR results for clostridial strains.

RESULTS: Overall, no significant differences in clinical scores between the treatment groups over time were detected except on day 2 (higher AHDS index in the AT group compared to FMTT group; P = .046). The dysbiosis index increased and P hiranonis decreased on day 1 in some dogs, but these changes were transient in the symptomatic treatment and FMTT groups. In the AT group, the dysbiosis index was persistently elevated and 4 of 8 dogs showed a reduced abundance of P hiranonis on day 42. In 67% of the dogs on day 1, NetF-encoding Clostridium perfringens was detected and enterotoxin-encoding strains increased, but these changes were transient in all dogs, regardless of therapy.

CLINICAL RELEVANCE: Overall, in dogs with AHDS, neither FMT nor AT resulted in faster clinical improvement. In addition, C perfringens strains are self-limiting and do not require antibiotic therapy.}, } @article {pmid39087354, year = {2024}, author = {Zhang, H and Fu, L and Leiliang, X and Qu, C and Wu, W and Wen, R and Huang, N and He, Q and Cheng, Q and Liu, G and Cheng, Y}, title = {Beyond the Gut: The intratumoral microbiome's influence on tumorigenesis and treatment response.}, journal = {Cancer communications (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1002/cac2.12597}, pmid = {39087354}, issn = {2523-3548}, support = {82372943//National Natural Science Foundation of China/ ; 82303610//National Natural Science Foundation of China/ ; 2022JJ20095//Hunan Provincial Natural Science Foundation of China/ ; 2023RC3074//Hunan Youth Science and Technology Talent Project/ ; 2023MD734131//China Postdoctoral Science Foundation/ ; CSTB2023NSCQBHX0002//Chongqing Postdoctoral Science Foundation/ ; //Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University/ ; 2023CQBSHTB3095//Chongqing Postdoctoral Research Special Funding Project/ ; }, abstract = {The intratumoral microbiome (TM) refers to the microorganisms in the tumor tissues, including bacteria, fungi, viruses, and so on, and is distinct from the gut microbiome and circulating microbiota. TM is strongly associated with tumorigenesis, progression, metastasis, and response to therapy. This paper highlights the current status of TM. Tract sources, adjacent normal tissue, circulatory system, and concomitant tumor co-metastasis are the main origin of TM. The advanced techniques in TM analysis are comprehensively summarized. Besides, TM is involved in tumor progression through several mechanisms, including DNA damage, activation of oncogenic signaling pathways (phosphoinositide 3-kinase [PI3K], signal transducer and activator of transcription [STAT], WNT/β-catenin, and extracellular regulated protein kinases [ERK]), influence of cytokines and induce inflammatory responses, and interaction with the tumor microenvironment (anti-tumor immunity, pro-tumor immunity, and microbial-derived metabolites). Moreover, promising directions of TM in tumor therapy include immunotherapy, chemotherapy, radiotherapy, the application of probiotics/prebiotics/synbiotics, fecal microbiome transplantation, engineered microbiota, phage therapy, and oncolytic virus therapy. The inherent challenges of clinical application are also summarized. This review provides a comprehensive landscape for analyzing TM, especially the TM-related mechanisms and TM-based treatment in cancer.}, } @article {pmid38900442, year = {2024}, author = {Yazici, C and Priyadarshini, M and Boulay, B and Dai, Y and Layden, BT}, title = {Alterations in microbiome associated with acute pancreatitis.}, journal = {Current opinion in gastroenterology}, volume = {40}, number = {5}, pages = {413-421}, pmid = {38900442}, issn = {1531-7056}, support = {I01 BX003382/BX/BLRD VA/United States ; U01 DK127378/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Pancreatitis/microbiology ; *Gastrointestinal Microbiome/physiology ; Severity of Illness Index ; Dysbiosis/microbiology/complications/immunology ; Acute Disease ; Fecal Microbiota Transplantation ; }, abstract = {PURPOSE OF REVIEW: This review evaluates the current knowledge of gut microbiome alterations in acute pancreatitis, including those that can increase acute pancreatitis risk or worsen disease severity, and the mechanisms of gut microbiome driven injury in acute pancreatitis.

RECENT FINDINGS: Recent observational studies in humans showed the association of gut microbiome changes (decreased gut microbiome diversity, alterations in relative abundances of certain species, and association of unique species with functional pathways) with acute pancreatitis risk and severity. Furthermore, in-vivo studies highlighted the role of gut microbiome in the development and severity of acute pancreatitis using FMT models. The gut barrier integrity, immune cell homeostasis, and microbial metabolites appear to play key roles in acute pancreatitis risk and severity.

SUMMARY: Large human cohort studies that assess gut microbiome profile, its metabolites and impact on acute pancreatitis risk and severity will be crucial for development of innovative prediction, prevention and treatment strategies.}, } @article {pmid39093178, year = {2023}, author = {Von Muhlenbrock, C and Núñez, P and Espinoza, R and Quera, R}, title = {[Update in diagnosis and management of Clostridioides difficile].}, journal = {Revista medica de Chile}, volume = {151}, number = {7}, pages = {887-898}, doi = {10.4067/s0034-98872023000700887}, pmid = {39093178}, issn = {0717-6163}, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy ; *Clostridioides difficile/pathogenicity ; Anti-Bacterial Agents/therapeutic use ; Risk Factors ; Practice Guidelines as Topic ; Fecal Microbiota Transplantation ; Chile/epidemiology ; }, abstract = {Clostridioides difficile (C. difficile) is one of the leading causes of infection associated with health care with high morbidity and mortality, especially among hospitalized older adults. The increase in the use of antibiotics has been associated with a higher number of cases and greater virulence. Its clinical presentation ranges from asymptomatic carriers to toxic megacolon. Studies with stool tests (glutamate dehydrogenase, toxins A and B, and nuclear acid amplification techniques) should be considered in these cases. Fidaxomicin, fecal microbiota transplant, and new therapies such as monoclonal antibodies have been incorporated into the therapeutic arsenal, with a higher level of evidence. Nevertheless, the severity, patient comorbidity, recurrence risk factors, and the economic cost of each therapeutic option must be considered. This review aims to update the last guidelines proposed by the Chilean Societies of Gastroenterology and Infectious Diseases published in 2016, providing the latest recommendations regarding prevention, diagnosis, and treatment of C. difficile infection.}, } @article {pmid39084197, year = {2024}, author = {Zhang, Y and Wang, S and Wang, H and Cao, M and Wang, M and Zhang, B and Xiao, C and Zhu, H and Du, S}, title = {Efficacy of donor-recipient-matched faecal microbiota transplantation in patients with IBS-D: A single-centre, randomized, double-blind placebo-controlled study.}, journal = {Digestion}, volume = {}, number = {}, pages = {}, doi = {10.1159/000540420}, pmid = {39084197}, issn = {1421-9867}, abstract = {INTRODUCTION: The imbalance in gut microbiota is contributing to the development and progression of IBS. FMT can improve the gut microbiota, and donor-recipient-matched FMT can help develop individualised treatment plans according to different enterotypes. This study aimed to explore the efficacy of donor-recipient matched FMT in IBS-D and evaluate its effects on gut microbiota.

METHODS: Twenty-seven patients with IBS-D were randomly divided into donor-recipient matched FMT group (Group P), random-donor FMT group (Group R) and placebo group (Group B). All participants received corresponding FMT treatment after filling in IBS-S, IBS-QoL, GSRS, HADS questionnaires and having their stool samples collected at 4, 8 and 12 weeks after treatment. Analysed the improvement in the symptoms and the changes in the bacterial flora fo three groups.

RESULTS: 1. The IBS-SSS, IBS-Qol, GSRS and anxiety scores of Group P were significantly lower after treatment(P＜0.05). The IBS-Qol scores of Group R was significantly lower after treatment(P＜0.05). 2. Beta diversity analysis showed that the gut microbiota of Group P had an obvious trend of classification after treatment. 3. Seven bacterial genera were related to the differences in the IBS-SSS scores before and after treatment.

CONCLUSION: Donor-recipient-matched FMT significantly improved the clinical symptoms, quality of life, and anxiety scores of the patients with IBS-D than random-donor FMT.}, } @article {pmid39084184, year = {2024}, author = {Zhou, SK and Xu, JD and Gao, XQ and Zhang, RJ and Cheng, FF and Yao, WF and Zhang, Y and Geng, T and Zhang, L}, title = {Fructus Jujubae cooperated with water-expelling members in Shizao decoction alleviated intestinal injury and malignant ascites by modulating gut microbiota and metabolic homeostasis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {133}, number = {}, pages = {155895}, doi = {10.1016/j.phymed.2024.155895}, pmid = {39084184}, issn = {1618-095X}, abstract = {BACKGROUND: Shizao decoction (SZD) consisted of Euphorbia kansui (EK), Euphorbia pekinensis (EP), Daphne genkwa (DG), and Fructus Jujubae (FJ) is a classic Chinese herbal medicine formula for treating malignant ascites, which is closely related to the modulation of gut microbiota by our previous study. For water-expelling members (WEM) including EK, EP, and DG may have side effects on the intestine, FJ is employed for detoxification and effectivity enhancement of WEM. However, the underlying mechanism for the compatibility of WEM and FJ is still unknown.

PURPOSE: To investigate the effect of the compatibility of WEM with FJ in SZD on malignant ascites and elucidate the potential mechanism from the perspective of the modulation of gut microbiota and related metabolic function.

METHODS: Qualitative and quantitative evaluation of main components was conducted for comprehensive characterization of SZD and WEM. The effect of WEM and SZD was compared on malignant ascites effusion (MAE) rats. The intestinal injury was evaluated by HE staining and oxidative damage. Ascites weight, urine amount, fecal water content, the expression of aquaporins, and cytokines in ascites (IL-6, VEGF, and TNF-α) were measured to estimate the water-expelling activity. The intestinal flora was detected by 16S rDNA sequencing and the content of fecal short-chain fatty acids (SCFAs) was analyzed using gas chromatography-mass spectrometry. Pseudo-germ-free (PGF) and fecal bacteria transplantation animal experiments were subsequently employed to validate this finding. The fecal metabolomics and correlation analysis were finally conducted to explore the related metabolic changes.

RESULTS: 51 and 33 components were identified in SZD and WEM, respectively. Compared to WEM alone, the compatibility with FJ remarkably reduced intestinal oxidative damage in MAE rats. Ascites was also relieved by downregulating the expression of AQP3 in the colon and decreasing the levels of IL-6, TNF-α and VEGF in ascites. The diversity of gut microbiota was reversed with an increase in Lactobacillus and Clostridia_UCG-014 while a decrease in Colidextribacter. Under the PGF condition, compatibility of WEM with FJ failed to reduce intestinal injury and alleviate MA significantly, but this effect was further enhanced after FMT. 23 potential fecal metabolites were finally identified. Correlation analysis further showed that Lactobacillus and Clostridia_UCG-014 were positively correlated with SCFAs and l-tryptophan. Colidextribacter was negatively correlated with thymidine but positively correlated with ursodeoxycholic acid and deoxycholic acid.

CONCLUSION: FJ cooperated with WEM reduced intestinal injury and alleviated malignant ascites by modulating gut microbiota, short-chain fatty and tryptophan metabolism. These findings provide a scientific basis for the clinical application of FJ from SZD and the safe usage of SZD.}, } @article {pmid39083099, year = {2024}, author = {Heiss, MM and Lange, J and Knievel, J and Yohannes, A and Hügle, U and Dormann, AJ and Eisenberger, CF}, title = {Treatment of anastomotic leak in colorectal surgery by endoluminal vacuum therapy with the VACStent avoiding a stoma - a pilot study.}, journal = {Langenbeck's archives of surgery}, volume = {409}, number = {1}, pages = {234}, pmid = {39083099}, issn = {1435-2451}, mesh = {Humans ; Pilot Projects ; *Anastomotic Leak/prevention & control ; Female ; Male ; Middle Aged ; Aged ; Surgical Stomas/adverse effects ; Negative-Pressure Wound Therapy ; Treatment Outcome ; Anastomosis, Surgical/adverse effects ; Aged, 80 and over ; Adult ; }, abstract = {PURPOSE: Anastomotic leak (AL) represents the most relevant and devastating complication in colorectal surgery. Endoscopic vacuum therapy (EVT) using the VACStent is regarded as a significant improvement in the treatment of upper gastrointestinal wall defects. The innovative concept of the VACStent was transferred to the lower GI tract, gaining initial experience by investigating safety and efficacy in 12 patients undergoing colorectal resections.

METHODS: The pilot study, as part of a German registry, began with 2 patients suffering from AL, who were treated with the VACStent after stoma placement. Subsequently, 6 patients with AL were treated with the VACStent omitting a stoma placement, with a focus on fecal passage and wound healing. Finally, the preemptive anastomotic coverage was investigated in 4 patients with high-risk anastomoses to avoid prophylactic stoma placement.

RESULTS: In total 26 VACStents were placed without problems. The conditioning and drainage function were maintained, and no clogging problems of the sponge cylinder were observed. No relevant clinical VACStent-associated complications were observed; however, in 2 patients, a dislodgement of a VACStent occurred. The 6 patients with AL but without stoma had a median treatment with 3 VACStents per case with a laytime of 17 days, leading to complete wound healing in all cases. The 4 prophylactic VACStent applications were without complications.

CONCLUSION: The clinical application of the VACStent in the lower GI tract shows that successful treatment of anastomotic colonic leaks and avoidance of creation of an anus praeter is possible.

TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT04884334, date of registration 2021-05-04, retrospectively registered.}, } @article {pmid39081882, year = {2024}, author = {Sun, M and Lu, F and Yu, D and Wang, Y and Chen, P and Liu, S}, title = {Respiratory diseases and gut microbiota: relevance, pathogenesis, and treatment.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1358597}, pmid = {39081882}, issn = {1664-302X}, abstract = {Preclinical evidence has firmly established a bidirectional interaction among the lung, gut, and gut microbiome. There are many complex communication pathways between the lung and intestine, which affect each other's balance. Some metabolites produced by intestinal microorganisms, intestinal immune cells, and immune factors enter lung tissue through blood circulation and participate in lung immune function. Altered gut-lung-microbiome interactions have been identified in rodent models and humans of several lung diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, asthma, etc. Emerging evidence suggests that microbial therapies can prevent and treat respiratory diseases, but it is unclear whether this association is a simple correlation with the pathological mechanisms of the disease or the result of causation. In this review, we summarize the complex and critical link between the gut microbiota and the lung, as well as the influence and mechanism of the gut microbiota on respiratory diseases, and discuss the role of interventions such as prebiotics and fecal bacteria transplantation on respiratory diseases. To provide a reference for the rational design of large-scale clinical studies, the direct application of microbial therapy to respiratory-related diseases can reduce the incidence and severity of diseases and accompanying complications.}, } @article {pmid39081300, year = {2024}, author = {Zaidi, SMH and Haider, R and Kazmi, SAB and Husnain, A and Khan, S and Merchant, S and Tayyab, H and Wazeen, FR and Chaudhary, AJ}, title = {Beyond Antibiotics: Novel Approaches in the Treatment of Recurrent Clostridioides difficile Infection.}, journal = {ACG case reports journal}, volume = {11}, number = {8}, pages = {e01333}, pmid = {39081300}, issn = {2326-3253}, } @article {pmid39079886, year = {2024}, author = {Pedreira-Robles, G and Bach-Pascual, A and Collado-Nieto, S and Padilla, E and Burballa, C and Arias-Cabrales, C and Redondo-Pachón, D and Sánchez, F and Horcajada, JP and Pascual, J and Crespo, M and Villar-García, J and Pérez-Sáez, MJ}, title = {Screening for tropical and imported infections in migrant kidney transplant candidates from the kidney transplant access consultation.}, journal = {Nefrologia}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.nefroe.2024.07.006}, pmid = {39079886}, issn = {2013-2514}, abstract = {BACKGROUND AND OBJECTIVE: Kidney transplantation (KT) should be postponed in those people with active bacterial, fungal, viral and parasitic processes, since these must be treated and resolved previously. The objective of this study is to present the screening circuit implemented by the Nephrology clinic and describe the prevalence of tropical and imported infections in KT candidates born or coming from endemic areas.

MATERIALS AND METHODS: Descriptive cross-sectional study, carried out in 2021. Sociodemographic and clinical variables, serological data of general infections and specific tests of tropical infectious diseases were collected. A descriptive analysis of the data was carried out.

RESULTS: 67 TR candidates from Latin America (32.8%), North Africa (22.4%), Sub-Saharan Africa (14.9%) and Asia (29.9%) were included. 68.7% were men and the mean age was 48.9 ± 13.5 years. After the general and specific studies, 42 (62.7%) patients were referred to the Infectious Diseases Service to complete this study or indicate treatment. 35.8% of the patients had eosinophilia, and in one case parasites were detected in feces at the time of the study. Serology for strongyloidiasis was positive in 18 (26.9%) cases, while positive serology for other tropical infections was hardly detected. 34.3% of patients had latent tuberculosis infection.

CONCLUSIONS: The prevalence of tropical and imported infections in migrant candidates for RT was low, except for strongyloidiasis and latent tuberculosis infection. Its detection and treatment are essential to avoid serious complications in post-TR. To this end, the implementation of an interdisciplinary screening program from the KT access consultation is feasible, necessary and useful.}, } @article {pmid39079826, year = {2024}, author = {Wu, Q and Yang, LS and Huang, HL and Li, YF and Zhou, YJ and Xu, HM}, title = {Washed microbiota transplantation combined with biological agents promotes histological remission in refractory severe ulcerative colitis with recurrent intestinal infection: A case report.}, journal = {Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajg.2024.07.008}, pmid = {39079826}, issn = {2090-2387}, abstract = {Ulcerative colitis (UC) is a chronic non-specific colitis disease. In recent years, fecal microbiota transplantation (FMT), including improved washed microbiota transplantation (WMT), and biological agents have helped improve the prognosis of patients with UC. However, a significant number of patients with moderate to severe UC do not get relief from glucocorticoids, immunosuppressants, and TNF-α antagonists. Patients with severe UC are frequently burdened with opportunistic infections and subsequent surgical interventions. Combined treatment modalities are crucial for patients with severe UC and opportunistic infections. Herein, we reported a case of a 25-year-old female with refractory severe UC complicated with recurrent Clostridioides difficile infection and recurrent cytomegalovirus infection for six years. Surgical removal of the affected bowel segment was almost unavoidable. She showed endoscopic and histological recovery after comprehensive WMT and Vedolizumab treatment. The following are our learnings from the case: 1. A combination of WMT and biological agents can potentially obviate the necessity for surgical treatment in patients with refractory severe UC and promote histological remission. 2. Personalized comprehensive treatment and chronic disease management models for patients with UC should be emphasized. 3. WMT can help treat opportunistic infections, which may also strengthen the treatment with gut-targeted biological agents when traditional TNF-α antagonists show poor efficacy.}, } @article {pmid39078661, year = {2024}, author = {Kou, RW and Li, ZQ and Wang, JL and Jiang, SQ and Zhang, RJ and He, YQ and Xia, B and Gao, JM}, title = {Ganoderic Acid A Mitigates Inflammatory Bowel Disease through Modulation of AhR Activity by Microbial Tryptophan Metabolism.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c01166}, pmid = {39078661}, issn = {1520-5118}, abstract = {Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex gastrointestinal condition influenced by genetic, microbial, and environmental factors, among which the gut microbiota plays a crucial role and has emerged as a potential therapeutic target. Ganoderic acid A (GAA), which is a lanostane triterpenoid compound derived from edible mushroom Ganoderma lucidum, has demonstrated the ability to modulate gut dysbiosis. Thus, we investigated the impact of GAA on IBD using a dextran sodium sulfate (DSS)-induced colitis mouse model. GAA effectively prevented colitis, preserved epithelial and mucus layer integrity, and modulated the gut microbiota. In addition, GAA promoted tryptophan metabolism, especially 3-IAld generation, activated the aryl hydrocarbon receptor (AhR), and induced IL-22 production. Fecal microbiota transplantation validated the mediating role of the gut microbiota in the IBD protection conferred by GAA. Our study suggests that GAA holds potential as a nutritional intervention for ameliorating IBD by influencing the gut microbiota, thereby regulating tryptophan metabolism, enhancing AhR activity, and ultimately improving gut barrier function.}, } @article {pmid39078050, year = {2024}, author = {Lee, PJ and Hung, CM and Yang, AJ and Hou, CY and Chou, HW and Chang, YC and Chu, WC and Huang, WY and Kuo, WC and Yang, CC and Lin, KI and Hung, KH and Chang, LC and Lee, KY and Kuo, HP and Lu, KM and Lai, HC and Kuo, ML and Chen, WJ}, title = {MS-20 enhances the gut microbiota-associated antitumor effects of anti-PD1 antibody.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2380061}, pmid = {39078050}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Animals ; Mice ; *Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology/metabolism ; Humans ; *Tumor Microenvironment/immunology ; *CD8-Positive T-Lymphocytes/immunology ; Fecal Microbiota Transplantation ; Cell Line, Tumor ; Probiotics/administration & dosage/pharmacology ; Immunotherapy ; Female ; Colonic Neoplasms/immunology/therapy/drug therapy/microbiology ; Immune Checkpoint Inhibitors/pharmacology ; Lung Neoplasms/immunology/drug therapy/therapy ; Mice, Inbred BALB C ; Xenograft Model Antitumor Assays ; }, abstract = {Cancer immunotherapy has been regarded as a promising strategy for cancer therapy by blocking immune checkpoints and evoking immunity to fight cancer, but its efficacy seems to be heterogeneous among patients. Manipulating the gut microbiota is a potential strategy for enhancing the efficacy of immunotherapy. Here, we report that MS-20, also known as "Symbiota®", a postbiotic that comprises abundant microbial metabolites generated from a soybean-based medium fermented with multiple strains of probiotics and yeast, inhibited colon and lung cancer growth in combination with an anti-programmed cell death 1 (PD1) antibody in xenograft mouse models. Mechanistically, MS-20 remodeled the immunological tumor microenvironment by increasing effector CD8[+] T cells and downregulating PD1 expression, which were mediated by the gut microbiota. Fecal microbiota transplantation (FMT) from mice receiving MS-20 treatment to recipient mice increased CD8[+] T-cell infiltration into the tumor microenvironment and significantly improved antitumor activity when combined with anti-PD1 therapy. Notably, the abundance of Ruminococcus bromii, which increased following MS-20 treatment, was positively associated with a reduced tumor burden and CD8[+] T-cell infiltration in vivo. Furthermore, an ex vivo study revealed that MS-20 could alter the composition of the microbiota in cancer patients, resulting in distinct metabolic pathways associated with favorable responses to immunotherapy. Overall, MS-20 could act as a promising adjuvant agent for enhancing the efficacy of immune checkpoint-mediated antitumor therapy.}, } @article {pmid39073834, year = {2024}, author = {Scheperjans, F and Levo, R and Bosch, B and Lääperi, M and Pereira, PAB and Smolander, OP and Aho, VTE and Vetkas, N and Toivio, L and Kainulainen, V and Fedorova, TD and Lahtinen, P and Ortiz, R and Kaasinen, V and Satokari, R and Arkkila, P}, title = {Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial.}, journal = {JAMA neurology}, volume = {}, number = {}, pages = {}, pmid = {39073834}, issn = {2168-6157}, abstract = {IMPORTANCE: Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models.

OBJECTIVE: To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT.

This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn & Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis.

INTERVENTION: Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy.

MAIN OUTCOMES AND MEASURES: The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs).

RESULTS: The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P = .75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P = .003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group.

CONCLUSIONS AND RELEVANCE: FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04854291.}, } @article {pmid39073794, year = {2024}, author = {Sampson, TR}, title = {Fecal Microbiome Transplants For Parkinson Disease.}, journal = {JAMA neurology}, volume = {}, number = {}, pages = {}, doi = {10.1001/jamaneurol.2024.2293}, pmid = {39073794}, issn = {2168-6157}, } @article {pmid39073205, year = {2024}, author = {Zu, M and Liu, G and Xu, H and Zhu, Z and Zhen, J and Li, B and Shi, X and Shahbazi, MA and Reis, RL and Kundu, SC and Nie, G and Xiao, B}, title = {Extracellular Vesicles from Nanomedicine-Trained Intestinal Microbiota Substitute for Fecal Microbiota Transplant in Treating Ulcerative Colitis.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {}, number = {}, pages = {e2409138}, doi = {10.1002/adma.202409138}, pmid = {39073205}, issn = {1521-4095}, support = {82072060//National Natural Science Foundation of China/ ; 82360110//National Natural Science Foundation of China/ ; SWU-XDPY22006//Fundamental Research Funds for the Central Universities/ ; SWU-KQ22075//Fundamental Research Funds for the Central Universities/ ; 2205012980212766//Venture & Innovation Support Program for Chongqing Overseas Returnees/ ; 2022NSCQ-JQX5279//Science Fund for Distinguished Young Scholars of Chongqing Municipality/ ; 20212BDH81019//Key Science and Technology Research Project in Jiangxi Province Department of Education/ ; 20224BAB206073//Key Science and Technology Research Project in Jiangxi Province Department of Education/ ; }, abstract = {The biosafety concerns associated with fecal microbiota transplant (FMT) limit their clinical application in treating ulcerative colitis (UC). Gut microbiota secrete abundant extracellular vesicles (Gm-EVs), which play a critical role in bacteria-to-bacteria and bacteria-to-host communications. Herein, intestinal microbiota are trained using tea leaf lipid/pluronic F127-coated curcumin nanocrystals (CN@Lp127s), which can maintain stability during transit through the gastrointestinal tract. Compared with FMT, Gm-EVs derived from healthy mice significantly improve treatment outcomes against UC by reducing colonic inflammatory responses, restoring colonic barrier function, and rebalancing intestinal microbiota. Strikingly, Gm-EVs obtained from CN@Lp127-trained healthy mice exhibit a superior therapeutic effect on UC compared to groups receiving FMT from healthy mice, Gm-EVs from healthy mice, and FMT from CN@Lp127-trained healthy mice. Oral administration of Gm-EVs from CN@Lp127-trained healthy mice not only alleviates colonic inflammation, promotes mucosal repair, and regulates gut microbiota but also regulates purine metabolism to decrease the uric acid level, resulting in a robust improvement in the UC. This study demonstrates the UC therapeutic efficacy of Gm-EVs derived from nanomedicine-trained gut microbiota in regulating the immune microenvironment, microbiota, and purine metabolism of the colon. These EVs provide an alternative platform to replace FMT as a treatment for UC.}, } @article {pmid39071723, year = {2024}, author = {Huang, C and Huang, C and Tian, R and Pu, Y and Chen, P}, title = {Washed microbiota transplantation via colonic transendoscopic enteral tube rescues severe acute pancreatitis: A case series.}, journal = {Heliyon}, volume = {10}, number = {13}, pages = {e33678}, pmid = {39071723}, issn = {2405-8440}, abstract = {BACKGROUND: Gut microbiota dysbiosis plays a significant role in the development of acute pancreatitis (AP). However, a recent randomized trial reported negative findings regarding the use of fecal microbiota transplantation (FMT) via the mid-gut tube in severe AP. The case series presents the feasibility of washed microbiota transplantation (WMT) as a new methodology of FMT and its delivery via colonic transendoscopic enteral tubing (TET) for severe AP.

CASE SERIES: We presented two cases of severe AP rapidly rescued using WMT via colonic TET. Symptoms related to severe AP and the acute physiology and chronic health evaluation-II score improved soon after WMT. In Case 1, bilirubin and infection indexes continuously decreased after the initial WMT and the patient was successfully weaned off the ventilator and recovered from multiple organ system failures (MSOF) within ten days. In Case 2, the patient's consciousness rapidly improved within one day after WMT, with normal bowel sounds and stable blood pressure without vasoactive drug maintenance. Both Case 1 and Case 2 completed follow-ups of seven months and twenty-two months, respectively, with no reports of new-onset diabetes.

CONCLUSION: WMT via colonic TET played a critical therapeutic role in rescuing severe AP cases. This is the first report providing direct evidence for the clinical value of targeting microbiota through colonic TET in rescuing severe AP.}, } @article {pmid39071345, year = {2024}, author = {Debray, R and Dickson, CC and Webb, SE and Archie, EA and Tung, J}, title = {When is microbial strain sharing evidence for transmission?.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.07.18.604082}, pmid = {39071345}, issn = {2692-8205}, abstract = {In humans and other social animals, social partners have more similar microbiomes than expected by chance, suggesting that social contact transfers microorganisms. However, social microbiome transmission can be difficult to identify if social partners also have other traits in common or live in a shared environment. Strain-resolved metagenomics has been proposed as a solution for tracking microbial transmission. Using a fecal microbiota transplant dataset, we show that strain sharing can recapitulate true transmission networks under ideal settings when donor-recipient pairs are unambiguous. However, gut metagenomes from a wild baboon population, where social networks predict compositional similarity, show that strain sharing is also driven by demographic and environmental factors that can override signals of social interactions. We conclude that strain-level analyses provide useful information about microbiome similarity, but other facets of study design, especially longitudinal sampling and careful consideration of host characteristics, are essential for conclusions about the underlying mechanisms.}, } @article {pmid39071049, year = {2024}, author = {Ramos-Martínez, A and Múñez, E and Del-Campo, R and Nieto-Fernández, A and Gonzalez-Haba, M and Calderón-Parra, J}, title = {Fecal microbiota transplantation as a preventive treatment for recurrent acute cholangitis.}, journal = {IDCases}, volume = {37}, number = {}, pages = {e02025}, pmid = {39071049}, issn = {2214-2509}, abstract = {BACKGROUND: Recurrent acute cholangitis (RAC) is a relatively uncommon entity that presents significant management difficulties. We present the case of a patient with RAC in whom the number of episodes was reduced after a novel therapeutic procedure.

CASE REPORT: A 93-year-old male who in June 2019 was admitted for chills without fever, shivering, epigastric abdominal pain and moderate jaundice. Both abdominal ultrasound and CT scan showed intrahepatic and extrahepatic duct dilatation up to the papilla with no evidence of mass at that level. Endoscopic retrograde cholangiopancreatography (ERCP) was performed and abundant biliary sludge was removed. E. coli was identified as the cause of several of the episodes. Some isolates were shown to produce extended spectrum beta-lactamase (ESBL). Papillotomy was performed and plastic prosthesis and later a metallic prosthesis were implanted. Several months later a surgical bypass of the biliary tract was performed due to persistent episodes of cholangitis. When the chronic suppressive antibiotic treatment subsequently instituted to prevent new episodes of cholangitis failed, it was decided to perform a fecal microbiota transplant from a healthy donor and to suspend the chronic suppressive treatment. Since then, she has not presented new episodes of RAC for more than 10 months of clinical follow-up. BLEE-producing E. coli in the gastrointestinal tract could not be eradicated.

COMMENT: Chronic colonization of the biliary tract by certain enterobacteria such as E. coli has been identified as a relevant pathogenic factor in cases of RAC. FMT may be a promising tool to improve the clinical course of patients with RAC.}, } @article {pmid39070844, year = {2024}, author = {Zhang, JT and Zhang, N and Dong, XT and Wang, XR and Ma, HW and Liu, YD and Li, MR}, title = {Efficacy and safety of fecal microbiota transplantation for treatment of ulcerative colitis: A post-consensus systematic review and meta-analysis.}, journal = {World journal of clinical cases}, volume = {12}, number = {21}, pages = {4691-4702}, pmid = {39070844}, issn = {2307-8960}, abstract = {BACKGROUND: Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation (FMT) as a therapy for ulcerative colitis (UC). However, the treatment processes and outcomes of these studies vary.

AIM: To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis.

METHODS: The inclusion criteria involved reports of adult patients with UC treated with FMT, while studies that did not report clinical outcomes or that included patients with infection were excluded. Clinical remission (CR) and endoscopic remission (ER) were the primary and secondary outcomes, respectively.

RESULTS: We included nine studies retrieved from five electronic databases. The FMT group had better CR than the control group [relative risk (RR) = 1.53; 95% confidence interval (CI): 1.19-1.94; P < 0.0008]. ER was statistically significantly different between the two groups (RR = 2.80; 95%CI: 1.93-4.05; P < 0.00001). Adverse events did not differ significantly between the two groups.

CONCLUSION: FMT demonstrates favorable performance and safety; however, well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended. Furthermore, standardizing the FMT process is urgently needed for improved safety and efficacy.}, } @article {pmid39065063, year = {2024}, author = {Bottino, P and Vay, D and Leli, C and Ferrara, L and Pizzo, V and Gotta, F and Raiteri, A and Rapallo, F and Roveta, A and Maconi, A and Rocchetti, A}, title = {Evaluation of Bacterial Viability for Fecal Microbiota Transplantation: Impact of Thawing Temperature and Storage Time.}, journal = {Microorganisms}, volume = {12}, number = {7}, pages = {}, pmid = {39065063}, issn = {2076-2607}, abstract = {Fecal Microbiota Transplantation (FMT) represents a promising therapeutic tool under study for several purposes and is currently applied to the treatment of recurrent Clostridioides difficile infection. However, since the use of fresh stool was affected by several issues linked to donor screening, the development of a frozen stool bank is a reliable option to standardize FMT procedures. Nevertheless, different environmental factors impact microbial viability. Herein, we report the effect of different thawing temperatures and storage conditions on bacterial suspensions in the FMT procedure. In total, 20 stool samples were divided into aliquots and tested across a combination of different storing periods (15, 30; 90 days) and thawing procedures (4 °C overnight, room temperature for 1 h; 37 °C for 5 min). Focusing on storage time, our data showed a significant reduction in viability for aerobic and anaerobic bacteria after thawing for 15 days, while no further reductions were observed until after 90 days. Instead, among the different thawing procedures, no significant differences were observed for aerobic bacteria, while for anaerobes, thawing at 37 °C for 5 min was more effective in preserving the bacterial viability. In conclusion, the frozen fecal microbiota remained viable for at least three months, with an excellent recovery rate in all three thawing conditions.}, } @article {pmid39064809, year = {2024}, author = {Kuźniar, J and Kozubek, P and Czaja, M and Leszek, J}, title = {Correlation between Alzheimer's Disease and Gastrointestinal Tract Disorders.}, journal = {Nutrients}, volume = {16}, number = {14}, pages = {}, pmid = {39064809}, issn = {2072-6643}, mesh = {Humans ; *Alzheimer Disease/microbiology ; *Gastrointestinal Microbiome ; *Gastrointestinal Diseases/microbiology ; Brain-Gut Axis/physiology ; Helicobacter Infections/complications/microbiology ; Periodontitis/microbiology ; Gastrointestinal Tract/microbiology/metabolism ; Helicobacter pylori ; Inflammatory Bowel Diseases/microbiology/metabolism ; Brain/metabolism ; }, abstract = {Alzheimer's disease is the most common cause of dementia globally. The pathogenesis is multifactorial and includes deposition of amyloid-β in the central nervous system, presence of intraneuronal neurofibrillary tangles and a decreased amount of synapses. It remains uncertain what causes the progression of the disease. Nowadays, it is suggested that the brain is connected to the gastrointestinal tract, especially the enteric nervous system and gut microbiome. Studies have found a positive association between AD and gastrointestinal diseases such as periodontitis, Helicobacter pylori infection, inflammatory bowel disease and microbiome disorders. H. pylori and its metabolites can enter the CNS via the oropharyngeal olfactory pathway and may predispose to the onset and progression of AD. Periodontitis may cause systemic inflammation of low severity with high levels of pro-inflammatory cytokines and neutrophils. Moreover, lipopolysaccharide from oral bacteria accompanies beta-amyloid in plaques that form in the brain. Increased intestinal permeability in IBS leads to neuronal inflammation from transference. Chronic inflammation may lead to beta-amyloid plaque formation in the intestinal tract that spreads to the brain via the vagus nerve. The microbiome plays an important role in many bodily functions, such as nutrient absorption and vitamin production, but it is also an important factor in the development of many diseases, including Alzheimer's disease. Both the quantity and diversity of the microbiome change significantly in patients with AD and even in people in the preclinical stage of the disease, when symptoms are not yet present. The microbiome influences the functioning of the central nervous system through, among other things, the microbiota-gut-brain axis. Given the involvement of the microbiome in the pathogenesis of AD, antibiotic therapy, probiotics and prebiotics, and faecal transplantation are being considered as possible therapeutic options.}, } @article {pmid39064789, year = {2024}, author = {Liu, W and Xu, S and Zhang, B and Sun, X}, title = {Ramulus Mori (Sangzhi) Alkaloids Alleviate Diabetic Nephropathy through Improving Gut Microbiota Disorder.}, journal = {Nutrients}, volume = {16}, number = {14}, pages = {}, pmid = {39064789}, issn = {2072-6643}, support = {82274174//the National Natural Science Foundation of China/ ; No. 2022-I2M-1-018//the CAMS Innovation Fund for Medical Sciences (CIFMS)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diabetic Nephropathies/drug therapy ; *Alkaloids/pharmacology ; Mice ; Male ; *Mice, Inbred C57BL ; Diet, High-Fat/adverse effects ; Podocytes/drug effects ; Diabetes Mellitus, Experimental/drug therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Diabetic nephropathy (DN), one of the leading causes of end-stage kidney failure worldwide, is closely associated with high mortality in diabetic patients. However, therapeutic drugs for DN are still lacking. Ramulus Mori alkaloids (SZ-A), an effective component of alkaloids extracted from Ramulus Mori, have been found to improve glucose and lipid metabolism to mitigate diabetes and obesity; however, few studies have focused on their effects on DN progression. Thus, we investigated the protective role of SZ-A on DN through 16S rRNA sequencing, non-targeted metabolomics, and fecal microbiota transplantation (FMT) experiments. To address our hypothesis, we established the DN mouse model by combining a high-fat diet (HFD) with streptozotocin (STZ) injection. Herein, we demonstrated that SZ-A supplementation was recalcitrant to renal injury in DN mice, improving glomerular morphology, reversing the blood biochemistry parameters, and ameliorating podocyte injury. Importantly, the composition of the gut microbiota altered after SZ-A treatment, especially with the elevated abundance of Dubosiella and the increased level of serum pentadecanoic acid. FMT experiments further revealed that the gut microbiota exerted critical effects in mediating the beneficial roles of SZ-A. In vitro experiments proved that pentadecanoic acid administration improved podocyte apoptosis induced by AGEs. Taken together, SZ-A play a renoprotective role, possibly through regulating the gut microbiota and promoting pentadecanoic acid production. Our current study lends support to more extensive clinical applications of SZ-A.}, } @article {pmid39063080, year = {2024}, author = {Zhang, Y and Wang, C and Lang, H and Yu, H and Zhou, M and Rao, X and Zhang, Q and Yi, L and Zhu, J and Mi, M}, title = {The Contrasting Effects of Two Distinct Exercise Training Modalities on Exhaustive Exercise-Induced Muscle Damage in Mice May Be Associated with Alterations in the Gut Microbiota.}, journal = {International journal of molecular sciences}, volume = {25}, number = {14}, pages = {}, pmid = {39063080}, issn = {1422-0067}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Physical Conditioning, Animal ; Mice ; *Muscle, Skeletal/metabolism ; *Fatty Acids, Volatile/metabolism ; Male ; Oxidative Stress ; Mice, Inbred C57BL ; Swimming ; }, abstract = {Exhaustive exercise is known to induce muscle damage characterized by inflammation and oxidative stress. Although "regular" and "weekend warrior" exercise regimens have been shown to confer comparable health benefits in human studies, such as reduced risks of all-cause, cardiovascular disease (CVD), and cancer mortality, their differential impacts on muscle damage post-exhaustive exercise remain unclear. This study aimed to compare the effects of long-term, moderate-intensity (LTMI) and short-term, high-intensity (STHI) training modalities, matched for total exercise volume, on gut microbiota, short-chain fatty acids (SCFAs), and exhaustive exercise-induced muscle damage in mice, as well as to evaluate the correlation between these factors. LTMI is considered a regular exercise regimen, while STHI shares some similarities with the "weekend warrior" pattern, such as promoting exercise intensity and condensing training sessions into a short period. Our findings indicate that LTMI training significantly enhanced the abundance of SCFA-producing bacteria, including Akkermansia, Prevotellaceae_NK3B31_group, Odoribacter, Alistipes, and Lactobacillus, thereby increasing SCFA levels and attenuating muscle damage following exhaustive swimming. In contrast, STHI training increased the abundance of opportunistic pathogens such as Staphylococcus and Bilophila, without altering SCFA levels, and was associated with exacerbated muscle damage. Moreover, we observed a significant negative correlation between the abundance of SCFA-producing bacteria and SCFA levels with the expression of inflammatory cytokines in the muscle of mice post-exhaustive exercise. Conversely, the abundance of Staphylococcus and Bilophila showed a notable positive correlation with these cytokines. Additionally, the effects of LTMI and STHI on exhaustive exercise-induced muscle damage were transmissible to untrained mice via fecal microbiota transplantation, suggesting that gut microbiota changes induced by these training modalities may contribute to their contrasting impacts on muscle damage. These results underscore the significance of selecting an appropriate training modality prior to engaging in exhaustive exercise, with implications for athletic training and injury prevention.}, } @article {pmid39062985, year = {2024}, author = {Sadowski, K and Zając, W and Milanowski, Ł and Koziorowski, D and Figura, M}, title = {Exploring Fecal Microbiota Transplantation for Modulating Inflammation in Parkinson's Disease: A Review of Inflammatory Markers and Potential Effects.}, journal = {International journal of molecular sciences}, volume = {25}, number = {14}, pages = {}, pmid = {39062985}, issn = {1422-0067}, mesh = {Humans ; *Parkinson Disease/microbiology/therapy/metabolism ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Animals ; *Biomarkers ; *Inflammation/metabolism/microbiology ; Brain-Gut Axis ; }, abstract = {Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by numerous motor and non-motor symptoms. Recent data highlight a potential interplay between the gut microbiota and the pathophysiology of PD. The degeneration of dopaminergic neurons in PD leads to motor symptoms (tremor, rigidity, and bradykinesia), with antecedent gastrointestinal manifestations, most notably constipation. Consequently, the gut emerges as a plausible modulator in the neurodegenerative progression of PD. Key molecular changes in PD are discussed in the context of the gut-brain axis. Evidence suggests that the alterations in the gut microbiota composition may contribute to gastroenteric inflammation and influence PD symptoms. Disturbances in the levels of inflammatory markers, including tumor necrosis factor-α (TNF α), interleukin -1β (IL-1β), and interleukin-6 (IL-6), have been observed in PD patients. These implicate the involvement of systemic inflammation in disease pathology. Fecal microbiota transplantation emerges as a potential therapeutic strategy for PD. It may mitigate inflammation by restoring gut homeostasis. Preclinical studies in animal models and initial clinical trials have shown promising results. Overall, understanding the interplay between inflammation, the gut microbiota, and PD pathology provides valuable insights into potential therapeutic interventions. This review presents recent data about the bidirectional communication between the gut microbiome and the brain in PD, specifically focusing on the involvement of inflammatory biomarkers.}, } @article {pmid39062142, year = {2024}, author = {Goloshchapov, OV and Chukhlovin, AB and Polev, DE and Eismont, YA and Bug, DS and Kusakin, AV and Kosarev, OV and Klementeva, RV and Gostev, VV and Ageevets, VA and Volkov, NP and Ipatova, AS and Moiseev, IS and Spiridonova, AA and Sidorenko, SV and Kulagin, AD}, title = {Time-Dependent Shifts in Intestinal Bacteriome, Klebsiella Colonization and Incidence of Antibiotic-Resistance Genes after Allogeneic Hematopoietic Stem Cell Transplantation.}, journal = {Biomedicines}, volume = {12}, number = {7}, pages = {}, pmid = {39062142}, issn = {2227-9059}, support = {22-15-00149//Russian Science Foundation/ ; 22-15-00149//Russian Science Foundation/ ; }, abstract = {Dose-intensive cytostatic therapy and antibiotic treatment in allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause severe abnormalities in a composition of gut microbiota as well as the emergence of antibiotic resistance. The data on the longitudinal recovery of major bacterial phyla and the expansion of genes associated with antibiotic resistance are limited. We collected regular stool samples during the first year after allo-HSCT from 12 adult patients with oncohematological disorders after allo-HSCT and performed 16SrRNA sequencing, multiplex PCR, conventional bacteriology and CHROMagar testing. We observed a decline in Shannon microbiota diversity index as early as day 0 of allo-HSCT (p = 0.034) before any administration of antibiotics, which persisted up to 1 year after transplantation, when the Shannon index returned to pre-transplant levels (p = 0.91). The study confirmed the previously shown decline in Bacillota (Firmicutes) genera and the expansion of E. coli/Shigella, Klebsiella and Enterococci. The recovery of Firmicutes was slower than that of other phyla and occurred only a year post-transplant. A positive correlation was observed between the expansion of E. coli/Shigella genera and blaKPC, blaCTX-M-1 and blaTEM (p < 0.001), Klebsiella spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaTEM, and blaSHV (p < 0.001), Pseudomonas spp. and blaNDM (p = 0.002), Enterococcus spp. and blaOXA-48-like, blaNDM, blaCTX-M-1, blaSHV (p < 0.01). The correlation was observed between the expansion of Enterobacterales and and carbapenemase-positive CHROMagar samples (p < 0.001). Samples positive for carbapenem-resitant bacteria were at their maximum levels on day +30, and were gradually diminishing one year after allo-HSCT. From day +30 to +60, all isolated K. pneumoniae strains in fecal samples proved to be resistant to the main antibiotic groups (carbapenems, aminoglycosides, fluoroquinolones, third-generation cephalosporins). One year after HSCT, we documented the spontaneous decolonization of K. pneumoniae. The sensitivity of molecular biology techniques in the search for total and antibiotic-resistant Klebsiella seems to be superior to common bacteriological cultures. Future studies should be focused on searching for novel approaches to the efficient reconstitution and/or maintenance of strictly anaerobic microbiota in oncological patients.}, } @article {pmid39061970, year = {2024}, author = {Chen, JH and Chiu, CH and Chen, CC and Chen, YC and Yeh, PJ and Kuo, CJ and Chiu, CT and Cheng, HT and Pan, YB and Le, PH}, title = {Comparative Efficacy of Fecal Microbiota Transplantation in Treating Refractory or Recurrent Clostridioides difficile Infection among Patients with and without Inflammatory Bowel Disease: A Retrospective Cohort Study.}, journal = {Biomedicines}, volume = {12}, number = {7}, pages = {}, pmid = {39061970}, issn = {2227-9059}, abstract = {Clostridioides difficile infection (CDI) worsens inflammatory bowel disease (IBD) prognosis. While fecal microbiota transplantation (FMT) is effective for refractory or recurrent CDI (rrCDI), comparative success rates between IBD and non-IBD patients are scarce. This study addresses this gap. A retrospective cohort study was conducted at Chang Gung Memorial Hospital from April 2019 to October 2023. Patients receiving FMT for rrCDI were categorized into IBD and non-IBD groups. Baseline characteristics and outcomes were compared at one month and one year, with successful FMT defined as the resolution of diarrhea without CDI recurrence. The study included 88 patients: 30 with IBD and 58 without IBD. The IBD group was younger, with fewer comorbidities. Success rates at one month were similar between groups (IBD: 80.0% vs. non-IBD: 78.9%, p = 0.908), as were negative toxin tests (IBD: 83.3% vs. non-IBD: 63.8%, p = 0.174). One-year success rates (IBD: 70.0% vs. non-IBD: 67.6%, p = 0.857) and eradication rates (IBD: 94.4% vs. non-IBD: 73.9%, p = 0.112) were also similar. Poor bowel preparation predicted FMT failure at one month (OR = 0.23, p = 0.019). No safety issues were reported. FMT is a safe, effective treatment for rrCDI, demonstrating similar success rates in patients with and without IBD.}, } @article {pmid39061510, year = {2024}, author = {Kiełbik, P and Witkowska-Piłaszewicz, O}, title = {The Relationship between Canine Behavioral Disorders and Gut Microbiome and Future Therapeutic Perspectives.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {14}, pages = {}, pmid = {39061510}, issn = {2076-2615}, abstract = {Canine behavioral disorders have become one of the most common concerns and challenging issues among dog owners. Thus, there is a great demand for knowledge about various factors affecting dogs' emotions and well-being. Among them, the gut-brain axis seems to be particularly interesting, especially since in many instances the standard treatment or behavioral therapies insufficiently improve animal behavior. Therefore, to face this challenge, the search for novel therapeutic methods is highly required. Existing data show that mammals' gut microbiome, immune system, and nervous system are in continuous communication and influence animal physiology and behavior. This review aimed to summarize and discuss the most important scientific evidence on the relationship between mental disorders and gut microbiota in dogs, simultaneously presenting comparable outcomes in humans and rodent models. A comprehensive overview of crucial mechanisms of the gut-brain axis is included. This refers especially to the neurotransmitters crucial for animal behavior, which are regulated by the gut microbiome, and to the main microbial metabolites-short-chain fatty acids (SCFAs). This review presents summarized data on gut dysbiosis in relation to the inflammation process within the organism, as well as the activation of the hypothalamic-pituitary-adrenal (HPA) axis. All of the above mechanisms are presented in this review in strict correlation with brain and/or behavioral changes in the animal. Additionally, according to human and laboratory animal studies, the gut microbiome appears to be altered in individuals with mental disorders; thus, various strategies to manipulate the gut microbiota are implemented. This refers also to the fecal microbiome transplantation (FMT) method, based on transferring the fecal matter from a donor into the gastrointestinal tract of a recipient in order to modulate the gut microbiota. In this review, the possible effects of the FMT procedure on animal behavioral disorders are discussed.}, } @article {pmid39060829, year = {2024}, author = {Ding, G and Yang, X and Li, Y and Wang, Y and Du, Y and Wang, M and Ye, R and Wang, J and Zhang, Y and Chen, Y and Zhang, Y}, title = {Gut microbiota regulates gut homeostasis, mucosal immunity and influences immune-related diseases.}, journal = {Molecular and cellular biochemistry}, volume = {}, number = {}, pages = {}, pmid = {39060829}, issn = {1573-4919}, support = {KFJJ-2023-08//Key Laboratory of Anti-inflammatory and Immunological Drugs of the Ministry of Education of the People's Republic of China/ ; 2022KJZD08//Hefei Normal University School-level research project/ ; KJ2021ZD0113& 2022AH052166//Natural Science Foundation of Higher Education in Anhui Province/ ; HXXM2022129& HXXM2023075//Horizontal Development Project of Hefei Normal University/ ; }, abstract = {The intestinal microbiome constitutes a sophisticated and massive ecosystem pivotal for maintaining gastrointestinal equilibrium and mucosal immunity via diverse pathways. The gut microbiota is continuously reshaped by multiple environmental factors, thereby influencing overall wellbeing or predisposing individuals to disease state. Many observations reveal an altered microbiome composition in individuals with autoimmune conditions, coupled with shifts in metabolic profiles, which has spurred ongoing development of therapeutic interventions targeting the microbiome. This review delineates the microbial consortia of the intestine, their role in sustaining gastrointestinal stability, the association between the microbiome and immune-mediated pathologies, and therapeutic modalities focused on microbiome modulation. We emphasize the entire role of the intestinal microbiome in human health and recommend microbiome modulation as a viable strategy for disease prophylaxis and management. However, the application of gut microbiota modification for the treatment of immune-related diseases, such as fecal microbiota transplantation and probiotics, remain quite challenging. Therefore, more research is needed into the role and mechanisms of these therapeutics.}, } @article {pmid39060738, year = {2024}, author = {Levy, EI and Dinleyici, M and Dinleyici, E and Vandenplas, Y}, title = {Clostridioides difficile Infections: Prevention and Treatment Strategies.}, journal = {Advances in experimental medicine and biology}, volume = {1449}, number = {}, pages = {175-186}, pmid = {39060738}, issn = {0065-2598}, mesh = {Humans ; *Clostridium Infections/prevention & control/microbiology/therapy ; *Clostridioides difficile/pathogenicity/physiology ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; *Anti-Bacterial Agents/therapeutic use ; Gastrointestinal Microbiome ; Diarrhea/prevention & control/microbiology/therapy ; }, abstract = {Clostridioides difficile is the most common causative agent of antibiotic-associated diarrhea. This spore forming, obligate anaerobic, gram-positive bacillus is becoming responsible for an increasing number of infections worldwide, both in community and in hospital settings, whose severity can vary widely from an asymptomatic infection to a lethal disease. While discontinuation of antimicrobial agents and antibiotic treatment of the infection remain the cornerstone of therapy, more recent fecal microbiota transplantation has also been valid as a therapy. The use of probiotics, especially Saccharomyces boulardii CNCM I-745 have become valid forms of prevention therapy. Although there are studies in adults with microbiota-targeted new generation therapies and Clostridium difficile vaccines, there are no data in the paediatric age group yet.}, } @article {pmid39060734, year = {2024}, author = {Nicastro, E and D'Antiga, L}, title = {Nutritional Interventions, Probiotics, Synbiotics and Fecal Microbiota Transplantation in Steatotic Liver Disease : Pediatric Fatty Liver and Probiotics.}, journal = {Advances in experimental medicine and biology}, volume = {1449}, number = {}, pages = {113-133}, pmid = {39060734}, issn = {0065-2598}, mesh = {Humans ; *Probiotics/therapeutic use/administration & dosage ; *Synbiotics/administration & dosage ; Child ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Fatty Liver/therapy/microbiology/pathology ; Non-alcoholic Fatty Liver Disease/microbiology/therapy/metabolism ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major health problem worldwide, and the strongest determinant of liver disease in children. The possible influence of high-fat/low-fiber dietary patterns with microbiota (e.g., increased Firmicutes/Bacteroidetes ratio), and ultimately with MASLD occurrence and progression has been elucidated by several association studies. The possible mechanisms through which microbes exert their detrimental effects on MASLD include gut vascular barrier damage, a shift towards non-tolerogenic immunologic environment, and the detrimental metabolic changes, including a relative reduction of propionate and butyrate in favor of acetate, endogenous ethanol production, and impairment of the unconjugated bile acid-driven FXR-mediated gut-liver axis. The impact of nutritional and probiotic interventions in children with MASLD is described.}, } @article {pmid39059396, year = {2024}, author = {Kim, Y and Kim, G and Kim, S and Cho, B and Kim, SY and Do, EJ and Bae, DJ and Kim, S and Kweon, MN and Song, JS and Park, SH and Hwang, SW and Kim, MN and Kim, Y and Min, K and Kim, SH and Adams, MD and Lee, C and Park, H and Park, SR}, title = {Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2024.06.010}, pmid = {39059396}, issn = {1934-6069}, abstract = {The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers.}, } @article {pmid39057689, year = {2024}, author = {Vallianou, NG and Kounatidis, D and Psallida, S and Vythoulkas-Biotis, N and Adamou, A and Zachariadou, T and Kargioti, S and Karampela, I and Dalamaga, M}, title = {NAFLD/MASLD and the Gut-Liver Axis: From Pathogenesis to Treatment Options.}, journal = {Metabolites}, volume = {14}, number = {7}, pages = {}, pmid = {39057689}, issn = {2218-1989}, abstract = {Nonalcoholic fatty liver disease (NAFLD) poses an emerging threat topublic health. Nonalcoholic steatohepatitis (NASH) is reported to be the most rapidly rising cause of hepatocellular carcinoma in the western world. Recently, a new term has been proposed: metabolic dysfunction-associated steatotic liver disease (MASLD). The introduction of this new terminology has sparked a debate about the interchangeability of these terms. The pathogenesis of NAFLD/MASLD is thought to be multifactorial, involving both genetic and environmental factors. Among these factors, alterations in gut microbiota and gut dysbiosis have recently garnered significant attention. In this context, this review will further discuss the gut-liver axis, which refers to the bidirectional interaction between the human gut microbiota and the liver. Additionally, the therapeutic potential of probiotics, particularly next-generation probiotics and genetically engineered bacteria, will be explored. Moreover, the role of prebiotics, synbiotics, postbiotics, and phages as well as fecal microbiota transplantation will be analyzed. Particularly for lean patients with NAFLD/MASLD, who have limited treatment options, approaches that modify the diversity and composition of the gut microbiota may hold promise. However, due to ongoing safety concerns with approaches that modulate gut microbiota, further large-scale studies are necessary to better assess their efficacy and safety in treating NAFLD/MASLD.}, } @article {pmid39056206, year = {2024}, author = {Jiang, X and Gao, X and Ding, J and Pang, B and Pei, Y and Zhao, Z and Zhao, N and Wang, Z and Chen, C and Gao, D and Yan, F and Wang, F and Liu, C and Zhang, Z and Li, Z and Zhao, Z}, title = {Fecal microbiota transplantation alleviates mild-moderate COVID-19 associated diarrhoea and depression symptoms: A prospective study of a randomized, double-blind clinical trial.}, journal = {Journal of medical virology}, volume = {96}, number = {8}, pages = {e29812}, doi = {10.1002/jmv.29812}, pmid = {39056206}, issn = {1096-9071}, support = {//Construction Funds of Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment from The First Hospital of Hebei Medical University; and other Hebei Province Projects/ ; //National Natural Science Foundation of China/ ; //The Natural Science Foundation of Hebei/ ; //Hebei Provincial Department of Human Resources and Social Security/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *COVID-19/therapy/complications ; *Diarrhea/therapy/microbiology/virology ; Male ; Female ; Double-Blind Method ; Middle Aged ; *Depression/therapy ; Prospective Studies ; Adult ; Aged ; Feces/microbiology/virology ; SARS-CoV-2 ; Treatment Outcome ; Aspartate Aminotransferases/blood ; Gastrointestinal Microbiome ; }, abstract = {Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.}, } @article {pmid39055928, year = {2024}, author = {Lang, Y and Zhong, C and Guo, L and Liu, Z and Zuo, D and Chen, X and Ding, L and Huang, B and Li, B and Yuan, Y and Niu, Y and Qiu, J and Qian, C}, title = {Monoacylglycerol acyltransferase-2 inhibits colorectal carcinogenesis in APC[min+/-] mice.}, journal = {iScience}, volume = {27}, number = {7}, pages = {110205}, pmid = {39055928}, issn = {2589-0042}, abstract = {Monoacylglycerol acyltransferase-2 (MOGAT2), encodes MOGAT enzyme in the re-synthesis of triacylglycerol and protects from metabolism disorders. While, its precise involvement in colorectal cancer (CRC) progression remains inadequately understood. Our study demonstrated that knockout of Mogat2 in Apc[min/+] mice expedited intestinal tumor growth and progression, indicating that Mogat2 plays a tumor-suppressing role in CRC. Mechanically, Mogat2 deletion resulted in a significant alter the gut microbiota, while Fecal Microbiota Transplantation (FMT) experiments demonstrated that the gut microbiota in Mogat2 deleted mice promoted tumor growth. Furthermore, we identified Mogat2 as a functional regulator suppressing CRC cell proliferation and tumor growth by inhibiting the NF-κB signaling pathway in vivo. Collectively, these results provide novel insights into the protective double roles of Mogat2, inhibiting of NF-κB pathway and keeping gut microbiota homeostasis in colorectal cancer, which may help the development of novel cancer treatments for CRC.}, } @article {pmid39055874, year = {2024}, author = {Chen, R and Wu, F and Zeng, G and Chen, Y and Lu, S and Huang, H}, title = {Therapeutic effect of fecal microbiota transplantation on rats with liver cirrhosis and its influence on gut microbiota.}, journal = {Iranian journal of basic medical sciences}, volume = {27}, number = {9}, pages = {1148-1154}, pmid = {39055874}, issn = {2008-3866}, abstract = {OBJECTIVES: This study aimed to explore the therapeutic effect of fecal microbiota transplantation (FMT) on liver cirrhosis-induced rat models by studying changes in intestinal flora distribution and liver pathology.

MATERIALS AND METHODS: Cirrhosis was induced in adult male Sprague-Dawley rats using carbon tetrachloride; successful establishment of the cirrhosis model was verified using hematoxylin and eosin (HE) staining. Rats were divided into normal control, cirrhosis model+normal saline, and cirrhosis model+FMT groups. Fecal intestinal flora was analyzed using 16S rRNA high-throughput sequencing for each group. Alpha diversity, beta diversity, and functional prediction analyses were performed. Additionally, rat liver tissue was subjected to HE staining to compare the degree of fibrosis and liver damage between the groups.

RESULTS: FMT significantly improved the diversity, richness, and uniformity of the intestinal flora in rats with liver cirrhosis. Notably, post-FMT, the abundance of lactobacillaceae, bacilli, and bacteroidia increased, while the abundance of clostridia decreased. Moreover, hepatic fibrosis improved after FMT.

CONCLUSION: The dysbiosis of intestinal flora in rats with liver cirrhosis improved after FMT. Thus, FMT can regulate intestinal flora, reduce liver inflammation, and improve hepatic fibrosis and cirrhosis.}, } @article {pmid39054706, year = {2024}, author = {Lin, J and Chen, Y and Li, T and Zhu, C and Qiu, Y and Yu, E}, title = {Research Progress on Mechanisms of Modulating Gut Microbiota to Improve Symptoms of Major Depressive Disorder.}, journal = {Discovery medicine}, volume = {36}, number = {186}, pages = {1354-1362}, doi = {10.24976/Discov.Med.202436186.125}, pmid = {39054706}, issn = {1944-7930}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Depressive Disorder, Major/microbiology/therapy/immunology ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Brain-Gut Axis/physiology ; Animals ; }, abstract = {Major depressive disorder (MDD) is a clinical condition that significantly impacts patients' physical and mental well-being, quality of life, and social functioning. The pathogenesis of MDD remains unclear, but accumulating evidence suggests a close relationship between gut microbiota and the occurrence and progression of MDD. Gut microbiota refers to the microbial community in the human intestine, which engages in bidirectional communication with the host via the "gut-brain axis" and plays a pivotal role in influencing the host's metabolism, immune system, endocrine system, and nervous system. Modulating gut microbiota entails restoring the balance and function of the intestinal flora through methods such as probiotic intake, fecal transplantation, and dietary intervention. Such modulation has been shown to effectively alleviate depressive symptoms in the host. This review synthesizes recent advancements in research on gut microbiota modulation for ameliorating depressive symptoms and can serve as a foundation for further exploration of the gut microbiota's role in MDD and its potential therapeutic benefits.}, } @article {pmid39054479, year = {2024}, author = {Boldrini, L and Chiloiro, G and Di Franco, S and Romano, A and Smiljanic, L and Tran, EH and Bono, F and Charles Davies, D and Lopetuso, L and De Bonis, M and Minucci, A and Giacò, L and Cusumano, D and Placidi, L and Giannarelli, D and Sala, E and Gambacorta, MA}, title = {MOREOVER: multiomics MR-guided radiotherapy optimization in locally advanced rectal cancer.}, journal = {Radiation oncology (London, England)}, volume = {19}, number = {1}, pages = {94}, pmid = {39054479}, issn = {1748-717X}, support = {Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; Next Generation Clinician Scientist_ID 28614//Fondazione AIRC per la ricerca sul cancro ETS/ ; }, mesh = {*Rectal Neoplasms/radiotherapy/pathology/therapy ; Humans ; Neoadjuvant Therapy/methods ; Gastrointestinal Microbiome ; Magnetic Resonance Imaging ; Radiotherapy, Image-Guided/methods ; Chemoradiotherapy/methods ; Circulating Tumor DNA/genetics ; Biomarkers, Tumor ; Genomics/methods ; Male ; Female ; Multiomics ; }, abstract = {BACKGROUND: Complete response prediction in locally advanced rectal cancer (LARC) patients is generally focused on the radiomics analysis of staging MRI. Until now, omics information extracted from gut microbiota and circulating tumor DNA (ctDNA) have not been integrated in composite biomarkers-based models, thereby omitting valuable information from the decision-making process. In this study, we aim to integrate radiomics with gut microbiota and ctDNA-based genomics tracking during neoadjuvant chemoradiotherapy (nCRT).

METHODS: The main hypothesis of the MOREOVER study is that the incorporation of composite biomarkers with radiomics-based models used in the THUNDER-2 trial will improve the pathological complete response (pCR) predictive power of such models, paving the way for more accurate and comprehensive personalized treatment approaches. This is due to the inclusion of actionable omics variables that may disclose previously unknown correlations with radiomics. Aims of this study are: - to generate longitudinal microbiome data linked to disease resistance to nCRT and postulate future therapeutic strategies in terms of both type of treatment and timing, such as fecal microbiota transplant in non-responding patients. - to describe the genomics pattern and ctDNA data evolution throughout the nCRT treatment in order to support the prediction outcome and identify new risk-category stratification agents. - to mine and combine collected data through integrated multi-omics approaches (radiomics, metagenomics, metabolomics, metatranscriptomics, human genomics, ctDNA) in order to increase the performance of the radiomics-based response predictive model for LARC patients undergoing nCRT on MR-Linac.

EXPERIMENTAL DESIGN: The objective of the MOREOVER project is to enrich the phase II THUNDER-2 trial (NCT04815694) with gut microbiota and ctDNA omics information, by exploring the possibility to enhance predictive performance of the developed model. Longitudinal ctDNA genomics, microbiome and genomics data will be analyzed on 7 timepoints: prior to nCRT, during nCRT on a weekly basis and prior to surgery. Specific modelling will be performed for data harvested, according to the TRIPOD statements.

DISCUSSION: We expect to find differences in fecal microbiome, ctDNA and radiomics profiles between the two groups of patients (pCR and not pCR). In addition, we expect to find a variability in the stability of the considered omics features over time. The identified profiles will be inserted into dedicated modelling solutions to set up a multiomics decision support system able to achieve personalized treatments.}, } @article {pmid39053865, year = {2024}, author = {Lin, L and Tang, R and Liu, Y and Li, Z and Li, H and Yang, H}, title = {The brain-protective mechanism of fecal microbiota transplantation from young donor mice in the natural aging process via exosome, gut microbiota, and metabolomics analyses.}, journal = {Pharmacological research}, volume = {207}, number = {}, pages = {107323}, doi = {10.1016/j.phrs.2024.107323}, pmid = {39053865}, issn = {1096-1186}, abstract = {The natural aging process is accompanied by changes in exosomes, gut microbiota, and metabolites. This study aimed to reveal the anti-aging effect and mechanisms of fecal microbiota transplantation (FMT) from young donors on the natural aging process in mice by analyzing exosomes, gut microbiota, and metabolomics. Aging-relevant telomeric length, oxidative stress indexes in brain tissue, and serum cytokine levels were measured. Flow analysis of T-regulatory (Treg), CD4[+], and CD8[+] cells was performed, and the expression levels of aging-related proteins were quantified. High-throughput sequencing technology was used to identify differentially expressed serum exosomal miRNAs. Fecal microbiota was tested by 16 S rDNA sequencing. Changes in fecal metabolites were analyzed by UPLC-Q-TOF/MS. The results indicated that the expression of mmu-miR-7010-5p, mmu-miR-376b-5p, mmu-miR-135a-5p, and mmu-miR-3100-5p by serum exosomes was down-regulated and the abundance of opportunistic bacteria (Turicibacter, Allobaculum, Morganella.) was decreased, whereas the levels of protective bacteria (Akkermansia, Muribaculaceae, Helicobacter.) were increased after FMT. Metabolic analysis identified 25 potential biomarkers. Correlation analysis between the gut microbiota and metabolites suggested that the relative abundance of protective bacteria was positively correlated with the levels of spermidine and S-adenosylmethionine. The study indicated that FMT corrected brain injury due to aging via lipid metabolism, the metabolism of cofactors and vitamins, and amino acid metabolism.}, } @article {pmid39052747, year = {2024}, author = {Kelly, BJ and Kwon, JH and Woodworth, MH}, title = {Escape Velocity-the Launch of Microbiome Therapies.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {1}, pages = {2-4}, doi = {10.1093/infdis/jiae099}, pmid = {39052747}, issn = {1537-6613}, support = {U54CK000601/CC/CDC HHS/United States ; K23AI144036//National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Clostridium Infections/therapy/microbiology ; *Clostridioides difficile ; *Gastrointestinal Microbiome ; United States ; Microbiota ; United States Food and Drug Administration ; }, abstract = {Food and Drug Administration approval of the first microbiome therapies represents a true expansion the treatment paradigm for Clostridioides difficile but raises new questions about the future role of fecal microbiota transplantation. The authors outline the advances in microbiome therapeutic development that have addressed fecal microbiota transplantation's (FMT's) inherent limitations of safety and scalability. The authors also suggest that as microbiome therapeutic development continues for other indications, FMT will likely remain a necessary model of human microbiota dynamics for translational research.}, } @article {pmid39047173, year = {2024}, author = {Weber, D and Meedt, E and Poeck, H and Thiele-Orberg, E and Hiergeist, A and Gessner, A and Holler, E}, title = {Fecal Microbiota Transfer in Acute Graft-versus-Host Disease following Allogeneic Stem Cell Transplantation.}, journal = {Visceral medicine}, volume = {}, number = {}, pages = {1-6}, pmid = {39047173}, issn = {2297-4725}, abstract = {BACKGROUND: Acute graft-versus-host disease (GvHD) is a major and sometimes lethal complication following allogeneic stem cell transplantation (aSCT). In the last 10 years, a massive loss of microbiota diversity with suppression of commensal bacteria and their protective metabolites has been identified as a major risk factor of GvHD.

SUMMARY: Since 2018, several studies have been published showing some efficacy of fecal microbiota transfer (FMT) in aSCT patients. FMT was used (1) to eliminate antibiotic resistant bacteria, (2) to restore microbiota diversity after hematopoietic recovery, or (3) in most cases to treat steroid-resistant GvHD. Overall response rates between 30 and 50% have been reported, but randomized trials are still pending. Newer approaches try to evaluate the role of prophylactic FMT in order to prevent GvHD and other complications. Although aSCT patients are heavily immunosuppressed, no major safety concerns regarding FMT have been reported so far.

KEY MESSAGE: FMT is a promising approach for modulation of GvHD after aSCT and should be further explored in randomized trials.}, } @article {pmid39045766, year = {2024}, author = {Stair, SL and Yoon, JH and Dymanus, KA and Lee, UJ and Adelstein, SA}, title = {Fecal incontinence is not associated with UTI: A contemporary case-control study.}, journal = {Neurourology and urodynamics}, volume = {}, number = {}, pages = {}, doi = {10.1002/nau.25544}, pmid = {39045766}, issn = {1520-6777}, abstract = {INTRODUCTION: Urinary tract infections (UTIs) are a leading cause of infection in adults. The most common cause is gastrointestinal bacteria ascending the urethra into the bladder. Studies showing fecal incontinence (FI) is a risk factor for UTI have been limited to nursing home populations. Healthy patients with recurrent UTI, especially women, often receive counseling, suggesting improper personal hygiene contributes to UTIs. This advice can be stigmatizing. Given UTI prevalence, it is important to elucidate risk factors for improved diagnosis, treatment, and patient education. Our objective was to perform a hospital-centered, retrospective case-control analysis to assess the effect of FI on UTI development in ambulatory patients.

METHODS: Patients (n = 3035) with a diagnosis of FI were identified from a single institution and propensity score-matched with screening colonoscopy patients (n = 3035) from 2018 to 2021. Patients were matched on age, sex, race, ethnicity, body mass index, and comorbidities, for example, diabetes, vesicoureteral reflux, and urinary incontinence. The association between FI and UTI was tested using Pearson's χ[2] test.

RESULTS: Median age was 64 years with more females than males (73.81% vs. 71.20% female for case/control, p = 0.02). Patients with FI were more often to have concurrent urinary incontinence (18.62% vs. 10.25% for case/control, p < 0.001), as well as specifically urgency incontinence (13.28% vs. 11.57% for case/control, p = 0.04). There was no significant difference in the incidence of UTI between patients with FI and those presenting for screening colonoscopy (p = 0.44).

CONCLUSION: FI was not associated with an increased number of UTIs. Based on our results, current stigmatizing beliefs regarding the association between FI and UTI should be reevaluated.}, } @article {pmid39044834, year = {2024}, author = {Tabrizi, E and Pourteymour Fard Tabrizi, F and Mahmoud Khaled, G and Sestito, MP and Jamie, S and Boone, BA}, title = {Unraveling the gut microbiome's contribution to pancreatic ductal adenocarcinoma: mechanistic insights and therapeutic perspectives.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1434771}, pmid = {39044834}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Carcinoma, Pancreatic Ductal/therapy/microbiology/immunology ; *Pancreatic Neoplasms/microbiology/therapy/immunology ; Animals ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immunotherapy/methods ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {The gut microbiome plays a significant role in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), influencing oncogenesis, immune responses, and treatment outcomes. Studies have identified microbial species like Porphyromonas gingivalis and Fusobacterium nucleatum, that promote PDAC progression through various mechanisms. Additionally, the gut microbiome affects immune cell activation and response to immunotherapy, including immune checkpoint inhibitors and CAR-T therapy. Specific microbes and their metabolites play a significant role in the effectiveness of immune checkpoint inhibitors (ICIs). Alterations in the gut microbiome can either enhance or diminish responses to PD-1/PD-L1 and CTLA-4 blockade therapy. Additionally, bacterial metabolites like trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS) impact antitumor immunity, offering potential targets to augment immunotherapy responses. Modulating the microbiome through fecal microbiota transplantation, probiotics, prebiotics, dietary changes, and antibiotics shows promise in PDAC treatment, although outcomes are highly variable. Dietary modifications, particularly high-fiber diets and specific fat consumption, influence microbiome composition and impact cancer risk. Combining microbiome-based therapies with existing treatments holds potential for improving PDAC therapy outcomes, but further research is needed to optimize their effectiveness.}, } @article {pmid39043769, year = {2024}, author = {Song, Y and Cui, Y and Wang, Y and Wang, T and Zhong, Y and Liu, J and Zheng, X}, title = {The effect and potential mechanism of inulin combined with fecal microbiota transplantation on early intestinal immune function in chicks.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {16973}, pmid = {39043769}, issn = {2045-2322}, support = {21ZGN16//the key technology research project of the Changchun Key R&D Program/ ; 2021YFD2101003-2//the National Key R&D Program of China/ ; 20220203096SF//the Science and Technology Development Plan Program of Jilin Province/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Inulin/pharmacology ; *Chickens/microbiology/immunology ; Gastrointestinal Microbiome/drug effects ; Intestines/immunology/microbiology ; Intestinal Mucosa/metabolism/immunology/microbiology ; Cecum/microbiology ; }, abstract = {Our previous research found that fecal microbiota transplantation (FMT) and inulin synergistically affected the intestinal barrier and immune system function in chicks. However, does it promote the early immunity of the poultry gut-associated lymphoid tissue (GALT)? How does it regulate the immunity? We evaluated immune-related indicators in the serum, cecal tonsil, and intestine to determine whether FMT synergistic inulin had a stronger impact on gut health and which gene expression regulation was affected. The results showed that FMT synergistic inulin increased TGF-β secretion and intestinal goblet cell number and MUC2 expression on day 14. Expression of BAFFR, PAX5, CXCL12, and IL-2 on day 7 and expression of CXCR4 and IL-2 on day 14 in the cecal tonsils significantly increased. The transcriptome indicated that CD28 and CTLA4 were important regulatory factors in intestinal immunity. Correlation analysis showed that differential genes were related to the immunity and development of the gut and cecal tonsil. FMT synergistic inulin promoted the development of GALT, which improved the early-stage immunity of the intestine by regulating CD28 and CTLA4. This provided new measures for replacing antibiotic use and reducing the use of therapeutic drugs while laying a technical foundation for achieving anti-antibiotic production of poultry products.}, } @article {pmid39043421, year = {2024}, author = {Fan, C and Li, R and Wang, L and Li, K and Jia, X and Gao, H and Zhang, B and Xu, X and Qian, S}, title = {Fecal Microbiota Transplantation for Severe Infant Botulism, China.}, journal = {Emerging infectious diseases}, volume = {30}, number = {8}, pages = {1732-1734}, doi = {10.3201/eid3008.231702}, pmid = {39043421}, issn = {1080-6059}, mesh = {*Botulism/therapy/microbiology ; Humans ; Infant ; Male ; *Fecal Microbiota Transplantation ; China ; Feces/microbiology ; Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {Infant botulism in a 4-month-old boy in China who continued to excrete toxins for over a month despite antitoxin therapy was further treated with fecal microbiota transplantation. After treatment, we noted increased gut microbial diversity and altered fecal metabolites, which may help reduce intestinal pH and enhance anti-inflammatory capabilities.}, } @article {pmid39042929, year = {2024}, author = {Leclercq, S}, title = {Involvement of the gut microbiome-brain axis in alcohol use disorder.}, journal = {Alcohol and alcoholism (Oxford, Oxfordshire)}, volume = {59}, number = {5}, pages = {}, doi = {10.1093/alcalc/agae050}, pmid = {39042929}, issn = {1464-3502}, support = {//Fonds de la Recherche Scientifique - FNRS/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Brain-Gut Axis/physiology ; *Alcoholism/microbiology/therapy ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Prebiotics ; Animals ; Brain/metabolism ; }, abstract = {The human intestine is colonized by a variety of microorganisms that influence the immune system, the metabolic response, and the nervous system, with consequences for brain function and behavior. Unbalance in this microbial ecosystem has been shown to be associated with psychiatric disorders, and altered gut microbiome composition related to bacteria, viruses, and fungi has been well established in patients with alcohol use disorder. This review describes the gut microbiome-brain communication pathways, including the ones related to the vagus nerve, the inflammatory cytokines, and the gut-derived metabolites. Finally, the potential benefits of microbiota-based therapies for the management of alcohol use disorder, such as probiotics, prebiotics, and fecal microbiota transplantation, are also discussed.}, } @article {pmid39042868, year = {2024}, author = {Moutsoglou, D and Vaughn, BP}, title = {Rethinking Faecal Microbiota Transplant for Pouchitis.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjae100}, pmid = {39042868}, issn = {1876-4479}, } @article {pmid39041052, year = {2024}, author = {Ezenabor, EH and Adeyemi, AA and Adeyemi, OS}, title = {Gut Microbiota and Metabolic Syndrome: Relationships and Opportunities for New Therapeutic Strategies.}, journal = {Scientifica}, volume = {2024}, number = {}, pages = {4222083}, pmid = {39041052}, issn = {2090-908X}, abstract = {Since its discovery, numerous studies have shown the role of the microbiota in well-being and disease. The gut microbiota represents an essential factor that plays a multidirectional role that affects not just the gut but also other parts of the body, including the brain, endocrine system, humoral system, immune system, and metabolic pathways, as well as host-microbiome interactions. Through a comprehensive analysis of existing literature using the desktop research methodology, this review elucidates the mechanisms by which gut microbiota dysbiosis contributes to metabolic dysfunction, including obesity, dyslipidaemia, hypertension, atherosclerosis, hyperuricemia, and hyperglycaemia. Furthermore, it examines the bidirectional communication pathways between gut microbiota and host metabolism, highlighting the role of microbial-derived metabolites, immune modulation, and gut barrier integrity in shaping metabolic homeostasis. Importantly, the review identifies promising therapeutic strategies targeting the gut microbiota as potential interventions for metabolic syndrome, including probiotics, prebiotics, symbiotics, dietary modifications, and faecal microbiota transplantation. By delineating the bidirectional interactions between gut microbiota and metabolic syndrome, the review not only advances our understanding of disease pathophysiology but also underscores the potential for innovative microbiota-based interventions to mitigate the global burden of metabolic syndrome and its associated complications.}, } @article {pmid39040423, year = {2024}, author = {Zhang, X and Li, Y and Li, B and Wu, J and Zhang, J and Ding, X}, title = {Washed microbiota transplantation in an elderly patient with lymphocytic leukemia and Clostridioides difficile infection: A case report illustrating a triumph over complexity.}, journal = {Heliyon}, volume = {10}, number = {13}, pages = {e32450}, pmid = {39040423}, issn = {2405-8440}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is recommended for treating patients with recurrent Clostridioides difficile infection (CDI). However, the therapeutic efficacy of FMT in elderly patients with complex medical conditions remains uncertain. The new method of FMT, washed microbiota transplantation (WMT) has been widely used in China to improve the safety of transplantation.

CASE REPORT: A 94-year-old man with chronic lymphocytic leukemia (CLL) was admitted to our hospital due to recurrent diarrhea persisting for eight months. The patient had experienced multiple relapses of CDI despite receiving standard therapies. He underwent colonic transendoscopic enteral tubing (TET) and subsequently received WMT during the procedure. Following the treatment, no episodes of diarrhea or adverse events were observed, and the patient remained stable over a three-month follow-up period.

CONCLUSION: This case demonstrates the efficacy and safety of WMT in treating elderly patients with CLL. The successful management of this case offers valuable clinical insights into the use of WMT for elderly CDI patients with complex medical conditions. Moreover, this report contributes practical experience regarding the administration of WMT through the colonic TET.}, } @article {pmid39040013, year = {2024}, author = {Sasidharan Pillai, S and Gagnon, CA and Foster, C and Ashraf, AP}, title = {Exploring the Gut Microbiota: Key Insights into Its Role in Obesity, Metabolic Syndrome, and Type 2 Diabetes.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1210/clinem/dgae499}, pmid = {39040013}, issn = {1945-7197}, abstract = {The gut microbiota (GM), comprising trillions of microorganisms in the gastrointestinal tract, is a key player in the development of obesity and related metabolic disorders, such as type 2 diabetes (T2D), metabolic syndrome (MS), and cardiovascular diseases. This mini-review delves into the intricate roles and mechanisms of the GM in these conditions, offering insights into potential therapeutic strategies targeting the microbiota. The review elucidates the diversity and development of the human GM, highlighting its pivotal functions in host physiology, including nutrient absorption, immune regulation, and energy metabolism. Studies show that GM dysbiosis is linked to increased energy extraction, altered metabolic pathways, and inflammation, contributing to obesity, MS, and T2D. The interplay between dietary habits and GM composition is explored, underscoring the influence of diet on microbial diversity and metabolic functions. Additionally, the review addresses the impact of common medications and therapeutic interventions like fecal microbiota transplantation on GM composition. The evidence so far advocates for further research to delineate the therapeutic potential of GM modulation in mitigating obesity and metabolic diseases, emphasizing the necessity of clinical trials to establish effective and sustainable treatment protocols.}, } @article {pmid39036641, year = {2024}, author = {He, J and Wu, J and Liu, J and Wu, H and Hua, H}, title = {Cognitive impairment and the gut-brain axis during 2014-2023: a bibliometric analysis.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1407956}, pmid = {39036641}, issn = {1664-2295}, abstract = {BACKGROUND: The burden on society grows as the number of individuals with cognitive impairment rises. Numerous research have discovered a connection between cognitive impairment and the gut-brain axis, which is useful in examining the pathophysiology of cognitive impairment and potential therapeutic approaches. As a result, this article explores developments and trends in the research concerning the gut-brain axis and cognitive impairment through a bibliometric analysis of the contributions made by various countries/regions, institutions, authors, and journals.

METHODS: We looked for articles on gut-brain axis and cognitive impairment from 2014 to 2023 in the Web of Science Core Collection. For the descriptive analysis, figures and tables were taken using GraphPad Prism 6 and WPS Office 2024. For the visual analysis of the countries/regions, institutions, authors, and keywords, VOSviewer was utilized.

RESULTS: We obtained 458 publications from 1 January 2014 to 9 September 2023. The country with the most publications (175, 38.21%) was China. The country with the greatest total number of citations (3,138, 17.22%) was the United States of America. The highest number of articles (15, 3.26%) was issued by Zhejiang University. The most published first author is Karsas M. In this field, Nutrients have published the most articles (24). The most often occurring keywords include "Alzheimer's disease," "cognitive impairment," "gut microbiota," "inflammation," "diet," etc. "Stroke," "tau," "probiotics," "exercise," "fecal microbiota transplantation," etc. emerged later.

CONCLUSION: An increasing amount of research has focused on the connection between cognitive impairment and the gut-brain axis. In this area, the United States of America and China have both made significant contributions. The author team's collaboration has to be improved. Our study contributes to understanding the field's current state and predicting its future trend.}, } @article {pmid38920288, year = {2024}, author = {Liang, F and Song, Y and Lin, D and He, H and Xu, J and He, X and Wu, L}, title = {Washed Microbiota Transplantation Is Associated With Improved Lipid Profiles: Long-Term Efficacy and Safety in an Observational Cohort From South China.}, journal = {Clinical and translational gastroenterology}, volume = {15}, number = {7}, pages = {e00735}, pmid = {38920288}, issn = {2155-384X}, support = {2023M740782//China postdoctoral science foundation/ ; B2022209//Medical Scientific Research Foundation of Guangdong Province/ ; }, mesh = {Humans ; Male ; Female ; Middle Aged ; China/epidemiology ; *Hyperlipidemias/blood/therapy/complications ; Treatment Outcome ; *Lipids/blood ; Adult ; *Fecal Microbiota Transplantation ; Triglycerides/blood ; Aged ; Dyslipidemias/blood/therapy ; Cholesterol, LDL/blood ; Gastrointestinal Microbiome ; }, abstract = {INTRODUCTION: Dyslipidemia is one of the main risk factors of chronic metabolic diseases. Our previous studies have shown that washed microbiota transplantation (WMT) has a significant improvement effect on patients with hyperlipidemia and hypolipemia in the Chinese population. The purpose of this study was to further explore the long-term efficacy and safety of WMT in patients with hyperlipidemia.

METHODS: Clinical data of patients who received WMT for multicourse were collected. Changes of blood lipid indexes before and after WMT, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein A, and Apolipoprotein B.

RESULTS: A total of 124 patients were enrolled, including 56 cases in the hyperlipidemia group and 68 cases with normal lipids. The mean observation time was 787.80 ± 371.45 days, and the longest follow-up time was 1,534 days. TC and non-HDL-C in the hyperlipidemia group with 1-4 courses of WMT were significantly reduced (P < 0.05); TG decreased significantly after the second course (P < 0.05); low-density lipoprotein cholesterol also significantly decreased after the fourth course of treatment (P < 0.05); TG, TC, and non-HDL-C significantly decreased in single course, double course, and multiple course, respectively (P < 0.05). In terms of time period, over 1 year, the improvement in multicourse treatment was more significant than the single and double-course ones. In terms of comprehensive efficacy, WMT restored 32.14% of patients in the hyperlipidemia group to the normal lipid group (P < 0.001), of which 30.00% recovered to the normal lipid group within 1 year (P = 0.004) and 65.38% were reassigned to the normal lipid group over 1 year (P = 0.003). In addition, over the 1-year treatment period, WMT significantly degraded the high-risk and medium-risk groups of atherosclerotic cardiovascular disease risk stratification in hyperlipidemia cases. There were no serious adverse events.

DISCUSSION: WMT had a long-term improvement effect on patients with hyperlipidemia. The effect of multiple courses over 1 year was more significant than that of single/double courses and also had a significant destratification effect on the risk of atherosclerotic cardiovascular disease with high safety. Therefore, WMT provides a safe and long-term effective clinical treatment for patients with dyslipidemia.}, } @article {pmid38446696, year = {2024}, author = {Kelly, BJ and Kwon, JH and Woodworth, MH}, title = {Escape Velocity - The Launch of Microbiome Therapies.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {1}, pages = {2-4}, pmid = {38446696}, issn = {1537-6613}, abstract = {Food and Drug Administration approval of the first microbiome therapies represents a true expansion the treatment paradigm for Clostridioides difficile but raises new questions about the future role of fecal microbiota transplantation. The authors outline the advances in microbiome therapeutic development that have addressed fecal microbiota transplantation’s (FMT's) inherent limitations of safety and scalability. The authors also suggest that as microbiome therapeutic development continues for other indications, FMT will likely remain a necessary model of human microbiota dynamics for translational research.}, } @article {pmid34283837, year = {2021}, author = {Velasco, C and Dunn, C and Sturdy, C and Izda, V and Martin, J and Rivas, A and McNaughton, J and Jeffries, MA}, title = {Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0248322}, pmid = {34283837}, issn = {1932-6203}, support = {K08 AR070891/AR/NIAMS NIH HHS/United States ; P20 GM125528/GM/NIGMS NIH HHS/United States ; R01 AR076440/AR/NIAMS NIH HHS/United States ; R61 AR078075/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Wound Healing ; Mice ; Female ; Male ; *Mice, Inbred C57BL ; Ear/microbiology ; Fecal Microbiota Transplantation ; Cecum/microbiology ; }, abstract = {OBJECTIVE: Adult elastic cartilage has limited repair capacity. MRL/MpJ (MRL) mice, by contrast, are capable of spontaneously healing ear punctures. This study was undertaken to characterize microbiome differences between healer and non-healer mice and to evaluate whether this healing phenotype can be transferred via gut microbiome transplantation.

METHODS: We orally transplanted C57BL/6J (B6) mice with MRL/MpJ cecal contents at weaning and as adults (n = 57) and measured ear hole closure 4 weeks after a 2.0mm punch and compared to vehicle-transplanted MRL and B6 (n = 25) and B6-transplanted MRL (n = 20) mice. Sex effects, timing of transplant relative to earpunch, and transgenerational heritability were evaluated. In a subset (n = 58), cecal microbiomes were profiled by 16S sequencing and compared to ear hole closure. Microbial metagenomes were imputed using PICRUSt.

RESULTS: Transplantation of B6 mice with MRL microbiota, either in weanlings or adults, improved ear hole closure. B6-vehicle mice healed ear hole punches poorly (0.25±0.03mm, mm ear hole healing 4 weeks after a 2mm ear hole punch [2.0mm-final ear hole size], mean±SEM), whereas MRL-vehicle mice healed well (1.4±0.1mm). MRL-transplanted B6 mice healed roughly three times as well as B6-vehicle mice, and half as well as MRL-vehicle mice (0.74±0.05mm, P = 6.9E-10 vs. B6-vehicle, P = 5.2E-12 vs. MRL-vehicle). Transplantation of MRL mice with B6 cecal material did not reduce MRL healing (B6-transplanted MRL 1.3±0.1 vs. MRL-vehicle 1.4±0.1, p = 0.36). Transplantation prior to ear punch was associated with the greatest ear hole closure. Offspring of transplanted mice healed significantly better than non-transplanted control mice (offspring:0.63±0.03mm, mean±SEM vs. B6-vehicle control:0.25±0.03mm, n = 39 offspring, P = 4.6E-11). Several microbiome clades were correlated with healing, including Firmicutes (R = 0.84, P = 8.0E-7), Lactobacillales (R = 0.65, P = 1.1E-3), and Verrucomicrobia (R = -0.80, P = 9.2E-6). Females of all groups tended to heal better than males (B6-vehicle P = 0.059, MRL-transplanted B6 P = 0.096, offspring of MRL-transplanted B6 P = 0.0038, B6-transplanted MRL P = 1.6E-6, MRL-vehicle P = 0.0031). Many clades characteristic of female mouse cecal microbiota vs. males were the same as clades characteristic of MRL and MRL-transplanted B6 mice vs. B6 controls, including including increases in Clostridia and reductions in Verrucomicrobia in female mice.

CONCLUSION: In this study, we found an association between the microbiome and tissue regeneration in MRL mice and demonstrate that this trait can be transferred to non-healer mice via microbiome transplantation. We identified several microbiome clades associated with healing.}, } @article {pmid39036426, year = {2024}, author = {Sun, W and Reeves, W and Fagan, MM and Welch, CB and Scheulin, KM and Sneed, SE and Callaway, TR and Duberstein, KJ and West, FD and Zhao, Q}, title = {Evaluation of Brain Function Recovery After Traumatic Brain Injury Treatment in a Porcine Model by Cross-Group Temporal-Spatial Correlation Analysis.}, journal = {Neurotrauma reports}, volume = {5}, number = {1}, pages = {617-627}, pmid = {39036426}, issn = {2689-288X}, abstract = {Traumatic brain injury (TBI), a significant global health issue, is affecting ∼69 million annually. To better understand TBI's impact on brain function and assess the efficacy of treatments, this study uses a novel temporal-spatial cross-group approach with a porcine model, integrating resting-state functional magnetic resonance imaging (rs-fMRI) for temporal and arterial spin labeling for spatial information. Our research used 18 four-week-old pigs divided into three groups: TBI treated with saline (SLN, n = 6), TBI treated with fecal microbial transplant (FMT, n = 6), and a sham group (sham, n = 6) with only craniectomy surgery as the baseline. By applying machine learning techniques-specifically, independent component analysis and sparse dictionary learning-across seven identified resting-state networks, we assessed the temporal and spatial correlations indicative of treatment efficacy. Both temporal and spatial analyses revealed a consistent increase of correlation between the FMT and sham groups in the executive control and salience networks. Our results are further evidenced by a simulation study designed to mimic the progression of TBI severity through the introduction of variable Gaussian noise to an independent rs-fMRI dataset. The results demonstrate a decreasing temporal correlation between the sham and TBI groups with increasing injury severity, consistent with the experimental results. This study underscores the effectiveness of the methodology in evaluating post-TBI treatments such as the FMT. By presenting comprehensive experimental and simulated data, our research contributes significantly to the field and opens new paths for future investigations into TBI treatment evaluations.}, } @article {pmid39036341, year = {2024}, author = {You, M and Chen, N and Yang, Y and Cheng, L and He, H and Cai, Y and Liu, Y and Liu, H and Hong, G}, title = {The gut microbiota-brain axis in neurological disorders.}, journal = {MedComm}, volume = {5}, number = {8}, pages = {e656}, pmid = {39036341}, issn = {2688-2663}, abstract = {Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota-gut-brain axis (MGBA). The MGBA influences the host's nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's and Parkinson's disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe-based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.}, } @article {pmid39035457, year = {2024}, author = {Lin, Z and Jiang, T and Chen, M and Ji, X and Wang, Y}, title = {Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects.}, journal = {Open life sciences}, volume = {19}, number = {1}, pages = {20220910}, pmid = {39035457}, issn = {2391-5412}, abstract = {Sleep is crucial for wellness, and emerging research reveals a profound connection to gut microbiota. This review explores the bidirectional relationship between gut microbiota and sleep, exploring the mechanisms involved and the therapeutic opportunities it presents. The gut-brain axis serves as a conduit for the crosstalk between gut microbiota and the central nervous system, with dysbiosis in the microbiota impairing sleep quality and vice versa. Diet, circadian rhythms, and immune modulation all play a part. Specific gut bacteria, like Lactobacillus and Bifidobacterium, enhance sleep through serotonin and gamma-aminobutyric acid production, exemplifying direct microbiome influence. Conversely, sleep deprivation reduces beneficial bacteria, exacerbating dysbiosis. Probiotics, prebiotics, postbiotics, and fecal transplants show therapeutic potential, backed by animal and human research, yet require further study on safety and long-term effects. Unraveling this intricate link paves the way for tailored sleep therapies, utilizing microbiome manipulation to improve sleep and health. Accelerated research is essential to fully tap into this promising field for sleep disorder management.}, } @article {pmid39034613, year = {2024}, author = {Krigul, KL and Feeney, RH and Wongkuna, S and Aasmets, O and Holmberg, SM and Andreson, R and Puértolas-Balint, F and Pantiukh, K and Sootak, L and Org, T and Tenson, T and Org, E and Schroeder, BO}, title = {A history of repeated antibiotic usage leads to microbiota-dependent mucus defects.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2377570}, doi = {10.1080/19490976.2024.2377570}, pmid = {39034613}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; Animals ; *Anti-Bacterial Agents/pharmacology ; Mice ; *Fecal Microbiota Transplantation ; *Mucus/metabolism/microbiology ; *Bacteria/classification/genetics/drug effects/isolation & purification/metabolism ; Intestinal Mucosa/microbiology/metabolism/drug effects ; Male ; Female ; Feces/microbiology ; Adult ; Middle Aged ; Akkermansia ; Mice, Inbred C57BL ; Colon/microbiology ; Bacteroides fragilis/drug effects ; }, abstract = {Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and ultimately changes the gut microbiota community. However, the physiological effects of repeated - but not recent - antibiotic usage on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from the deeply phenotyped Estonian Microbiome Cohort (EstMB), we here utilized human-to-mouse fecal microbiota transplantation to explore long-term impacts of repeated antibiotic use on intestinal mucus function. While a healthy mucus layer protects the intestinal epithelium against infection and inflammation, using ex vivo mucus function analyses of viable colonic tissue explants, we show that microbiota from humans with a history of repeated antibiotic use causes reduced mucus growth rate and increased mucus penetrability compared to healthy controls in the transplanted mice. Moreover, shotgun metagenomic sequencing identified a significantly altered microbiota composition in the antibiotic-shaped microbial community, with known mucus-utilizing bacteria, including Akkermansia muciniphila and Bacteroides fragilis, dominating in the gut. The altered microbiota composition was further characterized by a distinct metabolite profile, which may be caused by differential mucus degradation capacity. Consequently, our proof-of-concept study suggests that long-term antibiotic use in humans can result in an altered microbial community that has reduced capacity to maintain proper mucus function in the gut.}, } @article {pmid39034349, year = {2024}, author = {Zhuang, Y and Liu, S and Gao, D and Xu, Y and Jiang, W and Chen, T and Xiao, J and Wang, J and Hou, G and Li, S and Zhao, X and Huang, Y and Li, S and Zhang, S and Li, M and Wang, W and Li, S and Cao, Z}, title = {The Bifidobacterium-dominated fecal microbiome in dairy calves shapes the characteristic growth phenotype of host.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {59}, pmid = {39034349}, issn = {2055-5008}, mesh = {Animals ; *Feces/microbiology ; Cattle ; *RNA, Ribosomal, 16S/genetics ; *Bifidobacterium/genetics/growth & development ; *Gastrointestinal Microbiome ; Mice ; *Fecal Microbiota Transplantation/methods ; Phenotype ; Probiotics/administration & dosage ; Phylogeny ; DNA, Bacterial/genetics ; }, abstract = {The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.}, } @article {pmid39032279, year = {2024}, author = {Zhang, H and Hao, Z and Zhang, R and Tong, J and Wang, X and Liu, J and Gao, Y and Wang, X and Su, Q and Wen, H and Fan, Y and Liu, F and Li, X and Tong, C and Wang, X}, title = {Artemisia argyi polyphenols Attenuates DSS-induced colitis in mice by regulating the structural composition of gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {132}, number = {}, pages = {155897}, doi = {10.1016/j.phymed.2024.155897}, pmid = {39032279}, issn = {1618-095X}, abstract = {BACKGROUND: Intestinal health is affected by heredity, lifestyle, and structure of gut microbiota. The imbalance of symbiotic and harmful bacteria in gut microbiota may increase the occurrence of colonic inflammation. Supplementary A. muciniphila can improve the survival rate of colitis mice, reduce colon tissue injury, and the expression of anti-inflammatory factors was upregulated. Artemisia argyi has been reported to have anti-inflammatory, antioxidant, bactericidal, and immunomodulatory effects. However, its anti-inflammatory effect and mechanism, and its influence on gut microbiota and metabolites are still unclear yet.

PURPOSE: To explore whether Artemisia argyi Polyphenols(AAPs) can alleviate ulcerative colitis (UC) by changing gut microbiota.

METHODS: The therapeutic effect of AAPs on colitis was investigated by inducing ulcerative colitis in mice using dextran sodium sulfate (DSS) and administering different doses of AAPs orally to mice. Exploring the levels of inflammatory proteins, oxidative stress proteins, and barrier proteins using western blotting and immunofluorescence, and explored the structural changes of gut microbiota and its metabolites. Meanwhile, in order to explore whether the role of AAPs in alleviating colitis is based on the regulation of gut microbiota structure, we conducted fecal microbiota transplantation (FMT).

RESULTS: It showed that AAPs and FMT trial alleviated DSS-induced colonic injury, including clinical parameters and pathological injury of colon tissue, reduction in the expression of inflammatory proteins: IL-6, TNF-α, p-p65, p-IκBα, and increase in the expression of antioxidant proteins: Nrf2, NQO-1 and HO-1 and barrier proteins: Claudin-1, Occludin, ZO-1 and MUC2. AAPs and FMT promoted the content of beneficial bacteria, such as Butyricimonas and Lactobacillus, and the content of beneficial metabolites for instance acetic acid, butyric acid, and valeric acid has also increased.

CONCLUSION: These results suggested that AAPs might improve DSS-induced colonic injury by changing the structural of gut microbiota while promoting the synthesis of fatty acids in the intestine, thereby providing a theoretical basis for using AAPs to treat ulcerative colitis.}, } @article {pmid39031494, year = {2024}, author = {Koller, T and Vrbova, P and Kubanek, N and Zilincanova, D and Selcanova, SA and Havaj, DJ and Skladany, L}, title = {Assessment of intestinal inflammation via fecal calprotectin for early prediction of adverse outcomes in advanced chronic liver disease.}, journal = {United European gastroenterology journal}, volume = {}, number = {}, pages = {}, doi = {10.1002/ueg2.12633}, pmid = {39031494}, issn = {2050-6414}, abstract = {BACKGROUND AND AIMS: Intestinal inflammation assessed by fecal calprotectin (F-CAL) in advanced chronic liver disease (ACLD) may represent an early sign of intestinal barrier dysfunction. We aimed to explore the usefulness of F-CAL testing in ACLD in the prediction of adverse outcomes (AO, death, or LT) and refinement of prognostic stratification.

PATIENTS AND METHODS: We explored the RH7 cirrhosis registry comprising consecutive hospitalized patients and a control group with data on disease phenotype, demographics, anthropometrics, prognostic indices, and medication. The F-CAL was evaluated on admission and reported in multiples of the upper limit of normal or terciles. Predictive power was tested in the Cox model for AO over 180 days. Additional risk refinement by F-CAL was tested for both groups.

RESULTS: We enrolled 263 cases in the study group with a median age of 57.2 years, M/F ratio 167/96, with alcohol, metabolic dysfunction-associated steatotic liver disease, MetALD, and viral etiologies in 72.2%, 9.1, 8.0, 3.4%. The median F-CAL was 3.92 × ULN. The control group comprised 108 cases. The adjusted Cox model confirmed F-CAL (hazard ratio [HR] = 1.05, p < 0.001) and F-CAL terciles (HR = 1.413, p = 0.009) as independent predictors of AO. F-CAL terciles had higher predictive accuracy in CLIF-C-AD<50 (HR = 2.49, p = 0.013) and Child stages A and B (HR = 1.706, p = 0.025), in whom high F-CAL (cut-off >11 × ULN) could identify patients having 2-3 times higher risk of AO. This approach has been validated in the control group.

CONCLUSION: Among hospitalized patients with ACLD, F-CAL values were independently proportional to the risk of AO, particularly in early disease stages when high F-CAL values could refine prognostic stratification.}, } @article {pmid39030978, year = {2024}, author = {Dong, Y and Dong, J and Xiao, H and Li, Y and Wang, B and Zhang, S and Cui, M}, title = {A gut microbial metabolite cocktail fights against obesity through modulating the gut microbiota and hepatic leptin signaling.}, journal = {Journal of the science of food and agriculture}, volume = {}, number = {}, pages = {}, doi = {10.1002/jsfa.13758}, pmid = {39030978}, issn = {1097-0010}, abstract = {BACKGROUND: Excessive body weight and obesity elevate the risk of chronic non-communicable diseases. The judicious application of the gut microbiome, encompassing both microorganisms and their derived compounds, holds considerable promise in the treatment of obesity.

RESULTS: In this study, we showed that a cocktail of gut microbiota-derived metabolites, comprising indole 3-propionic acid (IPA), sodium butyrate (SB) and valeric acid (VA), alleviated various symptoms of obesity in both male and female mice subjected to a high-fat diet (HFD). The 16S ribosomal RNA (rRNA) sequencing revealed that administering the cocktail via oral gavage retained the gut microbiota composition in obese mice. Fecal microbiota transplantation using cocktail-treated mice as donors mitigated the obesity phenotype of HFD-fed mice. Transcriptomic sequencing analysis showed that the cocktail preserved the gene expression profile of hepatic tissues in obese mice, especially up-regulated the expression level of leptin receptor. Gene delivery via in vivo fluid dynamics further validated that the anti-obesity efficacy of the cocktail was dependent on leptin signaling at least partly. The cocktail also inhibited the expression of appetite stimulators in hypothalamus. Together, the metabolite cocktail combated adiposity by retaining the gut microbiota configuration and activating the hepatic leptin signaling pathway.

CONCLUSIONS: Our findings provide a sophisticated regulatory network between the gut microbiome and host, and highlight a cocktail of gut microbiota-derived metabolites, including IPA, SB, and VA, might be a prospective intervention for anti-obesity in a preclinical setting. © 2024 Society of Chemical Industry.}, } @article {pmid39029231, year = {2024}, author = {Du, HX and Yue, SY and Niu, D and Liu, XH and Li, WY and Wang, X and Chen, J and Hu, DK and Zhang, LG and Guan, Y and Ji, DX and Chen, XG and Zhang, L and Liang, CZ}, title = {Alcohol intake exacerbates experimental autoimmune prostatitis through gut microbiota driving cholesterol biosynthesis-mediated Th17 differentiation.}, journal = {International immunopharmacology}, volume = {139}, number = {}, pages = {112669}, doi = {10.1016/j.intimp.2024.112669}, pmid = {39029231}, issn = {1878-1705}, abstract = {BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is very common worldwide, and alcohol consumption is a notable contributing factor. Researches have shown that gut microbiota can be influenced by alcohol consumption and is an important mediator in regulating Th17 cell immunity. However, it is still unclear the exact mechanism by which alcohol exacerbates the CP/CPPS and the role of gut microbiota in this process.

METHOD: We first constructed the most-commonly used animal model for CP/CPPS, the experimental autoimmune prostatitis (EAP) model, through immunoassay. Based on this, mice were divided into EAP group and alcohol-consuming EAP group. By 16S rRNA sequencing and non-targeted metabolomics analysis, differential gut microbiota and their metabolites between the two groups were identified. Subsequently, metabolomics detection targeting cholesterols was carried out to identify the exact difference in cholesterol. Furthermore, multiple methods such as flow cytometry and immunohistochemistry were used to detect the differentiation status of Th17 cells and severity of prostatitis treated with 27-hydroxycholesterol (the differential cholesterol) and its upstream regulatory factor-sterol regulatory element-binding protein 2 (SREBP2). Lastly, fecal transplantation was conducted to preliminary study on whether alcohol intake exacerbates EAP in immune receptor mice.

RESULTS: Alcohol intake increased the proportion of Th17 cells and levels of related inflammatory factors. It also led to an altered gut bacterial richness and increased gut permeability. Further metabolomic analysis showed that there were significant differences in a variety of metabolites between EAP and alcohol-fed EAP mice. Metabolic pathway enrichment analysis showed that the pathways related to cholesterol synthesis and metabolism were significantly enriched, which was subsequently confirmed by detecting the expression of metabolic enzymes. By targeting cholesterol synthesis, 27-hydroxycholesterol was significantly increased in alcohol-fed EAP mice. Subsequent mechanistic research showed that supplementation with 27-hydroxycholesterol could aggravate EAP and promote Th17 cell differentiation both in vivo and in vitro, which is regulated by SREBP2. In addition, we observed that fecal transplantation from mice with alcohol intake aggravated EAP in immunized recipient mice fed a normal diet.

CONCLUSION: Our study is the first to show that alcohol intake promotes Th17 cell differentiation and exacerbates EAP through microbiota-derived cholesterol biosynthesis.}, } @article {pmid39027904, year = {2024}, author = {Li, Y and Zhang, B and Jiang, L and Cheng, T and Cheng, H and Qian, P}, title = {Gut microbiota plays pivotal roles in benign and malignant hematopoiesis.}, journal = {Blood science (Baltimore, Md.)}, volume = {6}, number = {4}, pages = {e00200}, pmid = {39027904}, issn = {2543-6368}, abstract = {Accumulated evidence emerges that dynamic changes in human gut microbiota and microbial metabolites can alter the ecological balance of symbiotic hosts. The gut microbiota plays a role in various diseases through different mechanisms. More and more attention has been paid to the effects that human microbiota extends beyond the gut. This review summarized the current understanding of the roles that gut microbiota plays in hematopoietic regulation and the occurrence and development of benign and malignant hematologic diseases. The progress of the application of microbiota in treatment was discussed in order to provide new insights into clinical diagnosis and treatment in the future.}, } @article {pmid39027446, year = {2024}, author = {Khaledi, M and Sameni, F and Gholipour, A and Shahrjerdi, S and Golmohammadi, R and Gouvarchin Ghaleh, HE and Poureslamfar, B and Hemmati, J and Mobarezpour, N and Milasi, YE and Rad, F and Mehboodi, M and Owlia, P}, title = {Potential role of gut microbiota in major depressive disorder: A review.}, journal = {Heliyon}, volume = {10}, number = {12}, pages = {e33157}, pmid = {39027446}, issn = {2405-8440}, abstract = {Interactions between the gut microbiota and host immunity are sophisticated, dynamic, and host-dependent. Scientists have recently conducted research showing that disturbances in the gut bacterial community can lead to a decrease in some metabolites and, consequently, to behaviors such as depression. Exposure to stressors dropped the relative abundance of bacteria in the genus Bacteroides while soaring the relative abundance of bacteria in the genus Clostridium, Coprococcus, Dialister, and Oscillibacter, which were also reduced in people with depression. Microbiota and innate immunity are in a bilateral relationship. The gut microbiota has been shown to induce the synthesis of antimicrobial proteins such as catalysidins, type C lectins, and defensins. Probiotic bacteria can modulate depressive behavior through GABA signaling. The gut microbiome produces essential metabolites such as neurotransmitters, tryptophan metabolites, and short-chain fatty acids (SCFAs) that can act on the CNS. In the case of dysbiosis, due to mucin changes, the ratio of intestinal-derived molecules may change and contribute to depression. Psychotropics, including Bifidobacterium longum NCC3001, Clostridium butyricum CBM588, and Lactobacillus acidophilus, have mental health benefits, and can have a positive effect on the host-brain relationship, and have antidepressant effects. This article reviews current studies on the association between gut microbiota dysbiosis and depression. Comprehensively, these findings could potentially lead to novel approaches to improving depressive symptoms via gut microbiota alterations, including probiotics, prebiotics, and fecal microbiota transplantation.}, } @article {pmid39027096, year = {2024}, author = {Cui, X and Wu, Z and Zhou, Y and Deng, L and Chen, Y and Huang, H and Sun, X and Li, Y and Wang, H and Zhang, L and He, J}, title = {A bibliometric study of global trends in T1DM and intestinal flora research.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1403514}, pmid = {39027096}, issn = {1664-302X}, abstract = {BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that seriously jeopardizes human physical and mental health and reduces quality of life. Intestinal flora is one of the critical areas of exploration in T1DM research.

OBJECTIVE: This study aims to explore the research hotspot and development trend of T1DM and intestinal flora to provide research direction and ideas for researchers.

METHODS: We used the Web of Science (WOS) Core Collection and searched up to 18 November 2023, for articles on studies of the correlation between T1DM and intestinal flora. CiteSpace, VOSviewers and R package "bibliometrix" were used to conduct this bibliometric analysis.

RESULTS: Eventually, 534 documents met the requirements to be included, and as of 18 November 2023, there was an upward trend in the number of publications in the field, with a significant increase in the number of articles published after 2020. In summary, F Susan Wong (UK) was the author with the most publications (21), the USA was the country with the most publications (198), and the State University System of Florida (the United States) was the institution with the most publications (32). The keywords that appeared more frequently were T cells, fecal transplants, and short-chain fatty acids. The results of keywords with the most robust citation bursts suggest that Faecalibacterium prausnitzii and butyrate may become a focus of future research.

CONCLUSION: In the future, intestinal flora will remain a research focus in T1DM. Future research can start from Faecalibacterium prausnitzii and combine T cells, fecal bacteria transplantation, and short-chain fatty acids to explore the mechanism by which intestinal flora affects blood glucose in patients with T1DM, which may provide new ideas for the prevention and treatment of T1DM.}, } @article {pmid39026673, year = {2024}, author = {Chen, Y and Sun, K and Qi, Y and Tang, J and Zhu, H and Wang, Z}, title = {L-valine derived from the gut microbiota protects sepsis-induced intestinal injury and negatively correlates with the severity of sepsis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1424332}, pmid = {39026673}, issn = {1664-3224}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Sepsis/microbiology ; Animals ; Mice ; Humans ; *Valine/pharmacology/therapeutic use ; Male ; Female ; Middle Aged ; Fecal Microbiota Transplantation ; Severity of Illness Index ; Metabolomics/methods ; Aged ; Feces/microbiology ; Disease Models, Animal ; Mice, Inbred C57BL ; Intestinal Mucosa/metabolism/microbiology ; Intestines/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The protective role of gut microbiota and its metabolites against intestinal damage in sepsis patients remain unclear.

METHODS: Fecal samples were acquired from patients categorized into sepsis and non-sepsis groups for analysis of microbial composition via 16S rRNA sequencing and untargeted metabolomics analysis. We assessed the impact of gut microbiota from sepsis patients on intestinal barriers in antibiotic-treated mice. Furthermore, We conducted spearman's correlation analysis to examine the relationship between metabolites and the severity of sepsis. Additionally, we performed animal experiments to validate the functionality of identified metabolites.

RESULTS: The diversity of intestinal flora is decreased in patients with sepsis compared to the control group. Through fecal microbiota transplantation experiments, it was discovered that the gut microbiota derived from sepsis patients could induce intestinal damage in antibiotic-treated mice. Metabolomics analysis of the microbiota revealed a significant enrichment of the Valine, leucine, and isoleucine biosynthesis pathway. Further analysis showed a significant decrease in the abundance of L-valine in sepsis patients, which was negatively correlated with APACHE-II and SOFA scores. In sepsis mouse experiments, it was found that L-valine could alleviate sepsis-induced intestinal damage.

CONCLUSION: Alterations in microbial and metabolic features in the gut can affect the severity of sepsis. Furthermore, L-valine can protect against sepsis-induced intestinal injury.}, } @article {pmid39026313, year = {2024}, author = {Tian, X and Li, S and Wang, C and Zhang, Y and Feng, X and Yan, Q and Guo, R and Wu, F and Wu, C and Wang, Y and Huo, X and Ma, X}, title = {Gut virome-wide association analysis identifies cross-population viral signatures for inflammatory bowel disease.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {130}, pmid = {39026313}, issn = {2049-2618}, support = {82225048 and 82370563//National Natural Science Foundation of China/ ; 82225048 and 82370563//National Natural Science Foundation of China/ ; 2019RD15 and 2022RY18//Dalian Science and Technology Leading Talents Project/ ; 2019RD15 and 2022RY18//Dalian Science and Technology Leading Talents Project/ ; XLYC2002008//Distinguished professor of Liaoning Province/ ; }, mesh = {Humans ; *Virome ; *Gastrointestinal Microbiome/genetics ; Animals ; *Feces/virology/microbiology ; Mice ; *Inflammatory Bowel Diseases/virology/microbiology ; Female ; Male ; Adult ; Middle Aged ; Crohn Disease/virology/microbiology ; Bacteriophages/genetics/isolation & purification ; Colitis, Ulcerative/virology/microbiology ; Bacteria/classification/genetics/isolation & purification ; China ; Fecal Microbiota Transplantation ; Case-Control Studies ; Viruses/classification/isolation & purification/genetics ; }, abstract = {BACKGROUND: The gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking.

RESULTS: In this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn's disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models.

CONCLUSIONS: Building upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions. Video Abstract.}, } @article {pmid39023942, year = {2024}, author = {Yirmiya, K and Turjeman, S and Shtossel, O and Zagoory-Sharon, O and Moadi, L and Rubin, E and Sharon, E and Louzoun, Y and Koren, O and Feldman, R}, title = {Microbiome signature of posttraumatic stress disorder and resilience in youth.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {}, number = {}, pages = {}, doi = {10.1037/tra0001727}, pmid = {39023942}, issn = {1942-969X}, support = {//Bezos Family Foundation/ ; //theHarris Corporation/ ; //European Research Council (ERC)/ ; //Azrieli Foundation/ ; }, abstract = {OBJECTIVE: Identifying biomarkers that can distinguish trauma-exposed youth at risk for developing posttraumatic pathology from resilient individuals is essential for targeted interventions. As trauma can alter the microbiome with lasting effects on the host, our longitudinal, multimeasure, cross-species study aimed to identify the microbial signature of posttraumatic stress disorder (PTSD).

METHOD: We followed children exposed to war-related trauma and matched controls from early childhood (Mage = 2.76 years, N = 232) to adolescence (Mage = 16.13 years, N = 84), repeatedly assessing posttraumatic symptomatology and maternal caregiving. In late adolescence, we collected fecal samples from mothers and youth and assessed microbiome composition, diversity, and mother-child microbial synchrony. We then transplanted adolescents' fecal samples into germ-free mice to determine if behavioral changes are observed.

RESULTS: Youth with PTSD exhibited a distinct gut microbiome profile and lower diversity compared to resilient individuals, and microbiome diversity mediated the continuity of posttraumatic symptomatology throughout development. Low microbiome diversity correlated with more posttraumatic symptoms in early childhood, more emotional and behavioral problems in adolescence, and poor maternal caregiving. Youth with PTSD demonstrated less mother-child microbial synchrony, suggesting that low microbial concordance between mother and child may indicate susceptibility to posttraumatic illness. Germ-free mice transplanted with microbiomes from individuals with PTSD displayed increased anxious behavior.

CONCLUSIONS: Our findings provide evidence that the trauma-associated microbiome profile is at least partially responsible for the anxiety component of the PTSD phenotype and highlight microbial underpinnings of resilience. Further, our results suggest that the microbiome may serve as additional biological memory of early life stress and underscore the potential for microbiome-related diagnosis and treatment following trauma. (PsycInfo Database Record (c) 2024 APA, all rights reserved).}, } @article {pmid39022481, year = {2024}, author = {Beyer, BR and Sheppard, C and Mullins, J and Igbadumhe, A}, title = {Campylobacter Infection Introduced Following Fecal Microbiota Transplantation.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62541}, pmid = {39022481}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation is an evidence-based therapeutic option for recurrent Clostridium difficile infection, involving the transfer of healthy donor fecal material to restore gut microbial balance. Despite meticulous donor screening, Campylobacter jejuni, a prevalent cause of bacterial gastroenteritis, is not routinely tested, potentially impacting fecal microbiota transplant safety. We present a case of a female with recurrent C. difficile infection treated with fecal microbiota transplantation, complicated by a subsequent C. jejuni infection. The emergence of Campylobacter post fecal microbiota transplantation underscores the importance of comprehensive donor screening protocols. Our case prompts a reevaluation of fecal microbiota transplantation safety measures and advocates for inclusive screening to enhance patient outcomes.}, } @article {pmid39021924, year = {2024}, author = {Xu, D and Ren, L and Zhang, W and Wu, S and Yu, M and He, X and Wei, Z}, title = {Therapeutic effects and mechanisms of fecal microbiota transplantation on EAE partly through HPA axis-mediated neuroendocrine regulation.}, journal = {Heliyon}, volume = {10}, number = {12}, pages = {e33214}, pmid = {39021924}, issn = {2405-8440}, abstract = {BACKGROUND: The pathogenesis of multiple sclerosis (MS) may be closely related to immune regulation and inflammatory cytokines induced by specific flora. Repairing the intestinal flora may alter the immune response in MS patients, thus opening up novel approaches for the treatment of MS.

OBJECTIVE: We aimed to test the therapeutic effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and the characteristics of intestinal microbiota composition changes, explore the potential mechanisms of FMT treatment.

METHODS: EAE animals were treated with FMT, with the therapeutic effects were evaluated by observing neurological scores and measuring serum levels of cortisol, IL-17, and TLR-2. Fecal microbiome 16S rRNA sequencing was used to profile changes in microbiota composition, and adrenalectomy pretreatment was used to test whether FMT effects were dependent on HPA axis function.

RESULTS: FMT improved neurological function and reduced serum IL-17 to levels that were close to the control group. FMT reestablished intestinal homeostasis by altering the structure of the intestinal flora, increasing the abundance of beneficial flora, and regulating intestinal metabolites. We found that the therapeutic effects of FMT depended partly on the efferent function of the HPA axis; surgical disruption of the HPA axis altered the abundance and diversity of the intestinal flora.

CONCLUSION: FMT showed a neuroprotective effect on EAE by increasing the abundance of the beneficial flora, rebuilding intestinal homeostasis, reducing IL-17 and cortisol serum levels, and promoting serum TLR-2; the therapeutic effect of FMT on EAE is partly dependent on the HPA axis.}, } @article {pmid39021516, year = {2024}, author = {Xu, J and Xu, H and Yang, F and Xie, Y and Cai, F and Mao, S and Lu, M and Zhuang, H and Hua, ZC}, title = {Different depths of food restriction and high-fat diet refeeding in mice impact host obesity and metabolic phenotypes with correlative changes in the gut microbiota.}, journal = {MedComm}, volume = {5}, number = {8}, pages = {e641}, pmid = {39021516}, issn = {2688-2663}, abstract = {Overweight and obesity affect almost 2 billion adults worldwide, and food restriction (FR) is commonly used to reduce body fat. Whether refeeding (Re) after FR at different ages and to different degrees leads to overweight and its possible mechanisms are uncertain. In this study, adult and young mice were both restricted to 15% and 40% of their casual food intake, and then were fed 60% high-fat chow (FR15%-Re, FR40%-Re), whereas the control groups(CON) consumed high-fat or normal food throughout, respectively. The results of the study suggest that mild FR-heavy feeding may lead to more significant abnormal fat accumulation, liver damage, and increased recruitment of intestinal inflammatory factors and immune cells in mice of different ages and involves multiple types of alterations in the gut microbiota. Further fecal transplantation experiments as well as serum and liver enzyme-linked immunosorbent assay experiments preliminarily suggest that the link between lipid metabolism and inflammatory responses and the gut microbiota may be related to the regulation of the gut and live by Lipopolysaccharides(LPS) and Peroxisome Proliferator-Activated Receptor-Alpha(PPAR-α). In addition, our study may also serve as a reference for studying obesity prevention and treatment programs at different ages.}, } @article {pmid39017661, year = {2024}, author = {Rashidi, A and Pidala, J and Hamilton, BK and Pavletic, SZ and Kim, K and Zevin, A and Mays, JW and Lee, SJ}, title = {Oral and gut microbiome alterations in oral chronic graft-versus-host disease: results from Close Assessment and Testing for Chronic GVHD (CATCH study).}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {}, number = {}, pages = {}, doi = {10.1158/1078-0432.CCR-24-0875}, pmid = {39017661}, issn = {1557-3265}, abstract = {PURPOSE: Whether and how the oral microbiome and its changes in allogeneic hematopoietic cell transplantation (alloHCT) recipients may contribute to oral chronic graft-versus-host disease (cGVHD) pathogenesis is unknown. In addition, while the oral and colonic microbiota are distinct in healthy adults, whether oral microbes may ectopically colonize the gut in alloHCT patients is unknown.

EXPERIMENTAL DESIGN: To address these knowledge gaps, longitudinal oral and fecal samples were collected prospectively in the multicenter CATCH Study (Close Assessment and Testing for Chronic GVHD; NCT04188912). Through shotgun metagenomic sequencing of the samples collected at baseline, oral cGVHD onset, first post-cGVHD onset visit, and 1-year post-HCT timepoints in patients with oral cGVHD (cases; N = 29) or without any cGVHD (controls; N = 51), we examined whether (i) oral and/or gut microbiomes and their longitudinal trajectories differ between cases and controls, and (ii) oral and gut microbiomes overlap in alloHCT recipients, especially those developing cGVHD.

RESULTS: A total of 195 samples were analyzed. The onset of oral cGVHD was characterized by an expansion of Streptococcus salivarius and Veillonella parvula in the oral microbiome. High levels of oral/gut microbiota overlap were observed, particularly in patients with oral cGVHD, suggesting ectopic colonization of the gut by oral bacteria.

CONCLUSIONS: The unusual coalescence of two distant niches in these patients may have short- or long-term consequences for the host, a novel avenue for future research. In addition, this study suggests a contribution of the oral microbiome to oral cGVHD pathogenesis.}, } @article {pmid38720654, year = {2024}, author = {Khalid, A and Huang, Z and Khan, IM and Khalid, F and Nassar, N and Jiang, X and Cheng, M and Zhan, K and Wang, Z}, title = {Improving broiler health through cecal microbiota transplantation: a comprehensive study on growth, immunity, and microbial diversity.}, journal = {Journal of animal science}, volume = {102}, number = {}, pages = {}, doi = {10.1093/jas/skae131}, pmid = {38720654}, issn = {1525-3163}, mesh = {Animals ; *Chickens/growth & development/microbiology ; *Cecum/microbiology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Random Allocation ; Male ; Diet/veterinary ; }, abstract = {Cecal microbiota has emerged as a prominent intervention target for improving the production and welfare of poultry. This is essential for the overall health and performance of broiler chickens. The current study focused on investigating the effect of cecal microbiota transplantation (CMT) from healthy donor chickens on the growth performance, immunity, and microbial composition of newly hatched chicks and evaluated the effect of sample storage on the microbial diversity of the cecal samples. A healthy "Wannan Yellow Chicken line" was selected as the donor, and 180 1-d-old chicks from the same line were used as recipients for a 60-d feed trial. The chicks were randomly allocated to three groups (60 birds per group) with three replicates in each group. The three treatment groups were CMT-0 (control, normal saline solution), CMT-I (1:12 cecal content, normal saline supplemented with 10% glycerol), and CMT-II (1:6 cecal content, normal saline supplemented with 10% glycerol). The results of weight gain and absolute organ weight showed significant improvements in the CMT-II group compared with the CMT-0 group. Serum IgG level was significantly improved (P < 0.05) in CMT-I compared with that in the CMT-0. However, IL-6 levels increased in CMT-I and then significantly decreased in CMT-II. The cecal microbial diversity of CMT treatment was compared between two groups, fresh samples (FS) and stored samples at-80 °C (SS). The results showed that beneficial taxa, such as Firmicutes and Verrucomicrobiota, were substantially more abundant in both CMT-I and CMT-II than in CMT-0 in both FS and SS. Microbial function analysis at levels 1, 2, and 3 showed improved metabolism, genetic information processing, cellular processes, environmental information processing, and organismal systems in CMT-I and CMT-II for both FS and SS groups. However, the SS group showed decreased microbial diversity and function. To conclude, cecal microbiota transplantation is a promising strategy for enhancing the productivity and health of broiler chickens.}, } @article {pmid39012957, year = {2024}, author = {Zhao, S and Zhang, H and Zhu, H and Zhao, T and Tu, J and Yin, X and Yang, S and Zhang, W and Zhang, F and Zhang, M and Xu, B and Zhuge, Y and Xiao, J}, title = {Gut microbiota promotes macrophage M1 polarization in hepatic sinusoidal obstruction syndrome via regulating intestinal barrier function mediated by butyrate.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2377567}, pmid = {39012957}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Butyrates/metabolism ; *Macrophages/immunology ; Male ; Humans ; *Fecal Microbiota Transplantation ; *Hepatic Veno-Occlusive Disease/microbiology ; *Disease Models, Animal ; *Liver/metabolism ; Macrophage Activation ; Mice, Inbred C57BL ; Intestinal Mucosa/microbiology ; Female ; Feces/microbiology ; Bacteria/classification/isolation & purification/genetics ; Intestinal Barrier Function ; }, abstract = {BACKGROUND: The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options.

METHODS: The HSOS murine model was induced by gavage of monocrotaline (MCT). An analysis of 16S ribosomal DNA (16S rDNA) of the feces was conducted to determine the composition of the fecal microbiota. Macrophage clearance, fecal microbiota transplantation (FMT), and butyrate supplementation experiments were used to assess the role of intestinal flora, gut barrier, and macrophage activation and to explore the relationships among these three variables.

RESULTS: Activated macrophages and low microflora diversity were observed in HSOS patients and murine models. Depletion of macrophages attenuated inflammatory reactions and apoptosis in the mouse liver. Moreover, compared with control-FMT mice, the exacerbation of severe liver injury was detected in HSOS-FMT mice. Specifically, butyrate fecal concentrations were significantly reduced in HSOS mice, and administration of butyrate could partially alleviated liver damage and improved the intestinal barrier in vitro and in vivo. Furthermore, elevated lipopolysaccharides in the portal vein and high proportions of M1 macrophages in the liver were also detected in HSOS-FMT mice and mice without butyrate treatment, which resulted in severe inflammatory responses and further accelerated HSOS progression.

CONCLUSIONS: These results suggested that the gut microbiota exacerbated HSOS progression by regulating macrophage M1 polarization via altered intestinal barrier function mediated by butyrate. Our study has identified new strategies for the clinical treatment of HSOS.}, } @article {pmid39012675, year = {2024}, author = {Cheng, CK and Gao, J and Kang, L and Huang, Y}, title = {Fecal Microbiota Transfer from Young Mice Reverts Vascular Aging Hallmarks and Metabolic Impairments in Aged Mice.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.0384}, pmid = {39012675}, issn = {2152-5250}, abstract = {As a major risk factor for cardiometabolic diseases, aging refers to a gradual decline in physiological function, characterized with 12 conspicuous hallmarks, like telomere attrition, chronic inflammation, and dysbiosis. Common vascular aging hallmarks include endothelial dysfunction, telomere dysfunction, and vascular inflammation. In this study, we sought to test the hypothesis that young-derived gut microbiota retards vascular aging hallmarks and metabolic impairments in aged hosts. We also aimed to study the therapeutic efficacy of young microbiota in hosts of different ages. Fecal microbiota transplantation (FMT) from young to aged or middle-aged C57BL/6 mice was conducted for 6 consecutive weeks after antibiotic pretreatment. Endothelium-dependent relaxations (EDRs) in mouse arteries were determined by wire myography. Inflammation and AMPK/SIRT1 signaling in mouse aortas and intestines were studied by biochemical assays. The telomere function of aortas and intestines, in terms of telomerase reverse transcriptase expression, telomerase activity, and relative telomere length, were also studied. FMT significantly reverted vascular dysfunction and metabolic impairments in middle-aged mice than in aged mice. Besides, FMT significantly reverted inflammation and telomere dysfunction in aortas and intestines of middle-aged mice. Improved intestinal barrier function and activated AMPK/SIRT1 signaling potentially underlie benefits of FMT. The findings imply gut-vascular connection as potential target against age-associated cardiometabolic disorders, highlight crosstalk among aging hallmarks, and suggest a critical timepoint for efficacy of anti-aging interventions.}, } @article {pmid39012524, year = {2024}, author = {Tian, YQ and Ren, X and Wang, J and Li, X and Yin, YS and Guo, ZH and Qin, ZL and Zeng, XY}, title = {Berberine hydrochloride alleviates chronic prostatitis/chronic pelvic pain syndrome by modifying gut microbiome signaling.}, journal = {Asian journal of andrology}, volume = {}, number = {}, pages = {}, doi = {10.4103/aja202427}, pmid = {39012524}, issn = {1745-7262}, abstract = {Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is highly prevalent worldwide and poses a significant threat to men's health, particularly affecting young men. However, the exact causes and mechanisms behind CP/CPPS remain unclear, leading to challenges in its treatment. In this research, a CP/CPPS rat model was established with complete Freund's adjuvant (CFA), and berberine hydrochloride was administered through daily gavage to assess its therapeutic effects. The alterations in the gut microbiome induced by CP/CPPS and berberine hydrochloride were investigated through 16S ribosomal RNA sequencing of cecum content and colonic epithelial cells. To investigate the impact of the gut microbiome on CP/CPPS, a pseudo germ-free rat model was established, and fecal microbiome transplantation (FMT) was performed on these rats. In all, berberine hydrochloride demonstrated effective reduction of inflammation and oxidative stress in the prostate, offering significant therapeutic advantages for CP/CPPS. Through analysis of the gut microbiome using 16S ribosome RNA sequencing, distinct differences were observed between CP/CPPS rats and control rats, and Clostridium butyricum was identified as a key bacteria. Pseudo germ-free rats that underwent FMT from CP/CPPS rats or rats treated with berberine hydrochloride displayed varying levels of inflammatory cytokine production, oxidative stress, and activity of associated signaling pathways. In conclusion, the therapeutic potential of berberine hydrochloride in addressing CP/CPPS is highly significant. The gut microbiome has emerged as a critical factor in the development of CP/CPPS and plays a pivotal role in mediating the therapeutic effects of berberine hydrochloride.}, } @article {pmid39009513, year = {2024}, author = {Shoji, F}, title = {[The Role of Gut Microbiota in Lung Carcinogenesis and Cancer Immunotherapy].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {6}, pages = {597-602}, pmid = {39009513}, issn = {0385-0684}, mesh = {Animals ; Humans ; Carcinogenesis/immunology ; Dysbiosis/immunology/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; *Lung Neoplasms/immunology/therapy/microbiology ; }, abstract = {In recent years, the human microbiota, especially the gut microbiota, has been attracting attention in various fields, and it is one of the topics in the field of oncology. The human microbiota is known to act directly or indirectly on host immunity, and the gut and lung microbiota influence each other through the"gut-lung axis". It has been suggested that dysbiosis, a condition in which the symbiosis of the human microbiota is disrupted, induces lung inflammation and various respiratory diseases, and is also implicated in the immune microenvironment of lung cancer. It is also widely known that the gut microbiota modulates the efficacy of cancer immunotherapy, a major pillar of lung cancer treatment, and many clinical trials targeting the gut microbiota, such as fecal microbiome transplantation and biotics intervention, are currently being conducted. In the future, research on lung carcinogenesis mechanisms and lung cancer treatment focusing on the human microbiota will become increasingly active.}, } @article {pmid39009231, year = {2024}, author = {Réthi-Nagy, Z and Juhász, S}, title = {Microbiome's Universe: Impact on health, disease and cancer treatment.}, journal = {Journal of biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jbiotec.2024.07.002}, pmid = {39009231}, issn = {1873-4863}, abstract = {The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment.}, } @article {pmid39006746, year = {2024}, author = {Luo, C and Li, S and Chen, T}, title = {Editorial: The role of probiotics, postbiotics, and microbial metabolites in preventing and treating chronic diseases, volume II.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1442855}, pmid = {39006746}, issn = {2235-2988}, mesh = {*Probiotics/therapeutic use ; Humans ; Chronic Disease/prevention & control ; Gastrointestinal Microbiome ; }, } @article {pmid39006586, year = {2024}, author = {Sanzone, J and Life, M and Reiss, D and May, D and Hartley, B and Spiddle, P and Al-Kirwi, J and Grigoryan, T and Costin, J}, title = {Uses of Fecal Microbiota Transplantation in Neurodegenerative Disease: A Scoping Review.}, journal = {Cureus}, volume = {16}, number = {6}, pages = {e62265}, pmid = {39006586}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) is the administration of fecal bacteria from a healthy donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition and confer a health benefit. The relationship between the gut microbiome and the central nervous system, termed the gut-brain axis, has been a frequent topic of gut microbiome studies. Commensal gut bacteria communicate with the central nervous system through various hormones, cytokines, and neural pathways. Therefore, influencing the gut microbiome via FMT may have the potential in treating symptoms of neurodegenerative conditions. This study aims to identify current uses of FMT in treating neurodegenerative diseases and highlight areas of future investigation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, a literature search was conducted of peer-reviewed sources on September 27, 2022, from Embase, MEDLINE, Web of Science, and Cochrane Central. Search terms were utilized that were related to the application of FMT and neurodegenerative disorders and limited those human studies, those that were published in English, and those that were published between 2017 and 2022. The initial search yielded 450 unique articles, and after the assessment of the title and abstract for inclusion and exclusion criteria, six articles were identified for full-text review. Studies that focused on either Parkinson's disease (PD) or multiple sclerosis (MS) demonstrated improvements in both motor symptoms and non-motor symptoms. FMT was also shown to provide significant relief of constipation and general gastrointestinal (GI) symptoms in all conditions studied. The studies related to MS showed the most mixed results with regard to symptomatic improvement. The data on the use of FMT as a treatment for neurodegenerative disorders is limited; however, studies have shown not only improvement in GI symptoms but also improvement in the cognitive symptoms of PD and dementia. The data on FMT as a treatment to improve the motor symptoms of PD is both more complete and more compelling than the data on the motor symptoms of MS. The studies that were reviewed showed no major adverse effects of FMT and generally promising results. There is a strong case to be made for larger, more well-controlled studies to be done on FMT and its potential use as a treatment not only for GI symptoms but for the motor and cognitive symptoms of neurodegenerative diseases.}, } @article {pmid39006502, year = {2024}, author = {Lee, CS and Lin, CR and Chua, HH and Wu, JF and Chang, KC and Ni, YH and Chang, MH and Chen, HL}, title = {Gut Bifidobacterium longum is associated with better native liver survival in patients with biliary atresia.}, journal = {JHEP reports : innovation in hepatology}, volume = {6}, number = {7}, pages = {101090}, pmid = {39006502}, issn = {2589-5559}, abstract = {BACKGROUND & AIMS: The gut microbiome plays an important role in liver diseases, but its specific impact on biliary atresia (BA) remains to be explored. We aimed to investigate the microbial signature in the early life of patients with BA and to analyze its influence on long-term outcomes.

METHODS: Fecal samples (n = 42) were collected from infants with BA before and after Kasai portoenterostomy (KPE). The stool microbiota was analyzed using 16S rRNA next-generation sequencing and compared with that of age-matched healthy controls (HCs). Shotgun metagenomic sequencing analysis was employed to confirm the bacterial composition in 10 fecal samples before KPE. The correlation of the microbiome signature with liver function and long-term outcomes was assessed.

RESULTS: In the 16S rRNA next-generation sequencing analysis of fecal microbiota, the alpha and beta diversity analyses revealed significant differences between HCs and patients with BA before and after KPE. The difference in microbial composition analyzed by linear discriminant analysis and random forest classification revealed that the abundance of Bifidobacterium longum (B. longum) was significantly lower in patients before and after KPE than in HCs. The abundance of B. longum was negatively correlated with the gamma-glutamyltransferase level after KPE (p <0.05). Patients with early detectable B. longum had significantly lower total and direct bilirubin 3 months after KPE (p <0.005) and had a significantly lower liver transplantation rate (hazard ratio: 0.16, 95% CI 0.03-0.83, p = 0.029). Shotgun metagenomic sequencing also revealed that patients with BA and detectable B. longum had reduced total and direct bilirubin after KPE.

CONCLUSION: The gut microbiome of patients with BA differed from that of HCs, with a notable abundance of B. longum in early infancy correlating with better long-term outcomes.

IMPACT AND IMPLICATIONS: Bifidobacterium longum (B. longum) is a beneficial bacterium commonly found in the human gut. It has been studied for its potential impacts on various health conditions. In patients with biliary atresia, we found that a greater abundance of B. longum in the fecal microbiome is associated with improved clinical outcomes. This suggests that early colonization and increasing B. longum levels in the gut could be a therapeutic strategy to improve the prognosis of patients with biliary atresia.}, } @article {pmid39006130, year = {2024}, author = {Mao, Q and Wang, X and Cai, H and Yang, J and Zhang, Y and Min, W and Qian, Q and Zeng, Y}, title = {Research Progress on the Correlation of Atopic Dermatitis with Gut Microbiota.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {17}, number = {}, pages = {1613-1619}, pmid = {39006130}, issn = {1178-7015}, abstract = {Atopic dermatitis (AD) is a common skin disease, the pathogenesis of which has not been fully elucidated. The gut microbiota is the largest micro-ecosystem in the human body that affects the immune system and skin barrier function. Recent studies have shown that in addition to the environmental factors, skin barrier, genetic factors and immune response, gut microbiota disturbance may also cause AD. This review described the correlation of AD with gut microbiota and existing research status of AD treatment via targeting gut microbiota.}, } @article {pmid39003673, year = {2024}, author = {Schrock, J and Yan, M and Dolatyabi, S and Patil, V and Yadagiri, G and Renu, S and Ramesh, A and Wood, R and Hanson, J and Yu, Z and Renukaradhya, GJ}, title = {Human Infant Fecal Microbiota Differentially Influences the Mucosal Immune Pathways Upon Influenza Infection in a Humanized Gnotobiotic Pig Model.}, journal = {Current microbiology}, volume = {81}, number = {9}, pages = {267}, pmid = {39003673}, issn = {1432-0991}, support = {2018//College of Food, Agricultural, and Environmental Sciences, Ohio State University/ ; }, mesh = {Animals ; Swine ; *Germ-Free Life ; *Feces/microbiology/virology ; Humans ; *Gastrointestinal Microbiome ; *Immunity, Mucosal ; *Influenza A Virus, H1N1 Subtype/immunology ; *Disease Models, Animal ; *Cytokines/metabolism ; Orthomyxoviridae Infections/immunology/virology ; Viral Load ; Infant ; Influenza, Human/immunology/microbiology/virology ; }, abstract = {In this study, we evaluated the impact of human gut microbiota on the immune pathways in the respiratory tract using a gnotobiotic (Gn) piglet model. We humanized piglets with rural and urban infant fecal microbiota (RIFM and UIFM, respectively) and then infected them with a H1N1 swine influenza virus. We analyzed the microbial diversity and structure of the intestinal and respiratory tracts of the piglets before and after the influenza virus infection and measured the viral load and immune responses. We found that the viral load in the upper respiratory tract of UIFM transplanted piglets was higher than their rural cohorts (RIFM), while virus-specific antibody responses were comparable. The relative cytokine gene expression in the tracheobronchial (respiratory tract) and mesenteric (gastrointestinal) lymph nodes, lungs, blood, and spleen of RIFM and UIFM piglets revealed a trend in reciprocal regulation of proinflammatory, innate, and adaptive immune-associated cytokines as well as the frequency of T-helper/memory cells, cytotoxic T cells, and myeloid immune cell subsets. We also observed different phylum-level shifts of the fecal microbiota in response to influenza virus infection between the two piglet groups, suggesting the potential impact of the gut microbiota on the immune responses to influenza virus infection and lung microbiota. In conclusion, Gn piglets humanized with diverse infant fecal microbiota had differential immune regulation, with UIFM favoring the activation of proinflammatory immune mediators following an influenza virus infection compared to their rural RIFM cohorts. Furthermore, Gn piglets can be a useful model in investigating the impact of diverse human microbiota of the gastrointestinal tract, probably also the respiratory tract, on respiratory health and testing specific probiotic- or prebiotic-based therapeutics.}, } @article {pmid39002809, year = {2024}, author = {Liao, L and Zhang, L and Yang, C and Wang, T and Feng, L and Peng, C and Long, Y and Dai, G and Chang, L and Wei, Y and Fan, X}, title = {Sotagliflozin attenuates cardiac dysfunction and depression-like behaviors in mice with myocardial infarction through the gut-heart-brain axis.}, journal = {Neurobiology of disease}, volume = {199}, number = {}, pages = {106598}, doi = {10.1016/j.nbd.2024.106598}, pmid = {39002809}, issn = {1095-953X}, abstract = {Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.}, } @article {pmid39000282, year = {2024}, author = {Lin, X and Han, H and Wang, N and Wang, C and Qi, M and Wang, J and Liu, G}, title = {The Gut Microbial Regulation of Epigenetic Modification from a Metabolic Perspective.}, journal = {International journal of molecular sciences}, volume = {25}, number = {13}, pages = {}, pmid = {39000282}, issn = {1422-0067}, support = {2022YFD1300403//National Key R&D Program/ ; 2022JJ20027//Excellent Youth Foundation of Hunan Province/ ; CARS-35//Earmarked Fund for China Agriculture Research System/ ; }, mesh = {*Gastrointestinal Microbiome ; *Epigenesis, Genetic ; Humans ; *Obesity/metabolism/microbiology/genetics ; Animals ; Probiotics ; Fecal Microbiota Transplantation ; Prebiotics ; Energy Metabolism ; }, abstract = {Obesity is a global health challenge that has received increasing attention in contemporary research. The gut microbiota has been implicated in the development of obesity, primarily through its involvement in regulating various host metabolic processes. Recent research suggests that epigenetic modifications may serve as crucial pathways through which the gut microbiota and its metabolites contribute to the pathogenesis of obesity and other metabolic disorders. Hence, understanding the interplay between gut microbiota and epigenetic mechanisms is crucial for elucidating the impact of obesity on the host. This review primarily focuses on the understanding of the relationship between the gut microbiota and its metabolites with epigenetic mechanisms in several obesity-related pathogenic mechanisms, including energy dysregulation, metabolic inflammation, and maternal inheritance. These findings could serve as novel therapeutic targets for probiotics, prebiotics, and fecal microbiota transplantation tools in treating metabolic disruptions. It may also aid in developing therapeutic strategies that modulate the gut microbiota, thereby regulating the metabolic characteristics of obesity.}, } @article {pmid38999862, year = {2024}, author = {Wu, Y and Li, Y and Zheng, Q and Li, L}, title = {The Efficacy of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.}, journal = {Nutrients}, volume = {16}, number = {13}, pages = {}, pmid = {38999862}, issn = {2072-6643}, support = {No. 2022ZFJH003//The Fundamental Research Funds for the Central Universities/ ; SYS202202//Shandong Provincial Laboratory Project/ ; }, mesh = {*Irritable Bowel Syndrome/therapy/microbiology ; Humans ; *Prebiotics/administration & dosage ; *Probiotics/therapeutic use/administration & dosage ; *Synbiotics/administration & dosage ; *Fecal Microbiota Transplantation ; *Network Meta-Analysis ; Treatment Outcome ; Gastrointestinal Microbiome ; Randomized Controlled Trials as Topic ; Bifidobacterium ; Adult ; Female ; Lactobacillus ; Male ; }, abstract = {Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with gut microbiota imbalance playing a significant role. There are increasing numbers of research studies exploring treatment options involving probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), but it is still uncertain which treatment option is superior. The research was conducted on various databases and unpublished trial data (up to February 2023). Randomized controlled trials (RCTs) were screened for adult patients with IBS comparing interventions with placebo. Probiotics, prebiotics, synbiotics, and FMT were assessed for their impact using mean difference and Bayesian network meta-analysis. Out of 6528 articles, 54 were included for probiotics, 7 for prebiotics/synbiotics, and 6 for FMT. Probiotics showed improvement in IBS symptoms, particularly with Bifidobacterium and Lactobacillus strains. Prebiotics and synbiotics did not show significant improvement. Network meta-analysis indicated the favorable effects of probiotics (OR = 0.53, 95% CI, 0.48 to 0.59) and FMT (OR = 0.46, 95% CI, 0.33 to 0.64) on IBS, with no serious adverse events reported. In short, probiotics and FMT are effective for managing IBS, with Bifidobacterium and Lactobacillus being dominant strains. However, the most effective probiotic combination or strain remains unclear, while prebiotics and synbiotics did not show significant improvement.}, } @article {pmid38997819, year = {2024}, author = {Gefen, R and Strassmann, V and Stefano Hernandez, F and Garoufalia, Z and Horesh, N and Emile, SH and Da Silva, G and Wexner, S}, title = {Risk factors for complications following sacral neuromodulation for faecal incontinence: Long-term follow-up.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {}, number = {}, pages = {}, doi = {10.1111/codi.17092}, pmid = {38997819}, issn = {1463-1318}, abstract = {AIM: Sacral neuromodulation (SNM) has become a standard surgical treatment for faecal incontinence (FI). Prior studies have reported various adverse events of SNM, including suboptimal therapeutic response, infection, pain, haematoma, and potential need for redo SNM. The aim of this study was to identify the risk factors associated with long-term complications of SNM.

METHOD: This retrospective cohort reviewed patients who underwent two-stage SNM for FI at our institution between 2011-2021. Preoperative baseline characteristics and follow-up were obtained from the medical record and/or by telephone interview. Management and outcome of each postoperative event were evaluated by univariate and multivariate regression analyses.

RESULTS: A total of 291 patients (85.2% female) were included in this study. Postoperative complications were recorded in 219 (75.2%) patients and 154 (52.9%) patients required surgical intervention to treat complications. The most common postoperative event was loss of efficacy (46.4%). Other common adverse events were problems at the implant site (pain, infection, etc.) in 16.5% and pain during stimulation in 11.7%. Previous vaginal delivery (OR 2.74, p = 0.003) and anal surgery (OR = 2.46, p = 0.039) were independent predictors for complications. Previous colorectal (OR = 2.04, p = 0.026) and anal (OR = 1.98, p = 0.022) surgery and history of irritable bowel syndrome (IBS) (OR = 3.49, p = 0.003) were independent predictors for loss of efficacy.

CONCLUSION: Postoperative adverse events are frequently recorded after SNM. Loss of efficacy is the most common. Previous colorectal or anal surgery, vaginal delivery, and IBS are independent risk factors for complications.}, } @article {pmid38996677, year = {2024}, author = {Shao, W and Pan, B and Li, Z and Peng, R and Yang, W and Xie, Y and Han, D and Fang, X and Li, J and Zhu, Y and Zhao, Z and Kan, H and Ying, Z and Xu, Y}, title = {Gut microbiota mediates ambient PM2.5 exposure-induced abnormal glucose metabolism via short-chain fatty acids.}, journal = {Journal of hazardous materials}, volume = {476}, number = {}, pages = {135096}, doi = {10.1016/j.jhazmat.2024.135096}, pmid = {38996677}, issn = {1873-3336}, abstract = {PM2.5 exposure has been found to cause gut dysbiosis and impair glucose homeostasis in human and animals, yet their underlying biological connection remain unclear. In the present study, we aim to investigate the biological significance of gut microbiota in PM2.5-induced glucose metabolic abnormalities. Our results showed that microbiota depletion by antibiotics treatment significantly alleviated PM2.5-induced glucose intolerance and insulin resistance, as indicated by the intraperitoneal glucose tolerance test, glucose-induced insulin secretion, insulin tolerance test, insulin-induced phosphorylation levels of Akt and GSK-3β in insulin sensitive tissues. In addition, faecal microbiota transplantation (FMT) from PM2.5-exposed donor mice successfully remodeled the glucose metabolism abnormalities in recipient mice, while the transplantation of autoclaved faecal materials did not. Faecal microbiota analysis demonstrated that the composition and alpha diversity of the gut bacterial community were altered by PM2.5 exposure and in FMT recipient mice. Furthermore, short-chain fatty acids levels analysis showed that the circulating acetate was significantly decreased in PM2.5-exposed donor and FMT recipient mice, and supplementation of sodium acetate for 3 months successfully improved the glucose metabolism abnormalities induced by PM2.5 exposure. These results indicate that manipulating gut microbiota or its metabolites could be a potential strategy for preventing the adverse health effects of ambient PM2.5.}, } @article {pmid38996505, year = {2024}, author = {Jiang, ZM and Wang, FF and Zhao, YY and Lu, LF and Jiang, XY and Huang, TQ and Lin, Y and Guo, L and Weng, ZB and Liu, EH}, title = {Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1β pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {132}, number = {}, pages = {155847}, doi = {10.1016/j.phymed.2024.155847}, pmid = {38996505}, issn = {1618-095X}, abstract = {BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored.

PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL.

METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments.

RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1β pathway and increased proinflammatory IL1β in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1β pathway.

CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1β pathway, specifically by targeting AKK and tryptophan metabolites.}, } @article {pmid38993864, year = {2023}, author = {Dela Cruz, M and Lin, H and Han, J and Adler, E and Boissiere, J and Khalid, M and Sidebottom, A and Sundararajan, A and Lehmann, C and Moran, A and Odenwald, M and Stutz, M and Kim, G and Pinney, S and Jeevanandam, V and Alegre, ML and Pamer, E and Nguyen, AB}, title = {Reduced immunomodulatory metabolite concentrations in peri-transplant fecal samples from heart allograft recipients.}, journal = {Frontiers in transplantation}, volume = {2}, number = {}, pages = {1182534}, pmid = {38993864}, issn = {2813-2440}, abstract = {BACKGROUND: Emerging evidence is revealing the impact of the gut microbiome on hematopoietic and solid organ transplantation. Prior studies postulate that this influence is mediated by bioactive metabolites produced by gut-dwelling commensal bacteria. However, gut microbial metabolite production has not previously been measured among heart transplant (HT) recipients.

METHODS: In order to investigate the potential influence of the gut microbiome and its metabolites on HT, we analyzed the composition and metabolite production of the fecal microbiome among 48 HT recipients at the time of HT.

RESULTS: Compared to 20 healthy donors, HT recipients have significantly reduced alpha, i.e. within-sample, microbiota diversity, with significantly lower abundances of key anaerobic commensal bacteria and higher abundances of potentially pathogenic taxa that have been correlated with adverse outcomes in other forms of transplantation. HT recipients have a wide range of microbiota-derived fecal metabolite concentrations, with significantly reduced levels of immune modulatory metabolites such as short chain fatty acids and secondary bile acids compared to healthy donors. These differences were likely due to disease severity and prior antibiotic exposures but were not explained by other demographic or clinical factors.

CONCLUSIONS: Key potentially immune modulatory gut microbial metabolites are quantifiable and significantly reduced among HT recipients compared to healthy donors. Further study is needed to understand whether this wide range of gut microbial dysbiosis and metabolite alterations impact clinical outcomes and if they can be used as predictive biomarkers or manipulated to improve transplant outcomes.}, } @article {pmid38993521, year = {2024}, author = {Ge, Y and Wang, J and Wu, L and Wu, J}, title = {Gut microbiota: a potential new regulator of hypertension.}, journal = {Frontiers in cardiovascular medicine}, volume = {11}, number = {}, pages = {1333005}, pmid = {38993521}, issn = {2297-055X}, abstract = {Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases and has become a global public health concern. Although hypertension results from a combination of factors, the specific mechanism is still unclear. However, increasing evidence suggests that gut microbiota is closely associated with the development of hypertension. We provide a summary of the composition and physiological role of gut microbiota. We then delve into the mechanism of gut microbiota and its metabolites involved in the occurrence and development of hypertension. Finally, we review various regimens for better-controlling hypertension from the diet, exercise, drugs, antibiotics, probiotics, and fecal transplantation perspectives.}, } @article {pmid38992408, year = {2024}, author = {Ananthakrishnan, AN and Whelan, K and Allegretti, JR and Sokol, H}, title = {Diet and Microbiome-directed therapy 2.0 for IBD.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.05.049}, pmid = {38992408}, issn = {1542-7714}, abstract = {Inflammatory bowel disease (IBD) are chronic and relapsing disorders of the gastrointestinal tract, characterized by dysregulated immune responses to the gut microbiome. The gut microbiome and diet are key environmental factors that influence the onset and progression of IBD and can be leveraged for treatment. In this review, we summarize the current evidence on the role of the gut microbiome and diet in IBD pathogenesis, and the potential of microbiome-directed therapies and dietary interventions and improve IBD outcomes. We discuss available data, the advantages and drawbacks of the different approaches to manipulate the gut microbiome, such as fecal microbiota transplantation, next-generation and conventional probiotics, and postbiotics. We also review the use of diet as a therapeutic tool in IBD, including the effects in induction and maintenance, special diets, and exclusive enteral nutrition. Finally, we highlight the challenges and opportunities for the translation of diet and microbiome interventions into clinical practice, such as the need for personalization, manufacturing and regulatory hurdles, and the specificity to take into account for clinical trial design.}, } @article {pmid38992120, year = {2024}, author = {Ye, XX and Jiang, QY and Wu, MJ and Ye, QH and Zheng, H}, title = {Transplant of fecal microbiota from healthy young mice relieves cognitive defects in late-stage diabetic mice by reducing metabolic disorders and neuroinflammation.}, journal = {Acta pharmacologica Sinica}, volume = {}, number = {}, pages = {}, pmid = {38992120}, issn = {1745-7254}, abstract = {Fecal microbiota transplant (FMT) is becoming as a promising area of interest for treating refractory diseases. In this study, we investigated the effects of FMT on diabetes-associated cognitive defects in mice as well as the underlying mechanisms. Fecal microbiota was prepared from 8-week-aged healthy mice. Late-stage type 1 diabetics (T1D) mice with a 30-week history of streptozotocin-induced diabetics were treated with antibiotics for 7 days, and then were transplanted with bacterial suspension (100 μL, i.g.) once a day for 14 days. We found that FMT from healthy young mice significantly alleviated cognitive defects of late-stage T1D mice assessed in Morris water maze test. We revealed that FMT significantly reduced the relative abundance of Gram-negative bacteria in the gut microbiota and enhanced intestinal barrier integrity, mitigating LPS translocation into the bloodstream and NLRP3 inflammasome activation in the hippocampus, thereby reducing T1D-induced neuronal loss and astrocytic proliferation. FMT also reshaped the metabolic phenotypes in the hippocampus of T1D mice especially for alanine, aspartate and glutamate metabolism. Moreover, we showed that application of aspartate (0.1 mM) significantly inhibited NLRP3 inflammasome activation and IL-1β production in BV2 cells under a HG/LPS condition. We conclude that FMT can effectively relieve T1D-associated cognitive decline via reducing the gut-brain metabolic disorders and neuroinflammation, providing a potential therapeutic approach for diabetes-related brain disorders in clinic.}, } @article {pmid38990698, year = {2024}, author = {Wang, Z and Li, L and Li, W and Yan, H and Yuan, Y}, title = {Salidroside Alleviates Furan-Induced Impaired Gut Barrier and Inflammation via Gut Microbiota-SCFA-TLR4 Signaling.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c02433}, pmid = {38990698}, issn = {1520-5118}, abstract = {As a food contaminant that can be quickly absorbed through the gastrointestinal system, furan has been shown to disrupt the intestinal flora and barrier. Investigation of the intestinal toxicity mechanism of furan is of great significance to health. We previously identified the regulatory impact of salidroside (SAL) against furan-provoked intestinal damage, and the present work further explored whether the alleviating effect of SAL against furan-caused intestinal injury was based on the intestinal flora; three models, normal, pseudo-germ-free, and fecal microbiota transplantation (FMT), were established, and the changes in intestinal morphology, barrier, and inflammation were observed. Moreover, 16S rDNA sequencing observed the variation of the fecal flora associated with inflammation and short-chain fatty acids (SCFAs). Results obtained from the LC-MS/MS suggested that SAL increased furan-inhibited SCFA levels, activated the mRNA expressions of SCFA receptors (GPR41, GPR43, and GPR109A), and inhibited the furan-activated TLR4/MyD88/NF-κB signaling. Analysis of protein-protein interaction further confirmed the aforementioned effects of SAL, which inhibited furan-induced barrier damage and intestinal inflammation.}, } @article {pmid38990027, year = {2024}, author = {Yang, Y and Zhang, Z and Wang, Y and Rao, J and Sun, J and Wu, Z and He, J and Tan, X and Liang, L and Yu, Q and Wu, Z and Zou, H and Zhang, H and Dong, M and Zheng, J and Feng, S and Cheng, W and Wei, H}, title = {Colonization of microbiota derived from Macaca fascicularis, Bama miniature pigs, beagle dogs, and C57BL/6J mice alleviates DSS-induced colitis in germ-free mice.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0038824}, doi = {10.1128/spectrum.00388-24}, pmid = {38990027}, issn = {2165-0497}, abstract = {Fecal microbiota transplantation (FMT) is an innovative and promising treatment for inflammatory bowel disease (IBD), which is related to the capability of FMT to supply functional microorganisms to improve recipient gut health. Numerous studies have highlighted considerable variability in the efficacy of FMT interventions for IBD. Several factors, including the composition of the donor microorganisms, significantly affect the efficacy of FMT in the treatment of IBD. Consequently, identifying the functional microorganisms in the donor is crucial for enhancing the efficacy of FMT. To explore potential common anti-inflammatory bacteria with therapeutic implications for IBD, germ-free (GF) BALB/c mice were pre-colonized with fecal microbiota obtained from diverse donors, including Macaca fascicularis (MCC_FMT), Bama miniature pigs (BP_FMT), beagle dogs (BD_FMT), and C57BL/6 J mice (Mice_FMT). Subsequently, mice were treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by MCC_FMT, BP_FMT, BD_FMT, and Mice_FMT, as demonstrated by the prevention of an elevated disease activity index in mice. Additionally, the utilization of distinct donors protected the intestinal barrier and contributed to the regulation of cytokine homeostasis. Metagenomic sequencing data showed that the microbial community structure and dominant species were significantly different among the four groups, which may be linked to variations in the anti-inflammatory efficacy observed in the respective groups. Notably, Lactobacillus reuteri and Flavonifractor plautii were consistently present in all four groups. L. reuteri exhibited a significant negative correlation with IL-1β, and animal studies further confirmed its efficacy in alleviating IBD, suggesting the presence of common functional bacteria across different donors that exert anti-inflammatory effects. This study provides essential foundational data for the potential clinical applications of FMT.IMPORTANCEDespite variations in efficacy observed among donors, numerous studies have underscored the potential of fecal microbiota transplantation (FMT) for managing inflammatory bowel disease (IBD), indicating the presence of shared anti-IBD bacterial species. In the present study, the collective anti-inflammatory efficacy observed across all four donor groups prompted the identification of two common bacterial species using metagenomics. A significant negative correlation between Lactobacillus reuteri and IL-1β was revealed. Furthermore, mice gavaged with L. reuteri successfully managed the colitis challenge induced by dextran sodium sulfate (DSS), suggesting that L. reuteri may act as an efficacious bacterium mediating shared anti-inflammatory effects among variable donors. This finding highlights the utilization of variable donors to screen FMT core bacteria, which may be a novel strategy for developing FMT applications.}, } @article {pmid38989869, year = {2024}, author = {Gu, X and Yang, Z and Kou, Y and Yang, F and Wang, Y and Chen, Y and Wang, E and Jiang, X and Bai, Y and Zhang, Z and Zhang, S}, title = {Effects of Retrograde Colonic Enema Based Fecal Microbiota Transplantation in the Treatment of Childhood Constipation: A Randomized, Double-blind Controlled Trial.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000002958}, pmid = {38989869}, issn = {1572-0241}, support = {30700917//National Natural Science Foundation of China/ ; 81570465//National Natural Science Foundation of China/ ; }, abstract = {OBJECTIVE: Management of intractable childhood constipation is still challenging. The efficacy of retrograde colonic enema (RCE) with fecal microbiota transplantation (FMT) in intractable childhood constipation has not been established although both have demonstrated potential in gastrointestinal diseases. The aim of the current study was to determine the safety and efficacy of RCE-based FMT in the treatment of intractable constipation in children.

METHODS: A randomized, double-blind, controlled trial with 110 children was conducted. The subjects were randomly assigned to the FMT with RCE group or the placebo with RCE group. All participants received a daily RCE followed by a 4-week FMT treatment (twice a week) and a 12-week follow-up period. Spontaneous bowel movements (SBMs) ≥ 3 per week were the main outcomes and the risk ratio (RR) with 95% CI was calculated. Changes in the intestinal bacterial profile were analyzed by BOX-PCR-based DNA fingerprinting and sequencing. The adverse effects were assessed based on symptoms.

RESULTS: At the end of the follow-up period, 22 patients (40.0%) in the FMT with RCE group and 10 patients (18.2%) in the placebo with RCE group had ≥ 3 SBMs per week (net difference = 21.8%, 95% CI: 13.2%-30.4%; RR: 1.364, 95% CI: 1.063-1.749; P<0.05). Both RCE and FMT enriched the intestinal bacterial diversity of patients with constipation. The adverse events were all mild self-limiting gastrointestinal symptoms.

CONCLUSIONS: FMT enhances the efficacy of RCE and the use of RCE-based FMT is a safe and effective method in the treatment of intractable constipation in children.}, } @article {pmid38989699, year = {2024}, author = {Boyle, BL and Khanna, S}, title = {Fecal microbiota live - jslm (Rebyota™/RBL) for management of recurrent Clostridioides difficile infection.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/17460913.2024.2364583}, pmid = {38989699}, issn = {1746-0921}, abstract = {There is an unmet need for effective treatments of Clostridioides difficile infection, an emerging health crisis in the United States. The management of C. difficile infection should include treatment of active infection and a strategy to prevent recurrence. Current gold standard therapy includes oral antibiotics which predispose patients to gut dysbiosis and increase the risk of recurrent infection. Addressing dysbiosis via fecal microbiota transplantation is an active and promising area of research, but studies have lacked standardization which makes outcome and safety data difficult to interpret. Rebyota™, formerly known as RBX2660, is a live biotherapeutic product designed using a standardized protocol and manufacturing process that has been shown to be effective for preventing recurrent C. difficile infection.}, } @article {pmid38989143, year = {2024}, author = {Peng, Y and Huang, Y and Li, H and Li, C and Wu, Y and Chen, ZS and Wang, X and Liao, F and Miao, C}, title = {Huangqin Qingre Chubi Capsule inhibits rheumatoid arthritis by regulating intestinal flora and improving intestinal barrier.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1422245}, pmid = {38989143}, issn = {1663-9812}, abstract = {BACKGROUND: Changes in intestinal flora and intestinal barrier in patients with preclinical and diagnosed rheumatoid arthritis (RA) suggest that intestinal flora and intestinal barrier play an important role in the induction and persistence of RA. Huangqin Qingre Chubi Capsule (HQC) is a clinically effective herbal formula for the treatment of RA, but its therapeutic mechanism has not been fully clarified.

MATERIALS AND METHODS: In this study, real-time qPCR (RT-qPCR), 16SrRNA sequencing, Western blot (WB), immunofluorescence and other methods were used to investigate whether HQC inhibited RA.

RESULTS: Based on research in collages-induced arthritis (CIA) model in mice, human colon cancer cell line (Caco-2), and fibroblast-like synoviocytes (FLS) from RA patients, we found that intestinal flora was disturbed in CIA model group, intestinal barrier was damaged, and lipolyaccharide (LPS) level was increased, and HQC could regulate intestinal flora and intestinal barrier and reduce LPS translocation into blood. Antibiotic depletion weakened the anti-RA effect of HQC, and HQC fecal microbiota transplantation alleviated RA pathology. In addition, LPS increased the expression of RA pathologic factors MMP3, Fibronectin and inflammatory factors IL-6, TNF-α, IL-1β and IL-8, indicating that elevated peripheral blood level of LPS was related to RA pathology.

CONCLUSION: The dysregulation of intestinal flora and the disruption of intestinal barrier are significant factors in the development of RA. HQC improves RA by regulating intestinal flora, intestinal barrier and inhibiting LPS translocation into blood. The study unveiles RA's new pathogenesis and laid a scientific groundwork for advancing HQC therapy for RA.}, } @article {pmid38988813, year = {2024}, author = {Sipos, D and Varga, A and Kappéter, Á and Halda-Kiss, B and Kása, P and Pál, S and Kocsis, B and Péterfi, Z}, title = {Encapsulation protocol for fecal microbiota transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1424376}, pmid = {38988813}, issn = {2235-2988}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Clostridium Infections/therapy/microbiology ; *Feces/microbiology ; Treatment Outcome ; Female ; Clostridioides difficile ; Freeze Drying ; Male ; Middle Aged ; Aged ; Adult ; }, abstract = {INTRODUCTION: Clostridioides difficile infections (CDI) continue to pose a challenge for clinicians. Fecal microbiota transplantation (FMT) is an effective treatment option in CDI. Furthermore, recent and ongoing studies suggest potential benefits of FMT in other diseases as well.

METHODS: We would like to present a novel protocol for encapsulation of lyophilized fecal material. Our method provides with better compliance as well as improved flexibility, storage and safety.

RESULTS: FMT was conducted in 28 patients with an overall success rate of 82,14% using apsules containing lyophilized stool. 16 of patients were given capsules with lessened bacteria counts. The success rate in this group was 93,75%.

DISCUSSION: The results highlight the still unanswered questions about the mechanism of action and contribute to a wider use of FMT in the clinical praxis and in research.}, } @article {pmid38987780, year = {2024}, author = {Long, AE and Pitta, D and Hennessy, M and Indugu, N and Vecchiarelli, B and Luethy, D and Aceto, H and Hurcombe, S}, title = {Assessment of fecal bacterial viability and diversity in fresh and frozen fecal microbiota transplant (FMT) product in horses.}, journal = {BMC veterinary research}, volume = {20}, number = {1}, pages = {306}, pmid = {38987780}, issn = {1746-6148}, support = {580-5805-1-461612-xxxx-2000-5872//Raymond Firestone Trust/ ; 580-5805-1-461612-xxxx-2000-5872//Raymond Firestone Trust/ ; }, mesh = {Animals ; Horses/microbiology ; *Feces/microbiology ; *Bacteria/classification/genetics/isolation & purification ; *RNA, Ribosomal, 16S/genetics ; *Fecal Microbiota Transplantation/veterinary ; *Freezing ; Microbial Viability ; Cryopreservation/veterinary ; DNA, Bacterial/genetics ; }, abstract = {BACKGROUND: Currently, lack of standardization for fecal microbiota transplantation (FMT) in equine practice has resulted in highly variable techniques, and there is no data on the bacterial metabolic activity or viability of the administered product. The objectives of this study were to compare the total and potentially metabolically active bacterial populations in equine FMT, and assess the effect of different frozen storage times, buffers, and temperatures on an equine FMT product. Fresh feces collected from three healthy adult horses was subjected to different storage methods. This included different preservation solutions (saline plus glycerol or saline only), temperature (-20 °C or -80 °C), and time (fresh, 30, 60, or 90 days). Samples underwent DNA extraction to assess total bacterial populations (both live and dead combined) and RNA extraction followed by reverse transcription to cDNA as a proxy to assess viable bacteria, then 16s rRNA gene amplicon sequencing using the V1-V2 region.

RESULTS: The largest difference in population indices and taxonomic composition at the genus level was seen when evaluating the results of DNA-based (total) and cDNA-based (potentially metabolically active) extraction method. At the community level, alpha diversity (observed species, Shannon diversity) was significantly decreased in frozen samples for DNA-based analysis (P < 0.05), with less difference seen for cDNA-based sequencing. Using DNA-based analysis, length of storage had a significant impact (P < 0.05) on the bacterial community profiles. For potentially metabolically active populations, storage overall had less of an effect on the bacterial community composition, with a significant effect of buffer (P < 0.05). Individual horse had the most significant effect within both DNA and cDNA bacterial communities.

CONCLUSIONS: Frozen storage of equine FMT material can preserve potentially metabolically active bacteria of the equine fecal microbiome, with saline plus glycerol preservation more effective than saline alone. Larger studies are needed to determine if these findings apply to other individual horses. The ability to freeze FMT material for use in equine patients could allow for easier clinical use of fecal transplant in horses with disturbances in their intestinal microbiome.}, } @article {pmid38987677, year = {2024}, author = {van Rossen, TM and van Beurden, YH and Bogaards, JA and Budding, AE and Mulder, CJJ and Vandenbroucke-Grauls, CMJE}, title = {Fecal microbiota composition is a better predictor of recurrent Clostridioides difficile infection than clinical factors in a prospective, multicentre cohort study.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {687}, pmid = {38987677}, issn = {1471-2334}, support = {848016009//Netherlands Organization for Health Research and Development (ZonMw)/ ; 645.001.002//Dutch Organization for Scientific Research (NWO)/ ; }, mesh = {Humans ; *Clostridium Infections/microbiology/therapy ; Male ; Prospective Studies ; Female ; *Feces/microbiology ; Middle Aged ; Aged ; *Gastrointestinal Microbiome ; Clostridioides difficile/genetics ; Fecal Microbiota Transplantation ; Adult ; Recurrence ; Anti-Bacterial Agents/therapeutic use ; Aged, 80 and over ; Fidaxomicin/therapeutic use ; }, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhoea. Fidaxomicin and fecal microbiota transplantation (FMT) are effective, but expensive therapies to treat recurrent CDI (reCDI). Our objective was to develop a prediction model for reCDI based on the gut microbiota composition and clinical characteristics, to identify patients who could benefit from early treatment with fidaxomicin or FMT.

METHODS: Multicentre, prospective, observational study in adult patients diagnosed with a primary episode of CDI. Fecal samples and clinical data were collected prior to, and after 5 days of CDI treatment. Follow-up duration was 8 weeks. Microbiota composition was analysed by IS-pro, a bacterial profiling technique based on phylum- and species-specific differences in the 16-23 S interspace regions of ribosomal DNA. Bayesian additive regression trees (BART) and adaptive group-regularized logistic ridge regression (AGRR) were used to construct prediction models for reCDI.

RESULTS: 209 patients were included, of which 25% developed reCDI. Variables related to microbiota composition provided better prediction of reCDI and were preferentially selected over clinical factors in joint prediction models. Bacteroidetes abundance and diversity after start of CDI treatment, and the increase in Proteobacteria diversity relative to baseline, were the most robust predictors of reCDI. The sensitivity and specificity of a BART model including these factors were 95% and 78%, but these dropped to 67% and 62% in out-of-sample prediction.

CONCLUSION: Early microbiota response to CDI treatment is a better predictor of reCDI than clinical prognostic factors, but not yet sufficient enough to predict reCDI in daily practice.}, } @article {pmid38987594, year = {2024}, author = {Fujimoto, K and Hayashi, T and Yamamoto, M and Sato, N and Shimohigoshi, M and Miyaoka, D and Yokota, C and Watanabe, M and Hisaki, Y and Kamei, Y and Yokoyama, Y and Yabuno, T and Hirose, A and Nakamae, M and Nakamae, H and Uematsu, M and Sato, S and Yamaguchi, K and Furukawa, Y and Akeda, Y and Hino, M and Imoto, S and Uematsu, S}, title = {An enterococcal phage-derived enzyme suppresses graft-versus-host disease.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {38987594}, issn = {1476-4687}, abstract = {Changes in the gut microbiome have pivotal roles in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogenic haematopoietic cell transplantation (allo-HCT)[1-6]. However, effective methods for safely resolving gut dysbiosis have not yet been established. An expansion of the pathogen Enterococcus faecalis in the intestine, associated with dysbiosis, has been shown to be a risk factor for aGVHD[7-10]. Here we analyse the intestinal microbiome of patients with allo-HCT, and find that E. faecalis escapes elimination and proliferates in the intestine by forming biofilms, rather than by acquiring drug-resistance genes. We isolated cytolysin-positive highly pathogenic E. faecalis from faecal samples and identified an anti-E. faecalis enzyme derived from E. faecalis-specific bacteriophages by analysing bacterial whole-genome sequencing data. The antibacterial enzyme had lytic activity against the biofilm of E. faecalis in vitro and in vivo. Furthermore, in aGVHD-induced gnotobiotic mice that were colonized with E. faecalis or with patient faecal samples characterized by the domination of Enterococcus, levels of intestinal cytolysin-positive E. faecalis were decreased and survival was significantly increased in the group that was treated with the E. faecalis-specific enzyme, compared with controls. Thus, administration of a phage-derived antibacterial enzyme that is specific to biofilm-forming pathogenic E. faecalis-which is difficult to eliminate with existing antibiotics-might provide an approach to protect against aGVHD.}, } @article {pmid38985782, year = {2024}, author = {Liow, YJ and Kamimura, I and Umezaki, M and Suda, W and Takayasu, L}, title = {Dietary fiber induces a fat preference associated with the gut microbiota.}, journal = {PloS one}, volume = {19}, number = {7}, pages = {e0305849}, pmid = {38985782}, issn = {1932-6203}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Dietary Fiber ; Male ; Mice ; *Mice, Inbred C57BL ; *Food Preferences ; *Diet, High-Fat/adverse effects ; Feces/microbiology ; Inulin/pharmacology/administration & dosage ; Dietary Fats/pharmacology ; Feeding Behavior ; Bacteroides ; Clostridiales ; }, abstract = {Eating behavior is essential to human health. However, whether future eating behavior is subjected to the conditioning of preceding dietary composition is unknown. This study aimed to investigate the effect of dietary fiber consumption on subsequent nutrient-specific food preferences between palatable high-fat and high-sugar diets and explore its correlation with the gut microbiota. C57BL/6NJcl male mice were subjected to a 2-week dietary intervention and fed either a control (n = 6) or inulin (n = 6) diet. Afterward, all mice were subjected to a 3-day eating behavioral test to self-select from the simultaneously presented high-fat and high-sugar diets. The test diet feed intakes were recorded, and the mice's fecal samples were analyzed to evaluate the gut microbiota composition. The inulin-conditioned mice exhibited a preference for the high-fat diet over the high-sugar diet, associated with distinct gut microbiota composition profiles between the inulin-conditioned and control mice. The gut microbiota Oscillospiraceae sp., Bacteroides acidifaciens, and Clostridiales sp. positively correlated with a preference for fat. Further studies with fecal microbiota transplantation and eating behavior-related neurotransmitter analyses are warranted to establish the causal role of gut microbiota on host food preferences. Food preferences induced by dietary intervention are a novel observation, and the gut microbiome may be associated with this preference.}, } @article {pmid38985582, year = {2024}, author = {Guzzardi, MA and La Rosa, F and Faita, F and Ait-Ali, L and Panetta, D and Kusmic, C and Granziera, F and Festa, P and Pardo-Tendero, M and Brigidi, P and Monelon, D and Iozzo, P}, title = {The transfer of gut microbiota/metabolites from children to mice affects cardiometabolic development and induces sex-dimorphism in recipients.}, journal = {Vascular pharmacology}, volume = {155}, number = {}, pages = {107325}, doi = {10.1016/j.vph.2024.107325}, pmid = {38985582}, issn = {1879-3649}, mesh = {*Gastrointestinal Microbiome ; Animals ; Humans ; Female ; Male ; Sex Factors ; Child ; Fecal Microbiota Transplantation ; Age Factors ; Mice ; Bacteria/metabolism/growth & development/genetics ; Cardiometabolic Risk Factors ; Mice, Inbred C57BL ; }, } @article {pmid38984661, year = {2024}, author = {Zhao, JT and Zhang, Y and Wang, XW and Zou, PY and Zhao, Z and Mei, H and Liu, YX and Su, NY and Zhu, YJ and Wang, B and Wei, YL and Chen, DF and Lan, CH}, title = {Long-term effects of fecal microbiota transplantation on gut microbiota after Helicobacter pylori eradication with bismuth quadruple therapy: A randomized controlled trial.}, journal = {Helicobacter}, volume = {29}, number = {4}, pages = {e13079}, doi = {10.1111/hel.13079}, pmid = {38984661}, issn = {1523-5378}, support = {82072253//National Natural Science Foundation of China/ ; 2022jstg020//Chongqing Appropriate Health Technology Promotion/ ; }, mesh = {Humans ; *Helicobacter Infections/therapy/microbiology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Middle Aged ; *Helicobacter pylori/drug effects ; Adult ; *Anti-Bacterial Agents/therapeutic use ; Prospective Studies ; *Bismuth/therapeutic use ; Drug Therapy, Combination ; China ; Amoxicillin/therapeutic use ; Clarithromycin/therapeutic use ; Treatment Outcome ; Aged ; Feces/microbiology ; }, abstract = {BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known.

MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment.

RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group.

CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.}, } @article {pmid38983955, year = {2024}, author = {Ma, BT and Sang, LX and Chang, B}, title = {Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis.}, journal = {World journal of gastroenterology}, volume = {30}, number = {24}, pages = {3123-3125}, pmid = {38983955}, issn = {2219-2840}, mesh = {Humans ; *Immune Checkpoint Inhibitors/adverse effects ; *Gastritis/microbiology/immunology/therapy/chemically induced ; *Gastrointestinal Microbiome/immunology/drug effects ; *Fecal Microbiota Transplantation/methods/adverse effects ; Treatment Outcome ; Stomach/microbiology/immunology/surgery ; Gastric Mucosa/microbiology/immunology/pathology/drug effects ; }, abstract = {Immune-related adverse events (irAEs) are complications of the use of immune checkpoint inhibitors (ICIs). ICI-associated gastritis is one of the main irAEs. The gastric microbiota is often related to the occurrence and development of many gastric diseases. Gastric microbiota adjustment may be used to treat gastric disorders in the future. Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis. Therefore, we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.}, } @article {pmid38983862, year = {2024}, author = {Zhang, Q and Bi, Y and Zhang, B and Jiang, Q and Mou, CK and Lei, L and Deng, Y and Li, Y and Yu, J and Liu, W and Zhao, J}, title = {Current landscape of fecal microbiota transplantation in treating depression.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1416961}, pmid = {38983862}, issn = {1664-3224}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; *Depression/therapy/microbiology ; *Brain-Gut Axis ; *Dysbiosis/therapy ; Animals ; Treatment Outcome ; }, abstract = {Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecal microbiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the long-term safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies.}, } @article {pmid38980456, year = {2024}, author = {Azuma, T and Sato, Y and Chiba, H and Haga, J}, title = {Appendiceal goblet cell adenocarcinoma newly classified by WHO 5th edition: a case report (a secondary publication).}, journal = {Surgical case reports}, volume = {10}, number = {1}, pages = {168}, pmid = {38980456}, issn = {2198-7793}, abstract = {BACKGROUND: Appendiceal goblet cell adenocarcinoma (AGCA) is a newly proposed cancer type in the 5th edition of the WHO Classification of Tumours in 2019. We experienced this rare form of appendiceal primary neoplasm.

CASE PRESENTATION: An 85-year-old male presented a positive fecal occult blood test. A series of imagings revealed a type 1 tumor, located on the appendiceal orifice. The subsequent biopsy made the diagnosis of signet-ring cell carcinoma. Consequently, he underwent the laparoscopic-assisted ileocecal resection. Initially, the tumor was suspected to be a Goblet cell carcinoid (GCC). There was a discrepancy between the histological and immunostaining findings: the tumor cells exhibited morphological similarities to GCCs, however displayed limited staining upon immunostaining. Ultimately, we concluded that the tumor should be classified as AGCA, by following WHO 5th Edition. AGCA represents a newly categorized subtype of adenocarcinomas. Because of our preoperative suspicion of malignancy, we performed tumor resection with regional lymph node dissection, despite the fact that most appendiceal malignant tumors are typically identified after an appendectomy.

CONCLUSION: We experienced a case that provides valuable insights into the comprehension of AGCA, a recently established pathological entity in the WHO 5th Edition. This article is an acceptable secondary publication of a case report that appeared in Azuma et al. (J Jpn Surg Assoc 83:1103-1108, 2022).}, } @article {pmid38979196, year = {2024}, author = {Yang, Y and Chi, L and Hsiao, YC and Lu, K}, title = {Sex-specific effects of gut microbiome on shaping bile acid metabolism.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38979196}, issn = {2692-8205}, abstract = {Gut microbiome is a group of microorganisms that plays important roles in contributing to health and diseases. These bacterial compositions have been demonstrated to impact bile acids (BAs) profiles, either by directly metabolizing primary BAs to secondary BAs or indirect ways through host metabolism by influencing BAs synthesis, transportation and conjugation in liver. It has been observed sexually dimorphic gut microbiome and bile acids composition, with variations in expression levels of bile acid metabolizing genes in the liver. However, associations betweensex-specific differences in gut microbiome and BAs profiles are not well understood. This study aimed to investigate whether gut microbiome could influence BAs profiles in host in a sex-specific manner. We transplanted cecum feces of male and female C57BL/6 mice to male mice and measured BAs concentrations in feces, serum and liver samples 7 days after fecal transplantation. We found different BAs profiles between mice with male and female gut microbiome, including altering levels and proportions of secondary BAs. We also observed varied expression levels of genes related to bile acid metabolism in the liver and distal ileum.Our results highlight sex-specific effects of gut microbiome on shaping bile acid metabolism through gut bacteria and regulation of host genes.}, } @article {pmid38979127, year = {2024}, author = {He, H and Li, M and Qiu, Y and Wu, Z and Wu, L}, title = {Washed microbiota transplantation improves sleep quality in patients with sleep disorder by the gut-brain axis.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1415167}, pmid = {38979127}, issn = {1662-4548}, abstract = {BACKGROUND: The clinical impact of washed microbiota transplantation (WMT) from healthy donors in sleep disorder (SD) patients is unclear. This study aimed to investigate the effect of WMT in SD patients.

METHODS: The clinical data were collected from patients with different indications receiving 1-3 courses of WMT, divided into two groups by 7 points of PSQI scale. The score of PQSI and SF-36 scale was used to assess the improvement in sleep quality and life quality among patients with sleep disorders following WMT. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of patients with sleep disorders before and after WMT.

RESULTS: WMT significantly improved sleep quality in patients with sleep disorder in the short and medium term. WMT significantly improved sleep latency, sleep time and total score in the short term. WMT significantly improved sleep quality and total score in the medium term. In terms of sleep quality and sleep latency, the improvement value also increased with the increase of treatment course, and the improvement effect of multiple treatment course was better than that of single and double treatment course. In the total score, the improvement effect of double and multiple treatment was better than that of single treatment. WMT also improved quality of life in the sleep disorder group. WMT significantly improved general health, vitality, social function and mental health in the short term. WMT significantly improved role-physical, general health, vitality, and mental health in the medium term. WMT regulated the disturbed gut microbiota in patients with sleep disorders. In the normal sleep group, WMT had no effect on the decline of sleep quality in the short, medium and long term, and had an improving effect on the quality of life.

CONCLUSION: WMT could significantly improve sleep quality and life quality in patients with sleep disorders with no adverse events. The improvement in sleep quality resulting from WMT could lead to an overall enhancement in life quality. WMT could be a potentially effective treatment for patients with sleep disorders by regulating the gut microbiota.}, } @article {pmid38978633, year = {2024}, author = {Watanangura, A and Meller, S and Farhat, N and Suchodolski, JS and Pilla, R and Khattab, MR and Lopes, BC and Bathen-Nöthen, A and Fischer, A and Busch-Hahn, K and Flieshardt, C and Gramer, M and Richter, F and Zamansky, A and Volk, HA}, title = {Behavioral comorbidities treatment by fecal microbiota transplantation in canine epilepsy: a pilot study of a novel therapeutic approach.}, journal = {Frontiers in veterinary science}, volume = {11}, number = {}, pages = {1385469}, pmid = {38978633}, issn = {2297-1769}, abstract = {INTRODUCTION: Anxiety and cognitive dysfunction are frequent, difficult to treat and burdensome comorbidities in human and canine epilepsy. Fecal microbiota transplantation (FMT) has been shown to modulate behavior in rodent models by altering the gastrointestinal microbiota (GIM). This study aims to investigate the beneficial effects of FMT on behavioral comorbidities in a canine translational model of epilepsy.

METHODS: Nine dogs with drug-resistant epilepsy (DRE) and behavioral comorbidities were recruited. The fecal donor had epilepsy with unremarkable behavior, which exhibited a complete response to phenobarbital, resulting in it being seizure-free long term. FMTs were performed three times, two weeks apart, and the dogs had follow-up visits at three and six months after FMTs. Comprehensive behavioral analysis, including formerly validated questionnaires and behavioral tests for attention deficit hyperactivity disorder (ADHD)- and fear- and anxiety-like behavior, as well as cognitive dysfunction, were conducted, followed by objective computational analysis. Blood samples were taken for the analysis of antiseizure drug (ASD) concentrations, hematology, and biochemistry. Urine neurotransmitter concentrations were measured. Fecal samples were subjected to analysis using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based Dysbiosis Index (DI) assessment, and short-chain fatty acid (SCFA) quantification.

RESULTS: Following FMT, the patients showed improvement in ADHD-like behavior, fear- and anxiety-like behavior, and quality of life. The excitatory neurotransmitters aspartate and glutamate were decreased, while the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABA/glutamate ratio were increased compared to baseline. Only minor taxonomic changes were observed, with a decrease in Firmicutes and a Blautia_A species, while a Ruminococcus species increased. Functional gene analysis, SCFA concentration, blood parameters, and ASD concentrations remained unchanged.

DISCUSSION: Behavioral comorbidities in canine IE could be alleviated by FMT. This study highlights FMT's potential as a novel approach to improving behavioral comorbidities and enhancing the quality of life in canine patients with epilepsy.}, } @article {pmid38976982, year = {2024}, author = {Vehreschild, MJGT and Schreiber, S and von Müller, L and Epple, HJ and Manthey, C and Oh, J and Weinke, T and Wahler, S and Stallmach, A}, title = {[Need for improvement in the care of patients with Clostridioides difficile infections (CDI) - expert opinion in international comparison].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {62}, number = {7}, pages = {1032-1041}, doi = {10.1055/a-2293-7760}, pmid = {38976982}, issn = {1439-7803}, mesh = {Humans ; *Clostridium Infections/therapy/epidemiology ; Germany ; Quality Improvement ; Internationality ; Expert Testimony ; Fecal Microbiota Transplantation ; Evidence-Based Medicine ; Needs Assessment ; Cross Infection/prevention & control/epidemiology/therapy ; Practice Guidelines as Topic ; }, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI), as a nosocomial disease, is associated with high morbidity and mortality. Even though the incidence of CDI has been declining in Germany in recent years, the individual infection may pose a medical challenge despite therapeutic advances. The aim here is to clarify which gaps practitioners consider to be particularly serious in care and in the existing evidence base.

METHODS: In a moderated workshop of German CDI experts the topics considered as relevant were identified. A survey already conducted in five other countries (Australia, France, Great Britain, Canada, and Italy) was adapted and processed by 27 practitioners. During the evaluation, the topics perceived as particularly important were identified, the statements of the specialist groups were compared and changes in opinion were considered.

RESULTS: 27 fully completed questionnaires were evaluated. The need for improvement was primarily seen in the prevention of CDI recurrences (74.1%) and the treatment of recurrences (55.6%). Evidence deficits were noted in the treatment of recurrences (55.6%) and identification of risk factors for recurrences (48.1%). Improving care via fecal microbiota transfer (FMT) was named by 70.4%. For guidelines, more clarity (48.1%) and more regular updates (40.7%) were desired. For patients, better education on appropriate antibiotic use (52.0%) and choice of FMT were desired (48.1%).

SUMMARY: The German expert view and the international assessment is similar, when asked about the need for improvement in care and evidence gaps in the treatment of patients with CDI: The focus is on prevention and therapy of recurrent CDI. The problem of access to FMT is a German peculiarity that seems to need improvement.}, } @article {pmid38976078, year = {2024}, author = {Fang, L and Ning, J}, title = {Gut virome and diabetes: discovering links, exploring therapies.}, journal = {Archives of microbiology}, volume = {206}, number = {8}, pages = {346}, pmid = {38976078}, issn = {1432-072X}, support = {NO.2022003//the Scientific Research Projects of Medical and Health Institutions of Longhua District, Shenzhen/ ; NO.2022003//the Scientific Research Projects of Medical and Health Institutions of Longhua District, Shenzhen/ ; No. HLPM201907020104//the High Level Project of Medicine in Longhua, ShenZhen/ ; No. HLPM201907020104//the High Level Project of Medicine in Longhua, ShenZhen/ ; NO.2024027//the Scientific Research Projects of Medical and Health Institutions of Longhua District, Shenzhen,/ ; NO.2024027//the Scientific Research Projects of Medical and Health Institutions of Longhua District, Shenzhen,/ ; }, mesh = {Humans ; *Virome ; *Gastrointestinal Microbiome ; *Diabetes Mellitus, Type 1/therapy/virology/immunology ; *Diabetes Mellitus, Type 2/therapy/virology ; *Fecal Microbiota Transplantation ; Animals ; Bacteriophages/genetics/physiology ; Viruses/genetics/classification ; }, abstract = {This review offers a comprehensive analysis of the intricate relationship between the gut virome and diabetes, elucidating the mechanisms by which the virome engages with both human cells and the intestinal bacteriome. By examining a decade of scientific literature, we provide a detailed account of the distinct viral variations observed in type 1 diabetes (T1D) and type 2 diabetes (T2D). Our synthesis reveals that the gut virome significantly influences the development of both diabetes types through its interactions, which indirectly modulate immune and inflammatory responses. In T1D, the focus is on eukaryotic viruses that stimulate the host's immune system, whereas T2D is characterized by a broader spectrum of altered phage diversities. Promisingly, in vitro and animal studies suggest fecal virome transplantation as a potential therapeutic strategy to alleviate symptoms of T2D and obesity. This study pioneers a holistic overview of the gut virome's role in T1D and T2D, its interplay with host immunity, and the innovative potential of fecal transplantation therapy in clinical diabetes management.}, } @article {pmid38975247, year = {2024}, author = {Mehta, N and Goodenough, D and Gupta, NK and Thomas, S and Mehta, C and Prakash, R and Woodworth, MH and Kraft, CS and Fridkin, SK}, title = {Recurrent Clostridioides difficile Infection and Outcome of Fecal Microbiota Transplantation Use: A Population-Based Assessment.}, journal = {Open forum infectious diseases}, volume = {11}, number = {7}, pages = {ofae309}, pmid = {38975247}, issn = {2328-8957}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; U54CK000485/ACL/ACL HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; U54 CK000485/CK/NCEZID CDC HHS/United States ; TL1 TR002382/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection (rCDI). In the current study, we evaluated rates of rCDI and subsequent FMT in a large metropolitan area. We compared demographic and clinical differences in FMT recipients and nonrecipients and quantified differences in outcomes based on treatment modality.

METHODS: A retrospective community-wide cohort study was conducted using surveillance data from the Georgia Emerging Infections Program, the Georgia Discharge Data System, and locally maintained lists of FMTs completed across multiple institutions to evaluate all episodes of C. difficile infection (CDI) in this region between 2016 and 2019. Cases were limited to patients with rCDI and ≥1 documented hospitalization. A propensity-matched cohort was created to compare rates of recurrence and mortality among matched patients based on FMT receipt.

RESULTS: A total of 3038 (22%) of 13 852 patients with CDI had rCDI during this period. In a propensity-matched cohort, patients who received an FMT had lower rates of rCDI (odds ratio, 0.6 [95% confidence interval, .38-.96) and a lower mortality rate (0.26 [.08-.82]). Of patients with rCDI, only 6% had received FMT. Recipients were more likely to be young, white, and female and less likely to have renal disease, diabetes, or liver disease, though these chronic illnesses were associated with higher rates of rCDI.

CONCLUSIONS: These data suggest FMT has been underused in a population-based assessment and that FMT substantially reduced risk of recurrence and death.}, } @article {pmid38974034, year = {2024}, author = {Benvenuti, L and Di Salvo, C and Bellini, G and Seguella, L and Rettura, F and Esposito, G and Antonioli, L and Ceravolo, R and Bernardini, N and Pellegrini, C and Fornai, M}, title = {Gut-directed therapy in Parkinson's disease.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1407925}, pmid = {38974034}, issn = {1663-9812}, abstract = {Parkinson's disease (PD) is a common and slow-progressing neurodegenerative disorder characterized by motor and non-motor symptoms, including gastrointestinal (GI) dysfunctions. Over the last years, the microbiota-gut-brain (MGB) axis is emerging as a bacterial-neuro-immune ascending pathway that contributes to the progression of PD. Indeed, PD patients are characterized by changes in gut microbiota composition, alterations of intestinal epithelial barrier (IEB) and enteric neurogenic/inflammatory responses that, besides determining intestinal disturbances, contribute to brain pathology. In this context, despite the causal relationship between gut dysbiosis, impaired MGB axis and PD remains to be elucidated, emerging evidence shows that MGB axis modulation can represent a suitable therapeutical strategy for the treatment of PD. This review provides an overview of the available knowledge about the beneficial effects of gut-directed therapies, including dietary interventions, prebiotics, probiotics, synbiotics and fecal microbiota transplantation (FMT), in both PD patients and animal models. In this context, particular attention has been devoted to the mechanisms by which the modulation of MGB axis could halt or slow down PD pathology and, most importantly, how these approaches can be included in the clinical practice.}, } @article {pmid38974001, year = {2024}, author = {Li, Y and Zhou, Z and Liang, X and Ding, J and He, Y and Sun, S and Cheng, W and Ni, Z and Yu, C}, title = {Gut Microbiota Disorder Contributes to the Production of IL-17A That Exerts Chemotaxis via Binding to IL-17RA in Endometriosis.}, journal = {Journal of inflammation research}, volume = {17}, number = {}, pages = {4199-4217}, pmid = {38974001}, issn = {1178-7031}, abstract = {INTRODUCTION: Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized.

METHODS: Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry.

RESULTS: High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects.

DISCUSSION: Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential.}, } @article {pmid38973782, year = {2024}, author = {Kim, NH and Hamadani, M and Abedin, S}, title = {New investigational drugs for steroid-refractory acute graft-versus-host disease: a review of the literature.}, journal = {Expert opinion on investigational drugs}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/13543784.2024.2377322}, pmid = {38973782}, issn = {1744-7658}, abstract = {INTRODUCTION: Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a formidable obstacle in the field of allogeneic hematopoietic cell transplantation (allo-HCT), significantly contributing to patient morbidity and mortality. The current therapeutic landscape for SR-aGVHD is limited, often yielding suboptimal results, thereby emphasizing the urgent need for innovative and effective treatments.

AREAS COVERED: In light of the pivotal REACH2 trial, ruxolitinib phosphate, a Janus kinase inhibitor, has gained prominence as the standard treatment for SR-aGVHD. Nevertheless, a considerable number of patients either do not respond to or cannot tolerate this therapy. This review delves into emerging treatments for SR-aGVHD, including mesenchymal stromal cells (MSCs), fecal microbiota transplantation (FMT), CD3/CD7 blockade, neihulizumab, begelomab, tocilizumab, and vedolizumab. While some of these agents have shown encouraging results in early-phase trials, issues such as treatment-related toxicities and inconsistent responses in larger studies highlight the necessity for ongoing research.

EXPERT OPINION: Current trials exploring new agents and combination therapies offer hope for fulfilling the unmet clinical needs in SR-aGVHD, potentially leading to more effective and precise treatment strategies.}, } @article {pmid38973540, year = {2024}, author = {Khalaf, R and Sciberras, M and Ellul, P}, title = {The role of the fecal microbiota in inflammatory bowel disease.}, journal = {European journal of gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MEG.0000000000002818}, pmid = {38973540}, issn = {1473-5687}, abstract = {The understanding of the potential role of the microbiota in the pathogenesis of inflammatory bowel disease (IBD) is ever-evolving. Traditionally, the management of IBD has involved medical therapy and/or surgical intervention. IBD can be characterized by gut microbiome alterations through various pathological processes. Various studies delve into nontraditional methods such as probiotics and fecal microbiota transplant and their potential therapeutic effects. Fecal microbiota transplant involves the delivery of a balanced composition of gut microorganisms into an affected patient via multiple possible routes and methods, while probiotics consist of live microorganisms given via the oral route. At present, neither method is considered first-line treatment, however, fecal microbiota transplant has shown potential success in inducing and maintaining remission in ulcerative colitis. In a study by Kruis and colleagues, Escherichia coli Nissle 1917 was considered to be equivalent to mesalamine in mild ulcerative colitis. Alteration of the microbiome in the management of Crohn's disease is less well defined. Furthermore, variation in the clinical usefulness of 5-aminosalicylic acid medication has been attributed, in part, to its acetylation and inactivation by gut microbes. In summary, our understanding of the microbiome's role is continually advancing, with the possibility of paving the way for personalized medicine based on the microbiome.}, } @article {pmid38973202, year = {2024}, author = {Sui, Y and Feng, X and Ma, Y and Zou, Y and Liu, Y and Huang, J and Zhu, X and Wang, J}, title = {BHBA attenuates endoplasmic reticulum stress-dependent neuroinflammation via the gut-brain axis in a mouse model of heat stress.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {7}, pages = {e14840}, pmid = {38973202}, issn = {1755-5949}, support = {2023YFD1801100//National Key Research and Development Program of China/ ; 32272967//National Natural Science Foundation of China/ ; 32273085//National Natural Science Foundation of China/ ; 2024GH-ZDXM-33//International Science and Technology Cooperation Program of China/ ; }, mesh = {Animals ; Mice ; *Endoplasmic Reticulum Stress/drug effects/physiology ; *Brain-Gut Axis/physiology/drug effects ; *Neuroinflammatory Diseases/metabolism/drug therapy ; *Gastrointestinal Microbiome/drug effects/physiology ; *Mice, Inbred C57BL ; Male ; *Disease Models, Animal ; *3-Hydroxybutyric Acid/pharmacology ; Heat Stress Disorders/metabolism ; Endoplasmic Reticulum Chaperone BiP ; Neuroprotective Agents/pharmacology ; Heat-Shock Response/physiology/drug effects ; }, abstract = {BACKGROUND: Heat stress (HS) commonly occurs as a severe pathological response when the body's sensible temperature exceeds its thermoregulatory capacity, leading to the development of chronic brain inflammation, known as neuroinflammation. Emerging evidence suggests that HS leads to the disruption of the gut microbiota, whereas abnormalities in the gut microbiota have been demonstrated to affect neuroinflammation. However, the mechanisms underlying the effects of HS on neuroinflammation are poorly studied. Meanwhile, effective interventions have been unclear. β-Hydroxybutyric acid (BHBA) has been found to have neuroprotective and anti-inflammatory properties in previous studies. This study aims to explore the modulatory effects of BHBA on neuroinflammation induced by HS and elucidate the underlying molecular mechanisms.

METHODS: An in vivo and in vitro model of HS was constructed under the precondition of BHBA pretreatment. The modulatory effects of BHBA on HS-induced neuroinflammation were explored and the underlying molecular mechanisms were elucidated by flow cytometry, WB, qPCR, immunofluorescence staining, DCFH-DA fluorescent probe assay, and 16S rRNA gene sequencing of colonic contents.

RESULTS: Heat stress was found to cause gut microbiota disruption in HS mouse models, and TM7 and [Previotella] spp. may be the best potential biomarkers for assessing the occurrence of HS. Fecal microbiota transplantation associated with BHBA effectively reversed the disruption of gut microbiota in HS mice. Moreover, BHBA may inhibit microglia hyperactivation, suppress neuroinflammation (TNF-α, IL-1β, and IL-6), and reduce the expression of cortical endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP) mainly through its modulatory effects on the gut microbiota (TM7, Lactobacillus spp., Ruminalococcus spp., and Prevotella spp.). In vitro experiments revealed that BHBA (1 mM) raised the expression of the ERS marker GRP78, enhanced cellular activity, and increased the generation of reactive oxygen species (ROS) and anti-inflammatory cytokines (IL-10), while also inhibiting HS-induced apoptosis, ROS production, and excessive release of inflammatory cytokines (TNF-α and IL-1β) in mouse BV2 cells.

CONCLUSION: β-Hydroxybutyric acid may be an effective agent for preventing neuroinflammation in HS mice, possibly due to its ability to inhibit ERS and subsequent microglia neuroinflammation via the gut-brain axis. These findings lay the groundwork for future research and development of BHBA as a preventive drug for HS and provide fresh insights into techniques for treating neurological illnesses by modifying the gut microbiota.}, } @article {pmid38971546, year = {2024}, author = {Tang, L and Zhang, X and Zhang, B and Chen, T and Du, Z and Song, W and Chen, W and Wang, C}, title = {Electroacupuncture remodels gut microbiota and metabolites in mice with perioperative neurocognitive impairment.}, journal = {Experimental gerontology}, volume = {}, number = {}, pages = {112507}, doi = {10.1016/j.exger.2024.112507}, pmid = {38971546}, issn = {1873-6815}, abstract = {Gut microbiota and metabolites are considered key factors in the pathogenesis of perioperative neurocognitive disorders (PND), and the brain-gut axis may be a promising target for PND treatment. Electroacupuncture has been shown to improve a wide range of neurological disorders and to restore function to the gastrointestinal tract. Thus, we hypothesized whether electroacupuncture could remodel gut microbiota and neuroinflammation induced by anesthesia/surgery. First, we observed electroacupuncture at acupoints GV20, LI4 and PC6 significantly improved memory in behavioral tests. Next, we found electroacupuncture decreased the levels of inflammatory factors (NSE, S-100β, IL-6, etc.) in the hippocampus, indicating that nerve inflammation was blocked by electroacupuncture. Furthermore, via 16S rRNA sequence analysis and LC-MS analysis, the gut microbiota and its metabolites were appropriately restored after electroacupuncture treatment. Additionally, we further confirmed the restorative effect of electroacupuncture on PND by fecal transplantation. In conclusion, the role of electroacupuncture in improving cognitive function and protecting neurons may be related to the modulation of gut microbiota and their metabolite dysregulation, thereby inhibiting neuroinflammation in PND mice.}, } @article {pmid38971010, year = {2024}, author = {Zeng, C and Wan, SR and Guo, M and Tan, XZ and Zeng, Y and Wu, Q and Xie, JJ and Yan, P and Long, Y and Zheng, L and Jiang, ZZ and Teng, FY and Xu, Y}, title = {Fecal virome transplantation: A promising strategy for the treatment of metabolic diseases.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {177}, number = {}, pages = {117065}, doi = {10.1016/j.biopha.2024.117065}, pmid = {38971010}, issn = {1950-6007}, abstract = {Metabolic diseases are a group of disorders caused by metabolic abnormalities, including obesity, diabetes, non-alcoholic fatty liver disease, and more. Increasing research indicates that, beyond inherent metabolic irregularities, the onset and progression of metabolic diseases are closely linked to alterations in the gut microbiota, particularly gut bacteria. Additionally, fecal microbiota transplantation (FMT) has demonstrated effectiveness in clinically treating metabolic diseases, notably diabetes. Recent attention has also focused on the role of gut viruses in disease onset. This review first introduces the characteristics and influencing factors of gut viruses, then summarizes their potential mechanisms in disease development, highlighting their impact on gut bacteria and regulation of host immunity. We also compare FMT, fecal filtrate transplantation (FFT), washed microbiota transplantation (WMT), and fecal virome transplantation (FVT). Finally, we review the current understanding of gut viruses in metabolic diseases and the application of FVT in treating these conditions. In conclusion, FVT may provide a novel and promising treatment approach for metabolic diseases, warranting further validation through basic and clinical research.}, } @article {pmid38970126, year = {2024}, author = {Zuppi, M and Vatanen, T and Wilson, BC and Golovina, E and Portlock, T and Cutfield, WS and Vickers, MH and O'Sullivan, JM}, title = {Fecal microbiota transplantation alters gut phage communities in a clinical trial for obesity.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {122}, pmid = {38970126}, issn = {2049-2618}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Bacteriophages/physiology/classification/isolation & purification/genetics ; *Feces/microbiology/virology ; *Obesity/therapy/microbiology ; Double-Blind Method ; Female ; Adolescent ; Male ; Bacteria/classification/virology/genetics ; Metagenomics/methods ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a therapeutic intervention used to treat diseases associated with the gut microbiome. In the human gut microbiome, phages have been implicated in influencing human health, with successful engraftment of donor phages correlated with FMT treatment efficacy. The impact that gastrointestinal phages exert on human health has primarily been connected to their ability to modulate the bacterial communities in the gut. Nonetheless, how FMT affects recipients' phage populations, and in turn, how this influences the gut environment, is not yet fully understood. In this study, we investigated the effects of FMT on the phageome composition of participants within the Gut Bugs Trial (GBT), a double-blind, randomized, placebo-controlled trial that investigated the efficacy of FMT in treating obesity and comorbidities in adolescents. Stool samples collected from donors at the time of treatment and recipients at four time points (i.e., baseline and 6 weeks, 12 weeks, and 26 weeks post-intervention), underwent shotgun metagenomic sequencing. Phage sequences were identified and characterized in silico to examine evidence of phage engraftment and to assess the extent of FMT-induced alterations in the recipients' phageome composition.

RESULTS: Donor phages engrafted stably in recipients following FMT, composing a significant proportion of their phageome for the entire course of the study (33.8 ± 1.2% in females and 33.9 ± 3.7% in males). Phage engraftment varied between donors and donor engraftment efficacy was positively correlated with their phageome alpha diversity. FMT caused a shift in recipients' phageome toward the donors' composition and increased phageome alpha diversity and variability over time.

CONCLUSIONS: FMT significantly altered recipients' phage and, overall, microbial populations. The increase in microbial diversity and variability is consistent with a shift in microbial population dynamics. This proposes that phages play a critical role in modulating the gut environment and suggests novel approaches to understanding the efficacy of FMT in altering the recipient's microbiome.

TRIAL REGISTRATION: The Gut Bugs Trial was registered with the Australian New Zealand Clinical Trials Registry (ACTR N12615001351505). Trial protocol: the trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.}, } @article {pmid38970007, year = {2024}, author = {Wang, Y and Hu, Y and Shi, P}, title = {A meta-analysis of randomized controlled trials evaluating the effectiveness of fecal microbiota transplantation for patients with irritable bowel syndrome.}, journal = {BMC gastroenterology}, volume = {24}, number = {1}, pages = {217}, pmid = {38970007}, issn = {1471-230X}, mesh = {*Irritable Bowel Syndrome/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Humans ; *Randomized Controlled Trials as Topic ; Treatment Outcome ; Gastrointestinal Microbiome ; Adult ; Emotions ; }, abstract = {OBJECTIVE: Multiple randomized controlled trials (RCTs) have investigated the efficacy of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), but have yielded inconsistent results. We updated the short-term and long-term efficacy of FMT in treating IBS, and performed a first-of-its-kind exploration of the relationship between gut microbiota and emotions.

METHODS: We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library using various search strategies to identify all eligible studies. The inclusion criteria for data extraction were randomized controlled trials (RCTs) that investigated the efficacy of fecal microbiota transplantation (FMT) compared to placebo in adult patients (≥ 18 years old) with irritable bowel syndrome (IBS). A meta-analysis was then performed to assess the summary relative risk (RR) and corresponding 95% confidence intervals (CIs).

RESULTS: Out of 3,065 potentially relevant records, a total of 10 randomized controlled trials (RCTs) involving 573 subjects met the eligibility criteria for inclusion in the meta-analysis. The meta-analyses revealed no significant differences in short-term (12 weeks) (RR 0.20, 95% CI -0.04 to 0.44), long-term (52 weeks) global improvement (RR 1.38, 95% CI 0.87 to 2.21), besides short-term (12 weeks) (SMD - 48.16, 95% CI -102.13 to 5.81, I[2] = 90%) and long-term (24 weeks) (SMD 2.16, 95% CI -60.52 to 64.83, I[2] = 68%) IBS-SSS. There was statistically significant difference in short-term improvement of IBS-QoL (SMD 10.11, 95% CI 0.71 to 19.51, I[2] = 82%), although there was a high risk of bias. In terms of long-term improvement (24 weeks and 54 weeks), there were no significant differences between the FMT and placebo groups (SMD 7.56, 95% CI 1.60 to 13.52, I[2] = 0%; SMD 6.62, 95% CI -0.85 to 14.08, I[2] = 0%). Sensitivity analysis indicated that there were visible significant effects observed when the criteria were based on Rome IV criteria (RR 16.48, 95% CI 7.22 to 37.62) and Gastroscopy (RR 3.25, 95%CI 2.37 to 4.47), Colonoscopy (RR 1.42, 95% CI 0.98 to 2.05). when using mixed stool FMT based on data from two RCTs, no significant difference was observed (RR 0.94, 95% CI 0.66 to -1.34). The remission of depression exhibited no significant difference between the FMT and placebo groups at the 12-week mark (SMD - 0.26, 95% CI -3.09 to 2.58), and at 24 weeks (SMD - 2.26, 95% CI -12.96 to 8.45). Furthermore, major adverse events associated with FMT were transient and self-limiting.

DISCUSSION: Based on the available randomized controlled trials (RCTs), the current evidence does not support the efficacy of FMT in improving global IBS symptoms in the long term. The differential results observed in subgroup analyses raise questions about the accurate identification of suitable populations for FMT. Further investigation is needed to better understand the reasons behind these inconsistent findings and to determine the true potential of FMT as a treatment for IBS.}, } @article {pmid38969601, year = {2024}, author = {Yu, J and Chen, X and Yang, X and Zhang, B}, title = {Understanding gut dysbiosis for hepatocellular carcinoma diagnosis and treatment.}, journal = {Trends in endocrinology and metabolism: TEM}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tem.2024.06.003}, pmid = {38969601}, issn = {1879-3061}, abstract = {The gut microbiome can play a crucial role in hepatocellular carcinoma (HCC) progression through the enterohepatic circulation, primarily acting via metabolic reprogramming and alterations in the hepatic immune microenvironment triggered by microbe-associated molecular patterns (MAMPs), metabolites, and fungi. In addition, the gut microbiome shows potential as a biomarker for early HCC diagnosis and for assessing the efficacy of immunotherapy in unresectable HCC. This review examines how gut microbiota dysbiosis, with varied functional profiles, contributes to HCCs of different etiologies. We discuss therapeutic strategies to modulate the gut microbiome including diets, antibiotics, probiotics, fecal microbiota transplantation, and nano-delivery systems, and underscore their potential as an adjunctive treatment modality for HCC.}, } @article {pmid38969161, year = {2024}, author = {Li, X and Shang, S and Wu, M and Song, Q and Chen, D}, title = {Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis.}, journal = {Cancer letters}, volume = {}, number = {}, pages = {217096}, doi = {10.1016/j.canlet.2024.217096}, pmid = {38969161}, issn = {1872-7980}, abstract = {Metabolic derivatives of numerous microorganisms inhabiting the human gut can participate in physiological activities and immune status of the lungs through the gut-lung axis. The current well-established microbial metabolites include short-chain fatty acids (SCFAs), tryptophan and its derivatives, polyamines (PAs), secondary bile acids (SBAs), etc. As the study continues to deepen, the critical function of microbial metabolites in the occurrence and treatment of lung cancer has gradually been revealed. Microbial derivates can enter the circulation system to modulate the immune microenvironment of lung cancer. Mechanistically, oncometabolites damage host DNA and promote the occurrence of lung cancer, while tumor-suppresive metabolites directly affect the immune system to combat the malignant properties of cancer cells and even show considerable application potential in improving the efficacy of lung cancer immunotherapy. Considering the crosstalk along the gut-lung axis, in-depth exploration of microbial metabolites in patients' feces or serum will provide novel guidance for lung cancer diagnosis and treatment selection strategies. In addition, targeted therapeutics on microbial metabolites are expected to overcome the bottleneck of lung cancer immunotherapy and alleviate adverse reactions, including fecal microbiota transplantation, microecological preparations, metabolite synthesis and drugs targeting metabolic pathways. In summary, this review provides novel insights and explanations on the intricate interplay between gut microbial metabolites and lung cancer development, and immunotherapy through the lens of the gut-lung axis, which further confirms the possible translational potential of the microbiome metabolome in lung cancer treatment.}, } @article {pmid38969094, year = {2024}, author = {Cheng, Z and Yang, L and Chu, H}, title = {The role of gut microbiota, exosomes, and their interaction in the pathogenesis of ALD.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.07.002}, pmid = {38969094}, issn = {2090-1224}, abstract = {BACKGROUND: The liver disorders caused by alcohol abuse are termed alcoholic-related liver disease (ALD), including alcoholic steatosis, alcoholic steatohepatitis alcoholic hepatitis, and alcoholic cirrhosis, posing a significant threat to human health. Currently, ALD pathogenesis has not been completely clarified, which is likely to be related to the direct damage caused by alcohol and its metabolic products, oxidative stress, gut dysbiosis, and exosomes.

AIMS: The existing studies suggest that both the gut microbiota and exosomes contribute to the development of ALD. Moreover, there exists an interaction between the gut microbiota and exosomes. We discuss whether this interaction plays a role in the pathogenesis of ALD and whether it can be a potential therapeutic target for ALD treatment.

Chronic alcohol intake alters the diversity and composition of gut microbiota, which greatly contributes to ALD's progression. Some approaches targeting the gut microbiota, including probiotics, fecal microbiota transplantation, and phage therapy, have been confirmed to effectively ameliorate ALD in many animal experiments and/or several clinical trials. In ALD, the levels of exosomes and the expression profile of microRNA have also changed, which affects the pathogenesis of ALD. Moreover, there is an interplay between exosomes and the gut microbiota, which also putatively acts as a pathogenic factor of ALD.}, } @article {pmid38969093, year = {2024}, author = {Bai, X and Duan, Z and Deng, J and Zhang, Z and Fu, R and Zhu, C and Fan, D}, title = {Ginsenoside Rh4 inhibits colorectal cancer via the modulation of gut microbiota-mediated bile acid metabolism.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.06.028}, pmid = {38969093}, issn = {2090-1224}, abstract = {INTRODUCTION: Dysbiosis of the gut microbiota is emerging as a pivotal factor in the pathogenesis of colorectal cancer (CRC). Ginsenoside Rh4 (Rh4) is an active compound isolated from ginseng with beneficial effects in modulating intestinal inflammation and gut microbiota dysbiosis, but how Rh4 regulates the gut microbiota to alleviate CRC remains underexplored.

OBJECTIVES: We investigated the impact of Rh4 on CRC and the mechanism of its action in inhibiting CRC via modulation of gut microbiota.

METHODS: We used the AOM/DSS model and employed transcriptomics, genomics and metabolomics techniques to explore the inhibitory impact of Rh4 on CRC. Furthermore, we employed experiments involving antibiotic treatment and fecal microbiota transplantation (FMT) to investigate the role of the gut microbiota. Finally, we elucidated the pivotal role of key functional bacteria and metabolites regulated by Rh4 in CRC.

RESULTS: Our research findings indicated that Rh4 repaired intestinal barrier damage caused by CRC, alleviated intestinal inflammation, and inhibited the development of CRC. Additionally, Rh4 inhibited CRC in a gut microbiota-dependent manner. Rh4 increased the diversity of gut microbiota, enriched the probiotic Akkermansia muciniphila (A. muciniphila), and alleviated gut microbiota dysbiosis caused by CRC. Subsequently, Rh4 regulated A. muciniphila-mediated bile acid metabolism. A. muciniphila promoted the production of UDCA by enhancing the activity of 7α-hydroxysteroid dehydrogenase (7α-HSDH). UDCA further activated FXR, modulated the TLR4-NF-κB signaling pathway, thus inhibiting the development of CRC.

CONCLUSION: Our results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-κB signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.}, } @article {pmid38968058, year = {2024}, author = {Beckers, M and Coburn, B and Kalia, LV and Bloem, BR}, title = {A Randomized Controlled Trial of Fecal Microbiota Transplantation for Parkinson's Disease: Getting it right, if not PARFECT.}, journal = {Journal of Parkinson's disease}, volume = {}, number = {}, pages = {}, doi = {10.3233/JPD-249007}, pmid = {38968058}, issn = {1877-718X}, } @article {pmid38967596, year = {2024}, author = {Zhang, R and Yan, Z and Zhong, H and Luo, R and Liu, W and Xiong, S and Liu, Q and Liu, M}, title = {Gut microbial metabolites in MASLD: Implications of mitochondrial dysfunction in the pathogenesis and treatment.}, journal = {Hepatology communications}, volume = {8}, number = {7}, pages = {}, pmid = {38967596}, issn = {2471-254X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Mitochondria/metabolism ; Probiotics/therapeutic use ; Fatty Liver/metabolism/microbiology/therapy ; Prebiotics ; Anti-Bacterial Agents/therapeutic use ; Animals ; Oxidative Stress ; }, abstract = {With an increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health problem. MASLD is well-known as a multifactorial disease. Mitochondrial dysfunction and alterations in the gut bacteria are 2 vital events in MASLD. Recent studies have highlighted the cross-talk between microbiota and mitochondria, and mitochondria are recognized as pivotal targets of the gut microbiota to modulate the host's physiological state. Mitochondrial dysfunction plays a vital role in MASLD and is associated with multiple pathological changes, including hepatocyte steatosis, oxidative stress, inflammation, and fibrosis. Metabolites are crucial mediators of the gut microbiota that influence extraintestinal organs. Additionally, regulation of the composition of gut bacteria may serve as a promising therapeutic strategy for MASLD. This study reviewed the potential roles of several common metabolites in MASLD, emphasizing their impact on mitochondrial function. Finally, we discuss the current treatments for MASLD, including probiotics, prebiotics, antibiotics, and fecal microbiota transplantation. These methods concentrate on restoring the gut microbiota to promote host health.}, } @article {pmid38966558, year = {2024}, author = {Lin, L and Tang, R and Liu, Y and Li, Z and Li, H and Yang, H}, title = {Research on the anti-aging mechanisms of Panax ginseng extract in mice: a gut microbiome and metabolomics approach.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1415844}, pmid = {38966558}, issn = {1663-9812}, abstract = {Introduction: Aged-related brain damage and gut microbiome disruption are common. Research affirms that modulating the microbiota-gut-brain axis can help reduce age-related brain damage. Methods: Ginseng, esteemed in traditional Chinese medicine, is recognized for its anti-aging capabilities. However, previous Ginseng anti-aging studies have largely focused on diseased animal models. To this end, efforts were hereby made to explore the potential neuroprotective effects of fecal microbiota transplantation (FMT) from Ginseng-supplemented aged mice to those pre-treated with antibiotics. Results: As a result, FMT with specific modifications in natural aging mice improved animal weight gain, extended the telomere length, anti-oxidative stress in brain tissue, regulated the serum levels of cytokine, and balanced the proportion of Treg cells. Besides, FMT increased the abundance of beneficial bacteria of Lachnospiraceae, Dubosiella, Bacteroides, etc. and decreased the levels of potential pathogenic bacteria of Helicobacter and Lachnoclostridium in the fecal samples of natural aged mice. This revealed that FMT remarkably reshaped gut microbiome. Additionally, FMT-treated aged mice showed increased levels of metabolites of Ursolic acid, β-carotene, S-Adenosylmethionine, Spermidine, Guanosine, Celecoxib, Linoleic acid, etc., which were significantly positively correlated with critical beneficial bacteria above. Additionally, these identified critical microbiota and metabolites were mainly enriched in the pathways of Amino acid metabolism, Lipid metabolism, Nucleotide metabolism, etc. Furthermore, FMT downregulated p53/p21/Rb signaling and upregulated p16/p14, ATM/synapsin I/synaptophysin/PSD95, CREB/ERK/AKT signaling in brain damage following natural aging. Discussion: Overall, the study demonstrates that reprogramming of gut microbiota by FMT impedes brain damage in the natural aging process, possibly through the regulation of microbiota-gut-brain axis.}, } @article {pmid38966047, year = {2024}, author = {Tominaga, K and Kojima, Y and Kawata, Y and Takahashi, K and Sato, H and Tsuchiya, A and Kamimura, K and Terai, S}, title = {An updated review on the treatment for diversion colitis and pouchitis, with a focus on the utility of autologous fecal microbiota transplantation and its relationship with the intestinal microbiota.}, journal = {Bioscience of microbiota, food and health}, volume = {43}, number = {3}, pages = {162-169}, pmid = {38966047}, issn = {2186-6953}, abstract = {Diversion colitis (DC) is characterized by mucosal inflammation in the defunctioned segment of the colon following a colostomy or ileostomy. The major causes of DC are an increase in the number of aerobic bacteria, a lack of short-chain fatty acids (SCFAs), and immune disorders in the diverted colon. However, its exact pathogenesis remains unknown. Various treatment strategies for DC have been explored, although none have been definitively established. Treatment approaches such as SCFAs, 5-aminosalicylic acid enemas, steroid enemas, and irrigation with fibers have been attempted, yielding various degrees of efficacies in mitigating mucosal inflammation. However, only individual case reports demonstrating the limited effect of the following therapies have been published: leukocytapheresis, dextrose (hypertonic glucose) spray, infliximab, an elemental diet, and coconut oil. The usefulness of probiotics for treating DC has recently been reported. Furthermore, fecal microbiota transplantation (FMT) has emerged as a promising treatment for DC. This review provides an update on the treatment strategies of DC, with a particular focus on FMT and its relationship with the intestinal microbiota. FMT may become the first choice of treatment for some patients in the future because of its low medical costs, ease of use, and minimal side effects. Furthermore, FMT can also be used for postoperative DC prophylaxis.}, } @article {pmid38965449, year = {2024}, author = {Drew, L}, title = {Faecal transplants can treat some cancers - but probably won't ever be widely used.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {38965449}, issn = {1476-4687}, } @article {pmid38964948, year = {2024}, author = {Zhu, Y and Self, WK and Holtzman, DM}, title = {An emerging role for the gut microbiome in tauopathy.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {e00423}, doi = {10.1016/j.neurot.2024.e00423}, pmid = {38964948}, issn = {1878-7479}, abstract = {Tauopathies constitute a group of neurodegenerative diseases characterized by abnormal aggregation of the protein tau, progressive neuronal and synaptic loss, and eventual cognitive and motor impairment. In this review, we will highlight the latest efforts investigating the intricate interplay between the gut microbiome and tauopathies. We discuss the physiological interactions between the microbiome and the brain as well as clinical and experimental evidence that suggests that the presence of tauopathy alters the composition of gut microbiota. We explore both animal and human studies that define causative relationships between the gut microbiome and tauopathy by directly manipulating or transferring gut microbiota. This review highlights future directions into identifying and mechanistically elucidating microbial species causally linked to tauopathies, with an ultimate goal of devising therapeutic targets towards the gut microbiome to treat tauopathies.}, } @article {pmid38964511, year = {2024}, author = {Davido, B and Watson, AR and de Truchis, P and Galazzo, G and Dinh, A and Batista, R and Terveer, EM and Lawrence, C and Michelon, H and Jobard, M and Saleh-Mghir, A and Kuijper, EJ and Caballero, S}, title = {Bacterial diversity and specific taxa are associated with decolonization of carbapenemase-producing enterobacterales after fecal microbiota transplantation.}, journal = {The Journal of infection}, volume = {89}, number = {2}, pages = {106216}, doi = {10.1016/j.jinf.2024.106216}, pmid = {38964511}, issn = {1532-2742}, abstract = {OBJECTIVES: We evaluated the effect of fecal microbiota transplantation (FMT) on the clearance of carbapenemase-producing Enterobacterales (CPE) carriage.

METHODS: We performed a prospective, multi-center study, conducted among patients who received a single dose of FMT from one of four healthy donors. The primary endpoint was complete clearance of CPE carriage two weeks after FMT with a secondary endpoint at three months. Shotgun metagenomic sequencing was performed to assess gut microbiota composition of donors and recipients before and after FMT.

RESULTS: Twenty CPE-colonized patients were included in the study, where post-FMT 20% (n = 4/20) of patients met the primary endpoint and 40% (n = 8/20) of patients met the secondary endpoint. Kaplan-Meier curves between patients with FMT intervention and the control group (n = 82) revealed a similar rate of decolonization between groups. Microbiota composition analyses revealed that response to FMT was not donor-dependent. Responders had a significantly lower relative abundance of CPE species pre-FMT than non-responders, and 14 days post-FMT responders had significantly higher bacterial species richness and alpha diversity compared to non-responders (p < 0.05). Responder fecal samples were also enriched in specific species, with significantly higher relative abundances of Faecalibacterium prausnitzii, Parabacteroides distasonis, Collinsella aerofaciens, Alistipes finegoldii and Blautia_A sp900066335 (q<0.01) compared to non-responders.

CONCLUSION: FMT administration using the proposed regimen did not achieve statistical significance for complete CPE decolonization but was correlated with the relative abundance of specific bacterial taxa, including CPE species.}, } @article {pmid38964253, year = {2024}, author = {Chen, S and Liu, H and Yan, C and Li, Y and Xiao, J and Zhao, X}, title = {Fecal microbiota transplantation provides insights into the consequences of transcriptome profiles and cell energy in response to circadian misalignment of chickens.}, journal = {Poultry science}, volume = {103}, number = {9}, pages = {103926}, doi = {10.1016/j.psj.2024.103926}, pmid = {38964253}, issn = {1525-3171}, abstract = {The circadian misalignment (CM) disordered circadian rhythms exert adverse effects on animals. Poultry as one of animals suffers health and welfare problems due to long-term lighting photoperiods caused by CM. However, the roles of CM on organ development, cell growth, metabolism and immune are still unclear in chickens. In this study, a Chinese dual-purpose native breed, was used to explore the effects of CM on transcriptomic pattern of brain and cell energy biogenesis, and further fecal microbiota transplantation (FMT) was applied to investigate its "therapy" effect from CM suffering. Our results showed that the CM led to stunting in brain and small intestine of chicken. CM decreased of cell proliferation, and energy production, mtDNA copies and expression of genes related to cell cycle or mitochondrial biogenetics, while it upregulated the reactive oxygen species (ROS) level and the sensitivity to inflammation. Interestingly, FMT rescued the organ developmental defects and cell dysfunctions induced by CM. Circadian misalignment brought about abnormal tissue and cell developments, energy biogenesis, and immune response in birds. This study provided a comprehensive perspective on understanding the regulation of CM and FMT on bird development and welfare.}, } @article {pmid38963317, year = {2024}, author = {Xiong, Y and Pu, YN and Li, LY and Su, Y and Niu, JY and Xiao, ZY}, title = {Gut microbiota-derived metabolite trimethylamine N-oxide aggravates cognitive dysfunction induced by femoral fracture operation in mice.}, journal = {The Kaohsiung journal of medical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1002/kjm2.12873}, pmid = {38963317}, issn = {2410-8650}, abstract = {An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N-oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO-induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ-free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO-related POCD and improving the quality of life for elderly patients.}, } @article {pmid38962126, year = {2024}, author = {Zou, S and Li, Y and Zou, Q and Yang, M and Li, H and Niu, R and Lai, H and Wang, J and Yang, X and Zhou, L}, title = {Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1403892}, pmid = {38962126}, issn = {1664-302X}, abstract = {INTRODUCTION: The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear.

METHODS: We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models.

RESULTS: We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation.

CONCLUSION: In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.}, } @article {pmid38961596, year = {2024}, author = {Mehra, P and Kumar, A}, title = {Emerging importance of stool preservation methods in OMICS studies with special focus on cancer biology.}, journal = {Cell biochemistry and function}, volume = {42}, number = {5}, pages = {e4063}, doi = {10.1002/cbf.4063}, pmid = {38961596}, issn = {1099-0844}, support = {//National Institute of Immunology/ ; }, mesh = {Humans ; *Feces/microbiology/chemistry ; *Gastrointestinal Microbiome ; *Neoplasms/metabolism ; Metabolomics ; Metagenomics ; }, abstract = {The intricate consortium of microorganisms in the human gut plays a crucial role in different physiological functions. The complex known-unknown elements of the gut microbiome are perplexing and the absence of standardized procedures for collecting and preserving samples has hindered continuous research in comprehending it. The technological bias produced because of lack of standard protocols has affected the reproducibility of results. The complex nature of diseases like colorectal cancer, gastric cancer, hepatocellular carcinoma and breast cancer require a thorough understanding of its etiology for an efficient and timely diagnosis. The designated protocols for collection and preservation of stool specimens have great variance, hence generate inconsistencies in OMICS studies. Due to the complications associated to the nature of sample, it is important to preserve the sample to be studied later in a laboratory or to be used in the future research purpose. Stool preservation is gaining importance due to the increased use of treatment options like fecal microbiota transplantation to cure conditions like recurrent Clostridium difficile infections and for OMICS studies including metagenomics, metabolomics and culturomics. This review provides an insight into the importance of omics studies for the identification and development of novel biomarkers for quick and noninvasive diagnosis of various diseases.}, } @article {pmid38961326, year = {2024}, author = {Wang, B and Qiu, Y and Xie, M and Huang, P and Yu, Y and Sun, Q and Shangguan, W and Li, W and Zhu, Z and Xue, J and Feng, Z and Zhu, Y and Yang, Q and Wu, P}, title = {Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {237}, pmid = {38961326}, issn = {1471-2180}, support = {82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 82173304//National Natural Science Foundation of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; 2023B03J1245//Science and Technology Planning Project of Guangdong Province of China/ ; }, mesh = {*Urinary Bladder Neoplasms/therapy/immunology/microbiology ; *Gastrointestinal Microbiome ; Animals ; Humans ; Mice ; *Immunotherapy/methods ; *Fecal Microbiota Transplantation ; *Bacteroidetes/genetics/immunology ; Female ; Male ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Middle Aged ; Aged ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVE: Bladder cancer(BCa) was a disease that seriously affects patients' quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer.

METHODS: We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms.

RESULTS: The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4[+]T and CD8[+]T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group.

CONCLUSION: P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.}, } @article {pmid38959670, year = {2024}, author = {Bum Lee, J and Huang, Y and Oya, Y and Nutzinger, J and LE Ang, Y and Sooi, K and Chul Cho, B and Soo, RA}, title = {Modulating the gut microbiome in non-small cell lung cancer: Challenges and opportunities.}, journal = {Lung cancer (Amsterdam, Netherlands)}, volume = {194}, number = {}, pages = {107862}, doi = {10.1016/j.lungcan.2024.107862}, pmid = {38959670}, issn = {1872-8332}, abstract = {Despite the efficacy of immunotherapy in non-small cell lung cancer (NSCLC), the majority of the patients experience relapse with limited subsequent treatment options. Preclinical studies of various epithelial tumors, such as melanoma and NSCLC, have shown that harnessing the gut microbiome resulted in improvement of therapeutic responses to immunotherapy. Is this review, we summarize the role of microbiome, including lung and gut microbiome in the context of NSCLC, provide overview of the mechanisms of microbiome in efficacy and toxicity of chemotherapies and immunotherapies, and address current ongoing clinical trials for NSCLC including fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs).}, } @article {pmid38959643, year = {2024}, author = {Cheng, X and Hu, Y and Kuang, J and Guo, X and Cao, H and Wu, H and Hu, G and Zhuang, Y}, title = {Berberine alleviates high-energy and low-protein diet-induced fatty liver hemorrhagic syndrome in laying hens: insights from microbiome and metabolomics.}, journal = {Poultry science}, volume = {103}, number = {8}, pages = {103968}, doi = {10.1016/j.psj.2024.103968}, pmid = {38959643}, issn = {1525-3171}, abstract = {Berberine (BBR), a well-known quaternary ammonium alkaloid, is recognized for its ability to prevent and alleviate metabolic disorders because of its anti-oxidative and anti-inflammatory properties. However, the underlying mechanisms of BBR to mitigate fatty liver hemorrhagic syndrome (FLHS) through the modulation of gut microbiota and their metabolism remained unclear. The results revealed that BBR ameliorates lipid metabolism disorder in high-energy and low-protein (HELP) diet-induced FLHS laying hens, as evidenced by improved liver function and lipid deposition of the liver, reduced blood lipids, and the expression of liver lipid synthesis-related factors. Moreover, BBR alleviated HELP diet-induced barrier dysfunction, increased microbial population, and dysregulated lipid metabolism in the ileum. BBR reshaped the HELP-perturbed gut microbiota, particularly declining the abundance of Desulfovibrio_piger and elevating the abundance of Bacteroides_salanitronis_DSM_18170. Meanwhile, metabolomic profiling analysis revealed that BBR reshaped microbial metabolism and function, particularly by reducing the levels of hydrocinnamic acid, dehydroanonaine, and leucinic acid. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that BBR-enriched gut microbiota alleviated hepatic lipid deposition and intestinal inflammation compared with those chicks that received a gut microbiota by HELP. Collectively, our study provided evidence that BBR effectively alleviated FLHS induced by HELP by reshaping the microbial and metabolic homeostasis within the liver-gut axis.}, } @article {pmid38956725, year = {2024}, author = {Chen, J and Zhang, C and Yang, Z and Wu, W and Zou, W and Xin, Z and Zheng, S and Liu, R and Yang, L and Peng, H}, title = {Intestinal microbiota imbalance resulted by anti-Toxoplasma gondii immune responses aggravate gut and brain injury.}, journal = {Parasites & vectors}, volume = {17}, number = {1}, pages = {284}, pmid = {38956725}, issn = {1756-3305}, support = {82330072//Key project of National Natural Science Foundation of China/ ; 82272364//National Natural Science Foundation of China/ ; 2023A1515011733//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Toxoplasma/immunology ; *Mice, Knockout ; *Brain Injuries/immunology ; Probiotics/administration & dosage ; Brain/immunology ; Lactobacillus ; Disease Models, Animal ; Immunocompromised Host ; Toxoplasmosis/immunology ; RNA, Ribosomal, 16S/genetics ; Male ; Intestines/immunology ; }, abstract = {BACKGROUND: Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. gondii infection, disruption of gut microbiota further exacerbates the damage to intestinal and brain barriers. Therefore, identifying imbalanced probiotics during infection and restoring their equilibrium can regulate the balance of gut microbiota metabolites, thereby alleviating tissue damage.

METHODS: Vimentin gene knockout (vim-/-) mice were employed as an immunocompromised model to evaluate the influence of host immune responses on gut microbiota balance during T. gondii infection. Behavioral experiments were performed to assess changes in cognitive levels and depressive tendencies between chronically infected vim-/- and wild-type (WT) mice. Fecal samples were subjected to 16S ribosomal RNA (rRNA) sequencing, and serum metabolites were analyzed to identify potential gut probiotics and their metabolites for the treatment of T. gondii infection.

RESULTS: Compared to the immunocompetent WT sv129 mice, the immunocompromised mice exhibited lower levels of neuronal apoptosis and fewer neurobehavioral abnormalities during chronic infection. 16S rRNA sequencing revealed a significant decrease in the abundance of probiotics, including several species of Lactobacillus, in WT mice. Restoring this balance through the administration of Lactobacillus murinus and Lactobacillus gasseri significantly suppressed the T. gondii burden in the intestine, liver, and brain. Moreover, transplantation of these two Lactobacillus spp. significantly improved intestinal barrier damage and alleviated inflammation and neuronal apoptosis in the central nervous system. Metabolite detection studies revealed that the levels of various Lactobacillus-related metabolites, including indole-3-lactic acid (ILA) in serum, decreased significantly after T. gondii infection. We confirmed that L. gasseri secreted much more ILA than L. murinus. Notably, ILA can activate the aromatic hydrocarbon receptor signaling pathway in intestinal epithelial cells, promoting the activation of CD8[+] T cells and the secretion of interferon-gamma.

CONCLUSION: Our study revealed that host immune responses against T. gondii infection severely disrupted the balance of gut microbiota, resulting in intestinal and brain damage. Lactobacillus spp. play a crucial role in immune regulation, and the metabolite ILA is a promising therapeutic compound for efficient and safe treatment of T. gondii infection.}, } @article {pmid38955400, year = {2024}, author = {Swarte, JC and Zhang, S and Nieuwenhuis, LM and Gacesa, R and Knobbe, TJ and , and De Meijer, VE and Damman, K and Verschuuren, EAM and Gan, TC and Fu, J and Zhernakova, A and Harmsen, HJM and Blokzijl, H and Bakker, SJL and Björk, JR and Weersma, RK and , }, title = {Multiple indicators of gut dysbiosis predict all-cause and cause-specific mortality in solid organ transplant recipients.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2023-331441}, pmid = {38955400}, issn = {1468-3288}, abstract = {OBJECTIVE: Gut microbiome composition is associated with multiple diseases, but relatively little is known about its relationship with long-term outcome measures. While gut dysbiosis has been linked to mortality risk in the general population, the relationship with overall survival in specific diseases has not been extensively studied. In the current study, we present results from an in-depth analysis of the relationship between gut dysbiosis and all-cause and cause-specific mortality in the setting of solid organ transplant recipients (SOTR).

DESIGN: We analysed 1337 metagenomes derived from faecal samples of 766 kidney, 334 liver, 170 lung and 67 heart transplant recipients part of the TransplantLines Biobank and Cohort-a prospective cohort study including extensive phenotype data with 6.5 years of follow-up. To analyze gut dysbiosis, we included an additional 8208 metagenomes from the general population of the same geographical area (northern Netherlands). Multivariable Cox regression and a machine learning algorithm were used to analyse the association between multiple indicators of gut dysbiosis, including individual species abundances, and all-cause and cause-specific mortality.

RESULTS: We identified two patterns representing overall microbiome community variation that were associated with both all-cause and cause-specific mortality. The gut microbiome distance between each transplantation recipient to the average of the general population was associated with all-cause mortality and death from infection, malignancy and cardiovascular disease. A multivariable Cox regression on individual species abundances identified 23 bacterial species that were associated with all-cause mortality, and by applying a machine learning algorithm, we identified a balance (a type of log-ratio) consisting of 19 out of the 23 species that were associated with all-cause mortality.

CONCLUSION: Gut dysbiosis is consistently associated with mortality in SOTR. Our results support the observations that gut dysbiosis is associated with long-term survival. Since our data do not allow us to infer causality, more preclinical research is needed to understand mechanisms before we can determine whether gut microbiome-directed therapies may be designed to improve long-term outcomes.}, } @article {pmid38951925, year = {2024}, author = {Rasmussen, TS and Mao, X and Forster, S and Larsen, SB and Von Münchow, A and Tranæs, KD and Brunse, A and Larsen, F and Mejia, JLC and Adamberg, S and Hansen, AK and Adamberg, K and Hansen, CHF and Nielsen, DS}, title = {Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {119}, pmid = {38951925}, issn = {2049-2618}, support = {R324-2019-1880//The Lundbeck Foundation/ ; NNF-20OC0063874//Novo Nordisk Fonden/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Animals ; Mice ; *Bacteriophages/physiology/isolation & purification ; *Clostridium Infections/therapy/microbiology ; *Gastrointestinal Microbiome ; *Feces/microbiology/virology ; *Clostridioides difficile ; Disease Models, Animal ; Humans ; Mice, Inbred C57BL ; Female ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases.

METHODS: To overcome these challenges, we developed methods to broaden FVT's clinical application while maintaining efficacy and increasing safety. Specifically, we employed the following approaches: (1) chemostat-fermentation to reproduce the bacteriophage FVT donor component and remove eukaryotic viruses (FVT-ChP), (2) solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT), and (3) pyronin-Y treatment to inhibit RNA virus replication (FVT-PyT). We assessed the efficacy of these processed FVTs in a C. difficile infection mouse model and compared them with untreated FVT (FVT-UnT), FMT, and saline.

RESULTS: FVT-SDT, FVT-UnT, and FVT-ChP reduced the incidence of mice reaching the humane endpoint (0/8, 2/7, and 3/8, respectively) compared to FMT, FVT-PyT, and saline (5/8, 7/8, and 5/7, respectively) and significantly reduced the load of colonizing C. difficile cells and associated toxin A/B levels. There was a potential elimination of C. difficile colonization, with seven out of eight mice treated with FVT-SDT testing negative with qPCR. In contrast, all other treatments exhibited the continued presence of C. difficile. Moreover, the results were supported by changes in the gut microbiome profiles, cecal cytokine levels, and histopathological findings. Assessment of viral engraftment following FMT/FVT treatment and host-phage correlations analysis suggested that transfer of phages likely were an important contributing factor associated with treatment efficacy.

CONCLUSIONS: This proof-of-concept study shows that specific modifications of FVT hold promise in addressing challenges related to donor variability and infection risks. Two strategies lead to treatments significantly limiting C. difficile colonization in mice, with solvent/detergent treatment and chemostat propagation of donor phages emerging as promising approaches. Video Abstract.}, } @article {pmid38948828, year = {2024}, author = {Ngo, VL and Wang, Y and Shi, Z and Ramani, S and Jiang, B and T Gewirtz, A}, title = {Gut-resident C. perfringens impedes rotavirus vaccine efficacy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.06.17.599343}, pmid = {38948828}, issn = {2692-8205}, abstract = {BACKGROUND & AIMS: The extent to which live orally-administered rotavirus (RV) vaccines elicit protective immunity is highly heterogeneous. We hypothesized microbiota composition might influence vaccine efficacy.

METHODS: We tested this concept by examining extent to which colonizing mice with segmented filamentous bacteria (SFB) influenced RV vaccine efficacy.Influence of human microbiomes on RV vaccination was studied via administering germ-free mice fecal microbial transplants (FMT) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to vaccination and challenge doses of RV.

RESULTS: SFB administration resulted in a phenotype reminiscent of RV vaccine failure, i.e. minimal generation of RV antigens and, consequently, lack of anti-RV antibodies resulting in proneness to RV challenge once SFB levels diminished. Transplant of microbiomes from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMT from high-responding children exhibited high levels of fecal RV antigen shedding and RV antibodies in response to RV vaccination and, concomitantly, were impervious to RV challenge. In contrast, mice receiving FMT from children who had not responded to RV vaccination exhibited only modest responses to RV challenge and, accordingly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested that RV vaccine failure might involve Clostridium perfringens . Oral administration of cultured C. perfringens to gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of previously-reported microbiome data found C. perfringens abundance in children associated with RV vaccine failure.

CONCLUSION: Microbiota composition influences RV vaccine virus infection and, consequently, protective immunity. C. perfringens may be one, perhaps of many, bacterial species harbored in the intestine of RV-vaccine non-responders that influences RV vaccine outcomes.}, } @article {pmid38948060, year = {2024}, author = {Yan, J and Zhang, X and Zhu, K and Yu, M and Liu, Q and De Felici, M and Zhang, T and Wang, J and Shen, W}, title = {Sleep deprivation causes gut dysbiosis impacting on systemic metabolomics leading to premature ovarian insufficiency in adolescent mice.}, journal = {Theranostics}, volume = {14}, number = {9}, pages = {3760-3776}, pmid = {38948060}, issn = {1838-7640}, mesh = {Animals ; Female ; *Primary Ovarian Insufficiency/metabolism ; *Gastrointestinal Microbiome ; Mice ; *Dysbiosis/microbiology/metabolism ; *Metabolomics/methods ; *Sleep Deprivation/complications/metabolism ; Ovarian Follicle/metabolism ; Oocytes/metabolism ; Fecal Microbiota Transplantation ; Disease Models, Animal ; Apoptosis ; }, abstract = {Rationale: Currently, there are occasional reports of health problems caused by sleep deprivation (SD). However, to date, there remains a lack of in-depth research regarding the effects of SD on the growth and development of oocytes in females. The present work aimed to investigate whether SD influences ovarian folliculogenesis in adolescent female mice. Methods: Using a dedicated device, SD conditions were established in 3-week old female mice (a critical stage of follicular development) for 6 weeks and gut microbiota and systemic metabolomics were analyzed. Analyses were related to parameters of folliculogenesis and reproductive performance of SD females. Results: We found that the gut microbiota and systemic metabolomics were severely altered in SD females and that these were associated with parameters of premature ovarian insufficiency (POI). These included increased granulosa cell apoptosis, reduced numbers of primordial follicles (PmFs), correlation with decreased AMH, E2, and increased LH in blood serum, and a parallel increased number of growing follicles and changes in protein expression compatible with PmF activation. SD also reduced oocyte maturation and reproductive performance. Notably, fecal microbial transplantation from SD females into normal females induced POI parameters in the latter while niacinamide (NAM) supplementation alleviated such symptoms in SD females. Conclusion: Gut microbiota and alterations in systemic metabolomics caused by SD induced POI features in juvenile females that could be counteracted with NAM supplementation.}, } @article {pmid38942038, year = {2024}, author = {Dhanda, AD and Allgar, V and Bhala, N and Callaghan, L and Castro, J and Chokshi, S and Clements, A and Drummond, C and Forrest, EH and Manning, L and Parker, R and Shawcross, DL and Towey, J}, title = {Breaking down barriers between liver, addiction, and mental health services for people with alcohol-related liver disease.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2468-1253(24)00189-4}, pmid = {38942038}, issn = {2468-1253}, } @article {pmid38941942, year = {2024}, author = {Teng, M and Sun, J and Zhao, L and Li, Y and Zhang, Z and Zhu, W and Zhang, Y and Xu, F and Xing, S and Zhao, X and Wu, F}, title = {Effects of BBIBP-CorV vaccine on gut microbiota and short-chain fatty acids in mice exposed to bis (2-ethylhexyl) phthalate and dioctyl terephthalate.}, journal = {Environment international}, volume = {190}, number = {}, pages = {108851}, doi = {10.1016/j.envint.2024.108851}, pmid = {38941942}, issn = {1873-6750}, abstract = {As the COVID-19 pandemic has progressed, increasing evidences suggest that the gut microbiota may play a crucial role in the effectiveness of SARS-CoV-2 vaccine. Thus, this study was aimed at investigating the influence of SARS-CoV-2 vaccine on the gut microbiota and short-chain fatty acids (SCFAs) of organisms exposed to environmental contaminants, i.e., plasticizers: phthalate esters. We found that in mice, exposure to dioctyl terephthalate (DOTP) and bis -2-ethylhexyl phthalate (DEHP) decreased the blood glucose level and white fat weight, induced inflammatory responses, caused damage to liver and intestinal tissues, and disrupted the gut microbiota composition and SCFAs metabolism. Specifically, the Bacteroidetes phylum was positively correlated with BBIBP-CorV vaccine, while acetic acid was negatively associated with the vaccine. Interestingly, the BBIBP-CorV vaccine somewhat alleviated tissue inflammation and reduced the contents of acetic acid and propionic acid in mice exposed to DEHP and DOTP. These findings were confirmed by a fecal microbiota transplantation assay. Overall, this study revealed that exposure to DEHP and DOTP adversely affects the gut microbiota and SCFAs, while the BBIBP-CorV vaccine can protect mice against these effects. This work highlighted the relationship between BBIBP-CorV vaccination, gut microbiome composition, and responses to plasticizers, which may facilitate the development and risk assessment of SARS-CoV-2 vaccines and environmental contaminants on microbiota health.}, } @article {pmid38941818, year = {2024}, author = {Yang, S and Wei, Z and Luo, J and Wang, X and Chen, G and Guan, X and She, Z and Liu, W and Tong, Y and Liu, H and Wen, M and Chen, H and Zhu, P and Li, G and Wang, D and Huang, L and Xu, S and Chen, D and Zhang, Q and Wei, Y}, title = {Integrated bioinformatics and multiomics reveal Liupao tea extract alleviating NAFLD via regulating hepatic lipid metabolism and gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {132}, number = {}, pages = {155834}, doi = {10.1016/j.phymed.2024.155834}, pmid = {38941818}, issn = {1618-095X}, abstract = {BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) poses a significant global public health concern. Liupao tea (LPT) is a Chinese national geographical indication product renowned for its lipid-lowering properties. However, the precise mechanisms and active constituents contributing to the efficacy of LPT against NAFLD remain unclear.

PURPOSE: This study aims to comprehensively explore the therapeutic potential of Liupao tea extract (LPTE) in alleviating NAFLD through an integrated strategy.

METHODS: Initially, network pharmacology analysis was conducted based on LPTE chemical ingredient analysis, identifying core targets and key components. Potential active ingredients were validated through chemical standards based on LC-MS/MS. To confirm the pharmacological efficacy of LPTE in NAFLD, NAFLD mice models were employed. Alterations in hepatic lipid metabolism were comprehensively elucidated through integration of metabolomics, lipidomics, network pharmacology analysis, and real-time PCR analysis. To further explore the binding interactions between key components and core targets, molecular docking and microscale thermophoresis (MST) analysis were employed. Furthermore, to investigate LPTE administration effectiveness on gut microbiota in NAFLD mice, a comprehensive approach was employed. This included Metorigin analysis, 16S rRNA sequencing, molecular docking, and fecal microbiome transplantation (FMT).

RESULTS: Study identified naringenin, quercetin, luteolin, and kaempferol as the potential active ingredients of LPTE. These compounds exhibited therapeutic potential for NAFLD by targeting key proteins such as PTGS2, CYP3A4, and ACHE, which are involved in the metabolic pathways of hepatic linoleic acid (LA) and glycerophospholipid (GP) metabolism. The therapeutic effectiveness of LPTE was observed to be comparable to that of simvastatin. Furthermore, LPTE exhibited notable efficacy in alleviating NAFLD by influencing alterations in gut microbiota composition (Proteobacteria phylum, Lactobacillus and Dubosiella genus) that perhaps impact LA and GP metabolic pathways.

CONCLUSION: LPTE could be effective in preventing high-fat diet (HFD)-induced NAFLD by modulating hepatic lipid metabolism and gut microbiota. This study firstly integrated bioinformatics and multi-omics technologies to identify the potential active components and key microbiota associated with LPTE's effects, while also primally elucidating the action mechanisms of LPTE in alleviating NAFLD. The findings offer a conceptual basis for LPTE's potential transformation into an innovative pharmaceutical agent for NAFLD prevention.}, } @article {pmid38940400, year = {2024}, author = {Zhong, HJ and Zhuang, YP and Xie, X and Song, JY and Wang, SQ and Wu, L and Zhan, YQ and Wu, Q and He, XX}, title = {Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2372881}, pmid = {38940400}, issn = {1949-0984}, mesh = {Animals ; *Receptors, CXCR6/metabolism ; *Chemokine CXCL16/metabolism ; Mice ; *Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; *Liver/metabolism/microbiology ; Lymphocytes/immunology/metabolism ; Mice, Inbred C57BL ; Male ; Immunity, Innate ; Fatty Liver/therapy/metabolism/microbiology ; Interleukin-22 ; Non-alcoholic Fatty Liver Disease/therapy/microbiology/metabolism/immunology ; Interleukins/metabolism ; Female ; }, abstract = {Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.}, } @article {pmid38940030, year = {2024}, author = {Li, Y and Fang, Y and Wang, H and Zhang, H}, title = {Balancing Act: Exploring the Gut Microbiota-Brown Adipose Tissue Axis in PCOS Pathogenesis and Therapeutic Frontiers.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {29}, number = {6}, pages = {208}, doi = {10.31083/j.fbl2906208}, pmid = {38940030}, issn = {2768-6698}, support = {2023YFC2705400//National Key Research and Development Program of China/ ; }, mesh = {*Polycystic Ovary Syndrome/microbiology/metabolism/therapy/physiopathology ; Humans ; Female ; *Gastrointestinal Microbiome/physiology ; *Adipose Tissue, Brown/metabolism ; Animals ; Insulin Resistance ; Fecal Microbiota Transplantation ; Obesity/microbiology/metabolism/therapy ; }, abstract = {Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.}, } @article {pmid38938213, year = {2024}, author = {Wu, Y and Gu, D and Li, J and Li, J and Hou, G}, title = {Role of the gut microbiota in cefoperazone/sulbactam-induced epilepsy in mice with chronic renal failure.}, journal = {Renal failure}, volume = {46}, number = {2}, pages = {2371551}, pmid = {38938213}, issn = {1525-6049}, mesh = {Animals ; *Cefoperazone/therapeutic use ; *Sulbactam/therapeutic use ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Disease Models, Animal ; *Kidney Failure, Chronic/therapy/complications ; *Epilepsy/drug therapy ; Male ; Anti-Bacterial Agents/adverse effects ; Fecal Microbiota Transplantation ; Feces/microbiology ; }, abstract = {OBJECTIVES: The mechanism of cefoperazone/sulbactam-induced epilepsy in chronic kidney disease (CKD) patients is not yet clear. We hypothesized that cefoperazone/sulbactam-induced epilepsy could be based on two main factors: neurotoxicity caused by drug accumulation after renal failure and an abnormal gut microbiota (GM).

METHODS: A chronic renal failure (CRF) model in mice was established, and then different doses of cefoperazone/sulbactam were injected to induce epilepsy in mice. Normal mouse feces for fecal microbiota transplantation (FMT) were collected. We observed the changes in feces, mental state, and activity of each group of mice. After killing, we collected kidneys and colon for H&E staining. We collected mouse feces for the 16S RNA sequencing of bacteria.

RESULTS: All CRF mice injected with different concentrations of cefoperazone/sulbactam experienced grade-V seizures and eventually died, whereas normal control mice did not. However, after FMT intervention, the time of epilepsy onset and death in mice was delayed. Early FMT intervention resulted in more mice surviving (p = .0359). Moreover, the villi in the mucosal of group-CS layer fell off, goblet cells missed, and crypts disappeared. The mucosal layer and submucosa were clearly separated. The morphology of intestinal tissue of the CFS and FS group was improved. After FMT, the changes of the GM were observed.

CONCLUSIONS: The GM may be involved in the epilepsy induced by cefoperazone/sulbactam in CRF mice. FMT can delay the onset of epilepsy in CRF mice induced by cefoperazone/sulbactam, and the earlier the intervention, the better the effect.}, } @article {pmid38935618, year = {2024}, author = {Sun, J and Teng, M and Zhu, W and Zhao, X and Zhao, L and Li, Y and Zhang, Z and Liu, Y and Bi, S and Wu, F}, title = {MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.}, journal = {ACS nano}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsnano.4c06298}, pmid = {38935618}, issn = {1936-086X}, abstract = {Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.}, } @article {pmid38935586, year = {2024}, author = {Colt, SF and Choi, RJ and Wexler, A}, title = {To Counsel or Not to Counsel: Physician Attitudes and Experiences with Do-It-Yourself (DIY) Fecal Microbiota Transplant (FMT).}, journal = {AJOB empirical bioethics}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/23294515.2024.2370776}, pmid = {38935586}, issn = {2329-4523}, abstract = {BACKGROUND: In the early 2010s, a phenomenon known as do-it-yourself (DIY) fecal microbiota transplant (FMT) emerged as lay individuals began self-administering FMTs at home. Although prior research indicates that many individuals who perform DIY FMT have sought advice from healthcare providers, to date there has been no investigation of physicians' experiences with DIY FMT. The objective of this qualitative study was to examine the attitudes of physicians who offer FMT regarding the practice of DIY FMT and to assess how they navigated the ethical challenges of patient requests for DIY FMT.

METHODS: We recruited physicians listed on two patient-created online databases of FMT providers. All physicians who indicated having been approached for advice about DIY FMT were included in the study. Semi-structured interviews with physicians explored their attitudes toward and experiences with DIY FMT.

RESULTS: Of 18 physicians interviewed, one reported having provided counsel in response to an initial patient inquiry about DIY FMT, 2 indicated they explicitly advised against DIY FMT and refused to provide advice, and 15 fell in a middle category of discouraging DIY FMT and discussing reasons why. Among the physicians in this third category, four reported that they had changed their approach to providing counsel in response to a patient telling them they were going to perform DIY FMT anyway.

CONCLUSIONS: Physicians in our study employed a wide range of strategies for promoting safety in the DIY FMT context, from explicitly advising against the procedure to the provision of guidance aimed at mitigating potential harms. While there has been increasing attention to the practices of DIY medicine, this study underscores the need for greater attention to the ethically complex situations that physicians face when patients request guidance for unapproved at-home treatments.}, } @article {pmid38934721, year = {2024}, author = {Kooij, KL and Andreani, NA and van der Gun, LL and Keller, L and Trinh, S and van der Vijgh, B and Luijendijk, M and Dempfle, A and Herpertz-Dahlmann, B and Seitz, J and van Elburg, A and Danner, UN and Baines, J and Adan, RAH}, title = {Fecal microbiota transplantation of patients with anorexia nervosa did not alter flexible behavior in rats.}, journal = {The International journal of eating disorders}, volume = {}, number = {}, pages = {}, doi = {10.1002/eat.24231}, pmid = {38934721}, issn = {1098-108X}, support = {//NWO-ALW Open Competition grant/ ; MIGBANFKZ//ERA-NET neuron 2018/ ; 01EW1906A//ERA-NET neuron 2018/ ; }, abstract = {OBJECTIVE: Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression.

METHODS: In a preclinical study, we explored whether AN-derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase-cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety-like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests.

RESULTS: Neither antibiotic-induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose-stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients.

DISCUSSION: No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic-induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies.

PUBLIC SIGNIFICANCE: While our study did not reveal direct impacts of AN-associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic-induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa.}, } @article {pmid38934542, year = {2024}, author = {Yang, X and Xu, Y and Li, J and Ran, X and Gu, Z and Song, L and Zhang, L and Wen, L and Ji, G and Wang, R}, title = {Bile acid-gut microbiota imbalance in cholestasis and its long-term effect in mice.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0012724}, doi = {10.1128/msystems.00127-24}, pmid = {38934542}, issn = {2379-5077}, abstract = {UNLABELLED: Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In the hepatic cholestasis mouse model, which was induced by a temporary complete blockage of the bile duct, the stasis of bile acids and liver damage typically recovered within a short period. However, we found that the temporary hepatic cholestasis had a long-term effect on gut microbiota dysbiosis, including overgrowth of small intestinal bacteria, decreased diversity of the gut microbiota, and an overall imbalance in its composition accompanied by an elevated inflammation level. Additionally, we observed an increase in Escherichia-Shigella (represented by ASV136078), rich in virulence factors, in both small and large intestines following cholestasis. To confirm the causal role of dysregulated gut microbiota in promoting hepatic inflammation and injury, we conducted gut microbiota transplantation into germ-free mice. We found that recipient mice transplanted with feces from cholestasis mice exhibited liver inflammation, damage, and accumulation of hepatic bile acids. In conclusion, our study demonstrates that cholestasis disrupts the overall load and structural composition of the gut microbiota in mice, and these adverse effects persist after recovery from cholestatic liver injury. This finding suggests the importance of monitoring the structural composition of the gut microbiota in patients with cholestasis and during their recovery.

IMPORTANCE: Our pre-clinical study using a mouse model of cholestasis underscores that cholestasis not only disrupts the equilibrium and structural configuration of the gut microbiota but also emphasizes the persistence of these adverse effects even after bile stasis restoration. This suggests the need of monitoring and initiating interventions for gut microbiota structural restoration in patients with cholestasis during and after recovery. We believe that our study contributes to novel and better understanding of the intricate interplay among bile acid homeostasis, gut microbiota, and cholestasis-associated complications. Our pre-clinical findings may provide implications for the clinical management of patients with cholestasis.}, } @article {pmid38934224, year = {2024}, author = {Pereira, LTG and Vilela, WR and Bellozi, PMQ and Engel, DF and de Paula, GC and de Andrade, RR and Mortari, MR and de Melo Teixeira, M and Coleine, C and Figueiredo, CP and de Bem, AF and Amato, AA}, title = {Fecal microbiota transplantation ameliorates high-fat diet-induced memory impairment in mice.}, journal = {Journal of neurochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1111/jnc.16156}, pmid = {38934224}, issn = {1471-4159}, support = {408703/2021-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 424809-2018-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 00193-00000229/2021-21//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 00193-00000889/2021-10//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 00193-00001324/2019-27//Fundação de Apoio à Pesquisa do Distrito Federal/ ; 485489/2014-1//Instituto Nacional de Ciência e Tecnologia e NeuroImunomodulação/ ; }, abstract = {Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high-fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3-day fecal microbiota transplantation (FMT) regimen from low-fat (control) diet-fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD-induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD-induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns.}, } @article {pmid38932733, year = {2024}, author = {Kalra, S and Sharma, S and Verma, SK and Thakor, P and Malve, H and Chamle, V and Patil, A and Meer, T and Naik, I}, title = {Assessment of Hydration Status Using Conventional Method and Salivary Osmolarity as a Point-of-care Tool.}, journal = {The Journal of the Association of Physicians of India}, volume = {72}, number = {6S}, pages = {30-38}, doi = {10.59556/japi.72.0545}, pmid = {38932733}, issn = {0004-5772}, mesh = {Humans ; *Saliva/chemistry ; Osmolar Concentration ; *Dehydration/diagnosis ; Biomarkers/analysis ; Point-of-Care Systems ; Organism Hydration Status/physiology ; Point-of-Care Testing ; }, abstract = {Dehydration is a well-known problem worldwide, and its assessment can be challenging due to confusing physical signs. The most effective way to assess hydration status is through the costly stable isotope methodology, but this approach has practical limitations. More commonly accepted and utilized indicators of hydration status are hematological and urinary parameters. However, hematological markers require invasive methods, and urinary markers have varying degrees of success in tracking hydration changes. While alterations in body weight can serve as a means of promptly evaluating hydration status, various factors such as food consumption, fluid intake, fecal losses, and urine production can impact these changes. Researchers have turned their attention to saliva as a potential marker and point-of-care (POC) testing to address the limitations of existing biomarkers. Saliva is appealing due to its easy collection process and similarities to extracellular fluid in terms of water and ion concentrations. Recent studies have shown that saliva flow rate, osmolarity/osmolality, and total protein concentration can effectively monitor changes in body mass during acute dehydration. Misdiagnosing dehydration can have severe clinical consequences, leading to morbidity and even mortality. This narrative review focuses on recognizing the significance of hydration assessment, monitoring, and the potential of salivary osmolarity (SOSM) as an assessment tool. Healthcare professionals can improve their practices and interventions to optimize hydration and promote overall wellness using such tools.}, } @article {pmid38931292, year = {2024}, author = {Młynarska, E and Wasiak, J and Gajewska, A and Steć, G and Jasińska, J and Rysz, J and Franczyk, B}, title = {Exploring the Significance of Gut Microbiota in Diabetes Pathogenesis and Management-A Narrative Review.}, journal = {Nutrients}, volume = {16}, number = {12}, pages = {}, doi = {10.3390/nu16121938}, pmid = {38931292}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/microbiology/therapy ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; *Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; Animals ; }, abstract = {Type 2 diabetes is a disease with significant health consequences for the individual. Currently, new mechanisms and therapeutic approaches that may affect this disease are being sought. One of them is the association of type 2 diabetes with microbiota. Through the enteric nervous system and the gut-microbiota axis, the microbiota affects the functioning of the body. It has been proven to have a real impact on influencing glucose and lipid metabolism and insulin sensitivity. With dysbiosis, there is increased bacterial translocation through the disrupted intestinal barrier and increased inflammation in the body. In diabetes, the microbiota's composition is altered with, for example, a more abundant class of Betaproteobacteria. The consequences of these disorders are linked to mechanisms involving short-chain fatty acids, branched-chain amino acids, and bacterial lipopolysaccharide, among others. Interventions focusing on the gut microbiota are gaining traction as a promising approach to diabetes management. Studies are currently being conducted on the effects of the supply of probiotics and prebiotics, as well as fecal microbiota transplantation, on the course of diabetes. Further research will allow us to fully develop our knowledge on the subject and possibly best treat and prevent type 2 diabetes.}, } @article {pmid38926934, year = {2024}, author = {Abrahamsson, T}, title = {We need more evidence about the risks and benefits of giving children faecal microbiota transplants.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {}, number = {}, pages = {}, doi = {10.1111/apa.17339}, pmid = {38926934}, issn = {1651-2227}, } @article {pmid38922808, year = {2024}, author = {Mullish, BH and Thursz, MR}, title = {Alcohol-Associated liver disease: Emerging therapeutic strategies.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/HEP.0000000000000986}, pmid = {38922808}, issn = {1527-3350}, abstract = {The large and growing burden of alcohol-related liver disease (ALD) - and the considerable burden of morbidity and mortality associated with it - has been a drive towards ongoing research into novel strategies for its treatment, with a particular focus upon alcohol-related hepatitis (AH). Management of alcohol-use disorder (AUD) forms the central pillar of ALD care, with evidence-based psychological and pharmacological approaches being well-established, and certain models demonstrating improved clinical outcomes when hepatology and addiction services are co-located. Corticosteroids have previously been used somewhat indiscriminately in patients with severe AH, but effective tools now exist to assess early response (and limit futile ongoing exposure). Techniques to predict risk of corticosteroid-related infection are also available, although current clinical strategies to mitigate this risk are limited. A variety of novel therapeutic approaches to AH are at different phases of trials and evidence-gathering, with some of the most promising signals related to cytokine manipulation, epigenetic modulation, and targeting of the gut microbiota (i.e. via faecal microbiota transplant). While remaining an ongoing source of debate, early liver transplant in severe AH has grown in interest and acceptability over the past decade as evidence supporting its efficacy builds, in the process challenging paradigms about mandatory pre-transplant sobriety periods. However, uncertainty remains regarding the optimal selection criteria, and whether liver transplant has a role for only a highly-limited proportion of AH patients or more widespread application. This review aims to provide an overview of this fast-moving field.}, } @article {pmid38922353, year = {2024}, author = {Ali, AQ and Sabir, DK and Dawood, AF and Abu-Rashed, M and Hasari, A and Gharqan, F and Alnefaie, S and Mohiddin, LE and Tatry, MM and Albadan, DA and Alyami, MM and Almutairi, MF and Shawky, LM}, title = {The potential liver injury induced by metronidazole-provoked disturbance of gut microbiota: modulatory effect of turmeric supplementation.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {38922353}, issn = {1432-1912}, abstract = {It has been reported that the gut-liver axis and intestinal microbiome contribute crucially to different liver diseases. So, targeting this hepato-intestinal connection may provide a novel treatment modality for hepatic disorders such as drug-induced liver injury (DILI). The present study thought to investigate the protective effect of turmeric (TUR) on metronidazole (MNZ)-induced liver damage and the possible association of the gut-liver axis and gut microbiota as a suggested underlying mechanism. In the first experiment, a MNZ-induced liver injury rat model was reproduced after 130 mg/kg oral MNZ administration for 30 days. Meanwhile, the treatment group was orally treated with 100 mg/kg turmeric daily. In the second experiment, fecal microbiome transplantation (FMT) was conducted, in which the fecal microbiome of each group in the first experiment was transplanted to a healthy corresponding group in the second experiment. The liver enzymes (aminotransferase (ALT) and aspartate aminotransferase (AST)) and histopathological examination were estimated to assess liver function. Inflammatory cytokines and oxidative markers were evaluated in the liver tissues. Histological analysis, intestinal barrier markers, and expression of tight junction proteins were measured for assessment of the intestinal injury. Changes in the gut microbial community and possible hepatic bacterial transmission were analyzed using 16S rRNA sequencing. MNZ induced intestinal and liver injuries which were significantly improved by turmeric. Increased firmicutes/bacteroidetes ratio and bacterial transmission due to gut barrier disruption were suggested. Moreover, TUR has maintained the gut microbial community by rebalancing and restoring bacterial proportions and abundance, thereby repairing the gut mucosal barrier and suppressing bacterial translocation. TUR protected against MNZ-induced gut barrier disruption. Reshaping of the intestinal bacterial composition and prohibition of the hepatic microbial translocation were suggested turmeric effects, potentially mitigating MNZ-related liver toxicity.}, } @article {pmid38918470, year = {2024}, author = {Sinha, AK and Laursen, MF and Brinck, JE and Rybtke, ML and Hjørne, AP and Procházková, N and Pedersen, M and Roager, HM and Licht, TR}, title = {Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {38918470}, issn = {2058-5276}, support = {19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; 35040//Villum Fonden (Villum Foundation)/ ; 35040//Villum Fonden (Villum Foundation)/ ; }, abstract = {Tryptophan is catabolized by gut microorganisms resulting in a wide range of metabolites implicated in both beneficial and adverse host effects. How gut microbial tryptophan metabolism is directed towards indole, associated with chronic kidney disease, or towards protective indolelactic acid (ILA) and indolepropionic acid (IPA) is unclear. Here we used in vitro culturing and animal experiments to assess gut microbial competition for tryptophan and the resulting metabolites in a controlled three-species defined community and in complex undefined human faecal communities. The generation of specific tryptophan-derived metabolites was not predominantly determined by the abundance of tryptophan-metabolizing bacteria, but rather by substrate-dependent regulation of specific metabolic pathways. Indole-producing Escherichia coli and ILA- and IPA-producing Clostridium sporogenes competed for tryptophan within the three-species community in vitro and in vivo. Importantly, fibre-degrading Bacteroides thetaiotaomicron affected this competition by cross-feeding monosaccharides to E. coli. This inhibited indole production through catabolite repression, thus making more tryptophan available to C. sporogenes, resulting in increased ILA and IPA production. The fibre-dependent reduction in indole was confirmed using human faecal cultures and faecal-microbiota-transplanted gnotobiotic mice. Our findings explain why consumption of fermentable fibres suppresses indole production but promotes the generation of other tryptophan metabolites associated with health benefits.}, } @article {pmid38915399, year = {2024}, author = {Zhang, H and Hong, Y and Wu, T and Ben, E and Li, S and Hu, L and Xie, T}, title = {Role of gut microbiota in regulating immune checkpoint inhibitor therapy for glioblastoma.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1401967}, pmid = {38915399}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Glioblastoma/immunology/drug therapy/therapy/microbiology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Brain Neoplasms/immunology/drug therapy/therapy/microbiology ; Animals ; Brain-Gut Axis/immunology ; Fecal Microbiota Transplantation ; Tumor Microenvironment/immunology/drug effects ; }, abstract = {Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong patient survival. With the deepening of research, it has been found that gut microbiota plays a certain role in GBM, and can directly or indirectly affect the efficacy of immune checkpoint inhibitors (ICIs) in various ways. (1) The metabolites produced by gut microbiota directly affect the host's immune homeostasis, and these metabolites can affect the function and distribution of immune cells, promote or inhibit inflammatory responses, affect the phenotype, angiogenesis, inflammatory response, and immune cell infiltration of GBM cells, thereby affecting the effectiveness of ICIs. (2) Some members of the gut microbiota may reverse T cell function inhibition, increase T cell anti-tumor activity, and ultimately improve the efficacy of ICIs by targeting specific immunosuppressive metabolites and cytokines. (3) Some members of the gut microbiota directly participate in the metabolic process of drugs, which can degrade, transform, or produce metabolites, affecting the effective concentration and bioavailability of drugs. Optimizing the structure of the gut microbiota may help improve the efficacy of ICIs. (4) The gut microbiota can also regulate immune cell function and inflammatory status in the brain through gut brain axis communication, indirectly affecting the progression of GBM and the therapeutic response to ICIs. (5) Given the importance of gut microbiota for ICI therapy, researchers have begun exploring the use of fecal microbiota transplantation (FMT) to transplant healthy or optimized gut microbiota to GBM patients, in order to improve their immune status and enhance their response to ICI therapy. Preliminary studies suggest that FMT may enhance the efficacy of ICI therapy in some patients. In summary, gut microbiota plays a crucial role in regulating ICIs in GBM, and with a deeper understanding of the relationship between gut microbiota and tumor immunity, it is expected to develop more precise and effective personalized ICI therapy strategies for GBM, in order to improve patient prognosis.}, } @article {pmid38915068, year = {2024}, author = {Yan, J and Zhou, G and Ren, R and Zhang, X and Zhang, N and Wang, Z and Peng, L and Yang, Y}, title = {Siderophore-harboring gut bacteria and fecal siderophore genes for predicting the responsiveness of fecal microbiota transplantation for active ulcerative colitis.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {589}, pmid = {38915068}, issn = {1479-5876}, support = {2015AA020701//National High-tech Research and Development Program/ ; 82200609//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Colitis, Ulcerative/therapy/microbiology/genetics ; Male ; Female ; *Feces/microbiology ; *Fecal Microbiota Transplantation ; Adult ; Middle Aged ; *Gastrointestinal Microbiome/genetics ; *Siderophores/metabolism ; Treatment Outcome ; Bacteria/genetics ; Genes, Bacterial ; Gene Dosage ; ROC Curve ; }, abstract = {BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness.

METHODS: Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy.

RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness.

CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.}, } @article {pmid38914878, year = {2024}, author = {Leclercq, S and de Timary, P}, title = {Role of the Microbiome and the Gut-Brain Axis in Alcohol Use Disorder: Potential Implication for Treatment Development.}, journal = {Current topics in behavioral neurosciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/7854_2024_478}, pmid = {38914878}, issn = {1866-3370}, abstract = {The gut microbiota is constituted by trillions of microorganisms colonizing the human intestine. Studies conducted in patients with alcohol use disorder (AUD) have shown altered microbial composition related to bacteria, viruses, and fungi.This review describes the communication pathways between the gut and the brain, including the ones related to the bacterial metabolites, the inflammatory cytokines, and the vagus nerve. We described in more detail the gut-derived metabolites that have been shown to be implicated in AUD or that could potentially be involved in the development of AUD due to their immune and/or neuroactive properties, including tryptophan-derivatives, tyrosine-derivatives, short chain fatty acids.Finally, we discussed the potential beneficial effects of microbiome-based therapies for AUD such as probiotics, prebiotics, postbiotic, and phage therapy.}, } @article {pmid38914259, year = {2024}, author = {Yu, JM and Liang, ZY and Fu, YH and Peng, XL and Zheng, YP and Dong, YJ and He, JS}, title = {Coexistence of adeno-associated virus 2 with adenovirus 18 or herpesvirus may be associated with severe lingual papillomatosis in an immunocompromised individual.}, journal = {Virologica Sinica}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.virs.2024.06.006}, pmid = {38914259}, issn = {1995-820X}, abstract = {Next-generation sequencing (NGS) has significantly improved the accuracy and efficiency of pathogen diagnosis for a wide range of diseases. In this study, viral metagenomics analysis was conducted on fecal and tissue samples from a 13-year-old recipient of hematopoietic stem cell transplantation (HSCT) afflicted with severe lingual papillomatosis. The analysis revealed a high abundance of adeno-associated virus 2 (AAV2), alongside potential helper viruses, herpesvirus type 1 (HSV-1), and the uncommon adenovirus serotype 18 (AdV18). Although a direct causal relationship was not definitively established, the concurrence of these viruses indicated a plausible link to the development of severe lingual papillomatosis in immunocompromised individuals. Notably, the study generated a complete genome sequence of AdV18, offering insights into adenovirus genetic variability, origin, and pathogenicity. Noteworthy findings include three amino acid substitutions in the polymerase and one in the hexon, distinguishing them from previously published strains of AdV18. Phylogenetic analysis unveiled a close relationship between both the polymerase and hexon regions of AdV18 in our study and previously reported AdV18 sequences. This study underscores the pivotal role of comprehensive viral scrutiny in elucidating infections among HSCT patients with lingual papillomatosis.}, } @article {pmid38913690, year = {2024}, author = {Yu, C and Xu, D and Luo, Y and Jiao, J and Liu, G and Wang, F and Gao, Y and Sun, X and Lv, X and Wu, H and Kong, X}, title = {Osteopontin Depletion in Non-haematopoietic Cells Improves Outcomes in Septic Mice by Enhancing Antimicrobial Peptide Production.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiae320}, pmid = {38913690}, issn = {1537-6613}, abstract = {Osteopontin (Opn) depletion can improve septic outcomes, but the underlying mechanism remains unknown. In this study, we demonstrated that non-haematopoietic but not haematopoietic Opn depletion improved septic outcomes. Compared to wild-type (WT) mice, co-housed Opn-/- mice displayed enhanced production of antibacterial peptides (AMPs), decreased bacterial loads, and a distinct bacterial composition of gut microbiota. Fecal microbiota transplantation (FMT) and OPN neutralization assay showed that Opn depletion could reduce the bacterial loads and improve septic inflammation. By employing an intestinal organoid culture system, we proved that OPN neutralization in WT organoids could inactivate AKT and decrease FOXO3a phosphorylation, resulting in enhanced AMP production, whereas OPN treatment in OPN deficient organoids could activate AKT and increase FOXO3a phosphorylation, leading to reduced AMP production. Our findings identified OPN as a novel regulatory factor of AMP production to modulate bacterial loads and composition of gut microbiota, in turn affecting sepsis outcomes.}, } @article {pmid38911589, year = {2024}, author = {Liu, H and Wei, Y and Xu, Z and Lin, H and Zhao, Y and Wang, S and Gao, F and Feng, N and Wolfe, AJ and Liu, F}, title = {Exploring Factors Affecting Acceptance of Fecal Microbiota Transplantation for Patients with Recurrent Urinary Tract Infections: a Descriptive Qualitative Study.}, journal = {Patient preference and adherence}, volume = {18}, number = {}, pages = {1257-1269}, pmid = {38911589}, issn = {1177-889X}, abstract = {PURPOSE: Patients with recurrent urinary tract infections face complex management challenges. Fecal microbiota transplantation is a superior treatment for chronic infectious diseases, but limited patient knowledge affects treatment decisions. This study aims to identify factors associated with hesitancy towards fecal microbiota transplantation among patients with recurrent urinary tract infections, to help physicians and nurses in providing accurate and useful information to patients.

PATIENTS AND METHODS: A descriptive qualitative approach was employed, utilizing semi-structured interviews conducted with patients experiencing recurrent urinary tract infections who expressed hesitancy towards fecal microbiota transplantation. The interviews took place between September 2021 and December 2022. Thematic analysis was conducted on the semi-structured interviews to identify perceived facilitators and barriers associated with fecal microbiota transplantation.

RESULTS: The analysis included interviews with thirty adult female patients with recurrent urinary tract infections. Four facilitators influencing patients' decision-making regarding fecal microbiota transplantation were identified: (1) the motivating role of hope and expectations for active patient participation; (2) the influence of healthcare providers, as well as family members and friends on patients' decisions to pursue fecal microbiota transplantation; (3) the patients' perception of fecal microbiota transplantation as a low-risk treatment option; and (4) the dedication to the advancement of medical treatments. In contrast, two primary barriers to accepting fecal microbiota transplantation were identified: (1) that conventional treatment controls disease activity, while fecal microbiota transplantation effects remain uncertain; and (2) that safety concerns surrounding fecal microbiota transplantation.

CONCLUSION: Comprehensive information about fecal microbiota transplantation, including donor selection, sample processing, the procedure, and potential discomfort, is essential for patients and families to make informed treatment decisions.

REGISTRATION: CHiCTR2100048970.}, } @article {pmid38910461, year = {2024}, author = {Wu, B and Quan, C and He, Y and Matsika, J and Huang, J and Liu, B and Chen, J}, title = {Targeting gut and intratumoral microbiota: a novel strategy to improve therapy resistance in cancer with a focus on urologic tumors.}, journal = {Expert opinion on biological therapy}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/14712598.2024.2371543}, pmid = {38910461}, issn = {1744-7682}, abstract = {INTRODUCTION: Growing attention has been drawn to urologic tumors due to their rising incidence and suboptimal clinical treatment outcomes. Cancer therapy resistance poses a significant challenge in clinical oncology, limiting the efficacy of conventional treatments and contributing to disease progression. Recent research has unveiled a complex interplay between the host microbiota and cancer cells, highlighting the role of the microbiota in modulating therapeutic responses.

AREAS COVERED: We used the PubMed and Web of Science search engines to identify key publications in the fields of tumor progression and urologic tumor treatment, specifically focusing on the role of the microbiota. In this review, we summarize the current literature on how microbiota influence the tumor microenvironment and anti-tumor immunity, as well as their impact on treatments for urinary system malignancies, highlighting promising future applications.

EXPERT OPINION: We explore how the composition and function of the gut microbiota influence the tumor microenvironment and immune response, ultimately impacting treatment outcomes. Additionally, we discuss emerging strategies targeting the microbiota to enhance therapeutic efficacy and overcome resistance. The application of antibiotics, fecal microbiota transplantation, and oncolytic bacteria has improved tumor treatment outcomes, which provides a novel insight into developing therapeutic strategies for urologic cancer.}, } @article {pmid38910152, year = {2024}, author = {Byndloss, M and Devkota, S and Duca, F and Niess, JH and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L}, title = {The gut microbiota and diabetes: research, translation, and clinical applications - 2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.}, journal = {Diabetologia}, volume = {}, number = {}, pages = {}, pmid = {38910152}, issn = {1432-0428}, abstract = {This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.}, } @article {pmid38908958, year = {2024}, author = {Haddad, A and Holder, AM}, title = {Microbiome and Immunotherapy for Melanoma: Are We Ready for Clinical Application?.}, journal = {Hematology/oncology clinics of North America}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.hoc.2024.05.010}, pmid = {38908958}, issn = {1558-1977}, abstract = {The microbiome plays a substantial role in the efficacy of immune checkpoint blockade (ICB) in patients with metastatic melanoma. While the exact gut microbiome composition and the pathways involved in this interaction are not clearly delineated, novel studies and ongoing clinical trials are likely to reveal findings applicable to the clinical setting for the prediction and optimization of response to ICB. Nevertheless, lifestyle modifications, including high fiber diet, avoidance of unnecessary antibiotic prescriptions, and careful use of probiotics may be helpful to optimize the "health" of the gut microbiome and potentially enhance response to ICB in patients with melanoma.}, } @article {pmid38908733, year = {2024}, author = {Lau, RI and Su, Q and Ching, JYL and Lui, RN and Chan, TT and Wong, MTL and Lau, LHS and Wing, YK and Chan, RNY and Kwok, HYH and Ho, AHY and Tse, YK and Cheung, CP and Li, MKT and Siu, WY and Liu, C and Lu, W and Wang, Y and Chiu, EOL and Cheong, PK and Chan, FKL and Ng, SC}, title = {Faecal microbiota transplantation for sleep disturbance in post-acute COVID-19 syndrome.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.06.004}, pmid = {38908733}, issn = {1542-7714}, abstract = {BACKGROUND & AIMS: Post-acute COVID-19 syndrome (PACS) is associated with sleep disturbance but treatment options are limited. The aetiology of PACS may be secondary to alterations in the gut microbiome. Here, we report the efficacy of faecal microbiota transplantation (FMT) in alleviating post-COVID insomnia symptoms in a non-randomised, open-label prospective interventional study.

METHODS: Between September 22, 2022 and May 22, 2023, we recruited 60 PACS patients with insomnia defined as Insomnia Severity Index (ISI) ≥ 8 and assigned them to the FMT group (FMT at weeks 0, 2, 4 and 8; n=30) or the control group (n=30). The primary outcome was clinical remission defined by an ISI of less than eight at 12 weeks. Secondary outcomes included changes in the Pittsburgh Sleep Quality Index (PSQI), Generalised Anxiety Disorder-7 scale (GAD-7), Epworth Sleepiness Scale (ESS), Multidimensional Fatigue Inventory (MFI), blood cortisol and melatonin, and gut microbiome analysis on metagenomic sequencing.

RESULTS: At week 12, more patients in the FMT than the control group had insomnia remission (37.9% vs 10.0%; p=0.018). The FMT group showed a decrease in ISI score (p<0.0001), PSQI (p<0.0001), GAD-7 (p=0.0019), ESS (p=0.0057) and blood cortisol concentration (p=0.035) from baseline to week 12, but there was no significant change in the control group. There was enrichment of bacteria such as Gemmiger formicilis and depletion of microbial pathways producing menaquinol derivatives after FMT. Gut microbiome profile resembled that of the donor in FMT responders but not in non-responders at week 12. There was no serious adverse event.

CONCLUSION: This pilot study showed that FMT could be effective and safe in alleviating post-COVID insomnia and further clinical trials are warranted.

CLINICALTRIALS: gov identifier: NCT05556733.}, } @article {pmid38908691, year = {2024}, author = {Mu, YY and Qi, WP and Zhang, T and Zhang, JY and Li, M and Mao, SY}, title = {Changes in Rumen Epithelial Morphology and Transcriptome, Rumen Metabolome, and Blood Biochemical Parameters in Lactating Dairy Cows with Subacute Rumen Acidosis Following Rumen Content Transplantation.}, journal = {Journal of dairy science}, volume = {}, number = {}, pages = {}, doi = {10.3168/jds.2024-24694}, pmid = {38908691}, issn = {1525-3198}, abstract = {Interventions targeting the gut microbiota, such as fecal microbiota transplantation, prove effective in repairing the intestinal barrier and facilitating the recovery of its function and metabolism. However, the regulatory mechanisms governing the remodeling of rumen epithelial morphology and function, rumen metabolism, and host metabolism in cows of subacute ruminal acidosis (SARA) remain poorly understood. Here, we explored the changes in rumen epithelial morphology and transcriptome, rumen metabolome, and blood biochemical parameters in SARA cows following rumen content transplantation (RCT). The entire experiment consisted of 2 periods: the SARA induction period and the RCT period. During the SARA induction period, 12 ruminally cannulated lactating Holstein cows were randomly allocated into 2 groups, fed either a conventional diet [CON; n = 4; 40% concentrate, dry matter (DM) basis] or a high-grain diet (HG; n = 8; 60% concentrate, DM basis). Following the SARA induction period, the RCT period started. The HG cows were randomly assigned to 2 groups: the donor-recipient (DR) group and the self-recipient (SR) group. Rumen contents were entirely removed from both groups before RCT. For the DR group, cows were administered 70% rumen content from the CON cows, paired based on comparable body weight; for the SR group, each cow received 70% self-derived rumen content. The results revealed no significant differences in the thicknesses of the stratum corneum, granulosum, and spinosum/basale layers, as well as the total depth of the epithelium between the SR and DR groups. All these measurements exhibited a decreasing trend and fluctuations over time after the transfer. Notably, these fluctuations tended to stabilize at 13 or 16 d after RCT in the SR group, whereas they tended to stabilize after 8 or 13 d of transfer for the DR group. Transcriptome sequencing revealed that a total of 277 differentially expressed genes (DEGs) were identified between the 2 groups. Enrichment analysis showed that the DEGs were significantly enriched in 11 Gene Ontology biological processes and 14 KEGG pathways. The DEGs corresponding to almost any of these 11 biological process terms and 14 pathways showed mixed up- or downregulation following RCT. Metabolomics analysis indicated that a total of 33 differential metabolites were detected between the SR and DR groups, mainly enriched in 5 key metabolic pathways, including plant polysaccharides and starch degradation, lipid metabolism, amino sugar and nucleotide metabolism, purine metabolism, and Krebs cycle. Among them, the levels of differential metabolites associated with the degradation of plant polysaccharides and starches, metabolism of amino sugars and nucleotides, and purine metabolism pathways were significantly elevated in the DR cows. The results of blood biochemical parameters showed that the triglyceride concentration of the DR cows was increased than that of the SR cows, comparable to the level observed in the CON cows during the SARA induction period. Generally, our findings indicated that RCT facilitated the recovery of rumen epithelial morphological structure but did not promote its function recovery. Moreover, RCT enhanced rumen plant polysaccharide and starch degradation, amino sugar and nucleotide sugar metabolism, as well as purine metabolism. Additionally, it further promoted the recovery of plasma metabolites related to lipid metabolism.}, } @article {pmid38908615, year = {2024}, author = {Hu, S and Tang, B and Lu, C and Wang, S and Wu, L and Lei, Y and Tang, L and Zhu, H and Wang, D and Yang, S}, title = {Lactobacillus rhamnosus GG ameliorates triptolide-induced liver injury through modulation of the bile acid-FXR axis.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107275}, doi = {10.1016/j.phrs.2024.107275}, pmid = {38908615}, issn = {1096-1186}, abstract = {Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic.}, } @article {pmid38908613, year = {2024}, author = {Xu, Q and Gao, J and Zhao, R and Li, H and Cui, H and Yuan, Z and Ren, H and Cao, B and Wei, B}, title = {Akkermansia muciniphila-derived pentadecanoic acid enhances oxaliplatin sensitivity in gastric cancer by modulating glycolysis.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107278}, doi = {10.1016/j.phrs.2024.107278}, pmid = {38908613}, issn = {1096-1186}, abstract = {Accumulating evidence has proved the close association between alterations in gut microbiota and resistance to chemotherapeutic drugs. However, the potential roles of gut microbiota in regulating oxaliplatin sensitivity in gastric cancer (GC) have not been investigated before. We first found that antibiotic treatment diminished the therapeutic efficacy of oxaliplatin in a GC mouse model. Importantly, this effect could be transmitted to germ-free mice via fecal microbiota transplantation, indicating a potential role of gut microbiota modulation in oxaliplatin efficacy. Further, metagenomics data showed that Akkermansia muciniphila (A. muciniphila) ranked first among the bacterial species with decreased relative abundances after antibiotic treatment. Metabolically active A. muciniphila promotes oxaliplatin efficacy. As shown by metabolomics analysis, the metabolic pattern of gut microbiota was disrupted with significantly downregulated levels of pentadecanoic acid (PEA), and the use of PEA significantly promoted oxaliplatin efficacy. Mechanistically, FUBP1 positively regulated aerobic glycolysis of GC cells to hinder the therapeutic efficacy of oxaliplatin. A. muciniphila-derived PEA functioned as an inhibitory factor of glycolysis by directly antagonizing the activity of FUBP1, which potentiated GC responses to oxaliplatin. Our research suggested a key role for intestinal A. muciniphila and its metabolite PEA in promoting oxaliplatin efficacy, thus providing a new perspective for probiotic and prebiotic intervention in GC patients during chemotherapy.}, } @article {pmid38908272, year = {2024}, author = {Deng, Z and Li, L and Jing, Z and Luo, X and Yu, F and Zeng, W and Bi, W and Zou, J}, title = {Association between environmental phthalates exposure and gut microbiota and metabolome in dementia with Lewy bodies.}, journal = {Environment international}, volume = {190}, number = {}, pages = {108806}, doi = {10.1016/j.envint.2024.108806}, pmid = {38908272}, issn = {1873-6750}, abstract = {BACKGROUND: Emerging evidence has shown the potential involvement of phthalates (PAEs) exposure in the development of dementia with Lewy bodies (DLB). Metabolomics can reflect endogenous metabolites variation in the progress of disease after chemicals exposure. However, little is known about the association between PAEs, gut microbiota and metabolome in DLB.

OBJECTIVE: We aim to explore the intricate relationship among urinary PAEs metabolites (mPAEs), dysbiosis of gut bacteria, and metabolite profiles in DLB.

METHODS: A total of 43 DLB patients and 45 normal subjects were included in this study. Liquid chromatography was used to analyze the levels of mPAEs in the urine of the two populations. High-throughput sequencing and liquid chromatography-mass spectrometry were used to analyze gut microbiota and the profile of gut metabolome, respectively. The fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of mPAEs on gut dysbiosis contribute to aggravating cognitive dysfunction in α-synuclein tg DLB/PD mice.

RESULTS: The DLB patients had higher DEHP metabolites (MEOHP, MEHHP and MEHP), MMP and MnBP, lower MBP and MBzP than the control group and different microbiota. A significantly higher abundance of Ruminococcus gnavus and lower Prevotella copri, Prevotella stercorea and Bifidobacterium were observed in DLB. Higher 3 DEHP metabolites, MMP, MnBP and lower MBP and MBzP were significantly negatively associated with Prevotella copri, Prevotella stercorea and Bifidobacterium. Additionally, using metabolomics, we found that altered bile acids, short-chain fatty acids and amino acids metabolism are linked to these mPAEs. We further found that FMT of fecal microbiota from highest DEHP metabolites donors significantly impaired cognitive function in the germ-free DLB/PD mice.

CONCLUSION: Our study suggested that PAEs exposure may alter the microbiota-gut-brain axis and providing novel insights into the interactions among environmental perturbations and microbiome-host in pathogenesis of DLB.}, } @article {pmid38908193, year = {2024}, author = {Li, J and Shi, B and Ren, X and Hu, J and Li, Y and He, S and Zhang, G and Maolan, A and Sun, T and Qi, X and Zhang, X and Luo, Y and Liu, R and Hua, B}, title = {Lung-intestinal axis, Shuangshen granules attenuate lung metastasis by regulating the intestinal microbiota and related metabolites.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {132}, number = {}, pages = {155831}, doi = {10.1016/j.phymed.2024.155831}, pmid = {38908193}, issn = {1618-095X}, abstract = {BACKGROUND: Based on the proposed lung-intestinal axis, there is a significant correlation between the microbiota and lung metastasis. Targeting the microbial composition is valuable in modulating the host response to cancer therapeutics. As a traditional Chinese medicine (TCM) formula, Shuangshen granules (SSG) are clinically useful in delaying lung metastasis, but its underlying mechanisms remain unknown.

METHODS: The C57BL/6N mice were chosen to establish the Lewis lung cancer models. The broad-spectrum antibiotics (ABX) group was set up to estimate the effect of microbiota composition on metastasis. The therapeutic effects of different doses of SSG in treating lung metastasis were investigated through histopathology, immunohistochemistry, and Western blot analysis methods. Additionally, the phenotype of tumor-associated macrophages (TAMs) in the lung and blood was evaluated by flow cytometry. The fecal microbiota transplantation (FMT) and negative control (ABX plus high dose SSG group) experiments were also designed to assess intestinal microbiota's role in SSG intervention's outcome in lung metastasis. The 16S rRNA amplicon sequencing and Untargeted metabolomic analysis were used to analyze intestinal microbiota and metabolite changes mediated by SSG in tumor-bearing mice with lung metastasis.

RESULT: ABX could observably lead to intestinal microbiota dysbiosis and enhance metastasis. SSG showed a significant chemopreventive effect in lung metastasis, reduced metastatic nodules and the expression levels of pre-metastatic niche biomarkers, and enriched the ratio of CD86+F4/80+CD11b+ cells, while FMT delayed metastasis similarly. The analysis of microbiota and metabolites revealed that SSG significantly enriched probiotics in feces, including Akkermansia muciniphila, Lachnoclostridium sp YL32, Limosilactobacillus reuteri, and potential anti-cancer serum metabolites, including Ginsenoside Rb1, Isoquinoline, Betulin and so on. We also investigated the mechanism of SSG protection against lung metastasis and showed that SSG regulated microbiota, improved TAMs polarization, and inhibited the expression of the NF-κB pathway.

CONCLUSION: The results presented in our article demonstrated that SSG improved TAMs polarization and inhibited the NF-κB pathway by alleviating intestinal microbiota imbalance and metabolic disorders in tumor-bearing mice, resulting in delayed lung metastasis.}, } @article {pmid38907332, year = {2024}, author = {Zhou, X and Ji, S and Chen, L and Liu, X and Deng, Y and You, Y and Wang, M and He, Q and Peng, B and Yang, Y and Chen, X and Kwan, HY and Zhou, L and Chen, J and Zhao, X}, title = {Gut microbiota dysbiosis in hyperuricaemia promotes renal injury through the activation of NLRP3 inflammasome.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {109}, pmid = {38907332}, issn = {2049-2618}, support = {82305130//National Natural Science Foundation of China/ ; 82274499//National Natural Science Foundation of China/ ; 2022A1515110810//Natural Science Foundation of Guangdong Province, China/ ; 2023A1515012429//Natural Science Foundation of Guangdong Province, China/ ; 81830117//Key Project of National Natural Science Foundation of China/ ; U22A20365//Joint Funds of National Natural Science Foundation of China/ ; ZYYCXTD-C-202001//Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine/ ; }, mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; *Inflammasomes/metabolism ; Mice ; Rats ; *Hyperuricemia ; Male ; Disease Models, Animal ; Kidney ; Mice, Knockout ; RNA, Ribosomal, 16S/genetics ; Fecal Microbiota Transplantation ; Urate Oxidase/metabolism ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown.

RESULTS: A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3[-/-]) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated.

CONCLUSION: Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract.}, } @article {pmid38907315, year = {2024}, author = {Brenchley, JM and Serrano-Villar, S}, title = {From dysbiosis to defense: harnessing the gut microbiome in HIV/SIV therapy.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {113}, pmid = {38907315}, issn = {2049-2618}, support = {ICI20/00058//Instituto de Salud Carlos III/ ; }, mesh = {*Gastrointestinal Microbiome ; *Dysbiosis/therapy/microbiology ; Humans ; *HIV Infections/microbiology/therapy/immunology ; *Simian Acquired Immunodeficiency Syndrome/therapy/immunology/microbiology ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation ; Animals ; *Simian Immunodeficiency Virus ; Prebiotics/administration & dosage ; HIV/physiology ; }, abstract = {BACKGROUND: Although the microbiota has been extensively associated with HIV pathogenesis, the majority of studies, particularly those using omics techniques, are largely correlative and serve primarily as a basis for hypothesis generation. Furthermore, most have focused on characterizing the taxonomic composition of the bacterial component, often overlooking other levels of the microbiome. The intricate mechanisms by which the microbiota influences immune responses to HIV are still poorly understood. Interventional studies on gut microbiota provide a powerful tool to test the hypothesis of whether we can harness the microbiota to improve health outcomes in people with HIV.

RESULTS: Here, we review the multifaceted role of the gut microbiome in HIV/SIV disease progression and its potential as a therapeutic target. We explore the complex interplay between gut microbial dysbiosis and systemic inflammation, highlighting the potential for microbiome-based therapeutics to open new avenues in HIV management. These include exploring the efficacy of probiotics, prebiotics, fecal microbiota transplantation, and targeted dietary modifications. We also address the challenges inherent in this research area, such as the difficulty in inducing long-lasting microbiome alterations and the complexities of study designs, including variations in probiotic strains, donor selection for FMT, antibiotic conditioning regimens, and the hurdles in translating findings into clinical practice. Finally, we speculate on future directions for this rapidly evolving field, emphasizing the need for a more granular understanding of microbiome-immune interactions, the development of personalized microbiome-based therapies, and the application of novel technologies to identify potential therapeutic agents.

CONCLUSIONS: Our review underscores the importance of the gut microbiome in HIV/SIV disease and its potential as a target for innovative therapeutic strategies.}, } @article {pmid38905983, year = {2024}, author = {Zhao, C and Chen, G and Huang, Y and Zhang, Y and Li, S and Jiang, Z and Peng, H and Wang, J and Li, D and Hou, R and Peng, C and Wan, X and Cai, H}, title = {Alleviation of fluoride-induced colitis by tea polysaccharides: Insights into the role of Limosilactobacillus vaginalis and butyric acid.}, journal = {Journal of hazardous materials}, volume = {476}, number = {}, pages = {134858}, doi = {10.1016/j.jhazmat.2024.134858}, pmid = {38905983}, issn = {1873-3336}, abstract = {Endemic fluorosis has gained increasing attention as a public health concern, and the escalating risk of colitis resulting from excessive fluoride intake calls for effective mitigation strategies. This study aimed to investigate the potential mechanisms underlying the alleviation of fluoride-induced colitis by Tea polysaccharides (TPS). Under conditions of excessive fluoride intake, significant changes were observed in the gut microbiota of rats, leading to aggravated colitis. However, the intervention of TPS exerted a notable alleviating effect on colitis symptoms. Antibiotic intervention and fecal microbiota transplantation (FMT) experiments provided evidence that TPS-mediated relief of fluoride-induced colitis is mediated through its effects on the gut microbiota. Furthermore, TPS supplementation was found to modulate the structure of gut microbiota, enhance the relative abundance of Limosilactobacillus vaginalis in the gut microbiota, and promote the expression of short-chain fatty acid (SCFAs) receptors in colonic tissue. Notably, L. vaginalis played a significant role in alleviating fluoride-induced colitis and facilitating the absorption of butyric acid in the rat colon. Subsequent butyric acid intervention experiments confirmed its remarkable alleviating effect on fluoride-induced colitis. Overall, these findings provide a potential preventive strategy for fluoride-induced colitis by TPS intervention, which is mediated by L. vaginalis and butyric acid.}, } @article {pmid38904913, year = {2024}, author = {Calabrese, FM and Genchi, VA and Serale, N and Celano, G and Vacca, M and Palma, G and Svelto, M and Gesualdo, L and De Angelis, M and Giorgino, F and Perrini, S}, title = {Gut microbiota and fecal volatilome profile inspection in metabolically healthy and unhealthy obesity phenotypes.}, journal = {Journal of endocrinological investigation}, volume = {}, number = {}, pages = {}, pmid = {38904913}, issn = {1720-8386}, support = {ARS0101220//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, abstract = {BACKGROUND: People with metabolically healthy (MHO) and metabolically unhealthy obesity (MUO) differ for the presence or absence of cardio-metabolic complications, respectively.

OBJECTIVE: Based on these differences, we are interested in deepening whether these obesity phenotypes could be linked to changes in microbiota and metabolome profiles. In this respect, the overt role of microbiota taxa composition and relative metabolic profiles is not completely understood. At this aim, biochemical and nutritional parameters, fecal microbiota, metabolome and SCFA compositions were inspected in patients with MHO and MUO under a restrictive diet regimen with a daily intake ranging from 800 to 1200 kcal.

METHODS: Blood, fecal samples and food questionnaires were collected from healthy controls (HC), and an obese cohort composed of both MHO and MUO patients. Most impacting biochemical/anthropometric variables from an a priori sample stratification were detected by applying a robust statistics approach useful in lowering the background noise. Bacterial taxa and volatile metabolites were assessed by qPCR and gas chromatography coupled with mass spectrometry, respectively. A targeted GC-MS analyses on SCFAs was also performed.

RESULTS: Instructed to follow a controlled and restricted daily calorie intake, MHO and MUO patients showed differences in metabolic, gut microbial and volatilome signatures. Our data revealed higher quantities of specific pro-inflammatory taxa (i.e., Desulfovibrio and Prevotella genera) and lower quantities of Clostridium coccoides group in MUO subset. Higher abundances in alkane, ketone, aldehyde, and indole VOC classes together with a lower amount of butanoic acid marked the faecal MUO metabolome.

CONCLUSIONS: Compared to MHO, MUO subset symptom picture is featured by specific differences in gut pro-inflammatory taxa and metabolites that could have a role in the progression to metabolically unhealthy status and developing of obesity-related cardiometabolic diseases. The approach is suitable to better explain the crosstalk existing among dysmetabolism-related inflammation, nutrient intake, lifestyle, and gut dysbiosis.}, } @article {pmid38903987, year = {2024}, author = {Sun, W and Mei, X and Wang, J and Mai, Z and Xu, D}, title = {Zn(II)-curcumin prevents cadmium-aggravated diabetic nephropathy by regulating gut microbiota and zinc homeostasis.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1411230}, pmid = {38903987}, issn = {1663-9812}, abstract = {Background: Diabetic nephropathy (DN) is known as the most common complication of diabetes, resulting from a complex inheritance-environment interaction without effective clinical treatments. Herein, we revealed the protective effects and mechanisms of Zn(II)-curcumin, a curcumin derivative, against streptozotocin-induced DN in rats in the presence or absence of cadmium exposure. Methods: The present study focused on investigating the therapy of Zn(II)-curcumin against cadmium-aggravated DN by regulating gut microbiota, metabolism, inflammation and zinc homeostasis based on pathological changes, TLR4/NF-κB signaling pathway, inductively coupled plasma-mass spectrometry (ICP-MS), 16S rRNA gene sequencing and gas chromatography-mass spectrometer (GC-MS). Results: We found Zn(II)-curcumin significantly mitigated the cadmium-aggravated phenotypes of diabetic nephropathy, as indicated by the remission of renal dysfunction, pathological changes, inflammation and zinc dyshomeostasis in streptozotocin-treated rats exposed to cadmium. Administration of Zn(II)-curcumin significantly alleviated the dysbiosis of gut microbiota and the changes of serum metabolite profiles in rats treated with streptozotocin in combination with cadmium. Notably, fecal microbial transplantation identified the ability of Zn(II)-curcumin to regulate renal function, inflammation and zinc homeostasis was partly dependent on the gut microbiota. Conclusion: These findings revealed that Zn(II)-curcumin alleviated cadmium-aggravated diabetic nephropathy by reshaping the gut microbiota and zinc homeostasis, which provided unique insights into the mechanisms of the treatment and prevention of diabetic nephropathy.}, } @article {pmid38903943, year = {2024}, author = {Tang, Y and Chen, L and Yang, J and Zhang, S and Jin, J and Wei, Y}, title = {Gut microbes improve prognosis of Klebsiella pneumoniae pulmonary infection through the lung-gut axis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1392376}, pmid = {38903943}, issn = {2235-2988}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Klebsiella Infections/microbiology/therapy ; *Klebsiella pneumoniae ; Mice ; *Fecal Microbiota Transplantation ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; *Lung/microbiology/pathology ; *Sepsis/microbiology/therapy ; Prognosis ; Disease Models, Animal ; Humans ; Male ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: The gut microbiota plays a vital role in the development of sepsis and in protecting against pneumonia. Previous studies have demonstrated the existence of the gut-lung axis and the interaction between the gut and the lung, which is related to the prognosis of critically ill patients; however, most of these studies focused on chronic lung diseases and influenza virus infections. The purpose of this study was to investigate the effect of faecal microbiota transplantation (FMT) on Klebsiella pneumoniae-related pulmonary infection via the gut-lung axis and to compare the effects of FMT with those of traditional antibiotics to identify new therapeutic strategies.

METHODS: We divided the mice into six groups: the blank control (PBS), pneumonia-derived sepsis (KP), pneumonia-derived sepsis + antibiotic (KP + PIP), pneumonia-derived sepsis + faecal microbiota transplantation(KP + FMT), antibiotic treatment control (KP+PIP+PBS), and pneumonia-derived sepsis+ antibiotic + faecal microbiota transplantation (KP + PIP + FMT) groups to compare the survival of mice, lung injury, inflammation response, airway barrier function and the intestinal flora, metabolites and drug resistance genes in each group.

RESULTS: Alterations in specific intestinal flora can occur in the gut of patients with pneumonia-derived sepsis caused by Klebsiella pneumoniae. Compared with those in the faecal microbiota transplantation group, the antibiotic treatment group had lower levels of proinflammatory factors and higher levels of anti-inflammatory factors but less amelioration of lung pathology and improvement of airway epithelial barrier function. Additionally, the increase in opportunistic pathogens and drug resistance-related genes in the gut of mice was accompanied by decreased production of favourable fatty acids such as acetic acid, propionic acid, butyric acid, decanoic acid, and secondary bile acids such as chenodeoxycholic acid 3-sulfate, isodeoxycholic acid, taurodeoxycholic acid, and 3-dehydrocholic acid; the levels of these metabolites were restored by faecal microbiota transplantation. Faecal microbiota transplantation after antibiotic treatment can gradually ameliorate gut microbiota disorder caused by antibiotic treatment and reduce the number of drug resistance genes induced by antibiotics.

CONCLUSION: In contrast to direct antibiotic treatment, faecal microbiota transplantation improves the prognosis of mice with pneumonia-derived sepsis caused by Klebsiella pneumoniae by improving the structure of the intestinal flora and increasing the level of beneficial metabolites, fatty acids and secondary bile acids, thereby reducing systemic inflammation, repairing the barrier function of alveolar epithelial cells, and alleviating pathological damage to the lungs. The combination of antibiotics with faecal microbiota transplantation significantly alleviates intestinal microbiota disorder, reduces the selection for drug resistance genes caused by antibiotics, and mitigates lung lesions; these effects are superior to those following antibiotic monotherapy.}, } @article {pmid38903520, year = {2024}, author = {Xie, Y and Liu, F}, title = {The role of the gut microbiota in tumor, immunity, and immunotherapy.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1410928}, pmid = {38903520}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods ; Animals ; Dysbiosis/immunology ; Neoplasms/immunology/therapy/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immune Checkpoint Inhibitors/therapeutic use ; Prebiotics/administration & dosage ; }, abstract = {In recent years, with the deepening understanding of the gut microbiota, it has been recognized to play a significant role in the development and progression of diseases. Particularly in gastrointestinal tumors, the gut microbiota influences tumor growth by dysbiosis, release of bacterial toxins, and modulation of host signaling pathways and immune status. Immune checkpoint inhibitors (ICIs) have greatly improved cancer treatment efficacy by enhancing immune cell responses. Current clinical and preclinical studies have demonstrated that the gut microbiota and its metabolites can enhance the effectiveness of immunotherapy. Furthermore, certain gut microbiota can serve as biomarkers for predicting immunotherapy responses. Interventions targeting the gut microbiota for the treatment of gastrointestinal diseases, especially colorectal cancer (CRC), include fecal microbiota transplantation, probiotics, prebiotics, engineered bacteria, and dietary interventions. These approaches not only improve the efficacy of ICIs but also hold promise for enhancing immunotherapy outcomes. In this review, we primarily discuss the role of the gut microbiota and its metabolites in tumors, host immunity, and immunotherapy.}, } @article {pmid38903498, year = {2024}, author = {Yang, X and Huang, J and Peng, J and Wang, P and Wong, FS and Wang, R and Wang, D and Wen, L}, title = {Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10[+] Breg cells and protect against T1D.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1413177}, pmid = {38903498}, issn = {1664-3224}, mesh = {Animals ; *Toll-Like Receptor 9/deficiency/genetics/metabolism ; *Gastrointestinal Microbiome/immunology ; *Mice, Inbred NOD ; *Interleukin-10/metabolism ; Mice ; *Diabetes Mellitus, Type 1/immunology/microbiology ; Mice, Knockout ; B-Lymphocytes, Regulatory/immunology ; Female ; B-Lymphocytes/immunology/metabolism ; }, abstract = {INTRODUCTION: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β cells. Toll-like receptor 9 (TLR9) plays a role in autoimmune diseases, and B cell-specific TLR9 deficiency delays T1D development. Gut microbiota are implicated in T1D, although the relationship is complex. However, the impact of B cell-specific deficiency of TLR9 on intestinal microbiota and the impact of altered intestinal microbiota on the development of T1D are unclear.

OBJECTIVES: This study investigated how gut microbiota and the intestinal barrier contribute to T1D development in B cell-specific TLR9-deficient NOD mice. Additionally, this study explored the role of microbiota in immune regulation and T1D onset.

METHODS: The study assessed gut permeability, gene expression related to gut barrier integrity, and gut microbiota composition. Antibiotics depleted gut microbiota, and fecal samples were transferred to germ-free mice. The study also examined IL-10 production, Breg cell differentiation, and their impact on T1D development.

RESULTS: B cell-specific TLR9-deficient NOD mice exhibited increased gut permeability and downregulated gut barrier-related gene expression. Antibiotics restored gut permeability, suggesting microbiota influence. Altered microbiota were enriched in Lachnospiraceae, known for mucin degradation. Transferring this microbiota to germ-free mice increased gut permeability and promoted IL-10-expressing Breg cells. Rag[-/-] mice transplanted with fecal samples from Tlr9 [fl/fl] Cd19-Cre[+] mice showed delayed diabetes onset, indicating microbiota's impact.

CONCLUSION: B cell-specific TLR9 deficiency alters gut microbiota, increasing gut permeability and promoting IL-10-expressing Breg cells, which delay T1D. This study uncovers a link between TLR9, gut microbiota, and immune regulation in T1D, with implications for microbiota-targeted T1D therapies.}, } @article {pmid38899956, year = {2024}, author = {Zhan, H and Wan, Y and Sun, Y and Xu, Z and Zhang, F and Yang, K and Zhu, W and Cheung, CP and Tang, W and Ng, EK and Wong, SK and Yeoh, YK and Kl Chan, F and Miao, Y and Zuo, T and Zeng, Z and Ng, SC}, title = {Gut mycobiome alterations in obesity in geographically different regions.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2367297}, doi = {10.1080/19490976.2024.2367297}, pmid = {38899956}, issn = {1949-0984}, mesh = {*Obesity/microbiology ; Humans ; Animals ; *Gastrointestinal Microbiome ; *Fungi/classification/isolation & purification/genetics ; Male ; Mice ; China ; Female ; *Mycobiome ; *Feces/microbiology ; Adult ; Bacteria/classification/isolation & purification/genetics ; Middle Aged ; Mice, Inbred C57BL ; Body Mass Index ; }, abstract = {The gut fungi play important roles in human health and are involved in energy metabolism. This study aimed to examine gut mycobiome composition in obese subjects in two geographically different regions in China and to identify specific gut fungi associated with obesity. A total of 217 subjects from two regions with different urbanization levels [Hong Kong (HK): obese, n = 59; lean, n = 59; Kunming (KM): obese, n = 50; lean, n = 49. Mean body mass index (BMI) for obesity = 33.7] were recruited. We performed deep shotgun metagenomic sequencing on fecal samples to compare gut mycobiome composition and trophic functions in lean and obese subjects across these two regions. The gut mycobiome of obese subjects in both HK and KM were altered compared to those of lean subjects, characterized by a decrease in the relative abundance of Nakaseomyces, Schizosaccharomyces pombe, Candida dubliniensis and an increase in the abundance of Lanchanceathermotolerans, Saccharomyces paradox, Parastagonospora nodorum and Myceliophthorathermophila. Reduced fungal - bacterial and fungal - fungal correlations as well as increased negative fungal-bacterial correlations were observed in the gut of obese subjects. Furthermore, the anti-obesity effect of fungus S. pombe was further validated using a mouse model. Supplementing high-fat diet-induced obese mice with the fungus for 12 weeks led to a significant reduction in body weight gain (p < 0.001), and an improvement in lipid and glucose metabolism compared to mice without intervention. In conclusion, the gut mycobiome composition and functionalities of obese subjects were altered. These data shed light on the potential of utilizing fungus-based therapeutics for the treatment of obesity. S. pombe may serve as a potential fungal probiotic in the prevention of diet-induced obesity and future human trials are needed.}, } @article {pmid38898924, year = {2024}, author = {Lin, C and Song, D and Wang, S and Chu, Y and Chi, C and Jia, S and Lin, M and He, C and Jiang, C and Gong, F and Chen, Q}, title = {Polygonatum cyrtonema polysaccharides reshape the gut microbiota to ameliorate dextran sodium sulfate-induced ulcerative colitis in mice.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1424328}, pmid = {38898924}, issn = {1663-9812}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized inflammatory imbalance, intestinal epithelial mucosal damage, and dysbiosis of the gut microbiota. Polygonatum cyrtonema polysaccharides (PCPs) can regulate gut microbiota and inflammation. Here, the different doses of PCPs were administered to dextran sodium sulfate-induced UC mice, and the effects of the whole PCPs were compared with those of the fractionated fractions PCP-1 (19.9 kDa) and PCP-2 (71.6 and 4.2 kDa). Additionally, an antibiotic cocktail was administered to UC mice to deplete the gut microbiota, and PCPs were subsequently administered to elucidate the potential role of the gut microbiota in these mice. The results revealed that PCP treatment significantly optimized the lost weight and shortened colon, restored the balance of inflammation, mitigated oxidative stress, and restored intestinal epithelial mucosal damage. And, the PCPs exhibited superior efficacy in ameliorating these symptoms compared with PCP-1 and PCP-2. However, depletion of the gut microbiota diminished the therapeutic effects of PCPs in UC mice. Furthermore, fecal transplantation from PCP-treated UC mice to new UC-afflicted mice produced therapeutic effects similar to PCP treatment. So, PCPs significantly ameliorated the symptoms, inflammation, oxidative stress, and intestinal mucosal damage in UC mice, and gut microbiota partially mediated these effects.}, } @article {pmid38898418, year = {2024}, author = {Song, J and Dong, H and Wang, T and Yu, H and Yu, J and Ma, S and Song, X and Sun, Q and Xu, Y and Liu, M}, title = {What is the impact of microbiota on dry eye: a literature review of the gut-eye axis.}, journal = {BMC ophthalmology}, volume = {24}, number = {1}, pages = {262}, pmid = {38898418}, issn = {1471-2415}, support = {2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; 2023ky003//The Third People's Hospital of Dalian/ ; }, mesh = {*Dry Eye Syndromes/metabolism/microbiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; Tears/metabolism ; }, abstract = {BACKGROUND: Dry eye is a chronic and multifactorial ocular surface disease caused by tear film instability or imbalance in the microenvironment of the ocular surface. It can lead to various discomforts such as inflammation of the ocular surface and visual issues. However, the mechanism of dry eye is not clear, which results in dry eye being only relieved but not cured in clinical practice. Finding multiple environmental pathways for dry eye and exploring the pathogenesis of dry eye have become the focus of research. Studies have found that changes in microbiota may be related to the occurrence and development of dry eye disease.

METHODS: Entered the keywords "Dry eye", "Microbiota", "Bacteria" through PUBMED, summarised the articles that meet the inclusion criteria and then filtered them while the publication time range of the literature was defined in the past 5 years, with a deadline of 2023.A total of 13 clinical and 1 animal-related research articles were screened out and included in the summary.

RESULTS: Study found that different components of bacteria can induce ocular immune responses through different receptors present on the ocular surface, thereby leading to an imbalance in the ocular surface microenvironment. Changes in the ocular surface microbiota and gut microbiota were also found when dry eye syndrome occurs, including changes in diversity, an increase in pro-inflammatory bacteria, and a decrease in short-chain fatty acid-related bacterial genera that produce anti-inflammatory effects. Fecal microbiota transplantation or probiotic intervention can alleviate signs of inflammation on the ocular surface of dry eye animal models.

CONCLUSIONS: By summarizing the changes in the ocular surface and intestinal microbiota when dry eye occurs, it is speculated and concluded that the intestine may affect the occurrence of eye diseases such as dry eye through several pathways and mechanisms, such as the occurrence of abnormal immune responses, microbiota metabolites- intervention of short-chain fatty acids, imbalance of pro-inflammatory and anti-inflammatory factors, and release of neurotransmitters, etc. Analyzing the correlation between the intestinal tract and the eyes from the perspective of microbiota can provide a theoretical basis and a new idea for relieving dry eyes in multiple ways in the future.}, } @article {pmid38897131, year = {2024}, author = {Ma, F and Zhang, W and Zhou, G and Qi, Y and Mao, HR and Chen, J and Lu, Z and Wu, W and Zou, X and Deng, D and Lv, S and Xiang, N and Wang, X}, title = {Epimedii Folium decoction ameliorates osteoporosis in mice through NLRP3/caspase-1/IL-1β signalling pathway and gut-bone axis.}, journal = {International immunopharmacology}, volume = {137}, number = {}, pages = {112472}, doi = {10.1016/j.intimp.2024.112472}, pmid = {38897131}, issn = {1878-1705}, abstract = {AIM OF THE STUDY: This study aimed to determine the effect of Epimedium brevicornu Maxim. (EF) on osteoporosis (OP) and its underlying molecular mechanisms, and to explore the existence of the "Gut-Bone Axis".

MATERIAL AND METHODS: The impact of EF decoction (EFD) on OP was evaluated using istopathological examination and biochemical assays. Targeted metabolomics was employed to identify key molecules and explore their molecular mechanisms. Alterations in the gut microbiota (GM) were evaluated by 16S rRNA gene sequencing. The role of the GM was clarified using an antibiotic cocktail and faecal microbiota transplantation.

RESULTS: EFD significantly increased the weight (14.06%), femur length (4.34%), abdominal fat weight (61.14%), uterine weight (69.86%), and insulin-like growth factor 1 (IGF-1) levels (59.48%), while reducing serum type I collagen cross-linked carboxy-terminal peptide (CTX-I) levels (15.02%) in osteoporotic mice. The mechanism of action may involve the regulation of the NLRP3/cleaved caspase-1/IL-1β signalling pathway in improving intestinal tight junction proteins and bone metabolism. Additionally, EFD modulated the abundance of related GM communities, such as Lactobacillus, Coriobacteriaceae, bacteria of family S24-7, Clostridiales, and Prevotella, and increased propionate and butyrate levels. Antibiotic-induced dysbiosis of gut bacteria disrupted OP regulation of bone metabolism, which was restored by the recovery of GM.

CONCLUSIONS: Our study is the first to demonstrate that EFD works in an OP mouse model by utilising GM and butyric acid. Thus, EF shows promise as a potential remedy for OP in the future.}, } @article {pmid38896362, year = {2024}, author = {Agrawal, G and Borody, TJ and Aitken, JM}, title = {Mapping Crohn's Disease Pathogenesis with Mycobacterium paratuberculosis: A Hijacking by a Stealth Pathogen.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {38896362}, issn = {1573-2568}, abstract = {Mycobacterium avium ssp. paratuberculosis (MAP) has been implicated in the development of Crohn's disease (CD) for over a century. Similarities have been noted between the (histo)pathological presentation of MAP in ruminants, termed Johne's disease (JD), and appearances in humans with CD. Analyses of disease presentation and pathology suggest a multi-step process occurs that consists of MAP infection, dysbiosis of the gut microbiome, and dietary influences. Each step has a role in the disease development and requires a better understanding to implementing combination therapies, such as antibiotics, vaccination, faecal microbiota transplants (FMT) and dietary plans. To optimise responses, each must be tailored directly to the activity of MAP, otherwise therapies are open to interpretation without microbiological evidence that the organism is present and has been influenced. Microscopy and histopathology enables studies of the mycobacterium in situ and how the associated disease processes manifest in the patient e.g., granulomas, fissuring, etc. The challenge for researchers has been to prove the relationship between MAP and CD with available laboratory tests and methodologies, such as polymerase chain reaction (PCR), MAP-associated DNA sequences and bacteriological culture investigations. These have, so far, been inconclusive in revealing the relationship of MAP in patients with CD. Improved and accurate methods of detection will add to evidence for an infectious aetiology of CD. Specifically, if the bacterial pathogen can be isolated, identified and cultivated, then causal relationships to disease can be confirmed, especially if it is present in human gut tissue. This review discusses how MAP may cause the inflammation seen in CD by relating its known pathogenesis in cattle, and from examples of other mycobacterial infections in humans, and how this would impact upon the difficulties with diagnostic tests for the organism.}, } @article {pmid38892659, year = {2024}, author = {Ju, X and Jiang, Z and Ma, J and Yang, D}, title = {Changes in Fecal Short-Chain Fatty Acids in IBS Patients and Effects of Different Interventions: A Systematic Review and Meta-Analysis.}, journal = {Nutrients}, volume = {16}, number = {11}, pages = {}, pmid = {38892659}, issn = {2072-6643}, mesh = {*Irritable Bowel Syndrome/diet therapy/therapy ; Humans ; *Feces/chemistry/microbiology ; *Fatty Acids, Volatile/analysis/metabolism ; Fecal Microbiota Transplantation ; Probiotics ; Propionates/metabolism/analysis ; Randomized Controlled Trials as Topic ; Acetates/analysis ; Female ; Gastrointestinal Microbiome ; Biomarkers/analysis ; Male ; Adult ; Case-Control Studies ; }, abstract = {CONTEXT: Short-chain fatty acids (SCFAs) have been reported to be associated with the pathogenesis of irritable bowel syndrome (IBS), but the results are conflicting.

OBJECTIVE: Here, a systematic review of case-control studies detecting fecal SCFAs in IBS patients compared with healthy controls (HCs) and self-controlled studies or randomized controlled trials (RCTs) investigating fecal SCFA alterations after interventions were identified from several databases.

DATA SOURCES: A systematic search of databases (PubMed, Web of Science, and Embase) identified 21 studies published before 24 February 2023. Data extractions: Three independent reviewers completed the relevant data extraction.

DATA ANALYSIS: It was found that the fecal propionate concentration in IBS patients was significantly higher than that in HCs, while the acetate proportion was significantly lower. Low-FODMAP diets significantly reduced the fecal propionate concentration in the IBS patients while fecal microbiota transplantation and probiotic administration did not significantly change the fecal propionate concentration or acetate proportion.

CONCLUSIONS: The results suggested that the fecal propionate concentration and acetate proportion could be used as biomarkers for IBS diagnosis. A low-FODMAP diet intervention could potentially serve as a treatment for IBS while FMT and probiotic administration need more robust trials.}, } @article {pmid38892602, year = {2024}, author = {Popov, J and Despot, T and Avelar Rodriguez, D and Khan, I and Mech, E and Khan, M and Bojadzija, M and Pai, N}, title = {Implications of Microbiota and Immune System in Development and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Nutrients}, volume = {16}, number = {11}, pages = {}, pmid = {38892602}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Disease Progression ; Fecal Microbiota Transplantation ; Immune System/metabolism ; Probiotics/therapeutic use ; Fatty Liver/microbiology/immunology ; Animals ; Non-alcoholic Fatty Liver Disease/microbiology/immunology/metabolism ; Anti-Bacterial Agents/therapeutic use ; Liver/metabolism ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent type of liver disease worldwide. The exact pathophysiology behind MASLD remains unclear; however, it is thought that a combination of factors or "hits" act as precipitants for disease onset and progression. Abundant evidence supports the roles of diet, genes, metabolic dysregulation, and the intestinal microbiome in influencing the accumulation of lipids in hepatocytes and subsequent progression to inflammation and fibrosis. Currently, there is no cure for MASLD, but lifestyle changes have been the prevailing cornerstones of management. Research is now focusing on the intestinal microbiome as a potential therapeutic target for MASLD, with the spotlight shifting to probiotics, antibiotics, and fecal microbiota transplantation. In this review, we provide an overview of how intestinal microbiota interact with the immune system to contribute to the pathogenesis of MASLD and metabolic dysfunction-associated steatohepatitis (MASH). We also summarize key microbial taxa implicated in the disease and discuss evidence supporting microbial-targeted therapies in its management.}, } @article {pmid38892281, year = {2024}, author = {Bose, D and Saha, P and Roy, S and Trivedi, A and More, M and Klimas, N and Tuteja, A and Chatterjee, S}, title = {A Double-Humanized Mouse Model for Studying Host Gut Microbiome-Immune Interactions in Gulf War Illness.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38892281}, issn = {1422-0067}, support = {I01CX0001923//United States Department of Veterans Affairs/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Persian Gulf Syndrome/immunology/microbiology ; Humans ; Mice ; *Disease Models, Animal ; *Cytokines/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Unraveling the multisymptomatic Gulf War Illness (GWI) pathology and finding an effective cure have eluded researchers for decades. The chronic symptom persistence and limitations for studying the etiologies in mouse models that differ significantly from those in humans pose challenges for drug discovery and finding effective therapeutic regimens. The GWI exposome differs significantly in the study cohorts, and the above makes it difficult to recreate a model closely resembling the GWI symptom pathology. We have used a double engraftment strategy for reconstituting a human immune system coupled with human microbiome transfer to create a humanized-mouse model for GWI. Using whole-genome shotgun sequencing and blood immune cytokine enzyme linked immunosorbent assay (ELISA), we show that our double humanized mice treated with Gulf War (GW) chemicals show significantly altered gut microbiomes, similar to those reported in a Veteran cohort of GWI. The results also showed similar cytokine profiles, such as increased levels of IL-1β, IL-6, and TNF R-1, in the double humanized model, as found previously in a human cohort. Further, a novel GWI Veteran fecal microbiota transfer was used to create a second alternative model that closely resembled the microbiome and immune-system-associated pathology of a GWI Veteran. A GWI Veteran microbiota transplant in humanized mice showed a human microbiome reconstitution and a systemic inflammatory pathology, as reflected by increases in interleukins 1β, 6, 8 (IL-1β, IL-6, IL-8), tumor necrosis factor receptor 1 (TNF R-1), and endotoxemia. In conclusion, though preliminary, we report a novel in vivo model with a human microbiome reconstitution and an engrafted human immune phenotype that may help to better understand gut-immune interactions in GWI.}, } @article {pmid38891979, year = {2024}, author = {Gavriilaki, E and Christoforidi, M and Ouranos, K and Minti, F and Mallouri, D and Varelas, C and Lazaridou, A and Baldoumi, E and Panteliadou, A and Bousiou, Z and Batsis, I and Sakellari, I and Gioula, G}, title = {Alteration of Gut Microbiota Composition and Diversity in Acute and/or Chronic Graft-versus-Host Disease Following Hematopoietic Stem Cell Transplantation: A Prospective Cohort Study.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38891979}, issn = {1422-0067}, mesh = {*Graft vs Host Disease/microbiology/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; Chronic Disease ; Feces/microbiology ; Transplantation, Homologous/adverse effects ; Acute Disease ; Young Adult ; Aged ; Bacteria/classification/isolation & purification/genetics ; Bronchiolitis Obliterans Syndrome ; }, abstract = {Changes in gut microbiome composition have been implicated in the pathogenesis of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our objective was to explore the microbial abundance in patients with GvHD after allo-HSCT. We conducted a single-center, prospective study in patients who underwent allo-HSCT and developed grade II or higher acute GvHD and/or moderate or severe chronic GvHD, to explore the microbial abundance of taxa at the phylum, family, genus, and species level, and we utilized alpha and beta diversity indices to further describe our findings. We collected fecal specimens at -2 to +2 (T1), +11 to +17 (T2), +25 to +30 (T3), +90 (T4), and +180 (T5) days to assess changes in gut microbiota, with day 0 being the day of allo-HSCT. We included 20 allo-HSCT recipients in the study. Compared with timepoint T1, at timepoint T4 we found a significant decrease in the abundance of Proteobacteria phylum (14.22% at T1 vs. 4.07% at T4, p = 0.01) and Enterobacteriaceae family (13.3% at T1 vs. <0.05% at T4, p < 0.05), as well as a significant increase in Enterococcus species (0.1% at T1 vs. 12.8% at T4, p < 0.05) in patients who developed acute GvHD. Regarding patients who developed chronic GvHD after allo-HSCT, there was a significant reduction in the abundance of Eurobactereaceae family (1.32% at T1 vs. 0.53% at T4, p < 0.05) and Roseruria genus (3.97% at T1 vs. 0.09% at T4, p < 0.05) at T4 compared with T1. Alpha and beta diversity analyses did not reveal a difference in the abundance of bacteria at the genus level in GvHD patients at T4 compared with T1. Our study reinforces results from previous studies regarding changes in gut microbiota in patients with acute GvHD and provides new data regarding the gut microbiome changes in chronic GvHD. Future studies will need to incorporate clinical parameters in their analyses to establish their association with specific changes in gut microbiota in patients with GvHD after allo-HSCT.}, } @article {pmid38891970, year = {2024}, author = {Averina, OV and Poluektova, EU and Zorkina, YA and Kovtun, AS and Danilenko, VN}, title = {Human Gut Microbiota for Diagnosis and Treatment of Depression.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38891970}, issn = {1422-0067}, support = {20-14-00132//Russian Science Foundation/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Depression/therapy/microbiology/diagnosis ; *Probiotics/therapeutic use ; Biomarkers ; Fecal Microbiota Transplantation ; Brain-Gut Axis ; Prebiotics/administration & dosage ; }, abstract = {Nowadays, depressive disorder is spreading rapidly all over the world. Therefore, attention to the studies of the pathogenesis of the disease in order to find novel ways of early diagnosis and treatment is increasing among the scientific and medical communities. Special attention is drawn to a biomarker and therapeutic strategy through the microbiota-gut-brain axis. It is known that the symbiotic interactions between the gut microbes and the host can affect mental health. The review analyzes the mechanisms and ways of action of the gut microbiota on the pathophysiology of depression. The possibility of using knowledge about the taxonomic composition and metabolic profile of the microbiota of patients with depression to select gene compositions (metagenomic signature) as biomarkers of the disease is evaluated. The use of in silico technologies (machine learning) for the diagnosis of depression based on the biomarkers of the gut microbiota is given. Alternative approaches to the treatment of depression are being considered by balancing the microbial composition through dietary modifications and the use of additives, namely probiotics, postbiotics (including vesicles) and prebiotics as psychobiotics, and fecal transplantation. The bacterium Faecalibacterium prausnitzii is under consideration as a promising new-generation probiotic and auxiliary diagnostic biomarker of depression. The analysis conducted in this review may be useful for clinical practice and pharmacology.}, } @article {pmid38889450, year = {2024}, author = {Zhang, H and Li, C and Han, L and Xiao, Y and Bian, J and Liu, C and Gong, L and Liu, Z and Wang, M}, title = {MUP1 mediates urolithin A alleviation of chronic alcohol-related liver disease via gut-microbiota-liver axis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2367342}, doi = {10.1080/19490976.2024.2367342}, pmid = {38889450}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; Mice ; *Liver/metabolism/drug effects ; *Liver Diseases, Alcoholic/microbiology/metabolism/prevention & control ; Male ; *Endoplasmic Reticulum Stress/drug effects ; *Mice, Inbred C57BL ; *Coumarins/pharmacology/metabolism ; Dysbiosis/microbiology ; Humans ; Bacteria/metabolism/classification/genetics/isolation & purification ; }, abstract = {Alcohol-related liver disease (ALD) is recognized as a global health crisis, contributing to approximately 20% of liver cancer-associated fatalities. Dysbiosis of the gut microbiome is associated with the development of ALD, with the gut microbial metabolite urolithin A (UA) exhibiting a potential for alleviating liver symptoms. However, the protective efficacy of UA against ALD and its underlying mechanism mediated by microbiota remain elusive. In this study, we provide evidence demonstrating that UA effectively ameliorates alcohol-induced metabolic disorders and hepatic endoplasmic reticulum (ER) stress through a specific gut-microbiota-liver axis mediated by major urinary protein 1 (MUP1). Moreover, UA exhibited the potential to restore alcohol-induced dysbiosis of the intestinal microbiota by enriching the abundance of Bacteroides sartorii (B. sartorii), Parabacteroides distasonis (P. distasonis), and Akkermansia muciniphila (A. muciniphila), along with their derived metabolite propionic acid. Partial attenuation of the hepatoprotective effects exerted by UA was observed upon depletion of gut microbiota using antibiotics. Subsequently, a fecal microbiota transplantation (FMT) experiment was conducted to evaluate the microbiota-dependent effects of UA in ALD. FMT derived from mice treated with UA exhibited comparable efficacy to direct UA treatment, as it effectively attenuated ER stress through modulation of MUP1. It was noteworthy that strong associations were observed among the hepatic MUP1, gut microbiome, and metabolome profiles affected by UA. Intriguingly, oral administration of UA-enriched B. sartorii, P. distasonis, and A. muciniphila can enhance propionic acid production to effectively suppress ER stress via MUP1, mimicking UA treatment. Collectively, these findings elucidate the causal mechanism that UA alleviated ALD through the gut-microbiota-liver axis. This unique mechanism sheds light on developing novel microbiome-targeted therapeutic strategies against ALD.}, } @article {pmid38886569, year = {2024}, author = {Lin, G and Zhang, F and Weng, X and Hong, Z and Ye, D and Wang, G}, title = {Role of gut microbiota in the pathogenesis of castration-resistant prostate cancer: a comprehensive study using sequencing and animal models.}, journal = {Oncogene}, volume = {}, number = {}, pages = {}, pmid = {38886569}, issn = {1476-5594}, abstract = {CRPC remains a significant challenge in prostate cancer research. We aimed to elucidate the role of gut microbiota and its specific mechanisms in CRPC using a multidisciplinary approach. We analyzed 16S rRNA sequencing data from mouse fecal samples, revealing substantial differences in gut microbiota composition between CRPC and castration-sensitive prostate cancer mice, particularly in Firmicutes and Bacteroidetes. Functional analysis suggested different bacteria may influence CRPC via the α-linolenic acid metabolism pathway. In vivo, experiments utilizing mouse models and fecal microbiota transplantation (FMT) demonstrated that FMT from healthy control mice could decelerate tumor growth in CRPC mice, reduce TNF-α levels, and inhibit the activation of the TLR4/MyD88/NF-κB signaling pathway. Transcriptome sequencing identified crucial genes and pathways, with rescue experiments confirming the gut microbiota's role in modulating CRPC progression through the TLR4/MyD88/NF-κB pathway. The activation of this pathway by TNF-α has been corroborated by in vitro cell experiments, indicating its role in promoting prostate cancer cell proliferation, migration, and invasion while inhibiting apoptosis. Gut microbiota dysbiosis may promote CRPC development through TNF-α activation of the TLR4/MyD88/NF-κB signaling pathway, potentially linked to α-linolenic acid metabolism.}, } @article {pmid38885604, year = {2024}, author = {Balasundaram, D and Veerasamy, V and Sylvia Singarayar, M and Neethirajan, V and Ananth Devanesan, A and Thilagar, S}, title = {Therapeutic potential of probiotics in gut microbial homeostasis and Rheumatoid arthritis.}, journal = {International immunopharmacology}, volume = {137}, number = {}, pages = {112501}, doi = {10.1016/j.intimp.2024.112501}, pmid = {38885604}, issn = {1878-1705}, abstract = {Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint damage. Existing treatment options primarily focus on managing symptoms and slowing disease progression, often with side effects and limitations. The gut microbiome, a vast community of microorganisms present in the gastrointestinal tract, plays a crucial role in health and disease. Recent research suggests a bidirectional relationship between the gut microbiome and RA, highlighting its potential as a therapeutic option. This review focuses on the interaction between the gut microbiome and RA development, by discussing how dysbiosis, an imbalance in gut bacteria, can contribute to RA through multiple mechanisms such as molecular mimicry, leaky gut, and metabolic dysregulation. Probiotics, live microorganisms with health benefits, are emerging as promising tools for managing RA. They can prevent the negative effects of dysbiosis by displacing harmful bacteria, producing anti-inflammatory metabolites like short-chain fatty acids (SCFA), Directly influencing immune cells, and modifying host metabolism. animal and clinical studies demonstrate the potential of probiotics in improving RA symptoms and disease outcomes. However, further research is needed to optimize probiotic strains, dosages, and treatment protocols for personalized and effective management of RA. This review summarizes the current understanding of the gut microbiome and its role in RA and discusses future research directions. In addition to the established role of gut dysbiosis in RA, emerging strategies like fecal microbiota transplantation, prebiotics, and postbiotics offer exciting possibilities. However, individual variations in gut composition necessitate personalized treatment plans. Long-term effects and clear regulations need to be established. Future research focusing on metagenomic analysis, combination therapies, and mechanistic understanding will unlock the full potential of gut microbiome modulation for effective RA management.}, } @article {pmid38885258, year = {2024}, author = {Ma, X and Shin, YJ and Yun, SW and Jang, SW and Han, SW and Kim, DH}, title = {Probiotic LB101 alleviates dry eye in mice by suppressing matrix metalloproteinase-9 expression through the regulation of gut microbiota-involved NF-κB signaling.}, journal = {PloS one}, volume = {19}, number = {6}, pages = {e0303423}, pmid = {38885258}, issn = {1932-6203}, mesh = {Animals ; *Matrix Metalloproteinase 9/metabolism ; *Dry Eye Syndromes/metabolism/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Mice ; *NF-kappa B/metabolism ; *Probiotics/pharmacology/administration & dosage ; *Signal Transduction/drug effects ; Mice, Inbred C57BL ; Tears/metabolism ; Fecal Microbiota Transplantation ; Tumor Necrosis Factor-alpha/metabolism ; Conjunctiva/metabolism/microbiology/pathology ; }, abstract = {Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1β, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1β, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1β expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1β with the regulation of gut microbiota-involved NF-κB signaling.}, } @article {pmid38879538, year = {2024}, author = {Hu, L and Sun, L and Yang, C and Zhang, DW and Wei, YY and Yang, MM and Wu, HM and Fei, GH}, title = {Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {570}, pmid = {38879538}, issn = {1479-5876}, support = {82170050//National Natural Science Foundation of China/ ; 202304295107020038//Anhui Province clinical medical research transformation project/ ; 2023AH010082//Anhui university excellent research and innovation team plan/ ; 2020xkjT061//Anhui Medical University scientific research platform base construction promotion plan/ ; }, mesh = {Animals ; *Tight Junctions/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Acetates/metabolism ; Humans ; *Lung Injury ; *Orthomyxoviridae Infections/complications ; Mice, Inbred C57BL ; Influenza A virus ; Fecal Microbiota Transplantation ; Receptors, G-Protein-Coupled/metabolism ; Mice ; Epithelial Cells/metabolism ; Dysbiosis ; Fatty Acids, Volatile/metabolism ; }, abstract = {BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown.

METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA).

RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1β). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner.

CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.}, } @article {pmid38879003, year = {2024}, author = {Wu, J and Chen, X and Qian, J and Li, G}, title = {Clinical improvement effect of regulating gut microbiota on metabolic dysfunction-associated steatotic liver disease: systematic review and meta-analysis of randomized controlled trials.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {}, number = {}, pages = {102397}, doi = {10.1016/j.clinre.2024.102397}, pmid = {38879003}, issn = {2210-741X}, abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is constantly rising globally. There are barely any effective medications or supplements for the management of MASLD. We aim to systematically evaluate the most current evidence for gut microbiota-regulating supplements in patients with MASLD.

METHODS: We searched multiple electronic data for randomized controlled trials (RCTs) published from January 1, 2012, to July 15, 2023. The intervention measures included probiotics, prebiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The control group was treated with a placebo or usual care. The intervention duration was divided into two periods (>12 weeks and ≤12 weeks). Adequate evaluation data for antibiotics and FMT have not been obtained. Therefore, the other three microbiota regulators are the primary evaluation measures in this study.

RESULTS: We found that probiotics alone could not improve clinical indicators in MASLD patients. However, synbiotics exhibited an improvement in reducing liver steatosis, TNF-ɑ levels, and increasing HDL-c levels, and the inflammatory markers of liver cells (ALT and AST) were also improved. For the effective intervention duration, this systematic review suggested that around 12 weeks is an ideal intervention cycle for MASLD patients.

CONCLUSIONS: This meta-analysis supported the modulation of gut microbiota with synbiotics in the management of MASLD.}, } @article {pmid38878554, year = {2024}, author = {Mincic, AM and Antal, M and Filip, L and Miere, D}, title = {Modulation of gut microbiome in the treatment of neurodegenerative diseases: A systematic review.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {7}, pages = {1832-1849}, doi = {10.1016/j.clnu.2024.05.036}, pmid = {38878554}, issn = {1532-1983}, abstract = {BACKGROUND AND AIMS: Microbiota plays an essential role in maintaining body health, through positive influences on metabolic, defensive, and trophic processes and on intercellular communication. Imbalance in intestinal flora, with the proliferation of harmful bacterial species (dysbiosis) is consistently reported in chronic illnesses, including neurodegenerative diseases (ND). Correcting dysbiosis can have a beneficial impact on the symptoms and evolution of ND. This review examines the effects of microbiota modulation through administration of probiotics, prebiotics, symbiotics, or prebiotics' metabolites (postbiotics) in patients with ND like multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).

METHODS: PubMed, Web of Science, Medline databases and ClinicalTrials.gov registry searches were performed using pre-/pro-/postbiotics and ND-related terms. Further references were obtained by checking relevant articles.

RESULTS: Although few compared to animal studies, the human studies generally show positive effects on disease-specific symptoms, overall health, metabolic parameters, on oxidative stress and immunological markers. Therapy with probiotics in various forms (mixtures of bacterial strains, fecal microbiota transplant, diets rich in fermented foods) exert favorable effects on patients' mental health, cognition, and quality of life, targeting pathogenetic ND mechanisms and inducing reparatory mechanisms at the cellular level. More encouraging results have been observed in prebiotic/postbiotic therapy in some ND.

CONCLUSIONS: The effects of probiotic-related interventions depend on the patients' ND stage and pre-existing allopathic medication. Further studies on larger cohorts and long term comprehensive neuropsychiatric, metabolic, biochemical testing, and neuroimaging monitoring are necessary to optimize therapeutic protocols in ND.}, } @article {pmid38878524, year = {2024}, author = {Jia, R and Shao, S and Zhang, P and Yuan, Y and Rong, W and An, Z and Lv, S and Feng, Y and Liu, N and Feng, Q and Wang, Y and Li, Q}, title = {PRM1201 effectively inhibits colorectal cancer metastasis via shaping gut microbiota and short- chain fatty acids.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {132}, number = {}, pages = {155795}, doi = {10.1016/j.phymed.2024.155795}, pmid = {38878524}, issn = {1618-095X}, abstract = {BACKGROUND: PRM1201 is a traditional medicine with beneficial effects against colorectal cancer (CRC) metastasis. However, the underlying mechanism of this action remains to be determined.

HYPOTHESIS: Remodeling microbiota and short-chain fatty acids (SCFAs) metabolism might be a potential mechanism to explain the anti-metastatic action of PRM1201, as this gut-microbiota dependent effect involves downregulation of histone deacetylation and EMT.

METHODS: To investigate this possibility, clinical specimens were sequenced and the correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFA-producing bacteria was studied. To obtain solid causal evidence, a mouse metastasis model was established to detect the influence of PRM1201 on cancer metastasis. Specifically, 16S amplicon sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, and bacterial manipulation were used to examine the gut microbiota-driven anti-metastatic action of PRM1201.

RESULTS: Clinical data showed that PRM1201 increased both the number of SCFA-producing bacteria and generation of SCFAs in the feces of CRC patients. A positive correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFAs observed. The animal experiments demonstrated that PRM1201 effectively blocked CRC metastasis in a dose-dependent manner. PRM1201 treatment modulated the composition of gut microbiota, and promoted the proliferation of beneficial SCFAs producers such as Akkermansia, Lachnospiraceae_NK4A136_group and Blautia, while simultaneously reducing the abundance of pathogenic bacteria like Escherichia-Shigella. In addition, PRM1201 led to augmentation of SCFAs content. Further results indicated that the anti-cancer metastatic mechanism of PRM1201 was linked to inhibition of histone deacetylation and suppression of epithelial-to-mesenchymal transition (EMT) in metastatic lesions. Microbiota depletion treatment and fecal microbiota transplantation (FMT) underscored the microbiota-dependent nature of this phenomenon. Moreover, this anti-colorectal cancer metastatic effect and mechanism of total SCFAs and single SCFA were also confirmed.

CONCLUSION: In summary, PRM1201 exerts its anti-metastatic effects by modulating SCFA-producing bacteria and enhancing the production of SCFAs. Furthermore, the prebiotic-like actions of PRM1201, along with the PRM1201-treated bacteria, function as inhibitors of histone deacetylases (DHACs) thereby effectively suppressing EMT events.}, } @article {pmid38878076, year = {2024}, author = {Jawanda, IK and Soni, T and Kumari, S and Prabha, V}, title = {The evolving facets of vaginal microbiota transplantation: reinvigorating the unexplored frontier amid complex challenges.}, journal = {Archives of microbiology}, volume = {206}, number = {7}, pages = {306}, pmid = {38878076}, issn = {1432-072X}, mesh = {Humans ; *Vagina/microbiology ; Female ; *Microbiota ; *Probiotics/administration & dosage ; *Dysbiosis/microbiology/therapy ; Animals ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Lactobacillus ; }, abstract = {In an age of cutting-edge sequencing methods and worldwide endeavors such as The Human Microbiome Project and MetaHIT, the human microbiome stands as a complex and diverse community of microorganisms. A central theme in current scientific inquiry revolves around reinstating a balanced microbial composition, referred to as "eubiosis," as a targeted approach for treating vast array of diseases. Vaginal Microbiota Transplantation (VMT), inspired by the success of fecal microbiota transplantation, emerges as an innovative therapy addressing vaginal dysbacteriosis by transferring the complete microbiota from a healthy donor. Antibiotics, while effective, pose challenges with adverse effects, high recurrence rates, and potential harm to beneficial Lactobacillus strains. Continued antibiotic usage also sparks worries regarding the development of resistant strains. Probiotics, though showing promise, exhibit inconsistency in treating multifactorial diseases, and concerns linger about their suitability for diverse genetic backgrounds. Given the recurrent challenges associated with antibiotic and probiotic treatments, VMT emerges as an imperative alternative, offering a unique and promising avenue for efficiently and reliably managing vaginal dysbiosis among a majority of women. This review critically evaluates findings from both animal and human studies, offering nuanced insights into the efficacy and challenges of VMT. An extensive analysis of clinical trials, provides a current overview of ongoing and completed trials, shedding light on the evolving clinical landscape and therapeutic potential of VMT. Delving into the origins, mechanisms, and optimized protocols of VMT, the review underscores the imperative for sustained research efforts to advance this groundbreaking gynecological therapy.}, } @article {pmid38877311, year = {2024}, author = {Mu, YF and Gao, ZX and Mao, ZH and Pan, SK and Liu, DW and Liu, ZS and Wu, P}, title = {Perspectives on the involvement of the gut microbiota in salt-sensitive hypertension.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {}, number = {}, pages = {}, pmid = {38877311}, issn = {1348-4214}, abstract = {Salt-sensitivity hypertension (SSH) is an independent predictor of cardiovascular event-related death. Despite the extensiveness of research on hypertension, which covers areas such as the sympathetic nervous system, the renin-angiotensin system, the vascular system, and the immune system, its pathogenesis remains elusive, with sub-optimal blood pressure control in patients. The gut microbiota is an important component of nutritional support and constitutes a barrier in the host. Long-term high salt intake can lead to gut microbiota dysbiosis and cause significant changes in the expression of gut microbiota-related metabolites. Of these metabolites, short chain fatty acids (SCFAs), trimethylamine oxide, amino acids, bile acids, and lipopolysaccharide are essential mediators of microbe-host crosstalk. These metabolites may contribute to the incidence and development of SSH via inflammatory, immune, vascular, and nervous pathways, among others. In addition, recent studies, including those on the histone deacetylase inhibitory mechanism of SCFAs and the blood pressure-decreasing effects of H2S via vascular activation, suggest that several proteins and factors in the classical pathway elicit their effects through multiple non-classical pathways. This review summarizes changes in the gut microbiota and its related metabolites in high-salt environments, as well as corresponding treatment methods for SSH, such as diet management, probiotic and prebiotic use, antibiotic use, and fecal transplantation, to provide new insights and perspectives for understanding SSH pathogenesis and the development of strategies for its treatment.}, } @article {pmid38874788, year = {2024}, author = {Hazra, R and Chattopadhyay, S and Mallick, A and Gayen, S and Roy, S}, title = {Revealing the therapeutic properties of gut microbiota: transforming cancer immunotherapy from basic to clinical approaches.}, journal = {Medical oncology (Northwood, London, England)}, volume = {41}, number = {7}, pages = {175}, pmid = {38874788}, issn = {1559-131X}, mesh = {*Gastrointestinal Microbiome/immunology ; Humans ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology ; Fecal Microbiota Transplantation/methods ; Immune Checkpoint Inhibitors/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {The immune system plays a pivotal role in the battle against cancer, serving as a formidable guardian in the ongoing fight against malignant cells. To combat these malignant cells, immunotherapy has emerged as a prevalent approach leveraging antibodies and peptides such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 to inhibit immune checkpoints and activate T lymphocytes. The optimization of gut microbiota plays a significant role in modulating the defense system in the body. This study explores the potential of certain gut-resident bacteria to amplify the impact of immunotherapy. Contemporary antibiotic treatments, which can impair gut flora, may diminish the efficacy of immune checkpoint blockers. Conversely, probiotics or fecal microbiota transplantation can help re-establish intestinal microflora equilibrium. Additionally, the gut microbiome has been implicated in various strategies to counteract immune resistance, thereby enhancing the success of cancer immunotherapy. This paper also acknowledges cutting-edge technologies such as nanotechnology, CAR-T therapy, ACT therapy, and oncolytic viruses in modulating gut microbiota. Thus, an exhaustive review of literature was performed to uncover the elusive link that could potentiate the gut microbiome's role in augmenting the success of cancer immunotherapy.}, } @article {pmid38780275, year = {2024}, author = {Cai, L and Wang, X and Zhu, X and Xu, Y and Qin, W and Ren, J and Jiang, Q and Yan, X}, title = {Lactobacillus-derived protoporphyrin IX and SCFAs regulate the fiber size via glucose metabolism in the skeletal muscle of chickens.}, journal = {mSystems}, volume = {9}, number = {6}, pages = {e0021424}, doi = {10.1128/msystems.00214-24}, pmid = {38780275}, issn = {2379-5077}, support = {2023YFD1301304//the National Key Research and Development Project/ ; Project 2662023DKPY002//MOE | Fundamental Research Funds for the Central Universities (Fundamental Research Fund for the Central Universities)/ ; 2019TQ0108//China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)/ ; }, mesh = {Animals ; *Chickens/metabolism/microbiology ; *Glucose/metabolism ; *Gastrointestinal Microbiome/physiology ; *Fatty Acids, Volatile/metabolism ; *Lactobacillus/metabolism ; Muscle, Skeletal/metabolism ; Muscle Fibers, Skeletal/metabolism ; Energy Metabolism ; Fecal Microbiota Transplantation ; }, abstract = {The gut microbiota contributes to skeletal muscle energy metabolism and is an indirect factor affecting meat quality. However, the role of specific gut microbes in energy metabolism and fiber size of skeletal muscle in chickens remains largely unknown. In this study, we first performed cecal microbiota transplantation from Chinese indigenous Jingyuan chickens (JY) to Arbor Acres chickens (AA), to determine the effects of microbiota on skeletal muscle fiber and energy metabolism. Then, we used metagenomics, gas chromatography, and metabolomics analysis to identify functional microbes. Finally, we validated the role of these functional microbes in regulating the fiber size via glucose metabolism in the skeletal muscle of chickens through feeding experiments. The results showed that the skeletal muscle characteristics of AA after microbiota transplantation tended to be consistent with that of JY, as the fiber diameter was significantly increased, and glucose metabolism level was significantly enhanced in the pectoralis muscle. L. plantarum, L. ingluviei, L. salivarius, and their mixture could increase the production of the microbial metabolites protoporphyrin IX and short-chain fatty acids, therefore increasing the expression levels of genes related to the oxidative fiber type (MyHC SM and MyHC FRM), mitochondrial function (Tfam and CoxVa), and glucose metabolism (PFK, PK, PDH, IDH, and SDH), thereby increasing the fiber diameter and density. These three Lactobacillus species could be promising probiotics to improve the meat quality of chicken.IMPORTANCEThis study revealed that the L. plantarum, L. ingluviei, and L. salivarius could enhance the production of protoporphyrin IX and short-chain fatty acids in the cecum of chickens, improving glucose metabolism, and finally cause the increase in fiber diameter and density of skeletal muscle. These three microbes could be potential probiotic candidates to regulate glucose metabolism in skeletal muscle to improve the meat quality of chicken in broiler production.}, } @article {pmid38874578, year = {2024}, author = {Liu, H and Yan, C and Teng, Y and Guo, J and Liang, C and Xia, X}, title = {Gut microbiota and D-ribose mediate the anti-colitic effect of punicalagin in DSS-treated mice.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo00741g}, pmid = {38874578}, issn = {2042-650X}, abstract = {Background: Inflammatory bowel disease (IBD) is an increasing health burden worldwide. Punicalagin, a bioactive component rich in pomegranate rind, has been shown to attenuate chemical or bacteria-induced experimental colitis in mice, but whether punicalagin exerts its function through modulating gut microbiota and metabolites remains unexplored. Results: Punicalagin (100 mg per kg per day) administered orally to mice alleviated dextran-sodium sulfate (DSS)-induced colitis. Gut microbiota analyzed by 16S rRNA sequencing showed that punicalagin altered gut microbiota by increasing the Lachnospiraceae_NK4A136_group and Bifidobacterium abundance. To evaluate the effect of punicalagin-modulated microbiota and its metabolites in colitis mice, we transplanted fecal microbiota and sterile fecal filtrate (SFF) to mice treated with oral antibiotics. The results of fecal microbiota transplantation (FMT) demonstrated that punicalagin's anti-colitic effect is transferable by transplanting punicalagin-modulated gut microbiota and its metabolites. Additionally, we discovered that punicalagin-modulated sterile fecal filtrate also exhibits anti-colitis effects, as evidenced by improved intestinal barrier integrity and decreased inflammation. Subsequently, fecal metabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). The analysis revealed that punicalagin significantly increased the level of D-ribose. In vitro experiments showed that D-ribose has both anti-inflammatory and antioxidant properties. Furthermore, D-ribose significantly mitigated DSS-induced colitis symptoms in mice. Conclusions: Overall, this study demonstrated that gut microbiota and its metabolites partly mediate the protective effect of punicalagin against DSS-induced colitis in mice. D-ribose is a key metabolite that contributes to the anti-colitic effect of punicalagin in mice.}, } @article {pmid38874442, year = {2024}, author = {Bulnes, R and Utay, NS}, title = {Therapeutic microbiome modulation: new frontiers in HIV treatment.}, journal = {Current opinion in HIV and AIDS}, volume = {}, number = {}, pages = {}, doi = {10.1097/COH.0000000000000864}, pmid = {38874442}, issn = {1746-6318}, abstract = {PURPOSE OF REVIEW: Dysbiosis may be a key driver of systemic inflammation, which increases the risk of non-AIDS events in people living with HIV (PLWH). Modulation of the microbiome to reverse this dysbiosis may be a novel approach to decrease inflammation and therefore morbidity and mortality in PLWH.

RECENT FINDINGS: Fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, postbiotics, and dietary modifications have the potential to modulate the microbiome. These interventions have been well tolerated in clinical trials to date. However, these interventions have not resulted in consistent or lasting changes to the microbiome or consistent changes in biomarkers of intestinal permeability, microbial translocation, inflammation, immune activation, or CD4+ T cell counts. Sustained engraftment may require prebiotics and/or dietary modifications added to either probiotics or FMT.

SUMMARY: Adequately powered randomized controlled trials are needed to elucidate whether microbiome modulation can be achieved and impact systemic inflammation in PLWH.}, } @article {pmid38873648, year = {2024}, author = {Levy, B and Fliss Isakov, N and Ziv-Baran, T and Leshno, M and Maharshak, N and Werner, L}, title = {Economic and Chronologic Optimization of Fecal Donors Screening Process.}, journal = {MDM policy & practice}, volume = {9}, number = {1}, pages = {23814683241254809}, pmid = {38873648}, issn = {2381-4683}, abstract = {UNLABELLED: Background. Fecal microbial transplantation (FMT) is the delivery of fecal microbiome, isolated from healthy donors, into a patient's gastrointestinal tract. FMT is a safe and efficient treatment for recurrent Clostridioides difficile infection. Donors undergo strict screening to avoid disease transmission. This consists of several blood and stool tests, which are performed in a multistage, costly process. We performed a cost-minimizing analysis to find the optimal order in which the tests should be performed. Methods. An algorithm to optimize the order of tests in terms of cost was defined. Performance analysis for disqualifying a potential healthy donor was carried out on data sets based on either the published literature or our real-life data. For both data sets, we calculated the total cost to qualify a single donor according to the optimal order of tests, suggested by the algorithm. Results. Applying the algorithm to the published literature revealed potential savings of 94.2% of the cost of screening a potential donor and 7.05% of the cost to qualify a single donor. In our cohort of 87 volunteers, 53 were not eligible for donation. Of 34 potential donors, 10 were disqualified due to abnormal lab tests. Applying our algorithm to optimize the order of tests, the average cost for screening a potential donor resulted in potential savings of 49.9% and a 21.3% savings in the cost to qualify a single donor. Conclusions. Improving the order and timing of the screening tests of potential FMT stool donors can decrease the costs by about 50% per subject.

HIGHLIGHTS: What is known:Fecal microbial transplantation (FMT) is the transfer of microbiome from healthy donors to patients.Fecal donors undergo multiple strict screening tests to exclude any transmissible disease.Screening tests of potential fecal donors is expensive and time consuming.FMT is the most efficient treatment for recurrent C difficile infection.What is new here:An algorithm to optimize the order of donors' screening tests in terms of cost was defined.Optimizing the order tests can save nearly 50% in costs of screening a potential donor.}, } @article {pmid38873568, year = {2024}, author = {Shang, Z and Pai, L and Patil, S}, title = {Unveiling the dynamics of gut microbial interactions: a review of dietary impact and precision nutrition in gastrointestinal health.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1395664}, pmid = {38873568}, issn = {2296-861X}, abstract = {The human microbiome, a dynamic ecosystem within the gastrointestinal tract, plays a pivotal role in shaping overall health. This review delves into six interconnected sections, unraveling the intricate relationship between diet, gut microbiota, and their profound impact on human health. The dance of nutrients in the gut orchestrates a complex symphony, influencing digestive processes and susceptibility to gastrointestinal disorders. Emphasizing the bidirectional communication between the gut and the brain, the Brain-Gut Axis section highlights the crucial role of dietary choices in physical, mental, and emotional well-being. Autoimmune diseases, particularly those manifesting in the gastrointestinal tract, reveal the delicate balance disrupted by gut microbiome imbalances. Strategies for reconciling gut microbes through diets, precision nutrition, and clinical indications showcase promising avenues for managing gastrointestinal distress and revolutionizing healthcare. From the Low-FODMAP diet to neuro-gut interventions, these strategies provide a holistic understanding of the gut's dynamic world. Precision nutrition, as a groundbreaking discipline, holds transformative potential by tailoring dietary recommendations to individual gut microbiota compositions, reshaping the landscape of gastrointestinal health. Recent advancements in clinical indications, including exact probiotics, fecal microbiota transplantation, and neuro-gut interventions, signify a new era where the gut microbiome actively participates in therapeutic strategies. As the microbiome takes center stage in healthcare, a paradigm shift toward personalized and effective treatments for gastrointestinal disorders emerges, reflecting the symbiotic relationship between the human body and its microbial companions.}, } @article {pmid38871148, year = {2024}, author = {Paaske, SE and Dahl Baumwall, SM and Rubak, T and Birn, FH and Rågård, N and Kelsen, J and Hansen, MM and Svenningsen, L and Krarup, AL and Culmbach Fernis, CM and Neumann, A and Lødrup, AB and Glerup, H and Vinter-Jensen, L and Helms, M and Erikstrup, LT and Grosen, AK and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Real-world effectiveness of fecal microbiota transplantation for first or second Clostridioides difficile infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.05.038}, pmid = {38871148}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Clostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting.

METHODS: This multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) eight weeks after the last FMT treatment. Secondary outcomes included CDAD cure one and eight weeks after the first FMT treatment and 90-day mortality following positive C. difficile test.

RESULTS: We included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range (IQR) 58-82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%, 95% confidence interval (CI) 71-79%) at week one. At week eight, 255 patients (55%, 95% CI 50-59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%, 95% CI 75-82%). The 90-day mortality was 10% (95% CI 8-14%).

CONCLUSION: Repeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival.}, } @article {pmid38870892, year = {2024}, author = {Dubois, L and Valles-Colomer, M and Ponsero, A and Helve, O and Andersson, S and Kolho, KL and Asnicar, F and Korpela, K and Salonen, A and Segata, N and de Vos, WM}, title = {Paternal and induced gut microbiota seeding complement mother-to-infant transmission.}, journal = {Cell host & microbe}, volume = {32}, number = {6}, pages = {1011-1024.e4}, doi = {10.1016/j.chom.2024.05.004}, pmid = {38870892}, issn = {1934-6069}, mesh = {Humans ; *Gastrointestinal Microbiome ; Female ; *Fecal Microbiota Transplantation ; Male ; Infant, Newborn ; Infant ; Fathers ; Mothers ; Feces/microbiology ; Cesarean Section ; Pregnancy ; Infectious Disease Transmission, Vertical ; Bacteria/genetics ; }, abstract = {Microbial colonization of the neonatal gut involves maternal seeding, which is partially disrupted in cesarean-born infants and after intrapartum antibiotic prophylaxis. However, other physically close individuals could complement such seeding. To assess the role of both parents and of induced seeding, we analyzed two longitudinal metagenomic datasets (health and early life microbiota [HELMi]: N = 74 infants, 398 samples, and SECFLOR: N = 7 infants, 35 samples) with cesarean-born infants who received maternal fecal microbiota transplantation (FMT). We found that the father constitutes a stable source of strains for the infant independently of the delivery mode, with the cumulative contribution becoming comparable to that of the mother after 1 year. Maternal FMT increased mother-infant strain sharing in cesarean-born infants, raising the average bacterial empirical growth rate while reducing pathogen colonization. Overall, our results indicate that maternal seeding is partly complemented by that of the father and support the potential of induced seeding to restore potential deviations in this process.}, } @article {pmid38868710, year = {2022}, author = {Hu, H and Tan, Y and Li, C and Chen, J and Kou, Y and Xu, ZZ and Liu, YY and Tan, Y and Dai, L}, title = {StrainPanDA: Linked reconstruction of strain composition and gene content profiles via pangenome-based decomposition of metagenomic data.}, journal = {iMeta}, volume = {1}, number = {3}, pages = {e41}, pmid = {38868710}, issn = {2770-596X}, abstract = {Microbial strains of variable functional capacities coexist in microbiomes. Current bioinformatics methods of strain analysis cannot provide the direct linkage between strain composition and their gene contents from metagenomic data. Here we present Strain-level Pangenome Decomposition Analysis (StrainPanDA), a novel method that uses the pangenome coverage profile of multiple metagenomic samples to simultaneously reconstruct the composition and gene content variation of coexisting strains in microbial communities. We systematically validate the accuracy and robustness of StrainPanDA using synthetic data sets. To demonstrate the power of gene-centric strain profiling, we then apply StrainPanDA to analyze the gut microbiome samples of infants, as well as patients treated with fecal microbiota transplantation. We show that the linked reconstruction of strain composition and gene content profiles is critical for understanding the relationship between microbial adaptation and strain-specific functions (e.g., nutrient utilization and pathogenicity). Finally, StrainPanDA has minimal requirements for computing resources and can be scaled to process multiple species in a community in parallel. In short, StrainPanDA can be applied to metagenomic data sets to detect the association between molecular functions and microbial/host phenotypes to formulate testable hypotheses and gain novel biological insights at the strain or subspecies level.}, } @article {pmid38868519, year = {2024}, author = {Wang, L and Tu, YX and Chen, L and Yu, KC and Wang, HK and Yang, SQ and Zhang, Y and Zhang, SJ and Song, S and Xu, HL and Yin, ZC and Feng, MQ and Yue, JQ and Huang, XH and Tang, T and Wei, SZ and Liang, XJ and Chen, ZX}, title = {Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway.}, journal = {iMeta}, volume = {3}, number = {1}, pages = {e165}, pmid = {38868519}, issn = {2770-596X}, abstract = {Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus. Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health.}, } @article {pmid38868343, year = {2023}, author = {Liu, J and Ding, M and Bai, J and Luo, R and Liu, R and Qu, J and Li, X}, title = {Decoding the role of immune T cells: A new territory for improvement of metabolic-associated fatty liver disease.}, journal = {iMeta}, volume = {2}, number = {1}, pages = {e76}, pmid = {38868343}, issn = {2770-596X}, abstract = {Metabolic-associated fatty liver disease (MAFLD) is a new emerging concept and is associated with metabolic dysfunction, generally replacing the name of nonalcoholic fatty liver disease (NAFLD) due to heterogeneous liver condition and inaccuracies in definition. The prevalence of MAFLD is rising by year due to dietary changes, metabolic disorders, and no approved therapy, affecting a quarter of the global population and representing a major economic problem that burdens healthcare systems. Currently, in addition to the common causative factors like insulin resistance, oxidative stress, and lipotoxicity, the role of immune cells, especially T cells, played in MAFLD is increasingly being emphasized by global scholars. Based on the diverse classification and pathophysiological effects of immune T cells, we comprehensively analyzed their bidirectional regulatory effects on the hepatic inflammatory microenvironment and MAFLD progression. This interaction between MAFLD and T cells was also associated with hepatic-intestinal immune crosstalk and gut microbiota homeostasis. Moreover, we pointed out several T-cell-based therapeutic approaches including but not limited to adoptive transfer of T cells, fecal microbiota transplantation, and drug therapy, especially for natural products and Chinese herbal prescriptions. Overall, this study contributes to a better understanding of the important role of T cells played in MAFLD progression and corresponding therapeutic options and provides a potential reference for further drug development.}, } @article {pmid38867928, year = {2023}, author = {Chen, AT and Zhang, J and Zhang, Y}, title = {Gut microbiota in heart failure and related interventions.}, journal = {iMeta}, volume = {2}, number = {3}, pages = {e125}, pmid = {38867928}, issn = {2770-596X}, abstract = {Heart failure (HF) is a sophisticated syndrome with structural or functional impairment of ventricular filling or ejection of blood, either causing symptoms and signs or being asymptomatic. HF is a major global health issue affecting about 64.3 million people worldwide. The gut microbiota refers to the complex ecosystem of microorganisms, mainly bacteria, in the gut. Studies have revealed that the gut microbiota is associated with many diseases ranging from neurodegenerative diseases to inflammatory bowel disease and cardiovascular diseases. The gut hypothesis of HF suggests that low cardiac output and systemic circulation congestion would cause insufficient intestinal perfusion, leading to ischemia and intestinal barrier dysfunction. The resulting bacterial translocation would contribute to inflammation. Recent studies have refined the hypothesis that changes of metabolites in the gut microbiota have a close relationship with HF. Thus, the gut microbiota has emerged as a potential therapeutic target for HF due to both its critical role in regulating host physiology and metabolism and its pivotal role in the development of HF. This review article aims to provide an overview of the current understanding of the gut microbiota's involvement in HF, including the introduction of the gut hypothesis of HF, its association with HF progression, the potential mechanisms involved mediated by the gut microbiota metabolites, and the impact of various interventions on the gut microbiota, including dietary interventions, probiotic therapy, fecal microbiota transplantation, antibiotics, and so on. While the gut hypothesis of HF is refined with up-to-date knowledge and the gut microbiota presents a promising target for HF therapy, further research is still needed to further understand the underlying mechanisms between gut microbiota and HF, the efficacy of these interventions, and contribute to the health of HF patients.}, } @article {pmid38867886, year = {2024}, author = {Jia, X and Wang, Q and Liu, M and Ding, JY}, title = {The interplay between gut microbiota and the brain-gut axis in Parkinson's disease treatment.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1415463}, pmid = {38867886}, issn = {1664-2295}, abstract = {This study delves into the pivotal role of the gut microbiota and the brain-gut axis in Parkinson's Disease (PD), a neurodegenerative disorder with significant motor and non-motor implications. It posits that disruptions in gut microbiota-dysbiosis-and alterations in the brain-gut axis contribute to PD's pathogenesis. Our findings highlight the potential of the gastrointestinal system's early involvement in PD, suggested by the precedence of gastrointestinal symptoms before motor symptoms emerge. This observation implies a possible gut-originated disease pathway. The analysis demonstrates that dysbiosis in PD patients leads to increased intestinal permeability and systemic inflammation, which in turn exacerbates neuroinflammation and neurodegeneration. Such insights into the interaction between gut microbiota and the brain-gut axis not only elucidate PD's underlying mechanisms but also pave the way for novel therapeutic interventions. We propose targeted treatment strategies, including dietary modifications and fecal microbiota transplantation, aimed at modulating the gut microbiota. These approaches hold promise for augmenting current PD treatment modalities by alleviating both motor and non-motor symptoms, thereby potentially improving patient quality of life. This research underscores the significance of the gut microbiota in the progression and treatment of PD, advocating for an integrated, multidisciplinary approach to develop personalized, efficacious management strategies for PD patients, combining insights from neurology, microbiology, and nutritional science.}, } @article {pmid38867599, year = {2024}, author = {Ma, C and Yin, B and Hu, X}, title = {Advances in clinical treatment of liver disease: fecal microbiota transplantation for liver disease.}, journal = {Minerva medica}, volume = {}, number = {}, pages = {}, doi = {10.23736/S0026-4806.24.09363-7}, pmid = {38867599}, issn = {1827-1669}, } @article {pmid38868341, year = {2023}, author = {Wang, XW and Wu, L and Dai, L and Yin, X and Zhang, T and Weiss, ST and Liu, YY}, title = {Ecological dynamics imposes fundamental challenges in community-based microbial source tracking.}, journal = {iMeta}, volume = {2}, number = {1}, pages = {e75}, pmid = {38868341}, issn = {2770-596X}, abstract = {Quantifying the contributions of possible environmental sources ("sources") to a specific microbial community ("sink") is a classical problem in microbiology known as microbial source tracking (MST). Solving the MST problem will not only help us understand how microbial communities were formed, but also have far-reaching applications in pollution control, public health, and forensics. MST methods generally fall into two categories: target-based methods (focusing on the detection of source-specific indicator species or chemicals); and community-based methods (using community structure to measure similarity between sink samples and potential source environments). As next-generation sequencing becomes a standard community-assessment method in microbiology, numerous community-based computational methods, referred to as MST solvers hereafter have been developed and applied to various real datasets to demonstrate their utility across different contexts. Yet, those MST solvers do not consider microbial interactions and priority effects in microbial communities. Here, we revisit the performance of several representative MST solvers. We show compelling evidence that solving the MST problem using existing MST solvers is impractical when ecological dynamics plays a role in community assembly. In particular, we clearly demonstrate that the presence of either microbial interactions or priority effects will render the MST problem mathematically unsolvable for MST solvers. We further analyze data from fecal microbiota transplantation studies, finding that the state-of-the-art MST solvers fail to identify donors for most of the recipients. Finally, we perform community coalescence experiments to demonstrate that the state-of-the-art MST solvers fail to identify the sources for most of the sinks. Our findings suggest that ecological dynamics imposes fundamental challenges in MST. Interpretation of results of existing MST solvers should be done cautiously.}, } @article {pmid38867907, year = {2022}, author = {Ma, Y and Ke, D and Li, D and Zhang, Q}, title = {Donors' experiences and attitudes of fecal microbiota transplantation: An empirical bioethics study from China.}, journal = {iMeta}, volume = {1}, number = {4}, pages = {e62}, pmid = {38867907}, issn = {2770-596X}, abstract = {Donor participation is a critical part of ensuring the development of human microbiome research and the clinical application of fecal microbiota transplantation (FMT). Most FMT donors are still not sufficiently aware of the risks associated with the act of donating gut microbiota, especially the risk of data privacy disclosure. Enhanced awareness of the moral responsibility of the researchers and ethical oversight by ethics committees are needed.}, } @article {pmid38866215, year = {2024}, author = {Chen, CY and Wang, YF and Lei, L and Zhang, Y}, title = {Impacts of microbiota and its metabolites through gut-brain axis on pathophysiology of major depressive disorder.}, journal = {Life sciences}, volume = {}, number = {}, pages = {122815}, doi = {10.1016/j.lfs.2024.122815}, pmid = {38866215}, issn = {1879-0631}, abstract = {Major depressive disorder (MDD) is characterized by a high rate of recurrence and disability, which seriously affects the quality of life of patients. That's why a deeper understanding of the mechanisms of MDD pathology is an urgent task, and some studies have found that intestinal symptoms accompany people with MDD. The microbiota-gut-brain axis is the bidirectional communication between the gut microbiota and the central nervous system, which was found to have a strong association with the pathogenesis of MDD. Previous studies have focused more on the communication between the gut and the brain through neuroendocrine, neuroimmune and autonomic pathways, and the role of gut microbes and their metabolites in depression is unclear. Metabolites of intestinal microorganisms (e.g., tryptophan, kynurenic acid, indole, and lipopolysaccharide) can participate in the pathogenesis of MDD through immune and inflammatory pathways or by altering the permeability of the gut and blood-brain barrier. In addition, intestinal microbes can communicate with intestinal neurons and glial cells to affect the integrity and function of intestinal nerves. However, the specific role of gut microbes and their metabolites in the pathogenesis of MDD is not well understood. Hence, the present review summarizes how gut microbes and their metabolites are directly or indirectly involved in the pathogenesis of MDD.}, } @article {pmid38862291, year = {2024}, author = {Gopalarathinam, R and Sankar, R and Zhao, SS}, title = {Role of Anti-Inflammatory Diet and Fecal Microbiota Transplant in Psoriatic Arthritis.}, journal = {Clinical therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clinthera.2024.05.005}, pmid = {38862291}, issn = {1879-114X}, abstract = {PURPOSE: Psoriatic arthritis (PsA) is a chronic inflammatory condition with complex and heterogenous manifestations. Although a myriad of treatment options including biologic medications are available to alleviate symptoms and slow disease progression, there is currently no cure for this condition. There has been a recent emergence of understanding about the relationship between the gut microbiome and immune-mediated inflammatory diseases. This has generated interest in the potential role of dietary interventions, particularly anti-inflammatory diets, and fecal microbiota transplant (FMT) as novel therapeutic approaches. The purpose of this narrative review is to examine the role of an anti-inflammatory diet and FMT in turn and whether their combination may offer alternate approaches for the management of PsA.

METHODS: Our non-systematic narrative review was informed by a literature search using PubMed and Google Scholar using the terms anti-inflammatory diet, FMT, nutrition supplements, and PsA. Preclinical studies and non-English language articles were excluded when synthesizing the narrative review.

FINDINGS: Current randomized controlled trials (RCTs) and observational evidence suggest that a hypocaloric diet or Mediterranean diet can help achieve weight loss among PsA patients who are overweight or obese, which in turn reduces inflammation and improves disease activity. However, there is no strong data to support the beneficial effects of intermittent fasting, vitamin supplements, turmeric supplements, probiotics, or omega-3 fatty acid supplements in PsA. Current evidence on the use of FMT in PsA is limited as only one small RCT has been conducted which did not demonstrate efficacy for improving clinical symptoms.

IMPLICATIONS: Clinicians can consider recommending hypocaloric or Mediterranean diets as an adjunct to standard management of PsA, possibly under the guidance of a dietician. Further research is needed to explore the beneficial effects of the synergistic role of combining an anti-inflammatory diet with FMT in PsA.}, } @article {pmid38858775, year = {2024}, author = {Lin, D and Hu, D and Song, Y and He, X and Wu, L}, title = {Long-term efficacy of washed microbiota transplantation in overweight patients.}, journal = {European journal of clinical investigation}, volume = {}, number = {}, pages = {e14260}, doi = {10.1111/eci.14260}, pmid = {38858775}, issn = {1365-2362}, support = {2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; 2023M740782//China Postdoctoral Science Foundation/ ; 20221232//the Scientific Research Projects of Guangdong Bureau of Traditional Chinese Medicine/ ; B2022209//Medical Scientific Research Foundation of Guangdong Province/ ; 2021KCXTD025//Guangdong Innovation Research Team for Higher Education/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation holds promise in mitigating fat accumulation and improving obesity. This study aimed to evaluate the long-term efficacy of washed microbiota transplantation (WMT) among overweight patients.

METHODS: The clinical data pertaining to the treatment of patients with WMT were collected retrospectively. Compared alterations in body mass index (BMI), blood glucose, blood lipids and blood pressure prior to and following WMT treatment. Comprehensive efficacy evaluation and atherosclerosis cardiovascular disease (ASCVD) grading evaluation were carried out, with an analysis of gut microbiota composition before and after WMT.

RESULTS: A total of 186 patients were included (80 overweight, 106 normal weight). WMT not only had the effect of improving overweight patients to the normal weight patients (p < .001), but also could significantly reduce BMI in the long term by restoring gut microbiota homeostasis (p < .001). In addition, the BMI improvement value of multi course was more significant than that of single course or double course. WMT had a significant ASCVD downgrade effect on the high-risk and medium-risk groups outside 1 year, while it did not increase the risk of upgrading ASCVD for low-risk group.

CONCLUSIONS: WMT could significantly reduce the BMI of overweight patients and still had an improvement effect in the long term.}, } @article {pmid38858330, year = {2024}, author = {Guo, Q and Cheng, Y and Li, T and Huang, J and Li, J and Zhang, Z and Qu, Y}, title = {The Gut Microbiota Contributes to the Development of LPS-Induced Orchitis by Disrupting the Blood-Testosterone Barrier in Mice.}, journal = {Reproductive sciences (Thousand Oaks, Calif.)}, volume = {}, number = {}, pages = {}, pmid = {38858330}, issn = {1933-7205}, support = {XYB201910//Doctoral Starting Up Foundation of the Heilongjiang Bayi Agricultural University/ ; LH2023C080//Natural Science Foundation of Heilongjiang Province of China/ ; 2023M731028//China Postdoctoral Science Foundation/ ; 2021ZX12B03//Heilongjiang Province Hundred Million Project Science and Technology Major project/ ; 32072758//National Natural Science Foundation of China/ ; LBH-Q20054//Heilongjiang Postdoctoral Found/ ; }, abstract = {Orchitis is a frequent inflammatory reproductive disease that causes male infertility and a decline in sperm quality. Gut microbiota can regulate systemic and local inflammation, spermatogenesis and blood-testosterone barrier (BTB). In this study, we investigated correlation between gut microbiota and orchitis by establishing a mouse gut microbiota imbalance model induced by antibiotics (ABX) treatment and orchitis model induced by lipopolysaccharide (LPS) infection. Based on these two models, 16s rRNA sequencing and feces microbiota transplantation (FMT) experiments were combined to examine the function and regulatory mechanisms of the gut microbiota in host defense against orchitis. Compared with control mice, gut microbiota imbalance resulted in increasing inflammatory responses, modulating oxidative stress related enzyme activity, testosterone levels and the permeability of blood testosterone barrier, which are restored after FMT. Subsequently, we tested the relationship between the gut microbiota imbalance and testicular inflammation severity in orchitis. It was found that the ABX and LPS co-treated mice had more severe inflammatory responses, lower testosterone levels and greater permeability of the BTB than the LPS-treated mice, but these changes could be partially recovered by gut microbiota transplantation. In conclusion, these above results proved for the first time that gut microbiota is involved in the pathogenesis of orchitis, which laid a good foundation for the subsequent development of anti-orchitis drugs and probiotic targeting intestinal flora.}, } @article {pmid38858151, year = {2024}, author = {Skjevling, L and Goll, R and Hanssen, HM and Johnsen, PH}, title = {Faecal microbiota transplantation (FMT) in Norwegian outpatients with mild to severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): protocol for a 12-month randomised double-blind placebo-controlled trial.}, journal = {BMJ open}, volume = {14}, number = {6}, pages = {e073275}, pmid = {38858151}, issn = {2044-6055}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Fatigue Syndrome, Chronic/therapy ; Double-Blind Method ; Norway ; Randomized Controlled Trials as Topic ; Adult ; Gastrointestinal Microbiome ; Treatment Outcome ; Female ; Male ; }, abstract = {INTRODUCTION: The observed alteration of the intestinal microbiota in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the effect of transferring a healthy gut flora from a faecal donor using a faecal microbiota transplantation (FMT) will be explored in this trial.

METHODS AND ANALYSIS: This is a protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial, with 12 months follow-up. 80 participants will be included and randomised (1:1:2) to either donor FMT (from two different donors) or placebo (autologous FMT). Participants will be included by the International Clinical Criteria for ME/CFS. The clinical measures of ME/CFS and disease activity include Modified DePaul Questionnaire, Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), 36-Item Short Form Health Survey (SF-36), ROMA IV criteria, Food Frequency Questionnaire, Repeatable Battery for the Assessment of Neuropsychological Status, heart rate variability testing and reports on the use of antibiotics and food supplements, as well as biobanking of blood, urine and faeces.The primary endpoint is proportion with treatment success in FSS score in donor versus autologous FMT group 3 months after treatment. Treatment success is defined as an FSS improvement of more than 1.2 points from baseline at 3 months after treatment. Adverse events will be registered throughout the study.

ETHICS AND DISSEMINATION: The Regional Committee for Medical Research Ethics Northern Norway has approved the study. The study has commenced in May 2019. Findings will be disseminated in international peer-reviewed journal(s), submitted to relevant conferences, and trial participants will be informed via phone calls.

TRIAL REGISTRATION NUMBER: NCT03691987.}, } @article {pmid38857378, year = {2024}, author = {Xu, R and Feng, N and Li, Q and Wang, H and Li, L and Feng, X and Su, Y and Zhu, W}, title = {Pectin supplementation accelerates post-antibiotic gut microbiome reconstitution orchestrated with reduced gut redox potential.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrae101}, pmid = {38857378}, issn = {1751-7370}, abstract = {Antibiotic-induced gut dysbiosis (AID) is a big challenge for host health, and the recovery from this dysbiosis is often slow and incomplete. AID is typically featured by elevation in redox potential, Enterobacteriaceae load, and aerobic metabolism. In our previous study, pectin-enriched diet could decrease fecal redox potential and modulate gut microbiome. Therefore, we propose that pectin supplementation may modulate gut redox potential and favor post-antibiotic gut microbiome reconstitution from dysbiosis. In the present study, AID rats were applied to investigate the effects of pectin supplementation on post-antibiotic gut microbiome reconstitution from dysbiosis. The results showed that pectin supplementation accelerated post-antibiotic reconstitution of gut microbiome composition and function, and led to enhancement of anabolic reductive metabolism and weakening of catabolic oxidative pathways. These results were corroborated by the measurement of redox potential suggesting that pectin favors post-antibiotic recovery from dysbiosis. Transplantation of the pectin-modulated fecal microbiota (P-FMT) accelerated the decrease in antibiotics-elevated redox potential and Enterobacteriaceae load similarly to pectin supplementation. Moreover, both pectin supplementation and P-FMT enriched anaerobic members primarily from Lachnospiraceae orchestrating with enhancement on microbial reductive metabolism in post-antibiotic rats. The findings suggested that pectin supplementation accelerated post-antibiotic gut microbiome reconstitution orchestrated with reduced gut redox potential, and the effect of pectin on redox potential was mediated by intestinal microbiota remodeling.}, } @article {pmid38855295, year = {2024}, author = {Hazan, S and Haroon, J and Jordan, S and Walker, SJ}, title = {Correction to: Improvements in Gut Microbiome Composition and Clinical Symptoms Following Familial Fecal Microbiota Transplantation in a Nineteen-Year-Old Adolescent With Severe Autism.}, journal = {Journal of medical cases}, volume = {15}, number = {6}, pages = {115}, pmid = {38855295}, issn = {1923-4163}, abstract = {[This corrects the article DOI: 10.14740/jmc4209.].}, } @article {pmid38854967, year = {2024}, author = {Wanyi, Z and Jiao, Y and Wen, H and Bin, X and Xuefei, W and Lan, J and Liuyin, Z}, title = {Bidirectional communication of the gut-brain axis: new findings in Parkinson's disease and inflammatory bowel disease.}, journal = {Frontiers in neurology}, volume = {15}, number = {}, pages = {1407241}, pmid = {38854967}, issn = {1664-2295}, abstract = {Parkinson's disease (PD) and inflammatory bowel disease (IBD) are the two chronic inflammatory diseases that are increasingly affecting millions of people worldwide, posing a major challenge to public health. PD and IBD show similarities in epidemiology, genetics, immune response, and gut microbiota. Here, we review the pathophysiology of these two diseases, including genetic factors, immune system imbalance, changes in gut microbial composition, and the effects of microbial metabolites (especially short-chain fatty acids). We elaborate on the gut-brain axis, focusing on role of gut microbiota in the pathogenesis of PD and IBD. In addition, we discuss several therapeutic strategies, including drug therapy, fecal microbiota transplantation, and probiotic supplementation, and their potential benefits in regulating intestinal microecology and relieving disease symptoms. Our analysis will provide a new understanding and scientific basis for the development of more effective therapeutic strategies for these diseases.}, } @article {pmid38853707, year = {2024}, author = {Ni, S and Huang, X and Li, X and Shi, C and Fan, M and Zhao, L and Rong, Z and Zhang, H}, title = {METTL3 promotes nucleus pulposus cell senescence in intervertebral disc degeneration by regulating TLR2 m6A methylation and gut microbiota.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1093/gerona/glae150}, pmid = {38853707}, issn = {1758-535X}, abstract = {BACKGROUND: Nucleus pulposus cell (NPC) senescence in intervertebral disc (IVD) tissue is the major pathological cause during intervertebral disc degeneration (IDD). N6-methyladenosine (m6A) methylation and gut microbiota play important roles in the progression of IDD. This study investigated whether methyltransferase-like 3 (METTL3) regulates TLR2 m6A modification and gut microbiota to influence NPC senescence.

METHODS: An IDD rat model was established by lumbar intervertebral disc puncture and NPCs were challenged with IL-1β to mimic IVD injury. IDD rats and IL-1β-exposed NPCs were treated with METTL3-interfering lentivirus and the TLR2 agonist Pam3CSK4. Compositional changes in the rat gut microbiota were analyzed and fecal microbiota transplantation procedures were used. NPC senescence, cell cycle and the expression of senescence-associated secretory phenotype (SASP) factors were assessed. The m6A enrichment of TLR2 and the binding of IGF2BP1 to TLR2 mRNA were examined.

RESULTS: METTL3 and TLR2 were highly expressed in IDD rats. METTL3 silencing attenuated senescent phenotypes and reduced secretion of SASP factors. Pam3CSK4 reversed the beneficial effects of METTL3 silencing on NPC senescence and IVD injury. METTL3 stabilized TLR2 mRNA in an IGF2BP1-dependent manner. METTL3 silencing restored specific gut microbiota levels in IDD rats, which was further reversed by administration of Pam3CSK4. Fecal microbiota from METTL3 silenced IDD rats altered the pathological phenotypes of IDD rats.

CONCLUSIONS: These results demonstrate the beneficial effects of METTL3 silencing on NPC senescence and amelioration of IVD injury, involving modulation of TLR2 m6A modification and gut microbiota. These findings support METTL3 silencing as a potential therapeutic target for IDD.}, } @article {pmid38852729, year = {2024}, author = {Liu, L and Zhao, Z and Liu, H and Xia, X and Ai, C and Song, S and Yan, C}, title = {Haematococcus pluvialis polysaccharides improve microbiota-driven gut epithelial and vascular barrier and prevent alcoholic steatohepatitis development.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {133014}, doi = {10.1016/j.ijbiomac.2024.133014}, pmid = {38852729}, issn = {1879-0003}, abstract = {Algal polysaccharides possess many biological activities and health benefits, such as antioxidant, anti-tumor, anti-coagulant, and immunomodulatory potential. Gut microbiota has emerged as one of the major contributor in mediating the health benefits of algal polysaccharides. In this study we showed that Haematococcus pluvialis polysaccharides (HPP) decreased serum transaminase levels and hepatic triglyceride content, alleviated inflammation and oxidative stress in the liver of chronic and binge ethanol diet-fed mice. Furthermore, HPP reduced endotoxemia, improved gut microbiota dysbiosis, inhibited epithelial barrier disruption and gut vascular barrier (GVB) damage in ethanol diet-fed mice. Co-housing vehicle-fed mice with HPP-fed mice alleviated ethanol-induced liver damage and endotoxemia. Moreover, fecal microbiota transplantation from HPP-fed mice into antibiotic-induced microbiota-depleted recipients also alleviated ethanol-induced liver injury and improved gut epithelial and vascular barrier. Our study demonstrated that HPP ameliorated ethanol-induced gut epithelial and vascular barrier dysfunction through alteration of gut microbiota, therefore preventing alcoholic liver damage.}, } @article {pmid38852024, year = {2024}, author = {Georgin-Lavialle, S and Delplanque, M and Bachmeyer, C and Savey, L and Sokol, H and , }, title = {Clostridioides difficile infection as a potential trigger for Familial Mediterranean Fever attacks and fecal transplantation as a rescue.}, journal = {European journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ejim.2024.05.023}, pmid = {38852024}, issn = {1879-0828}, } @article {pmid38850943, year = {2024}, author = {Ye, L and Chen, H and Wang, J and Tsim, KWK and Wang, Y and Shen, X and Lei, H and Liu, Y}, title = {Aflatoxin B1-induced liver pyroptosis is mediated by disturbing the gut microbial metabolites: The roles of pipecolic acid and norepinephrine.}, journal = {Journal of hazardous materials}, volume = {474}, number = {}, pages = {134822}, doi = {10.1016/j.jhazmat.2024.134822}, pmid = {38850943}, issn = {1873-3336}, abstract = {The disturbed gut microbiota is a key factor in activating the aflatoxin B1 (AFB1)-induced liver pyroptosis by promoting inflammatory hepatic injury; however, the pathogen associated molecular pattern (PAMP) from disturbed gut microbiota and its mechanism in activating liver pyroptosis remain undefined. By transplanting AFB1-originated fecal microbiota and sterile fecal microbial metabolites filtrate, we determined the association of PAMP in AFB1-induced liver pyroptosis. Notably, AFB1-originated sterile fecal microbial metabolites filtrate were more active in triggering liver pyroptosis in mice, as compared to parental fecal microbiota. This result supported a critical role of the metabolic homeostasis of gut microbiota in AFB1-induced liver pyroptosis, rather than an injurious response to direct exposure of AFB1 in liver. Among the gut-microbial metabolites, pipecolic acid and norepinephrine were proposed to bind TLR4 and NLRP3, the upstream proteins of pyroptosis signaling pathway. Besides, the activations of TLR4 and NLRP3 were linearly correlated with the concentrations of pipecolic acid and norepinephrine in the serum of mice. In silenced expression of TLR4 and NLRP3 in HepG2 cells, pipecolic acid or norepinephrine did not able to activate hepatocyte pyroptosis. These results demonstrated the necessity of gut microbial metabolism in sustaining liver homeostasis, as well as the potential to provide new insights into targeted intervention for AFB1 hepatotoxicity.}, } @article {pmid38848972, year = {2024}, author = {Zhou, H and Wang, X and She, Z and Huang, L and Wei, H and Yang, S and Wei, Z and Chen, H and Yang, B and Hu, Z and Feng, X and Zhu, P and Li, Z and Shen, J and Liu, H and Dong, H and Chen, G and Zhang, Q}, title = {Combining bioinformatics and multiomics strategies to investigate the key microbiota and active components of Liupao tea ameliorating hyperlipidemia.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {118438}, doi = {10.1016/j.jep.2024.118438}, pmid = {38848972}, issn = {1872-7573}, abstract = {Hyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear.

AIM OF THE STUDY: This study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia.

MATERIALS AND METHODS: Firstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses.

RESULTS: Results showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of bile acid (BA) and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice.

CONCLUSIONS: LPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia.}, } @article {pmid38848942, year = {2024}, author = {Nguyen, NN and Lin, CY and Tsai, WL and Huang, HY and Chen, CM and Tung, YT and Chen, YC}, title = {Natural sweetener glycyrrhizin protects against precocious puberty by modulating the gut microbiome.}, journal = {Life sciences}, volume = {350}, number = {}, pages = {122789}, doi = {10.1016/j.lfs.2024.122789}, pmid = {38848942}, issn = {1879-0631}, abstract = {AIMS: Precocious puberty (PP) may lead to many adverse outcomes. Recent evidence suggests that PP is a gut-brain disease. On the other hand, the use of glycyrrhizin, a natural sweetener, has become popular in the past decade. Glycyrrhizin possesses various health benefits, but its impact on PP has yet to be investigated. We aimed to explore the protective effects of glycyrrhizin against PP in both humans (observational) and animals (interventional).

MATERIALS AND METHODS: In the human cohort, we investigated the association between glycyrrhizin consumption and risk of PP. In the animal experiment, we observed puberty onset after feeding danazol-induced PP rats with glycyrrizin. Blood, fecal, and hypothalamic samples were harvested to evaluate potential mechanistic pathways. We also performed a fecal microbiota transplantation to confirm to causal relationship between glycyrrhizin and PP risk.

KEY FINDINGS: Glycyrrhizin exhibited a protective effect against PP in children (OR 0.60, 95%CI: 0.39-0.89, p = 0.013), primarily driven by its significance in girls, while no significant effect was observed in boys. This effect was consistent with findings in rodents. These benefits were achieved through the modulation of the gut microbiome, which functionally suppressed the hypothalamic-pituitary-gonadal axis and prevented PP progression. A fecal microbiota transplantation indicated that the causal correlation between glycyrrhizin intake and PP is mediated by the gut microbiome alterations.

SIGNIFICANCE: Our findings suggest that glycyrrhizin can protect against PP by altering the gut microbiome. Long term use of glycyrrhizin is safe and tolerable. Therefore, glycyrrhizin can serve as a safe and affordable complementary therapy for PP.}, } @article {pmid38846356, year = {2024}, author = {Pfail, J and Drobner, J and Doppalapudi, K and Saraiya, B and Packiam, V and Ghodoussipour, S}, title = {The Role of Tumor and Host Microbiome on Immunotherapy Response in Urologic Cancers.}, journal = {Journal of cancer immunology}, volume = {6}, number = {1}, pages = {1-13}, pmid = {38846356}, issn = {2689-968X}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; }, abstract = {INTRODUCTION & OBJECTIVE: The role of the microbiome in the development and treatment of genitourinary malignancies is just starting to be appreciated. Accumulating evidence suggests that the microbiome can modulate immunotherapy through signaling in the highly dynamic tumor microenvironment. Nevertheless, much is still unknown about the immuno-oncology-microbiome axis, especially in urologic oncology. The objective of this review is to synthesize our current understanding of the microbiome's role in modulating and predicting immunotherapy response to genitourinary malignancies.

METHODS: A literature search for peer-reviewed publications about the microbiome and immunotherapy response in bladder, kidney, and prostate cancer was conducted. All research available in PubMed, Google Scholar, clinicaltrials.gov, and bioRxiv up to September 2023 was analyzed.

RESULTS: Significant differences in urinary microbiota composition have been found in patients with genitourinary cancers compared to healthy controls. Lactic acid-producing bacteria, such as Bifidobacterium and Lactobacillus genera, may have value in augmenting BCG responsiveness to bladder cancer. BCG may also be a dynamic regulator of PD-L1. Thus, the combination of BCG and immune checkpoint inhibitors may be an effective strategy for bladder cancer management. In advanced renal cell carcinoma, studies show that recent antibiotic administration negatively impacts survival outcomes in patients undergoing immunotherapy, while administration of CBM588, a live bacterial product, is associated with improved progression-free survival. Specific bacterial taxa, such as Streptococcus salivarius, have been linked with response to pembrolizumab in metastatic castrate-resistant prostate cancer. Fecal microbiota transplant has been shown to overcome resistance and reduce toxicity to immunotherapy; it is currently being investigated for both kidney and prostate cancers.

CONCLUSIONS: Although the exact mechanism is unclear, several studies identify a symbiotic relationship between microbiota-centered interventions and immunotherapy efficacy. It is possible to improve immunotherapy responsiveness in genitourinary malignancies using the microbiome, but further research with more standardized methodology is warranted.}, } @article {pmid38844081, year = {2024}, author = {Leng, Y and Zhang, X and Zhang, Q and Xia, J and Zhang, Y and Ma, C and Liu, K and Li, H and Hong, Y and Xie, Z}, title = {Gallic acid attenuates murine ulcerative colitis by promoting group 3 innate lymphocytes, affecting gut microbiota, and bile acid metabolism.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109677}, doi = {10.1016/j.jnutbio.2024.109677}, pmid = {38844081}, issn = {1873-4847}, abstract = {Gallic acid (GA), a plant phenol that is widely distributed in fruits and vegetables, and exhibits a protective role against ulcerative colitis (UC). UC is an inflammatory disease characterized by immune response disorders. However, the role and mechanism of action of GA in gut immunity remain unknown. Here, we observed that GA treatment improved enteritis symptoms, decreased the concentrations of cytokines TNF-α, IFN-γ, IL-6, IL-17A, and IL-23, increased the concentrations of cytokines IL-10, TGF-β and IL-22, and increased the proportion of group 3 innate lymphoid cells (ILC3) in mesenteric lymph nodes and lamina propria. However, GA did not upregulate ILC3 or impair UC in antibody-treated sterile mice. Notably, transplantation of fecal bacteria derived from GA-treated UC mice, instead of UC mice, increased ILC3 levels. Therefore, we analyzed the gut microbiota and related metabolites to elucidate the mechanism promoting ILC3. We determined that GA treatment altered the diversity of the gut microbiota and activated the bile acid (BA) metabolic pathway. We evaluated three BAs, namely, UDCA, isoalloLCA, and 3-oxoLCA that were significantly upregulated after GA treatment, improved UC symptoms, and elevated the proportion of ILC3 in vivo and in vitro. Collectively, these data indicate that GA attenuates UC by elevating ILC3 proportion, regulating the gut microbiota, and impacting BA metabolism. Additionally, we highlight the modulatory effects of BAs on ILC3 for the first time. Our findings provide novel insights into the multiple roles of GA in alleviating UC and provide a mechanistic explanation that supports the dietary nutrition in UC therapy.}, } @article {pmid38843950, year = {2024}, author = {El-Salhy, M and Gilja, OH and Hatlebakk, JG}, title = {Factors underlying the Long-term Efficacy of Faecal Microbiota Transplantation for Patients with Irritable Bowel Syndrome.}, journal = {Microbes and infection}, volume = {}, number = {}, pages = {105372}, doi = {10.1016/j.micinf.2024.105372}, pmid = {38843950}, issn = {1769-714X}, abstract = {The long-term effects of the transplant dose, its administration route and repeated faecal microbiota transplantation (FMT) on the outcomes of FMT for patients with irritable bowel syndrome (IBS) are unknown. This study included 171 patients (125 females and 46 males): 90 g of donor feces was administered into the large intestine (LI) in 58, into the small intestine (SI) in 57, and into the SI twice (repeated SI) in 56. The patients provided a fecal sample and completed five questionnaires at the baseline and at 2 years after FMT. Fecal bacteria and the dysbiosis index were analyzed using 16S rRNA gene PCR DNA amplification/probe. The response rates at 2 years after FMT were 47.2%, 80.9%, and 76.6% in the LI, SI, and repeated-SI groups, respectively. The response rate was significantly higher in the SI and repeated SI groups than in the LI group. IBS symptoms at 2 years after FMT were less severe in the SI and repeated-SI groups than in the LI group. Fluorescent signals of several bacteria were significantly correlated with IBS symptoms and fatigue after FMT. No long-term adverse events were observed. In conclusion, administering the transplant to the SI increased the long-term response rate and reduced IBS symptom severity compared with administering it to the LI, and led to the long-term colonization of beneficial bacteria. There was no long-term difference between one and two FMT procedures. (www.clinicaltrials.gov: NCT04236843).}, } @article {pmid38841848, year = {2024}, author = {Montrose, JA and Kurada, S and Fischer, M}, title = {Current and future microbiome-based therapies in inflammatory bowel disease.}, journal = {Current opinion in gastroenterology}, volume = {40}, number = {4}, pages = {258-267}, pmid = {38841848}, issn = {1531-7056}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy/microbiology ; Inflammatory Bowel Diseases/microbiology/therapy ; Randomized Controlled Trials as Topic ; }, abstract = {PURPOSE OF REVIEW: The role of the microbiome and dysbiosis is increasingly recognized in the pathogenesis of inflammatory bowel disease (IBD). Intestinal microbiota transplant (IMT), previously termed fecal microbiota transplant has demonstrated efficacy in restoring a healthy microbiome and promoting gut health in recurrent Clostridioides difficile infection. Several randomized trials (RCTs) highlighted IMT's potential in treating ulcerative colitis, while smaller studies reported on its application in managing Crohn's disease and pouchitis.

RECENT FINDINGS: This review delves into the current understanding of dysbiosis in IBD, highlighting the distinctions in the microbiota of patients with IBD compared to healthy controls. It explores the mechanisms by which IMT can restore a healthy microbiome and provides a focused analysis of recent RCTs using IMT for inducing and maintaining remission in IBD. Lastly, we discuss the current knowledge gaps that limit its widespread use.

SUMMARY: The body of evidence supporting the use of IMT in IBD is growing. The lack of a standardized protocol impedes its application beyond clinical trials. Further research is needed to identify patient profile and disease phenotypes that benefit from IMT, to delineate key donor characteristics, optimize the delivery route, dosage, and frequency.}, } @article {pmid38841589, year = {2024}, author = {Luo, ZQ and Huang, YJ and Chen, ZH and Lu, CY and Zhou, B and Gong, XH and Shen, Z and Wang, T}, title = {A decade of insight: bibliometric analysis of gut microbiota's role in osteoporosis (2014-2024).}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1409534}, pmid = {38841589}, issn = {2296-858X}, abstract = {PURPOSE: Osteoporosis represents a profound challenge to public health, underscoring the critical need to dissect its complex etiology and identify viable targets for intervention. Within this context, the gut microbiota has emerged as a focal point of research due to its profound influence on bone metabolism. Despite this growing interest, the literature has yet to see a bibliometric study addressing the gut microbiota's contribution to both the development and management of osteoporosis. This study aims to fill this gap through an exhaustive bibliometric analysis. Our objective is to uncover current research hotspots, delineate key themes, and identify future research trends. In doing so, we hope to provide direction for future studies and the development of innovative treatment methods.

METHODS: Relevant publications in this field were retrieved from the Web of Science Core Collection database. We used VOSviewer, CiteSpace, an online analysis platform and the R package "Bibliometrix" for bibliometric analysis.

RESULTS: A total of 529 publications (including 351 articles and 178 reviews) from 61 countries, 881 institutions, were included in this study. China leads in publication volume and boast the highest cumulative citation. Shanghai Jiao Tong University and Southern Medical University are the leading research institutions in this field. Nutrients contributed the largest number of articles, and J Bone Miner Res is the most co-cited journal. Of the 3,166 scholars who participated in the study, Ohlsson C had the largest number of articles. Li YJ is the most co-cited author. "Probiotics" and "inflammation" are the keywords in the research.

CONCLUSION: This is the first bibliometric analysis of gut microbiota in osteoporosis. We explored current research status in recent years and identified frontiers and hot spots in this research field. We investigate the impact of gut microbiome dysregulation and its associated inflammation on OP progression, a topic that has garnered international research interest in recent years. Additionally, our study delves into the potential of fecal microbiota transplantation or specific dietary interventions as promising avenues for future research, which can provide reference for the researchers who focus on this research filed.}, } @article {pmid38841199, year = {2024}, author = {Karna, R and Babich, M}, title = {Fecal microbiota transplant in liver diseases: Current evidence and future directions.}, journal = {Clinical liver disease}, volume = {23}, number = {1}, pages = {e0154}, pmid = {38841199}, issn = {2046-2484}, } @article {pmid38840756, year = {2024}, author = {Qin, H and Fu, Y and Deng, C and Chen, Y and Huang, K and Ruan, Y and Liu, K}, title = {The role of gut microbiota and the gut-lung axis in sepsis: A case study of a pregnant woman with severe rickettsial pneumonia and septic shock complicated by MODS.}, journal = {Clinical case reports}, volume = {12}, number = {6}, pages = {e8815}, pmid = {38840756}, issn = {2050-0904}, abstract = {KEY CLINICAL MESSAGE: In this case report, we describe the successful management of severe scrub typhus with pneumonia, sepsis, and multiple organ dysfunction in a pregnant woman. Despite initial challenges, the patient responded favorably to fecal microbiota transplantation and oral fecal microbiota capsule therapy.

ABSTRACT: Scrub typhus, caused by Orientia tsutsugamushi, can lead to severe multiorgan dysfunction and carries a mortality rate of up to 70% if not treated properly. In this report, we present the case of a 27-year-old pregnant woman at 18 + 6 weeks gestation whose symptoms worsened 15 days after onset and progressed to severe pneumonia with sepsis and multiple organ dysfunction syndrome. After the pathogen was confirmed by next-generation sequencing analysis of bronchoalveolar-lavage fluid and blood samples, the patient's treatment was switched to antiinfective chloramphenicol. The patient also underwent uterine evacuation due to a miscarriage. Extracorporeal membrane oxygenation was discontinued once the pulmonary infection significantly improved. Subsequently, the patient had recurrent diarrhea, abdominal distension, and difficulty eating. The antibiotic regimen was adjusted according to the drug sensitivity, but the diarrhea and abdominal distension still did not improve. Following a comprehensive multidisciplinary risk assessment, we initiated fecal microbiota transplantation and oral fecal microbiota capsule therapy. As a result, the patient's condition was effectively managed, and they were gradually discharged. Fecal microbiota transplantation may be a safe and effective treatment for severe pneumonia and shock in pregnant women. This has significant implications for maternal health. However, further clinical cases are required to observe its long-term effectiveness.}, } @article {pmid38840189, year = {2024}, author = {Amati, AL and Ebert, R and Maier, L and Panah, AK and Schwandner, T and Sander, M and Reichert, M and Grau, V and Petzoldt, S and Hecker, A}, title = {Reduced preoperative serum choline esterase levels and fecal peritoneal contamination as potential predictors for the leakage of intestinal sutures after source control in secondary peritonitis.}, journal = {World journal of emergency surgery : WJES}, volume = {19}, number = {1}, pages = {21}, pmid = {38840189}, issn = {1749-7922}, support = {GU405/14-1//German Research Foundation (DFG)/ ; GU405/14-1//German Research Foundation (DFG)/ ; }, mesh = {Humans ; Female ; Male ; Retrospective Studies ; *Peritonitis/surgery ; Middle Aged ; Aged ; *Feces ; Sutures ; Anastomotic Leak ; Postoperative Complications ; Risk Factors ; Biomarkers/blood ; Laparotomy/methods/adverse effects ; }, abstract = {BACKGROUND: The high rate of stoma placement during emergency laparotomy for secondary peritonitis is a paradigm in need of change in the current fast-track surgical setting. Despite growing evidence for the feasibility of primary bowel reconstruction in a peritonitic environment, little data substantiate a surgeons' choice between a stoma and an anastomosis. The aim of this retrospective analysis is to identify pre- and intraoperative parameters that predict the leakage risk for enteric sutures placed during source control surgery (SCS) for secondary peritonitis.

METHODS: Between January 2014 and December 2020, 497 patients underwent SCS for secondary peritonitis, of whom 187 received a primary reconstruction of the lower gastro-intestinal tract without a diverting stoma. In 47 (25.1%) patients postoperative leakage of the enteric sutures was directly confirmed during revision surgery or by computed tomography. Quantifiable predictors of intestinal suture outcome were detected by multivariate analysis.

RESULTS: Length of intensive care, in-hospital mortality and failure of release to the initial home environment were significantly higher in patients with enteric suture leakage following SCS compared to patients with intact anastomoses (p < 0.0001, p = 0.0026 and p =0.0009, respectively). Reduced serum choline esterase (sCHE) levels and a high extent of peritonitis were identified as independent risk factors for insufficiency of enteric sutures placed during emergency laparotomy.

CONCLUSIONS: A preoperative sCHE < 4.5 kU/L and generalized fecal peritonitis associate with a significantly higher incidence of enteric suture insufficiency after primary reconstruction of the lower gastro-intestinal tract in a peritonitic abdomen. These parameters may guide surgeons when choosing the optimal surgical procedure in the emergency setting.}, } @article {pmid38839272, year = {2024}, author = {Bedke, T and Stumme, F and Tomczak, M and Steglich, B and Jia, R and Bohmann, S and Wittek, A and Kempski, J and Göke, E and Böttcher, M and Reher, D and Franke, A and Lennartz, M and Clauditz, T and Sauter, G and Fründt, T and Weidemann, S and Tiegs, G and Schramm, C and Gagliani, N and Pelczar, P and Huber, S}, title = {Protective function of sclerosing cholangitis on IBD.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2023-330856}, pmid = {38839272}, issn = {1468-3288}, abstract = {OBJECTIVE: There is a strong clinical association between IBD and primary sclerosing cholangitis (PSC), a chronic disease of the liver characterised by biliary inflammation that leads to strictures and fibrosis. Approximately 60%-80% of people with PSC will also develop IBD (PSC-IBD). One hypothesis explaining this association would be that PSC drives IBD. Therefore, our aim was to test this hypothesis and to decipher the underlying mechanism.

DESIGN: Colitis severity was analysed in experimental mouse models of colitis and sclerosing cholangitis, and people with IBD and PSC-IBD. Foxp3[+] Treg-cell infiltration was assessed by qPCR and flow cytometry. Microbiota profiling was carried out from faecal samples of people with IBD, PSC-IBD and mouse models recapitulating these diseases. Faecal microbiota samples collected from people with IBD and PSC-IBD were transplanted into germ-free mice followed by colitis induction.

RESULTS: We show that sclerosing cholangitis attenuated IBD in mouse models. Mechanistically, sclerosing cholangitis causes an altered intestinal microbiota composition, which promotes Foxp3[+] Treg-cell expansion, and thereby protects against IBD. Accordingly, sclerosing cholangitis promotes IBD in the absence of Foxp3[+] Treg cells. Furthermore, people with PSC-IBD have an increased Foxp3[+] expression in the colon and an overall milder IBD severity. Finally, by transplanting faecal microbiota into gnotobiotic mice, we showed that the intestinal microbiota of people with PSC protects against colitis.

CONCLUSION: This study shows that PSC attenuates IBD and provides a comprehensive insight into the mechanisms involved in this effect.}, } @article {pmid38839189, year = {2024}, author = {Voth, E and Khanna, S}, title = {Rise to the Challenge: Master the Management of Clostridioides difficile Infection.}, journal = {Mayo Clinic proceedings}, volume = {99}, number = {6}, pages = {971-979}, doi = {10.1016/j.mayocp.2024.02.022}, pmid = {38839189}, issn = {1942-5546}, mesh = {Humans ; *Clostridium Infections/therapy/diagnosis ; *Anti-Bacterial Agents/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Clostridioides difficile ; Gastrointestinal Microbiome ; Risk Factors ; }, abstract = {Clostridioides difficile infection (CDI) is a significant public health challenge in the developed world. Although previously CDI was primarily a health care-acquired infection, there are now rising numbers of community-acquired cases in patients without traditional risk factors, such as antibiotic exposure. The landscape for the treatment of CDI has changed significantly during the past decade, including newer diagnostic tests, novel antibiotic regimens, and strategies for microbiome restoration in the form of traditional fecal microbiota transplant and approved live biotherapeutics in an effort to address the underlying pathophysiologic process of gut microbial dysbiosis. We present a concise review for clinicians on the diagnosis and management of both primary and recurrent CDI.}, } @article {pmid38838972, year = {2024}, author = {Antman, G and Ritzer, L and Galor, A and Verticchio Vercellin, A and Siesky, BA and Alabi, D and Vayner, J and Segev, F and Harris, A}, title = {The Relationship Between Dry Eye Disease and Human Microbiota: A Review of the Science.}, journal = {Experimental eye research}, volume = {}, number = {}, pages = {109951}, doi = {10.1016/j.exer.2024.109951}, pmid = {38838972}, issn = {1096-0007}, abstract = {A complex relationship exists between human microbiota and the risk for ophthalmic disease. While the homeostatic composition of human microbiota is still being established, including what defines dysbiosis (i.e. changes in diversity and abundance), pilot research has begun to identify the potential influence of demographics, geography, and co-morbidities on the microbiota and describe their impact on ocular health. This review specifically focuses on the scientific relationships of the human oral and gut microbiota to dry eye disease (DED), a set of conditions impacting the tear film and ocular surface. Although data are sparse and often conflict across studies, the literature generally supports associations between microbial imbalance (dysbiosis) and DED and alterations in microbial diversity and abundance to specific aspects of DED. This review examines the relevant science and mechanistic relationships linking gut and oral dysbiosis and DED. Various physiochemical factors and therapeutic approaches that alter microbiota, including medications and fecal transplants are examined in relation to DED.}, } @article {pmid38838927, year = {2024}, author = {Meng, Y and Sun, J and Zhang, G}, title = {A viable remedy for overcoming resistance to anti-PD-1 immunotherapy: fecal microbiota transplantation.}, journal = {Critical reviews in oncology/hematology}, volume = {}, number = {}, pages = {104403}, doi = {10.1016/j.critrevonc.2024.104403}, pmid = {38838927}, issn = {1879-0461}, abstract = {Anti-PD-1 immunotherapy is a cancer therapy that focuses explicitly on the PD-1 receptor found on the surface of immune cells. This targeted therapeutic strategy is specifically designed to amplify the immune system's innate capacity to detect and subsequently eliminate cells that have become cancerous. Nevertheless, it should be noted that not all patients exhibit a favourable response to this particular therapeutic modality, necessitating the exploration of novel strategies to augment the effectiveness of immunotherapy. Previous studies have shown that fecal microbiota transplantation (FMT) can enhance the efficacy of anti-PD-1 immunotherapy in advanced melanoma patients. To investigate this intriguing possibility further, we turned to PubMed and conducted a comprehensive search for studies that analyzed the interplay between FMT and anti-PD-1 therapy in the context of tumor treatment. Our search criteria were centred around two key phrases: "fecal microbiota transplantation" and "anti-PD-1 therapy." The studies we uncovered all echo a similar sentiment. They pointed towards the potential of FMT to improve the effectiveness of immunotherapy. FMT may enhance the effectiveness of immunotherapy by altering the gut microbiota and boosting the patient's immunological response. Although promising, additional investigation is needed to improve the efficacy of FMT in the context of cancer therapy and attain a comprehensive understanding of the possible advantages and drawbacks associated with this therapeutic strategy.}, } @article {pmid38838871, year = {2024}, author = {Chen, X and Mo, X and Zhang, Y and He, D and Xiao, R and Cheng, Q and Wang, H and Liu, L and Li, WW and Xie, P}, title = {A comprehensive analysis of the differential expression in the hippocampus of depression induced by gut microbiota compared to traditional stress.}, journal = {Gene}, volume = {}, number = {}, pages = {148633}, doi = {10.1016/j.gene.2024.148633}, pmid = {38838871}, issn = {1879-0038}, abstract = {Depression, which is a disease of heterogeneous etiology, is characterized by high disability and mortality rates. Gut microbiota are associated with the development of depression. To further explore any differences in the mechanisms of depression induced by gut microbiota and traditional stresses, as well as facilitate the development of microbiota-based interventions, a fecal microbiota transplantation (FMT) depression model was made. This was achieved by transplanting feces from major depressive disorder (MDD) patients into germ-free mice. Second, the mechanisms of the depression induced by gut microbiota were analyzed in comparison with those of the depression caused by different forms of stress It turned out that mice exhibited depressive-like behavior after FMT. Then, PCR array analysis was performed on the hippocampus of the depressed mice to identify differentially expressed genes (DEGs). The KEGG analysis revealed that the pathways of depression induced by gut microbes are closely associated with immuno-inflammation. To determine the pathogenic pathways of physiological stress and psychological stress-induced depression, raw data was extracted from several databases and KEGG analysis was performed. The results from the analysis revealed that the mechanisms of depression induced by physiological and psychological stress are closely related to the regulation of neurotransmitters and energy metabolism. Interestingly, the immunoinflammatory response was distinct across different etiologies that induced depression. The findings showed that gut microbiota dysbiosis-induced depression was mainly associated with adaptive immunity, while physiological stress-induced depression was more linked to innate immunity. This study compared the pathogenesis of depression caused by gut microbiota dysbiosis, and physiological and psychological stress. We explored new intervention methods for depression and laid the foundation for precise treatment.}, } @article {pmid38838169, year = {2024}, author = {Han, M and Liang, J and Hou, M and Liu, Y and Li, H and Gao, Z}, title = {Bifidobacterium bifidum Ameliorates DSS-Induced Colitis in Mice by Regulating Microbial Metabolome and Targeting Gut Microbiota.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c00365}, pmid = {38838169}, issn = {1520-5118}, abstract = {Inflammatory bowel disease (IBD) is a recurrent inflammatory condition affecting the gastrointestinal tract, and its clinical treatment remains suboptimal. Probiotics have shown effectiveness in alleviating dextran sulfate sodium salt (DSS)-induced colitis, exhibiting strain-specific anti-inflammatory properties. In this study, we compared the therapeutic effects of five strains of Bifidobacterium bifidum isolated from healthy adult feces on DSS-induced colitis in mice. Additionally, we investigated the underlying mechanisms by examining gut microbiota composition and microbial metabolome. Our findings highlighted the superior efficacy of B. bifidum M1-3 compared to other strains. It significantly improved colitis symptoms, mitigated gut barrier disruption, and reduced colonic inflammation in DSS-treated mice. Moreover, gut microbiota composition analysis revealed that B. bifidum M1-3 treatment increased the abundance and diversity of gut microbiota. Specifically, it significantly increased the abundance of Muribaculaceae, Lactobacillus, Bacteroides, and Enterorhabdus, while decreasing the abundance of Escherichia-Shigella. Furthermore, our nontargeted metabolomics analysis illustrated that B. bifidum M1-3 treatment had a regulatory effect on various metabolic pathways, including tyrosine metabolism, lysine degradation, and tryptophan metabolism. Importantly, we confirmed that the therapeutic efficiency of B. bifidum M1-3 was dependent on the gut microbiota. These results are conducive to the development of probiotic products for alleviating colitis.}, } @article {pmid38835159, year = {2024}, author = {Lyu, W and Li, DF and Li, SY and Hu, H and Zhou, JY and Wang, L}, title = {Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/10408398.2024.2361306}, pmid = {38835159}, issn = {1549-7852}, abstract = {The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.}, } @article {pmid38835057, year = {2024}, author = {Gu, N and Yan, J and Tang, W and Zhang, Z and Wang, L and Li, Z and Wang, Y and Zhu, Y and Tang, S and Zhong, J and Cheng, C and Sun, X and Huang, Z}, title = {Prevotella copri transplantation promotes neurorehabilitation in a mouse model of traumatic brain injury.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {147}, pmid = {38835057}, issn = {1742-2094}, support = {82172193//National Natural Science Foundation of China/ ; 82071397//National Natural Science Foundation of China/ ; 82102316//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Brain Injuries, Traumatic ; Mice ; Male ; *Mice, Inbred C57BL ; *Disease Models, Animal ; Neurological Rehabilitation/methods ; Prevotella ; Gastrointestinal Microbiome/physiology ; Phosphatidylinositol 3-Kinases/metabolism ; }, abstract = {BACKGROUND: The gut microbiota plays a critical role in regulating brain function through the microbiome-gut-brain axis (MGBA). Dysbiosis of the gut microbiota is associated with neurological impairment in Traumatic brain injury (TBI) patients. Our previous study found that TBI results in a decrease in the abundance of Prevotella copri (P. copri). P. copri has been shown to have antioxidant effects in various diseases. Meanwhile, guanosine (GUO) is a metabolite of intestinal microbiota that can alleviate oxidative stress after TBI by activating the PI3K/Akt pathway. In this study, we investigated the effect of P. copri transplantation on TBI and its relationship with GUO-PI3K/Akt pathway.

METHODS: In this study, a controlled cortical impact (CCI) model was used to induce TBI in adult male C57BL/6J mice. Subsequently, P. copri was transplanted by intragastric gavage for 7 consecutive days. To investigate the effect of the GUO-PI3K/Akt pathway in P. copri transplantation therapy, guanosine (GUO) was administered 2 h after TBI for 7 consecutive days, and PI3K inhibitor (LY294002) was administered 30 min before TBI. Various techniques were used to assess the effects of these interventions, including quantitative PCR, neurological behavior tests, metabolite analysis, ELISA, Western blot analysis, immunofluorescence, Evans blue assays, transmission electron microscopy, FITC-dextran permeability assay, gastrointestinal transit assessment, and 16 S rDNA sequencing.

RESULTS: P. copri abundance was significantly reduced after TBI. P. copri transplantation alleviated motor and cognitive deficits tested by the NSS, Morris's water maze and open field test. P. copri transplantation attenuated oxidative stress and blood-brain barrier damage and reduced neuronal apoptosis after TBI. In addition, P. copri transplantation resulted in the reshaping of the intestinal flora, improved gastrointestinal motility and intestinal permeability. Metabolomics and ELISA analysis revealed a significant increase in GUO levels in feces, serum and injured brain after P. copri transplantation. Furthermore, the expression of p-PI3K and p-Akt was found to be increased after P. copri transplantation and GUO treatment. Notably, PI3K inhibitor LY294002 treatment attenuated the observed improvements.

CONCLUSIONS: We demonstrate for the first time that P. copri transplantation can improve GI functions and alter gut microbiota dysbiosis after TBI. Additionally, P. copri transplantation can ameliorate neurological deficits, possibly via the GUO-PI3K/Akt signaling pathway after TBI.}, } @article {pmid38833830, year = {2024}, author = {Ma, B and Wang, D and Chen, X and Wang, Q and Zhang, T and Wen, R and Yang, M and Li, C and Lei, C and Wang, H}, title = {Dietary α-linolenic acid supplementation enhances resistance to Salmonella Typhimurium challenge in chickens by altering the intestinal mucosal barrier integrity and cecal microbes.}, journal = {Microbiological research}, volume = {285}, number = {}, pages = {127773}, doi = {10.1016/j.micres.2024.127773}, pmid = {38833830}, issn = {1618-0623}, abstract = {Salmonella is an important foodborne pathogen. Given the ban on the use of antibiotics during the egg-laying period in China, finding safe and effective alternatives to antibiotics to reduce Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infections in chickens is essential for the prevention and control of this pathogen and the protection of human health. Numerous studies have shown that unsaturated fatty acids have a positive effect on intestinal inflammation and resistance to infection by intestinal pathogens. Here we investigated the protective effect of α-linolenic acid (ALA) against S. Typhimurium infection in chickens and further explored its mechanism of action. We added different proportions of ALA to the feed and observed the effect of ALA on S. Typhimurium colonization using metagenomic sequencing technology and physiological index measurements. The role of gut flora on S. Typhimurium colonization was subsequently verified by fecal microbiota transplantation (FMT). We found that ALA protects chickens from S. Typhimurium infection by reducing intestinal inflammation through remodeling the gut microbiota, up-regulating the expression of ileocecal barrier-related genes, and maintaining the integrity of the intestinal epithelium. Our data suggest that supplementation of feed with ALA may be an effective strategy to alleviate S. Typhimurium infection in chickens.}, } @article {pmid38831430, year = {2024}, author = {Gao, X and Zhu, Z and Bao, Y and Li, Y and Zhu, W and He, X and Ge, X and Huang, W and Wang, H and Wei, W and Du, J and Chen, L and Li, H and Sheng, L}, title = {Chrysanthemum morifolium Ramat extract and probiotics combination ameliorates metabolic disorders through regulating gut microbiota and PPARα subcellular localization.}, journal = {Chinese medicine}, volume = {19}, number = {1}, pages = {76}, pmid = {38831430}, issn = {1749-8546}, support = {82273624//National Natural Science Foundation of China/ ; U21A20413//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Chrysanthemum morifolium Ramat, a traditional Chinese medicine, has the effects on liver clearing, vision improving, and anti-inflammation. C. morifolium and probiotics have been individually studied for their beneficial effects on metabolic diseases. However, the underlying molecular mechanisms were not completely elucidated. This study aims to elucidate the potential molecular mechanisms of C. morifolium and probiotics combination (CP) on alleviating nonalcoholic fatty liver disease (NAFLD) and the dysregulation of glucose metabolism in high-fat diet (HFD)-fed mice.

METHODS: The therapeutic effect of CP on metabolism was evaluated by liver histology and serum biochemical analysis, as well as glucose tolerance test. The impact of CP on gut microbiota was analyzed by 16S rRNA sequencing and fecal microbiota transplantation. Hepatic transcriptomic analysis was performed with the key genes and proteins validated by RT-qPCR and western blotting. In addition, whole body Pparα knockout (Pparα[-/-]) mice were used to confirm the CP-mediated pathway.

RESULTS: CP supplementation ameliorated metabolic disorders by reducing body weight and hepatic steatosis, and improving glucose intolerance and insulin resistance in HFD fed mice. CP intervention mitigated the HFD-induced gut microbiota dysbiosis, which contributed at least in part, to the beneficial effect of improving glucose metabolism. In addition, hepatic transcriptomic analysis showed that CP modulated the expression of genes associated with lipid metabolism. CP downregulated the mRNA level of lipid droplet-binding proteins, such as Cidea and Cidec in the liver, leading to more substrates for fatty acid oxidation (FAO). Meanwhile, the expression of CPT1α, the rate-limiting enzyme of FAO, was significantly increased upon CP treatment. Mechanistically, though CP didn't affect the total PPARα level, it promoted the nuclear localization of PPARα, which contributed to the reduced expression of Cidea and Cidec, and increased expression of CPT1α, leading to activated FAO. Moreover, whole body PPARα deficiency abolished the anti-NAFLD effect of CP, suggesting the importance of PPARα in CP-mediated beneficial effect.

CONCLUSION: This study revealed the hypoglycemic and hepatoprotective effect of CP by regulating gut microbiota composition and PPARα subcellular localization, highlighting its potential for therapeutic candidate for metabolic disorders.}, } @article {pmid38831225, year = {2024}, author = {Raghani, N and Postwala, H and Shah, Y and Chorawala, M and Parekh, P}, title = {From Gut to Brain: Unraveling the Intricate Link Between Microbiome and Stroke.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {38831225}, issn = {1867-1314}, abstract = {Stroke, a neurological disorder, is intricately linked to the gut microbiota, influencing microbial composition and elevating the risk of ischemic stroke. The neuroprotective impact of short-chain fatty acids (SCFAs) derived from dietary fiber fermentation contrasts with the neuroinflammatory effects of lipopolysaccharide (LPS) from gut bacteria. The pivotal role of the gut-brain axis, facilitating bidirectional communication between the gut and the brain, is crucial in maintaining gastrointestinal equilibrium and influencing cognitive functions. An in-depth understanding of the interplay among the gut microbiota, immune system, and neurological outcomes in stroke is imperative for devising innovative preventive and therapeutic approaches. Strategies such as dietary adjustments, probiotics, prebiotics, antibiotics, or fecal transplantation offer promise in modulating stroke outcomes. Nevertheless, comprehensive research is essential to unravel the precise mechanisms governing the gut microbiota's involvement in stroke and to establish effective therapeutic interventions. The initiation of large-scale clinical trials is warranted to assess the safety and efficacy of interventions targeting the gut microbiota in stroke management. Tailored strategies that reinstate eubiosis and foster a healthy gut microbiota hold potential for both stroke prevention and treatment. This review underscores the gut microbiota as a promising therapeutic target in stroke and underscores the need for continued research to delineate its precise role and develop microbiome-based interventions effectively.}, } @article {pmid38830845, year = {2024}, author = {Mao, X and Larsen, SB and Zachariassen, LSF and Brunse, A and Adamberg, S and Mejia, JLC and Larsen, F and Adamberg, K and Nielsen, DS and Hansen, AK and Hansen, CHF and Rasmussen, TS}, title = {Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4704}, pmid = {38830845}, issn = {2041-1723}, support = {R324-2019-1880//Lundbeckfonden (Lundbeck Foundation)/ ; NNF-20OC0063874//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; }, mesh = {Animals ; Male ; *Metabolic Syndrome/therapy ; *Obesity/therapy ; *Gastrointestinal Microbiome ; *Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; Mice ; *Diet, High-Fat/adverse effects ; *Virome ; *Mice, Obese ; Dysbiosis/therapy ; Feces/virology/microbiology ; Bacteriophages/physiology ; Blood Glucose/metabolism ; Disease Models, Animal ; Liver/pathology/metabolism ; Adipose Tissue ; }, abstract = {Metabolic syndrome encompasses amongst other conditions like obesity and type-2 diabetes and is associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM; however, concerns on accidentally transferring pathogenic microbes remain. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred. FVT from lean male donors have shown promise in alleviating the metabolic effects of high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, recently developed methods are applied for removing or inactivating eukaryotic viruses in the viral component of FVT. Modified FVTs are compared with unmodified FVT and saline in a diet-induced obesity model on male C57BL/6 N mice. Contrasted with obese control, mice administered a modified FVT (nearly depleted for eukaryotic viruses) exhibits enhanced blood glucose clearance but not weight loss. The unmodified FVT improves liver pathology and reduces the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggests that bacteriophage-mediated GM modulation influences outcomes. Optimizing these approaches could lead to the development of safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration.}, } @article {pmid38829940, year = {2024}, author = {Tan, S and Zhang, W and Zeng, P and Yang, Y and Chen, S and Li, Y and Bian, Y and Xu, C}, title = {Clinical effects of chemical drugs, fecal microbiota transplantation, probiotics, dietary fiber, and acupuncture in the treatment of chronic functional constipation: a systematic review and network meta-analysis.}, journal = {European journal of gastroenterology & hepatology}, volume = {36}, number = {7}, pages = {815-830}, doi = {10.1097/MEG.0000000000002786}, pmid = {38829940}, issn = {1473-5687}, mesh = {*Constipation/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/adverse effects ; *Dietary Fiber/therapeutic use ; *Probiotics/therapeutic use/adverse effects ; Chronic Disease ; *Acupuncture Therapy/methods ; Treatment Outcome ; Network Meta-Analysis ; Randomized Controlled Trials as Topic ; Quality of Life ; Laxatives/therapeutic use ; }, abstract = {Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10 mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.}, } @article {pmid38828853, year = {2024}, author = {Chasov, V and Zmievskaya, E and Ganeeva, I and Gilyazova, E and Davletshin, D and Filimonova, M and Valiullina, A and Kudriaeva, A and Bulatov, E}, title = {Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation.}, journal = {Journal of biomedical research}, volume = {}, number = {}, pages = {1-16}, doi = {10.7555/JBR.38.20240009}, pmid = {38828853}, issn = {1674-8301}, abstract = {Systemic lupus erythematosus (SLE) is characterized by a systemic dysfunction of the innate and adaptive immune systems, leading to an attack on healthy tissues of the body. During the development of SLE, pathogenic features, such as the formation of autoantibodies to self-nuclear antigens, caused tissue damage including necrosis and fibrosis, with an increased expression of type Ⅰ interferon (IFN) regulated genes. Treatment of lupus with immunosuppressants and glucocorticoids, which are used as the standard therapy, is not effective enough and causes side effects. As an alternative, more effective immunotherapies have been developed, including monoclonal and bispecific antibodies that target B cells, T cells, co-stimulatory molecules, cytokines or their receptors, and signaling molecules. Encouraging results have been observed in clinical trials with some of these therapies. Furthermore, a chimeric antigen receptor T cells (CAR-T) therapy has emerged as the most effective, safe, and promising treatment option for SLE, as demonstrated by successful pilot studies. Additionally, emerging evidence suggests that gut microbiota dysbiosis may play a significant role in the severity of SLE, and the use of methods to normalize the gut microbiota, particularly fecal microbiota transplantation (FMT), opens up new opportunities for effective treatment of SLE.}, } @article {pmid38828210, year = {2024}, author = {Ravel, SJ and Hollifield, VM}, title = {Fecal Microbiota Transplantation in a Domestic Ferret Suffering from Chronic Diarrhea and Maldigestion-Fecal Microbiota and Clinical Outcome: A Case Report.}, journal = {Veterinary medicine (Auckland, N.Z.)}, volume = {15}, number = {}, pages = {171-180}, pmid = {38828210}, issn = {2230-2034}, abstract = {This case report describes the effects of fecal microbiota transplantation (FMT) administered via enema in a 4-year-old spayed, champagne Domestic Ferret (Mustela putorius furo) with chronic diarrhea, maldigestion and weight loss. We aimed to establish a protocol for FMT as a novel therapeutic treatment for chronic diarrhea in domestic ferrets. We mapped the fecal microbiome by 16S rRNA gene amplicon sequencing to track the patient's fecal microbiota throughout the treatment and observation period. Initial oral FMTs were associated with temporary weight improvement but subsequent treatments, via enema and oral delivery, showed varied outcomes. Molecular analysis highlighted distinct gut microbiota composition profiles between the healthy donor and the diseased ferret. The diseased ferret initially exhibited high abundance of Enterobacteriaceae, Escherichia, and Enterobacter, which ultimately normalized to level like those found in the donor ferret. Overall, the gut microbiota of the recipient became more similar to the donor microbiota using a Yue-Clayton theta coefficients analysis. After a restoration of the gut microbiota and clinical improvement, the recipient's symptoms returned indicating that repeated FMTs might be required for long-term resolution of symptoms and complete restructuring of the gut microbiota. Future studies are warranted to map the microbiome of a larger population of domestic ferrets to investigate a potential correlation between fecal microbiota profiles and chronic/acute gastrointestinal disorders.}, } @article {pmid38826830, year = {2024}, author = {Sahle, Z and Engidaye, G and Shenkute Gebreyes, D and Adenew, B and Abebe, TA}, title = {Fecal microbiota transplantation and next-generation therapies: A review on targeting dysbiosis in metabolic disorders and beyond.}, journal = {SAGE open medicine}, volume = {12}, number = {}, pages = {20503121241257486}, pmid = {38826830}, issn = {2050-3121}, abstract = {The human microbiome, particularly the gut microbiome, has emerged as a central determinant of health and disease. Dysbiosis, an imbalance in the microbial composition of the gut, is associated with a variety of metabolic and other diseases, highlighting the potential for microbiota-targeted treatments. Fecal microbiota transplantation has received considerable attention as a promising therapy to modulate the gut microbiome and restore microbial homeostasis. However, challenges remain, including standardization, safety, and long-term efficacy. This review summarizes current knowledge on fecal microbiota transplantation and describes the next generation therapies targeting microbiome. This review looked at the mechanistic understanding of fecal microbiota transplantation and alternative strategies, elucidating their potential role in improving dysbiosis-associated metabolic disorders, such as obesity, and type 2 diabetes and others. Additionally, this review discussed the growing application of therapies targeting the gut microbiome. Insights from clinical trials, preclinical studies, and emerging technologies provide a comprehensive overview of the evolving landscape of microbiome-based interventions. Through a critical assessment of current advances and prospects, this review aims to highlight the therapeutic potential of targeting gut microbiome and pave the way for innovative approaches in precision medicine and personalized treatments.}, } @article {pmid38825293, year = {2024}, author = {Wu, L and Hu, Z and Lv, Y and Ge, C and Luo, X and Zhan, S and Huang, W and Shen, X and Yu, D and Liu, B}, title = {Hericium erinaceus polysaccharides ameliorate nonalcoholic fatty liver disease via gut microbiota and tryptophan metabolism regulation in an aged laying hen model.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {132735}, doi = {10.1016/j.ijbiomac.2024.132735}, pmid = {38825293}, issn = {1879-0003}, abstract = {Polysaccharides extracted from Hericium erinaceus (HEP) exhibit hepatoprotective activity in the alleviation of non-alcoholic fatty liver disease (NAFLD); however, the mechanisms underlying whether and how HEP regulation of the gut microbiota to alleviate liver-associated metabolic disorders are not well understood. This study used an aged laying hen model to explore the mechanisms through which HEP alleviates NAFLD, with a focus on regulatory function of HEP in the gut microbiome. The results showed that HEP ameliorated hepatic damage and metabolic disorders by improving intestinal barrier function and shaping the gut microbiota and tryptophan metabolic profiles. HEP increased the abundance of Lactobacillus and certain tryptophan metabolites, including indole-3-carboxylic acid, kynurenic acid, and tryptamine in the cecum. These metabolites upregulated the expression of ZO-1 and Occludin by activating the AhR and restoring the intestinal barrier integrity. The increased intestinal barrier functions decreased LPS transferring from the intestine to the liver, inhibited hepatic LPS/TLR4/MyD88/NF-κB pathway activation, and reduced hepatic inflammatory response and apoptosis. Fecal microbiota transplantation experiments further confirmed that the hepatoprotective effect is likely mediated by HEP-altered gut microbiota and their metabolites. Overall, dietary HEP could ameliorate the hepatic damage and metabolic disorders of NAFLD through regulating the "gut-liver" axis.}, } @article {pmid38824460, year = {2024}, author = {He, Z and Liu, Y and Li, Z and Sun, T and Li, Z and Liu, C and Xiang, H}, title = {Gut Microbiota-Mediated Alterations of Hippocampal CB1R Regulating the Diurnal Variation of Cognitive Impairment Induced by Hepatic Ischemia-Reperfusion Injury in Mice.}, journal = {Neurochemical research}, volume = {}, number = {}, pages = {}, pmid = {38824460}, issn = {1573-6903}, support = {82070302//National Natural Science Foundation of China/ ; }, abstract = {Patients suffering from hepatic ischemia-reperfusion injury (HIRI) frequently exhibit postoperative cognitive deficits. Our previous observations have emphasized the diurnal variation in hepatic ischemia-reperfusion injury-induced cognitive impairment, in which gut microbiota-associated hippocampal lipid metabolism plays an important role. Herein, we further investigated the molecular mechanisms involved in the process. Hepatic ischemia-reperfusion surgery was performed under morning (ZT0, 08:00) and evening (ZT12, 20:00). Fecal microbiota transplantation was used to associate HIRI model with pseudo-germ-free mice. The novel object recognition test and Y-maze test were used to assess cognitive function. 16S rRNA gene sequencing and analysis were used for microbial analysis. Western blotting was used for hippocampal protein analysis. Compared with the ZT0-HIRI group, ZT12-HIRI mice showed learning and short term memory impairment, accompanied by down-regulated expression of hippocampal CB1R, but not CB2R. Both gut microbiota composition and microbiota metabolites were significantly different in ZT12-HIRI mice compared with ZT0-HIRI. Fecal microbiota transplantation from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior and down-regulated hippocampal CB1R and β-arrestin1. Intraperitoneal administration of CB1R inhibitor AM251 (1 mg/kg) down-regulated hippocampal CB1R and caused cognitive impairment in ZT0-HIRI mice. And intraperitoneal administration of CB1R agonist WIN 55,212-2 (1 mg/kg) up-regulated hippocampal CB1R and improved cognitive impairment in ZT12-HIRI mice. In summary, the results suggest that gut microbiota may regulate the diurnal variation of HIRI-induced cognitive function by interfering with hippocampal CB1R.}, } @article {pmid38823462, year = {2024}, author = {Xu, H and Li, O and Kim, D and Xue, M and Bao, Z and Yang, F}, title = {Aged microbiota exacerbates cardiac failure by PPARα/PGC1α pathway.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {}, number = {}, pages = {167271}, doi = {10.1016/j.bbadis.2024.167271}, pmid = {38823462}, issn = {1879-260X}, abstract = {The dysbiosis of gut microbiota with aging has been extensively studied, revealing its substantial contribution to variety of diseases. However, the impact of aged microbiota in heart failure (HF) remains unclear. In this study, we employed the method of fecal microbiota transplantation (FMT) from aged donors to investigate its role in the context of HF. Our results demonstrate that FMT from aged donors alters the recipient's gut microbiota composition and abundance. Furthermore, FMT impairs cardiac function and physical activity in HF mice. Aged FMT induces metabolic alterations, leading to body weight gain, impaired glucose tolerance, increased respiratory exchange ratio (RER), and enhanced fat accumulation. The epicardium of aged FMT recipients shows fat accumulation, accompanied by cardiomyocyte hypertrophy, cardiac fibrosis and increased cellular apoptosis. Mechanistically, aged FMT suppresses the PPARα/PGC1α signaling pathway in HF. Notably, activation of PPARα effectively rescues the metabolic changes and myocardial injury caused by aged FMT. In conclusion, our study emphasizes the role of the PPARα/PGC1α signaling pathway in aged FMT-mediated HF.}, } @article {pmid38821245, year = {2024}, author = {Huang, Y and Li, Y and Guan, D and Pan, Y and Yang, C and Liu, H and Chen, C and Chen, W and Liu, J and Wan, T and Zhuang, L and Wang, Q and Zhang, Y}, title = {Acorus tatarinowii oils exert protective effects on microglia-mediated inflammatory injury via restoring gut microbiota composition in experimental stroke rats.}, journal = {Brain research bulletin}, volume = {213}, number = {}, pages = {110990}, doi = {10.1016/j.brainresbull.2024.110990}, pmid = {38821245}, issn = {1873-2747}, abstract = {Growing evidence has demonstrated that gut microbiota could be developed as a therapeutic target due to its contribution to microglia activation in the pathological process of ischemic stroke. Acorus tatarinowii oils (AT oils), which is considered as the active fraction of a traditional Chinese herbal medicine Acorus tatarinowii, exerts various bioactivities and prebiotic effects. However, it remains unclear that the effect of AT oils on inflammatory response after ischemic stroke and whether its underlying mechanism is associated to gut microbiota and the intestinal barrier. In the current study, we aim to investigate the anti-microglial neuroinflammation mechanism of AT oils in a middle cerebral artery occlusion model of ischemic stroke. The compositions of AT oils were identified by GC-MS. Our results demonstrated that AT oils could effectively relieve cerebral infarction, inhibit neuronal apoptosis, degrade the release of pro-inflammatory factors (TNF-α, IL-17, IL-6 and IFN-γ), and mediate the polarization of microglia. Moreover, AT oils restored the composition and the balance of gut microbiota in stroke rats, and reduced abundance of opportunistic genera including Verrucomicrobia, Akkermansia and Tenericutes, as well as increased beneficial bacteria abundance such as Tenericutes and Prevotella_copri. To investigate the role of gut microbiota on AT oils against ischemic stroke, we conducted the fecal microbiota transplantation (FMT) experiments with gut microbiota consumption, which suggested that the depletion of gut microbiota took away the protective effect of AT oils, confirming the importance of gut microbiota in the protective effect of AT oils on ischemic stroke. FMT experiments have demonstrated that AT oils preserved the gut permeability and blood-brain barrier, as well as mediated the microglial phenotype under the intervention of gut microbiota. In summary, AT oils could efficaciously moderate neuronal damage and intervene microglial phenotype by reversing gut microbiota disorder in ischemic stroke rats.}, } @article {pmid38821056, year = {2024}, author = {Swisa, A and Kieckhaefer, J and Daniel, SG and El-Mekkoussi, H and Kolev, HM and Tigue, M and Jin, C and Assenmacher, CA and Dohnalová, L and Thaiss, CA and Karlsson, NG and Bittinger, K and Kaestner, KH}, title = {The evolutionarily ancient FOXA transcription factors shape the murine gut microbiome via control of epithelial glycosylation.}, journal = {Developmental cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.devcel.2024.05.006}, pmid = {38821056}, issn = {1878-1551}, abstract = {Evolutionary adaptation of multicellular organisms to a closed gut created an internal microbiome differing from that of the environment. Although the composition of the gut microbiome is impacted by diet and disease state, we hypothesized that vertebrates promote colonization by commensal bacteria through shaping of the apical surface of the intestinal epithelium. Here, we determine that the evolutionarily ancient FOXA transcription factors control the composition of the gut microbiome by establishing favorable glycosylation on the colonic epithelial surface. FOXA proteins bind to regulatory elements of a network of glycosylation enzymes, which become deregulated when Foxa1 and Foxa2 are deleted from the intestinal epithelium. As a direct consequence, microbial composition shifts dramatically, and spontaneous inflammatory bowel disease ensues. Microbiome dysbiosis was quickly reversed upon fecal transplant into wild-type mice, establishing a dominant role for the host epithelium, in part mediated by FOXA factors, in controlling symbiosis in the vertebrate holobiont.}, } @article {pmid38820960, year = {2024}, author = {Zheng, D and Ke, X and Cai, H and Yan, C and Chen, Y and Sun, J and Chen, G}, title = {Oral administration of RDP58 ameliorated DSS-induced colitis in intestinal microbiota dependent manner.}, journal = {International immunopharmacology}, volume = {136}, number = {}, pages = {112325}, doi = {10.1016/j.intimp.2024.112325}, pmid = {38820960}, issn = {1878-1705}, abstract = {BACKGROUND: Although the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has not been fully elucidated, accumulating researches suggest that intestinal microbiota imbalance contributes to the development of IBD in patients and animal models. RDP58, a peptide-based computer-assisted rational design, has been demonstrated to be effective in protecting against a wide range of autoimmune and inflammatory diseases. However, the underlying mechanism by which RDP58 protects against IBD mediated by intestinal microbiota has yet to be elucidated.

METHODS: The colitis model was induced by continuously administering 2.5 % (wt/vol) dextran sodium sulfate (DSS) solution for 7 days. The manifestations of colon inflammation were assessed via daily weight changes, colon length, tumor necrosis factor-alpha (TNF-α) level, disease activity index (DAI) score, pathology score, and intestinal barrier permeability. Intestinal microbiota analysis was carried out by 16S-rRNA sequencing. Colonic short chain fatty acids (SCFAs) and regulatory T cells (Tregs) were also detected. To further confirm the protective effect of RDP58 on intestinal microbiota, broad-spectrum antibiotic cocktail (ABX) treatment and fecal microbial transplantation (FMT) experiment were performed.

RESULTS: Oral administration of RDP58 ameliorated DSS-induced mice colitis by altering the diversity and composition of intestinal microbiota. Notably, RDP58 significantly upregulated SCFAs-producing microbiota, thereby promoting the generation of Tregs. ABX and FMT were performed to verify the above mechanism.

CONCLUSIONS: RDP58 ameliorated DSS-induced colitis through altering intestinal microbiota and enhancing SCFAs and Tregs production in intestinal microbiota dependent manner, potentially provide a novel therapy for IBD.}, } @article {pmid38818298, year = {2024}, author = {Samanta, A and Sen Sarma, M}, title = {Fecal microbiota transplantation in the treatment of hepatic encephalopathy: A perspective.}, journal = {World journal of hepatology}, volume = {16}, number = {5}, pages = {678-683}, pmid = {38818298}, issn = {1948-5182}, abstract = {Due to its complex pathogenesis, treatment of hepatic encephalopathy (HE) continues to be a therapeutic challenge. Of late, gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use. New evidence suggests that gut microbiota plays a significant role in cerebral homeostasis. Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies. Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics, prebiotics and the latest fecal microbiota transplantation (FMT). Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE. However, questions over the appropriate dose, duration and route of administration for best treatment outcome remains unsettled.}, } @article {pmid38818289, year = {2024}, author = {Li, Y and Zhang, XH and Wang, ZK}, title = {Microbiota treatment of functional constipation: Current status and future prospects.}, journal = {World journal of hepatology}, volume = {16}, number = {5}, pages = {776-783}, pmid = {38818289}, issn = {1948-5182}, abstract = {Functional constipation (FC) is a common disorder that is characterized by difficult stool passage, infrequent bowel movement, or both. FC is highly prevalent, recurs often, accompanies severe diseases, and affects quality of life; therefore, safe and effective therapy with long-term benefits is urgently needed. Microbiota treatment has potential value for FC treatment. Microbiota treatments include modulators such as probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). Some probiotics and prebiotics have been adopted, and the efficacy of other microbiota modulators is being explored. FMT is considered an emerging field because of its curative effects; nevertheless, substantial work must be performed before clinical implementation.}, } @article {pmid38817661, year = {2024}, author = {Wang, L and Li, Y and Zhang, YJ and Peng, LH}, title = {Intestinal microecological transplantation for a patient with chronic radiation enteritis: A case report.}, journal = {World journal of gastroenterology}, volume = {30}, number = {19}, pages = {2603-2611}, pmid = {38817661}, issn = {2219-2840}, mesh = {Humans ; Female ; Middle Aged ; *Enteritis/microbiology/diagnosis/etiology/therapy ; *Radiation Injuries/diagnosis/microbiology/etiology/surgery ; *Gastrointestinal Microbiome/radiation effects ; *Fecal Microbiota Transplantation/methods ; *Uterine Cervical Neoplasms/radiotherapy ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; Chronic Disease ; Colonoscopy ; Intestines/microbiology/radiation effects ; Feces/microbiology ; Radiotherapy/adverse effects ; }, abstract = {BACKGROUND: The gut microbiota is strongly associated with radiation-induced gut damage. This study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation enteritis.

CASE SUMMARY: A 64-year-old female with cervical cancer developed abdominal pain, diarrhea, and blood in the stool 1 year after radiotherapy. An electronic colonoscopy was performed to diagnose chronic radiation enteritis. Two courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were performed. The patient experienced short- and long-term relief from symptoms without adverse effects. Whole 16S rRNA sequencing revealed significant differences in the intestinal flora's composition between patient and healthy donors. Pathogenic bacteria, such as Escherichia fergusonii and Romboutsia timonensis, were more in the patient. Beneficial bacteria such as Faecalibacterium prausnitzii, Fusicatenibacter saccharivorans, Ruminococcus bromii, and Bifidobacterium longum were more in the healthy donors. Intestinal microbiota transplantation resulted in a significant change in the patient's intestinal flora composition. The composition converged with the donor's flora, with an increase in core beneficial intestinal bacteria, such as Eubacterium rectale, and a decrease in pathogenic bacteria. Changes in the intestinal flora corresponded with the patients' alleviating clinical symptoms.

CONCLUSION: Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal flora. This study provides a new approach for treating patients with chronic radiation enteritis.}, } @article {pmid38816750, year = {2024}, author = {Li, Y and Sun, R and Lai, C and Liu, K and Yang, H and Peng, Z and Xu, D and Huang, F and Tang, K and Peng, Y and Liu, X}, title = {Hyperbaric oxygen therapy ameliorates intestinal and systematic inflammation by modulating dysbiosis of the gut microbiota in Crohn's disease.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {518}, pmid = {38816750}, issn = {1479-5876}, support = {82230019//National Natural Science Foundation of China/ ; 82170599//National Natural Science Foundation of China/ ; 82070651//National Natural Science Foundation of China/ ; }, mesh = {*Crohn Disease/therapy/microbiology ; Humans ; *Dysbiosis/therapy/microbiology ; *Hyperbaric Oxygenation ; *Gastrointestinal Microbiome ; Animals ; Female ; Male ; *Inflammation/therapy ; Adult ; Intestines/microbiology ; Middle Aged ; Fecal Microbiota Transplantation ; Mice ; Mice, Inbred C57BL ; Young Adult ; }, abstract = {BACKGROUND: Dysbiosis of the gut microbiota is pivotal in Crohn's disease (CD) and modulated by host physiological conditions. Hyperbaric oxygen therapy (HBOT) is a promising treatment for CD that can regulate gut microbiota. The relationship between HBOT and the gut microbiota in CD remains unknown.

METHODS: CD patients were divided into an HBOT group (n = 10) and a control group (n = 10) in this open-label prospective interventional study. The fecal samples before and after HBOT were used for 16 S rRNA gene sequencing and fecal microbiota transplantation (FMT). A colitis mouse model was constructed using dextran sulfate sodium, and intestinal and systematic inflammation was evaluated. The safety and long-term effect of HBOT were observed.

RESULTS: HBOT significantly reduced the level of C-reactive protein (CRP) (80.79 ± 42.05 mg/L vs. 33.32 ± 18.31 mg/L, P = 0.004) and the Crohn's Disease Activity Index (CDAI) (274.87 ± 65.54 vs. 221.54 ± 41.89, P = 0.044). HBOT elevated the declined microbial diversity and ameliorated the altered composition of gut microbiota in patients with CD. The relative abundance of Escherichia decreased, and that of Bifidobacterium and Clostridium XIVa increased after HBOT. Mice receiving FMT from donors after HBOT had significantly less intestinal inflammation and serum CRP than the group before HBOT. HBOT was safe and well-tolerated by patients with CD. Combined with ustekinumab, more patients treated with HBOT achieved clinical response (30%vs.70%, P = 0.089) and remission (20%vs.50%, P = 0.160) at week 4.

CONCLUSIONS: HBOT modulates the dysbiosis of gut microbiota in CD and ameliorates intestinal and systematic inflammation. HBOT is a safe option for CD and exhibits a promising auxiliary effect to ustekinumab.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061193. Registered 15 June 2022, https://www.chictr.org.cn/showproj.html?proj=171605 .}, } @article {pmid38810793, year = {2024}, author = {Li, H and Liu, S and Chen, H and Zhou, L and Chen, B and Wang, M and Zhang, D and Han, TL and Zhang, H}, title = {Gut dysbiosis contributes to SCFAs reduction-associated adipose tissue macrophage polarization in gestational diabetes mellitus.}, journal = {Life sciences}, volume = {350}, number = {}, pages = {122744}, doi = {10.1016/j.lfs.2024.122744}, pmid = {38810793}, issn = {1879-0631}, abstract = {AIMS: The prevalence of gestational diabetes mellitus (GDM) has spurred investigations into various interconnected factors, among which gut dysbiosis is notably prominent. Although gut dysbiosis is strongly associated with GDM, the specific role of the gut microbiome in the pathogenesis of GDM remains unknown. This study aims to explore the pathogenesis of GDM from gut microbiota.

MATERIALS AND METHODS: In our study, we constructed two GDM mice models: one induced by a high-fat diet (HFD) and the other through fecal microbiota transplantation (FMT) from GDM patients. In vitro, we used a co-culture system of RAW264.7 and 3T3-L1 adipocytes.

KEY FINDINGS: We induced a GDM-like state in pregnant mice by FMT from GDM patients, which was consistent with the HFD model. A potential mechanism identified involves the diminished abundance of SCFA-producing microbiota, which reduces SCFAs, particularly propionic acid and butyric acid. In vitro, butyric and propionic acids were observed to alleviate LPS-induced TLR4-NF-κB activation, thereby reducing inflammation levels and inhibiting adipose insulin resistance via the PI3K/AKT signaling pathway. This reduction appears to trigger the polarization of adipose tissue macrophages toward M1 and promote insulin resistance in adipose tissue.

SIGNIFICANCE: Our study fills this knowledge gap by finding that alterations in gut microbiota have an independent impact on hyperglycemia and insulin resistance in the GDM state. In vivo and in vitro, gut dysbiosis is linked to adipose tissue inflammation and insulin resistance via the bacterial product SCFAs in the GDM state, providing new insights into the pathogenesis of GDM.}, } @article {pmid38810309, year = {2024}, author = {Feng, R and Wang, Q and Yu, T and Hu, H and Wu, G and Duan, X and Jiang, R and Xu, Y and Huang, Y}, title = {Quercetin ameliorates bone loss in OVX rats by modulating the intestinal flora-SCFAs-inflammatory signaling axis.}, journal = {International immunopharmacology}, volume = {136}, number = {}, pages = {112341}, doi = {10.1016/j.intimp.2024.112341}, pmid = {38810309}, issn = {1878-1705}, abstract = {BACKGROUND: Osteoporosis (OP) is a common systemic skeletal disorder characterized by an imbalance in bone homeostasis, involving increased osteoclastic bone formation and decreased osteoblastic bone resorption. Quercetin is a plant polyphenol that has been found to exhibit various biological activities, including antioxidant, anti-inflammatory, and antimicrobial effects. Previous studies have demonstrated its potential to improve postmenopausal OP, although the exact mechanism remains unclear. This study aims to investigate the anti-osteoporotic mechanism of quercetin based on the "intestinal flora - short-chain fatty acids (SCFAs) - inflammatory" signaling axis.

METHODS: In this study, we established an ovariectomized (OVX)-induced rat model, quercetin intervention and evaluated the effects on rats following antibiotic (ABX) treatment and fecal microbiota transplantation (FMT). After 6 weeks of intervention, the rats were euthanized, and samples from their femur, tibia, lumbar spine, serum, colon and feces were collected, and bone strength, intestinal flora structure, SCFAs levels and cytokine levels were assessed.

RESULTS: Quercetin modulates the intestinal flora by increasing potentially probiotic bacteria (i.e., Lactobacillales, Prevotellaceae, and Blautia) and decreasing potentially pathogenic bacteria (Desulfobacterota, Erysipelotrichales, Romboutsia, and Butyricoccaceae). It also increases SCFAs content and reduces colonic permeability by enhancing tight junction proteins (ZO-1, Occludin). Furthermore, quercetin lowers proinflammatory cytokine levels (LPS, IL-1β, and TNF-α), which enhances bone strength and prevents OVX-induced bone loss.

CONCLUSIONS: Quercetin may effectively reduce bone loss in OVX rats via the "intestinal flora - SCFAs - inflammatory" signaling pathway.}, } @article {pmid38807723, year = {2024}, author = {Kardan, R and Hemmati, J and Nazari, M and Ahmadi, A and Asghari, B and Azizi, M and Khaledi, M and Arabestani, MR}, title = {Novel therapeutic strategy for obesity through the gut microbiota-brain axis: A review article.}, journal = {Caspian journal of internal medicine}, volume = {15}, number = {2}, pages = {215-227}, pmid = {38807723}, issn = {2008-6164}, abstract = {Background: The interaction between commensal bacteria and the host is essential for health and the gut microbiota-brain axis plays a vital role in this regard. Obesity as a medical problem not only affect the health of the individuals, but also the economic and social aspects of communities. The presence of any dysbiosis in the composition of the gut microbiota disrupts in the gut microbiota-brain axis, which in turn leads to an increase in appetite and then obesity. Because common treatments for obesity have several drawbacks, the use of microbiota-based therapy in addition to treatment and prevention of obesity can have other numerous benefits for the individual. In this review, we intend to investigate the relationship between obesity and the gut microbiota-brain axis as well as novel treatment strategies based on this axis with an emphasis on gut microbiota.}, } @article {pmid38807706, year = {2024}, author = {Gao, T and Li, Y and Wang, X and Ren, F}, title = {Alginate oligosaccharide-mediated butyrate-HIF-1α axis improves skin aging in mice.}, journal = {Journal of pharmaceutical analysis}, volume = {14}, number = {5}, pages = {100911}, pmid = {38807706}, issn = {2214-0883}, abstract = {The "gut-skin" axis has been proved and is considered as a novel therapy for the prevention of skin aging. The antioxidant efficacy of oligomannonic acid (MAOS) make it an intriguing target for use to improve skin aging. The present study further explored whereby MAOS-mediated gut-skin axis balance prevented skin aging in mice. The data indicated the skin aging phenotypes, oxidative stress, skin mitochondrial dysfunction, and intestinal dysbiosis (especially the butyrate and HIF-1α levels decreased) in aging mice. Similarly, fecal microbiota transplantation (FMT) from aging mice rebuild the aging-like phenotypes. Further, we demonstrated MAOS-mediated colonic butyrate-HIF-1α axis homeostasis promoted the entry of butyrate into the skin, upregulated mitophagy level and ultimately improving skin aging via HDAC3/PHD/HIF-1α/mitophagy loop in skin of mice. Overall, our study offered a better insights of the effectiveness of alginate oligosaccharides (AOS), promised to become a personalized targeted therapeutic agents, on gut-skin axis disorder inducing skin aging.}, } @article {pmid38806933, year = {2024}, author = {Hubert, M}, title = {[Not Available].}, journal = {MMW Fortschritte der Medizin}, volume = {166}, number = {10}, pages = {70}, doi = {10.1007/s15006-024-3992-2}, pmid = {38806933}, issn = {1613-3560}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, } @article {pmid38804766, year = {2024}, author = {Smith, A and Roy, T}, title = {Fecal Microbiota Spores, Live-Brpk (Vowst) to Prevent Clostridioides difficile Infection.}, journal = {American family physician}, volume = {109}, number = {5}, pages = {472-473}, pmid = {38804766}, issn = {1532-0650}, mesh = {Humans ; *Clostridium Infections/prevention & control ; *Clostridioides difficile ; *Feces/microbiology ; Fecal Microbiota Transplantation/methods ; }, } @article {pmid38802927, year = {2024}, author = {Zhao, L and Zhang, Z and Wang, P and Zhang, N and Shen, H and Wu, H and Wei, Z and Yang, F and Wang, Y and Yu, Z and Li, H and Hu, Z and Zhai, H and Wang, Z and Su, F and Xie, K and Li, Y}, title = {NHH promotes Sepsis-associated Encephalopathy with the expression of AQP4 in astrocytes through the gut-brain Axis.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {138}, pmid = {38802927}, issn = {1742-2094}, support = {2022MS08002//Natural Science Foundation of Inner Mongolia Autonomous Region/ ; TJWJ2023QN007//Tianjin Municipal Health Commission/ ; 82302413//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Aquaporin 4/metabolism/genetics/biosynthesis ; *Astrocytes/metabolism ; *Hyperammonemia/metabolism ; *Sepsis-Associated Encephalopathy/metabolism ; Male ; *Brain-Gut Axis/physiology ; Mice, Inbred C57BL ; Ammonia/metabolism/blood ; Brain/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Sepsis-associated encephalopathy (SAE) is a significant cause of mortality in patients with sepsis. Despite extensive research, its exact cause remains unclear. Our previous research indicated a relationship between non-hepatic hyperammonemia (NHH) and SAE. This study aimed to investigate the relationship between NHH and SAE and the potential mechanisms causing cognitive impairment. In the in vivo experimental results, there were no significant abnormalities in the livers of mice with moderate cecal ligation and perforation (CLP); however, ammonia levels were elevated in the hippocampal tissue and serum. The ELISA study suggest that fecal microbiota transplantation in CLP mice can reduce ammonia levels. Reduction in ammonia levels improved cognitive dysfunction and neurological impairment in CLP mice through behavioral, neuroimaging, and molecular biology studies. Further studies have shown that ammonia enters the brain to regulate the expression of aquaporins-4 (AQP4) in astrocytes, which may be the mechanism underlying brain dysfunction in CLP mice. The results of the in vitro experiments showed that ammonia up-regulated AQP4 expression in astrocytes, resulting in astrocyte damage. The results of this study suggest that ammonia up-regulates astrocyte AQP4 expression through the gut-brain axis, which may be a potential mechanism for the occurrence of SAE.}, } @article {pmid38800353, year = {2024}, author = {DuPont, HL and DuPont, AW and Tillotson, GS}, title = {Microbiota restoration therapies for recurrent Clostridioides difficile infection reach an important new milestone.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241253089}, pmid = {38800353}, issn = {1756-283X}, abstract = {Microbiota restoration therapy has become a standard treatment for recurrent Clostridioides difficile infection (rCDI). In this article, we review the studies supporting the licensure of two live biotherapeutic products (LBPs) designed to prevent rCDI and to provide clinicians with a perspective on their differences. PubMed was reviewed on 1 October 2023, for all papers published concerning the current Food and Drug Administration allowance of the use of fecal microbiota transplantation (FMT) and the studies that led to the licensure of RBX2660 (REBYOTA™), generic name, fecal microbiota, live-jslm, and SER-109 (VOWST™), generic name, fecal microbiota spores, live-brpk. OpenBiome continues to produce fecal products for patients with rCDI at their treatment sites, and the American Gastroenterology Association has a National Registry focused on long-term safety of administering fecal microbiota products. The science behind the licensing of fecal microbiota, live-jslm, a consortium of fecal anaerobes found in stool augmented with strains of Bacteroidetes and fecal microbiota spores, live-brpk, a mixture of 50 species of purified Firmicutes spores is reviewed. Both products appear to be safe in clinical trials and effective in reducing rCDI episodes by mechanisms established for FMT, including normalization of α- and β-diversity of the microbiome and by increasing fecal secondary bile acids. The different makeup of the two LBPs suggests that rCDI responds to a variety of engrafting microbiota which explains why nearly all donors in FMT of rCDI are generally effective. Fecal microbiota, live-jslm has also been shown to successfully treat rCDI in elderly patients with advanced comorbidities. With the licensure of two novel LBPs, we are entering a new phase of microbiota replacement therapy. Having standardized manufacturing and proper monitoring of products, harnessing the microbiome to control and prevent disease has a new beginning.}, } @article {pmid38799623, year = {2024}, author = {Meng, Q and Guo, J and Lv, K and Liu, Y and Zhang, J and Li, M and Cheng, X and Chen, S and Huo, X and Zhang, Q and Chen, Y and Li, J}, title = {5S-Heudelotinone alleviates experimental colitis by shaping the immune system and enhancing the intestinal barrier in a gut microbiota-dependent manner.}, journal = {Acta pharmaceutica Sinica. B}, volume = {14}, number = {5}, pages = {2153-2176}, pmid = {38799623}, issn = {2211-3835}, abstract = {Aberrant changes in the gut microbiota are implicated in many diseases, including inflammatory bowel disease (IBD). Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity, indicating that microbe-mediated modulation may be a promising strategy for preventing and treating IBD. Although fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies, novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently needed. Herein, we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone (an enantiomer) as a potent agent against experimental colitis that acts by modulating the gut microbiota. 5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids (SCFAs); thus, it regulates the intestinal immune system by reducing proinflammatory immune cell numbers, and maintains intestinal mucosal integrity by modulating tight junctions (TJs). Moreover, 5S-heudelotinone (2) ameliorates colitis-associated colorectal cancer (CAC) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced in situ carcinoma model. Together, these findings reveal the potential of a novel natural product, namely, 5S-heudelotinone, to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.}, } @article {pmid38797998, year = {2024}, author = {Bourragat, A and Escoula, Q and Bellenger, S and Zemb, O and Beaumont, M and Chaumonnot, K and Farine, JP and Jacotot, E and Bonnotte, A and Avoscan, L and Lherminier, J and Luo, K and Narce, M and Bellenger, J}, title = {The transplantation of the gut microbiome of fat-1 mice protects against colonic mucus layer disruption and endoplasmic reticulum stress induced by high fat diet.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2356270}, pmid = {38797998}, issn = {1949-0984}, mesh = {Animals ; *Endoplasmic Reticulum Stress ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Mice ; Male ; *Fatty Acids, Omega-3/metabolism ; *Colon/microbiology/metabolism ; *Intestinal Mucosa/metabolism/microbiology ; *Mice, Transgenic ; Obesity/metabolism/microbiology ; Mucus/metabolism ; Mice, Inbred C57BL ; Mucins/metabolism ; Goblet Cells/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {High-fat diets alter gut barrier integrity, leading to endotoxemia by impacting epithelial functions and inducing endoplasmic reticulum (ER) stress in intestinal secretory goblet cells. Indeed, ER stress, which is an important contributor to many chronic diseases such as obesity and obesity-related disorders, leads to altered synthesis and secretion of mucins that form the protective mucus barrier. In the present study, we investigated the relative contribution of omega-3 polyunsaturated fatty acid (PUFAs)-modified microbiota to alleviating alterations in intestinal mucus layer thickness and preserving gut barrier integrity. Male fat-1 transgenic mice (exhibiting endogenous omega-3 PUFAs tissue enrichment) and wild-type (WT) littermates were fed either an obesogenic high-fat diet (HFD) or a control diet. Unlike WT mice, HFD-fed fat-1 mice were protected against mucus layer alterations as well as an ER stress-mediated decrease in mucin expression. Moreover, cecal microbiota transferred from fat-1 to WT mice prevented changes in the colonic mucus layer mainly through colonic ER stress downregulation. These findings highlight a novel feature of the preventive effects of omega-3 fatty acids against intestinal permeability in obesity-related conditions.}, } @article {pmid38797111, year = {2024}, author = {Zhou, L and Fan, S and Zhang, W and Wang, D and Tang, D}, title = {Microbes in the tumor microenvironment: New additions to break the tumor immunotherapy dilemma.}, journal = {Microbiological research}, volume = {285}, number = {}, pages = {127777}, doi = {10.1016/j.micres.2024.127777}, pmid = {38797111}, issn = {1618-0623}, abstract = {Immunotherapies currently used in clinical practice are unsatisfactory in terms of therapeutic response and toxic side effects, and therefore new immunotherapies need to be explored. Intratumoral microbiota (ITM) exists in the tumor environment (TME) and reacts with its components. On the one hand, ITM promotes antigen delivery to tumor cells or provides cross-antigens to promote immune cells to attack tumors. On the other hand, ITM affects the activity of immune cells and stromal cells. We also summarize the dialog pathways by which ITM crosstalks with components within the TME, particularly the interferon pathway. This interaction between ITM and TME provides new ideas for tumor immunotherapy. By analyzing the bidirectional role of ITM in TME and combining it with its experimental and clinical status, we summarized the adjuvant role of ITM in immunotherapy. We explored the potential applications of using ITM as tumor immunotherapy, such as a healthy diet, fecal transplantation, targeted ITM, antibiotics, and probiotics, to provide a new perspective on the use of ITM in tumor immunotherapy.}, } @article {pmid38795515, year = {2024}, author = {Liu, M and Li, L and Xue, Y and Sun, M and Xiang, F and Zhao, K and Zhang, W and Lei, B and Shang, C and Hu, Y and Yuan, W}, title = {Effect of intestinal microbiota on duck short-beak and dwarf syndrome caused by novel goose parvovirus.}, journal = {Poultry science}, volume = {103}, number = {7}, pages = {103853}, doi = {10.1016/j.psj.2024.103853}, pmid = {38795515}, issn = {1525-3171}, abstract = {Short-beak and dwarf syndrome (SBDS) is caused by infection with novel goose parvovirus (NGPV), which leads to intestinal dysbiosis, developmental delay, short beak, lameness, and paralysis in ducks and is the cause of skeletal health problems. NGPV infection can cause intestinal microbial disturbances, but it is still unclear whether the intestinal microbiota affects the pathogenicity of NGPV. Here, the effects of intestinal microbiota on NGPV-induced SBDS in Cherry Valley ducks were assessed by establishing a duck model for gut microflora depletion/reestablishment through antibiotics (ABX) treatment/fecal microbiota transplanted (FMT). By measuring body weight, beak length, beak width and tarsal length, we found that SBDS clinical symptoms were alleviated in ducks treated with ABX, but not in FMT ducks. Next, we conducted a comprehensive analysis of bone metabolism, gut barrier integrity, and inflammation levels using quantitative real-time PCR (qPCR), enzyme linked immunosorbent assay (ELISA), biochemical analysis and histological analysis. The results showed that ABX treatment improved bone quality reduced bone resorption, mitigated tissue lesions, protected intestinal barrier integrity, and inhibited systemic inflammation in NGPV-infected ducks. Moreover, cecal microflora composition and short-chain fatty acids (SCFAs) production were examined by bacterial 16S rRNA sequencing and gas chromatography. The results revealed that ABX treatment mitigated the decreased abundance of Firmicutes and Bacteroidota in NGPV-infected ducks, as well as increased SCFAs production. Furthermore, ABX treatment reduced the mucosa-associated lymphoid tissue lymphoma translocation protein 1 (Malt1) and nuclear factor κB (NF-κB) expression, which are correlated with systemic inflammation in SBDS ducks. These findings suggested that intestinal microflora depletion alleviated NGPV-induced SBDS by maintaining intestinal homeostasis, inhibiting inflammatory response and alleviating bone resorption. These results provide evidence for the pivotal role of intestinal microbiota in the process of SBDS and contribute a theoretical basis for the feasibility of microecological preparation as a method to control SBDS.}, } @article {pmid38794880, year = {2024}, author = {Corte-Iglesias, V and Saiz, ML and Andrade-Lopez, AC and Salazar, N and Bernet, CR and Martin-Martin, C and Borra, JM and Lozano, JJ and Aransay, AM and Diaz-Corte, C and Lopez-Larrea, C and Suarez-Alvarez, B}, title = {Propionate and butyrate counteract renal damage and progression to chronic kidney disease.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {}, number = {}, pages = {}, doi = {10.1093/ndt/gfae118}, pmid = {38794880}, issn = {1460-2385}, abstract = {BACKGROUND: Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies.

METHODS: SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD.

RESULTS: Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by TNF-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term.

CONCLUSIONS: Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.}, } @article {pmid35934088, year = {2022}, author = {Zhu, X and Zhang, Z and Yang, X and Qi, L and Guo, Y and Tang, X and Xie, Y and Chen, D}, title = {RETRACTED: Improvement of extraction from Hericium erinaceus on the gut-brain axis in AD-like mice.}, journal = {Brain research}, volume = {1793}, number = {}, pages = {148038}, doi = {10.1016/j.brainres.2022.148038}, pmid = {35934088}, issn = {1872-6240}, mesh = {*Alzheimer Disease/pathology ; Animals ; Brain-Gut Axis ; Hericium ; Inflammation ; Mice ; RNA, Ribosomal, 16S ; }, abstract = {This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the lead author, Dr. Diling Chen. Dr. Chen alerted the Editor-in-Chief that data previously published in Aging (Albany NY). 2020 Jan 6; 12:260-287 https://doi.org/10.18632/aging.102614 were accidently reused in the above-referenced Brain Research article. Dr. Chen is a co-author on both articles. The reused content pertains to the fecal transplantation data of the model group, represented by Figure 2 in the Aging article and Figure 5 in the Brain Research article. Dr. Chen did not carefully check the data published by the team before the final submission, resulting in repeated use. The lead author states further that it was an honest mistake, and the team had no intention to plagiarize previously published material. All authors were notified and all are in agreement with the retraction. The authors apologize to the scientific community for any inconvenience or challenges resulting from the publication and retraction of this article.}, } @article {pmid38793089, year = {2024}, author = {Gyriki, D and Nikolaidis, C and Stavropoulou, E and Bezirtzoglou, I and Tsigalou, C and Vradelis, S and Bezirtzoglou, E}, title = {Exploring the Gut Microbiome's Role in Inflammatory Bowel Disease: Insights and Interventions.}, journal = {Journal of personalized medicine}, volume = {14}, number = {5}, pages = {}, pmid = {38793089}, issn = {2075-4426}, abstract = {Inflammatory Bowel Disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic and relapsing inflammatory condition of the intestine that significantly impairs quality of life and imposes a heavy burden on healthcare systems globally. While the exact etiology of IBD is unclear, it is influenced by genetic, environmental, immunological, and microbial factors. Recent advances highlight the gut microbiome's pivotal role in IBD pathogenesis. The microbial dysbiosis characteristic of IBD, marked by a decline in beneficial bacteria and an increase in pathogenic microbes, suggests a profound connection between microbial imbalance and disease mechanisms. This review explores diagnostic approaches to IBD that integrate clinical assessment with advanced microbiological analyses, highlighting the potential of microbiome profiling as a non-invasive diagnostic tool. In addition, it evaluates conventional and emerging treatments and discusses microbiome-targeted intervention prospects, such as probiotics, symbiotics, and faecal microbiota transplantation. The necessity for future research to establish their efficacy and safety is emphasised.}, } @article {pmid38792682, year = {2024}, author = {Reveles, KR and Hickmott, AJ and Strey, KA and Mustoe, AC and Arroyo, JP and Power, ML and Ridenhour, BJ and Amato, KR and Ross, CN}, title = {Developing the Common Marmoset as a Translational Geroscience Model to Study the Microbiome and Healthy Aging.}, journal = {Microorganisms}, volume = {12}, number = {5}, pages = {}, pmid = {38792682}, issn = {2076-2607}, support = {R01AG065546/NH/NIH HHS/United States ; }, abstract = {Emerging data support associations between the depletion of the healthy gut microbiome and aging-related physiological decline and disease. In humans, fecal microbiota transplantation (FMT) has been used successfully to restore gut microbiome structure and function and to treat C. difficile infections, but its application to healthy aging has been scarcely investigated. The marmoset is an excellent model for evaluating microbiome-mediated changes with age and interventional treatments due to their relatively shorter lifespan and many social, behavioral, and physiological functions that mimic human aging. Prior work indicates that FMT is safe in marmosets and may successfully mediate gut microbiome function and host health. This narrative review (1) provides an overview of the rationale for FMT to support healthy aging using the marmoset as a translational geroscience model, (2) summarizes the prior use of FMT in marmosets, (3) outlines a protocol synthesized from prior literature for studying FMT in aging marmosets, and (4) describes limitations, knowledge gaps, and future research needs in this field.}, } @article {pmid38791997, year = {2024}, author = {Machado, AP and Shaikh, AS and Saji, A and Shatila, M and Oliva, IG and Wang, Y and Shirwaikar Thomas, A}, title = {Outcomes of Budesonide as a Treatment Option for Immune Checkpoint Inhibitor-Related Colitis in Patients with Cancer.}, journal = {Cancers}, volume = {16}, number = {10}, pages = {}, pmid = {38791997}, issn = {2072-6694}, abstract = {BACKGROUND: Current treatment guidelines for moderate to severe colitis (IMC) secondary to immune checkpoint inhibitors (ICI) recommend systemic corticosteroids as the primary therapy in conjunction with biologics, namely infliximab and/or vedolizumab. We aimed to explore the efficacy and safety of oral budesonide in the treatment of IMC.

METHODS: We performed a retrospective analysis at MD Anderson Cancer Center of adult cancer patients with a confirmed (based on clinical, radiographic and laboratory assessment) diagnosis of IMC between 1 January 2015 and 31 November 2022, treated with budesonide. Data collection included demographics, oncologic history, IMC-related information and outcomes up to 6 months after the last dose of ICI.

RESULTS: Our sample (n = 69) comprised primarily of Caucasian (76.8%) females (55.1%). The majority of patients received combination therapy with anti-PD-1/L1 and anti-CTLA-4 (49.3%), and the most common malignancy treated was melanoma (37.6%). The median grade of diarrhea was 3 and of colitis was 2. Of the 50 patients who underwent endoscopic evaluation, a majority had non-ulcerative inflammation (64%) and active colitis on histology (78%). Budesonide was used as primary treatment at onset of IMC in 56.5% patients, as well as a bridging therapy from systemic corticosteroids in 33.3%. Less than half of the patients (44.9%) required additional therapies such as biologics or fecal microbiota transplant. Additionally, 75.3% of patients achieved full remission of IMC and 24.6% had a recurrence of IMC. ICI was resumed in 31.9% of patients and 17.4% received other forms of cancer therapies.

CONCLUSIONS: Budesonide may be an effective strategy to treat and prevent the recurrence of IMC. The remission rates observed in our analysis with budesonide alone are comparable to systemic corticosteroids. Patients that require an extended duration of steroid exposure and those with moderate to severe colitis may benefit from budesonide given its lower risk of infection and complications. Furthermore, we observe that budesonide may serve as a successful bridge from systemic corticosteroids with subsequent biologic treatment. Larger prospective studies are necessary to determine the role of budesonide as well as its safety profile.}, } @article {pmid38791599, year = {2024}, author = {Olteanu, G and Ciucă-Pană, MA and Busnatu, ȘS and Lupuliasa, D and Neacșu, SM and Mititelu, M and Musuc, AM and Ioniță-Mîndrican, CB and Boroghină, SC}, title = {Unraveling the Microbiome-Human Body Axis: A Comprehensive Examination of Therapeutic Strategies, Interactions and Implications.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791599}, issn = {1422-0067}, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Microbiota ; Animals ; Human Body ; Host Microbial Interactions/physiology ; }, abstract = {This review scrutinizes the intricate interplay between the microbiome and the human body, exploring its multifaceted dimensions and far-reaching implications. The human microbiome, comprising diverse microbial communities inhabiting various anatomical niches, is increasingly recognized as a critical determinant of human health and disease. Through an extensive examination of current research, this review elucidates the dynamic interactions between the microbiome and host physiology across multiple organ systems. Key topics include the establishment and maintenance of microbiota diversity, the influence of host factors on microbial composition, and the bidirectional communication pathways between microbiota and host cells. Furthermore, we delve into the functional implications of microbiome dysbiosis in disease states, emphasizing its role in shaping immune responses, metabolic processes, and neurological functions. Additionally, this review discusses emerging therapeutic strategies aimed at modulating the microbiome to restore host-microbe homeostasis and promote health. Microbiota fecal transplantation represents a groundbreaking therapeutic approach in the management of dysbiosis-related diseases, offering a promising avenue for restoring microbial balance within the gut ecosystem. This innovative therapy involves the transfer of fecal microbiota from a healthy donor to an individual suffering from dysbiosis, aiming to replenish beneficial microbial populations and mitigate pathological imbalances. By synthesizing findings from diverse fields, this review offers valuable insights into the complex relationship between the microbiome and the human body, highlighting avenues for future research and clinical interventions.}, } @article {pmid38789466, year = {2024}, author = {Algavi, YM and Borenstein, E}, title = {Relative dispersion ratios following fecal microbiota transplant elucidate principles governing microbial migration dynamics.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4447}, pmid = {38789466}, issn = {2041-1723}, support = {2435/19//Israel Science Foundation (ISF)/ ; U19AG057377//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome/physiology ; *Feces/microbiology ; Gastrointestinal Tract/microbiology ; Bacteria/metabolism/genetics/classification ; }, abstract = {Microorganisms frequently migrate from one ecosystem to another. Yet, despite the potential importance of this process in modulating the environment and the microbial ecosystem, our understanding of the fundamental forces that govern microbial dispersion is still lacking. Moreover, while theoretical models and in-vitro experiments have highlighted the contribution of species interactions to community assembly, identifying such interactions in vivo, specifically in communities as complex as the human gut, remains challenging. To address this gap, here we introduce a robust and rigorous computational framework, termed Relative Dispersion Ratio (RDR) analysis, and leverage data from well-characterized fecal microbiota transplant trials, to rigorously pinpoint dependencies between taxa during the colonization of human gastrointestinal tract. Our analysis identifies numerous pairwise dependencies between co-colonizing microbes during migration between gastrointestinal environments. We further demonstrate that identified dependencies agree with previously reported findings from in-vitro experiments and population-wide distribution patterns. Finally, we explore metabolic dependencies between these taxa and characterize the functional properties that facilitate effective dispersion. Collectively, our findings provide insights into the principles and determinants of community dynamics following ecological translocation, informing potential opportunities for precise community design.}, } @article {pmid38788981, year = {2024}, author = {Ketagoda, DHK and Varga, P and Fitzsimmons, TR and Moore, NE and Weyrich, LS and Zilm, PS}, title = {Development of an in vitro biofilm model of the human supra-gingival microbiome for Oral microbiome transplantation.}, journal = {Journal of microbiological methods}, volume = {}, number = {}, pages = {106961}, doi = {10.1016/j.mimet.2024.106961}, pmid = {38788981}, issn = {1872-8359}, abstract = {The high prevalence of dental caries and periodontal disease place a significant burden on society, both socially and economically. Recent advances in genomic technologies have linked both diseases to shifts in the oral microbiota - a community of >700 bacterial species that live within the mouth. The development of oral microbiome transplantation draws on the success of fecal microbiome transplantation for the treatment of gut pathologies associated with disease. Many current in vitro oral biofilm models have been developed but do not fully capture the complexity of the oral microbiome which is required for successful OMT. To address this, we developed an in vitro biofilm system that maintained an oral microbiome with 252 species on average over 14 days. Six human plaque samples were grown in 3D printed flow cells on hydroxyapatite discs using artificial saliva medium (ASM). Biofilm composition and growth were monitored by high throughput sequencing and confocal microscopy/SEM, respectively. While a significant drop in bacterial diversity occurred, up to 291 species were maintained in some flow cells over 14 days with 70% viability grown with ASM. This novel in vitro biofilm model represents a marked improvement on existing oral biofilm systems and provides new opportunities to develop oral microbiome transplant therapies.}, } @article {pmid38788915, year = {2024}, author = {Caenepeel, C and Deleu, S and Vazquez Castellanos, JF and Arnauts, K and Braekeleire, S and Machiels, K and Baert, F and Mana, F and Pouillon, L and Hindryckx, P and Lobaton, T and Louis, E and Franchimont, D and Verstockt, B and Ferrante, M and Sabino, J and Vieira-Silva, S and Falony, G and Raes, J and Vermeire, S}, title = {RIGOROUS DONOR SELECTION FOR FMT IN ACTIVE ULCERATIVE COLITIS: KEY LESSONS FROM A RANDOMIZED CONTROLLED TRIAL HALTED FOR FUTILITY.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2024.05.017}, pmid = {38788915}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Rigorous donor preselection on microbiota level, strict anaerobic processing, and repeated FMT administration were hypothesized to improve FMT induction of remission in UC.

METHODS: The RESTORE-UC trial was a multi-centric, double-blind, sham-controlled, randomized trial. Patients with moderate to severe UC (defined by total Mayo 4-10) were randomly allocated to receive four anaerobic-prepared allogenic or autologous donor FMTs. Allogenic donor material was selected after a rigorous screening based on microbial cell count, enterotype, and the abundance of specific genera. The primary endpoint was steroid-free clinical remission (total Mayo ≤2, no sub-score >1) at week 8. A pre-planned futility analysis was performed after 66% (n=72) of intended inclusions (n=108). Quantitative microbiome profiling (n=44) was performed at weeks 0 and 8.

RESULTS: In total, 72 patients were included of which 66 received at least one FMT (allogenic-FMT n=30 and autologous-FMT n=36). At week 8, respectively 3 and 5 patients reached the primary endpoint of steroid-free clinical remission (p=0.72), indicating no treatment difference of at least 5% in favour of allogenic-FMT. Hence, the study was stopped due to futility. Microbiome analysis showed numerically more enterotype transitions upon allogenic-FMT compared to autologous-FMT and more transitions were observed when patients were treated with a different enterotype than their own at baseline (p=0.01). Primary response was associated with lower total Mayo scores, lower bacterial cell counts, and higher Bacteroides 2 prevalence at baseline.

CONCLUSION: The RESTORE-UC trial did not meet its primary endpoint of increased steroid-free clinical remission at week 8. Further research should additionally consider patient-selection, sterilized sham-control, increased frequency, density, and viability of FMT prior to administration.}, } @article {pmid38788173, year = {2024}, author = {Nguyen, CB and Vaishampayan, UN}, title = {Clinical Applications of the Gut Microbiome in Genitourinary Cancers.}, journal = {American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting}, volume = {44}, number = {3}, pages = {e100041}, doi = {10.1200/EDBK_100041}, pmid = {38788173}, issn = {1548-8756}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Urogenital Neoplasms/microbiology ; Immunotherapy/methods ; Probiotics/therapeutic use ; }, abstract = {Recently recognized as one of the hallmarks of cancer, the microbiome consists of symbiotic microorganisms that play pivotal roles in carcinogenesis, the tumor microenvironment, and responses to therapy. With recent advances in microbiome metagenomic sequencing, a growing body of work has demonstrated that changes in gut microbiome composition are associated with differential responses to immune checkpoint inhibitors (ICIs) because of alterations in cytokine signaling and cytotoxic T-cell recruitment. Therefore, strategies to shape the gut microbiome into a more favorable, immunogenic profile may lead to improved responses with ICIs. Immunotherapy is commonly used in genitourinary (GU) cancers such as renal cell carcinoma, urothelial cancer, and to a limited extent, prostate cancer. However, a subset of patients do not derive clinical benefit with ICIs. Gut microbiome-based interventions are of particular interest given the potential to boost responses to ICIs in preclinical and early-phase prospective studies. Novel approaches using probiotic therapy (live bacterial supplementation) and fecal microbiota transplantation in patients with GU cancers are currently under investigation.}, } @article {pmid37353002, year = {2024}, author = {Gao, Y and Liang, Z and Mao, B and Zheng, X and Shan, J and Jin, C and Liu, S and Kolliputi, N and Chen, Y and Xu, F and Shi, L}, title = {Gut microbial GABAergic signaling improves stress-associated innate immunity to respiratory viral infection.}, journal = {Journal of advanced research}, volume = {60}, number = {}, pages = {41-56}, pmid = {37353002}, issn = {2090-1224}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; Mice ; *gamma-Aminobutyric Acid/metabolism ; *Immunity, Innate/immunology ; *Stress, Psychological/immunology/metabolism ; *COVID-19/immunology ; *Macrophages, Alveolar/immunology/metabolism ; Disease Models, Animal ; Signal Transduction/immunology ; Male ; SARS-CoV-2/immunology ; Influenza A virus/immunology ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation/methods ; Respiratory Tract Infections/immunology/metabolism/microbiology/virology ; }, abstract = {INTRODUCTION: Epidemiological evidences reveal that populations with psychological stress have an increased likelihood of respiratory viral infection involving influenza A virus (IAV) and SARS-CoV-2.

OBJECTIVES: This study aims to explore the potential correlation between psychological stress and increased susceptibility to respiratory viral infections and how this may contribute to a more severe disease progression.

METHODS: A chronic restraint stress (CRS) mouse model was used to infect IAV and estimate lung inflammation. Alveolar macrophages (AMs) were observed in the numbers, function and metabolic-epigenetic properties. To confirm the central importance of the gut microbiome in stress-exacerbated viral pneumonia, mice were conducted through microbiome depletion and gut microbiome transplantation.

RESULTS: Stress exposure induced a decline in Lactobacillaceae abundance and hence γ-aminobutyric acid (GABA) level in mice. Microbial-derived GABA was released in the peripheral and sensed by AMs via GABAAR, leading to enhanced mitochondrial metabolism and α-ketoglutarate (αKG) generation. The metabolic intermediator in turn served as the cofactor for the epigenetic regulator Tet2 to catalyze DNA hydroxymethylation and promoted the PPARγ-centered gene program underpinning survival, self-renewing, and immunoregulation of AMs. Thus, we uncover an unappreciated GABA/Tet2/PPARγ regulatory circuitry initiated by the gut microbiome to instruct distant immune cells through a metabolic-epigenetic program. Accordingly, reconstitution with GABA-producing probiotics, adoptive transferring of GABA-conditioned AMs, or resumption of pulmonary αKG level remarkably improved AMs homeostasis and alleviated severe pneumonia in stressed mice.

CONCLUSION: Together, our study identifies microbiome-derived tonic signaling tuned by psychological stress to imprint resident immune cells and defensive response in the lungs. Further studies are warranted to translate these findings, basically from murine models, into the individuals with psychiatric stress during respiratory viral infection.}, } @article {pmid38786164, year = {2024}, author = {Wang, Y and Hunt, A and Danziger, L and Drwiega, EN}, title = {A Comparison of Currently Available and Investigational Fecal Microbiota Transplant Products for Recurrent Clostridioides difficile Infection.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {}, pmid = {38786164}, issn = {2079-6382}, abstract = {Clostridioides difficile infection (CDI) is an intestinal infection that causes morbidity and mortality and places significant burden and cost on the healthcare system, especially in recurrent cases. Antibiotic overuse is well recognized as the leading cause of CDI in high-risk patients, and studies have demonstrated that even short-term antibiotic exposure can cause a large and persistent disturbance to human colonic microbiota. The recovery and sustainability of the gut microbiome after dysbiosis have been associated with fewer CDI recurrences. Fecal microbiota transplantation (FMT) refers to the procedure in which human donor stool is processed and transplanted to a patient with CDI. It has been historically used in patients with pseudomembranous colitis even before the discovery of Clostridioides difficile. More recent research supports the use of FMT as part of the standard therapy of recurrent CDI. This article will be an in-depth review of five microbiome therapeutic products that are either under investigation or currently commercially available: Rebyota (fecal microbiota, live-jslm, formerly RBX2660), Vowst (fecal microbiota spores, live-brpk, formerly SER109), VE303, CP101, and RBX7455. Included in this review is a comparison of the products' composition and dosage forms, available safety and efficacy data, and investigational status.}, } @article {pmid38786141, year = {2024}, author = {Abbas, W and Bi, R and Hussain, MD and Tajdar, A and Guo, F and Guo, Y and Wang, Z}, title = {Antibiotic Cocktail Effects on Intestinal Microbial Community, Barrier Function, and Immune Function in Early Broiler Chickens.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {5}, pages = {}, pmid = {38786141}, issn = {2079-6382}, support = {No. 32172774//National Natural Science Foundation of China/ ; (No. 32172774)//National Natural Science Foundation of China/ ; }, abstract = {This study investigated the effects of an antibiotic cocktail on intestinal microbial composition, mechanical barrier structure, and immune functions in early broilers. One-day-old healthy male broiler chicks were treated with a broad-spectrum antibiotic cocktail (ABX; neomycin, ampicillin, metronidazole, vancomycin, and kanamycin, 0.5 g/L each) or not in drinking water for 7 and 14 days, respectively. Sequencing of 16S rRNA revealed that ABX treatment significantly reduced relative Firmicutes, unclassified Lachnospiraceae, unclassified Oscillospiraceae, Ruminococcus torques, and unclassified Ruminococcaceae abundance in the cecum and relative Firmicutes, Lactobacillus and Baccillus abundance in the ileum, but significantly increased richness (Chao and ACE indices) and relative Enterococcus abundance in the ileum and cecum along with relatively enriched Bacteroidetes, Proteobacteria, Cyanobacteria, and Enterococcus levels in the ileum following ABX treatment for 14 days. ABX treatment for 14 days also significantly decreased intestinal weight and length, along with villus height (VH) and crypt depth (CD) of the small intestine, and remarkably increased serum LPS, TNF-α, IFN-γ, and IgG levels, as well as intestinal mucosa DAO and MPO activity. Moreover, prolonged use of ABX significantly downregulated occludin, ZO-1, and mucin 2 gene expression, along with goblet cell numbers in the ileum. Additionally, chickens given ABX for 14 days had lower acetic acid, butyric acid, and isobutyric acid content in the cecum than the chickens treated with ABX for 7 days and untreated chickens. Spearman correlation analysis found that those decreased potential beneficial bacteria were positively correlated with gut health-related indices, while those increased potential pathogenic strains were positively correlated with gut inflammation and gut injury-related parameters. Taken together, prolonged ABX application increased antibiotic-resistant species abundance, induced gut microbiota dysbiosis, delayed intestinal morphological development, disrupted intestinal barrier function, and perturbed immune response in early chickens. This study provides a reliable lower-bacteria chicken model for further investigation of the function of certain beneficial bacteria in the gut by fecal microbiota transplantation into germ-free or antibiotic-treated chickens.}, } @article {pmid38785512, year = {2024}, author = {Panaitescu, PȘ and Răzniceanu, V and Mocrei-Rebrean, ȘM and Neculicioiu, VS and Dragoș, HM and Costache, C and Filip, GA}, title = {The Effect of Gut Microbiota-Targeted Interventions on Neuroinflammation and Motor Function in Parkinson's Disease Animal Models-A Systematic Review.}, journal = {Current issues in molecular biology}, volume = {46}, number = {5}, pages = {3946-3974}, pmid = {38785512}, issn = {1467-3045}, abstract = {Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in delaying the onset and progression of Parkinson's disease by rebalancing the gut microbiome in the context of the gut-brain axis. Our study aims to organize recent findings regarding these interventions in Parkinson's disease animal models to identify how they affect neuroinflammation and motor outcomes. A systematic literature search was applied in PubMed, Web of Science, Embase, and SCOPUS for gut microbiome-targeted non-dietary interventions. Studies that investigated gut-targeted interventions by using in vivo murine PD models to follow dopaminergic cell loss, motor tests, and neuroinflammatory markers as outcomes were considered to be eligible. A total of 1335 studies were identified in the databases, out of which 29 were found to be eligible. A narrative systematization of the resulting data was performed, and the effect direction for the outcomes was represented. Quality assessment using the SYRCLE risk of bias tool was also performed. Out of the 29 eligible studies, we found that a significant majority report that the intervention reduced the dopaminergic cell loss (82.76%, 95% CI [64.23%, 94.15%]) produced by the induction of the disease model. Also, most studies reported a reduction in microglial (87.5%, 95% CI [61.65%, 98.45%]) and astrocytic activation (84,62%, 95% CI [54.55%, 98.08%]) caused by the induction of the disease model. These results were also mirrored in the majority (96.4% 95% CI [81.65%, 99.91%]) of the studies reporting an increase in performance in behavioral motor tests. A significant limitation of the study was that insufficient information was found in the studies to assess specific causes of the risk of bias. These results show that non-dietary gut microbiome-targeted interventions can improve neuroinflammatory and motor outcomes in acute Parkinson's disease animal models. Further studies are needed to clarify if these benefits transfer to the long-term pathogenesis of the disease, which is not yet fully understood. The study had no funding source, and the protocol was registered in the PROSPERO database with the ID number CRD42023461495.}, } @article {pmid38784794, year = {2024}, author = {Obaid, NA}, title = {Alternative treatment of recurrent Clostridioides difficile infection in adults by fecal transplantation: an overview of phase I-IV studies from Clinicaltrials.gov.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1374774}, pmid = {38784794}, issn = {1664-302X}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an interventional approach to treat chronic and recurrent Clostridioides difficile infection (CDI). However, there is insufficient evidence regarding its effectiveness and safety. Clinical trials have been conducted to inspect the safety and effectiveness of FMT with and without comparison to pharmacological treatments.

AIM: This review explored the treatment of CDI in adults using FMT and evaluated the safety of this intervention based on phase I-IV studies registered on Clinicaltrials.gov.

METHOD: A comprehensive search of Clinicaltrials.gov was conducted to identify relevant studies that investigated CDI in adults. Data on study type, study design, sample size, intervention details, and outcomes related to FMT were examined and evaluated.

RESULTS: In total, 13 clinical trials on FMT for CDI published through 17 November 2023 were identified, all of which were interventional studies. The investigation focused on both terminated and completed studies. Basic and advanced outcome measures were examined.

CONCLUSION: Some studies were terminated during phase II, and FMT was less effective than antibiotics such as vancomycin and fidaxomicin. However, colonoscopy and oral FMT were explored in several completed studies with promising results, but the evidence remains limited and inconclusive.}, } @article {pmid38783921, year = {2024}, author = {Li, Y and Xiao, P and Cao, R and Le, J and Xu, Q and Xiao, F and Ye, L and Wang, X and Wang, Y and Zhang, T}, title = {Effects and microbiota changes following oral lyophilized fecal microbiota transplantation in children with autism spectrum disorder.}, journal = {Frontiers in pediatrics}, volume = {12}, number = {}, pages = {1369823}, pmid = {38783921}, issn = {2296-2360}, abstract = {BACKGROUND AND PURPOSE: Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental disorders that is characterized by core features in social communication impairment and restricted, repetitive sensory-motor behaviors. This study aimed to further investigate the utilization of fecal microbiota transplantation (FMT) in children with ASD, both with and without gastrointestinal (GI) symptoms, evaluate the effect of FMT and analyze the alterations in bacterial and fungal composition within the gut microbiota.

METHODS: A total of 38 children diagnosed with ASD participated in the study and underwent oral lyophilized FMT treatment. The dosage of the FMT treatment was determined based on a ratio of 1 g of donor stool per 1 kg of recipient body weight, with a frequency of once every 4 weeks for a total of 12 weeks. In addition, 30 healthy controls (HC) were included in the analysis. The clinical efficacy of FMT was evaluated, while the composition of fecal bacteria and fungi was determined using 16S rRNA and ITS gene sequencing methods.

RESULTS: Median age of the 38 children with ASD was 7 years. Among these children, 84.2% (32 of 38) were boys and 81.6% (31 of 38) exhibited GI symptoms, with indigestion, constipation and diarrhea being the most common symptoms. Sample collections and assessments were conducted at baseline (week 0), post-treatment (week 12) and follow-up (week 20). At the end of the follow-up phase after FMT treatment, the autism behavior checklist (ABC) scores decreased by 23% from baseline, and there was a 10% reduction in scores on the childhood autism rating scale (CARS), a 6% reduction in scores on the social responsiveness scale (SRS) and a 10% reduction in scores on the sleep disturbance scale for children (SDSC). In addition, short-term adverse events observed included vomiting and fever in 2 participants, which were self-limiting and resolved within 24 h, and no long-term adverse events were observed. Although there was no significant difference in alpha and beta diversity in children with ASD before and after FMT therapy, the FMT treatment resulted in alterations in the relative abundances of various bacterial and fungal genera in the samples of ASD patients. Comparisons between children with ASD and healthy controls (HC) revealed statistically significant differences in microbial abundance before and after FMT. Blautia, Sellimonas, Saccharomycopsis and Cystobasidium were more abundant in children with ASD than in HC, while Dorea were less abundant. After FMT treatment, levels of Blautia, Sellimonas, Saccharomycopsis and Cystobasidium decreased, while levels of Dorea increased. Moreover, the increased abundances of Fusicatenibacter, Erysipelotrichaceae_UCG-003, Saccharomyces, Rhodotorula, Cutaneotrichosporon and Zygosaccharomyces were negatively correlated with the scores of ASD core symptoms.

CONCLUSIONS: Oral lyophilized FMT could improve GI and ASD related symptoms, as well as sleep disturbances, and alter the gut bacterial and fungal microbiota composition in children with ASD.

CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055943. Registered 28 January 2022, www.chictr.org.cn.}, } @article {pmid38783798, year = {2024}, author = {Ma, X and Zhang, L and Gao, J and Chen, F}, title = {[Advances in the application of fecal microbiota transplantation for the treatment of nervous system diseases].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {40}, number = {5}, pages = {1293-1308}, doi = {10.13345/j.cjb.230448}, pmid = {38783798}, issn = {1872-2075}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Gastrointestinal Microbiome ; Animals ; *Nervous System Diseases/therapy/microbiology ; Brain-Gut Axis ; Parkinson Disease/therapy/microbiology ; Alzheimer Disease/therapy/microbiology ; Depression/therapy/microbiology ; }, abstract = {The intestinal microbiota exhibits a strong correlation with the function of the central nervous system, exerting influence on the host brain through neural pathways, immune pathways, and microbial metabolites along the gut-brain axis. Disorders in the composition of the intestinal microbial are closely associated with the onset and progression of neurological disorders, such as depression, Alzheimer's disease, and Parkinson's disease. It has been proven that fecal microbiota transplantation can improve symptoms in animal models of neurological diseases and clinical patients. This paper provides a comprehensive review of the composition and function of the human intestinal microbiota, as well as the intricate the relationship between the human intestinal microbiota and nervous system diseases through the gut-brain axis. Additionally, it delves into the research advancements and underlying mechanism of fecal microbiota transplantation in the treatment of nervous system diseases. These findings offer novel insights and potential avenues for clinical interventions targeting nervous system diseases.}, } @article {pmid38783543, year = {2024}, author = {Horváthová, T and Lafuente, E and Bartels, JA and Wallisch, J and Vorburger, C}, title = {Tolerance to environmental pollution in the freshwater crustacean Asellus aquaticus: A role for the microbiome.}, journal = {Environmental microbiology reports}, volume = {16}, number = {3}, pages = {e13252}, pmid = {38783543}, issn = {1758-2229}, support = {//DUE-Mobil Grant from the University of Duisburg-Essen/ ; CZ.02.2.69/0.0/0.0/20_079/0017809//Ministry of Education, Youth and Sports of the Czech Republic/ ; 5221.00979.008.08//Eawag Academic Transition Grant/ ; //Individual Travel Grant from the Radboud University Nijmegen/ ; }, mesh = {Animals ; *Fresh Water/microbiology/chemistry ; *Microbiota/drug effects ; *Isopoda/microbiology ; Feces/microbiology ; Water Pollutants, Chemical ; Bacteria/classification/isolation & purification/genetics/drug effects ; Environmental Pollution ; }, abstract = {Freshwater habitats are frequently contaminated by diverse chemicals of anthropogenic origin, collectively referred to as micropollutants, that can have detrimental effects on aquatic life. The animals' tolerance to micropollutants may be mediated by their microbiome. If polluted aquatic environments select for contaminant-degrading microbes, the acquisition of such microbes by the host may increase its tolerance to pollution. Here we tested for the potential effects of the host microbiome on the growth and survival of juvenile Asellus aquaticus, a widespread freshwater crustacean. Using faecal microbiome transplants, we provided newly hatched juveniles with the microbiome isolated from donor adults reared in either clean or micropollutant-contaminated water and, after transplantation, recipient juveniles were reared in water with and without micropollutants. The experiment revealed a significant negative effect of the micropollutants on the survival of juvenile isopods regardless of the received faecal microbiome. The micropollutants had altered the composition of the bacterial component of the donors' microbiome, which in turn influenced the microbiome of juvenile recipients. Hence, we show that relatively high environmental concentrations of micropollutants reduce survival and alter the microbiome composition of juvenile A. aquaticus, but we have no evidence that tolerance to micropollutants is modulated by their microbiome.}, } @article {pmid38782893, year = {2024}, author = {Chen, H and Fu, X and Wu, X and Zhao, J and Qiu, F and Wang, Z and Wang, Z and Chen, X and Xie, D and Huang, J and Fan, J and Yang, X and Song, Y and Li, J and He, D and Xiao, G and Lu, A and Liang, C}, title = {Gut microbial metabolite targets HDAC3-FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis.}, journal = {Bone research}, volume = {12}, number = {1}, pages = {31}, pmid = {38782893}, issn = {2095-4700}, support = {82172386//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81922081//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82100943//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2021KTSCX104//Department of Education of Guangdong Province (Guangdong Province Education Department)/ ; }, mesh = {*Arthritis, Rheumatoid/metabolism/pathology/drug therapy/microbiology ; Animals ; *Histone Deacetylases/metabolism ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Mice, Inbred C57BL ; Mice ; *Synoviocytes/metabolism/drug effects/pathology ; *Arthritis, Experimental/pathology/metabolism ; Forkhead Transcription Factors/metabolism ; Fibroblasts/metabolism/drug effects ; Mice, Inbred DBA ; Male ; Signal Transduction/drug effects ; }, abstract = {Rheumatoid arthritis (RA) is an autoimmune disease. Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility. However, accumulating evidence demonstrates that genetics also shape the gut microbiota. It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis (CIA), while the others are resistant to CIA. Here, we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice. C57BL/6J mice and healthy human individuals have enriched B. fragilis than DBA/1J mice and RA patients. Transplantation of B. fragilis prevents CIA in DBA/1J mice. We identify that B. fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate. Fibroblast-like synoviocytes (FLSs) in RA are activated to undergo tumor-like transformation. Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1, resulting in reduced FOXK1 stability, blocked interferon signaling and deactivation of RA-FLSs. We treat CIA mice with propionate and show that propionate attenuates CIA. Moreover, a combination of propionate with anti-TNF etanercept synergistically relieves CIA. These results suggest that B. fragilis or propionate could be an alternative or complementary approach to the current therapies.}, } @article {pmid38782148, year = {2024}, author = {Wu, C and Wu, C and Peng, L and Wu, M and Li, Z and Chen, J}, title = {Multi-omics approaches for the understanding of therapeutic mechanism for Huang-Qi-Long-Dan Granule against ischemic stroke.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107229}, doi = {10.1016/j.phrs.2024.107229}, pmid = {38782148}, issn = {1096-1186}, abstract = {After long-term clinical application, traditional Chinese medicine (TCM) has accumulated rich experience in the stroke treatment. Huang-Qi-Long-Dan Granule (HQLDG) is a TCM formula that was used in clinical for the treatment of acute ischemic stroke. However, its mechanism against ischemic stroke still unknown. This study aimed to identify HQLDG's effect against ischemic stroke and explore its underlying mechanism. 16s rRNA sequencing, metabolomics/tryptophan (Trp)-targeted metabolomics analysis and transcriptomic analysis were used to investigate HQLDG underlying therapeutic mechanism. Our results revealed that HQLDG significantly decreased the infarct volume, improved mouse behavior and brain slices pathological staining. In addition, it could ameliorate intestinal barrier damage and regulate tight junction gene expression. 16s rRNA, metabolomics and transcriptomics analysis revealed that HQLDG treatment significantly improved the composition of gut microbiota and Trp metabolism pathway, and further downregulated Th17/IL-17 signaling pathway. HQLDG treatment could significantly decrease serum inflammatory cytokines, IL-17A and IL-22; down-regulate Trp metabolism receptor gene (Ahr), inflammatory cytokines genes (IL-17a, IL-22), and an important coding gene for maintaining the mature Th17 (rorc) in both brain and intestinal tissues. In the contrary, after gut microbiota removal, this effect of HQLDG was impaired. HQLDG treated mouse fecal microbiota transplantation also had positive effect against tMCAO injury. Moreover, AhR inhibitor could decrease IL-17A immunofluorescence. These results suggested that the gut microbiota regulation might be an important intermediate in HQLDG against tMCAO injury. HQLDG might exerts anti-ischemic stroke effects through the gut microbiota-Trp metabolism-Th17/IL-17 signaling, which provides new insights into HQLDG-mediated prevention in ischemic stroke.}, } @article {pmid38781732, year = {2024}, author = {Wu, G and Liao, J and Zhu, X and Zhang, Y and Lin, Y and Zeng, Y and Zhao, J and Zhang, J and Yao, T and Shen, X and Li, H and Hu, L and Zhang, W}, title = {Shexiang Baoxin Pill enriches Lactobacillus to regulate purine metabolism in patients with stable coronary artery disease.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {130}, number = {}, pages = {155727}, doi = {10.1016/j.phymed.2024.155727}, pmid = {38781732}, issn = {1618-095X}, abstract = {BACKGROUND: It has been clinically confirmed that the Shexiang Baoxin Pill (SBP) dramatically reduces the frequency of angina in patients with stable coronary artery disease (SCAD). However, potential therapeutic mechanism of SBP has not been fully explored.

PURPOSE: The study explored the therapeutic mechanism of SBP in the treatment of SCAD patients.

METHODS: We examined the serum metabolic profiles of patients with SCAD following SBP treatment. A rat model of acute myocardial infarction (AMI) was established, and the potential therapeutic mechanism of SBP was explored using metabolomics, transcriptomics, and 16S rRNA sequencing.

RESULTS: SBP decreased inosine production and improved purine metabolic disorders in patients with SCAD and in animal models of AMI. Inosine was implicated as a potential biomarker for SBP efficacy. Furthermore, SBP inhibited the expression of genes involved in purine metabolism, which are closely associated with thrombosis, inflammation, and platelet function. The regulation of purine metabolism by SBP was associated with the enrichment of Lactobacillus. Finally, the effects of SBP on inosine production and vascular function could be transmitted through the transplantation of fecal microbiota.

CONCLUSION: Our study reveals a novel mechanism by which SBP regulates purine metabolism by enriching Lactobacillus to exert cardioprotective effects in patients with SCAD. The data also provide previously undocumented evidence indicating that inosine is a potential biomarker for evaluating the efficacy of SBP in the treatment of SCAD.}, } @article {pmid38780265, year = {2024}, author = {Zheng, L and Jiao, Y and Zhong, H and Tan, Y and Yin, Y and Liu, Y and Liu, D and Wu, M and Wang, G and Huang, J and Wang, P and Qin, M and Wang, M and Xiao, Y and Lv, T and Luo, Y and Hu, H and Hou, S-T and Kui, L}, title = {Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B6 metabolism.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0025724}, doi = {10.1128/msystems.00257-24}, pmid = {38780265}, issn = {2379-5077}, abstract = {Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific Bacteroides species and vitamin B6 metabolism. Indeed, vitamin B6 supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B6 metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.IMPORTANCEAccumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B6 metabolism. Bacterial species and compounds with beneficial roles in vitamin B6 metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.}, } @article {pmid38779440, year = {2024}, author = {Kasapoglu, M and Yadavalli, R and Nawaz, S and Althwanay, A and AlEdani, EM and Kaur, H and Butt, S}, title = {The Impact of Microbiome Interventions on the Progression and Severity of Inflammatory Bowel Disease: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {5}, pages = {e60786}, pmid = {38779440}, issn = {2168-8184}, abstract = {Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation. The dysbiotic gut microbiome likely contributes to IBD pathogenesis. Microbiome-directed therapies such as fecal microbiota transplantation (FMT), probiotics, and synbiotics may help induce and maintain remission. This systematic review aimed to determine the efficacy of microbiome interventions compared to standard therapy or placebo for IBD treatment. PubMed, EMBASE, Cochrane CENTRAL, and Web of Science were searched for randomized controlled trials on microbiome interventions in IBD from inception to October 2023. The risk of bias was assessed using Cochrane tools. Outcomes included disease activity, endoscopy, histology, quality of life, and adverse events. A total of 18 randomized controlled trials were included. Three trials found intensive (i.e., high frequency of administration and/or large volumes of fecal material) multi-donor FMT superior to autologous FMT or glucocorticoids for UC remission induction. Seven placebo-controlled trials demonstrated higher remission rates with FMT, especially intensive protocols, versus control for mild-to-moderate UC. However, a single FMT did not prevent relapses. Seven probiotic trials showed the potential to improve UC activity and maintain remission. One synbiotic trial reported reduced inflammation and symptoms versus placebo. Serious adverse events were rare. Small sample sizes and protocol heterogeneity limited the conclusions. Current evidence indicates the potential benefits of microbiome interventions, particularly intensive multi-donor FMT, for inducing and maintaining remission in UC. Probiotics may also improve outcomes. Adequately powered trials using standardized protocols are still needed to firmly establish efficacy and safety. Microbiome-directed therapies represent a promising approach for improving IBD outcomes.}, } @article {pmid38778483, year = {2024}, author = {Yan, J and Chen, H and Zhang, Y and Peng, L and Wang, Z and Lan, X and Yu, S and Yang, Y}, title = {Fecal microbiota transplantation significantly improved respiratory failure of amyotrophic lateral sclerosis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2353396}, doi = {10.1080/19490976.2024.2353396}, pmid = {38778483}, issn = {1949-0984}, mesh = {*Amyotrophic Lateral Sclerosis/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation ; *Respiratory Insufficiency/therapy/microbiology ; Male ; Middle Aged ; Aged ; Female ; Bacteroides ; Gastrointestinal Microbiome ; Faecalibacterium prausnitzii ; Treatment Outcome ; Respiration, Artificial ; Feces/microbiology ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to respiratory failure, and eventually death. However, there is a lack of effective treatments for ALS. Here we report the results of fecal microbiota transplantation (FMT) in two patients with late-onset classic ALS with a Japan ALS severity classification of grade 5 who required tracheostomy and mechanical ventilation. In both patients, significant improvements in respiratory function were observed following two rounds of FMT, leading to weaning off mechanical ventilation. Their muscle strength improved, allowing for assisted standing and mobility. Other notable treatment responses included improved swallowing function and reduced muscle fasciculations. Metagenomic and metabolomic analysis revealed an increase in beneficial Bacteroides species (Bacteroides stercoris, Bacteroides uniformis, Bacteroides vulgatus), and Faecalibacterium prausnitzii after FMT, as well as elevated levels of metabolites involved in arginine biosynthesis and decreased levels of metabolites involved in branched-chain amino acid biosynthesis. These findings offer a potential rescue therapy for ALS with respiratory failure and provide new insights into ALS in general.}, } @article {pmid38778379, year = {2024}, author = {Xu, W and Li, Y and Liu, L and Xie, J and Hu, Z and Kuang, S and Fu, X and Li, B and Sun, T and Zhu, C and He, Q and Sheng, W}, title = {Icaritin-curcumol activates CD8[+] T cells through regulation of gut microbiota and the DNMT1/IGFBP2 axis to suppress the development of prostate cancer.}, journal = {Journal of experimental & clinical cancer research : CR}, volume = {43}, number = {1}, pages = {149}, pmid = {38778379}, issn = {1756-9966}, support = {22B0370//Excellent Youth Project of Scientific Research Program of Hunan Education Department/ ; B2023034//Project of Traditional Chinese Medicine Administration of Hunan Province/ ; 2023JJ40511//Natural Science Foundation of Hunan Province/ ; kq2208204//Changsha Natural Science Foundation/ ; Z2023XJYQ05//Excellent Youth Project of Hunan University of Chinese Medicine/ ; W20243165//Hunan Provincial Hygiene and Health Commission Health Research Project/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Male ; *DNA (Cytosine-5-)-Methyltransferase 1/metabolism ; Humans ; *CD8-Positive T-Lymphocytes/metabolism/immunology ; *Prostatic Neoplasms/metabolism/pathology/drug therapy ; Insulin-Like Growth Factor Binding Protein 2/metabolism ; Flavonoids/pharmacology/therapeutic use ; Disease Models, Animal ; }, abstract = {BACKGROUND: Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa.

METHODS: A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development.

RESULTS: After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3[+]CD8[+]IFN-γ, CD3[+]CD8[+]Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2.

CONCLUSIONS: ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa.}, } @article {pmid38777572, year = {2024}, author = {Li, ZH and Weng, J and Yan, J and Zeng, YH and Hao, QY and Sheng, HF and Hua, YQ and Deng, Y and Wen, ZP and Wu, ZY and Li, GH and Li, X and Tan, RH and Ding, JC and Yang, PZ and Zhou, HW and Li, Z}, title = {Puerarin alleviates atherosclerosis via the inhibition of Prevotella copri and its trimethylamine production.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-331880}, pmid = {38777572}, issn = {1468-3288}, abstract = {OBJECTIVE: Puerarin (PU) is a natural compound that exhibits limited oral bioavailability but has shown promise in the treatment of atherosclerosis (AS). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood. This study aimed to investigate the effects of PU and its mechanisms in mitigating AS in both mice and humans.

DESIGN: The impact of PU on AS was examined in ApoE [-/-] mice fed a high-fat diet (HFD) and in human patients with carotid artery plaque. To explore the causal link between PU-associated gut microbiota and AS, faecal microbiota transplantation (FMT) and mono-colonisation of mice with Prevotella copri (P. copri) were employed.

RESULTS: PU alleviated AS by modulating the gut microbiota, as evidenced by alterations in gut microbiota composition and the amelioration of AS following FMT from PU-treated mice into ApoE[-/-] mice fed HFD. Specifically, PU reduced the abundance of P. copri, which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation of P. copri undermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance of P. copri and plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreased P. copri levels and reduced TMAO concentrations in patients with carotid artery plaque.

CONCLUSION: PU may provide therapeutic benefits in combating AS by targeting P. copri and its production of TMA.

TRIAL REGISTRATION NUMBER: ChiCTR1900022488.}, } @article {pmid38777056, year = {2024}, author = {He, G and Zhang, B and Yi, K and Chen, T and Shen, C and Cao, M and Wang, N and Zong, J and Wang, Y and Liu, K and Chang, F and Chen, X and Chen, L and Luo, Y and Meng, Y and Li, C and Zhou, X}, title = {Heat stress-induced dysbiosis of the gut microbiota impairs spermatogenesis by regulating secondary bile acid metabolism in the gut.}, journal = {The Science of the total environment}, volume = {}, number = {}, pages = {173305}, doi = {10.1016/j.scitotenv.2024.173305}, pmid = {38777056}, issn = {1879-1026}, abstract = {Heat stress (HS) poses a substantial challenge to livestock. Studies have demonstrated that HS reduces fertility and leads to gut microbiota dysbiosis in bulls. However, the impact of the gut microbiota on fertility in bulls during HS is still unclear. Our research revealed that HS exposure decreased semen quality in bulls, and fecal microbiota transplantation (FMT) from heat-stressed bulls to recipient mice resulted in a significant decrease in number of testicular germ cells and epididymal sperm. Untargeted metabolomics methodology and 16S rDNA sequencing conjoint analysis revealed that Akkermansia muciniphila (A. muciniphila) seemed to be a key bacterial regulator of spermatogenesis after HS exposure. Moreover, the research indicated that A. muciniphila regulated secondary bile acid metabolism by promoting the colonization of bile salt hydrolase (BSH)-metabolizing bacteria, leading to increase of retinol absorption in the host gut and subsequently elevation of testicular retinoic acid level, thereby improving spermatogenesis. This study sheds light on the relationship between HS-induced microbiota dysbiosis and spermatogenesis, offering a potential therapeutic approach for addressing bull spermatogenic dysfunction triggered by HS exposure.}, } @article {pmid38772789, year = {2024}, author = {Marasco, G and Cremon, C and Barbaro, MR and Bianco, F and Stanghellini, V and Barbara, G}, title = {Microbiota modulation in disorders of gut-brain interaction.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2024.05.004}, pmid = {38772789}, issn = {1878-3562}, abstract = {Disorders of gut-brain interaction (DGBI) are common chronic conditions characterized by persistent and recurring gastrointestinal symptoms triggered by several pathophysiological factors, including an altered gut microbiota. The most common DGBI are irritable bowel syndrome (IBS), functional constipation (FC) and functional dyspepsia (FD). Recently, a deep understanding of the role of the gut microbiota in these diseases was possible due to multi-omics methods capable to provide a comprehensive assessment. Most of the therapies recommended for these patients, can modulate the gut microbiota such as diet, prebiotics, probiotics and non-absorbable antibiotics, which were shown to be safe and effective. Since patients complain symptoms after food ingestion, diet represents the first line therapeutic approach. Avoiding dietary fat and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, and increasing the number of soluble fibers represent the therapeutic choices for FD, IBS and FC respectively. Probiotics, as a category, have been employed with good results in all the abovementioned DGBI. Rifaximin has been shown to be useful in the context of bowel related disorders, although a recent trial showed positive results for FD. Fecal microbiota transplantation has been tested for IBS and FC with promising results. In this review, we will briefly summarize the current understanding on dysbiosis and discuss microbiota modulation strategies to treat patients with DGBI.}, } @article {pmid38772541, year = {2024}, author = {Xu, Z and Wang, S and Liu, C and Kang, J and Pan, Y and Zhang, Z and Zhou, H and Xu, M and Li, X and Wang, H and Niu, S and Liu, L and Sun, D and Liu, X}, title = {The Role of Gut Microbiota in Male Erectile Dysfunction of Rats.}, journal = {The world journal of men's health}, volume = {}, number = {}, pages = {}, doi = {10.5534/wjmh.230337}, pmid = {38772541}, issn = {2287-4208}, support = {82171594/NSFC/National Natural Science Foundation of China/China ; }, abstract = {PURPOSE: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function.

MATERIALS AND METHODS: Male Sprague-Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection.

RESULTS: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways.

CONCLUSIONS: Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.}, } @article {pmid38770714, year = {2024}, author = {González-Correa, C and Moleón, J and Miñano, S and Robles-Vera, I and Toral, M and Barranco, AM and Martín-Morales, N and O'Valle, F and Guerra-Hernández, E and Sánchez, M and Gómez-Guzmán, M and Jiménez, R and Romero, M and Duarte, J}, title = {Differing contributions of the gut microbiota to the blood pressure lowering effects induced by first-line antihypertensive drugs.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.16410}, pmid = {38770714}, issn = {1476-5381}, support = {//Agencia Estatal de Investigación (AEI)/ ; PID2020-116347RB-I00//Ministerio de Ciencia e Innovación (MCIN)/ ; CTS 164//Junta de Andalucía/ ; P20_00193//Junta de Andalucía/ ; A-CTS-318-UGR20//Junta de Andalucía/ ; }, abstract = {BACKGROUND AND PURPOSE: This study analyses whether first-line antihypertensive drugs ameliorate the dysbiosis state in hypertension, and to test if this modification contributes to their blood pressure (BP) lowering properties in a genetic model of neurogenic hypertension.

EXPERIMENTAL APPROACH: Twenty-week-old male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were untreated or treated with captopril, amlodipine or hydrochlorothiazide. A faecal microbiota transplantation (FMT) experiment was also performed by gavage of faecal content from donor SHR-treated groups to SHR recipients for 3 weeks.

KEY RESULTS: Faeces from SHR showed gut dysbiosis, characterized by lower acetate- and higher lactate-producing bacteria and lower strict anaerobic bacteria. All three drugs increased the anaerobic bacteria proportion, captopril and amlodipine restored the proportion of acetate-producing bacterial populations to WKY levels, whereas hydrochlorothiazide decreased butyrate-producing bacteria. Captopril and amlodipine decreased gut pathology and permeability and attenuated sympathetic drive in the gut. Both drugs decreased neuroinflammation and oxidative stress in the hypothalamic paraventricular nuclei. Hydrochlorothiazide was unable to reduce neuroinflammation, gut sympathetic tone and gut integrity. FMT from SHR-amlodipine to SHR decreased BP, ameliorated aortic endothelium-dependent relaxation to acetylcholine, lowered NADPH oxidase activity, aortic Th17 infiltration and reduced neuroinflammation, whereas FMT from SHR-hydrochlorothiazide did not have these effects.

CONCLUSIONS AND IMPLICATIONS: First-line antihypertensive drugs induced different modifications of gut integrity and gut dysbiosis in SHR, which result in no contribution of microbiota in the BP lowering effects of hydrochlorothiazide, whereas the vasculo-protective effect induced by amlodipine involves gut microbiota reshaping and gut-immune system communication.}, } @article {pmid38770226, year = {2024}, author = {Hayes, AG and Penny, MJ and Aivazian, K and Greenfield, JR}, title = {Acute Interstitial Nephritis and Oxalate Nephropathy After Rapid Pasireotide Response in Treatment-resistant Acromegaly.}, journal = {JCEM case reports}, volume = {2}, number = {5}, pages = {luae071}, pmid = {38770226}, issn = {2755-1520}, abstract = {We report a case of interstitial nephritis, likely secondary to oxalate nephropathy, due to the development of pancreatic exocrine dysfunction after commencement of pasireotide for acromegaly. Pasireotide is known to impair insulin secretion but can also impair pancreatic exocrine function, hypothezised to result from high-affinity binding of somatostatin receptors 1, 2, 3, and 5. This has been an advantage in postoperative tissue anastomoses after pancreatic surgery, but exocrine insufficiency has not been reported when used for the treatment of acromegaly. A 73-year-old woman, diagnosed with acromegaly, was unable to achieve biochemical control despite 2 surgical resections of an invasive mammosomatotroph pituitary tumor and treatment with cabergoline and maximal-dose lanreotide. The tumor expressed somatostatin receptor type 5 but not somatostatin receptor type 2, predicting good response from pasireotide, which was commenced at 40 mg every 4 weeks. IGF-1 rapidly normalized, but the patient presented with nausea, anorexia, and acute kidney injury. Renal biopsy revealed acute-on-chronic interstitial nephritis, with numerous oxalate crystals. Increased fecal fat globules were noted on fat stain (3+), supporting malabsorption as an etiology of secondary enteric hyperoxaluria. Renal function recovered to near baseline over months following pasireotide withdrawal and high-dose glucocorticoids.}, } @article {pmid38770171, year = {2024}, author = {Cui, X and Zhang, T and Xie, T and Guo, FX and Zhang, YY and Deng, YJ and Wang, Q and Guo, YX and Dong, MH and Luo, XT}, title = {Research Progress on the Correlation Between Hypertension and Gut Microbiota.}, journal = {Journal of multidisciplinary healthcare}, volume = {17}, number = {}, pages = {2371-2387}, pmid = {38770171}, issn = {1178-2390}, abstract = {Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut-brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations.}, } @article {pmid38767452, year = {2024}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Kazadi, D and Halaweish, H and Khan, MH and Hoeschen, A and Cao, Q and Luo, X and Kabage, AJ and Lopez, S and Ramamoorthy, S and Holtan, SG and Weisdorf, DJ and Khoruts, A and Staley, C}, title = {Multi-omics analysis of a fecal microbiota transplantation trial identifies novel aspects of acute graft-versus-host disease pathogenesis.}, journal = {Cancer research communications}, volume = {}, number = {}, pages = {}, doi = {10.1158/2767-9764.CRC-24-0138}, pmid = {38767452}, issn = {2767-9764}, abstract = {Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (alloHCT) associated with gut microbiota disruptions. However, whether therapeutic microbiota modulation prevents aGVHD is unknown. We conducted a randomized, placebo-controlled trial of third-party fecal microbiota transplantation (FMT) administered at the peak of microbiota injury in 100 patients with acute myeloid leukemia receiving induction chemotherapy and alloHCT recipients. Despite improvements in microbiome diversity, expansion of commensals, and shrinkage of potential pathogens, aGVHD occurred more frequently after FMT than placebo. Although this unexpected finding could be explained by clinical differences between the two arms, we asked whether a microbiota explanation might be also present. To this end, we performed multi-omics analysis of pre- and post-intervention gut microbiome and serum metabolome. We found that post-intervention expansion of Faecalibacterium, a commensal genus with gut-protective and anti-inflammatory properties under homeostatic conditions, predicted a higher risk for aGVHD. Faecalibacterium expansion occurred predominantly after FMT and was due to engraftment of unique donor taxa, suggesting that donor Faecalibacterium-derived antigens might have stimulated allogeneic immune cells. Faecalibacterium and ursodeoxycholic acid (an anti-inflammatory secondary bile acid) were negatively correlated, offering an alternative mechanistic explanation. In conclusion, we demonstrate context dependence of microbiota effects where a normally beneficial bacteria may become detrimental in disease. While FMT is a broad, community-level intervention, it may need precision engineering in ecologically complex settings where multiple perturbations (e.g. antibiotics, intestinal damage, alloimmunity) are concurrently in effect.}, } @article {pmid38765739, year = {2024}, author = {Davoutis, E and Gkiafi, Z and Lykoudis, PM}, title = {Bringing gut microbiota into the spotlight of clinical research and medical practice.}, journal = {World journal of clinical cases}, volume = {12}, number = {14}, pages = {2293-2300}, pmid = {38765739}, issn = {2307-8960}, abstract = {Despite the increasing scientific interest and expanding role of gut microbiota (GM) in human health, it is rarely reported in case reports and deployed in clinical practice. Proteins and metabolites produced by microbiota contribute to immune system development, energy homeostasis and digestion. Exo- and endogenous factors can alter its composition. Disturbance of microbiota, also known as dysbiosis, is associated with various pathological conditions. Specific bacterial taxa and related metabolites are involved in disease pathogenesis and therefore can serve as a diagnostic tool. GM could also be a useful prognostic factor by predicting future disease onset and preventing hospital-associated infections. Additionally, it can influence response to treatments, including those for cancers, by altering drug bioavailability. A thorough understanding of its function has permitted significant development in therapeutics, such as probiotics and fecal transplantation. Hence, GM should be considered as a ground-breaking biological parameter, and it is advisable to be investigated and reported in literature in a more consistent and systematic way.}, } @article {pmid38761425, year = {2024}, author = {Tian, R and Wang, X and Tang, S and Zhao, L and Hao, Y and Li, R and Zhou, X}, title = {Gut microbiota mediates the protective effects of β-hydroxybutyrate against cisplatin-induced acute kidney injury.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {175}, number = {}, pages = {116752}, doi = {10.1016/j.biopha.2024.116752}, pmid = {38761425}, issn = {1950-6007}, abstract = {The gut microbiota has been reported to be perturbed by chemotherapeutic agents and to modulate side effects. However, the critical role of β-hydroxybutyrate (BHB) in the regulation of the gut microbiota and the pathogenesis of chemotherapeutic agents related nephrotoxicity remains unknown. We conducted a comparative analysis of the composition and function of gut microbiota in healthy, cisplatin-challenged, BHB-treated, and high-fat diet-treated mice using 16 S rDNA gene sequencing. To understand the crucial involvement of intestinal flora in BHB's regulation of cisplatin -induced nephrotoxicity, we administered antibiotics to deplete the gut microbiota and performed fecal microbiota transplantation (FMT) before cisplatin administration. 16 S rDNA gene sequencing analysis demonstrated that both endogenous and exogenous BHB restored gut microbiota dysbiosis and cisplatin-induced intestinal barrier disruption in mice. Additionally, our findings suggested that the LPS/TLR4/NF-κB pathway was responsible for triggering renal inflammation in the gut-kidney axis. Furthermore, the ablation of the gut microbiota ablation using antibiotics eliminated the renoprotective effects of BHB against cisplatin-induced acute kidney injury. FMT also confirmed that administration of BHB-treated gut microbiota provided protection against cisplatin-induced nephrotoxicity. This study elucidated the mechanism by which BHB affects the gut microbiota mediation of cisplatin-induced nephrotoxicity by inhibiting the inflammatory response, which may help develop novel therapeutic approaches that target the composition of the microbiota.}, } @article {pmid38759313, year = {2024}, author = {Xu, D and Liu, D and Jiang, N and Xie, Y and He, D and Cheng, J and Liu, J and Fu, S and Hu, G}, title = {Narirutin mitigates dextrose sodium sulfate-induced colitis in mice by modulating intestinal flora.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {130}, number = {}, pages = {155730}, doi = {10.1016/j.phymed.2024.155730}, pmid = {38759313}, issn = {1618-095X}, abstract = {BACKGROUND: Ulcerative colitis (UC) is a prolonged inflammatory disease of the gastrointestinal tract. Current therapeutic options remain limited, underscoring the imperative to explore novel therapeutic strategies. Narirutin (NR), a flavonoid naturally present in citrus fruits, exhibits excellent anti-inflammatory effects in vitro, yet its in vivo efficacy, especially in UC, remains underexplored.

OBJECTIVE: This work examined the effect of NR on dextrose sodium sulfate (DSS)-induced UC in mice in vivo, with a specific focus on the role of gut flora in it.

METHODS: The effects of NR (10, 20, and 40 mg/kg) on DSS-induced UC in mice were investigated by monitoring changes in body weight, disease activity index (DAI) scores, colon length, and histological damage. Colonic levels of pro-inflammatory mediators, tight junction (TJ) proteins, and inflammation-related signaling pathway proteins were analyzed via enzyme-linked immunosorbent assay, western blot, and immunofluorescence. The role of gut microbiota in NR against colitis was analyzed through 16S rRNA sequencing, flora clearance assays, and fecal microbiota transplantation (FMT) assays.

RESULTS: NR administration suppressed DSS-induced colitis as reflected in a decrease in body weight loss, DAI score, colon length shortening, and histological score. Furthermore, NR administration preserved the integrity of the DSS-induced intestinal barrier by inhibiting the reduction of TJ proteins (claudin3, occludin, and zonula occludens-1). Moreover, NR administration markedly repressed the activation of the toll-like receptor 4-mitogen-activated protein kinase/nuclear factor-κB pathway and reduced the amount of pro-inflammatory mediators in the colon. Importantly, the results of 16S rRNA sequencing showed that the intestinal flora of mice with colitis exhibited richer microbial diversity following NR administration, with elevated abundance of Lactobacillaceae (Lactobacillus) and decreased abundance of Bacteroidaceae (Bacteroides) and Shigella. In addition, the anti-colitis effect of NR almost disappeared after gut flora clearance. Further FMT assay also validated this gut flora-dependent protective mechanism of NR.

CONCLUSION: Our findings suggest that NR is a prospective natural compound for the management of UC by modulating intestinal flora.}, } @article {pmid38676422, year = {2024}, author = {Tang, M and Wang, C and Xia, Y and Tang, J and Wang, J and Shen, L}, title = {Clostridioides difficile infection in inflammatory bowel disease: a clinical review.}, journal = {Expert review of anti-infective therapy}, volume = {22}, number = {5}, pages = {297-306}, doi = {10.1080/14787210.2024.2347955}, pmid = {38676422}, issn = {1744-8336}, mesh = {Humans ; *Clostridium Infections/therapy/microbiology ; *Inflammatory Bowel Diseases/complications/therapy/microbiology ; *Probiotics/administration & dosage ; *Anti-Bacterial Agents/administration & dosage ; Risk Factors ; Fecal Microbiota Transplantation ; Clostridioides difficile/isolation & purification ; Gastrointestinal Microbiome ; Prebiotics/administration & dosage ; Coinfection ; Immunotherapy/methods ; Child ; Prevalence ; Severity of Illness Index ; Age Factors ; Aged ; }, abstract = {INTRODUCTION: Strong clinical data demonstrate that inflammatory bowel disease (IBD) is an independent risk factor for Clostridiodes difficile infection (CDI) and suggest a globally increased prevalence and severity of C. difficile coinfection in IBD patients (CDI-IBD). In addition to elderly individuals, children are also at higher risk of CDI-IBD. Rapid diagnosis is essential since the clinical manifestations of active IBD and CDI-IBD are indistinguishable. Antibiotics have been well established in the treatment of CDI-IBD, but they do not prevent recurrence.

AREAS COVERED: Herein, the authors focus on reviewing recent research advances on the new therapies of CDI-IBD. The novel therapies include gut microbiota restoration therapies (such as prebiotics, probiotics and FMT), immunotherapy (such as vaccines and monoclonal antibodies) and diet strategies (such as groningen anti-inflammatory diet and mediterranean diet). Future extensive prospective and placebo-controlled studies are required to evaluate their efficacy and long-term safety.

EXPERT OPINION: Available studies show that the prevalence of CDI-IBD is not optimistic. Currently, potential treatment options for CDI-IBD include a number of probiotics and novel antibiotics. This review updates the knowledge on the management of CDI in IBD patients, which is timely and important for GI doctors and scientists.}, } @article {pmid38758227, year = {2024}, author = {Long, C and Zhang, C and Xie, Y}, title = {Study on the mechanism of hirudin multi target delaying renal function decline in chronic kidney disease based on the "gut-kidney axis" theory.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {}, number = {}, pages = {}, pmid = {38758227}, issn = {1432-1912}, support = {82060804//2020 National Natural Science Foundation Project/ ; 2023GXNSFAA026212//2023 Guangxi Natural Science Foundation Program/ ; 2022MS010//2022 Guangxi University of Traditional Chinese Medicine (GXUTCM) School-level Surface Projects/ ; }, abstract = {The disorder of the "gut-kidney axis" exacerbates renal function decline in chronic kidney disease (CKD), and current CKD therapy is insufficient to address this issue. Hirudin has a palliative effect on the decline of renal function. However, whether hirudin can delay CKD by regulating the "intestinal renal axis" disorder remains unclear. Unilateral ureteral ligation (UUO) induced CKD rat model, and the rats were treated with bifidobacterium and hirudin for 36 days. After 14 and 36 days of modeling, kidney and colon tissues were collected for pathology, western blot (WB) assay, and quantitative real-time PCR (qPCR) detection. Serum samples were collected for renal function testing. Fecal samples were used for 16S rRNA sequencing and research on fecal bacterial transplantation. Lipopolysaccharide combine with adenosine 5'-triphosphate (LPS + ATP)-induced intestinal epithelial cell injury was treated with a nod-like receptor pyrin domain-associated protein 3 (NLRP3) inhibitor and hirudin. Protein expression was detected using WB and qPCR. The kidneys and colons of the CKD rats exhibited varying degrees of lesions. Creatinine (CRE), blood urea nitrogen (BUN), N-acetyl-β-D-glucosidase (NAG) enzyme, and serum uremic toxins were elevated. The expression of claudin-1 and occludin was decreased, NLRP3 inflammatory-related proteins were increased, and the gut microbiota was disrupted. These pathological changes were more pronounced after 36 days of modeling. Meanwhile, high-dose hirudin treatment significantly improved these lesions and restored the intestinal flora to homeostasis in CKD rats. In vitro, hirudin demonstrated comparable effects to NLRP3 inhibitors by upregulating claudin-1 and occludin expression, and downregulating NLRP3 inflammatory-related proteins expression. The dysbiosis of the gut microbiota and impaired intestinal epithelial barrier function in CKD are associated with renal dysfunction in CKD. Hirudin delays the progression of CKD by regulating the disorder of the "gut-kidney axis" and inhibiting the activation of the NLRP3-ASC-caspase-1 pathway.}, } @article {pmid38757304, year = {2024}, author = {Wu, P and Xue, J and Zhu, Z and Yu, Y and Sun, Q and Xie, M and Wang, B and Huang, P and Feng, Z and Zhao, J}, title = {Puerariae lobatae Radix ameliorates chronic kidney disease by reshaping gut microbiota and downregulating Wnt/β‑catenin signaling.}, journal = {Molecular medicine reports}, volume = {30}, number = {1}, pages = {}, doi = {10.3892/mmr.2024.13241}, pmid = {38757304}, issn = {1791-3004}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Renal Insufficiency, Chronic/drug therapy/metabolism ; *Wnt Signaling Pathway/drug effects ; Mice ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; Male ; *Pueraria/chemistry ; Disease Models, Animal ; Dysbiosis/drug therapy ; Down-Regulation/drug effects ; Kidney/drug effects/pathology/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; }, abstract = {Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote the gut microbiota homeostasis; however, its role in renoprotection remains unknown. The present study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8‑week 2% NaCl‑feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, The medium and high doses of PLR significantly alleviated CKD‑associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and downregulating the canonical Wnt/β‑catenin pathway. Furthermore, PLR rescued the gut microbiota dysbiosis and protected against high salt‑induced gut barrier dysfunction. Enrichment of Akkermansia and Bifidobacterium was found after PLR intervention, the relative abundances of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was, at least partially, exerted through gut microbiota reestablishment and downregulation of the Wnt/β‑catenin pathway. The present study provided evidence for a new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.}, } @article {pmid38754739, year = {2024}, author = {Allegretti, JR and Khanna, S and Mullish, BH and Feuerstadt, P}, title = {The Progression of Microbiome Therapeutics for the Management of Gastrointestinal Diseases and Beyond.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.05.004}, pmid = {38754739}, issn = {1528-0012}, abstract = {There has been an increased ability to investigate human microbiota through next generation sequencing and functional assessment. This advancement has rapidly expanded our ability to study and manipulate the gastrointestinal microbiome to mitigate disease. Fecal microbiota transplantation (FMT), a therapy which broadly transfers the entire intestinal ecosystem, has been explored as a potential therapeutic in a variety of gastrointestinal, hepatic and extraintestinal conditions. The field however continues to evolve with a movement towards precision microbiome therapeutics individualizing care for various disorders. This review will describe the use of FMT, microbiota restoration and precision microbiome therapeutics focusing in gastrointestinal and hepatic diseases.}, } @article {pmid38754198, year = {2024}, author = {Liu, JL and Chen, LJ and Liu, Y and Li, JH and Zhang, KK and Hsu, C and Li, XW and Yang, JZ and Chen, L and Zeng, JH and Xie, XL and Wang, Q}, title = {The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.}, journal = {Ecotoxicology and environmental safety}, volume = {279}, number = {}, pages = {116457}, doi = {10.1016/j.ecoenv.2024.116457}, pmid = {38754198}, issn = {1090-2414}, abstract = {Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.}, } @article {pmid38753616, year = {2024}, author = {Pidala, J and Carpenter, PA and Onstad, L and Pavletic, SZ and Hamilton, BK and Chen, GL and Farhadfar, N and Hall, M and Lee, SJ}, title = {Study protocol: Close Assessment and Testing for Chronic Graft-vs.-Host disease (CATCH).}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0298026}, pmid = {38753616}, issn = {1932-6203}, mesh = {*Graft vs Host Disease/diagnosis/etiology ; Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Chronic Disease ; Prospective Studies ; Longitudinal Studies ; Adult ; Male ; Female ; Transplantation, Homologous ; Biomarkers ; Middle Aged ; }, abstract = {Chronic graft-versus-host disease (GVHD) is an immune-mediated disorder that causes significant late morbidity and mortality following allogeneic hematopoietic cell transplantation. The "Close Assessment and Testing for Chronic GVHD (CATCH)" study is a multi-center Chronic GVHD Consortium prospective, longitudinal cohort study designed to enroll patients before hematopoietic cell transplantation and follow them closely to capture the development of chronic GVHD and to identify clinical and biologic biomarkers of chronic GVHD onset. Data are collected pre-transplant and every two months through one-year post-transplant with chart review thereafter. Evaluations include clinician assessment of chronic GVHD and its manifestations, patient-reported outcomes, multiple biospecimens (blood, saliva, tears, buccal mucosa and fecal samples, biopsies of skin and mouth), laboratory testing, and medical record abstraction. This report describes the rationale, design, and methods of the CATCH study, and invites collaboration with other investigators to leverage this resource. trial registration: This study is registered at www.clinicaltrials.gov as NCT04188912.}, } @article {pmid38651930, year = {2024}, author = {Reygner, J and Delannoy, J and Barba-Goudiaby, M-T and Gasc, C and Levast, B and Gaschet, E and Ferraris, L and Paul, S and Kapel, N and Waligora-Dupriet, A-J and Barbut, F and Thomas, M and Schwintner, C and Laperrousaz, B and Corvaïa, N}, title = {Reduction of product composition variability using pooled microbiome ecosystem therapy and consequence in two infectious murine models.}, journal = {Applied and environmental microbiology}, volume = {90}, number = {5}, pages = {e0001624}, doi = {10.1128/aem.00016-24}, pmid = {38651930}, issn = {1098-5336}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Clostridioides difficile ; *Clostridium Infections/therapy/microbiology ; *Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Feces/microbiology ; Bacteria/classification/genetics ; Humans ; Mice, Inbred C57BL ; Female ; }, abstract = {Growing evidence demonstrates the key role of the gut microbiota in human health and disease. The recent success of microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on its potential in conditions associated with gut dysbiosis, such as acute graft-versus-host disease, intestinal bowel diseases, neurodegenerative diseases, or even cancer. However, the difficulty in defining a "good" donor as well as the intrinsic variability of donor-derived products' taxonomic composition limits the translatability and reproducibility of these studies. Thus, the pooling of donors' feces has been proposed to homogenize product composition and achieve higher taxonomic richness and diversity. In this study, we compared the metagenomic profile of pooled products to corresponding single donor-derived products. We demonstrated that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria known to produce anti-inflammatory short chain fatty acids compared to single donor-derived products. We then evaluated pooled products' efficacy compared to corresponding single donor-derived products in Salmonella and C. difficile infectious mouse models. We were able to demonstrate that pooled products decreased pathogenicity by inducing a structural change in the intestinal microbiota composition. Single donor-derived product efficacy was variable, with some products failing to control disease progression. We further performed in vitro growth inhibition assays of two extremely drug-resistant bacteria, Enterococcus faecium vanA and Klebsiella pneumoniae oxa48, supporting the use of pooled microbiotherapies. Altogether, these results demonstrate that the heterogeneity of donor-derived products is corrected by pooled fecal microbiotherapies in several infectious preclinical models.IMPORTANCEGrowing evidence demonstrates the key role of the gut microbiota in human health and disease. Recent Food and Drug Administration approval of fecal microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on their potential to treat pathological conditions associated with gut dysbiosis. In this study, we combined metagenomic analysis with in vitro and in vivo studies to compare the efficacy of pooled microbiotherapy products to corresponding single donor-derived products. We demonstrate that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria compared to single donor-derived products. We further reveal that pooled products decreased Salmonella and Clostridioides difficile pathogenicity in mice, while single donor-derived product efficacy was variable, with some products failing to control disease progression. Altogether, these findings support the development of pooled microbiotherapies to overcome donor-dependent treatment efficacy.}, } @article {pmid38752739, year = {2024}, author = {Anderson, BG and Raskind, A and Hissong, R and Dougherty, MK and McGill, SK and Gulati, AS and Theriot, CM and Kennedy, RT and Evans, CR}, title = {Offline Two-Dimensional Liquid Chromatography-Mass Spectrometry for Deep Annotation of the Fecal Metabolome Following Fecal Microbiota Transplantation.}, journal = {Journal of proteome research}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jproteome.4c00022}, pmid = {38752739}, issn = {1535-3907}, abstract = {Biological interpretation of untargeted LC-MS-based metabolomics data depends on accurate compound identification, but current techniques fall short of identifying most features that can be detected. The human fecal metabolome is complex, variable, incompletely annotated, and serves as an ideal matrix to evaluate novel compound identification methods. We devised an experimental strategy for compound annotation using multidimensional chromatography and semiautomated feature alignment and applied these methods to study the fecal metabolome in the context of fecal microbiota transplantation (FMT) for recurrent C. difficile infection. Pooled fecal samples were fractionated using semipreparative liquid chromatography and analyzed by an orthogonal LC-MS/MS method. The resulting spectra were searched against commercial, public, and local spectral libraries, and annotations were vetted using retention time alignment and prediction. Multidimensional chromatography yielded more than a 2-fold improvement in identified compounds compared to conventional LC-MS/MS and successfully identified several rare and previously unreported compounds, including novel fatty-acid conjugated bile acid species. Using an automated software-based feature alignment strategy, most metabolites identified by the new approach could be matched to features that were detected but not identified in single-dimensional LC-MS/MS data. Overall, our approach represents a powerful strategy to enhance compound identification and biological insight from untargeted metabolomics data.}, } @article {pmid38752578, year = {2024}, author = {Fuhri Snethlage, CM and de Wit, D and Wortelboer, K and Rampanelli, E and Hanssen, NMJ and Nieuwdorp, M}, title = {Can fecal microbiota transplantations modulate autoimmune responses in type 1 diabetes?.}, journal = {Immunological reviews}, volume = {}, number = {}, pages = {}, doi = {10.1111/imr.13345}, pmid = {38752578}, issn = {1600-065X}, support = {09150172210019/ZONMW_/ZonMw/Netherlands ; 09150172210050/ZONMW_/ZonMw/Netherlands ; 09150182010020/ZONMW_/ZonMw/Netherlands ; 101141346//ERC advanced grant FATGAP/ ; 2021T055//Dekker grant of Dutch Heart Foundation/ ; 2020.10.002//Stichting Diabetes Onderzoek Nederland/ ; }, abstract = {Type 1 diabetes (T1D) is a chronic autoimmune disease targeting insulin-producing pancreatic beta cells. T1D is a multifactorial disease incorporating genetic and environmental factors. In recent years, the advances in high-throughput sequencing have allowed researchers to elucidate the changes in the gut microbiota taxonomy and functional capacity that accompany T1D development. An increasing number of studies have shown a role of the gut microbiota in mediating immune responses in health and disease, including autoimmunity. Fecal microbiota transplantations (FMT) have been largely used in murine models to prove a causal role of the gut microbiome in disease progression and have been shown to be a safe and effective treatment in inflammatory human diseases. In this review, we summarize and discuss recent research regarding the gut microbiota-host interactions in T1D, the current advancement in therapies for T1D, and the usefulness of FMT studies to explore microbiota-host immunity encounters in murine models and to shape the course of human type 1 diabetes.}, } @article {pmid38508697, year = {2024}, author = {Knudsen, LA and Zachariassen, LS and Strube, ML and Havelund, JF and Pilecki, B and Nexoe, AB and Møller, FT and Sørensen, SB and Marcussen, N and Faergeman, NJ and Franke, A and Bang, C and Holmskov, U and Hansen, AK and Andersen, V}, title = {Assessment of the Inflammatory Effects of Gut Microbiota from Human Twins Discordant for Ulcerative Colitis on Germ-free Mice.}, journal = {Comparative medicine}, volume = {74}, number = {2}, pages = {55-69}, pmid = {38508697}, issn = {2769-819X}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Colitis, Ulcerative/microbiology ; Humans ; Mice ; Female ; Germ-Free Life ; Dextran Sulfate/toxicity ; Feces/microbiology ; Pregnancy ; Male ; Disease Models, Animal ; Fecal Microbiota Transplantation ; }, abstract = {Disturbances in gut microbiota are prevalent in inflammatory bowel disease (IBD), which includes ulcerative colitis (UC). However, whether these disturbances contribute to development of the disease or are a result of the disease is unclear. In pairs of human twins discordant for IBD, the healthy twin has a higher risk of developing IBD and a gut microbiota that is more similar to that of IBD patients as compared with healthy individuals. Furthermore, appropriate medical treatment may mitigate these disturbances. To study the correlation between microbiota and IBD, we transferred stool samples from a discordant human twin pair: one twin being healthy and the other receiving treatment for UC. The stool samples were transferred from the disease-discordant twins to germ-free pregnant dams. Colitis was induced in the offspring using dextran sodium sulfate. As compared with offspring born to mice dams inoculated with stool from the healthy cotwin, offspring born to dams inoculated with stool from the UC-afflicted twin had a lower disease activity index, less gut inflammation, and a microbiota characterized by higher α diversity and a more antiinflammatory profile that included the presence and higher abundance of antiinflammatory species such as Akkermansia spp., Bacteroides spp., and Parabacteroides spp. These findings suggest that the microbiota from the healthy twin may have had greater inflammatory properties than did that of the twin undergoing UC treatment.}, } @article {pmid38750621, year = {2024}, author = {Hain, E and Lefèvre, JH and Ricardo, A and Lee, S and Zaghiyan, K and McLemore, E and Sherwinter, D and Rhee, R and Wilson, M and Martz, J and Maykel, J and Marks, J and Marcet, J and Rouanet, P and Maggiori, L and Komen, N and De Hous, N and Lakkis, Z and Tuech, JJ and Sylla, P and Attiyeh, F and Cotte, E}, title = {SafeHeal Colovac Colorectal Anastomosis Protection Device evaluation (SAFE-2) pivotal study: an international randomized controlled study to evaluate the safety and effectiveness of the Colovac Colorectal Anastomosis Protection Device.}, journal = {Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland}, volume = {}, number = {}, pages = {}, doi = {10.1111/codi.17012}, pmid = {38750621}, issn = {1463-1318}, abstract = {AIM: Although proximal faecal diversion is standard of care to protect patients with high-risk colorectal anastomoses against septic complications of anastomotic leakage, it is associated with significant morbidity. The Colovac device (CD) is an intraluminal bypass device intended to avoid stoma creation in patients undergoing low anterior resection. A preliminary study (SAFE-1) completed in three European centres demonstrated 100% protection of colorectal anastomoses in 15 patients, as evidenced by the absence of faeces below the CD. This phase III trial (SAFE-2) aims to evaluate the safety and effectiveness of the CD in a larger cohort of patients undergoing curative rectal cancer resection.

METHODS: SAFE-2 is a pivotal, multicentre, prospective, open-label, randomized, controlled trial. Patients will be randomized in a 1:1 ratio to either the CD arm or the diverting loop ileostomy arm, with a recruitment target of 342 patients. The co-primary endpoints are the occurrence of major postoperative complications within 12 months of index surgery and the effectiveness of the CD in reducing stoma creation rates. Data regarding quality of life and patient's acceptance and tolerance of the device will be collected.

DISCUSSION: SAFE-2 is a multicentre randomized, control trial assessing the efficacy and the safety of the CD in protecting low colorectal anastomoses created during oncological resection relative to standard diverting loop ileostomy.

TRIAL REGISTRATION: NCT05010850.}, } @article {pmid38749910, year = {2024}, author = {Cheng, CL and Wang, XJ and Fan, LX and Lv, YL and Xiong, K and Jiang, ZW and Gan, T and Fu, G}, title = {Successful allogeneic fecal microbiota transplantation for severe diversion colitis: a case report.}, journal = {The Journal of international medical research}, volume = {52}, number = {5}, pages = {3000605241241000}, doi = {10.1177/03000605241241000}, pmid = {38749910}, issn = {1473-2300}, mesh = {Humans ; Male ; Aged ; *Fecal Microbiota Transplantation/methods ; *Colitis/microbiology/therapy ; *Ileostomy ; *Gastrointestinal Microbiome ; Transplantation, Homologous/methods ; Treatment Outcome ; Colonoscopy ; }, abstract = {Ileostomy diverts the flow of feces, which can result in malnutrition in the distal part of the intestine. The diversity of the gut microbiota consequently decreases, ultimately leading to intestinal dysbiosis and dysfunction. This condition can readily result in diversion colitis (DC). Potential treatment strategies include interventions targeting the gut microbiota. In this case study, we effectively treated a patient with severe DC by ileostomy and allogeneic fecal microbiota transplantation (FMT). A 69-year-old man presented with a perforated malignant tumor in the descending colon and an iliac abscess. He underwent laparoscopic radical sigmoid colon tumor resection and prophylactic ileostomy. Follow-up colonoscopy 3 months postoperatively revealed diffuse intestinal mucosal congestion and edema along with granular inflammatory follicular hyperplasia, leading to a diagnosis of severe DC. After two rounds of allogeneic FMT, both the intestinal mucosal bleeding and edema significantly improved, as did the diversity of the gut microbiota. The positive outcome of allogeneic FMT in this case highlights the potential advantages that this procedure can offer patients with DC. However, few studies have focused on allogeneic FMT, and more in-depth research is needed to gain a better understanding.}, } @article {pmid38749861, year = {2024}, author = {Galvao, FHF}, title = {Microsurgical Technique and Results of Anorectal Transplantation in the Rat.}, journal = {Transplantation proceedings}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.transproceed.2024.03.025}, pmid = {38749861}, issn = {1873-2623}, abstract = {UNLABELLED: Anorectal transplantation (ART) is an obvious therapeutic option for treating permanent colostomy and severe fecal incontinence. The rat is the best model for beginning studies of a new surgical procedure. In this article, we review ART techniques in rats.

METHODS: We reviewed articles on rat and ART keywords throughout Cochrane Library, MEDLINE, and EMBASE. Five articles were found, of which 2 used autotransplantations, 1 performed only transplantation of the anal canal and extraperitoneal rectum, and another performed transplantation of the entire intestine, including the anus, but only followed for 2 hours.

RESULTS: In 2016, we performed the first series of isoART (n = 6) and alloART (n = 9) of the entire anorectal segment and micro-anastomosis of the inferior mesenteric vessels. Two animals died due to surgical complications, and the others survived until the endpoint of the experiment. Five animals with alloART showed clinical signs of immunologic rejection 3 weeks after transplantation, and autopsy histology on postoperative day 30 revealed moderate to severe rejection in the allografts.

CONCLUSIONS: In this review, we observed that ART in rats is viable and may allow further physiologic and immunologic studies of this procedure, a potential treatment for severe incontinence and permanent colostomy.}, } @article {pmid38748640, year = {2024}, author = {He, N and Chen, K and Yu, S and Cui, L and Vu, SH and Jung, S and Lee, MS and Li, S}, title = {Stachyose Exerts Anticolitis Efficacy by Re-balancing Treg/Th17 and Activating the Butyrate-Derived PPARγ Signaling Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c01387}, pmid = {38748640}, issn = {1520-5118}, abstract = {Ulcerative colitis (UC) is a complex chronic inflammatory disease closely associated with gut homeostasis dysfunction. The previous studies have shown that stachyose, a functional food additive, has the potential to enhance gut health and alleviate UC symptoms. However, the underlying mechanism of its effects remains unknown. In this study, our findings showed that dietary supplements of stachyose had a significant dose-dependent protective effect on colitis symptoms, regulation of gut microbiota, and restoration of the Treg/Th17 cell balance in dextran sulfate sodium (DSS) induced colitis mice. To further validate these findings, we conducted fecal microbiota transplantation (FMT) to treat DSS-induced colitis in mice. The results showed that microbiota from stachyose-treated mice exhibited a superior therapeutic effect against colitis and effectively regulated the Treg/Th17 cell balance in comparison to the control group. Moreover, both stachyose supplementation and FMT resulted in an increase in butyrate production and the activation of PPARγ. However, this effect was partially attenuated by PPARγ antagonist GW9662. These results suggested that stachyose alleviates UC symptoms by modulating gut microbiota and activating PPARγ. In conclusion, our work offers new insights into the benefical effects of stachyose on UC and its potential role in modulating gut microbiota.}, } @article {pmid38748594, year = {2024}, author = {Liu, S and Luo, X and Zhou, L and Xie, RH and He, Y}, title = {Microbiota transplantation in restoring cesarean-related infant dysbiosis: a new frontier.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2351503}, doi = {10.1080/19490976.2024.2351503}, pmid = {38748594}, issn = {1949-0984}, mesh = {Humans ; *Dysbiosis/microbiology ; Female ; *Cesarean Section/adverse effects ; *Gastrointestinal Microbiome ; Pregnancy ; *Fecal Microbiota Transplantation ; Infant, Newborn ; Vagina/microbiology ; Infant ; }, abstract = {C-section is crucial in reducing maternal and neonatal mortality when medically indicated, but one of its side effects could be the disruption of vertical transmission of maternal-infant microbiota during delivery, potentially leading to gut dysbiosis and increased disease risks in C-section infants. To address such dysbiosis, it seems reasonable to supplement "what is missing" during C-section procedure. This idea has prompted several clinical trials, including proof-of-concept, investigating interventions like vaginal microbial seeding, oral administration of maternal vaginal microbes and even oral administration of maternal fecal materials. Hereby, we have summarized these trials to help understand the current state of these researches, highlighting the predominantly pilot nature of most of these studies and emphasizing the need for well-designed studies with larger sample to guide evidence-based medicine in the future.}, } @article {pmid38746249, year = {2024}, author = {Ke, S and Villafuerte Gálvez, JA and Sun, Z and Cao, Y and Pollock, NR and Chen, X and Kelly, CP and Liu, YY}, title = {Rational Design of Live Biotherapeutic Products for the Prevention of Clostridioides difficile Infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.04.30.591969}, pmid = {38746249}, abstract = {Clostridioides difficile infection (CDI) is one of the leading causes of healthcare- and antibiotic-associated diarrhea. While fecal microbiota transplantation (FMT) has emerged as a promising therapy for recurrent CDI, its exact mechanisms of action and long-term safety are not fully understood. Defined consortia of clonal bacterial isolates, known as live biotherapeutic products (LBPs), have been proposed as an alternative therapeutic option. However, the rational design of LBPs remains challenging. Here, we employ a computational pipeline and three independent metagenomic datasets to systematically identify microbial strains that have the potential to inhibit CDI. We first constructed the CDI-related microbial genome catalog, comprising 3,741 non-redundant metagenome-assembled genomes (nrMAGs) at the strain level. We then identified multiple potential protective nrMAGs that can be candidates for the design of microbial consortia targeting CDI, including strains from Dorea formicigenerans , Oscillibacter welbionis , and Faecalibacterium prausnitzii . Importantly, some of these potential protective nrMAGs were found to play an important role in the success of FMT, and the majority of the top protective nrMAGs can be validated by various previously reported findings. Our results demonstrate a computational framework for the rational selection of microbial strains targeting CDI, paving the way for the computational design of microbial consortia against other enteric infections.}, } @article {pmid38743445, year = {2024}, author = {Cafaro, G and Cruciani, G and Bruno, L and Dal Pozzolo, R and Colangelo, A and Tromby, F and Nicchi, M and Pianese, B and Perricone, C and Gerli, R and Bartoloni, E}, title = {Microbiota and arthritis: cause or consequence?.}, journal = {Clinical and experimental rheumatology}, volume = {42}, number = {5}, pages = {1097-1103}, doi = {10.55563/clinexprheumatol/f6q4dc}, pmid = {38743445}, issn = {0392-856X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Dysbiosis ; Animals ; Probiotics/therapeutic use ; Arthritis/microbiology ; Fecal Microbiota Transplantation ; Host-Pathogen Interactions ; Risk Factors ; }, abstract = {The relationship between intestinal microbiota and arthritis has garnered significant attention, with emerging evidence suggesting a potential association between dysbiosis and various forms of inflammatory arthropathies. While observational studies have provided valuable insights into microbiota alterations in patients with arthritis, establishing causality remains challenging. Observational data, influenced by multiple confounders such as environmental factors, medication effects, and dietary habits, are insufficient to conclusively determine whether microbiota changes are somehow causally linked to arthritis. The heterogeneity of results across independent studies further complicates interpretation. To further support this hypothesis, interventional randomised trials are deemed necessary, yet their implementation in this area presents significant technical limitations. Experimental animal models offer insights into potential pathogenic mechanisms linking dysbiosis to arthritis, including compromised intestinal barrier function, the role of microbiota-derived metabolites and molecular mimicry. However, conflicting findings underscore the complexity of hostmicrobiota interactions and the challenges in establishing causality.Efforts to modulate the microbiota for arthritis treatment or prevention have shown promise, yet efficacy and applicability remains uncertain. Antibacterial drugs, dietary interventions, probiotics, and faecal microbiota transplantation have been explored, but their clinical utility awaits further validation. In conclusion, while the association between intestinal microbiota and arthritis is increasingly recognised, establishing causality remains elusive.}, } @article {pmid38743047, year = {2024}, author = {Namasivayam, S and Tilves, C and Ding, H and Wu, S and Domingue, JC and Ruiz-Bedoya, C and Shah, A and Bohrnsen, E and Schwarz, B and Bacorn, M and Chen, Q and Levy, S and Dominguez Bello, MG and Jain, SK and Sears, CL and Mueller, NT and Hourigan, SK}, title = {Fecal transplant from vaginally seeded infants decreases intraabdominal adiposity in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2353394}, pmid = {38743047}, issn = {1949-0984}, mesh = {Animals ; Humans ; Female ; Mice ; *Adiposity ; *Gastrointestinal Microbiome ; Male ; *Vagina/microbiology ; *Fecal Microbiota Transplantation ; *Feces/microbiology/chemistry ; Double-Blind Method ; Intra-Abdominal Fat/metabolism ; Infant ; Infant, Newborn ; }, abstract = {Exposing C-section infants to the maternal vaginal microbiome, coined "vaginal seeding", partially restores microbial colonization. However, whether vaginal seeding decreases metabolic disease risk is unknown. Therefore, we assessed the effect of vaginal seeding of human infants on adiposity in a murine model. Germ-free mice were colonized with transitional stool from human infants who received vaginal seeding or control (placebo) seeding in a double-blind randomized trial. There was a reduction in intraabdominal adipose tissue (IAAT) volume in male mice that received stool from vaginally seeded infants compared to control infants. Higher levels of isoleucine and lower levels of nucleic acid metabolites were observed in controls and correlated with increased IAAT. This suggests that early changes in the gut microbiome and metabolome caused by vaginal seeding have a positive impact on metabolic health.}, } @article {pmid38739944, year = {2024}, author = {Zhu, M and Huang, Y and Wang, Z and Jin, Z and Cao, J and Zhong, Q and Xiong, Z}, title = {Fecal Microbiota Transplantation Attenuates Frailty via Gut-Muscle Axis in Old Mice.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.0321}, pmid = {38739944}, issn = {2152-5250}, abstract = {Targeting adverse pathogenic gut microbiota regulation through fecal microbiota transplantation (FMT) may restore health and has been validated in some aging-related diseases. However, the mechanisms of the gut microbiota's role in frailty and whether modulation of the gut microbiota can treat age-related frailty remain largely unknown. To assess the effects of FMT on frailty, we used bidirectional fecal microbiota transplantation in young and old mice. We demonstrated that fecal bacteria transplanted from old mice into young mice reduced body weight and grip strength (p=0.002), and led to elevated inflammatory factors in young mice, but had no significant effect on intestinal barrier function. Notably, FMT treatment in older mice not only improved frailty (grip strength: p=0.036, low physical activity: p=0.020, running speed: p=0.048, running time: p=0.058, frailty score: p=0.027) and muscle mass, but also improved intestinal ecological imbalances, intestinal barrier function, and systemic inflammation (serum TNF-α: p=0.002, and IL-6: p<0.001). KEGG enrichment analysis of fecal metabolites showed that FMT may ameliorate frailty through the sphingolipid metabolism pathway. In addition, aged mice given FMT treatment showed a significant increase in the abundance of SCFA-producing bacteria and increased levels of short-chain fatty acids (butyric acid: p=0.084, propionic acid: p=0.028). Subsequent further verification found that FMT ameliorating frailty may be achieved through SCFAs metabolism. Another mechanism study found that FMT reduces lipopolysaccharide levels (p<0.001), thereby inhibiting the TLR4/NF-κB signaling pathway and its downstream pro-inflammatory products. Therefore, regulating SCFAs metabolism by altering gut microbial composition and targeting the gut-muscle axis with LPS/TLR4 pathways may be potential strategies to treat frailty in older adults.}, } @article {pmid38739837, year = {2024}, author = {Herbin, SR and Crum, H and Gens, K}, title = {Breaking the Cycle of Recurrent Clostridioides difficile Infections: A Narrative Review Exploring Current and Novel Therapeutic Strategies.}, journal = {Journal of pharmacy practice}, volume = {}, number = {}, pages = {8971900241248883}, doi = {10.1177/08971900241248883}, pmid = {38739837}, issn = {1531-1937}, abstract = {Clostridioides difficile is a toxin-producing bacteria that is a main cause of antibiotic-associated diarrhea. Clostridioides difficile infections (CDI) are associated with disruptions within the gastrointestinal (GI) microbiota which can be further exacerbated by CDI-targeted antibiotic treatment thereby causing recurrent CDI (rCDI) and compounding the burden placed on patients and the healthcare system. Treatment of rCDI consists of antibiotics which can be paired with preventative therapeutics, such as bezlotoxumab or fecal microbiota transplants (FMTs), if sustained clinical response is not obtained. Newer preventative strategies have been recently approved to assist in restoring balance within the GI system with the goal of preventing recurrent infections.}, } @article {pmid38738157, year = {2024}, author = {Shimodaira, Y and Fukuda, S and Okubo, R and Onochi, K and Iijima, K}, title = {A Report of Ulcerative Colitis With Relapse on the Rectal Side of the Loop Sigmoid Colostomy and Not on the Oral Side.}, journal = {Cureus}, volume = {16}, number = {4}, pages = {e57941}, pmid = {38738157}, issn = {2168-8184}, abstract = {A patient who received a loop sigmoid colostomy was diagnosed with ulcerative colitis (pancolitis type) and treated with infliximab. Thereafter, he relapsed with intestinal inflammation only on the rectal side of the loop sigmoid colostomy and not on the oral side. Autologous fecal microbiota transplantation from the proximal intestine to the distal intestine was performed to treat the inflammation but was ineffective. He was treated with oral prednisolone and induced into remission. After analyzing fecal samples from the patient, we observed an alteration of the composition of the intestinal microbiota with intestinal inflammation, including a reduction of phylum Firmicutes in the inflamed distal intestine, whereas Firmicutes was conserved in the proximal non-inflamed intestine and recovered in the distal intestine after induction of remission. Thus, our results indicated that the inflammation was associated with an alteration of the intestinal microbiota.}, } @article {pmid38737692, year = {2024}, author = {Sang, Y and Zheng, K and Zhao, Y and Liu, Y and Zhu, S and Xie, X and Shang, L and Liu, J and Li, L}, title = {Efficacy and regulatory strategies of gut microbiota in immunotherapy: a narrative review.}, journal = {Translational cancer research}, volume = {13}, number = {4}, pages = {2043-2063}, pmid = {38737692}, issn = {2219-6803}, abstract = {BACKGROUND AND OBJECTIVE: With advances in gut microbiome research, it has been recognized that the gut microbiome has an important and far-reaching impact on many human diseases, including cancer. Therefore, more and more researchers are focusing on the treatment of gut flora in tumors. In this article, we present a review of the mechanisms of gut microbes in tumor immunotherapy and related studies to provide reference for further research and insights into the clinical application of gut microbes.

METHODS: Between April 25, 2023, and November 25, 2023, we searched for articles published only in English between 1984 and 2023 using the databases PubMed, American Medical Association and Elsevier ScienceDirect using the keywords "gut microbiology" and "tumor" or "immunotherapy".

KEY CONTENT AND FINDINGS: The gastrointestinal tract contains the largest number of microorganisms in the human body. Microorganisms are involved in regulating many physiological activities of the body. Studies have shown that gut microbes and their derivatives are involved in the occurrence and development of a variety of inflammations and tumors, and changes in their abundance and proportion affect the degree of cancer progression and sensitivity to immunotherapy. Gut microbiota-based drug research is ongoing, and some anti-tumor studies have entered the clinical trial stage.

CONCLUSIONS: The abundance and proportion of intestinal microorganisms influence the susceptibility of tumors to tumor immunotherapy. This article reviewed the effects and mechanisms of gut microbes on tumor immunotherapy to further explore the medical value of gut microbes in tumor immunotherapy.}, } @article {pmid38734322, year = {2024}, author = {Liu, X and Li, S and Wang, L and Ma, K}, title = {Microecological regulation in HCC therapy: Gut microbiome enhances ICI treatment.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {6}, pages = {167230}, doi = {10.1016/j.bbadis.2024.167230}, pmid = {38734322}, issn = {1879-260X}, abstract = {The exploration of the complex mechanisms of cancer immunotherapy is rapidly evolving worldwide, and our focus is on the interaction of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs), particularly as it relates to the regulatory role of the gut microbiome. An important basis for the induction of immune responses in HCC is the presence of specific anti-tumor cells that can be activated and reinforced by ICIs, which is why the application of ICIs results in sustained tumor response rates in the majority of HCC patients. However, mechanisms of acquired resistance to immunotherapy in unresectable HCC result in no long-term benefit for some patients. The significant heterogeneity of inter-individual differences in the gut microbiome in response to treatment with ICIs makes it possible to target modulation of specific gut microbes to assist in augmenting checkpoint blockade therapies in HCC. This review focuses on the complex relationship between the gut microbiome, host immunity, and HCC, and emphasizes that manipulating the gut microbiome to improve response rates to cancer ICI therapy is a clinical strategy with unlimited potential.}, } @article {pmid38734214, year = {2024}, author = {Quan, M and Zhang, X and Fang, Q and Lv, X and Wang, X and Zong, Z}, title = {Fighting against Clostridioides difficile infection: Current medications.}, journal = {International journal of antimicrobial agents}, volume = {}, number = {}, pages = {107198}, doi = {10.1016/j.ijantimicag.2024.107198}, pmid = {38734214}, issn = {1872-7913}, abstract = {Clostridioides difficile (formerly Clostridium difficile) has been regarded as an "urgent threat" and a significant global health problem, as life-threatening diarrhea and refractory recurrence are common in patients with C. difficile infection (CDI). Unfortunately, the available anti-CDI drugs are limited. Recent guidelines recommend fidaxomicin and vancomycin as first-line drugs to treat CDI, bezlotoxumab to prevent recurrence, and fecal microbiota transplantation (FMT) for rescue treatment. Currently, researchers are investigating therapeutic antibacterial drugs (e.g., teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571), preventive medications against recurrence (e.g., Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2), primary prevention strategies (e.g., vaccine, ribaxamase, and DAV132) and other anti-CDI medications in the preclinical stage (e.g., Raja 42, Myxopyronin B, and bacteriophage). This narrative review summarizes current medications, including newly marketed drugs and products in development against CDI, to help clinicians treat CDI appropriately and to call for more research on innovation.}, } @article {pmid38733907, year = {2024}, author = {Ruan, Y and Ren, G and Wang, M and Lv, W and Shimizu, K and Zhang, C}, title = {The dual role of 20(S)-protopanaxadiol in alleviating pulmonary fibrosis through the gut-lung axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {129}, number = {}, pages = {155699}, doi = {10.1016/j.phymed.2024.155699}, pmid = {38733907}, issn = {1618-095X}, abstract = {BACKGROUND: Pulmonary Fibrosis (PF) is a progressive lung disease characterized by the diffuse interstitial tissue, leading to severe breathing difficulties. The existing treatment methods are primarily aimed at slowing the progression of the disease, underscoring the urgent need to discover new drug interventions targeting novel sites. The "gut-lung axis" represents a complex bidirectional communication system where the gut microbiota not only influences lung immunity but also responds to lung-derived signals. Recent advances have uncovered that alterations in gut microbiota composition can significantly impact respiratory diseases, offering new insights into their pathogenesis and potential therapeutic approaches.

METHODS: This study is based on the fundamental concepts of the lung-gut axis and our previous research, further exploring the potential mechanisms of 20(S)-Protopanaxadiol (PPD) in ginseng against PF. We utilized a bleomycin-induced mouse model of PF and employed metabolomics and 16S rRNA sequencing to investigate the pathways through which PPD regulates the pulmonary fibrosis process via the gut-lung axis. Finally, we employed strategies such as antibiotic-induced microbiota disruption and fecal microbiota transplantation (FMT) to provide a comprehensive perspective on how PPD regulates pulmonary fibrosis through gut microbiota.

RESULTS: The results of the bleomycin (BLM) mouse model of PF proved that PPD can directly act on the glycolysis- related metabolic reprogramming process in lung and the AMPK/STING pathway to improve PF. Combined the analysis of gut microbiota and related metabolites, we found that PPD can regulate the process of PF through the gut-lung axis target points G6PD and SPHK1. FMT and antibiotic-induced microbiota disruption further confirmed intermediate effect of gut microbiota in PF process and the treatment of PPD. Our study suggests that PPD can alleviate the process of pulmonary fibrosis either by directly acting on the lungs or by regulating the gut microbiota.

CONCLUSION: This study positions PPD as a vanguard in the therapeutic landscape for pulmonary fibrosis, offering a dual mechanism of action that encompasses both modulation of gut microbiota and direct intervention at molecular targets. These insights highlight the immense therapeutic potential of harnessing the gut-lung axis.}, } @article {pmid38733623, year = {2024}, author = {Ishikawa, D and Zhang, X and Nomura, K and Shibuya, T and Hojo, M and Yamashita, M and Koizumi, S and Yamazaki, F and Iwamoto, S and Saito, M and Kunigo, K and Nakano, R and Honma, N and Urakawa, I and Nagahara, A}, title = {Anti-inflammatory Effects of Bacteroidota Strains Derived From Outstanding Donors of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izae080}, pmid = {38733623}, issn = {1536-4844}, support = {JP22ae0121038//Japan Agency for Medical Research and Development/ ; }, abstract = {BACKGROUND: The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal microbiota transplantation therapy. We hypothesized that certain Bacteroidota may advance ulcerative colitis treatment. Accordingly, we aimed to evaluate the anti-inflammatory effects of Bacteroidota strains isolated from donors.

METHODS: Donors with proven efficacy of fecal microbiota transplantation for ulcerative colitis were selected, and Bacteroidota strains were isolated from their stools. The immune function of Bacteroidota isolates was evaluated through in vitro and in vivo studies.

RESULTS: Twenty-four Bacteroidota strains were isolated and identified. Using an in vitro interleukin (IL)-10 induction assay, we identified 4 Bacteroidota strains with remarkable IL-10-induction activity. Of these, an Alistipes putredinis strain exhibited anti-inflammatory effects in a mouse model of colitis induced by sodium dextran sulfate and oxazolone. However, 16S rRNA gene-based sequencing analysis of A. putredinis cultures in the in vivo study revealed unexpected Veillonella strain contamination. A second in vitro study confirmed that the coculture exhibited an even more potent IL-10-inducing activity. Furthermore, the production of A. putredinis-induced IL-10 was likely mediated via toll-like receptor 2 signaling.

CONCLUSIONS: This study demonstrated that A. putredinis, a representative Bacteroidota species, exhibits anti-inflammatory effects in vivo and in vitro; however, the effects of other Bacteroidota species remain unexplored. Our fecal microbiota transplantation-based reverse translation approach using promising bacterial species may represent a breakthrough in microbiome drug development for controlling dysbiosis during ulcerative colitis.}, } @article {pmid38732527, year = {2024}, author = {Ouyang, Q and Li, X and Liang, Y and Liu, R}, title = {Sea Buckthorn Polysaccharide Ameliorates Colitis.}, journal = {Nutrients}, volume = {16}, number = {9}, pages = {}, pmid = {38732527}, issn = {2072-6643}, mesh = {Animals ; *Hippophae/chemistry ; *Polysaccharides/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Mice ; Colitis/drug therapy/chemically induced/microbiology ; Colitis, Ulcerative/microbiology/drug therapy ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Oxidative Stress/drug effects ; Fecal Microbiota Transplantation ; Colon/drug effects/microbiology/metabolism ; Dextran Sulfate ; Anti-Inflammatory Agents/pharmacology ; Antioxidants/pharmacology ; Fruit/chemistry ; Fatty Acids, Volatile/metabolism ; }, abstract = {Ulcerative colitis (UC) is characterized by chronic inflammation and ulceration of the intestinal inner lining, resulting in various symptoms. Sea buckthorn berries contain a bioactive compound known as sea buckthorn polysaccharide (SBP). However, the precise mechanisms underlying the impact of SBP on UC remain unclear. In this study, we investigated the effects of pretreatment with SBP on colitis induced by DSS. Our findings demonstrate that SBP pretreatment effectively reduces inflammation, oxidative stress, and intestinal barrier damage associated with colitis. To further elucidate the role of SBP-modulated gut microbiota in UC, we performed fecal microbiota transplantation (FMT) on DSS-treated mice. The microbiota from SBP-treated mice exhibits notable anti-inflammatory and antioxidant effects, improves colonic barrier integrity, and increases the abundance of beneficial bacteria, as well as enhancing SCFA production. Collectively, these results strongly indicate that SBP-mediated amelioration of colitis is attributed to its impact on the gut microbiota, particularly through the promotion of SCFA-producing bacteria and subsequent elevation of SCFA levels. This study provides compelling evidence supporting the efficacy of pre-emptive SBP supplementation in alleviating colitis symptoms by modulating the gut microbiota, thereby offering novel insights into the potential of SBP as a regulator of the gut microbiota for colitis relief.}, } @article {pmid38530358, year = {2024}, author = {Pal, S and Morgan, X and Dar, HY and Gacasan, CA and Patil, S and Stoica, A and Hu, YJ and Weitzmann, MN and Jones, RM and Pacifici, R}, title = {Gender-affirming hormone therapy preserves skeletal maturation in young mice via the gut microbiome.}, journal = {The Journal of clinical investigation}, volume = {134}, number = {10}, pages = {}, pmid = {38530358}, issn = {1558-8238}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Mice ; Female ; Male ; *T-Lymphocytes, Regulatory/immunology/drug effects ; Bone Development/drug effects ; Osteogenesis/drug effects ; Bacteroides ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Gender-affirming hormone therapy (GAHT) is often prescribed to transgender (TG) adolescents to alleviate gender dysphoria, but the effect of GAHT on the growing skeleton is unclear. We found GAHT to improve trabecular bone structure via increased bone formation in young male mice and not to affect trabecular structure in female mice. GAHT modified gut microbiome composition in both male and female mice. However, fecal microbiota transfers (FMTs) revealed that GAHT-shaped gut microbiome was a communicable regulator of bone structure and turnover in male, but not in female mice. Mediation analysis identified 2 species of Bacteroides as significant contributors to the skeletal effects of GAHT in male mice, with Bacteroides supplementation phenocopying the effects of GAHT on bone. Bacteroides have the capacity to expand Treg populations in the gut. Accordingly, GAHT expanded intestinal Tregs and stimulated their migration to the bone marrow (BM) in male but not in female mice. Attesting to the functional relevance of Tregs, pharmacological blockade of Treg expansion prevented GAHT-induced bone anabolism. In summary, in male mice GAHT stimulated bone formation and improved trabecular structure by promoting Treg expansion via a microbiome-mediated effect, while in female mice, GAHT neither improved nor impaired trabecular structure.}, } @article {pmid38732276, year = {2024}, author = {Boicean, A and Ichim, C and Todor, SB and Anderco, P and Popa, ML}, title = {The Importance of Microbiota and Fecal Microbiota Transplantation in Pancreatic Disorders.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {9}, pages = {}, pmid = {38732276}, issn = {2075-4418}, abstract = {The role of the intestinal microbiota in the diagnosis and treatment of pancreatic diseases is increasingly significant. Consequently, fecal microbiota transplantation (FMT) is emerging as a promising therapeutic avenue for various pancreatic disorders, including cancer, pancreatitis, and type 1 diabetes (T1D). This innovative procedure entails transferring gut microbiota from healthy donors to individuals affected by pancreatic ailments with the potential to restore intestinal balance and alleviate associated symptoms. FMT represents a pioneering approach to improve patient outcomes in pancreatic diseases, offering tailored treatments customized to individual microbiomes and specific conditions. Recent research highlights the therapeutic benefits of targeting the gut microbiota for personalized interventions in pancreatic disorders. However, a comprehensive understanding of the intricate interplay between gut microbiota and pancreatic physiology warrants further investigation. The necessity for additional studies and research endeavors remains crucial, especially in elucidating both adult and pediatric cases affected by pathological pancreatic conditions.}, } @article {pmid38729481, year = {2024}, author = {Xia, T and He, W and Luo, Z and Wang, K and Tan, X}, title = {Achyranthes bidentata polysaccharide ameliorates type 2 diabetes mellitus by gut microbiota-derived short-chain fatty acids-induced activation of the GLP-1/GLP-1R/cAMP/PKA/CREB/INS pathway.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {132256}, doi = {10.1016/j.ijbiomac.2024.132256}, pmid = {38729481}, issn = {1879-0003}, abstract = {Gut microbiota variances reflecting the severity type 2 diabetes mellitus (T2DM). Achyranthes bidentata polysaccharide (ABP) can regulate gut microbiota. However, the hypoglycemic effect and underlying mechanism of ABP remain unclear. Herein, we characterized the structure of ABP and revealed the hypoglycemic effect of ABP in mice with T2DM. ABP repaired the intestinal barrier in T2DM mice and regulated the composition and abundance of gut microbiota, especially increasing bacteria which producing short-chain fatty acids (SCFAs), then increasing glucagon-like peptide-1 (GLP-1) level. The abundance of these bacteria was positively correlated with blood lipid and INS levels, negatively correlated with FBG levels. Colon transcriptome data and immunohistochemistry demonstrated that the alleviating T2DM effect of ABP was related to activation of the GLP-1/GLP-1 receptor (GLP-1R)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-response element binding protein (CREB)/INS pathway. Fecal microbiota transplantation (FMT) confirmed the transmissible efficacy of ABPs through gut microbiota. Overall, our research shows that ABP plays a hypoglycemic role by increasing gut microbiota-derived SCFAs levels, and activating the GLP-1/GLP-1R/cAMP/PKA/CREB/INS pathway, emphasizing ABP as promising T2DM therapeutic candidates.}, } @article {pmid38728472, year = {2024}, author = {Ugwu, OP and Alum, EU and Okon, MB and Obeagu, EI}, title = {Mechanisms of microbiota modulation: Implications for health, disease, and therapeutic interventions.}, journal = {Medicine}, volume = {103}, number = {19}, pages = {e38088}, pmid = {38728472}, issn = {1536-5964}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Anti-Bacterial Agents/therapeutic use ; Probiotics/therapeutic use ; Gastrointestinal Diseases/therapy/microbiology ; }, abstract = {Microbiota modulation, the intentional change in the structure and function of the microbial community, is an emerging trajectory that holds the promise to mitigate an infinite number of health issues. The present review illustrates the underlying principles of microbiota modulation and the various applications of this fundamental process to human health, healthcare management, and pharmacologic interventions. Different strategies, directing on dietary interventions, fecal microbiota transplantation, treatment with antibiotics, bacteriophages, microbiome engineering, and modulation of the immune system, are described in detail. This therapeutic implication is reflected in clinical applications to gastrointestinal disorders and immune-mediated diseases for microbiota-modulating agents. In addition to this, the review outlines the challenges of translating researched outcomes into clinical practice to consider safety and provides insights into future research directions of this rapidly developing area.}, } @article {pmid38727248, year = {2024}, author = {Hao, QY and Yan, J and Wei, JT and Zeng, YH and Feng, LY and Que, DD and Li, SC and Guo, JB and Fan, Y and Ding, YF and Zhang, XL and Yang, PZ and Gao, JW and Li, ZH}, title = {Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2351532}, doi = {10.1080/19490976.2024.2351532}, pmid = {38727248}, issn = {1949-0984}, mesh = {Animals ; *Vascular Calcification/metabolism/pathology ; *NF-kappa B/metabolism ; *Lipopolysaccharides/metabolism ; Rats ; *Renal Insufficiency, Chronic/metabolism/microbiology/chemically induced/pathology ; *Signal Transduction ; Humans ; Male ; *Toll-Like Receptor 4/metabolism/genetics ; *Gastrointestinal Microbiome ; *Prevotella/metabolism ; Rats, Sprague-Dawley ; Myocytes, Smooth Muscle/metabolism ; Osteogenesis/drug effects ; Muscle, Smooth, Vascular/metabolism/pathology ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; Feces/microbiology ; Inflammasomes/metabolism ; }, abstract = {Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.}, } @article {pmid38726585, year = {2024}, author = {Yakout, A and Bi, Y and Harris, DM}, title = {Clostridioides Difficile: A Concise Review of Best Practices and Updates.}, journal = {Journal of primary care & community health}, volume = {15}, number = {}, pages = {21501319241249645}, pmid = {38726585}, issn = {2150-1327}, mesh = {Humans ; *Clostridium Infections/prevention & control/diagnosis/therapy ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; Cross Infection/prevention & control ; Practice Guidelines as Topic ; Fidaxomicin/therapeutic use ; Metronidazole/therapeutic use ; }, abstract = {Clostridioides difficile infection (CDI) is one of the most common and severe nosocomial infections worldwide. It can also affect healthy individuals in the community. The incidence of CDI has been on the rise globally for the past decade, necessitating a proactive approach to combat its spread; new strategies are being developed to enhance diagnostic accuracy and optimize treatment outcomes. Implementing the 2-step testing has increased diagnostic specificity, reducing the usage of CD-specific antibiotics with no concomitant increase in surgical complication rates. In 2021, the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) shifted its preference for initial treatment to fidaxomicin over vancomycin and metronidazole due to its lower recurrence rate. It also prioritized fidaxomicin for the treatment of recurrent CDI. There are new developments on the frontiers of fecal microbiota therapies, with RBX2660 and SER-109 approved recently by the FDA for prevention, with other microbiome-based therapies in various development and clinical trials. This review offers providers an updated and practical guide for CDI management.}, } @article {pmid38724904, year = {2024}, author = {Wang, L and Guo, G and Xu, Y and Li, L and Yang, B and Zhao, D and Tian, H and Ye, C and Lin, Z and Cui, J and Li, N and Huang, L and Chen, Q}, title = {The effect of fecal microbiota transplantation on antibiotic-associated diarrhea and its impact on gut microbiota.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {160}, pmid = {38724904}, issn = {1471-2180}, mesh = {Humans ; *Diarrhea/microbiology/therapy ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Female ; Male ; Middle Aged ; *Anti-Bacterial Agents/adverse effects ; *Feces/microbiology ; Adult ; *RNA, Ribosomal, 16S/genetics ; Aged ; Treatment Outcome ; Bacteria/classification/isolation & purification/genetics ; }, abstract = {BACKGROUND: Antibiotic-associated diarrhea (AAD) refers to symptoms of diarrhea that cannot be explained by other causes after the use of antibiotics. AAD is thought to be caused by a disruption of intestinal ecology due to antibiotics. Fecal Microbiota Transplantation (FMT) is a treatment method that involves transferring microbial communities from the feces of healthy individuals into the patient's gut.

METHOD: We selected 23 AAD patients who received FMT treatment in our department. Before FMT, we documented patients' bowel movement frequency, abdominal symptoms, routine blood tests, and inflammatory markers, and collected fecal samples for 16S rRNA sequencing to observe changes in the intestinal microbiota. Patients' treatment outcomes were followed up 1 month and 3 months after FMT.

RESULTS: Out of the 23 AAD patients, 19 showed a clinical response to FMT with alleviation of abdominal symptoms. Among them, 82.61% (19/23) experienced relief from diarrhea, 65% (13/20) from abdominal pain, 77.78% (14/18) from abdominal distension, and 57.14% (4/7) from bloody stools within 1 month after FMT. Inflammatory markers IL-8 and CRP significantly decreased after FMT, but there were no noticeable changes in WBC, IL-6, and TNF-α before and after transplantation. After FMT, the abundance of Bacteroides and Faecalibacterium increased in patients' fecal samples, while the abundance of Escherichia-Shigella and Veillonella decreased.

CONCLUSION: FMT has a certain therapeutic effect on AAD, and can alleviate abdominal symptoms and change the intestinal microbiota of patients.}, } @article {pmid38722758, year = {2024}, author = {Imamura, Y and Motooka, D and Nakajima, Y and Ito, S and Kitakaze, M and Iida, T and Nakamura, S}, title = {Turicibacter faecis sp. nov., isolated from faeces of heart failure mouse model.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {74}, number = {5}, pages = {}, doi = {10.1099/ijsem.0.006379}, pmid = {38722758}, issn = {1466-5034}, mesh = {Animals ; *RNA, Ribosomal, 16S/genetics ; *Feces/microbiology ; *Phylogeny ; Mice ; *Base Composition ; *DNA, Bacterial/genetics ; *Bacterial Typing Techniques ; *Sequence Analysis, DNA ; *Heart Failure/microbiology ; *Disease Models, Animal ; Genome, Bacterial ; Male ; Fatty Acids ; }, abstract = {Strain TC023[T], a Gram-positive, long, rod-shaped, spore-forming anaerobe, was isolated from the faeces of a heart failure mouse model. The strain formed greyish-white coloured colonies with a convex elevation on brain-heart infusion medium supplemented with 0.1 % sodium taurocholate, incubated at 37 °C for 2 days. Taxonomic analysis based on the 16S rRNA gene sequence showed that TC023[T] belonged to the genus Turicibacter, and was closely related to Turicibacter bilis MMM721[T] (97.6 %) and Turicibacter sanguinis MOL361[T] (97.4 %). The whole genome of the strain has a G+C content of 37.3 mol%. The average nucleotide identity and genome-to-genome distance between TC023[T] and Turicibacter bilis MMM721[T] were 77.6 % and 24.3 %, respectively, and those with Turicibacter sanguinis MOL361[T] were 75.4 % and 24.3 %, respectively. These genotypic, phenotypic, and biochemical analyses indicated that the isolate represents a novel species in the genus Turicibacter, and the name Turicibacter faecis sp. nov. is proposed. The type strain is TC023[T] (RIMD 2002001[T]=TSD 372[T]).}, } @article {pmid38720628, year = {2024}, author = {Leibovitzh, H and Sarbagili Shabat, C and Hirsch, A and Zittan, E and Mentella, MC and Petito, V and Cohen, NA and Ron, Y and Fliss Isakov, N and Pfeffer, J and Yaakov, M and Fanali, C and Turchini, L and Masucci, L and Quaranta, G and Kolonimos, N and Godneva, A and Weinberger, A and Scaldaferri, F and Maharshak, N}, title = {Fecal transplantation for ulcerative colitis from diet conditioned donors followed by dietary intervention results in favorable gut microbial profile compared to fecal transplantation alone.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjae062}, pmid = {38720628}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: Several fecal microbial transplantation (FMT) approaches for ulcerative colitis (UC) have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT-UC Trial using FMT with the UC Exclusion Diet (UCED), compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function.

METHODS: Subjects recruited to the CRAFT-UC study with available pre- and post-intervention fecal samples were included. Donors received diet conditioning for 14 days based on the UCED principles. Group-1 received single FMT by colonoscopy (Day 1) and enemas (Days 2 and 14) without donors' dietary conditioning (N=11). Group-2 received FMT but with donors' dietary pre-conditioning and UCED for the patients (N=10). Fecal samples were assessed by DNA shotgun metagenomic sequencing.

RESULTS: Following diet conditioning, donors had depletion in metabolic pathways involved in sulfur-containing amino acids biosynthesis. Only Group-2 showed significant shifts towards the donors' microbial composition (ADONIS: R2=0.15, p=0.008) and significant increased Eubacterium_sp_AF228LB post-intervention (β-coefficient 2.66, 95%CI 2.1-3.3, q<0.05) which was inversely correlated with fecal calprotectin (rho=-0.52, p=0.035). Moreover, pathways involved in gut inflammation and barrier function including branched chain amino acids were enriched post intervention in Group-2 and were significantly inversely correlated with fecal calprotectin.

CONCLUSION: FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favorable microbial profile which correlated with decreased fecal calprotectin. Our findings support further exploration of additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC.}, } @article {pmid38720499, year = {2023}, author = {Ramakrishna, BS and Patankar, R}, title = {Antibiotic-associated Gut Dysbiosis.}, journal = {The Journal of the Association of Physicians of India}, volume = {71}, number = {11}, pages = {62-68}, doi = {10.59556/japi.71.0381}, pmid = {38720499}, issn = {0004-5772}, mesh = {*Dysbiosis/chemically induced ; Humans ; *Anti-Bacterial Agents/adverse effects ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Phage Therapy/methods ; }, abstract = {The human gut microbiota plays a crucial role in maintaining overall health. However, the widespread use of antibiotics has raised concerns about its impact on the microbial ecosystem. This review explores the multifaceted relationship between antibiotics and gut dysbiosis, highlighting the mechanisms underlying these interactions and their implications for human health. Antibiotics, while invaluable in treating infections, disrupt the gut microbiota by indiscriminately targeting both harmful and beneficial microorganisms. This disturbance leads to a reduction in microbial diversity, altered metabolite production, and compromised immune responses, resulting in a state referred to as dysbiosis. Broad-spectrum antibiotics tend to induce more severe dysbiosis compared to narrow-spectrum agents. Antibiotic-induced dysbiosis has been linked to the onset and progression of these disorders, emphasizing the far-reaching consequences of microbial imbalance. The review highlights various strategies to mitigate the adverse effects of antibiotics on gut health, like probiotics, fecal microbiota transplantation (FMT), and phage therapy, as promising approaches to restore and maintain a balanced gut microbiota. How to cite this article: Ramakrishna BS, Patankar R. Antibiotic-associated Gut Dysbiosis. J Assoc Physicians India 2023;71(11):62-68.}, } @article {pmid38720361, year = {2024}, author = {Huang, C and Li, X and Li, H and Chen, R and Li, Z and Li, D and Xu, X and Zhang, G and Qin, L and Li, B and Chu, XM}, title = {Role of gut microbiota in doxorubicin-induced cardiotoxicity: from pathogenesis to related interventions.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {433}, pmid = {38720361}, issn = {1479-5876}, support = {82172574//National Natural Science Foundation of China/ ; 81871231//National Natural Science Foundation of China/ ; ZR2020MH016//Natural Science Foundation of Shandong Province/ ; ZR202209280042//Natural Science Foundation of Shandong Province/ ; YJKT202171//Project of Shandong Province Higher Educational Science and Technology Program/ ; tsqn202103056//Taishan Scholar Foundation of Shandong Province/ ; }, mesh = {*Gastrointestinal Microbiome/drug effects ; Humans ; *Doxorubicin/adverse effects ; *Cardiotoxicity/etiology ; Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; }, abstract = {Doxorubicin (DOX) is a broad-spectrum and highly efficient anticancer agent, but its clinical implication is limited by lethal cardiotoxicity. Growing evidences have shown that alterations in intestinal microbial composition and function, namely dysbiosis, are closely linked to the progression of DOX-induced cardiotoxicity (DIC) through regulating the gut-microbiota-heart (GMH) axis. The role of gut microbiota and its metabolites in DIC, however, is largely unelucidated. Our review will focus on the potential mechanism between gut microbiota dysbiosis and DIC, so as to provide novel insights into the pathophysiology of DIC. Furthermore, we summarize the underlying interventions of microbial-targeted therapeutics in DIC, encompassing dietary interventions, fecal microbiota transplantation (FMT), probiotics, antibiotics, and natural phytochemicals. Given the emergence of microbial investigation in DIC, finally we aim to point out a novel direction for future research and clinical intervention of DIC, which may be helpful for the DIC patients.}, } @article {pmid38719790, year = {2024}, author = {Grodin, EN and Burnette, EM and Rodriguez, C and Fulcher, JA and Ray, LA}, title = {The gut microbiome in alcohol use disorder and alcohol-associated liver disease: A systematic review of clinical studies.}, journal = {Alcohol, clinical & experimental research}, volume = {}, number = {}, pages = {}, doi = {10.1111/acer.15338}, pmid = {38719790}, issn = {2993-7175}, support = {K08 AI124979/AI/NIAID NIH HHS/United States ; 2019086/DDCF/Doris Duke Charitable Foundation/United States ; F31 AA028976/AA/NIAAA NIH HHS/United States ; K01 AA029712/AA/NIAAA NIH HHS/United States ; K24 AA025704/AA/NIAAA NIH HHS/United States ; }, abstract = {Evidence suggests that a relationship exists between the gut microbiome and the pathogenesis of alcohol use disorder (AUD) and alcohol-associated liver disease (AALD). This systematic review identified studies that investigated the gut microbiome in individuals with an AUD or an AALD. A search was conducted on October 27, 2022, in PubMed, Web of Science, and Embase databases. Fifty studies satisfied eligibility criteria. Most studies found evidence for gut dysbiosis in individuals with AUD and AALD. Microbiome intervention studies have mostly been conducted in AALD patients; fecal microbial transplant interventions show the most promise. Because most studies were conducted cross-sectionally, the causal relationship between the gut microbiome and alcohol use is unknown. Furthermore, almost all studies have been conducted in predominantly male populations, leaving critical questions regarding sex differences and generalizability of the findings. The study summaries and recommendations provided in this review seek to identify areas for further research and to highlight potential gut microbial interventions for treating AUD and AALD.}, } @article {pmid38718729, year = {2024}, author = {Gu, T and Kong, M and Duan, M and Chen, L and Tian, Y and Xu, W and Zeng, T and Lu, L}, title = {Cu exposure induces liver inflammation via regulating gut microbiota/LPS/liver TLR4 signaling axis.}, journal = {Ecotoxicology and environmental safety}, volume = {278}, number = {}, pages = {116430}, doi = {10.1016/j.ecoenv.2024.116430}, pmid = {38718729}, issn = {1090-2414}, abstract = {Copper (Cu) serves as an essential cofactor in all organisms, yet excessive Cu exposure is widely recognized for its role in inducing liver inflammation. However, the precise mechanism by which Cu triggers liver inflammation in ducks, particularly in relation to the interplay in gut microbiota regulation, has remained elusive. In this investigation, we sought to elucidate the impact of Cu exposure on liver inflammation through gut-liver axis in ducks. Our findings revealed that Cu exposure markedly elevated liver AST and ALT levels and induced liver inflammation through upregulating pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and triggering the LPS/TLR4/NF-κB signaling pathway. Simultaneously, Cu exposure induced alterations in the composition of intestinal flora communities, notably increasing the relative abundance of Sphingobacterium, Campylobacter, Acinetobacter and reducing the relative abundance of Lactobacillus. Cu exposure significantly decreased the protein expression related to intestinal barrier (Occludin, Claudin-1 and ZO-1) and promoted the secretion of intestinal pro-inflammatory cytokines. Furthermore, correlation analysis was observed that intestinal microbiome and gut barrier induced by Cu were closely related to liver inflammation. Fecal microbiota transplantation (FMT) experiments further demonstrated the microbiota-depleted ducks transplanting fecal samples from Cu-exposed ducks disturbed the intestinal dysfunction, which lead to impaire liver function and activate the liver inflammation. Our study provided insights into the mechanism by which Cu exposure induced liver inflammation in ducks through the regulation of gut-liver axis. These results enhanced our comprehension of the potential mechanisms driving Cu-induced hepatotoxicity in avian species.}, } @article {pmid38717124, year = {2024}, author = {Yadegar, A and Bar-Yoseph, H and Monaghan, TM and Pakpour, S and Severino, A and Kuijper, EJ and Smits, WK and Terveer, EM and Neupane, S and Nabavi-Rad, A and Sadeghi, J and Cammarota, G and Ianiro, G and Nap-Hill, E and Leung, D and Wong, K and Kao, D}, title = {Fecal microbiota transplantation: current challenges and future landscapes.}, journal = {Clinical microbiology reviews}, volume = {}, number = {}, pages = {e0006022}, doi = {10.1128/cmr.00060-22}, pmid = {38717124}, issn = {1098-6618}, abstract = {SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main "whole gut microbiome replacement" strategy and has been integrated into clinical practice guidelines for treating recurrent Clostridioides difficile infection (rCDI). Furthermore, the potential application of FMT in other indications such as inflammatory bowel disease (IBD), metabolic syndrome, and solid tumor malignancies is an area of intense interest and active research. However, the complex and variable nature of FMT makes it challenging to address its precise functionality and to assess clinical efficacy and safety in different disease contexts. In this review, we outline clinical applications, efficacy, durability, and safety of FMT and provide a comprehensive assessment of its procedural and administration aspects. The clinical applications of FMT in children and cancer immunotherapy are also described. We focus on data from human studies in IBD in contrast with rCDI to delineate the putative mechanisms of this treatment in IBD as a model, including colonization resistance and functional restoration through bacterial engraftment, modulating effects of virome/phageome, gut metabolome and host interactions, and immunoregulatory actions of FMT. Furthermore, we comprehensively review omics technologies, metagenomic approaches, and bioinformatics pipelines to characterize complex microbial communities and discuss their limitations. FMT regulatory challenges, ethical considerations, and pharmacomicrobiomics are also highlighted to shed light on future development of tailored microbiome-based therapeutics.}, } @article {pmid38716216, year = {2024}, author = {Tetali, B and Suresh, S}, title = {Management of irritable bowel syndrome: a narrative review.}, journal = {Translational gastroenterology and hepatology}, volume = {9}, number = {}, pages = {26}, pmid = {38716216}, issn = {2415-1289}, abstract = {BACKGROUND AND OBJECTIVE: As our understanding of the pathophysiology of irritable bowel syndrome (IBS) has advanced, so too has the therapeutic landscape, offering a myriad of approaches to alleviate symptoms and enhance the well-being of patients. This review paper is dedicated to a comprehensive exploration of the diverse therapeutic modalities available for managing IBS. By delving into the complexities of IBS therapeutics, our aim is to contribute to the enhancement of patient care and the overall quality of life for patients grappling with this complex condition.

METHODS: This review utilized information from PubMed/MEDLINE using the key search term "irritable bowel syndrome" as well as the 2020 American College of Gastroenterology (ACG) and 2022 American Gastroenterological Association (AGA) society guidelines on IBS. The search was restricted to articles in the English language only and included peer-reviewed observational studies and randomized controlled trials (RCTs) in adult patients from April 22, 2020 to October 16, 2023.

KEY CONTENT AND FINDINGS: This review will start with an overview of the current guidelines for pharmacologic therapies for IBS as recommended by the ACG and the AGA, with an emphasis on clinical trials published after the most recent guidelines. It will then delve into the literature on dietary modifications, probiotics, fecal microbiota transplant, behavioral therapy, and complementary and alternative medicine approaches to IBS.

CONCLUSIONS: It is evident that the management of IBS has transcended a one-size-fits-all approach. As the field of IBS management continues to evolve, it is imperative for physicians to stay informed and receptive to the array of therapeutic options available, ultimately providing patients with the most effective and personalized care.}, } @article {pmid38098430, year = {2024}, author = {Neubauer, J and Kaiser, A and Hohmann, S}, title = {[Gut Microbiota and Autism Spectrum Disorders: An Overview of Correlations and Potential Implications for Therapeutic Interventions].}, journal = {Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie}, volume = {52}, number = {3}, pages = {151-165}, doi = {10.1024/1422-4917/a000962}, pmid = {38098430}, issn = {1422-4917}, mesh = {*Autism Spectrum Disorder/therapy/microbiology/diagnosis/psychology ; Humans ; *Gastrointestinal Microbiome ; Child ; *Probiotics/therapeutic use ; *Brain-Gut Axis ; *Fecal Microbiota Transplantation ; *Prebiotics ; Dysbiosis ; Correlation of Data ; }, abstract = {Gut Microbiota and Autism Spectrum Disorders: An Overview of Correlations and Potential Implications for Therapeutic Interventions Abstract: At the beginning of research on microbiota, researchers focused mainly on the role of microbiota dysbiosis in the development of gastrointestinal diseases. However, over the last years, researchers have also identified correlations with other physical processes and neuropsychiatric diseases such as autism spectrum disorder. These correlations are believed to be at least partly mediated through the brain-gut-microbiome axis. An altered composition of microbiota in patients with autism spectrum disorder was detected compared to healthy controls. Today, the discussion centers around a possible systemic impact of the metabolites of some microbiota or microbiota-induced chronic inflammatory processes on the brain (mediated through the brain-gut-microbiome axis) as an underlying mechanism. Still, the specific underlying mechanisms remain largely unknown, so conclusions on therapeutic implications are difficult to determine. Here, we describe some promising approaches to improving autistic behavior through dietary changes, the use of prebiotics and probiotics, stool transplantation from healthy controls, and restricted absorbance of certain metabolites. We need further clinical studies of high quality to fully understand the pathophysiology of autism spectrum disorder and to improve diagnostic and therapeutic strategies.}, } @article {pmid38715916, year = {2024}, author = {Hazan, S and Haroon, J and Jordan, S and Walker, SJ}, title = {Improvements in Gut Microbiome Composition and Clinical Symptoms Following Familial Fecal Microbiota Transplantation in a Nineteen-Year-Old Adolescent With Severe Autism.}, journal = {Journal of medical cases}, volume = {15}, number = {4-5}, pages = {82-91}, pmid = {38715916}, issn = {1923-4163}, abstract = {This case report describes a novel therapy for patients with severe autism spectrum disorder (ASD) that is worth further investigation. A 19-year-old male adolescent with ASD, who was not responding to standard treatment received fecal microbiota transplant (FMT) using donor material from his typically developing female sibling. The patient's ASD symptoms were assessed by assessors who were blind to the patient's past ASD symptomatology. Assessors used the Childhood Autism Rating Scale (CARS), an observation-based rating scale to assess developmental delay in children with autism (range of CARS scores is 15 - 60; a score > 28 is indicative of autism; higher score is positively correlated with degree of severity), at baseline and again at six timepoints post-FMT. The patient experienced marked improvements in microbiome diversity and composition over the year and a half period that followed the FMT procedure. Additionally, the patient who was previously nonverbal said his first two words and experienced a reduction in aggression 1-month post-FMT. To the authors' knowledge, this is the first report to demonstrate the use of familial FMT in an adolescent patient with ASD. Given that ASD symptom improvements post-FMT tend to occur in younger patients, the authors hypothesize that the use of a familial donor may be an important factor that contributed to the improved outcomes experienced by this older child.}, } @article {pmid38713722, year = {2024}, author = {Yang, M and Zheng, X and Fan, J and Cheng, W and Yan, TM and Lai, Y and Zhang, N and Lu, Y and Qi, J and Huo, Z and Xu, Z and Huang, J and Jiao, Y and Liu, B and Pang, R and Zhong, X and Huang, S and Luo, GZ and Lee, G and Jobin, C and Eren, AM and Chang, EB and Wei, H and Pan, T and Wang, X}, title = {Antibiotic-Induced Gut Microbiota Dysbiosis Modulates Host Transcriptome and m[6]A Epitranscriptome via Bile Acid Metabolism.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2307981}, doi = {10.1002/advs.202307981}, pmid = {38713722}, issn = {2198-3844}, support = {K22CA234399/NH/NIH HHS/United States ; }, abstract = {Gut microbiota can influence host gene expression and physiology through metabolites. Besides, the presence or absence of gut microbiome can reprogram host transcriptome and epitranscriptome as represented by N[6]-methyladenosine (m[6]A), the most abundant mammalian mRNA modification. However, which and how gut microbiota-derived metabolites reprogram host transcriptome and m[6]A epitranscriptome remain poorly understood. Here, investigation is conducted into how gut microbiota-derived metabolites impact host transcriptome and m[6]A epitranscriptome using multiple mouse models and multi-omics approaches. Various antibiotics-induced dysbiotic mice are established, followed by fecal microbiota transplantation (FMT) into germ-free mice, and the results show that bile acid metabolism is significantly altered along with the abundance change in bile acid-producing microbiota. Unbalanced gut microbiota and bile acids drastically change the host transcriptome and the m[6]A epitranscriptome in multiple tissues. Mechanistically, the expression of m[6]A writer proteins is regulated in animals treated with antibiotics and in cultured cells treated with bile acids, indicating a direct link between bile acid metabolism and m[6]A biology. Collectively, these results demonstrate that antibiotic-induced gut dysbiosis regulates the landscape of host transcriptome and m[6]A epitranscriptome via bile acid metabolism pathway. This work provides novel insights into the interplay between microbial metabolites and host gene expression.}, } @article {pmid38712927, year = {2024}, author = {Zhang, S and Swarte, JC and Gacesa, R and Knobbe, TJ and Kremer, D and Jansen, BH and de Borst, MH and , and Harmsen, HJM and Erasmus, ME and Verschuuren, EAM and Bakker, SJL and Gan, CT and Weersma, RK and Björk, JR}, title = {The gut microbiome in end-stage lung disease and lung transplantation.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0131223}, doi = {10.1128/msystems.01312-23}, pmid = {38712927}, issn = {2379-5077}, abstract = {Gut dysbiosis has been associated with impaired outcomes in liver and kidney transplant recipients, but the gut microbiome of lung transplant recipients has not been extensively explored. We assessed the gut microbiome in 64 fecal samples from end-stage lung disease patients before transplantation and 219 samples from lung transplant recipients after transplantation using metagenomic sequencing. To identify dysbiotic microbial signatures, we analyzed 243 fecal samples from age-, sex-, and BMI-matched healthy controls. By unsupervised clustering, we identified five groups of lung transplant recipients using different combinations of immunosuppressants and antibiotics and analyzed them in relation to the gut microbiome. Finally, we investigated the gut microbiome of lung transplant recipients in different chronic lung allograft dysfunction (CLAD) stages and longitudinal gut microbiome changes after transplantation. We found 108 species (58.1%) in end-stage lung disease patients and 139 species (74.7%) in lung transplant recipients that were differentially abundant compared with healthy controls, with several species exhibiting sharp longitudinal increases from before to after transplantation. Different combinations of immunosuppressants and antibiotics were associated with specific gut microbial signatures. We found that the gut microbiome of lung transplant recipients in CLAD stage 0 was more similar to healthy controls compared to those in CLAD stage 1. Finally, the gut microbial diversity of lung transplant recipients remained lower than the average gut microbial diversity of healthy controls up to more than 20 years post-transplantation. Gut dysbiosis, already present before lung transplantation was exacerbated following lung transplantation.IMPORTANCEThis study provides extensive insights into the gut microbiome of end-stage lung disease patients and lung transplant recipients, which warrants further investigation before the gut microbiome can be used for microbiome-targeted interventions that could improve the outcome of lung transplantation.}, } @article {pmid38711648, year = {2024}, author = {Yi, C and Chen, J and She, X}, title = {The emerging role of the gut virome in necrotizing enterocolitis.}, journal = {Heliyon}, volume = {10}, number = {9}, pages = {e30496}, pmid = {38711648}, issn = {2405-8440}, abstract = {Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates, particularly preterm infants. Many factors can lead to NEC, but microbial dysbiosis is one of the most important risk factors that can induce this disease. Given the major role of the gut virome in shaping bacterial homeostasis, virome research is a fledgling but rapidly evolving area in the field of microbiome that is increasingly connected to human diseases, including NEC. This review provides an overview of the development of the gut virome in newborns, discusses its emerging role in NEC, and explores promising therapeutic applications, including phage therapy and fecal virome transplantation.}, } @article {pmid38711536, year = {2024}, author = {Tuniyazi, M and Tang, R and Hu, X and Fu, Y and Zhang, N}, title = {Carbonate buffer mixture and fecal microbiota transplantation hold promising therapeutic effects on oligofructose-induced diarrhea in horses.}, journal = {Frontiers in veterinary science}, volume = {11}, number = {}, pages = {1388227}, pmid = {38711536}, issn = {2297-1769}, abstract = {Diarrhea is a common gastrointestinal disorder in horses, with diet-induced diarrhea being an emerging challenge. This study aimed to investigate the gut microbiota differences in healthy and diet-induced diarrheic horses and evaluate the effectiveness of fecal microbiota transplantation (FMT) and carbonate buffer mixture (CBM) as potential therapeutic approaches. Twenty healthy horses were included in the study, with four groups: Control, Diarrhea, CBM, and FMT. Diarrhea was induced using oligofructose, and fecal samples were collected for microbiota analysis. FMT and CBM treatments were administered orally using donor fecal matter, and formula mixture, respectively. Clinical parameters, serum levels, intestinal tissue histopathology, and fecal microbiota profiles were evaluated. The results showed that diarrhea induction disbalanced the gut microbiota with decreased diversity and richness, affected clinical parameters including elevated body temperature and diarrhea score, and decreased fecal pH, increased inflammatory responses such as increased serum LPS, IL-17A, lactic acid and total protein, and caused damage in the colon tissue. CBM and FMT treatments altered the gut microbiota composition, restoring it towards a healthier profile compared to diarrheic, restored the gut microbiota composition to healthier states, improved clinical symptoms including decreased body temperature and diarrhea score, and increased fecal pH, decreased inflammatory responses such as increased serum LPS, IL-17A, lactic acid and total protein, and repaired tissue damage. CBM and FMT Spearman correlation analysis identified specific bacterial taxa associated with host parameters and inflammation. FMT and CBM treatments showed promising therapeutic effects in managing oligofructose-induced diarrhea in horses. The findings provide valuable insights into the management and treatment of diarrhea in horses and suggest the potential of combined CBM and FMT approaches for optimal therapeutic outcomes.}, } @article {pmid38709933, year = {2024}, author = {Chen, J and Liu, X and Zou, Y and Gong, J and Ge, Z and Lin, X and Zhang, W and Huang, H and Zhao, J and Saw, PE and Lu, Y and Hu, H and Song, E}, title = {A high-fat diet promotes cancer progression by inducing gut microbiota-mediated leucine production and PMN-MDSC differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {20}, pages = {e2306776121}, doi = {10.1073/pnas.2306776121}, pmid = {38709933}, issn = {1091-6490}, support = {2019BT02Y198//Program for Guangdong Introducing Innovative and Enterpreneurial Teams/ ; 82330056//Natural Science Foundation of China/ ; 81730077//National Natural Science Foundation of China/ ; 92159303//National Natural Science Foundation of China/ ; 81930081//National Natural Science Foundation of China/ ; 82025026//National Natural Science Foundation of China/ ; 2022A1515110069//GDSTC | Basic and Applied Basic Research Foundation of Guangdong Province ()/ ; 2023B1212060013//Guangdong Science and Technology Department/ ; 20212200003//Bureau of Science and Technology of Guangzhou/ ; E2018096//Guang Dong Cheung Kong philanthropy Foundation/ ; }, mesh = {*Gastrointestinal Microbiome ; Animals ; *Diet, High-Fat/adverse effects ; *Leucine/metabolism ; Female ; Humans ; Mice ; *Myeloid-Derived Suppressor Cells/metabolism ; *Breast Neoplasms/pathology/microbiology/metabolism ; *Cell Differentiation ; *Disease Progression ; Obesity/microbiology/metabolism/pathology ; Cell Line, Tumor ; }, abstract = {A high-fat diet (HFD) is a high-risk factor for the malignant progression of cancers through the disruption of the intestinal microbiota. However, the role of the HFD-related gut microbiota in cancer development remains unclear. This study found that obesity and obesity-related gut microbiota were associated with poor prognosis and advanced clinicopathological status in female patients with breast cancer. To investigate the impact of HFD-associated gut microbiota on cancer progression, we established various models, including HFD feeding, fecal microbiota transplantation, antibiotic feeding, and bacterial gavage, in tumor-bearing mice. HFD-related microbiota promotes cancer progression by generating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, the HFD microbiota released abundant leucine, which activated the mTORC1 signaling pathway in myeloid progenitors for PMN-MDSC differentiation. Clinically, the elevated leucine level in the peripheral blood induced by the HFD microbiota was correlated with abundant tumoral PMN-MDSC infiltration and poor clinical outcomes in female patients with breast cancer. These findings revealed that the "gut-bone marrow-tumor" axis is involved in HFD-mediated cancer progression and opens a broad avenue for anticancer therapeutic strategies by targeting the aberrant metabolism of the gut microbiota.}, } @article {pmid38708959, year = {2024}, author = {Kousgaard, SJ and Cold, F and Halkjær, SI and Petersen, AM and Kjeldsen, J and Møller Hansen, J and Dall, SM and Albertsen, M and Nielsen, HL and Kirk, KF and Duch, K and Sønderkær, M and Thorlacius-Ussing, O}, title = {The effect of non-pooled multi-donor faecal microbiota transplantation for inducing clinical remission in patients with chronic pouchitis: Results from a multicentre randomised double-blinded placebo-controlled trial (MicroPouch).}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjae066}, pmid = {38708959}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: To investigate if treatment with non-pooled multi-donor faecal microbiota transplantation (FMT) for four weeks was superior to placebo to induce clinical remission in patients with chronic pouchitis.

METHODS: The study was a randomised double-blinded placebo-controlled study with a 4-week intervention period and 12-month follow-up. Eligible patients with chronic pouchitis were recruited from five Danish hospitals. Participants were randomised to non-pooled multi-donor FMT derived from four faecal donors, or placebo. Treatment was delivered daily by enema for two weeks followed by every second day for two weeks. Disease severity was accessed at inclusion and 30-day follow-up, using the Pouchitis Disease Activity Index (PDAI); PDAI <7 was considered equivalent to clinical remission. Faecal samples from participants and donors were analysed by shotgun metagenomic sequencing.

RESULTS: Inclusion was stopped after inclusion of 30 participants who were randomised 1:1 for treatment with FMT or placebo. There was no difference in participants achieving clinical remission between the two groups at 30-day follow-up, relative risk 1.0 (95%CI(0.55;1.81)). Treatment with FMT resulted in a clinically relevant increase in adverse events compared to placebo, incidence rate ratio 1.67 (95%CI(1.10;2.52)); no serious adverse events within either group. Faecal microbiota transplantation statistically significantly increased the similarity of participant faecal microbiome to the faecal donor microbiome at 30-days follow-up (p=0.01), which was not seen after placebo.

CONCLUSIONS: Non-pooled multi-donor FMT was comparable to placebo in inducing clinical remission in patients with chronic pouchitis but showed a clinically relevant increase in adverse events compared to placebo.}, } @article {pmid38708416, year = {2024}, author = {Zoghi, S and Sadeghpour Heravi, F and Nikniaz, Z and Shirmohamadi, M and Moaddab, SY and Ebrahimzadeh Leylabadlo, H}, title = {Gut microbiota and childhood malnutrition: Understanding the link and exploring therapeutic interventions.}, journal = {Engineering in life sciences}, volume = {24}, number = {5}, pages = {2300070}, pmid = {38708416}, issn = {1618-0240}, abstract = {Childhood malnutrition is a metabolic condition that affects the physical and mental well-being of children and leads to resultant disorders in maturity. The development of childhood malnutrition is influenced by a number of physiological and environmental factors including metabolic stress, infections, diet, genetic variables, and gut microbiota. The imbalanced gut microbiota is one of the main environmental risk factors that significantly influence host physiology and childhood malnutrition progression. In this review, we have evaluated the gut microbiota association with undernutrition and overnutrition in children, and then the quantitative and qualitative significance of gut dysbiosis in order to reveal the impact of gut microbiota modification using probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and engineering biology methods as new therapeutic challenges in the management of disturbed energy homeostasis. Understanding the host-microbiota interaction and the remote regulation of other organs and pathways by gut microbiota can improve the effectiveness of new therapeutic approaches and mitigate the negative consequences of childhood malnutrition.}, } @article {pmid38707810, year = {2024}, author = {León-Janampa, N and Boennec, N and Le Tilly, O and Ereh, S and Herbet, G and Moreau, A and Gatault, P and Longuet, H and Barbet, C and Büchler, M and Baron, C and Gaudy-Graffin, C and Brand, D and Marlet, J}, title = {Relevance of Tacrolimus Trough Concentration and Hepatitis E virus Genetic Changes in Kidney Transplant Recipients With Chronic Hepatitis E.}, journal = {Kidney international reports}, volume = {9}, number = {5}, pages = {1333-1342}, pmid = {38707810}, issn = {2468-0249}, abstract = {INTRODUCTION: Hepatitis E virus (HEV) can cause chronic infection (≥3 months) and cirrhosis in immunocompromised patients, especially kidney transplant recipients. Low alanine aminotransferase (ALT) levels and high HEV intrahost diversity have previously been associated with evolution toward chronicity in these patients. We hypothesized that additional clinical and viral factors could be associated with the risk of chronic HEV infection.

METHODS: We investigated a series of 27 kidney transplant recipients with HEV infection, including 20 patients with chronic hepatitis E.

RESULTS: High tacrolimus trough concentration at diagnosis was the most relevant marker associated with chronic hepatitis E (9.2 vs. 6.4 ng/ml, P = 0.04). Most HEV genetic changes selected during HEV infection were compartmentalized between plasma and feces.

CONCLUSION: This compartmentalization highlights the diversity and complexity of HEV replication compartments. Tacrolimus trough concentration at diagnosis of HEV infection could allow an early identification of patients at high risk of chronic hepatitis E and guide treatment initiation.}, } @article {pmid38702466, year = {2024}, author = {Ferreira, J}, title = {Effects of microbiome transplants on fly microbiome.}, journal = {Lab animal}, volume = {53}, number = {5}, pages = {109}, doi = {10.1038/s41684-024-01369-4}, pmid = {38702466}, issn = {1548-4475}, mesh = {Animals ; *Microbiota ; Drosophila melanogaster/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; }, } @article {pmid38701935, year = {2024}, author = {Xiao, K and Li, H and Li, Y and Zhan, B and Fang, X and Zhao, B and Zhang, X and Wu, Y and Wang, F and Jia, Y}, title = {Protective effects and mechanism of Sangyu granule on acetaminophen-induced liver injury in mice.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {118282}, doi = {10.1016/j.jep.2024.118282}, pmid = {38701935}, issn = {1872-7573}, abstract = {The Sang Yu granule (SY), a traditional Chinese medicine prescription of Xijing Hospital, was developed based on the Guanyin powder in the classical prescription "Hong's Collection of Proven Prescriptions" and the new theory of modern Chinese medicine. It has been proved to have a certain therapeutic effect on drug-induced liver injury (DILI), but the specific mechanism of action is still unclear.

AIM OF STUDY: Aim of the study was to explore the effect of SangYu granule on treating drug-induced liver injury induced by acetaminophen in mice.

MATERIALS AND METHODS: The chemical composition of SY, serum, and liver tissue was analyzed using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. To assess hepatic function, measurements were taken using kits for total bile acids, as well as serum AST, ALT, and ALP activity. Concentrations of IL-1β and TNF-α in serum were quantified using ELISA kits. Transcriptome Sequencing Analysis and 2bRAD-M microbial diversity analysis were employed to evaluate gene expression variance in liver tissue and fecal microbiota diversity among different groups, respectively. Western blotting was performed to observe differences in the activation levels of FXR, SHP, CYP7A1 and PPARα in the liver, and the levels of FXR and FGF-15 genes and proteins in the ileum of mice. Additionally, fecal microbiota transplantation (FMT) experiments were conducted to investigate the potential therapeutic effect of administering the intestinal microbial suspension from mice treated with SY on drug-induced liver injury.

RESULTS: SY treatment exhibited significant hepatoprotective effects in mice, effectively ameliorating drug-induced liver injury while concurrently restoring intestinal microbial dysbiosis. Furthermore, SY administration demonstrated a reduction in the concentration of total bile acids, the expression of FXR and SHP proteins in the liver was up-regulated, CYP7A1 protein was down-regulated, and the expressions of FXR and FGF-15 proteins in the ileum were up-regulated. However, no notable impact on PPARα was observed. Furthermore, results from FMT experiments indicated that the administration of fecal suspensions derived from mice treated with SY did not yield any therapeutic benefits in the context of drug-induced liver injury.

CONCLUSION: The aforementioned findings strongly suggest that SY exerts a pronounced ameliorative effect on drug-induced liver injury through its ability to modulate the expression of key proteins involved in bile acid secretion, thereby preserving hepato-enteric circulation homeostasis.}, } @article {pmid38701724, year = {2024}, author = {Chang, X and Shen, Y and Yang, M and Yun, L and Liu, Z and Feng, S and Yang, G and Meng, X and Su, X}, title = {Antipsychotic drug-induced behavioral abnormalities in common carp: The potential involvement of the gut microbiota-brain axis.}, journal = {Journal of hazardous materials}, volume = {472}, number = {}, pages = {134444}, doi = {10.1016/j.jhazmat.2024.134444}, pmid = {38701724}, issn = {1873-3336}, abstract = {The effects of antipsychotic drugs on aquatic organisms have received widespread attention owing to their widespread use and continued release in aquatic environments. The toxicological effects of antipsychotics on aquatic organisms, particularly fish, are unexplored, and the underlying mechanisms remain unelucidated. This study aimed to use common carp to explore the effects of antipsychotics (olanzapine [OLA] and risperidone [RIS]) on behavior and the potential mechanisms driving these effects. The fish were exposed to OLA (0.1 and 10 μg/L) and RIS (0.03 and 3 μg/L) for 60 days. Behavioral tests and neurological indicators showed that exposure to antipsychotics could cause behavioral abnormalities and neurotoxicity in common carp. Further, 16 S rRNA sequencing revealed gut microbiota alteration and decreased relative abundance of some strains related to SCFA production after OLA and RIS exposure. Subsequently, a pseudo-sterile common carp model was successfully constructed, and transplantation of the gut microbiota from antipsychotic-exposed fish caused behavioral abnormalities and neurotoxicity in pseudo-sterile fish. Further, SCFA supplementation demonstrated that SCFAs ameliorated the behavioral abnormalities and neurological damage caused by antipsychotic exposure. To our knowledge, the present study is the first to investigate the effects of antipsychotics on various complex behaviors (swimming performance and social behavior) in common carp, highlighting the potential health risks associated with antipsychotic drug-induced neurotoxicity in fish. Although these results do not fully elucidate the mechanisms underlying the effects of antipsychotic drugs on fish behavior, they serve as a valuable initial investigation and form the basis for future research.}, } @article {pmid38700306, year = {2023}, author = {Abraham, P and Pratap, N}, title = {Dysbiosis in Irritable Bowel Syndrome.}, journal = {The Journal of the Association of Physicians of India}, volume = {71}, number = {9}, pages = {75-81}, doi = {10.59556/japi.71.0353}, pmid = {38700306}, issn = {0004-5772}, mesh = {*Irritable Bowel Syndrome/microbiology/therapy ; *Dysbiosis/therapy ; Humans ; *Gastrointestinal Microbiome/physiology ; Anti-Bacterial Agents/therapeutic use ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; Prebiotics/administration & dosage ; }, abstract = {The human gut microbiota fosters the development of a dynamic group of microorganisms impacted by diverse variables that include genetics, diet, infection, stress, ingested drugs, such as antibiotics and small intestine bacterial overgrowth (SIBO) as well as the gut microbiota itself. These factors may influence the change in microbial composition, which results in dysbiosis (microbial imbalance) and exposes the gut to pathogenic insults. Dysbiosis is incidental to the etiology of inflammatory diseases such as irritable bowel syndrome (IBS) and metabolic diseases, including type 2 diabetes and obesity. IBS exhibits different symptoms like abdominal pain or discomfort, distention/bloating, and flatulence. To treat IBS, modification of dysregulated gut microbiota can be done using treatment strategies like a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, antibiotics that cannot be absorbed like rifaximin and neomycin, probiotics and prebiotics, and fecal microbiota transplantation (FMT). The remedial modalities in the existing literature have been demonstrated to be efficacious in the prevention and mitigation of IBS. Additionally, newer curative approaches with serum-derived bovine immunoglobulin (SBI) are an effective option. The focal point of the review paper is the pathophysiology of IBS, mainly due to dysbiosis and the various factors that advance dysbiosis. Here, we have also discussed the different treatment strategies targeting dysbiosis that effectively treat IBS. How to cite this article: Abraham P, Pratap N. Dysbiosis in Irritable Bowel Syndrome. J Assoc Physicians India 2023;71(9):75-81.}, } @article {pmid38699545, year = {2024}, author = {Lamas-Paz, A and Mesquita, M and Garcia-Lacarte, M and Estévez-Vázquez, O and Benedé-Ubieto, R and Gutierrez, AH and Wu, H and Leal Lasalle, H and Vaquero, J and Bañares, R and Martínez-Naves, E and Roa, S and Nevzorova, YA and Jorquera, G and Cubero, FJ}, title = {Fecal microbiota transplantation from female donors restores gut permeability and reduces liver injury and inflammation in middle-aged male mice exposed to alcohol.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1393014}, pmid = {38699545}, issn = {2296-861X}, abstract = {BACKGROUND: Alcohol misuse, binge drinking pattern, and gender-specific effects in the middle-aged population has been clearly underestimated. In the present study, we focused on understanding gender-specific effects of alcohol exposure on the gut-liver axis and the role of gut microbiota in modulating gender-specific responses to alcohol consumption.

METHODS: Fifty-two-week-old female and male C57BL/6 mice were fasted for 12 h, and then administered a single oral dose of ethanol (EtOH) (6 g/kg). Controls were given a single dose of PBS. Animals were sacrificed 8 h later. Alternatively, fecal microbiota transplantation (FMT) was performed in 52-week-old male mice from female donors of the same age. Permeability of the large intestine (colon), gut microbiota, liver injury, and inflammation was thoroughly evaluated in all groups.

RESULTS: Middle-aged male mice exposed to EtOH showed a significant increase in gut permeability in the large intestine, evaluated by FITC-dextran assay and ZO-1, OCCLUDIN and MUCIN-2 immuno-staining, compared to PBS-treated animals, whilst female mice of the same age also increased their gut permeability, but displayed a partially maintained intestinal barrier integrity. Moreover, there was a significant up-regulation of TLRs and markers of hepatocellular injury, cell death (AST, TUNEL-positive cells) and lipid accumulation (ORO) in male mice after EtOH exposure. Interestingly, FMT from female donors to male mice reduced gut leakiness, modified gut microbiota composition, ameliorated liver injury and inflammation, TLR activation and the senescence phenotype of middle-aged mice.

CONCLUSION: Our findings highlighted the relevance of gender in middle-aged individuals who are exposed to alcohol in the gut-liver axis. Moreover, our study revealed that gender-specific microbiota transplantation might be a plausible therapy in the management of alcohol-related disorders during aging.}, } @article {pmid38698178, year = {2024}, author = {Liao, C and Rolling, T and Djukovic, A and Fei, T and Mishra, V and Liu, H and Lindberg, C and Dai, L and Zhai, B and Peled, JU and van den Brink, MRM and Hohl, TM and Xavier, JB}, title = {Oral bacteria relative abundance in faeces increases due to gut microbiota depletion and is linked with patient outcomes.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {38698178}, issn = {2058-5276}, support = {U54 CA209975/CA/NCI NIH HHS/United States ; R01 AI093808/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R21 AI156157/AI/NIAID NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; }, abstract = {The detection of oral bacteria in faecal samples has been associated with inflammation and intestinal diseases. The increased relative abundance of oral bacteria in faeces has two competing explanations: either oral bacteria invade the gut ecosystem and expand (the 'expansion' hypothesis), or oral bacteria transit through the gut and their relative increase marks the depletion of other gut bacteria (the 'marker' hypothesis). Here we collected oral and faecal samples from mouse models of gut dysbiosis (antibiotic treatment and DSS-induced colitis) and used 16S ribosomal RNA sequencing to determine the abundance dynamics of oral bacteria. We found that the relative, but not absolute, abundance of oral bacteria increases, reflecting the 'marker' hypothesis. Faecal microbiome datasets from diverse patient cohorts, including healthy individuals and patients with allogeneic haematopoietic cell transplantation or inflammatory bowel disease, consistently support the 'marker' hypothesis and explain associations between oral bacterial abundance and patient outcomes consistent with depleted gut microbiota. By distinguishing between the two hypotheses, our study guides the interpretation of microbiome compositional data and could potentially identify cases where therapies are needed to rebuild the resident microbiome rather than protect against invading oral bacteria.}, } @article {pmid38697851, year = {2024}, author = {Wu, T and Li, L and Zhou, W and Bi, G and Jiang, X and Guo, M and Yang, X and Fang, J and Pang, J and Fan, S and Bi, H}, title = {Gut microbiota affects mPXR agonist PCN-induced hepatomegaly by regulating PXR and YAP activation.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {}, number = {}, pages = {}, doi = {10.1124/dmd.123.001604}, pmid = {38697851}, issn = {1521-009X}, abstract = {Pregnane X receptor (PXR) is essential in the regulation of liver homeostasis and the gut microbiota is closely linked to liver physiological and pathological status. We previously found that activation of PXR significantly promotes liver enlargement through interaction with yes-associated protein (YAP). However, whether gut microbiota is contributed to PXR-induced hepatomegaly and the involved mechanisms remain unclear. In this study, C57BL/6 mice were administered the mouse-specific agonist PCN for 5 days. Depletion of gut microbiota was achieved using broad-spectrum antibiotics (ABX) and fecal microbiota transplantation (FMT) was performed to restore the gut microbial. The composition of gut microbiota was analyzed by 16S rRNA sequencing, while the expression of PXR, YAP and their downstream target genes and proteins were assessed. The results indicated that PCN treatment altered the composition and abundance of specific bacterial taxa. Furthermore, depletion of gut microbiota using ABX significantly attenuated PCN-induced hepatomegaly. FMT experiment further demonstrated that the fecal microbiota from PCN-treated mice could induce liver enlargement. Mechanistic studies revealed that ABX treatment impeded the PXR and YAP activation induced by PCN, as evidenced by decreased expression of PXR, YAP, and their downstream targets. Moreover, alterations in PXR and YAP activation were likely contributing to hepatomegaly in recipient mice following FMT from PCN-treated mice. Collectively, the current study demonstrated that gut microbiota is involved in PCN-induced hepatomegaly via regulating PXR and YAP activation, providing potential novel insights into the involvement of gut microbiota in PXR-mediated hepatomegaly. Significance Statement This work describes that the composition of gut microbiota is altered in mPXR agonist PCN-induced hepatomegaly. The treatment with an antibiotic cocktail (ABX) depletes the intestinal microbiota, leading to the impairment of liver enlargement caused by PCN. Besides, fecal microbiota transplantation (FMT) from PCN-treated mice induces liver enlargement. Further study revealed that gut microbiota is involved in hepatomegaly via regulating PXR and YAP activation.}, } @article {pmid38697391, year = {2024}, author = {Soueges, S and Cheynet, V and Briot, T and Merveilleux du Vignaux, C and Benech, N and Ader, F}, title = {Clinical remission after faecal microbiota transplantation in transplanted recipients with refractory chronic Norovirus infections: a retrospective case series.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2024.04.015}, pmid = {38697391}, issn = {1469-0691}, } @article {pmid38697207, year = {2024}, author = {Tapasco-Tapasco, O and González, CA and Letourneur, A}, title = {Phase angle and impedance ratio as meta-inflammation biomarkers after a colon cleansing protocol in a group of overweight young women.}, journal = {Physiological measurement}, volume = {}, number = {}, pages = {}, doi = {10.1088/1361-6579/ad46df}, pmid = {38697207}, issn = {1361-6579}, abstract = {Blood C-reactive protein (CRP) and the electrical bioimpedance (EBI) variables phase angle (PhA) and impedance ratio (IR) have been proposed as biomarkers of metainflammation in overweight/obesity. CRP involves taking blood samples, while PhA and IR imply a less-than-2-minute-non-invasive procedure. In this study, values for these variables and percent body fat mass (PBFM) were obtained and compared immediately before and immediately after a colon cleansing protocol (CCP), aimed at modulating intestinal microbiota, as well as along a period of 8 weeks after it. Methods: 20 female volunteers (20.9-24.9 years old) participated: 12 in an overweight group (OG), and 8 in a lean group (LG). The OG was divided in two subgroups (n=6, each): control (SCG) and experimental (SEG). The ESG underwent a 6-day colon cleansing protocol (CCP) at week 2, while 5 volunteers in the CSG underwent it at week 9. Results: Pre/post-CCP mean values for the variables in the OG were: PBF (34.3/31.3%), CRP (3.7/0.6 mg/dL), PhA (6.9/7.5°) and IR*10 (0.78/0.77). Calculated R2 correlation factors among these variables are all above 0.89). The favorable changes first seen in the SEG were still present 8 weeks after the CCP. Conclusion: a) the CCP drastically lowers meta-inflammation, b) EBIS can be used to measure metainflammation, before and after treatment, c) for microbiota modulation, CCP could be a good alternative to more drastic procedures like fecal microbiota transplantation; d) reestablishing eubiosis by CCP could be an effective coadjutant in the treatment of overweight young adult overweight women. .}, } @article {pmid38355755, year = {2024}, author = {Zhang, J and Hasty, J and Zarrinpar, A}, title = {Live bacterial therapeutics for detection and treatment of colorectal cancer.}, journal = {Nature reviews. Gastroenterology & hepatology}, volume = {21}, number = {5}, pages = {295-296}, pmid = {38355755}, issn = {1759-5053}, support = {R01 EB030134/EB/NIBIB NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; R01 AI163483/AI/NIAID NIH HHS/United States ; U01 CA265719/CA/NCI NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; }, mesh = {*Colorectal Neoplasms/diagnosis/therapy ; Humans ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; }, abstract = {Live microorganisms can be manipulated and engineered for colorectal cancer detection and treatment through methods such as faecal microbiota transplantation, native bacteria engineering and synthetic circuit engineering. Although promising, substantial effort is required to translate these approaches for clinical use.}, } @article {pmid38696921, year = {2024}, author = {Mao, Q and Zhang, H and Zhang, Z and Lu, Y and Pan, J and Guo, D and Huang, L and Tian, H and Ma, K}, title = {Co-decoction of Lilii bulbus and Radix Rehmannia Recens and its key bioactive ingredient verbascoside inhibit neuroinflammation and intestinal permeability associated with chronic stress-induced depression via the gut microbiota-brain axis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {129}, number = {}, pages = {155510}, doi = {10.1016/j.phymed.2024.155510}, pmid = {38696921}, issn = {1618-095X}, abstract = {BACKGROUND: Gut microbiota plays a critical role in the pathogenesis of depression and are a therapeutic target via maintaining the homeostasis of the host through the gut microbiota-brain axis (GMBA). A co-decoction of Lilii bulbus and Radix Rehmannia Recens (LBRD), in which verbascoside is the key active ingredient, improves brain and gastrointestinal function in patients with depression. However, in depression treatment using verbascoside or LBRD, mechanisms underlying the bidirectional communication between the intestine and brain via the GMBA are still unclear.

PURPOSE: This study aimed to examine the role of verbascoside in alleviating depression via gut-brain bidirectional communication and to study the possible pathways involved in the GMBA.

METHODS: Key molecules and compounds involved in antidepressant action were identified using HPLC and transcriptomic analyses. The antidepressant effects of LBRD and verbascoside were observed in chronic stress induced depression model by behavioural test, neuronal morphology, and synaptic dendrite ultrastructure, and their neuroprotective function was measured in corticosterone (CORT)-stimulated nerve cell injury model. The causal link between the gut microbiota and the LBRD and verbascoside antidepressant efficacy was evaluate via gut microbiota composition analysis and faecal microbiota transplantation (FMT).

RESULTS: LBRD and Verbascoside administration ameliorated depression-like behaviours and synaptic damage by reversing gut microbiota disturbance and inhibiting inflammatory responses as the result of impaired intestinal permeability or blood-brain barrier leakiness. Furthermore, verbascoside exerted neuroprotective effects against CORT-induced cytotoxicity in an in vitro depression model. FMT therapy indicated that verbascoside treatment attenuated gut inflammation and central nervous system inflammatory responses, as well as eliminated neurotransmitter and brain-gut peptide deficiencies in the prefrontal cortex by modulating the composition of gut microbiota. Lactobacillus, Parabacteroides, Bifidobacterium, and Ruminococcus might play key roles in the antidepressant effects of LBRD via the GMBA.

CONCLUSION: The current study elucidates the multi-component, multi-target, and multi-pathway therapeutic effects of LBRD on depression by remodeling GMBA homeostasis and further verifies the causality between gut microbiota and the antidepressant effects of verbascoside and LBRD.}, } @article {pmid38694925, year = {2024}, author = {Elford, JD and Becht, N and Garssen, J and Kraneveld, AD and Perez-Pardo, P}, title = {Buty and the beast: the complex role of butyrate in Parkinson's disease.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1388401}, pmid = {38694925}, issn = {1663-9812}, abstract = {Parkinson's disease (PD) is a complex neurodegenerative disease which is often associated with gastrointestinal (GI) dysfunction. The GI tract is home to a wide range of microorganisms, among which bacteria, that can influence the host through various mechanisms. Products produced by these bacteria can act in the gut but can also exert effects in the brain via what is now well established to be the microbiota-gut-brain axis. In those with PD the gut-bacteria composition is often found to be different to that of non-PD individuals. In addition to compositional changes, the metabolic activity of the gut-microbiota is also changed in PD. Specifically, it is often reported that key producers of short chain fatty acids (SCFAs) as well as the concentration of SCFAs themselves are altered in the stool and blood of those with PD. These SCFAs, among which butyrate, are essential nutrients for the host and are a major energy source for epithelial cells of the GI tract. Additionally, butyrate plays a key role in regulating various host responses particularly in relation to inflammation. Studies have demonstrated that a reduction in butyrate levels can have a critical role in the onset and progression of PD. Furthermore, it has been shown that restoring butyrate levels in those with PD through methods such as probiotics, prebiotics, sodium butyrate supplementation, and fecal transplantation can have a beneficial effect on both motor and non-motor outcomes of the disease. This review presents an overview of evidence for the altered gut-bacteria composition and corresponding metabolite production in those with PD, with a particular focus on the SCFA butyrate. In addition to presenting current studies regarding SCFA in clinical and preclinical reports, evidence for the possibility to target butyrate production using microbiome based approaches in a therapeutic context is discussed.}, } @article {pmid38694298, year = {2024}, author = {Shariff, S and Kwan Su Huey, A and Parag Soni, N and Yahia, A and Hammoud, D and Nazir, A and Uwishema, O and Wojtara, M}, title = {Unlocking the gut-heart axis: exploring the role of gut microbiota in cardiovascular health and disease.}, journal = {Annals of medicine and surgery (2012)}, volume = {86}, number = {5}, pages = {2752-2758}, pmid = {38694298}, issn = {2049-0801}, abstract = {INTRODUCTION: Gut microbiota has emerged as a pivotal player in cardiovascular health and disease, extending its influence beyond the gut through intricate metabolic processes and interactions with the immune system. Accumulating evidence supports a significant association between gut microbiota and cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Dietary patterns have been identified as key factors shaping the composition of the gut microbiota and exerting notable impacts on cardiovascular health. Probiotics and prebiotics have shown promise in mitigating the risks of cardiovascular disease by modulating key cardiovascular parameters. Faecal microbiota transplantation (FMT) has recently emerged as a novel and intriguing therapeutic strategy.

AIM: This review paper aims to explore and elucidate the multifaceted role of gut microbiota in cardiovascular health. It will also address the prevailing challenges and limitations in gut microbiota studies, emphasizing the importance of future research in overcoming these obstacles to expand our understanding of the gut-heart axis.

MATERIALS AND METHODS: A comprehensive literature search was conducted using various databases including ClinicalTrials, Google Scholar, PubMed, ScienceDirect, MEDLINE, and Ovid Resources. The search strategy included utilizing keywords such as "Gut microbiota," "Randomized controlled trials (RCTs)," "Gut-heart axis," "Dysbiosis," "Diet," "Probiotics," "Prebiotics," "Faecal Microbiota transplantation," "cardiovascular disease," "Meta-analyses," and other compatible terms thereof. Only articles written in English were considered, and selection criteria included relevance to the research objectives, reasonable sample sizes, and robust methodology. In addition to the identified articles, meta-analyses, animal models and studies, and references from the selected articles were also examined to ensure a comprehensive review of the literature.

RESULTS: Dietary patterns exert a significant influence on the composition of the gut microbiota, and certain diets, such as the Mediterranean diet, have been associated with a favourable gut microbiota profile and a reduced risk of cardiovascular disease (CVD). Probiotics and prebiotics have emerged as potential interventions to mitigate CVD risks by modulating blood pressure, glycemic control, lipid profiles, and gut dysbiosis. Another innovative therapeutic approach is FMT, which involves transferring faecal material from a healthy donor to restore a balanced gut microbiota. FMT holds promise for improving cardiometabolic parameters in individuals with CVD, although further research is needed to elucidate its precise mechanisms and assess its effectiveness.

CONCLUSION: The gut microbiota is emerging as a potential therapeutic target for CVD prevention and management. However, current research has limitations, including the need for larger and more diverse studies, the challenges of establishing causality, and concerns regarding the long-term consequences and safety of gut microbiota modulation. Despite these limitations, understanding the gut-heart axis holds promise for the development of personalized therapies and interventions for cardiovascular health. Further research is needed to expand our knowledge and address the ethical and safety issues associated with gut microbiota modification.}, } @article {pmid38691831, year = {2024}, author = {Chen, H and Yu, Z and Qi, Z and Huang, X and Gao, J}, title = {Tongfu Lifei Decoction Attenuated Sepsis-Related Intestinal Mucosal Injury Through Regulating Th17/Treg Balance and Modulating Gut Microbiota.}, journal = {Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research}, volume = {44}, number = {5}, pages = {208-220}, doi = {10.1089/jir.2024.0001}, pmid = {38691831}, issn = {1557-7465}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Sepsis/immunology/drug therapy/complications ; *Th17 Cells/immunology/drug effects ; Rats ; *Drugs, Chinese Herbal/pharmacology ; *T-Lymphocytes, Regulatory/immunology/drug effects ; *Intestinal Mucosa/drug effects/immunology/pathology/microbiology ; Male ; Rats, Sprague-Dawley ; }, abstract = {Intestinal damage and secondary bacterial translocation are caused by the inflammatory response induced by sepsis. Tongfu Lifei (TLF) decoction has a protective effect on sepsis-related gastrointestinal function injury. However, the relation between gut microbiota, immune barrier, and sepsis under the treatment of TLF have not been well clarified yet. Here, rats were subjected to cecal ligation and puncture (CLP) to create a sepsis model. Subsequently, the TLF decoction was given to CLP rats by gavage, fecal microbiota transplantation (FMT), and antibiotic were used as positive control. TLF suppressed the inflammatory response and improved the pathological changes in the intestines of CLP rats. Besides, TLF promoted the balance of the percentage of the Th17 and Treg cells. Intestinal barrier function was also improved by TLF through enhancing ZO-1, and Occludin and Claudin 1 expression, preventing the secondary translocation of other gut microbiota. TLF dramatically boosted the gut microbiota's alpha- and beta-diversity in CLP rats. Moreover, it increased the relative abundance of anti-inflammatory gut microbiota and changed the progress of the glucose metabolism. In short, TLF regulated the gut microbiota to balance the ratio of Th17/Treg cells, reducing the inflammation in serum and intestinal mucosal injury in rats.}, } @article {pmid38690290, year = {2024}, author = {Paudel, D and Nair, DVT and Joseph, G and Castro, R and Tiwari, AK and Singh, V}, title = {Gastrointestinal microbiota-directed nutritional and therapeutic interventions for inflammatory bowel disease: opportunities and challenges.}, journal = {Gastroenterology report}, volume = {12}, number = {}, pages = {goae033}, pmid = {38690290}, issn = {2052-0034}, abstract = {Evidence-based research has confirmed the role of gastrointestinal microbiota in regulating intestinal inflammation. These data have generated interest in developing microbiota-based therapies for the prevention and management of inflammatory bowel disease (IBD). Despite in-depth understanding of the etiology of IBD, it currently lacks a cure and requires ongoing management. Accumulating data suggest that an aberrant gastrointestinal microbiome, often referred to as dysbiosis, is a significant environmental instigator of IBD. Novel microbiome-targeted interventions including prebiotics, probiotics, fecal microbiota transplant, and small molecule microbiome modulators are being evaluated as therapeutic interventions to attenuate intestinal inflammation by restoring a healthy microbiota composition and function. In this review, the effectiveness and challenges of microbiome-centered interventions that have the potential to alleviate intestinal inflammation and improve clinical outcomes of IBD are explored.}, } @article {pmid38690018, year = {2024}, author = {Dai, C and Huang, YH and Jiang, M}, title = {Fecal microbiota transplantation for irritable bowel syndrome: Current evidence and perspectives.}, journal = {World journal of gastroenterology}, volume = {30}, number = {16}, pages = {2179-2183}, pmid = {38690018}, issn = {2219-2840}, mesh = {*Irritable Bowel Syndrome/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; Humans ; Treatment Outcome ; *Gastrointestinal Microbiome ; Feces/microbiology ; Randomized Controlled Trials as Topic ; Clostridioides difficile/pathogenicity ; Clostridium Infections/therapy/microbiology ; }, abstract = {In this editorial we comment on the article published in the recent issue of the World journal of Gastroenterology. We focus specifically on the mechanisms un-derlying the effects of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), the factors which affect the outcomes of FMT in IBS patients, and challenges. FMT has emerged as a efficacious intervention for clostridium difficile infection and holds promise as a therapeutic modality for IBS. The utilization of FMT in the treatment of IBS has undergone scrutiny in numerous randomized controlled trials, yielding divergent outcomes. The current frontier in this field seeks to elucidate these variations, underscore the existing knowledge gaps that necessitate exploration, and provide a guideline for successful FMT imple-mentation in IBS patients. At the same time, the application of FMT as a treatment for IBS confronts several challenges.}, } @article {pmid38689371, year = {2024}, author = {Gooch, HCC and Labedan, M and Hall, LJ and Maxwell, A}, title = {Transplanting human infant gut microbiome species into Galleria mellonella.}, journal = {BMC research notes}, volume = {17}, number = {1}, pages = {123}, pmid = {38689371}, issn = {1756-0500}, support = {NC/R001782/1/NC3RS_/National Centre for the Replacement, Refinement and Reduction of Animals in Research/United Kingdom ; BB/P012523/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P012523/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P012523/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Humans ; *Moths/microbiology ; *Larva/microbiology ; Infant ; *Feces/microbiology ; Bifidobacterium/isolation & purification ; Enterococcus/isolation & purification ; }, abstract = {OBJECTIVE: Study of the human infant gut microbiome requires the use of surrogate mammalian species such as mice. We sought to investigate the usefulness of the greater wax moth larva, Galleria mellonella, as an alternative.

RESULTS: We have analysed the native gut microbiome of Galleria and developed methods for clearing the native microbiome and introducing species from human infant faecal samples. We find that some species, e.g. enterococci, are more successful at recolonisation, but that others, e.g. Bifidobacterium, are less so. The work paves the way for using Galleria rather than mice in this and similar work.}, } @article {pmid38687096, year = {2024}, author = {Song, XL and Liang, J and Lin, SZ and Xie, YW and Ke, CH and Ao, D and Lu, J and Chen, XM and He, YZ and Liu, XH and Li, W}, title = {Gut-lung axis and asthma: A historical review on mechanism and future perspective.}, journal = {Clinical and translational allergy}, volume = {14}, number = {5}, pages = {e12356}, pmid = {38687096}, issn = {2045-7022}, support = {32100602//National Natural Science Foundation of China/ ; 2023A1515012755//Guangdong Natural Science Foundation of China/ ; GCC2021009//Scientific Research Start-up Fund for High-level Talents of Affiliated Hospital of Guangdong Medical University/ ; }, abstract = {BACKGROUND: Gut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut-lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic. BODY: This review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut-lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed.

CONCLUSION: The gut-lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.}, } @article {pmid38686220, year = {2024}, author = {Bruggeman, A and Vandendriessche, C and Hamerlinck, H and De Looze, D and Tate, DJ and Vuylsteke, M and De Commer, L and Devolder, L and Raes, J and Verhasselt, B and Laukens, D and Vandenbroucke, RE and Santens, P}, title = {Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial.}, journal = {EClinicalMedicine}, volume = {71}, number = {}, pages = {102563}, pmid = {38686220}, issn = {2589-5370}, abstract = {BACKGROUND: Dysregulation of the gut microbiome has been implicated in Parkinson's disease (PD). This study aimed to evaluate the clinical effects and safety of a single faecal microbiota transplantation (FMT) in patients with early-stage PD.

METHODS: The GUT-PARFECT trial, a single-centre randomised, double-blind, placebo-controlled trial was conducted at Ghent University Hospital between December 01, 2020 and December 12, 2022. Participants (aged 50-65 years, Hoehn and Yahr stage 2) were randomly assigned to receive nasojejunal FMT with either healthy donor stool or their own stool. Computer-generated randomisation was done in a 1:1 ratio through permutated-block scheduling. Treatment allocation was concealed for participants and investigators. The primary outcome measure at 12 months was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score obtained during off-medication evaluations. Intention-to-treat analysis was performed using a mixed model for repeated measures analysis. This completed trial is registered on ClinicalTrials.gov (NCT03808389).

FINDINGS: Between December 2020 and December 2021, FMT procedures were conducted on 46 patients with PD: 22 in the healthy donor group and 24 in the placebo group. Clinical evaluations were performed at baseline, 3, 6, and 12 months post-FMT. Full data analysis was possible for 21 participants in the healthy donor group and 22 in the placebo group. After 12 months, the MDS-UPDRS motor score significantly improved by a mean of 5.8 points (95% CI -11.4 to -0.2) in the healthy donor group and by 2.7 points (-8.3 to 2.9) in the placebo group (p = 0.0235). Adverse events were limited to temporary abdominal discomfort.

INTERPRETATION: Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages.

FUNDING: Flemish PD patient organizations (VPL and Parkili), Research Foundation Flanders (FWO), Biocodex Microbiota Foundation.}, } @article {pmid38685762, year = {2024}, author = {Ishnaiwer, M and Le Bastard, Q and Naour, M and Zeman, M and Dailly, E and Montassier, E and Batard, E and Dion, M}, title = {Efficacy of an inulin-based treatment on intestinal colonization by multidrug-resistant E. coli: insight into the mechanism of action.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2347021}, pmid = {38685762}, issn = {1949-0984}, mesh = {Animals ; *Inulin/pharmacology/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Escherichia coli/drug effects/genetics ; *Feces/microbiology ; *Amoxicillin/pharmacology ; *Pantoprazole/pharmacology ; *Drug Resistance, Multiple, Bacterial ; beta-Lactamases/metabolism/genetics ; Dysbiosis/microbiology/drug therapy ; Anti-Bacterial Agents/pharmacology ; Escherichia coli Infections/drug therapy/microbiology ; Female ; Prebiotics/administration & dosage ; }, abstract = {Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant E. coli and to investigate its potential mechanisms of action. Mice with amoxicillin-induced intestinal dysbiosis mice were inoculated with extended spectrum beta-lactamase producing E. coli (ESBL-E. coli). The combination of inulin and pantoprazole (IP) significantly reduced ESBL-E. coli fecal titers, whereas pantoprazole alone did not and inulin had a delayed and limited effect. Fecal microbiome was assessed using shotgun metagenomic sequencing and qPCR. The efficacy of IP was predicted by increased abundance of 74 taxa, including two species of Adlercreutzia. Preventive treatments with A. caecimuris or A. muris also reduced ESBL-E. coli fecal titers. Fecal microbiota of mice effectively treated by IP was enriched in genes involved in inulin catabolism, production of propionate and expression of beta-lactamases. They also had increased beta-lactamase activity and decreased amoxicillin concentration. These results suggest that IP act through production of propionate and degradation of amoxicillin by the microbiota. The combination of pantoprazole and inulin is a potential treatment of intestinal colonization by multidrug-resistant E. coli. The ability of prebiotics to promote propionate and/or beta-lactamase producing bacteria may be used as a screening tool to identify potential treatments of intestinal colonization by multidrug resistant Enterobacterales.}, } @article {pmid38685731, year = {2024}, author = {Zhang, Z and Mocanu, V and Deehan, EC and Hotte, N and Zhu, Y and Wei, S and Kao, DH and Karmali, S and Birch, DW and Walter, J and Madsen, KL}, title = {Recipient microbiome-related features predicting metabolic improvement following fecal microbiota transplantation in adults with severe obesity and metabolic syndrome: a secondary analysis of a phase 2 clinical trial.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2345134}, pmid = {38685731}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Metabolic Syndrome/therapy/microbiology ; Male ; Female ; *Gastrointestinal Microbiome ; Adult ; Middle Aged ; *Feces/microbiology ; *Bile Acids and Salts/metabolism/blood ; *Bacteria/classification/isolation & purification/genetics/metabolism ; Obesity/therapy/microbiology ; Dietary Fiber/administration & dosage/metabolism ; Insulin Resistance ; Treatment Outcome ; }, abstract = {Microbial-based therapeutics in clinical practice are of considerable interest, and a recent study demonstrated fecal microbial transplantation (FMT) followed by dietary fiber supplements improved glucose homeostasis. Previous evidence suggests that donor and recipient compatibility and FMT protocol are key determinants, but little is known about the involvement of specific recipient factors. Using data from our recent randomized placebo-control phase 2 clinical trial in adults with obesity and metabolic syndrome, we grouped participants that received FMT from one of 4 donors with either fiber supplement into HOMA-IR responders (n = 21) and HOMA-IR non-responders (n = 8). We further assessed plasma bile acids using targeted metabolomics and performed subgroup analyzes to evaluate the effects of recipient parameters and gastrointestinal factors on microbiota engraftment and homeostatic model assessment of insulin resistance (HOMA2-IR) response. The baseline fecal microbiota composition at genus level of recipients could predict the improvements in HOMA2-IR at week 6 (ROC-AUC = 0.70). Prevotella was identified as an important predictor, with responders having significantly lower relative abundance than non-responders (p = .02). In addition, recipients displayed a highly individualized degree of microbial engraftment from donors. Compared to the non-responders, the responders had significantly increased bacterial richness (Chao1) after FMT and a more consistent engraftment of donor-specific bacteria ASVs (amplicon sequence variants) such as Faecalibacillus intestinalis (ASV44), Roseburia spp. (ASV103), and Christensenellaceae spp. (ASV140) (p < .05). Microbiota engraftment was strongly associated with recipients' factors at baseline including initial gut microbial diversity, fiber and nutrient intakes, inflammatory markers, and bile acid derivative levels. This study identified that responders to FMT therapy had a higher engraftment rate in the transplantation of specific donor-specific microbes, which were strongly correlated with insulin sensitivity improvements. Further, the recipient baseline gut microbiota and related factors were identified as the determinants for responsiveness to FMT and fiber supplementation. The findings provide a basis for the development of precision microbial therapeutics for the treatment of metabolic syndrome.}, } @article {pmid38684800, year = {2024}, author = {Liu, MT and Zhang, Y and Xiang, CG and Yang, T and Wang, XH and Lu, QK and Lu, HM and Fan, C and Feng, CL and Yang, XQ and Zou, DW and Li, H and Tang, W}, title = {Methionine-choline deficient diet deteriorates DSS-induced murine colitis through disturbance of gut microbes and infiltration of macrophages.}, journal = {Acta pharmacologica Sinica}, volume = {}, number = {}, pages = {}, pmid = {38684800}, issn = {1745-7254}, abstract = {Ulcerative colitis (UC) is associated with changed dietary habits and mainly linked with the gut microbiota dysbiosis, necroptosis of epithelial cells, and mucosal ulcerations. Liver dysfunction and abnormal level of liver metabolism indices were identified in UC patients, suggesting a close interaction between gut and liver disorders. Methionine-choline deficient diet (MCD) has been shown to induce persistent alterations of gut microbiota and metabolome during hepatitis. In this study we further explored the disease phenotypes in UC patients and investigated whether MCD functioned as a trigger for UC susceptibility. After assessing 88 serum specimens from UC patients, we found significant liver dysfunction and dyslipidemia including abnormal ALT, AST, TG, TC, LDL-c and HDL-c. Liver dysfunction and dyslipidemia were confirmed in DSS-induced colitis mice. We fed mice with MCD for 14 days to cause mild liver damage, and then treated with DSS for 7 days. We found that MCD intake significantly exacerbated the pathogenesis of mucosal inflammation in DSS-induced acute, progressive, and chronic colitis, referring to promotion of mucosal ulcers, colon shortening, diarrhea, inflammatory immune cell infiltration, cytokines release, and abnormal activation of inflammatory macrophages in colon and liver specimens. Intraperitoneal injection of clodronate liposomes to globally delete macrophages dramatically compromised the pathogenesis of MCD-triggering colitis. In addition, MCD intake markedly changed the production pattern of short-chain fatty acids (SCFAs) in murine stools, colons, and livers. We demonstrated that MCD-induced colitis pathogenesis largely depended on the gut microbes and the disease phenotypes could be transmissible through fecal microbiota transplantation (FMT). In conclusion, this study supports the concept that intake of MCD predisposes to experimental colitis and enhances its pathogenesis via modulating gut microbes and macrophages in mice.}, } @article {pmid38682201, year = {2024}, author = {Ayabe, RI and White, MG}, title = {Metastasis and the Microbiome: The Impact of Bacteria in Disseminated Colorectal Cancer.}, journal = {Frontiers in bioscience (Landmark edition)}, volume = {29}, number = {4}, pages = {152}, doi = {10.31083/j.fbl2904152}, pmid = {38682201}, issn = {2768-6698}, mesh = {Humans ; *Colorectal Neoplasms/microbiology/pathology/therapy ; *Gastrointestinal Microbiome/physiology ; *Neoplasm Metastasis ; Dysbiosis/microbiology ; Bacteria/classification/genetics ; Fecal Microbiota Transplantation ; }, abstract = {Metastasis remains a leading cause of mortality for patients with solid tumors. An expanding body of literature suggests interplay between the host, gut, and tumoral microbiomes may play a role in cancer initiation and distant dissemination. These associations have been particularly well-studied in colorectal cancer, where gut dysbiosis and an endotoxin-induced inflammatory milieu foster premalignant polyp formation, setting the stage for carcinogenesis. Subsequent violation of the gut vascular barrier enables dissemination of bacterial agents to sites such as the liver, where they contribute to establishment of pre-metastatic niches, which promote tumor cell extravasation and metastatic outgrowth. Intriguingly, breakdown of this vascular barrier has been shown to be aided by the presence of tumoral bacteria. The presence of similar species, including Fusobacterium nucleatum and Escherichia Coli, in both primary and metastatic colorectal tumors, supports this hypothesis and their presence is associated with chemotherapy resistance and an overall poor prognosis. Specific gut microbial populations are also associated with differential response to immunotherapy, which has a growing role in microsatellite unstable colorectal cancers. Recent work suggests that modulation of gut microbiome using dietary modification, targeted antibiotics, or fecal microbiota transplantation may improve response to immunotherapy and oncologic outcomes. Elucidation of the precise mechanistic links between the microbiome and cancer dissemination will open the doors to additional therapeutic possibilities.}, } @article {pmid38680517, year = {2024}, author = {Patel, P and Robinson, PD and Fisher, BT and Phillips, R and Morgan, JE and Lehrnbecher, T and Kuczynski, S and Koenig, C and Haeusler, GM and Esbenshade, A and Elgarten, C and Duong, N and Diorio, C and Castagnola, E and Beauchemin, MP and Ammann, RA and Dupuis, LL and Sung, L}, title = {Guideline for the management of Clostridioides difficile infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update.}, journal = {EClinicalMedicine}, volume = {72}, number = {}, pages = {102604}, pmid = {38680517}, issn = {2589-5370}, abstract = {Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI.}, } @article {pmid38679396, year = {2024}, author = {Benech, N and Cassir, N and Galperine, T and Alric, L and Scanzi, J and Sokol, H and , }, title = {Fecal microbiota transplantation for recurrent C. difficile infection can be the best therapeutic option in severely immunocompromised patients depending on a case-by-case assessment of the benefit/risk ratio.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.04.022}, pmid = {38679396}, issn = {1528-0012}, } @article {pmid38679228, year = {2024}, author = {Rondinella, D and Quaranta, G and Rozera, T and Dargenio, P and Fancello, G and Venturini, I and Guarnaccia, A and Porcari, S and Bibbò, S and Sanguinetti, M and Gasbarrini, A and Masucci, L and Cammarota, G and Ianiro, G}, title = {Donor screening for fecal microbiota transplantation with a direct stool testing-based strategy: a prospective cohort study.}, journal = {Microbes and infection}, volume = {}, number = {}, pages = {105341}, doi = {10.1016/j.micinf.2024.105341}, pmid = {38679228}, issn = {1769-714X}, abstract = {Fecal microbiota transplantation (FMT) is effective against recurrent Clostridioides difficile infection (rCDI), but its safety is jeopardized by the potential transmission of pathogens, so international guidelines recommend either a quarantine or a direct stool testing. Whereas reports of the quarantine-based approach are emerging, data on the direct testing-based approach are not available. Our aim is to report outcomes of a donor screening framework for FMT including direct stool testing. In this prospective cohort study, all donor candidates recruited at our FMT centre underwent a four-step screening process to be enrolled as actual donors. Each collected stool donation was then evaluated with a direct stool testing including a molecular assay for gut pathogens and a culture assay for multi-drug resistant organisms (MDRO). From January 2019 to June 2023, 72 of 227 candidates (32%) were considered eligible and provided 277 stool donations. Ninety-nine donations (36%) were discarded for positivity to intestinal pathogens, most commonly enteropathogenic Escherichia coli (n= 37) and Blastocystis hominis (n= 20). Overall, 337 stool aliquots were obtained from 165 approved donations. All suspensions were used for patients with rCDI, and no serious adverse events or clinically evident infections were observed at 12 weeks after procedures. In our study, screening of donor faeces including direct stool testing led to the discard of a considerable rate of stool donations but was also extremely safe. This approach may represent a reliable strategy to guarantee the safety of FMT programs, especially in countries with high prevalence of MDRO.}, } @article {pmid38678155, year = {2024}, author = {Corriero, A and Giglio, M and Soloperto, R and Inchingolo, F and Varrassi, G and Puntillo, F}, title = {Microbial Symphony: Exploring the Role of the Gut in Osteoarthritis-Related Pain. A Narrative Review.}, journal = {Pain and therapy}, volume = {}, number = {}, pages = {}, pmid = {38678155}, issn = {2193-8237}, abstract = {One of the most common musculoskeletal disorders, osteoarthritis (OA), causes worldwide disability, morbidity, and poor quality of life by degenerating articular cartilage, modifying subchondral bone, and inflaming synovial membranes. OA pathogenesis pathways must be understood to generate new preventative and disease-modifying therapies. In recent years, it has been acknowledged that gut microbiota (GM) can significantly contribute to the development of OA. Dysbiosis of GM can disrupt the "symphony" between the host and the GM, leading to a host immunological response that activates the "gut-joint" axis, ultimately worsening OA. This narrative review summarizes research supporting the "gut-joint axis" hypothesis, focusing on the interactions between GM and the immune system in its two main components, innate and adaptive immunity. Furthermore, the pathophysiological sequence of events that link GM imbalance to OA and OA-related pain is broken down and further investigated. We also suggest that diet and prebiotics, probiotics, nutraceuticals, exercise, and fecal microbiota transplantation could improve OA management and represent a new potential therapeutic tool in the light of the scarce panorama of disease-modifying osteoarthritis drugs (DMOADs). Future research is needed to elucidate these complex interactions, prioritizing how a particular change in GM, i.e., a rise or a drop of a specific bacterial strain, correlates with a certain OA subset to pinpoint the associated signaling pathway that leads to OA.}, } @article {pmid38674860, year = {2024}, author = {Wang, X and Jin, Y and Di, C and Zeng, Y and Zhou, Y and Chen, Y and Pan, Z and Li, Z and Ling, W}, title = {Supplementation of Silymarin Alone or in Combination with Salvianolic Acids B and Puerarin Regulates Gut Microbiota and Its Metabolism to Improve High-Fat Diet-Induced NAFLD in Mice.}, journal = {Nutrients}, volume = {16}, number = {8}, pages = {}, pmid = {38674860}, issn = {2072-6643}, support = {81973022//National Natural Science Foundation of China/ ; TY202101003//BYHEALTH Nutrition and Health Research Foundation/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Non-alcoholic Fatty Liver Disease/etiology/drug therapy ; *Diet, High-Fat/adverse effects ; *Mice, Inbred C57BL ; *Isoflavones/pharmacology ; Male ; Mice ; *Silymarin/pharmacology ; *Dietary Supplements ; Benzofurans/pharmacology ; Liver/metabolism/drug effects ; Disease Models, Animal ; Bile Acids and Salts/metabolism ; Plant Extracts/pharmacology ; *Depsides ; }, abstract = {Silymarin, salvianolic acids B, and puerarin were considered healthy food agents with tremendous potential to ameliorate non-alcoholic fatty liver disease (NAFLD). However, the mechanisms by which they interact with gut microbiota to exert benefits are largely unknown. After 8 weeks of NAFLD modeling, C57BL/6J mice were randomly divided into five groups and fed a normal diet, high-fat diet (HFD), or HFD supplemented with a medium or high dose of Silybum marianum extract contained silymarin or polyherbal extract contained silymarin, salvianolic acids B, and puerarin for 16 weeks, respectively. The untargeted metabolomics and 16S rRNA sequencing were used for molecular mechanisms exploration. The intervention of silymarin and polyherbal extract significantly improved liver steatosis and recovered liver function in the mice, accompanied by an increase in probiotics like Akkermansia and Blautia, and suppressed Clostridium, which related to changes in the bile acids profile in feces and serum. Fecal microbiome transplantation confirmed that this alteration of microbiota and its metabolites were responsible for the improvement in NAFLD. The present study substantiated that alterations of the gut microbiota upon silymarin and polyherbal extract intervention have beneficial effects on HFD-induced hepatic steatosis and suggested the pivotal role of gut microbiota and its metabolites in the amelioration of NAFLD.}, } @article {pmid38674803, year = {2024}, author = {Arteaga-Muller, GY and Flores-Treviño, S and Bocanegra-Ibarias, P and Robles-Espino, D and Garza-González, E and Fabela-Valdez, GC and Camacho-Ortiz, A}, title = {Changes in the Progression of Chronic Kidney Disease in Patients Undergoing Fecal Microbiota Transplantation.}, journal = {Nutrients}, volume = {16}, number = {8}, pages = {}, pmid = {38674803}, issn = {2072-6643}, mesh = {Humans ; *Renal Insufficiency, Chronic/therapy/microbiology ; *Fecal Microbiota Transplantation ; Male ; Female ; *Disease Progression ; Middle Aged ; Double-Blind Method ; *Gastrointestinal Microbiome ; Aged ; *Feces/microbiology ; Dysbiosis/therapy ; Treatment Outcome ; Adult ; Creatinine/blood ; }, abstract = {Chronic kidney disease (CKD) is a progressive loss of renal function in which gut dysbiosis is involved. Fecal microbiota transplantation (FMT) may be a promising alternative for restoring gut microbiota and treating CKD. This study evaluated the changes in CKD progression in patients treated with FMT. Patients with diabetes and/or hypertension with CKD clinical stages 2, 3, and 4 in this single-center, double-blind, randomized, placebo-controlled clinical trial (NCT04361097) were randomly assigned to receive either FMT or placebo capsules for 6 months. Laboratory and stool metagenomic analyses were performed. A total of 28 patients were included (15 FMT and 13 placebo). Regardless of CKD stages, patients responded similarly to FMT treatment. More patients (53.8%) from the placebo group progressed to CKD than the FMT group (13.3%). The FMT group maintained stable renal function parameters (serum creatinine and urea nitrogen) compared to the placebo group. Adverse events after FMT treatment were mild or moderate gastrointestinal symptoms. The abundance of Firmicutes and Actinobacteria decreased whereas Bacteroidetes, Proteobacteria and Roseburia spp. increased in the FMT group. CKD patients showed less disease progression after FMT administration. The administration of oral FMT in patients with CKD is a safe strategy, does not represent a risk, and has potential benefits.}, } @article {pmid38674209, year = {2024}, author = {Abenavoli, L and Gambardella, ML and Scarlata, GGM and Lenci, I and Baiocchi, L and Luzza, F}, title = {The Many Faces of Metabolic Dysfunction-Associated Fatty Liver Disease Treatment: From the Mediterranean Diet to Fecal Microbiota Transplantation.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {4}, pages = {}, pmid = {38674209}, issn = {1648-9144}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Diet, Mediterranean ; *Non-alcoholic Fatty Liver Disease/therapy/microbiology ; Probiotics/therapeutic use/administration & dosage ; Gastrointestinal Microbiome/physiology ; }, abstract = {The gastrointestinal tract is inhabited by the gut microbiota. The main phyla are Firmicutes and Bacteroidetes. In non-alcoholic fatty liver disease, now renamed metabolic dysfunction-associated fatty liver disease (MAFLD), an alteration in Firmicutes and Bacteroidetes abundance promotes its pathogenesis and evolution into non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. For this reason, early treatment is necessary to counteract its progression. The aim of the present narrative review is to evaluate the different therapeutic approaches to MAFLD. The most important treatment for MAFLD is lifestyle changes. In this regard, the Mediterranean diet could be considered the gold standard in the prevention and treatment of MAFLD. In contrast, a Western diet should be discouraged. Probiotics and fecal microbiota transplantation seem to be valid, safe, and effective alternatives for MAFLD treatment. However, more studies with a longer follow-up and with a larger cohort of patients are needed to underline the more effective approaches to contrasting MAFLD.}, } @article {pmid38673510, year = {2024}, author = {Bragazzi, MC and Pianigiani, F and Venere, R and Ridola, L}, title = {Dysbiosis in Inflammatory Bowel Disease and Spondyloarthritis: Still a Long Way to Go?.}, journal = {Journal of clinical medicine}, volume = {13}, number = {8}, pages = {}, pmid = {38673510}, issn = {2077-0383}, abstract = {The association between Inflammatory Bowel Disease (IBD) and Spondyloarthritis (SpA) has been known for years, as has the concept that IBD is associated with an altered intestinal bacterial composition, a condition known as "dysbiosis". Recently, a state of intestinal dysbiosis has also been found in SpA. Dysbiosis in the field of IBD has been well characterized so far, as well as in SpA. The aim of this review is to summarize what is known to date and to emphasize the similarities between the microbiota conditions in these two diseases: particularly, an altered distribution in the gut of Enterobacteriaceae, Streptococcus, Haemophilus, Clostridium, Akkermansia, Ruminococcus, Faecalibacterium Prausnitzii, Bacteroides Vulgatus, Dialister Invisus, and Bifidubacterium Adolescentis is common to both IBD and SpA. At the same time, little is known about intestinal dysbiosis in IBD-related SpA. Only a single recent study has found an increase in Escherichia and Shigella abundances and a decrease in Firmicutes, Ruminococcaceae, and Faecalibacterium abundances in an IBD-related SpA group. Based on what has been discovered so far about the altered distribution of bacteria that unite both pathologies, it is appropriate to carry out further studies aiming to improve the understanding of IBD-related SpA for the purpose of developing new therapeutic strategies.}, } @article {pmid38672797, year = {2024}, author = {Nayak, G and Dimitriadis, K and Pyrpyris, N and Manti, M and Kamperidis, N and Kamperidis, V and Ziakas, A and Tsioufis, K}, title = {Gut Microbiome and Its Role in Valvular Heart Disease: Not a "Gutted" Relationship.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {38672797}, issn = {2075-1729}, abstract = {The role of the gut microbiome (GM) and oral microbiome (OM) in cardiovascular disease (CVD) has been increasingly being understood in recent years. It is well known that GM is a risk factor for various CVD phenotypes, including hypertension, dyslipidemia, heart failure and atrial fibrillation. However, its role in valvular heart disease (VHD) is less well understood. Research shows that, direct, microbe-mediated and indirect, metabolite-mediated damage as a result of gut dysbiosis and environmental factors results in a subclinical, chronic, systemic inflammatory state, which promotes inflammatory cell infiltration in heart valves and subsequently, via pro-inflammatory molecules, initiates a cascade of reaction, resulting in valve calcification, fibrosis and dysfunction. This relationship between GM and VHD adds a pathophysiological link to the pathogenesis of VHD, which can be aimed therapeutically, in order to prevent or regress any risk for valvular pathologies. Therapeutic interventions include dietary modifications and lifestyle interventions, in order to influence environmental factors that can promote gut dysbiosis. Furthermore, the combination of probiotics and prebiotics, as well as fecal m transplantation and targeted treatment with inducers or inhibitors of microbial enzymes have showed promising results in animal and/or clinical studies, with the potential to reduce the inflammatory state and restore the normal gut flora in patients. This review, thus, is going to discuss the pathophysiological links behind the relationship of GM, CVD and VHD, as well as explore the recent data regarding the effect of GM-altering treatment in CVD, cardiac function and systemic inflammation.}, } @article {pmid38672155, year = {2024}, author = {Shin, J and Baek, GH and Cha, B and Park, SH and Lee, JH and Kim, JS and Kwon, KS}, title = {Complementary Therapeutic Effect of Fecal Microbiota Transplantation in Ulcerative Colitis after the Response to Anti-Tumor Necrosis Factor Alpha Agent Was Lost: A Case Report.}, journal = {Biomedicines}, volume = {12}, number = {4}, pages = {}, pmid = {38672155}, issn = {2227-9059}, support = {2021R1G1A1095241//National Research Foundation of Korea/ ; }, abstract = {In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.}, } @article {pmid38667013, year = {2024}, author = {Losurdo, G and Mezzapesa, M and Ditonno, I and Piazzolla, M and Pricci, M and Girardi, B and Celiberto, F and Galeano, G and Riezzo, G and Russo, F and Iannone, A and Ierardi, E and Di Leo, A}, title = {Helicobacter pylori Secondary Antibiotic Resistance after One or More Eradication Failure: A Genotypic Stool Analysis Study.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, pmid = {38667013}, issn = {2079-6382}, abstract = {Helicobacter pylori (H. pylori) antibiotic resistance is the leading cause for unsuccessful eradication therapy. After one or more failures, the chance of encountering secondary antibiotic resistance increases. The aim of this study was to characterize genotypic secondary resistance in a cohort of southern Italian H. pylori patients with at least one previous failure. Such patients collected stool samples using a dedicated kit (THD fecal test[TM]), and bacterial DNA was extracted and amplified using RT-PCR. Resistance to clarithromycin, amoxicillin, metronidazole, levofloxacin, and tetracycline was assessed using a high-resolution melting curve. We enrolled 50 patients. A total of 72% of patients failed one previous antibiotic course, 16% failed two, 10% failed three, and 2% failed four. The rate of secondary antibiotic resistance was 16% for clarithromycin, 18% for metronidazole, 14% for amoxicillin, 14% for levofloxacin, and 2% for tetracycline. Among the eight clarithromycin-resistant patients, five (62.5%) previously received a clarithromycin-based regimen. The same rate was 33.3% (3/9) for metronidazole. The only tetracycline-resistant patient had received Pylera. In conclusion, our data seem to show that, even though secondary resistance is not very high, resistance to clarithromycin could be very likely related to previous exposure to this antibiotic.}, } @article {pmid38666855, year = {2024}, author = {Long, C and Zhou, X and Xia, F and Zhou, B}, title = {Intestinal Barrier Dysfunction and Gut Microbiota in Non-Alcoholic Fatty Liver Disease: Assessment, Mechanisms, and Therapeutic Considerations.}, journal = {Biology}, volume = {13}, number = {4}, pages = {}, pmid = {38666855}, issn = {2079-7737}, support = {2022A1515010833//Natural Science Foundation of Guangdong Province/ ; 82074078//National Natural Science Foundation of China/ ; 81803816//National Natural Science Foundation of China/ ; ZDSYS20220606100801003//Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Re-search/ ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a type of metabolic stress liver injury closely related to insulin resistance (IR) and genetic susceptibility without alcohol consumption, which encompasses a spectrum of liver disorders ranging from simple hepatic lipid accumulation, known as steatosis, to the more severe form of steatohepatitis (NASH). NASH can progress to cirrhosis and hepatocellular carcinoma (HCC), posing significant health risks. As a multisystem disease, NAFLD is closely associated with systemic insulin resistance, central obesity, and metabolic disorders, which contribute to its pathogenesis and the development of extrahepatic complications, such as cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and certain extrahepatic cancers. Recent evidence highlights the indispensable roles of intestinal barrier dysfunction and gut microbiota in the onset and progression of NAFLD/NASH. This review provides a comprehensive insight into the role of intestinal barrier dysfunction and gut microbiota in NAFLD, including intestinal barrier function and assessment, inflammatory factors, TLR4 signaling, and the gut-liver axis. Finally, we conclude with a discussion on the potential therapeutic strategies targeting gut permeability and gut microbiota in individuals with NAFLD/NASH, such as interventions with medications/probiotics, fecal transplantation (FMT), and modifications in lifestyle, including exercise and diet.}, } @article {pmid38664425, year = {2024}, author = {Chui, ZSW and Chan, LML and Zhang, EWH and Liang, S and Choi, EPH and Lok, KYW and Tun, HM and Kwok, JYY}, title = {Effects of microbiome-based interventions on neurodegenerative diseases: a systematic review and meta-analysis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {9558}, pmid = {38664425}, issn = {2045-2322}, mesh = {Humans ; *Neurodegenerative Diseases/microbiology/therapy ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; Probiotics/therapeutic use ; Microbiota ; }, abstract = {Neurodegenerative diseases (NDDs) are characterized by neuronal damage and progressive loss of neuron function. Microbiome-based interventions, such as dietary interventions, biotics, and fecal microbiome transplant, have been proposed as a novel approach to managing symptoms and modulating disease progression. Emerging clinical trials have investigated the efficacy of interventions modulating the GM in alleviating or reversing disease progression, yet no comprehensive synthesis have been done. A systematic review of the literature was therefore conducted to investigate the efficacy of microbiome-modulating methods. The search yielded 4051 articles, with 15 clinical trials included. The overall risk of bias was moderate in most studies. Most microbiome-modulating interventions changed the GM composition. Despite inconsistent changes in GM composition, the meta-analysis showed that microbiome-modulating interventions improved disease burden (SMD, - 0.57; 95% CI - 0.93 to - 0.21; I[2] = 42%; P = 0.002) with a qualitative trend of improvement in constipation. However, current studies have high methodological heterogeneity and small sample sizes, requiring more well-designed and controlled studies to elucidate the complex linkage between microbiome, microbiome-modulating interventions, and NDDs.}, } @article {pmid38664378, year = {2024}, author = {Holmberg, SM and Feeney, RH and Prasoodanan P K, V and Puértolas-Balint, F and Singh, DK and Wongkuna, S and Zandbergen, L and Hauner, H and Brandl, B and Nieminen, AI and Skurk, T and Schroeder, BO}, title = {The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3502}, pmid = {38664378}, issn = {2041-1723}, support = {2018-02095//Vetenskapsrådet (Swedish Research Council)/ ; SMK-1959//Kempestiftelserna (Kempe Foundations)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Dietary Fiber/metabolism ; *Fatty Acids, Volatile/metabolism ; Mice ; *Colon/metabolism/microbiology ; Humans ; *Intestinal Mucosa/metabolism/microbiology ; Male ; Receptors, G-Protein-Coupled/metabolism/genetics ; Female ; Mice, Inbred C57BL ; Mucus/metabolism ; Fecal Microbiota Transplantation ; Symbiosis ; Propionates/metabolism ; Clostridiales/metabolism ; Acetates/metabolism ; Adult ; *Receptors, Cell Surface ; }, abstract = {Beneficial gut bacteria are indispensable for developing colonic mucus and fully establishing its protective function against intestinal microorganisms. Low-fiber diet consumption alters the gut bacterial configuration and disturbs this microbe-mucus interaction, but the specific bacteria and microbial metabolites responsible for maintaining mucus function remain poorly understood. By using human-to-mouse microbiota transplantation and ex vivo analysis of colonic mucus function, we here show as a proof-of-concept that individuals who increase their daily dietary fiber intake can improve the capacity of their gut microbiota to prevent diet-mediated mucus defects. Mucus growth, a critical feature of intact colonic mucus, correlated with the abundance of the gut commensal Blautia, and supplementation of Blautia coccoides to mice confirmed its mucus-stimulating capacity. Mechanistically, B. coccoides stimulated mucus growth through the production of the short-chain fatty acids propionate and acetate via activation of the short-chain fatty acid receptor Ffar2, which could serve as a new target to restore mucus growth during mucus-associated lifestyle diseases.}, } @article {pmid38663650, year = {2024}, author = {Fang, H and Hou, Q and Zhang, W and Su, Z and Zhang, J and Li, J and Lin, J and Wang, Z and Yu, X and Yang, Y and Wang, Q and Li, X and Li, Y and Hu, L and Li, S and Wang, X and Liao, L}, title = {Fecal Microbiota Transplantation Improves Clinical Symptoms of Fibromyalgia: An open-label, Randomized, Nonplacebo-Controlled Study.}, journal = {The journal of pain}, volume = {}, number = {}, pages = {104535}, doi = {10.1016/j.jpain.2024.104535}, pmid = {38663650}, issn = {1528-8447}, abstract = {Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study was aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label randomized, nonplacebo-controlled clinical study. The Numerical Rating Scale (NRS) scores in the FMT group were slightly lower than the control group at 1 month (P> 0.05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < 0.001). Besides, compared with the control group, the Widespread Pain Index (WPI), Symptom Severity (SS), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) scores were significantly lower in the FMT group at different time points (P < 0.001). After 6 months of treatment, there was a significant increase in serotonin (5-HT) and gamma-aminobutyric acid (GABA) levels (P < 0.001), while glutamate levels significantly decreased in the FMT group (P < 0.001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < 0.05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes of neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: Fecal microbiota transplantation (FMT) is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.}, } @article {pmid38663540, year = {2024}, author = {Liang, L and Zhang, J and Chen, J and Tian, Y and Li, W and Shi, M and Cheng, S and Zheng, Y and Wang, C and Liu, H and Yang, X and Ye, W}, title = {Bazedoxifene attenuates dextran sodium sulfate-induced colitis in mice through gut microbiota modulation and inhibition of STAT3 and NF-κB pathways.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {176611}, doi = {10.1016/j.ejphar.2024.176611}, pmid = {38663540}, issn = {1879-0712}, abstract = {Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract for which treatment options remain limited. In this study, we used a dual-luciferase-based screening of an FDA-approved drug library, identifying Bazedoxifene (BZA) as an inhibitor of the NF-κB pathway. We further investigated its therapeutic effects in a dextran sodium sulfate (DSS)-induced colitis model and explored its impact on gut microbiota regulation and the underlying molecular mechanisms. Our results showed that BZA significantly reduced DSS-induced colitis symptoms in mice, evidenced by decreased colon length shortening, lower histological scores, and increased expression of intestinal mucosal barrier-associated proteins, such as Claudin 1, Occludin, Zo-1, Mucin 2 (Muc2), and E-cadherin. Used independently, BZA showed therapeutic effects comparable to those of infliximab (IFX). In addition, BZA modulated the abundance of gut microbiota especially Bifidobacterium pseudolongum, and influenced microbial metabolite production. Crucially, BZA's alleviation of DSS-induced colitis in mice was linked to change in gut microbiota composition, as evidenced by in vivo gut microbiota depletion and fecal microbiota transplantation (FMT) mice model. Molecularly, BZA inhibited STAT3 and NF-κB activation in DSS-induced colitis in mice. In general, BZA significantly reduced DSS-induced colitis in mice through modulating the gut microbiota and inhibiting STAT3 and NF-κB activation, and its independent use demonstrated a therapeutic potential comparable to IFX. This study highlights gut microbiota's role in IBD drug development, offering insights for BZA's future development and its clinical applications.}, } @article {pmid38663526, year = {2024}, author = {Zhang, S and Tang, S and Liu, Z and Lv, H and Cai, X and Zhong, R and Chen, L and Zhang, H}, title = {Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107194}, doi = {10.1016/j.phrs.2024.107194}, pmid = {38663526}, issn = {1096-1186}, abstract = {Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.}, } @article {pmid38663295, year = {2024}, author = {Liu, A and Li, Y and Li, L and Chen, K and Tan, M and Zou, F and Zhang, X and Meng, X}, title = {Bile acid metabolism is altered in learning and memory impairment induced by chronic lead exposure.}, journal = {Journal of hazardous materials}, volume = {471}, number = {}, pages = {134360}, doi = {10.1016/j.jhazmat.2024.134360}, pmid = {38663295}, issn = {1873-3336}, abstract = {Lead is a neurotoxic contaminant that exists widely in the environment. Although lead neurotoxicity has been found to be tightly linked to gut microbiota disturbance, the effect of host metabolic disorders caused by gut microbiota disturbance on lead neurotoxicity has not been investigated. In this work, the results of new object recognition tests and Morris water maze tests showed that chronic low-dose lead exposure caused learning and memory dysfunction in mice. The results of 16 S rRNA sequencing of cecal contents and fecal microbiota transplantation showed that the neurotoxicity of lead could be transmitted through gut microbiota. The results of untargeted metabolomics and bile acid targeted metabolism analysis showed that the serum bile acid metabolism profile of lead-exposed mice was significantly changed. In addition, supplementation with TUDCA or INT-777 significantly alleviated chronic lead exposure-induced learning and memory impairment, primarily through inhibition of the NLRP3 inflammasome in the hippocampus to relieve neuroinflammation. In conclusion, our findings suggested that dysregulation of host bile acid metabolism may be one of the mechanisms of lead-induced neurotoxicity, and supplementation of specific bile acids may be a possible therapeutic strategy for lead-induced neurotoxicity.}, } @article {pmid38660489, year = {2024}, author = {Zhang, J and Wang, H and Liu, Y and Shi, M and Zhang, M and Zhang, H and Chen, J}, title = {Advances in fecal microbiota transplantation for the treatment of diabetes mellitus.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1370999}, pmid = {38660489}, issn = {2235-2988}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; *Diabetes Mellitus/therapy/microbiology ; Dysbiosis/therapy ; Animals ; Feces/microbiology ; }, abstract = {Diabetes mellitus (DM) refers to a group of chronic diseases with global prevalence, characterized by persistent hyperglycemia resulting from various etiologies. DM can harm various organ systems and lead to acute or chronic complications, which severely endanger human well-being. Traditional treatment mainly involves controlling blood sugar levels through replacement therapy with drugs and insulin; however, some patients still find a satisfactory curative effect difficult to achieve. Extensive research has demonstrated a close correlation between enteric dysbacteriosis and the pathogenesis of various types of DM, paving the way for novel therapeutic approaches targeting the gut microbiota to manage DM. Fecal microbiota transplantation (FMT), a method for re-establishing the intestinal microbiome balance, offers new possibilities for treating diabetes. This article provides a comprehensive review of the correlation between DM and the gut microbiota, as well as the current advancements in FMT treatment for DM, using FMT as an illustrative example. This study aims to offer novel perspectives and establish a theoretical foundation for the clinical diagnosis and management of DM.}, } @article {pmid38659636, year = {2024}, author = {Herman, C and Barker, BM and Bartelli, TF and Chandra, V and Krajmalnik-Brown, R and Jewell, M and Li, L and Liao, C and McAllister, F and Nirmalkar, K and Xavier, JB and Caporaso, JG}, title = {Assessing Engraftment Following Fecal Microbiota Transplant.}, journal = {ArXiv}, volume = {}, number = {}, pages = {}, pmid = {38659636}, issn = {2331-8422}, abstract = {Fecal Microbiota Transplant (FMT) is an FDA approved treatment for recurrent Clostridium difficile infections, and is being explored for other clinical applications, from alleviating digestive and neurological disorders, to priming the microbiome for cancer treatment, and restoring microbiomes impacted by cancer treatment. Quantifying the extent of engraftment following an FMT is important in determining if a recipient didn't respond because the engrafted microbiome didn't produce the desired outcomes (a successful FMT, but negative treatment outcome), or the microbiome didn't engraft (an unsuccessful FMT and negative treatment outcome). The lack of a consistent methodology for quantifying FMT engraftment extent hinders the assessment of FMT success and its relation to clinical outcomes, and presents challenges for comparing FMT results and protocols across studies. Here we review 46 studies of FMT in humans and model organisms and group their approaches for assessing the extent to which an FMT engrafts into three criteria: 1) Chimeric Asymmetric Community Coalescence investigates microbiome shifts following FMT engraftment. 2) Donated Microbiome Indicator Features tracks donated microbiome features as a signal of engraftment with methods such as differential abundance testing based on the current sample collection, or tracking changes in feature abundances that have been previously identified. 3) Temporal Stability examines how resistant post-FMT recipient's microbiomes are to reverting back to their baseline microbiome. Investigated together, these criteria provide a clear assessment of microbiome engraftment. We discuss the pros and cons of each of these criteria, providing illustrative examples of their application. We also introduce key terminology and recommendations on how FMT studies can be analyzed for rigorous engraftment extent assessment.}, } @article {pmid38659317, year = {2024}, author = {Xiao, N and He, W and Chen, S and Yao, Y and Wu, N and Xu, M and Du, H and Zhao, Y and Tu, Y}, title = {Protective Effect of Egg Yolk Lipids against Dextran Sulfate Sodium-Induced Colitis: The Key Role of Gut Microbiota and Short-Chain Fatty Acids.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2400048}, doi = {10.1002/mnfr.202400048}, pmid = {38659317}, issn = {1613-4133}, support = {82260642//National Natural Science Foundation of China/ ; 20224ACB205015//Key Program of Natural Science Foundation of Jiangxi Province, China/ ; 29202300002//Training Project of High-level and High-skilled Leading Talents of Jiangxi Province/ ; }, abstract = {Egg yolk lipids significantly alleviate dextran sulfate sodium (DSS)-induced colitis by inhibiting NLRP3 inflammasome, reversing gut microbiota dysbiosis, and increasing short chain fatty acids (SCFAs) concentrations. However, the role of gut microbiota and the relationship between SCFAs and NLRP3 inflammasome are still unknown. Here, this study confirms that antibiotic treatment abolishes the protective effect of egg yolk lipids on DSS-induced colonic inflammation, intestinal barrier damage, and lipopolysaccharide translocation. Fecal microbiota transplantation also supports that egg yolk lipids alleviate colitis in a gut microbiota-dependent manner. Then, the study investigates the relationship between SCFAs and NLRP3 inflammasome, and finds that SCFAs significantly suppress colitis via inhibiting colonic NLRP3 inflammasome activation and proinflammatory cytokines secretions (interleukin, IL)-1β and IL-18, and combined treatment of SCFAs and MCC950 (NLRP3 inhibitor) shows a better activity against colitis and NLRP3 inflammasome activation. Together, these findings provide positive evidence for gut microbiorta-SCFAs-NLRP3 axis as a novel target involving in the therapy of inflammatory bowel disease.}, } @article {pmid38655401, year = {2024}, author = {Shi, W and Li, Z and Wang, W and Liu, X and Wu, H and Chen, X and Zhou, X and Zhang, S}, title = {Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation.}, journal = {Journal of pharmaceutical analysis}, volume = {14}, number = {4}, pages = {100931}, pmid = {38655401}, issn = {2214-0883}, abstract = {Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap. ICGN was induced via the intravenous injection of cationized bovine serum albumin (c-BSA) into Sprague-Dawley (SD) rats for two weeks, after which mycophenolate mofetil (MMF) and losartan were administered orally. Two and six weeks after ICGN establishment, fecal samples were collected and 16S ribosomal DNA (rDNA) sequencing and untargeted metabolomic were conducted. Fecal microbiota transplantation (FMT) was conducted to determine whether gut normalization caused by MMF and losartan contributed to their renal protective effects. A gradual decline in microbial diversity and richness was accompanied by a loss of renal function. Approximately 18 genera were found to have significantly different relative abundances between the early and later stages, and Marvinbryantia and Allobaculum were markedly upregulated in both stages. Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN, characterized by the overproduction of indole and kynurenic acid, while the serotonin pathway was reduced. Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces. FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes (F/B) ratio but did not improve renal function. These findings indicate that ICGN induces serous gut dysbiosis, wherein an altered tryptophan metabolism may contribute to its progression. MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis, which partially contributed to their renoprotective effects.}, } @article {pmid38654015, year = {2024}, author = {Lachance, G and Robitaille, K and Laaraj, J and Gevariya, N and Varin, TV and Feldiorean, A and Gaignier, F and Julien, IB and Xu, HW and Hallal, T and Pelletier, JF and Bouslama, S and Boufaied, N and Derome, N and Bergeron, A and Ellis, L and Piccirillo, CA and Raymond, F and Fradet, Y and Labbé, DP and Marette, A and Fradet, V}, title = {The gut microbiome-prostate cancer crosstalk is modulated by dietary polyunsaturated long-chain fatty acids.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3431}, pmid = {38654015}, issn = {2041-1723}, support = {400345//Canadian Cancer Society Research Institute (Société Canadienne du Cancer)/ ; }, mesh = {Male ; *Gastrointestinal Microbiome ; *Prostatic Neoplasms/metabolism/diet therapy/microbiology ; Animals ; Humans ; Mice ; *Fecal Microbiota Transplantation ; *Feces/microbiology ; Fatty Acids, Omega-3/metabolism/administration & dosage ; Mice, Inbred C57BL ; Fatty Acids, Unsaturated/metabolism ; }, abstract = {The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction in fecal microbiota alpha-diversity correlating with increase tumour burden in two distinct groups of hormonotherapy naïve PCa patients and three murine PCa models. Fecal microbiota transplantation (FMT) from patients with high PCa volume is sufficient to stimulate the growth of mouse PCa revealing the existence of a gut microbiome-cancer crosstalk. Analysis of gut microbial-related pathways in mice with aggressive PCa identifies three enzymes responsible for the metabolism of long-chain fatty acids (LCFA). Supplementation with LCFA omega-3 MAG-EPA is sufficient to reduce PCa growth in mice and cancer up-grading in pre-prostatectomy PCa patients correlating with a reduction of gut Ruminococcaceae in both and fecal butyrate levels in PCa patients. This suggests that the beneficial effect of omega-3 rich diet is mediated in part by modulating the crosstalk between gut microbes and their metabolites in men with PCa.}, } @article {pmid38653643, year = {2024}, author = {Taghaddos, D and Saqib, Z and Bai, X and Bercik, P and Collins, SM}, title = {Post-infectious ibs following Clostridioides difficile infection; role of microbiota and implications for treatment.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2024.03.008}, pmid = {38653643}, issn = {1878-3562}, abstract = {Up to 25% of patients recovering from antibiotic-treated Clostridioides difficile infection (CDI) develop functional symptoms reminiscent of Post-Infectious Irritable Bowel Syndrome (PI-IBS). For patients with persistent symptoms following infection, a clinical dilemma arises as to whether to provide additional antibiotic treatment or to adopt a conservative symptom-based approach. Here, we review the literature on CDI-related PI-IBS and compare the findings with PI-IBS. We review proposed mechanisms, including the role of C. difficile toxins and the microbiota, and discuss implications for therapy. We suggest that gut dysfunction post-CDI may be initiated by toxin-induced damage to enteroglial cells and that a dysbiotic gut microbitota maintains the clinical phenotype over time, prompting consideration of microbiota-directed therapies. While Fecal Microbial Transplant (FMT) is currently reserved for recurrent CDI (rCDI), we propose that microbiota-directed therapies may have a role in primary CDI in order to avoid or mitigate futher antibiotic treatment that further disrupts the microbiota and thus prevent PI-IBS. We discuss novel microbial transfer therapies and as they emerge, we recommend clinical trials to determine whether microbial transfer therapy of the primary infection prevents both rCDI and CDI-related PI- IBS.}, } @article {pmid38648368, year = {2024}, author = {Muchhala, KH and Kallurkar, PS and Kang, M and Koseli, E and Poklis, JL and Xu, Q and Dewey, WL and Fettweis, JM and Jimenez, NR and Akbarali, HI}, title = {The role of morphine- and fentanyl-induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota-gut-brain axis.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {38}, number = {8}, pages = {e23603}, doi = {10.1096/fj.202301590RR}, pmid = {38648368}, issn = {1530-6860}, support = {P30DA033934//HHS | National Institutes of Health (NIH)/ ; R01DA024009//HHS | National Institutes of Health (NIH)/ ; T32DA007027//HHS | National Institutes of Health (NIH)/ ; 2214-A//TUBITAK/ ; }, abstract = {Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes intestinal dysbiosis. Depleting gut bacteria can preclude the development of tolerance to opioid-induced antinociception, suggesting an important role of the gut-brain axis in mediating opioid effects. The mechanism underlying opioid-induced dysbiosis, however, remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine or fentanyl exposure reduces the antimicrobial activity in the ileum, resulting in changes in the composition of bacteria. Fecal samples from morphine-treated mice had increased levels of Akkermansia muciniphila with a shift in the abundance ratio of Firmicutes and Bacteroidetes. Fecal microbial transplant (FMT) from morphine-naïve mice or oral supplementation with butyrate restored (a) the antimicrobial activity, (b) the expression of the antimicrobial peptide, Reg3γ, (c) prevented the increase in intestinal permeability and (d) prevented the development of antinociceptive tolerance in morphine-dependent mice. Improved epithelial barrier function with FMT or butyrate prevented the enrichment of the mucin-degrading A. muciniphila in morphine-dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which opioids disrupt the microbiota-gut-brain axis.}, } @article {pmid38647627, year = {2023}, author = {Zhuang, X and Zhao, M and Ji, X and Yang, S and Yin, H and Zhao, L}, title = {Chitobiose exhibited a lipid-lowering effect in ob/ob[-/-] mice via butyric acid enrolled liver-gut crosstalk.}, journal = {Bioresources and bioprocessing}, volume = {10}, number = {1}, pages = {79}, pmid = {38647627}, issn = {2197-4365}, support = {23ZR1417300//Shanghai Natural Science Foundation General program/ ; 2022153//Shanghai post-doctoral Excellence Program/ ; 2019YFD090180302//National key R&D Program of China/ ; B18022//111 Project/ ; }, abstract = {Chitobiose (COS2) efficiently lowers lipids in vivo and facilitates butyric acid enrichment during human fecal fermentation. However, whether COS2 can interact with butyric acid to generate a hypolipidemic effect remains unclear. This study examined the hypolipidemic mechanism of COS2 involving butyric acid, which could alleviate non-alcoholic fatty liver disease (NAFLD). The results revealed that COS2 administration modulated the β-oxidation pathway in the liver and restructured the short chain fatty acids in the fecal of ob/ob[-/-] mice. Moreover, the hypolipidemic effect of COS2 and its specific accumulated metabolite butyric acid was verified in sodium oleate-induced HepG2 cells. Butyric acid was more effective to reverse lipid accumulation and up-regulate β-oxidation pathway at lower concentrations. Furthermore, structural analysis suggested that butyric acid formed hydrogen bonds with key residues in hydrophilic ligand binding domains (LBDs) of PPARα and activated the transcriptional activity of the receptor. Therefore, the potential mechanism behind the lipid-lowering effect of COS2 in vivo involved restoring hepatic lipid disorders via butyric acid accumulation and liver-gut axis signaling.}, } @article {pmid38647957, year = {2024}, author = {Singh, V and Mahra, K and Jung, D and Shin, JH}, title = {Gut Microbes in Polycystic Ovary Syndrome and Associated Comorbidities; Type 2 Diabetes, Non-Alcoholic Fatty Liver Disease (NAFLD), Cardiovascular Disease (CVD), and the Potential of Microbial Therapeutics.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {38647957}, issn = {1867-1314}, support = {2021R1A6C101A416//Korea Basic Science Institute/ ; }, abstract = {Polycystic ovary syndrome (PCOS) is one of the most common endocrine anomalies among females of reproductive age, highlighted by hyperandrogenism. PCOS is multifactorial as it can be associated with obesity, insulin resistance, low-grade chronic inflammation, and dyslipidemia. PCOS also leads to dysbiosis by lowering microbial diversity and beneficial microbes, such as Faecalibacterium, Roseburia, Akkermenisa, and Bifidobacterium, and by causing a higher load of opportunistic pathogens, such as Escherichia/Shigella, Fusobacterium, Bilophila, and Sutterella. Wherein, butyrate producers and Akkermansia participate in the glucose uptake by inducing glucagon-like peptide-1 (GLP-1) and glucose metabolism, respectively. The abovementioned gut microbes also maintain the gut barrier function and glucose homeostasis by releasing metabolites such as short-chain fatty acids (SCFAs) and Amuc_1100 protein. In addition, PCOS-associated gut is found to be higher in gut-microbial enzyme β-glucuronidase, causing the de-glucuronidation of conjugated androgen, making it susceptible to reabsorption by entero-hepatic circulation, leading to a higher level of androgen in the circulatory system. Overall, in PCOS, such dysbiosis increases the gut permeability and LPS in the systemic circulation, trimethylamine N-oxide (TMAO) in the circulatory system, chronic inflammation in the adipose tissue and liver, and oxidative stress and lipid accumulation in the liver. Thus, in women with PCOS, dysbiosis can promote the progression and severity of type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). To alleviate such PCOS-associated complications, microbial therapeutics (probiotics and fecal microbiome transplantation) can be used without any side effects, unlike in the case of hormonal therapy. Therefore, this study sought to understand the mechanistic significance of gut microbes in PCOS and associated comorbidities, along with the role of microbial therapeutics that can ease the life of PCOS-affected women.}, } @article {pmid38647087, year = {2024}, author = {Zhou, F and Zhang, Q and Zheng, X and Shi, F and Ma, K and Ji, F and Meng, N and Li, R and Lv, J and Li, Q}, title = {Antiaging Effects of Human Fecal Transplants with Different Combinations of Bifidobacterium bifidum LTBB21J1 and Lactobacillus casei LTL1361 in d-Galactose-Induced Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c09815}, pmid = {38647087}, issn = {1520-5118}, abstract = {The feces of healthy middle-aged and old people were first transplanted into d-galactose-induced aging mice to construct humanized aging mice with gut microbiota (FMTC) to confirm the antiaging effect of probiotics produced from centenarians. The mouse model was then treated with centenarian-derived Bifidobacterium bifidum (FMTL), Lactobacillus casei (FMTB), and their mixtures (FMTM), and young mice were used as the control. Compared with the FMTC group, the results demonstrated that the probiotics and their combinations alleviated neuronal damage, increased antioxidant capacity, decreased inflammation, and enhanced cognitive and memory functions in aging mice. In the gut microbiota, the relative abundance of Lactobacillus, Ligilactobacillus, and Akkermansia increased and that of Desulfovibrio and Colidextribacter decreased in the FMTM group compared with that in the FMTC group. The three probiotic groups displayed significant changes in 15 metabolites compared with the FMTC group, with 4 metabolites showing increased expression and 11 metabolites showing decreased expression. The groups were graded as Control > FMTM > FMTB > FMTL > FMTC using a newly developed comprehensive quantitative scoring system that thoroughly analyzed the various indicators of this study. The beneficial antiaging effects of probiotics derived from centenarians were quantitatively described using a novel perspective in this study; it is confirmed that both probiotics and their combinations exert antiaging effects, with the probiotic complex group exhibiting a larger effect.}, } @article {pmid38646653, year = {2024}, author = {Liu, Q and Yang, Y and Pan, M and Yang, F and Yu, Y and Qian, Z}, title = {Role of the gut microbiota in tumorigenesis and treatment.}, journal = {Theranostics}, volume = {14}, number = {6}, pages = {2304-2328}, pmid = {38646653}, issn = {1838-7640}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Carcinogenesis ; *Neoplasms/microbiology/therapy ; *Dysbiosis/microbiology ; Animals ; }, abstract = {The gut microbiota is a crucial component of the intricate microecosystem within the human body that engages in interactions with the host and influences various physiological processes and pathological conditions. In recent years, the association between dysbiosis of the gut microbiota and tumorigenesis has garnered increasing attention, as it is recognized as a hallmark of cancer within the scientific community. However, only a few microorganisms have been identified as potential drivers of tumorigenesis, and enhancing the molecular understanding of this process has substantial scientific importance and clinical relevance for cancer treatment. In this review, we delineate the impact of the gut microbiota on tumorigenesis and treatment in multiple types of cancer while also analyzing the associated molecular mechanisms. Moreover, we discuss the utility of gut microbiota data in cancer diagnosis and patient stratification. We further outline current research on harnessing microorganisms for cancer treatment while also analyzing the prospects and challenges associated with this approach.}, } @article {pmid38644237, year = {2024}, author = {, and , and , }, title = {[Chinese expert consensus on the clinical diagnosis and treatment of gut microecology in chronic constipation (2024 edition)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {27}, number = {4}, pages = {326-337}, doi = {10.3760/cma.j.cn441530-20240313-00096}, pmid = {38644237}, issn = {1671-0274}, support = {2022YFC2010101//"Thirteenth Five-Year Plan" National Key Research and Development Program "Proactive Health and Aging Science and Technology Response" Key Project/ ; 82100698//National Natural Science Foundation of China/ ; 21Y11908300, 22DZ2203700//Shanghai Municipal Science and Technology Innovation Action Plan/ ; }, mesh = {Humans ; *Constipation/therapy/diagnosis ; *Gastrointestinal Microbiome ; Chronic Disease ; *Fecal Microbiota Transplantation ; China ; *Consensus ; Dysbiosis/therapy/diagnosis ; Quality of Life ; }, abstract = {Chronic constipation is one of the common gastrointestinal disorders, with an incidence rate that is gradually increasing yearly and becoming an important chronic disease that affects people's health and quality of life. In recent years, significant progress has been made in the basic and clinical research of chronic constipation, especially the gut microbiota therapy methods have received increasing attention. Therefore, under the initiative of the Parenteral and Enteral Nutrition Branch of the Chinese Medical Association, Chinese Society for the Promotion of Human Health Science and Technology, and Committee on Gut Microecology and Fecal Microbiota Transplantation, experts from relevant fields in China have been organized to establish the "Chinese Expert Consensus on the Clinical Diagnosis and Treatment of Gut Microecology in Chronic Constipation (2024 Edition)" committee. Focusing on the dysbiosis of gut microbiota, the indications for gut microbiota therapy, and the protocols for fecal microbiota transplantation, 16 consensus opinions were proposed based on the review of domestic and international literature and the clinical experience of experts, aiming to standardize the clinical application of gut microbiota in chronic constipation.}, } @article {pmid38642272, year = {2024}, author = {Chen, LA and Boyle, K}, title = {The Role of the Gut Microbiome in Health and Disease in the Elderly.}, journal = {Current gastroenterology reports}, volume = {}, number = {}, pages = {}, pmid = {38642272}, issn = {1534-312X}, abstract = {PURPOSE OF REVIEW: Growing evidence supports the contribution of age in the composition and function of the gut microbiome, with specific findings associated with health in old age and longevity.

RECENT FINDINGS: Current studies have associated certain microbiota, such as Butyricimonas, Akkermansia, and Odoribacter, with healthy aging and the ability to survive into extreme old age. Furthermore, emerging clinical and pre-clinical research have shown promising mechanisms for restoring a healthy microbiome in elderly populations through various interventions such as fecal microbiota transplant (FMT), dietary interventions, and exercise programs. Despite several conceptually exciting interventional studies, the field of microbiome research in the elderly remains limited. Specifically, large longitudinal studies are needed to better understand causative relationships between the microbiome and healthy aging. Additionally, individualized approaches to microbiome interventions based on patients' co-morbidities and the underlying functional capacity of their microbiomes are needed to achieve optimal results.}, } @article {pmid38639049, year = {2024}, author = {Peng, Z and Zhang, J and Zhang, M and Yin, L and Zhou, Z and Lv, C and Wang, Z and Tang, J}, title = {Tryptophan metabolites relieve intestinal Candida albicans infection by altering the gut microbiota to reduce IL-22 release from group 3 innate lymphoid cells of the colon lamina propria.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo00432a}, pmid = {38639049}, issn = {2042-650X}, abstract = {Invasive candidiasis may be caused by Candida albicans (C. albicans) colonization of the intestinal tract. Preventing intestinal damage caused by Candida albicans infection and protecting intestinal barrier function have become a critical issue. Integrated analyses of the microbiome with metabolome revealed a remarkable shift of the gut microbiota and tryptophan metabolites, kynurenic acid (KynA), and indolacrylic acid (IA) in mice infected with C. albicans. The transcriptome sequencing indicated that differentially expressed genes were significantly associated with innate immune responses and inflammatory responses. The results of this study suggest that KynA and IA (KI) can alleviate intestinal damage caused by Candida albicans infection in mice by reducing intestinal permeability, increasing intestinal firmness, alleviating intestinal inflammation, and reducing the secretion of interleukin-22 (IL-22) in the 3 groups of colon innate lymphoid cells (ILC3). We performed a fecal microbiota transplantation (FMT) experiment and found that the intestinal barrier function, inflammation, and IL-22 secretion of ILC3 in the colon lamina propria of the recipient mice subjected to C. albicans infection and KI treatment were consistent with the trends of the donor mice. Our results suggest that tryptophan metabolites may directly regulate colon lamina ILC3 to promote intestinal resistance to C. albicans invasion, or indirectly regulate the ILC3 secretion of IL-22 to play a protective role in the intestinal barrier by affecting intestinal microorganisms, which may become a potential target for alleviating intestine borne C. albicans infection.}, } @article {pmid38638595, year = {2024}, author = {Srikrishnaraj, A and Lanting, BA and Burton, JP and Teeter, MG}, title = {The Microbial Revolution in the World of Joint Replacement Surgery.}, journal = {JB & JS open access}, volume = {9}, number = {2}, pages = {}, pmid = {38638595}, issn = {2472-7245}, abstract = {BACKGROUND: The prevalence of revision surgery due to aseptic loosening and periprosthetic joint infection (PJI) following total hip and knee arthroplasty is growing. Strategies to prevent the need for revision surgery and its associated health-care costs and patient morbidity are needed. Therapies that modulate the gut microbiota to influence bone health and systemic inflammation are a novel area of research.

METHODS: A literature review of preclinical and clinical peer-reviewed articles relating to the role of the gut microbiota in bone health and PJI was performed.

RESULTS: There is evidence that the gut microbiota plays a role in maintaining bone mineral density, which can contribute to osseointegration, osteolysis, aseptic loosening, and periprosthetic fractures. Similarly, the gut microbiota influences gut permeability and the potential for bacterial translocation to the bloodstream, increasing susceptibility to PJI.

CONCLUSIONS: Emerging evidence supports the role of the gut microbiota in the development of complications such as aseptic loosening and PJI after total hip or knee arthroplasty. There is a potential for microbial therapies such as probiotics or fecal microbial transplantation to moderate the risk of developing these complications. However, further investigation is required.

CLINICAL RELEVANCE: Modulation of the gut microbiota may influence patient outcomes following total joint arthroplasty.}, } @article {pmid38637862, year = {2024}, author = {Zhao, H and Zhou, Y and Xu, J and Zhang, Y and Wang, H and Zhao, C and Huang, H and Yang, J and Huang, C and Li, Y and Wang, L and Nie, Y}, title = {Short-chain fatty acid-producing bacterial strains attenuate experimental ulcerative colitis by promoting M2 macrophage polarization via JAK/STAT3/FOXO3 axis inactivation.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {369}, pmid = {38637862}, issn = {1479-5876}, support = {82270577//National Natural Science Foundation of China/ ; 202201020297//Guangzhou Planned Project of Science and Technology/ ; 202201020248,202002020012//Guangzhou Planned Project of Science and Technology/ ; 202102080044//Guangzhou Planned Project of Science and Technology/ ; KY17010003//Guangzhou Key Laboratory of Digestive Diseases (2022-2023)/ ; 2020A1515011000//Natural Science Foundation of Guangdong Province/ ; 2020ZYGXZR024//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Humans ; Mice ; Animals ; *Colitis, Ulcerative/therapy ; RNA, Ribosomal, 16S/genetics/metabolism ; *Gastrointestinal Microbiome ; *Colitis ; *Inflammatory Bowel Diseases ; Fatty Acids, Volatile/adverse effects/metabolism ; Bacteria/metabolism ; Disease Models, Animal ; Inflammation ; Dextran Sulfate/adverse effects ; Mice, Inbred C57BL ; Colon ; Forkhead Box Protein O3/metabolism ; *STAT3 Transcription Factor ; }, abstract = {BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms.

METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays.

RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro.

CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.}, } @article {pmid38635481, year = {2024}, author = {Zambrano, LD and Newhams, MM and Simeone, RM and Payne, AB and Wu, M and Orzel-Lockwood, AO and Halasa, NB and Calixte, JM and Pannaraj, PS and Mongkolrattanothai, K and Boom, JA and Sahni, LC and Kamidani, S and Chiotos, K and Cameron, MA and Maddux, AB and Irby, K and Schuster, JE and Mack, EH and Biggs, A and Coates, BM and Michelson, KN and Bline, KE and Nofziger, RA and Crandall, H and Hobbs, CV and Gertz, SJ and Heidemann, SM and Bradford, TT and Walker, TC and Schwartz, SP and Staat, MA and Bhumbra, SS and Hume, JR and Kong, M and Stockwell, MS and Connors, TJ and Cullimore, ML and Flori, HR and Levy, ER and Cvijanovich, NZ and Zinter, MS and Maamari, M and Bowens, C and Zerr, DM and Guzman-Cottrill, JA and Gonzalez, I and Campbell, AP and Randolph, AG and , }, title = {Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron-Associated Hospitalization in Children and Adolescents - United States, 2021-2023.}, journal = {MMWR. Morbidity and mortality weekly report}, volume = {73}, number = {15}, pages = {330-338}, doi = {10.15585/mmwr.mm7315a2}, pmid = {38635481}, issn = {1545-861X}, mesh = {Humans ; Adolescent ; Child ; United States/epidemiology ; *COVID-19 Vaccines ; *COVID-19/epidemiology/prevention & control ; mRNA Vaccines ; Vaccine Efficacy ; SARS-CoV-2 ; Hospitalization ; RNA, Messenger ; }, abstract = {Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.}, } @article {pmid38635321, year = {2024}, author = {Wang, M and Lkhagva, E and Kim, S and Zhai, C and Islam, MM and Kim, HJ and Hong, ST}, title = {The gut microbe pair of Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270 confers complete protection against SARS-CoV-2 infection by activating CD8+ T cell-mediated immunity.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2342497}, pmid = {38635321}, issn = {1949-0984}, mesh = {Animals ; Cricetinae ; Ruminococcus ; *Gastrointestinal Microbiome ; *COVID-19 ; SARS-CoV-2 ; Clostridiales ; CD8-Positive T-Lymphocytes ; Immunity, Cellular ; }, abstract = {Despite the potential protective role of the gut microbiome against COVID-19, specific microbes conferring resistance to COVID-19 have not yet been identified. In this work, we aimed to identify and validate gut microbes at the species level that provide protection against SARS-CoV-2 infection. To identify gut microbes conferring protection against COVID-19, we conducted a fecal microbiota transplantation (FMT) from an individual with no history of COVID-19 infection or immunization into a lethal COVID-19 hamster model. FMT from this COVID-19-resistant donor resulted in significant phenotypic changes related to COVID-19 sensitivity in the hamsters. Metagenomic analysis revealed distinct differences in the gut microbiome composition among the hamster groups, leading to the identification of two previously unknown bacterial species: Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, both associated with COVID-19 resistance. Subsequently, we conducted a proof-of-concept confirmation animal experiment adhering to Koch's postulates. Oral administration of this gut microbe pair, Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, to the hamsters provided complete protection against SARS-CoV-2 infection through the activation of CD8+ T cell mediated immunity. The prophylactic efficacy of the gut microbe pair against SARS-CoV-2 infection was comparable to, or even superior to, current mRNA vaccines. This strong prophylactic efficacy suggests that the gut microbe pair could be developed as a host-directed universal vaccine for all betacoronaviruses, including potential future emerging viruses.}, } @article {pmid38635003, year = {2024}, author = {Lee, SH and Lee, JH and Lee, SW}, title = {Application of Microbiome-Based Therapies in Chronic Respiratory Diseases.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {}, number = {}, pages = {}, pmid = {38635003}, issn = {1976-3794}, support = {2020R1A2C1008431//National Research Foundation of Korea/ ; 2023R1A2C2006688//National Research Foundation of Korea/ ; RS-2023-00222687//National Research Foundation of Korea/ ; 2022M3A9G8017220//National Research Foundation of Korea/ ; }, abstract = {The application of microbiome-based therapies in various areas of human disease has recently increased. In chronic respiratory disease, microbiome-based clinical applications are considered compelling options due to the limitations of current treatments. The lung microbiome is ecologically dynamic and affected by various conditions, and dysbiosis is associated with disease severity, exacerbation, and phenotype as well as with chronic respiratory disease endotype. However, it is not easy to directly modulate the lung microbiome. Additionally, studies have shown that chronic respiratory diseases can be improved by modulating gut microbiome and administrating metabolites. Although the composition, diversity, and abundance of the microbiome between the gut and lung are considerably different, modulation of the gut microbiome could improve lung dysbiosis. The gut microbiome influences that of the lung via bacterial-derived components and metabolic degradation products, including short-chain fatty acids. This phenomenon might be associated with the cross-talk between the gut microbiome and lung, called gut-lung axis. There are multiple alternatives to modulate the gut microbiome, such as prebiotics, probiotics, and postbiotics ingestion and fecal material transplantation. Several studies have shown that high-fiber diets, for example, present beneficial effects through the production of short-chain fatty acids. Additionally, genetically modified probiotics to secrete some beneficial molecules might also be utilized to treat chronic respiratory diseases. Further studies on microbial modulation to regulate immunity and potentiate conventional pharmacotherapy will improve microbiome modulation techniques, which will develop as a new therapeutic area in chronic respiratory diseases.}, } @article {pmid38631415, year = {2024}, author = {Lee, CYQ and Margolis, KG}, title = {Unlocking the potential of fecal virome transplants (FVT): modulating the gut-brain axis in stress-related disorders.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.04.006}, pmid = {38631415}, issn = {1528-0012}, } @article {pmid38631285, year = {2024}, author = {Kang, X and Lau, HC and Yu, J}, title = {Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy.}, journal = {Cell reports. Medicine}, volume = {5}, number = {4}, pages = {101478}, pmid = {38631285}, issn = {2666-3791}, mesh = {Humans ; *Gastrointestinal Microbiome ; Immunotherapy ; Treatment Outcome ; *Microbiota ; Fecal Microbiota Transplantation ; *Neoplasms ; }, abstract = {Immunotherapy has emerged as a robust approach against cancer, yet its efficacy has varied among individuals, accompanied by the occurrence of immune-related adverse events. As a result, the efficacy of immunotherapy is far from satisfactory, and enormous efforts have been invested to develop strategies to improve patient outcomes. The gut microbiome is now well acknowledged for its critical role in immunotherapy, with better understanding on host-microbes interaction in the context of cancer treatment. Also, an increasing number of trials have been conducted to evaluate the potential and feasibility of microbiome-targeting approaches to enhance efficacy of cancer treatment in patients. Here, the role of the gut microbiome and metabolites (e.g., short-chain fatty acids, tryptophan metabolites) in immunotherapy and the underlying mechanisms are explored. The application of microbiome-targeting approaches that aim to improve immunotherapy efficacy (e.g., fecal microbiota transplantation, probiotics, dietary intervention) is also elaborated, with further discussion on current challenges and suggestions for future research.}, } @article {pmid38628492, year = {2024}, author = {Alghamdi, W and Mosli, M and Alqahtani, SA}, title = {Gut microbiota in MAFLD: therapeutic and diagnostic implications.}, journal = {Therapeutic advances in endocrinology and metabolism}, volume = {15}, number = {}, pages = {20420188241242937}, pmid = {38628492}, issn = {2042-0188}, abstract = {Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic fatty liver disease, is becoming a significant contributor to chronic liver disease globally, surpassing other etiologies, such as viral hepatitis. Prevention and early treatment strategies to curb its growing prevalence are urgently required. Recent evidence suggests that targeting the gut microbiota may help treat and alleviate disease progression in patients with MAFLD. This review aims to explore the complex relationship between MAFLD and the gut microbiota in relation to disease pathogenesis. Additionally, it delves into the therapeutic strategies targeting the gut microbiota, such as diet, exercise, antibiotics, probiotics, synbiotics, glucagon-like peptide-1 receptor agonists, and fecal microbiota transplantation, and discusses novel biomarkers, such as microbiota-derived testing and liquid biopsy, for their diagnostic and staging potential. Overall, the review emphasizes the urgent need for preventive and therapeutic strategies to address the devastating consequences of MAFLD at both individual and societal levels and recognizes that further exploration of the gut microbiota may open avenues for managing MAFLD effectively in the future.}, } @article {pmid38628273, year = {2024}, author = {Hao, L and Yu, Z and Sun, J and Li, Z and Li, J and Deng, Y and Huang, H and Huo, H and Li, H and Huang, L}, title = {Supplementation of Crataegi fructus alleviates functional dyspepsia and restores gut microbiota in mice.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1385159}, pmid = {38628273}, issn = {2296-861X}, abstract = {INTRODUCTION: Functional dyspepsia (FD), also known as non-ulcerative dyspepsia, is a common digestive system disorder.

METHODS: In this study, an FD model was established using hunger and satiety disorders combined with an intraperitoneal injection of L-arginine. Indices used to evaluate the efficacy of hawthorn in FD mice include small intestinal propulsion rate, gastric residual rate, general condition, food intake, amount of drinking water, gastric histopathological examination, and serum nitric oxide (NO) and gastrin levels. Based on the intestinal flora and their metabolites, short-chain fatty acids (SCFAs), the mechanism of action of Crataegi Fructus (hawthorn) on FD was studied. The fecal microbiota transplantation test was used to verify whether hawthorn altered the structure of the intestinal flora.

RESULTS: The results showed that hawthorn improved FD by significantly reducing the gastric residual rate, increasing the intestinal propulsion rate, the intake of food and drinking water, and the levels of gastrointestinal hormones. Simultaneously, hawthorn elevated substance P and 5-hydroxytryptamine expression in the duodenum, reduced serum NO levels, and increased vasoactive intestinal peptide expression in the duodenum. Notably, hawthorn increased the abundance of beneficial bacteria and SCFA-producing bacteria in the intestines of FD mice, decreased the abundance of conditional pathogenic bacteria, and significantly increased the SCFA content in feces.

DISCUSSION: The mechanism by which hawthorn improves FD may be related to the regulation of intestinal flora structure and the production of SCFAs.}, } @article {pmid38626129, year = {2024}, author = {Gong, J and Zhang, Q and Hu, R and Yang, X and Fang, C and Yao, L and Lv, J and Wang, L and Shi, M and Zhang, W and Ma, S and Xiang, H and Zhang, H and Hou, DX and Yin, Y and He, J and Peng, L and Wu, S}, title = {Effects of Prevotella copri on insulin, gut microbiota and bile acids.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2340487}, doi = {10.1080/19490976.2024.2340487}, pmid = {38626129}, issn = {1949-0984}, mesh = {Humans ; Child ; Animals ; Mice ; Insulin ; *Gastrointestinal Microbiome ; *Pediatric Obesity ; Bile Acids and Salts/pharmacology ; Blood Glucose ; *Diabetes Mellitus, Type 2 ; Mice, Obese ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; *Prevotella ; }, abstract = {Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the gut microbiota. However, the underlying mechanism remains unclear. In this study, a significant positive correlation was observed between Prevotella copri (P. copri) and obesity in children (p = 0.003). Next, the effect of P. copri on obesity was explored by using fecal microbiota transplantation (FMT) experiment. Transplantation of P. copri. increased serum levels of fasting blood glucose (p < 0.01), insulin (p < 0.01) and interleukin-1β (IL-1β) (p < 0.05) in high-fat diet (HFD)-induced obese mice, but not in normal mice. Characterization of the gut microbiota indicated that P. copri reduced the relative abundance of the Akkermansia genus in mice (p < 0.01). Further analysis on bile acids (BAs) revealed that P. copri increased the primary BAs and ursodeoxycholic acid (UDCA) in HFD-induced mice (p < 0.05). This study demonstrated for the first time that P. copri has a significant positive correlation with obesity in children, and can increase fasting blood glucose and insulin levels in HFD-fed obese mice, which are related to the abundance of Akkermansia genus and bile acids.}, } @article {pmid37368219, year = {2024}, author = {Tripathi, PR and Srivastava, A}, title = {Approach to a Child with Chronic Diarrhea.}, journal = {Indian journal of pediatrics}, volume = {91}, number = {5}, pages = {472-480}, pmid = {37368219}, issn = {0973-7693}, mesh = {Infant, Newborn ; Child ; Adolescent ; Humans ; *Diarrhea/diagnosis ; *Colonoscopy/adverse effects ; Feces ; Physical Examination/adverse effects ; Chronic Disease ; }, abstract = {Chronic diarrhea in children is challenging both with regards to etiological diagnosis and for management. Etiology and pathophysiological mechanisms vary widely from neonates to adolescents. Congenital or genetic causes are more frequent in neonates, while infections, allergy and immune-mediated mechanisms are more frequent in childhood. A thorough history and proper physical examination are required to decide for further diagnostic evaluation. The approach to a child with chronic diarrhea should be age specific and based predominantly on the pathophysiological mechanism involved. The nature of the stool like watery, bloody or fatty (steatorrhea) can suggest the probable etiology and organ system involved. After routine tests, evaluation with specific serological tests, imaging, endoscopy (gastroscopy/colonoscopy), histopathology of intestinal mucosa, breath tests or radionuclide imaging may be required to make a definitive diagnosis. Genetic evaluation is important in congenital diarrheas, monogenic inflammatory bowel disease (IBD) and immunodeficiency disorders. Management is aimed at stabilization, nutritional support and etiology specific treatment. Specific therapy can be as simple as exclusion of specific nutrient or as complicated as small bowel transplant. Evaluation and management require expertise and thus patients need to be referred in a timely fashion. This will minimise morbidity including nutritional consequences and improve outcome.}, } @article {pmid38625103, year = {2024}, author = {Zhao, Z and Li, C and Huang, J and Yuan, X and Cui, Y and Liu, Y and Zhou, Y and Zhu, Z and Zhang, Z}, title = {Phlorizin Limits Bovine Viral Diarrhea Virus Infection in Mice via Regulating Gut Microbiota Composition.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c01228}, pmid = {38625103}, issn = {1520-5118}, abstract = {Phlorizin (PHZ) is one of the main pharmacologically active ingredients in Lithocarpus polystachyus. We have previously shown that PHZ inhibits the replication of bovine viral diarrhea virus (BVDV), but the exact antiviral mechanism, especially in vivo, is still unknown. Here, we further confirm that PHZ has good protective effects in BVDV-infected mice. We analyzed BVDV-induced CD3[+], CD4[+], and CD8[+] T cells among peripheral blood lymphocytes and found that PHZ significantly restored their percentage. Metagenomic analyses revealed that PHZ markedly improved the richness and diversity of intestinal microbiota and increased the abundance of potentially health-related microbes (families Lachnosipiraceae, Ruminococcaceae, and Oscillospiraceae). Specifically, the relative abundance of short chain fatty acid (SCFA)-producing bacteria, including Lachnospiraceae_UCG-006, unclassified_f_Ruminococcaceae, Oscillibacter, Intestinimonas, Blautia, and Lachnoclostridium increased significantly after PHZ treatment. Interestingly, BVDV-infected mice that received fecal microbiota from PHZ-treated mice (PHZ-FMT) had a significantly lower viral load in the duodenum and jejunum than untreated mice. Pathological lesions of duodenum and jejunum were also greatly reduced in the PHZ-FMT group, confirming a significant antiviral effect. These findings show that gut microbiota play an important role in PHZ's antiviral activity and suggest that their targeted intervention might be a promising endogenous strategy to prevent and control BVDV.}, } @article {pmid38623584, year = {2024}, author = {Qu, B and Zhang, XE and Feng, H and Yan, B and Bai, Y and Liu, S and He, Y}, title = {Microbial perspective on the skin-gut axis and atopic dermatitis.}, journal = {Open life sciences}, volume = {19}, number = {1}, pages = {20220782}, doi = {10.1515/biol-2022-0782}, pmid = {38623584}, issn = {2391-5412}, abstract = {Atopic dermatitis (AD) is a relapsing inflammatory skin condition that has become a global health issue with complex etiology and mounting prevalence. The association of AD with skin and gut microbiota has been revealed by virtue of the continuous development of sequencing technology and genomics analysis. Also, the gut-brain-skin axis and its mutual crosstalk mechanisms have been gradually verified. Accordingly, the microbiota-skin-gut axis also plays an important role in allergic skin inflammation. Herein, we reviewed the relationship between the microbiota-skin-gut axis and AD, explored the underlying signaling molecules and potential pathways, and focused on the potential mechanisms of probiotics, antimicrobial peptides (AMPs), coagulase-negative staphylococci transplantation, fecal microbiota transplantation, AMPs, and addition of essential fatty acids in alleviating AD, with the aim to provide a new perspective for targeting microbiota in the treatment of allergic skin inflammation.}, } @article {pmid38622917, year = {2024}, author = {Lv, C and Cheng, L and Feng, W and Xie, H and Kou, J and Wang, L and Shi, M and Song, X and Wang, X and Chen, S and Xue, L and Zhang, C and Li, X and Zhao, H}, title = {Targeting microbiota-immune-synaptic plasticity to explore the effect of tea polyphenols on improving memory in the aged type 2 diabetic rat model.}, journal = {Nutritional neuroscience}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/1028415X.2024.2341188}, pmid = {38622917}, issn = {1476-8305}, abstract = {OBJECTIVES: The study aimed to explore whether TP could improve memory in the aged type 2 diabetic rat model by regulating microbiota-immune-synaptic plasticity axis.

METHODS: The experiment was divided into two parts. Firstly, to investigate the effects of TP on the physiopathology of the aged T2DM model rats, rats were randomly divided into the Normal control group, the aged group, the Aged T2DM model group, the TP 75, 150, 300 mg/kg groups, the 150 mg/kg Piracetam group and the 3 mg/kg Rosiglitazone group. Then, to further verify whether TP improved memory in aged T2DM rat model by regulating intestinal flora, the fecal microbiota transplantation (FMT) from the rats in the 300 mg/kg TP group into the rats in the aged T2DM model group was carried out. Effects on gut microbiota, colonic integrity (epithelial tight junction proteins), and endotoxemia (serum LPS) were examined, along with synaptic structure, synaptic plasticity-related structural proteins and inflammation signaling of the hippocampus in our study.

RESULTS: Our results demonstrated that TP alleviated memory impairments in the aged T2DM rat model. The specific outcomes were as follows: TP 300 mg/kg corrected the gut dysbacteriosis, alleviated intestinal permeability reduction and peripheral/central inflammation, inhibited the TLR4/NF-κB signaling pathway. Meanwhile, TP improved the synaptic plasticity in the hippocampus of the aged T2DM model rats, whose expressions of SYN, PSD 95, NMDAR1 and GluR1 in hippocampus were significantly up-regulated. Surprisingly, rats of the FMT group displayed the same changes.

DISCUSSION: TP improves the memory in aged T2DM rat model. The mechanism may be related to the alteration of gut flora, which can inhibit hippocampal TLR4/NF-κB signaling to attenuate neuroinflammation, then improve synaptic plasticity. The study proposes that TP interventions aimed at manipulating the gut microbiota may hold great potential as an effective approach for preventing and treating this disease.}, } @article {pmid38624958, year = {2021}, author = {Malhotra, S and Mohandas, S}, title = {Updates and Opinions in Diagnosis and Treatment of Clostridiodes difficile in Pediatrics.}, journal = {Current treatment options in pediatrics}, volume = {7}, number = {4}, pages = {203-216}, pmid = {38624958}, issn = {2198-6088}, abstract = {PURPOSE OF REVIEW: Clostridiodes difficile infection (CDI) has unique challenges for diagnosis and treatment in pediatrics. Though new antibiotics and biologics are being approved or developed for adults, most of the pediatric therapies still rely on multiple or extended antibiotic courses. This review aims to highlight emerging evidence and our clinical experience with CDI in children and can help inform readers' approach to pediatric CDI.

RECENT FINDINGS: Use of fidaxomicin for CDI in pediatrics has been shown to be to be non-inferior to vancomycin and is associated with higher global cure rates and decreased risk of recurrence. Fecal microbiota transplant is a successful emerging therapy with cure rates of up to 90%, though safety alerts should be noted. Diagnostic laboratory testing for C. difficile remains a challenge as it still cannot definitively distinguish between colonization and true infection, and this is particularly relevant to pediatric patients as they have the highest rates of colonization.

SUMMARY: The diagnosis and treatment of C. difficile infection in pediatrics remain challenging and recommendations lag behind advances made in the adult field. Recent data suggests that use of fidaxomicin both as treatment of first episode or recurrences may be beneficial in pediatrics just as in adults. At an experienced center, FMT is associated with high cure rates. Bezlotuxumab a monoclonal antibody to toxin B that is already recommended for use in adults is being studied in children and should be available for clinical use soon. Oral vancomycin prophylaxis is also an emerging strategy for high-risk patients. Finally, a possible vaccine may be on the horizon for pediatrics.}, } @article {pmid38622523, year = {2024}, author = {You, X and Qiu, J and Li, Q and Zhang, Q and Sheng, W and Cao, Y and Fu, W}, title = {Astragaloside IV-PESV inhibits prostate cancer tumor growth by restoring gut microbiota and microbial metabolic homeostasis via the AGE-RAGE pathway.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {472}, pmid = {38622523}, issn = {1471-2407}, support = {82104853//National Natural Science Foundation of China/ ; BAZYY20220703//Shenzhen Bao'an Chinese Medicine Hospital Research Program/ ; 2023-QNRC2-A10//Young Elite Scientists Sponsorship Program by CACM/ ; 2024A1515012209//Project of Guangdong Provincial Department of Science and Technology/ ; 2021JD082//Bao'an District Science and Technology Innovation Bureau Research Program/ ; }, mesh = {Male ; Humans ; Animals ; Mice ; Mice, Nude ; Receptor for Advanced Glycation End Products ; *Gastrointestinal Microbiome ; *Liver Neoplasms ; *Prostatic Neoplasms/drug therapy ; Homeostasis ; *Saponins ; *Triterpenes ; }, abstract = {BACKGROUND: Prostate cancer (PCa) is becoming the most common malignancy in men worldwide. We investigated the effect of astragaloside IV combined with PESV on the gut microbiota and metabolite of PCa mice and the process of treating PCa.

METHODS: Nude mice were genetically modified to develop tumors characteristic of PCa. The treatment of PCa mice involved the administration of a combination of astragaloside IV and peptides derived from scorpion venom (PESV). Feces were collected for both 16 S rDNA and metabolic analysis. Fecal supernatant was extracted and used for fecal transplantation in PCa mice. Tumor development was observed in both PCa mice and nude mice. Tumor histopathology was examined, and the expression of inflammatory factors and the AGE-RAGE axis in PCa tissues were analyzed.

RESULTS: PCa mice treated with Astragaloside IV in combination with PESV showed a significant reduction in tumor volume and weight, and stabilization of gut microbiota and metabolites. At the Genus level, significant differences were observed in Porphyromonas, Corynebacterium, Arthromitus and Blautia, and the differential metabolites were PA16_016_0, Astragaloside+, Vitamin A acid, Nardosinone, a-Nortestoster, D-Pantethine, Hypoxanthine, Pregnenolone, cinnamic acid, Pyridoxa, Cirtruline and Xanthurenate. There was a correlation between gut microbiota and metabolites. After the fecal transplantation, tumor growth was effectively suppressed in the PCa mice. Notably, both the mRNA and protein levels of the receptor for advanced glycation end products (RAGE) were significantly decreased. Furthermore, the expression of inflammatory factors, namely NF-κB, TNF-α, and IL-6, in the tumor tissues was significantly attenuated. Conversely, upregulation of RAGE led to increased inflammation and reversed tumor growth in the mice.

CONCLUSION: Astragaloside IV combined with PESV could treat PCa by intervening in gut microbiota composition and metabolite by targeting RAGE.}, } @article {pmid38621910, year = {2024}, author = {Yu, HC and Meng, YY and Wang, EK and Yuan, JY and Peng, Y and Li, XB}, title = {[Buzhong Yiqi Decoction ameliorates spleen deficiency syndrome by regulating gut microbiota].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {49}, number = {4}, pages = {1028-1043}, doi = {10.19540/j.cnki.cjcmm.20231013.701}, pmid = {38621910}, issn = {1001-5302}, mesh = {Humans ; Mice ; Animals ; *Spleen ; Tumor Necrosis Factor-alpha/pharmacology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Interleukin-2/pharmacology ; Serotonin ; Immunoglobulin A/pharmacology ; }, abstract = {This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1β, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1β, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500＿29＿marine＿group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1β level had a significantly positive correlation with Acinetobacter and CL500＿29＿marine＿group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.}, } @article {pmid38617735, year = {2024}, author = {Wang, MY and Sang, LX and Sun, SY}, title = {Gut microbiota and female health.}, journal = {World journal of gastroenterology}, volume = {30}, number = {12}, pages = {1655-1662}, pmid = {38617735}, issn = {2219-2840}, mesh = {Female ; Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; *Breast Neoplasms ; *Endometriosis ; Estrogens ; }, abstract = {The gut microbiota is recognized as an endocrine organ with the capacity to influence distant organs and associated biological pathways. Recent advancements underscore the critical role of gut microbial homeostasis in female health; with dysbiosis potentially leading to diseases among women such as polycystic ovarian syndrome, endometriosis, breast cancer, cervical cancer, and ovarian cancer etc. Despite this, there has been limited discussion on the underlying mechanisms. This editorial explores the three potential mechanisms through which gut microbiota dysbiosis may impact the development of diseases among women, namely, the immune system, the gut microbiota-estrogen axis, and the metabolite pathway. We focused on approaches for treating diseases in women by addressing gut microbiota imbalances through probiotics, prebiotics supplementation, and fecal microbiota transplantation (FMT). Future studies should focus on determining the molecular mechanisms underlying associations between dysbiosis of gut microbiota and female diseases to realize precision medicine, with FMT emerging as a promising intervention.}, } @article {pmid38617537, year = {2024}, author = {Yu, X and Li, W and Li, Z and Wu, Q and Sun, S}, title = {Influence of Microbiota on Tumor Immunotherapy.}, journal = {International journal of biological sciences}, volume = {20}, number = {6}, pages = {2264-2294}, pmid = {38617537}, issn = {1449-2288}, mesh = {Humans ; Immunotherapy ; *Microbiota ; *Probiotics/therapeutic use ; *Neoplasms/therapy ; }, abstract = {The role of the microbiome in immunotherapy has recently garnered substantial attention, with molecular studies and clinical trials providing emerging evidence on the pivotal influence of the microbiota in enhancing therapeutic outcomes via immune response modulation. However, the impact of microbial communities can considerably vary across individuals and different immunotherapeutic approaches, posing prominent challenges in harnessing their potential. In this comprehensive review, we outline the current research applications in tumor immunotherapy and delve into the possible mechanisms through which immune function is influenced by microbial communities in various body sites, encompassing those in the gut, extraintestinal barrier, and intratumoral environment. Furthermore, we discuss the effects of diverse microbiome-based strategies, including probiotics, prebiotics, fecal microbiota transplantation, and the targeted modulation of specific microbial taxa, and antibiotic treatments on cancer immunotherapy. All these strategies potentially have a profound impact on immunotherapy and pave the way for personalized therapeutic approaches and predictive biomarkers.}, } @article {pmid38617453, year = {2024}, author = {Chen, SJ and Zhang, DY and Wu, X and Zhang, FM and Cui, BT and Huang, YH and Zhang, ZL and Wang, R and Bai, FH}, title = {Washed microbiota transplantation for Crohn's disease: A metagenomic, metatranscriptomic, and metabolomic-based study.}, journal = {World journal of gastroenterology}, volume = {30}, number = {11}, pages = {1572-1587}, pmid = {38617453}, issn = {2219-2840}, mesh = {Humans ; Amino Acids ; *Antifibrinolytic Agents ; *Crohn Disease/diagnosis/therapy ; Escherichia coli ; Metagenome ; *Microbiota ; Prospective Studies ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapeutic approach for treating Crohn's disease (CD). The new method of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT). Most existing studies have focused on observing the clinical phenomena. However, the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome, metatranscriptome, and metabolome-has not yet been reported.

AIM: To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT.

METHODS: We conducted a prospective, open-label, single-center clinical study. Eleven CD patients underwent WMT. Their clinical responses (defined as a decrease in their CD Activity Index score of > 100 points) and their microbiome (metagenome, metatranscriptome) and metabolome profiles were evaluated three months after the procedure.

RESULTS: Seven of the 11 patients (63.6%) showed an optimal clinical response three months post-WMT. Gut microbiome diversity significantly increased after WMT, consistent with improved clinical symptoms. Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. In addition, metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors. However, levels of vital amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) were reduced after WMT.

CONCLUSION: WMT demonstrated therapeutic efficacy in CD treatment, likely due to the effective reconstruction of the patient's microbiome. Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.}, } @article {pmid38617293, year = {2024}, author = {Joldrichsen, MR and Kim, E and Steiner, HE and Jeong, YJ and Premanandan, C and Hsueh, W and Ziouzenkova, O and Cormet-Boyaka, E and Boyaka, PN}, title = {Loss of Paneth cells dysregulates gut ILC subsets and enhances weight gain response to high fat diet in a mouse model.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.29.587349}, pmid = {38617293}, abstract = {Obesity has been associated with dysbiosis, but innate mechanisms linking intestinal epithelial cell subsets and obesity remain poorly understood. Using mice lacking Paneth cells (Sox9 [ΔIEC] mice), small intestinal epithelial cells specialized in the production of antimicrobial products and cytokines, we show that dysbiosis alone does not induce obesity or metabolic disorders. Loss of Paneth cells reduced ILC3 and increased ILC2 numbers in the intestinal lamina propria. High-fat diet (HFD) induced higher weight gain and more severe metabolic disorders in Sox9 [ΔIEC] mice. Further, HFD enhances the number of ILC1 in the intestinal lamina propria of Sox9 [ΔIEC] mice and increases intestinal permeability and the accumulation of immune cells (inflammatory macrophages and T cells, and B cells) in abdominal fat tissues of obese Sox9 [ΔIEC] . Transplantation of fecal materials from Sox9 [ΔIEC] mice in germ-free mice before HFD further confirmed the regulatory role of Paneth cells for gut ILC subsets and the development of obesity.}, } @article {pmid38616586, year = {2024}, author = {Joshi, B and Yadav, SK and Shakya Hada, MS and Shrestha, S and Shrestha, KK and Shrestha, PC and Awal, BK}, title = {Post-Transplant Fecal Carriage of Antibiotic Resistant and B-Lactamases-Producing Enterobacteriales among Renal Transplant Recipients.}, journal = {Journal of Nepal Health Research Council}, volume = {21}, number = {4}, pages = {578-586}, doi = {10.33314/jnhrc.v21i4.4801}, pmid = {38616586}, issn = {1999-6217}, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Ceftazidime ; Transplant Recipients ; *Kidney Transplantation ; Escherichia coli ; Nepal ; beta-Lactamases ; Klebsiella ; }, abstract = {BACKGROUND: The intestinal colonization and transmission of antibiotic-resistant Enterobacteriales to renal transplant recipients may pose a threat to them because they are profoundly immunocompromised and vulnerable to infection. Hence, it is crucial to identify these antibiotic-resistant fecal Enterobacteriales harboring high-risk populations. The objective of this study was to determine antibiotic resistance as well as β-lactamases production in fecal Enterobacteriales among renal transplant recipients.

METHODS: The stool samples, one collected from each transplant recipient, were processed for isolation and identification of Enterobacteriales and were tested for their antibiotic susceptibility, extended-spectrum β-lactamase, and metallo-β-lactamase production by standard methods.

RESULTS: A total of 103 Enterobacteriales comprising of Escherichia coli (86.4%), Klebsiella species (11.7%), and Citrobacter species (1.9%) were isolated and more than 60% of the E. coli were found resistant to ceftazidime and ciprofloxacin and around half of the Klebsiella species were resistant to ceftazidime and fluroquinolones. The extended-spectrum β-lactamase production was seen in 3.4% and 8.3% and metallo-β-lactamase production in 24.7% and 33.3% of E. coli and Klebsiella species, respectively. The high proportion of β-lactamase-producers were resistant to piperacillin-tazobactam, meropenem, gentamicin, and amikacin than β-lactamases non-producers.

CONCLUSION: Since the antibiotic resistance is higher in fecal Enterobacteriales, each renal transplant recipient should be screened for these highly resistant intestinal colonizers after transplantation in order to prevent infections and to reduce the rate of transplant failure due to infections.}, } @article {pmid38613431, year = {2024}, author = {Lee, MA and Questa, M and Wanakumjorn, P and Kol, A and McLaughlin, B and Weimer, BC and Buono, A and Suchodolski, JS and Marsilio, S}, title = {Safety profile and effects on the peripheral immune response of fecal microbiota transplantation in clinically healthy dogs.}, journal = {Journal of veterinary internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1111/jvim.17061}, pmid = {38613431}, issn = {1939-1676}, support = {//2022 Comparative Gastroenterology Society (CGS)/IDEXX Veterinary Student Summer Scholar Award/ ; NCI P30 CA093373 (Comprehensive Cancer Center), S10 OD018223 (Astrios Cell Sorter), S10 RR 026825 (Fortessa Cytometer)//University of California Davis Flow Cytometry Shared Resource Laboratory/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used for gastrointestinal and extra-gastrointestinal diseases in veterinary medicine. However, its effects on immune responses and possible adverse events have not been systematically investigated.

HYPOTHESIS/OBJECTIVES: Determine the short-term safety profile and changes in the peripheral immune system after a single FMT administration in healthy dogs.

ANIMALS: Ten client-owned, clinically healthy dogs as FMT recipients, and 2 client-owned clinically healthy dogs as FMT donors.

METHODS: Prospective non-randomized clinical trial. A single rectal enema of 5 g/kg was given to clinically healthy canine recipients. During the 28 days after FMT administration, owners self-reported adverse events and fecal scores. On Days 0 (baseline), 1, 4, 10, and 28 after FMT, fecal and blood samples were collected. The canine fecal dysbiosis index (DI) was calculated using qPCR.

RESULTS: No significant changes were found in the following variables: CBC, serum biochemistry, C-reactive protein, serum cytokines (interleukins [IL]-2, -6, -8, tumor necrosis factor [TNF]-α), peripheral leukocytes (B cells, T cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, T regulatory cells), and the canine DI. Mild vomiting (n = 3), diarrhea (n = 4), decreased activity (n = 2), and inappetence (n = 1) were reported, and resolved without intervention.

Fecal microbiota transplantation did not significantly alter the evaluated variables and recipients experienced minimal adverse events associated with FMT administration. Fecal microbiota transplantation was not associated with serious adverse events, changes in peripheral immunologic variables, or the canine DI in the short-term.}, } @article {pmid38613119, year = {2024}, author = {Zhou, Y and Zeng, Y and Wang, R and Pang, J and Wang, X and Pan, Z and Jin, Y and Chen, Y and Yang, Y and Ling, W}, title = {Resveratrol Improves Hyperuricemia and Ameliorates Renal Injury by Modulating the Gut Microbiota.}, journal = {Nutrients}, volume = {16}, number = {7}, pages = {}, pmid = {38613119}, issn = {2072-6643}, support = {81730090//National Natural Science Foundation of China/ ; 81973022//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Mice ; *Hyperuricemia/drug therapy ; *Gastrointestinal Microbiome ; Resveratrol/pharmacology ; Uric Acid ; Kidney Tubules ; Inflammation ; }, abstract = {Resveratrol (RES) has been reported to prevent hyperuricemia (HUA); however, its effect on intestinal uric acid metabolism remains unclear. This study evaluated the impact of RES on intestinal uric acid metabolism in mice with HUA induced by a high-fat diet (HFD). Moreover, we revealed the underlying mechanism through metagenomics, fecal microbiota transplantation (FMT), and 16S ribosomal RNA analysis. We demonstrated that RES reduced the serum uric acid, creatinine, urea nitrogen, and urinary protein levels, and improved the glomerular atrophy, unclear renal tubule structure, fibrosis, and renal inflammation. The results also showed that RES increased intestinal uric acid degradation. RES significantly changed the intestinal flora composition of HFD-fed mice by enriching the beneficial bacteria that degrade uric acid, reducing harmful bacteria that promote inflammation, and improving microbial function via the upregulation of purine metabolism. The FMT results further showed that the intestinal microbiota is essential for the effect of RES on HUA, and that Lactobacillus may play a key role in this process. The present study demonstrated that RES alleviates HFD-induced HUA and renal injury by regulating the gut microbiota composition and the metabolism of uric acid.}, } @article {pmid38613109, year = {2024}, author = {Byerley, LO and Lorenzen, B and Chang, HM and Hartman, WG and Keenan, MJ and Page, R and Luo, M and Dowd, SE and Taylor, CM}, title = {Gut Microbial Dysbiosis Differs in Two Distinct Cachectic Tumor-Bearing Models Consuming the Same Diet.}, journal = {Nutrients}, volume = {16}, number = {7}, pages = {}, pmid = {38613109}, issn = {2072-6643}, support = {no number//American Institute for Cancer Research/ ; no number//California Walnut Commission/ ; }, mesh = {Male ; Animals ; Rats ; Cachexia/etiology ; Dysbiosis ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Diet ; *Sarcoma ; *Juglans ; }, abstract = {The impact of cancer cachexia on the colonic microbiota is poorly characterized. This study assessed the effect of two cachectic-producing tumor types on the gut microbiota to determine if a similar dysbiosis could be found. In addition, it was determined if a diet containing an immunonutrient-rich food (walnuts) known to promote the growth of probiotic bacteria in the colon could alter the dysbiosis and slow cachexia. Male Fisher 344 rats were randomly assigned to a semi-purified diet with or without walnuts. Then, within each diet group, rats were further assigned randomly to a treatment group: tumor-bearing ad libitum fed (TB), non-tumor-bearing ad libitum fed (NTB-AL), and non-tumor-bearing group pair-fed to the TB (NTB-PF). The TB group was implanted either with the Ward colon carcinoma or MCA-induced sarcoma, both transplantable tumor lines. Fecal samples were collected after the development of cachexia, and bacteria species were identified using 16S rRNA gene analysis. Both TB groups developed cachexia but had a differently altered gut microbiome. Beta diversity was unaffected by treatment (NTB-AL, TB, and NTB-PF) regardless of tumor type but was affected by diet. Also, diet consistently changed the relative abundance of several bacteria taxa, while treatment and tumor type did not. The control diet increased the abundance of A. Anaeroplasma, while the walnut diet increased the genus Ruminococcus. There were no common fecal bacterial changes characteristic of cachexia found. Diet consistently changed the gut microbiota, but these changes were insufficient to slow the progression of cachexia, suggesting cancer cachexia is more complex than a few gut microbiota shifts.}, } @article {pmid38613058, year = {2024}, author = {Lombardi, M and Troisi, J and Motta, BM and Torre, P and Masarone, M and Persico, M}, title = {Gut-Liver Axis Dysregulation in Portal Hypertension: Emerging Frontiers.}, journal = {Nutrients}, volume = {16}, number = {7}, pages = {}, pmid = {38613058}, issn = {2072-6643}, mesh = {Humans ; *Esophageal and Gastric Varices ; Gastrointestinal Hemorrhage ; *Hypertension, Portal/etiology ; Ascites ; }, abstract = {Portal hypertension (PH) is a complex clinical challenge with severe complications, including variceal bleeding, ascites, hepatic encephalopathy, and hepatorenal syndrome. The gut microbiota (GM) and its interconnectedness with human health have emerged as a captivating field of research. This review explores the intricate connections between the gut and the liver, aiming to elucidate how alterations in GM, intestinal barrier function, and gut-derived molecules impact the development and progression of PH. A systematic literature search, following PRISMA guidelines, identified 12 original articles that suggest a relationship between GM, the gut-liver axis, and PH. Mechanisms such as dysbiosis, bacterial translocation, altered microbial structure, and inflammation appear to orchestrate this relationship. One notable study highlights the pivotal role of the farnesoid X receptor axis in regulating the interplay between the gut and liver and proposes it as a promising therapeutic target. Fecal transplantation experiments further emphasize the pathogenic significance of the GM in modulating liver maladies, including PH. Recent advancements in metagenomics and metabolomics have expanded our understanding of the GM's role in human ailments. The review suggests that addressing the unmet need of identifying gut-liver axis-related metabolic and molecular pathways holds potential for elucidating pathogenesis and directing novel therapeutic interventions.}, } @article {pmid38609760, year = {2024}, author = {Mullish, BH and Merrick, B and Quraishi, MN and Bak, A and Green, CA and Moore, DJ and Porter, RJ and Elumogo, NT and Segal, JP and Sharma, N and Marsh, B and Kontkowski, G and Manzoor, SE and Hart, AL and Settle, C and Keller, JJ and Hawkey, P and Iqbal, TH and Goldenberg, SD and Williams, HRT}, title = {The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.}, journal = {The Journal of hospital infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhin.2024.03.001}, pmid = {38609760}, issn = {1532-2939}, abstract = {The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.}, } @article {pmid38609165, year = {2024}, author = {Mullish, BH and Merrick, B and Quraishi, MN and Bak, A and Green, CA and Moore, DJ and Porter, RJ and Elumogo, NT and Segal, JP and Sharma, N and Marsh, B and Kontkowski, G and Manzoor, SE and Hart, AL and Settle, C and Keller, JJ and Hawkey, P and Iqbal, TH and Goldenberg, SD and Williams, HRT}, title = {The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2023-331550}, pmid = {38609165}, issn = {1468-3288}, abstract = {The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.}, } @article {pmid38608743, year = {2024}, author = {Yang, X and Zhou, Y and Tan, S and Tian, X and Meng, X and Li, Y and Zhou, B and Zhao, G and Ge, X and He, C and Cheng, W and Zhang, Y and Zheng, K and Yin, K and Yu, Y and Pan, W}, title = {Alterations in gut microbiota contribute to cognitive deficits induced by chronic infection of Toxoplasma gondii.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2024.04.008}, pmid = {38608743}, issn = {1090-2139}, abstract = {Chronic infection with Toxoplasma gondii (T. gondii) emerges as a risk factor for neurodegenerative diseases in animals and humans. However, the underlying mechanisms are largely unknown. We aimed to investigate whether gut microbiota and its metabolites play a role in T. gondii-induced cognitive deficits. We found that T. gondii infection induced cognitive deficits in mice, which was characterized by synaptic ultrastructure impairment and neuroinflammation in the hippocampus. Moreover, the infection led to gut microbiota dysbiosis, barrier integrity impairment, and inflammation in the colon. Interestingly, broad-spectrum antibiotic ablation of gut microbiota attenuated the adverse effects of the parasitic infection on the cognitive function in mice; cognitive deficits and hippocampal pathological changes were transferred from the infected mice to control mice by fecal microbiota transplantation. In addition, the abundance of butyrate-producing bacteria and the production of serum butyrate were decreased in infected mice. Interestingly, dietary supplementation of butyrate ameliorated T. gondii-induced cognitive impairment in mice. Notably, compared to the healthy controls, the decreased butyrate production was negatively correlated with the levels of anti-T. gondii IgG antibody in the serum of human subjects. Overall, this study demonstrates that gut microbiota is a key regulator of T. gondii-induced cognitive impairment.}, } @article {pmid38608488, year = {2024}, author = {Bai, X and Deng, J and Duan, Z and Fu, R and Zhu, C and Fan, D}, title = {Ginsenoside Rh4 alleviates gastrointestinal mucositis and enhances chemotherapy efficacy through modulating gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {128}, number = {}, pages = {155577}, doi = {10.1016/j.phymed.2024.155577}, pmid = {38608488}, issn = {1618-095X}, abstract = {BACKGROUND: Gastrointestinal mucositis stands as one of the most severe side effects of irinotecan (CPT-11). however, only palliative treatment is available at present. Therefore, there is an urgent need for adjunctive medications to alleviate the side effects of CPT-11.

PURPOSE: In this study, our objective was to explore whether ginsenoside Rh4 could serve as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, thereby alleviating the side effects of CPT-11 and augmenting its anti-tumor efficacy.

STUDY DESIGN: A CPT-11-induced gastrointestinal mucositis model was used to investigate whether ginsenoside Rh4 alleviated CPT-11-induced gastrointestinal mucositis and enhanced the anti-tumor activity of CPT-11.

METHODS: In this study, we utilized CT26 cells to establish a xenograft tumor model, employing transcriptomics, genomics, and metabolomics techniques to investigate the impact of ginsenoside Rh4 on CPT-11-induced gastrointestinal mucositis and the effect on the anti-tumor activity of CPT-11. Furthermore, we explored the pivotal role of gut microbiota and their metabolites through fecal microbiota transplantation (FMT) experiments and supplementation of the key differential metabolite, hyodeoxycholic acid (HDCA).

RESULTS: The results showed that ginsenoside Rh4 repaired the impairment of intestinal barrier function and restored intestinal mucosal homeostasis in a gut microbiota-dependent manner. Ginsenoside Rh4 treatment modulated gut microbiota diversity and upregulated the abundance of beneficial bacteria, especially Lactobacillus_reuteri and Akkermansia_muciniphila, which further regulated bile acid biosynthesis, significantly promoted the production of the beneficial secondary bile acid hyodeoxycholic acid (HDCA), thereby alleviating CPT-11-induced gut microbiota dysbiosis. Subsequently, ginsenoside Rh4 further alleviated gastrointestinal mucositis through the TGR5-TLR4-NF-κB signaling pathway. On the other hand, ginsenoside Rh4 combination therapy could further reduce the weight and volume of colon tumors, promote tumor cell apoptosis, and enhance the anti-tumor activity of CPT-11 by inhibiting the PI3K-Akt signaling pathway, thus exerting a synergistic anti-tumor effect.

CONCLUSION: In summary, our findings confirm that ginsenoside Rh4 can alleviate CPT-11-induced gastrointestinal mucositis and enhance the anti-tumor activity of CPT-11 by modulating gut microbiota and its related metabolites. Our study validates the potential of ginsenoside Rh4 as a modulator of the gut microbiota and an adjunctive agent for chemotherapy, offering new therapeutic strategies for addressing chemotherapy side effects and improving chemotherapy efficacy.}, } @article {pmid38608440, year = {2024}, author = {Zhang, W and Ling, J and Xu, B and Wang, J and Chen, Z and Li, G}, title = {Gut microbiome-mediated monocytes promote liver metastasis.}, journal = {International immunopharmacology}, volume = {133}, number = {}, pages = {111877}, doi = {10.1016/j.intimp.2024.111877}, pmid = {38608440}, issn = {1878-1705}, abstract = {The gut microbiome plays an important role in tumor growth by regulating immune cell function. However, the role of the gut microbiome-mediated monocytes in liver metastasis remains unclear. In this study, we found that fecal microbiome transplantation (FMT) from the stool of patients with liver metastasis (LM) significantly promoted liver metastasis compared with healthy donors (HD). Monocytes were upregulated in liver tissues by the CCL2/CCR2 axis in LM patients' stool transplanted mouse model. CCL2/CCR2 inhibition and monocyte depletion significantly suppress liver metastasis. FMT using LM patients' stool enhanced the plasma lipopolysaccharides (LPS) concentration. The LPS/TLR4 signaling pathway is crucial for gut microbiome-mediated liver metastasis. These results indicated that monocytes contribute to liver metastasis via the CCL2/CCR2 axis.}, } @article {pmid38604201, year = {2024}, author = {Bethlehem, L and Estevinho, MM and Grinspan, A and Magro, F and Faith, JJ and Colombel, JF}, title = {Microbiota therapeutics for inflammatory bowel disease: the way forward.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {9}, number = {5}, pages = {476-486}, doi = {10.1016/S2468-1253(23)00441-7}, pmid = {38604201}, issn = {2468-1253}, abstract = {Microbiota therapeutics that transplant faecal material from healthy donors to people with mild-to-moderate ulcerative colitis have shown the potential to induce remission in about 30% of participants in small, phase 2 clinical trials. Despite this substantial achievement, the field needs to leverage the insights gained from these trials and progress towards phase 3 clinical trials and drug approval, while identifying the distinct clinical niche for this new therapeutic modality within inflammatory bowel disease (IBD) therapeutics. We describe the lessons that can be learned from past studies of microbiota therapeutics, from full spectrum donor stool to defined products manufactured in vitro. We explore the actionable insights these lessons provide on the design of near-term studies and future trajectories for the integration of microbiota therapeutics in the treatment of IBD. If successful, microbiota therapeutics will provide a powerful orthogonal approach (complementing or in combination with existing immunomodulatory drugs) to raise the therapeutic ceiling for the many non-responders and partial responders within the IBD patient population.}, } @article {pmid38604200, year = {2024}, author = {Porcari, S and Fusco, W and Spivak, I and Fiorani, M and Gasbarrini, A and Elinav, E and Cammarota, G and Ianiro, G}, title = {Fine-tuning the gut ecosystem: the current landscape and outlook of artificial microbiome therapeutics.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {9}, number = {5}, pages = {460-475}, doi = {10.1016/S2468-1253(23)00357-6}, pmid = {38604200}, issn = {2468-1253}, abstract = {The gut microbiome is acknowledged as a key determinant of human health, and technological progress in the past two decades has enabled the deciphering of its composition and functions and its role in human disorders. Therefore, manipulation of the gut microbiome has emerged as a promising therapeutic option for communicable and non-communicable disorders. Full exploitation of current therapeutic microbiome modulators (including probiotics, prebiotics, and faecal microbiota transplantation) is hindered by several factors, including poor precision, regulatory and safety issues, and the impossibility of providing reproducible and targeted treatments. Artificial microbiota therapeutics (which include a wide range of products, such as microbiota consortia, bacteriophages, bacterial metabolites, and engineered probiotics) have appeared as an evolution of current microbiota modulators, as they promise safe and reproducible effects, with variable levels of precision via different pathways. We describe the landscape of artificial microbiome therapeutics, from those already on the market to those still in the pipeline, and outline the major challenges for positioning these therapeutics in clinical practice.}, } @article {pmid38599497, year = {2024}, author = {Xu, Q and Sun, L and Chen, Q and Jiao, C and Wang, Y and Li, H and Xie, J and Zhu, F and Wang, J and Zhang, W and Xie, L and Wu, H and Zuo, Z and Chen, X}, title = {Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model.}, journal = {Brain, behavior, and immunity}, volume = {119}, number = {}, pages = {220-235}, doi = {10.1016/j.bbi.2024.04.002}, pmid = {38599497}, issn = {1090-2139}, abstract = {Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.}, } @article {pmid38599474, year = {2024}, author = {Wang, H and Zhou, L and Zheng, Q and Song, Y and Huang, W and Yang, L and Xiong, Y and Cai, Z and Chen, Y and Yuan, J}, title = {Kai-Xin-San improves cognitive impairment in D-gal and Aβ25-35 induced AD rats by regulating gut microbiota and reducing neuronal damage.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {118161}, doi = {10.1016/j.jep.2024.118161}, pmid = {38599474}, issn = {1872-7573}, abstract = {Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood.

AIM OF THE STUDY: To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota.

MATERIALS AND METHODS: AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aβ25-35. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl & HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments.

RESULTS: KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant.

CONCLUSION: KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.}, } @article {pmid38599367, year = {2024}, author = {Svačina, MKR and Gao, T and Sprenger-Svačina, A and Lin, J and Ganesh, BP and Lee, J and McCullough, LD and Sheikh, KA and Zhang, G}, title = {Rejuvenating fecal microbiota transplant enhances peripheral nerve repair in aged mice by modulating endoneurial inflammation.}, journal = {Experimental neurology}, volume = {376}, number = {}, pages = {114774}, doi = {10.1016/j.expneurol.2024.114774}, pmid = {38599367}, issn = {1090-2430}, abstract = {Peripheral nerve injury (PNI) resulting from trauma or neuropathies can cause significant disability, and its prognosis deteriorates with age. Emerging evidence suggests that gut dysbiosis and reduced fecal short-chain fatty acids (SCFAs) contribute to an age-related systemic hyperinflammation (inflammaging), which hinders nerve recovery after injury. This study thus aimed to evaluate the pro-regenerative effects of a rejuvenating fecal microbiota transplant (FMT) in a preclinical PNI model using aged mice. Aged C57BL/6 mice underwent bilateral crush injuries to their sciatic nerves. Subsequently, they either received FMT from young donors at three and four days after the injury or retained their aged gut microbiota. We analyzed gut microbiome composition and SCFA concentrations in fecal samples. The integrity of the ileac mucosal barrier was assessed by immunofluorescence staining of Claudin-1. Flow cytometry was utilized to examine immune cells and cytokine production in the ileum, spleen, and sciatic nerve. Various assessments, including behavioural tests, electrophysiological studies, and morphometrical analyses, were conducted to evaluate peripheral nerve function and repair following injury. Rejuvenating FMT reversed age-related gut dysbiosis by increasing Actinobacteria, especially Bifidobacteriales genera. This intervention also led to an elevation of gut SCFA levels and mitigated age-related ileac mucosal leakiness in aged recipients. Additionally, it augmented the number of T-helper 2 (Th2) and regulatory T (Treg) cells in the ileum and spleen, with the majority being positive for anti-inflammatory interleukin-10 (IL-10). In sciatic nerves, rejuvenating FMT resulted in increased M2 macrophage counts and a higher IL-10 production by IL-10[+]TNF-α[-] M2 macrophage subsets. Ultimately, restoring a youthful gut microbiome in aged mice led to improved nerve repair and enhanced functional recovery after PNI. Considering that FMT is already a clinically available technique, exploring novel translational strategies targeting the gut microbiome to enhance nerve repair in the elderly seems promising and warrants further evaluation.}, } @article {pmid38598636, year = {2024}, author = {Sizemore, N and Oliphant, K and Zheng, R and Martin, CR and Claud, EC and Chattopadhyay, I}, title = {A digital twin of the infant microbiome to predict neurodevelopmental deficits.}, journal = {Science advances}, volume = {10}, number = {15}, pages = {eadj0400}, pmid = {38598636}, issn = {2375-2548}, mesh = {Infant ; Humans ; Infant, Newborn ; Infant, Premature ; Artificial Intelligence ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Feces ; }, abstract = {Despite the recognized gut-brain axis link, natural variations in microbial profiles between patients hinder definition of normal abundance ranges, confounding the impact of dysbiosis on infant neurodevelopment. We infer a digital twin of the infant microbiome, forecasting ecosystem trajectories from a few initial observations. Using 16S ribosomal RNA profiles from 88 preterm infants (398 fecal samples and 32,942 abundance estimates for 91 microbial classes), the model (Q-net) predicts abundance dynamics with R[2] = 0.69. Contrasting the fit to Q-nets of typical versus suboptimal development, we can reliably estimate individual deficit risk (Mδ) and identify infants achieving poor future head circumference growth with ≈76% area under the receiver operator characteristic curve, 95% ± 1.8% positive predictive value at 98% specificity at 30 weeks postmenstrual age. We find that early transplantation might mitigate risk for ≈45.2% of the cohort, with potentially negative effects from incorrect supplementation. Q-nets are generative artificial intelligence models for ecosystem dynamics, with broad potential applications.}, } @article {pmid38593970, year = {2024}, author = {Seida, I and Al Shawaf, M and Mahroum, N}, title = {Fecal microbiota transplantation in autoimmune diseases - An extensive paper on a pathogenetic therapy.}, journal = {Autoimmunity reviews}, volume = {}, number = {}, pages = {103541}, doi = {10.1016/j.autrev.2024.103541}, pmid = {38593970}, issn = {1873-0183}, abstract = {The role of infections in the pathogenesis of autoimmune diseases has long been recognized and reported. In addition to infectious agents, the internal composition of the "friendly" living bacteria, (microbiome) and its correlation to immune balance and dysregulation have drawn the attention of researchers for decades. Nevertheless, only recently, scientific papers regarding the potential role of transferring microbiome from healthy donor subjects to patients with autoimmune diseases has been proposed. Fecal microbiota transplantation or FMT, carries the logic of transferring microorganisms responsible for immune balance from healthy donors to individuals with immune dysregulation or more accurately for our paper, autoimmune diseases. Viewing the microbiome as a pathogenetic player allows us to consider FMT as a pathogenetic-based treatment. Promising results alongside improved outcomes have been demonstrated in patients with different autoimmune diseases following FMT. Therefore, in our current extensive review, we aimed to highlight the implication of FMT in various autoimmune diseases, such as inflammatory bowel disease, autoimmune thyroid and liver diseases, systemic lupus erythematosus, and type 1 diabetes mellitus, among others. Presenting all the aspects of FMT in more than 12 autoimmune diseases in one paper, to the best of our knowledge, is the first time presented in medical literature. Viewing FMT as such could contribute to better understanding and newer application of the model in the therapy of autoimmune diseases, indeed.}, } @article {pmid38591915, year = {2024}, author = {Bratkovič, T and Zahirović, A and Bizjak, M and Rupnik, M and Štrukelj, B and Berlec, A}, title = {New treatment approaches for Clostridioides difficile infections: alternatives to antibiotics and fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2337312}, pmid = {38591915}, issn = {1949-0984}, mesh = {Humans ; Anti-Bacterial Agents/therapeutic use/pharmacology ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Vancomycin/pharmacology ; *Clostridium Infections/drug therapy/prevention & control ; }, abstract = {Clostridioides difficile causes a range of debilitating intestinal symptoms that may be fatal. It is particularly problematic as a hospital-acquired infection, causing significant costs to the health care system. Antibiotics, such as vancomycin and fidaxomicin, are still the drugs of choice for C. difficile infections, but their effectiveness is limited, and microbial interventions are emerging as a new treatment option. This paper focuses on alternative treatment approaches, which are currently in various stages of development and can be divided into four therapeutic strategies. Direct killing of C. difficile (i) includes beside established antibiotics, less studied bacteriophages, and their derivatives, such as endolysins and tailocins. Restoration of microbiota composition and function (ii) is achieved with fecal microbiota transplantation, which has recently been approved, with standardized defined microbial mixtures, and with probiotics, which have been administered with moderate success. Prevention of deleterious effects of antibiotics on microbiota is achieved with agents for the neutralization of antibiotics that act in the gut and are nearing regulatory approval. Neutralization of C. difficile toxins (iii) which are crucial virulence factors is achieved with antibodies/antibody fragments or alternative binding proteins. Of these, the monoclonal antibody bezlotoxumab is already in clinical use. Immunomodulation (iv) can help eliminate or prevent C. difficile infection by interfering with cytokine signaling. Small-molecule agents without bacteriolytic activity are usually selected by drug repurposing and can act via a variety of mechanisms. The multiple treatment options described in this article provide optimism for the future treatment of C. difficile infection.}, } @article {pmid37823484, year = {2024}, author = {Straub, TJ and Lombardo, MJ and Bryant, JA and Diao, L and Lodise, TP and Freedberg, DE and Wortman, JR and Litcofsky, KD and Hasson, BR and McGovern, BH and Ford, CB and Henn, MR}, title = {Impact of a Purified Microbiome Therapeutic on Abundance of Antimicrobial Resistance Genes in Patients With Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {78}, number = {4}, pages = {833-841}, pmid = {37823484}, issn = {1537-6591}, support = {//Seres Therapeutics/ ; }, mesh = {Adult ; Humans ; Female ; Aged ; Male ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; *Clostridioides difficile/genetics ; Drug Resistance, Bacterial ; *Microbiota ; *Clostridium Infections/microbiology ; Bacteria ; Firmicutes ; }, abstract = {BACKGROUND: The gastrointestinal microbiota is an important line of defense against colonization with antimicrobial resistant (AR) bacteria. In this post hoc analysis of the phase 3 ECOSPOR III trial, we assessed impact of a microbiota-based oral therapeutic (fecal microbiota spores, live; VOWST Oral Spores [VOS], formerly SER-109]; Seres Therapeutics) compared with placebo, on AR gene (ARG) abundance in patients with recurrent Clostridioides difficile infection (rCDI).

METHODS: Adults with rCDI were randomized to receive VOS or placebo orally for 3 days following standard-of-care antibiotics. ARG and taxonomic profiles were generated using whole metagenomic sequencing of stool at baseline and weeks 1, 2, 8, and 24 posttreatment.

RESULTS: Baseline (n = 151) and serial posttreatment stool samples collected through 24 weeks (total N = 472) from 182 patients (59.9% female; mean age: 65.5 years) in ECOSPOR III as well as 68 stool samples obtained at a single time point from a healthy cohort were analyzed. Baseline ARG abundance was similar between arms and significantly elevated versus the healthy cohort. By week 1, there was a greater decline in ARG abundance in VOS versus placebo (P = .003) in association with marked decline of Proteobacteria and repletion of spore-forming Firmicutes, as compared with baseline. We observed abundance of Proteobacteria and non-spore-forming Firmicutes were associated with ARG abundance, while spore-forming Firmicutes abundance was negatively associated.

CONCLUSIONS: This proof-of-concept analysis suggests that microbiome remodeling with Firmicutes spores may be a potential novel approach to reduce ARG colonization in the gastrointestinal tract.}, } @article {pmid38591029, year = {2024}, author = {Maurer, JJ and Cheng, Y and Pedroso, A and Thompson, KK and Akter, S and Kwan, T and Morota, G and Kinstler, S and Porwollik, S and McClelland, M and Escalante-Semerena, JC and Lee, MD}, title = {Peeling back the many layers of competitive exclusion.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1342887}, pmid = {38591029}, issn = {1664-302X}, abstract = {Baby chicks administered a fecal transplant from adult chickens are resistant to Salmonella colonization by competitive exclusion. A two-pronged approach was used to investigate the mechanism of this process. First, Salmonella response to an exclusive (Salmonella competitive exclusion product, Aviguard[®]) or permissive microbial community (chicken cecal contents from colonized birds containing 7.85 Log10Salmonella genomes/gram) was assessed ex vivo using a S. typhimurium reporter strain with fluorescent YFP and CFP gene fusions to rrn and hilA operon, respectively. Second, cecal transcriptome analysis was used to assess the cecal communities' response to Salmonella in chickens with low (≤5.85 Log10 genomes/g) or high (≥6.00 Log10 genomes/g) Salmonella colonization. The ex vivo experiment revealed a reduction in Salmonella growth and hilA expression following co-culture with the exclusive community. The exclusive community also repressed Salmonella's SPI-1 virulence genes and LPS modification, while the anti-virulence/inflammatory gene avrA was upregulated. Salmonella transcriptome analysis revealed significant metabolic disparities in Salmonella grown with the two different communities. Propanediol utilization and vitamin B12 synthesis were central to Salmonella metabolism co-cultured with either community, and mutations in propanediol and vitamin B12 metabolism altered Salmonella growth in the exclusive community. There were significant differences in the cecal community's stress response to Salmonella colonization. Cecal community transcripts indicated that antimicrobials were central to the type of stress response detected in the low Salmonella abundance community, suggesting antagonism involved in Salmonella exclusion. This study indicates complex community interactions that modulate Salmonella metabolism and pathogenic behavior and reduce growth through antagonism may be key to exclusion.}, } @article {pmid38589422, year = {2024}, author = {Wei, N and Ju, M and Su, X and Zhang, Y and Huang, Y and Rao, X and Cui, L and Lin, Z and Dong, Y}, title = {Transplantation of gut microbiota derived from patients with schizophrenia induces schizophrenia-like behaviors and dysregulated brain transcript response in mice.}, journal = {Schizophrenia (Heidelberg, Germany)}, volume = {10}, number = {1}, pages = {44}, pmid = {38589422}, issn = {2754-6993}, support = {2022M711171//China Postdoctoral Science Foundation/ ; }, abstract = {Schizophrenia (SCZ), as a neurodevelopmental disorder and devastating disease, affects approximately 1% of the world population. Although numerous studies have attempted to elucidate the causes of SCZ occurrence, it is not clearly understood. Recently, the emerging roles of the gut microbiota in a range of brain disorders, including SCZ, have attracted much attention. While the molecular mechanism of gut microbiota in regulating the pathogenesis of SCZ is still lacking. Here, we first confirmed the difference of gut microbiome between SCZ patients and healthy controls, and then, we performed fecal microbiota transplantation (FMT) to clarify the roles of SCZ patients-derived microbiota in a specific pathogen free (SPF) mice model. 16 S rDNA sequencing confirmed that a significant difference of gut microbiome was present between two groups of FMT mice, which has a similar trend with the above human gut microbiome. Furthermore, we found that transplantation of fecal microbiota from SCZ patients into SPF mice was sufficient to induce schizophrenia-like (SCZ-like) symptoms, such as deficits in sociability and hyperactivity. Furthermore, the brains of mice colonized with SCZ microbiota displayed dysregulated transcript response and alternative splicing of SCZ-relevant genes. Moreover, 10 key genes were identified to be correlated with SCZ by an integrative transcriptome data analysis. Finally, 4 key genes were identified to be correlated with the 12 differential genera between two groups of FMT mice. Our results thus demonstrated that the gut microbiome might modify the transcriptomic profile in the brain, thereby modulating social behavior, and our present study can help better understand the link between gut microbiota and SCZ pathogenesis through the gut-brain axis.}, } @article {pmid38589392, year = {2024}, author = {Dokoshi, T and Chen, Y and Cavagnero, KJ and Rahman, G and Hakim, D and Brinton, S and Schwarz, H and Brown, EA and O'Neill, A and Nakamura, Y and Li, F and Salzman, NH and Knight, R and Gallo, RL}, title = {Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3009}, pmid = {38589392}, issn = {2041-1723}, support = {R37AI052453//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01DK121760//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Hyaluronic Acid/metabolism ; *Colitis ; Intestinal Mucosa/metabolism ; Fecal Microbiota Transplantation ; Dextran Sulfate/toxicity ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/metabolism ; }, abstract = {The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.}, } @article {pmid38589368, year = {2024}, author = {Liu, P and Liu, Z and Wang, J and Wang, J and Gao, M and Zhang, Y and Yang, C and Zhang, A and Li, G and Li, X and Liu, S and Liu, L and Sun, N and Zhang, K}, title = {Immunoregulatory role of the gut microbiota in inflammatory depression.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3003}, pmid = {38589368}, issn = {2041-1723}, mesh = {Humans ; Mice ; Animals ; *Gastrointestinal Microbiome ; Depression/therapy ; Fecal Microbiota Transplantation ; Feces ; Fatty Acids, Volatile/metabolism ; }, abstract = {Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.}, } @article {pmid38585738, year = {2024}, author = {Hunter, C and Dia, K and Boykins, J and Perry, K and Banerjee, N and Cuffee, J and Armstrong, E and Morgan, G and Banerjee, HN and Banerjee, A and Bhattacharya, S}, title = {An investigation for phylogenetic characterization of human Pancreatic cancer microbiome by 16SrDNA Sequencing and Bioinformatics techniques.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-4140368/v1}, pmid = {38585738}, abstract = {Pancreatic cancer is a significant public health concern, with increasing incidence rates and limited treatment options. Recent studies have highlighted the role of the human microbiome, particularly the gut microbiota, in the development and progression of this disease. Microbial dysbiosis, characterized by alterations in the composition and function of the gut microbiota, has been implicated in pancreatic carcinogenesis through mechanisms involving chronic inflammation, immune dysregulation, and metabolic disturbances. Researchers have identified specific microbial signatures associated with pancreatic cancer, offering potential biomarkers for early detection and prognostication. By leveraging advanced sequencing and bioinformatics tools, scientists have delineated differences in the gut microbiota between pancreatic cancer patients and healthy individuals, providing insights into disease pathogenesis and potential diagnostic strategies. Moreover, the microbiome holds promise as a therapeutic target in pancreatic cancer treatment. Interventions aimed at modulating the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, have demonstrated potential in enhancing the efficacy of existing cancer therapies, including chemotherapy and immunotherapy. These approaches can influence immune responses, alter tumor microenvironments, and sensitize tumors to treatment, offering new avenues for improving patient outcomes and overcoming therapeutic resistance. Overall, understanding the complex interplay between the microbiome and pancreatic cancer is crucial for advancing our knowledge of disease mechanisms and identifying innovative therapeutic strategies. Here we report phylogenetic analysis of the 16S microbial sequences of the pancreatic cancer mice microbiome and corresponding age matched healthy mice microbiome. We successfully identified differentially abundance of microbiota in the pancreatic cancer.}, } @article {pmid38585101, year = {2024}, author = {Verma, A and Bhagchandani, T and Rai, A and Nikita, and Sardarni, UK and Bhavesh, NS and Gulati, S and Malik, R and Tandon, R}, title = {Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health.}, journal = {ACS omega}, volume = {9}, number = {13}, pages = {14648-14671}, pmid = {38585101}, issn = {2470-1343}, support = {D43 TW009345/TW/FIC NIH HHS/United States ; }, abstract = {The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut-lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut-lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.}, } @article {pmid38584861, year = {2024}, author = {Biedermann, L and Kreienbühl, A and Rogler, G}, title = {Microbiota Therapy in Inflammatory Bowel Disease.}, journal = {Visceral medicine}, volume = {40}, number = {2}, pages = {92-101}, pmid = {38584861}, issn = {2297-4725}, abstract = {BACKGROUND: In both Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel disease (IBD) the immune reaction is - at least partially - directed against components of the luminal microbiota of the gut. These immune responses as well as other factors contribute to a phenomenon frequently described as "dysbiosis" meaning an alteration of the composition of the colonic microbiota. To improve the dysbiosis and to restore the normal composition of the colonic microbiota, fecal microbiota transplantation (FMT) has been tested as a therapeutic option to induce and maintain remission in IBD patients.

SUMMARY: This review will first discuss changes in the composition of the intestinal microbiota found in IBD patients and second the therapeutic potential of microbiological interventions for the treatment of these patients. FMT has been studied in several clinical trials in both, CD and UC. Reported results and subsequent meta-analyses indicate that FMT may be effective to induce remission in UC. However, the optimal route of FMT, the necessary number of administrations and the question whether life bacteria of freshly prepared stool is more effective than frozen are still unclear. Concepts associated with an optimization of FMT such as the "super donor concept" or the "consortia-approach" will be discussed to illustrate open questions and difficulties associated with microbiota therapy in IBD.

KEY MESSAGES: The microbiota composition in IBD patients shows significant alterations compared to healthy individuals termed as "dysbiosis". FMT and other therapeutic approaches to modify the microbiota composition have been studied in clinical trials in recent years. Efficacy has been shown in UC; however, many questions with respect to the optimization of microbiota therapy remain to be answered.}, } @article {pmid38584858, year = {2024}, author = {Stallhofer, J and Steube, A and Katzer, K and Stallmach, A}, title = {Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent Clostridioides difficile Infection.}, journal = {Visceral medicine}, volume = {40}, number = {2}, pages = {82-91}, pmid = {38584858}, issn = {2297-4725}, abstract = {BACKGROUND: Clostridioides difficile (C. difficile) is a spore-forming bacterial species that ubiquitously exists in the environment. Colonization by C. difficile is highly prevalent in infants, while fewer than 5% of adults are asymptomatic carriers. Disruption of the microbiome, such as through antibiotic treatment, triggers the germination of bacterial spores into numerous vegetative cells. These cells then produce enterotoxins that result in watery diarrhea and colonic inflammation. If left untreated, C. difficile infection (CDI) can lead to pseudomembranous colitis with the potentially life-threatening complication of toxic megacolon.

SUMMARY: Over the past few decades, the incidence, morbidity, and mortality associated with CDIs have increased. They have emerged as the primary cause of nosocomial gastrointestinal infections in industrialized countries, posing a significant burden on healthcare systems. Despite antibiotics often being the cause of CDIs, they remain the standard treatment. However, a considerable number of patients treated with antibiotics will experience recurrent CDI (rCDI). Microbiota-based therapies targeting the core issue of CDI - antibiotic-induced dysbiosis - hold promise for rCDI treatment. While data for probiotics are insufficient, numerous studies have highlighted the effectiveness of fecal microbiota transplantation (FMT) as a safe and viable therapeutic option for rCDI. This approach is now endorsed by multiple guidelines. Nonetheless, regulatory prerequisites, such as comprehensive stool donor screening, restrict the widespread adoption of FMT beyond specialized centers. Recently, the US Food and Drug Administration has approved two commercial microbiota-based therapeutics to prevent CDI recurrence. These therapeutics are available by prescription in the USA. RBX2660 (REBYOTA™) comprises a diverse consortium of live microbes derived from human stool and is administered via enema. On the other hand, SER-109 (VOWST™) is an orally administered spore-based medication. In this review, we discuss the potential of microbiota-based treatments for rCDI against the background of medico-legal challenges associated with classical FMT.

KEY MESSAGES: FMT has emerged as a highly effective cure for rCDI. Nonetheless, regulatory prerequisites and laborious preparation procedures impede its widespread use. The establishment of ready-to-use microbiota-based therapeutics in clinical practice is necessary. In the USA, the recent approval of the first two commercial medications, including a spore-based oral preparation, marks a significant step forward.}, } @article {pmid38584284, year = {2024}, author = {Chen, C and Xu, JL and Gu, ZC and Zhou, SS and Wei, GL and Gu, JL and Ma, HL and Feng, YQ and Song, ZW and Yan, ZP and Deng, S and Ding, R and Li, SL and Huo, JG}, title = {Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.}, journal = {Chinese medicine}, volume = {19}, number = {1}, pages = {58}, pmid = {38584284}, issn = {1749-8546}, support = {82004339//Natural Science Foundation of China/ ; Z2022005//Medical Scientific Research Project of Jiangsu Provincial Health Commission/ ; No.2021.6//Jiangsu Clinical Innovation Center of Digestive Cancer of Traditional Chinese Medicine/ ; JD2019SZXYB16//Project of National Clinical Research Base of Traditional Chinese Medicine in Jiangsu Province/ ; BE2019767//Jiangsu science and technology department social development-clinical frontier technology/ ; BRA2019100//Jiangsu science and technology department social development-clinical frontier technology/ ; BK20210984//Natural Science Foundation of Jiangsu Province/ ; }, abstract = {BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated.

METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation.

RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota.

CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.}, } @article {pmid38582194, year = {2024}, author = {Rook, GAW}, title = {Evolution and the critical role of the microbiota in the reduced mental and physical health associated with low socioeconomic status (SES).}, journal = {Neuroscience and biobehavioral reviews}, volume = {}, number = {}, pages = {105653}, doi = {10.1016/j.neubiorev.2024.105653}, pmid = {38582194}, issn = {1873-7528}, abstract = {The evolution of the gut-microbiota-brain axis in animals reveals that microbial inputs influence metabolism, the regulation of inflammation and the development of organs, including the brain. Inflammatory, neurodegenerative and psychiatric disorders are more prevalent in people of low socioeconomic status (SES). Many aspects of low SES reduce exposure to the microbial inputs on which we are in a state of evolved dependence, whereas the lifestyle of wealthy citizens maintains these exposures. This partially explains the health deficit of low SES, so focussing on our evolutionary history and on environmental and lifestyle factors that distort microbial exposures might help to mitigate that deficit. But the human microbiota is complex and we have poor understanding of its functions at the microbial and mechanistic levels, and in the brain. Perhaps its composition is more flexible than the microbiota of animals that have restricted habitats and less diverse diets? These uncertainties are discussed in relation to the encouraging but frustrating results of attempts to treat psychiatric disorders by modulating the microbiota.}, } @article {pmid38579995, year = {2024}, author = {Zeng, Z and Lv, B and Tang, YE and Sun, H and Li, S and He, Y and Wang, J and Wang, Z}, title = {Effects of dietary selenized glucose on intestinal microbiota and tryptophan metabolism in rats: Assessing skatole reduction potential.}, journal = {Environmental research}, volume = {}, number = {}, pages = {118874}, doi = {10.1016/j.envres.2024.118874}, pmid = {38579995}, issn = {1096-0953}, abstract = {3-Methylindole (Skatole), a degradation product of tryptophan produced by intestinal microbial activity, significantly contributes to odor nuisance. Its adverse effects on animal welfare, human health, and environmental pollution have been noted. However, it is still unclear whether the intestinal microbiota mediates the impact of selenium (Se) on skatole production and what the underlying mechanisms remain elusive. A selenized glucose (SeGlu) derivative is a novel organic selenium compound. In this study, a diverse range of dietary SeGlu-treated levels, including SeGlu-deficient (CK), SeGlu-adequate (0.15 mg Se per L), and SeGlu-supranutritional (0.4 mg Se per L) conditions, were used to investigate the complex interaction of SeGlu on intestinal microbiome and serum metabolome changes in male Sprague-Dawley (SD) rats. The study showed that SeGlu supplementation enhanced the antioxidant ability in rats, significantly manifested in the increases of the activity of catalase (CAT) and glutathione peroxidase (GSH-Px), while no change in the level of malonaldehyde (MDA). Metagenomic sequencing analysis verified that the SeGlu treatment group significantly increased the abundance of beneficial microorganisms such as Clostridium, Ruminococcus, Faecalibacterium, Lactobacillus, and Alloprevotella while reducing the abundance of opportunistic pathogens such as Bacteroides and Alistipes significantly. Further metabolomic analysis revealed phenylalanine, tyrosine, and tryptophan biosynthesis changes in the SeGlu treatment group. Notably, the biosynthesis of indole, a critical pathway, was affected by SeGlu treatment, with several crucial enzymes implicated. Correlation analysis demonstrated strong associations between specific bacterial species - Treponema, Bacteroides, and Ruminococcus, and changes in indole and derivative concentrations. Moreover, the efficacy of SeGlu-treated fecal microbiota was confirmed through fecal microbiota transplantation, leading to a decrease in the concentration of skatole in rats. Collectively, the analysis of microbiota and metabolome response to diverse SeGlu levels suggests that SeGlu is a promising dietary additive in modulating intestinal microbiota and reducing odor nuisance in the livestock and poultry industry.}, } @article {pmid38578736, year = {2024}, author = {Lin, L and Xu, S and Cai, M and Li, S and Chen, Y and Chen, L and Lin, Y}, title = {Effects of fecal microbiota transfer on blood pressure in animal models: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {19}, number = {4}, pages = {e0300869}, pmid = {38578736}, issn = {1932-6203}, mesh = {Animals ; Blood Pressure ; *Fecal Microbiota Transplantation ; *Hypertension/therapy ; Feces ; Dysbiosis ; }, abstract = {BACKGROUND: Numerous recent studies have found a strong correlation between intestinal flora and the occurrence of hypertension. However, it remains unclear whether fecal microbiota transfer might affect the blood pressure of the host. This study aimed to quantify both associations.

METHODS: An electronic search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang database, Weipu, Embase, and SinoMed to retrieve relevant studies. The final search was completed on August 22, 2022. Two authors independently applied the inclusion criteria, extracted data, and assessed the risk of bias assessment. All data were analyzed using RevMan 5.4.

RESULTS: A total of 5 articles were selected for final inclusion. All studies were assessed as having a high risk of bias according to the SYRCLE risk of bias tool. The meta-analysis results showed that transplantation of fecal bacteria from the hypertensive model can significantly improve the host's systolic pressure (MD = 18.37, 95%CI: 9.74~26.99, P<0.001), and diastolic pressure (MD = 17.65, 95%CI: 12.37~22.93, P<0.001). Subgroup analyses revealed that the increase in systolic pressure in the hypertension model subgroup (MD = 29.56, 95%CI = 23.55-35.58, P<0.001) was more pronounced than that in the normotensive model subgroup (MD = 12.48, 95%CI = 3.51-21.45, P<0.001).

CONCLUSION: This meta-analysis suggests a relationship between gut microbiota dysbiosis and increased blood pressure, where transplantation of fecal bacteria from the hypertensive model can cause a significant increase in systolic pressure and diastolic pressure in animal models.}, } @article {pmid38577203, year = {2024}, author = {Koutromanos, I and Legaki, E and Gazouli, M and Vasilopoulos, E and Kouzoupis, A and Tzavellas, E}, title = {Gut microbiome in alcohol use disorder: Implications for health outcomes and therapeutic strategies-a literature review.}, journal = {World journal of methodology}, volume = {14}, number = {1}, pages = {88519}, pmid = {38577203}, issn = {2222-0682}, abstract = {Alcohol use disorder (AUD) represents a major public health issue which affects millions of people globally and consist a chronic relapsing condition associated with substantial morbidity and mortality. The gut microbiome plays a crucial role in maintaining overall health and has emerged as a significant contributor to the pathophysiology of various psychiatric disorders. Recent evidence suggests that the gut microbiome is intimately linked to the development and progression of AUD, with alcohol consumption directly impacting its composition and function. This review article aims to explore the intricate relationship between the gut microbiome and AUD, focusing on the implications for mental health outcomes and potential therapeutic strategies. We discuss the bidirectional communication between the gut microbiome and the brain, highlighting the role of microbiota-derived metabolites in neuroinflammation, neurotransmission, and mood regulation. Furthermore, we examine the influence of AUD-related factors, such as alcohol-induced gut dysbiosis and increased intestinal permeability, on mental health outcomes. Finally, we explore emerging therapeutic avenues targeting the gut microbiome in the management of AUD, including prebiotics, probiotics, and fecal microbiota transplantation. Understanding the complex interplay between the gut microbiome and AUD holds promise for developing novel interventions that could improve mental health outcomes in individuals with AUD.}, } @article {pmid38575121, year = {2024}, author = {Ren, J and Li, Y and Ni, H and Zhang, Y and Zhao, P and Xiao, Q and Hong, X and Zhang, Z and Yin, Y and Li, X and Zhang, Y and Yang, Y}, title = {Gut microbiota derived from fecal microbiota transplantation enhances body weight of Mimas squabs.}, journal = {Animal bioscience}, volume = {}, number = {}, pages = {}, doi = {10.5713/ab.23.0475}, pmid = {38575121}, issn = {2765-0189}, abstract = {OBJECTIVE: Compared to Mimas pigeons, Shiqi pigeons exhibit greater tolerance to coarse feeding because of their abundant gut microbiota. Here, to investigate the potential of utilizing intestinal flora derived from Shiqi pigeons, the intestinal flora and body indices of Mimas squabs were evaluated after fecal microbiota transplantation (FMT) from donors.

METHODS: A total of 90 one-day-old squabs were randomly divided into the control group (CON), the low-concentration group (LC) and the high-concentration group (HC): gavaged with 200 μL of bacterial solution at concentrations of 0, 0.1 and 0.2 g/15 mL, respectively.

RESULTS: The results suggested that FMT improved the body weight of Mimas squabs in the HC and LC groups (p < 0.01), and 0.1 g/15 mL was the optimal dose during FMT. After 16S rRNA sequencing was performed, compared to those in the CON group, the abundance levels of microflora, especially Lactobacillus, Muribaculaceae and Megasphaera (p < 0.05), in the FMT-treated groups were markedly greater. Random forest analysis indicated that the main functions of key microbes involve pathways associated with metabolism, further illustrating their important role in the host body.

CONCLUSION: FMT has been determined to be a viable method for augmenting the weight and intestinal microbiota of squabs, representing a unique avenue for enhancing the economic feasibility of squab breeding.}, } @article {pmid38574899, year = {2024}, author = {Stevens, LJ and van de Steeg, E and Doppenberg, JB and Alwayn, IPJ and Knibbe, CAJ and Dubbeld, J}, title = {Ex vivo Gut-Hepato-Biliary organ perfusion model to characterize oral absorption, gut-wall metabolism, pre-systemic hepatic metabolism and biliary excretion; application to midazolam.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {}, number = {}, pages = {106760}, doi = {10.1016/j.ejps.2024.106760}, pmid = {38574899}, issn = {1879-0720}, abstract = {To date, characterization of the first-pass effect of orally administered drugs consisting of local intestinal absorption and metabolism, portal vein transport and hepatobiliary processes remains challenging. Aim of this study was to explore the applicability of a porcine ex-vivo perfusion model to study oral absorption, gut-hepatobiliary metabolism and biliary excretion of midazolam. Slaughterhouse procured porcine en bloc organs (n=4), were perfused via the aorta and portal vein. After 120min of perfusion, midazolam, atenolol, antipyrine and FD4 were dosed via the duodenum and samples were taken from the systemic- and portal vein perfusate, intestinal faecal effluent and bile to determine drug and metabolite concentrations. Stable arterial and portal vein flow was obtained and viability of the perfused organs was confirmed. After intraduodenal administration, midazolam was rapidly detected in the portal vein together with 1-OH midazolam (EG-pv of 0.16±0.1) resulting from gut wall metabolism through oxidation. In the intestinal faecal effluent, 1-OH midazolam and 1-OH midazolam glucuronide (EG-intestine 0.051±0.03) was observed resulting from local gut glucuronidation. Biliary elimination of midazolam (0.04±0.01%) and its glucuronide (0.01±0.01%) only minimally contributed to the enterohepatic circulation. More extensive hepatic metabolism (FH 0.35±0.07) over intestinal metabolism (FG 0.78±0.11) was shown, resulting in oral bioavailability of 0.27±0.05. Ex vivo perfusion demonstrated to be a novel approach to characterize pre-systemic extraction of midazolam by measuring intestinal as well as hepatic extraction. The model can generate valuable insights into the absorption and metabolism of new drugs.}, } @article {pmid38574779, year = {2024}, author = {Yan, G and Zhang, L and Wu, D and Jiang, S and Wu, Q and Dai, M}, title = {Paeonol attenuates nonalcoholic steatohepatitis by regulating intestinal flora and AhR/NLRP3/Caspase-1 metabolic pathway.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {118147}, doi = {10.1016/j.jep.2024.118147}, pmid = {38574779}, issn = {1872-7573}, abstract = {Non-alcoholic steatohepatitis (NASH) is a common metabolic liver injury disease that is closely associated with obesity and metabolic disorders. Paeonol, an active ingredient found in Moutan Cortex, a traditional Chinese medicine which exhibits significant therapeutic effect on liver protection, has shown promising effects in treating liver diseases, particularly NASH. However, the specific intervention mechanism of paeonol on NASH is still unknown.

AIM OF THE STUDY: Our objective is to elucidate the pharmacological mechanism of paeonol in intervening NASH at the in vivo level, focusing on the impact on intestinal flora, tryptophan-related targeted metabolome, and related Aryl hydrocarbon receptor (AhR) pathways.

MATERIALS AND METHODS: Here, we explored the intervention effect of paeonol on NASH by utilizing the NASH mouse model. The Illumina highthroughput sequencing technology was preformed to determine the differences of gut microbiota of model and paeonol treatment group. The concentration of Indoleacetic acid is determined by ELISA. The intervention effect of NASH mouse and AhR/NLRP3/Caspase-1 metabolic pathway is analyzed by HE staining, oil red O staining, Immunohistochemistry, Immunofluorescence, Western blot and qRT-PCR assays. Fecal microbiota transplantation experiment also was performed to verify the intervention effect of paeonol on NASH by affecting gut microbiota.

RESULTS: Firstly, we discovered that paeonol effectively reduced liver pathology and blood lipid levels in NASH mice, thereby intervening in the progression of NASH. Subsequently, through 16S meta-analysis, we identified that paeonol can effectively regulate the composition of intestinal flora in NASH mice, transforming it to resemble that of normal mice. Specifically, paeonol decreased the abundance of certain Gram-negative tryptophan-metabolizing bacteria. Moreover, we discovered that paeonol significantly increased the levels of metabolites Indoleacetic acid, subsequently enhancing the expression of AhR-related pathway proteins. This led to the inhibition of the NOD-like receptor protein 3 (NLRP3) inflammasome production and inflammation generation in NASH. Lastly, we verified the efficacy of paeonol in intervening NASH by conducting fecal microbiota transplantation experiments, which confirmed its role in promoting the AhR/NLRP3/cysteinyl aspartate specific proteinase (Caspase-1) pathway.

CONCLUSIONS: Our findings suggest that paeonol can increase the production of Indoleacetic acid by regulating the gut flora, and promote the AhR/NLRP3/Caspase-1 metabolic pathway to intervene NASH.}, } @article {pmid38574772, year = {2024}, author = {Sottil, P and Lhomme, S and Saune, K and El Hayani, S and Oliveira-Mendes, K and Peron, JM and Kamar, N and Izopet, J and Abravanel, F}, title = {Evaluation of an automated platform for the detection of HEV RNA in plasma and stool.}, journal = {Journal of virological methods}, volume = {}, number = {}, pages = {114920}, doi = {10.1016/j.jviromet.2024.114920}, pmid = {38574772}, issn = {1879-0984}, abstract = {INTRODUCTION: We evaluated the performance of the automated Altostar HEV RNA platform for detecting HEV RNA.

METHODS AND RESULTS: Clinical performance was determined by testing 81 plasma samples and 10 fecal samples manually quantified previously with the Realstar RT-PCR assay using the Magnapure instrument for extraction. The assays were concordant for 79/81 plasma samples (97.5%) and 10/10 (100%) fecal samples. The two plasma samples that tested negative with the Altostar assay had a very low HEV RNA concentration (1.6 and 1.4 log10 IU/ml). Quantitative results obtained with the automated platform and the manual workflow were highly correlated (ρ= 0.98, p<0.01). The intra-run and inter-run standard deviation were 0.09 IU/ml and 0.13 IU/ml respectively. The assay was linear from 2 to 6log IU/ml. The limit of detection determined by Probit analysis with the WHO HEV RNA standard was 7.6 [95% CI: 4.4-52.5] IU/ml.

CONCLUSIONS: The Altostar platform enables highly accurate testing for the detection of HEV RNA in stool and the quantification of HEV RNA in plasma. This allowed us to shorten turnaround times and to save time for the technical staff.}, } @article {pmid38572783, year = {2024}, author = {Ren, S and Feng, L and Liu, H and Mao, Y and Yu, Z}, title = {Gut microbiome affects the response to immunotherapy in non-small cell lung cancer.}, journal = {Thoracic cancer}, volume = {}, number = {}, pages = {}, doi = {10.1111/1759-7714.15303}, pmid = {38572783}, issn = {1759-7714}, support = {ZR202102240880//Natural Science Foundation of Shandong Province/ ; 23-2-1-189-zyyd-jch//Natural Science Foundation of Qingdao Municipality/ ; 320.6750.2021-02-92//Wu Jieping Medical Foundation/ ; 82373170//National Natural Science Foundation of China/ ; Y-QL202101-0258//Chinese Society of Clinical Oncology/ ; Y-pierrefabre202101-0074//Chinese Society of Clinical Oncology/ ; YXH2022ZX02020//ShanDong Provincial Medical Association/ ; }, abstract = {BACKGROUND: Immunotherapy has revolutionized cancer treatment. Recent studies have suggested that the efficacy of immunotherapy can be further enhanced by the influence of gut microbiota. In this study, we aimed to investigate the impact of bacteria on the effectiveness of cancer immunotherapy by combining analysis of clinical samples with validation in animal models.

METHODS: In order to characterize the diversity and composition of microbiota and its relationship with response to immune checkpoint inhibitors (ICIs), 16S ribosomal RNA (rRNA) and GC-MS sequencing was performed on 71 stool samples from patients with advanced non-small cell lung cancer (NSCLC) prior to treatment with immune checkpoint blockade (ICB). Furthermore, fecal microbiota transplantation (FMT) was performed from different patients into mice and a subcutaneous tumor model established using the Lewis lung cancer cell line to evaluate the therapeutic effect of PD-1 on mice with varying gut microbiota.

RESULTS: The results demonstrated a significant association between elevated gut microbiota diversity and response to treatment with ICIs, p < 0.05. Faecalibacterium was markedly increased in the gut microbiota of responders (R), accompanied by increased short-chain fatty acid (SCFA) levels, especially butanoic acid, acetic acid and hexanoic acid, p < 0.05. Additionally, FMT from R and nonresponders (NR) could promote an anticancer effect and reduce the expression of Ki-67 cells in tumors in mice, p < 0.05. Moreover, R and NR FMT did not alter PD-L1 expression in the tumor tissues of mice, p > 0.05. The diversity of gut microbiota consistently correlated with an optimistic prognosis in NSCLC patients with immunotherapy, which could be functionally mediated by SCFAs.

CONCLUSION: The findings of the present study indicated that the diversity of gut microbiota and SCFAs is related to the efficacy of immunotherapy. FMT can effectively delay tumor progression, and enhance the effect of immunotherapy, thus providing evidence for improving the efficacy of immunotherapy in NSCLC patients.}, } @article {pmid38572716, year = {2024}, author = {van Lingen, E and Nooij, S and Terveer, E and Crossette, E and Prince, A and Bhattarai, S and Watson, A and Galazzo, G and Menon, R and Szabady, R and Bucci, V and Norman, J and van der Woude, J and van der Marel, S and Verspaget, H and van der Meulen-de Jong, A and Keller, J}, title = {Fecal Microbiota Transplantation engraftment after budesonide or placebo in patients with active ulcerative colitis using pre-selected donors: a randomized pilot study.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjae043}, pmid = {38572716}, issn = {1876-4479}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) shows some efficacy in treating patients with ulcerative colitis (UC), although variability has been observed among donors and treatment regimens. We investigated the effect of FMT using rationally selected donors after pretreatment with budesonide or placebo in active UC.

METHODS: Patients ≥ 18 years old with mild to moderate active UC were randomly assigned to three weeks budesonide (9 mg) or placebo followed by four weekly infusions of a donor feces suspension. Two donors were selected based on microbiota composition, Treg induction and SCFA production in mice. The primary endpoint was engraftment of donor microbiota after FMT. In addition, clinical efficacy was assessed.

RESULTS: In total, 24 patients were enrolled. Pretreatment with budesonide did not increase donor microbiota engraftment (p=0.56) nor clinical response, and engraftment was not associated with clinical response. At week 14, 10/24 (42%) of patients achieved (partial) remission. Remarkably, patients treated with FMT suspensions from one donor were associated with clinical response (80% of responders, p<0.05) but had lower overall engraftment of donor microbiota. Furthermore, differences in the taxonomic composition of the donors and the engraftment of certain taxa were associated with clinical response.

CONCLUSION: In this small study, pretreatment with budesonide did not significantly influence engraftment or clinical response after FMT. However, clinical response appeared donor-dependent. Response to FMT may be related to transfer of specific strains instead of overall engraftment, demonstrating the need to characterize mechanisms of actions of strains that maximize therapeutic benefit in ulcerative colitis.}, } @article {pmid38571533, year = {2024}, author = {Al Naser, Y and AlGashami, M and Aljashaami, L}, title = {Clostridioides difficile infection: a changing treatment paradigm.}, journal = {Przeglad gastroenterologiczny}, volume = {19}, number = {1}, pages = {1-5}, pmid = {38571533}, issn = {1895-5770}, abstract = {Clostridioides difficile infection (CDI) poses a persistent challenge in healthcare, with substantial morbidity and mortality implications. This comprehensive review explores current CDI management, emphasising guidelines from IDSA, SHEA, and ESCMID. Additionally, this study spotlights recent drug developments that have the potential to reshape CDI treatment paradigms. Within the current treatment landscape, fidaxomicin, vancomycin, bezlotoxumab, and faecal microbiota transplantation offer varied options, each with its unique strengths and limitations. Fidaxomicin, effective yet resource-constrained, presents a dilemma, with vancomycin emerging as a pragmatic alternative. Bezlotoxumab, though augmenting antibiotics, grapples with cost and safety concerns. Meanwhile, faecal microbiota transplantation, highly efficacious, confronts evolving safety considerations. The horizon of CDI treatment also features promising therapies such as SER-109 and Rebyota, epitomising the evolving paradigm. As CDI management advances, the critical role of standardised microbiome restoration therapies becomes evident, ensuring long-term safety and diversifying treatment strategies.}, } @article {pmid38570412, year = {2024}, author = {Menozzi, E and Schapira, AHV}, title = {The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications.}, journal = {CNS drugs}, volume = {}, number = {}, pages = {}, pmid = {38570412}, issn = {1179-1934}, support = {ASAP-000420//Aligning Science Across Parkinson's/ ; }, abstract = {The concept of a 'microbiota-gut-brain axis' has recently emerged as an important player in the pathophysiology of Parkinson disease (PD), not least because of the reciprocal interaction between gut bacteria and medications. The gut microbiota can influence levodopa kinetics, and conversely, drugs administered for PD can influence gut microbiota composition. Through a two-step enzymatic pathway, gut microbes can decarboxylate levodopa to dopamine in the small intestine and then dehydroxylate it to m-tyramine, thus reducing availability. Inhibition of bacterial decarboxylation pathways could therefore represent a strategy to increase levodopa absorption. Other bacterial perturbations common in PD, such as small intestinal bacterial overgrowth and Helicobacter pylori infection, can also modulate levodopa metabolism, and eradication therapies may improve levodopa absorption. Interventions targeting the gut microbiota offer a novel opportunity to manage disabling motor complications and dopa-unresponsive symptoms. Mediterranean diet-induced changes in gut microbiota composition might improve a range of non-motor symptoms. Prebiotics can increase levels of short-chain fatty acid-producing bacteria and decrease pro-inflammatory species, with positive effects on clinical symptoms and levodopa kinetics. Different formulations of probiotics showed beneficial outcomes on constipation, with some of them improving dopamine levels; however, the most effective dosage and duration and long-term effects of these treatments remain unknown. Data from faecal microbiota transplantation studies are preliminary, but show encouraging trends towards improvement in both motor and non-motor outcomes.This article summarises the most up-to-date knowledge in pharmacomicrobiomics in PD, and discusses how the manipulation of gut microbiota represents a potential new therapeutic avenue for PD.}, } @article {pmid38567141, year = {2024}, author = {Hopper, AL and Hudson, CL and Klair, D and Ding, Q and Gao, Z and Jha, A and Bryan, A and Tikekar, RV and Coolong, T and Dunn, LL and Micallef, SA}, title = {Rain splash-mediated dispersal of Escherichia coli from fecal deposits to field-grown lettuce in the mid- and south Atlantic U.S. regions is affected by mulch type.}, journal = {Frontiers in plant science}, volume = {15}, number = {}, pages = {1370495}, pmid = {38567141}, issn = {1664-462X}, abstract = {INTRODUCTION: Wildlife feces can contaminate vegetables when enteric bacteria are released by rain and splashed onto crops. Regulations require growers to identify and not harvest produce that is likely contaminated, but U.S. federal standards do not define dimensions for no-harvest zones. Moreover, mulching, used to retain soil moisture and maximize crop yield may impact rain-mediated bacterial dispersal from feces.

METHODS: To assess Escherichia coli dissemination from a fecal point source to lettuce grown on various mulches, lettuce cv. 'Magenta' was transplanted into raised beds with plastic, biodegradable plastic, straw, or left uncovered at field sites in Maryland and Georgia. Eleven days post-transplant, 10 g of rabbit manure spiked with ~8 log CFU g[-1] E. coli were deposited in each bed. One day following natural or simulated rain events, lettuce was sampled along 1.5 m transects on either side of fecal deposits. Lettuce-associated E. coli was semi-quantified with an MPN assay and dependence on fecal age (stale or fresh), lettuce age (baby leaf or mature head), distance from point source, mulch and post-rain days were statistically evaluated.

RESULTS: Distance (p<0.001), fecal age (p<0.001) and mulch (p<0.01) were factors for E. coli transfer from point source to lettuce. The highest and lowest E. coli estimates were measured from lettuce grown on biodegradable plastic and straw, respectively, with a 2-log MPN difference (p<0.001). Mulch and distance were also significant factors in E. coli recovery 3 days post-rain (both p<0.001), where plastic mulches differed from bare ground and straw (p<0.01). For all treatments, fewer E. coli were retrieved from lettuce at 0.3 m, 3 days post-rain compared to 1 day (p<0.001). Fitting the data to a Weibull Model predicated that a 7-log reduction in E. coli from fecal levels would be achieved at 1.2-1.4 m from the point source on plastic mulches, 0.75 m on bare soil (p<0.05) and 0.43 m on straw (p<0.01).

DISCUSSION: Straw and bare ground limited rain-mediated E. coli dispersal from feces to lettuce compared to plastic mulches. Fecal age was negatively associated with E. coli dispersal. These findings can inform harvesting recommendations for measures related to animal intrusion in vegetable production areas.}, } @article {pmid38565581, year = {2024}, author = {Boussamet, L and Montassier, E and Mathé, C and Garcia, A and Morille, J and Shah, S and Dugast, E and Wiertlewski, S and Gourdel, M and Bang, C and Stürner, KH and Masson, D and Nicot, AB and Vince, N and Laplaud, DA and Feinstein, DL and Berthelot, L}, title = {Investigating the metabolite signature of an altered oral microbiota as a discriminant factor for multiple sclerosis: a pilot study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {7786}, pmid = {38565581}, issn = {2045-2322}, support = {LOIRE-TIMES//Conseil Régional des Pays de la Loire/ ; I01BX002625//U.S. Department of Veterans Affairs/ ; }, mesh = {Humans ; *Multiple Sclerosis ; Pilot Projects ; RNA, Ribosomal, 16S/genetics/analysis ; *Microbiota/genetics ; Bacteria/genetics ; Inflammation ; }, abstract = {In multiple sclerosis (MS), alterations of the gut microbiota lead to inflammation. However, the role of other microbiomes in the body in MS has not been fully elucidated. In a pilot case-controlled study, we carried out simultaneous characterization of faecal and oral microbiota and conducted an in-depth analysis of bacterial alterations associated with MS. Using 16S rRNA sequencing and metabolic inference tools, we compared the oral/faecal microbiota and bacterial metabolism pathways in French MS patients (n = 14) and healthy volunteers (HV, n = 21). A classification model based on metabolite flux balance was established and validated in an independent German cohort (MS n = 12, HV n = 38). Our analysis revealed decreases in diversity indices and oral/faecal compartmentalization, the depletion of commensal bacteria (Aggregatibacter and Streptococcus in saliva and Coprobacter and Roseburia in faeces) and enrichment of inflammation-associated bacteria in MS patients (Leptotrichia and Fusobacterium in saliva and Enterobacteriaceae and Actinomyces in faeces). Several microbial pathways were also altered (the polyamine pathway and remodelling of bacterial surface antigens and energetic metabolism) while flux balance analysis revealed associated alterations in metabolite production in MS (nitrogen and nucleoside). Based on this analysis, we identified a specific oral metabolite signature in MS patients, that could discriminate MS patients from HV and rheumatoid arthritis patients. This signature allowed us to create and validate a discrimination model on an independent cohort, which reached a specificity of 92%. Overall, the oral and faecal microbiomes were altered in MS patients. This pilot study highlights the need to study the oral microbiota and oral health implications in patients with autoimmune diseases on a larger scale and suggests that knowledge of the salivary microbiome could help guide the identification of new pathogenic mechanisms associated with the microbiota in MS patients.}, } @article {pmid38565558, year = {2024}, author = {Yang, H and Wu, X and Li, X and Zang, W and Zhou, Z and Zhou, Y and Cui, W and Kou, Y and Wang, L and Hu, A and Wu, L and Yin, Z and Chen, Q and Chen, Y and Huang, Z and Wang, Y and Gu, B}, title = {A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2842}, pmid = {38565558}, issn = {2041-1723}, support = {82072380//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81871734//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82102408//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2022M712681//China Postdoctoral Science Foundation/ ; }, mesh = {Animals ; Mice ; *Clostridioides difficile ; Arginine ; Ornithine ; Intestines/microbiology ; Fecal Microbiota Transplantation ; *Clostridium Infections/therapy/microbiology ; }, abstract = {Antibiotic-induced dysbiosis is a major risk factor for Clostridioides difficile infection (CDI), and fecal microbiota transplantation (FMT) is recommended for treating CDI. However, the underlying mechanisms remain unclear. Here, we show that Tritrichomonas musculis (T.mu), an integral member of the mouse gut commensal microbiota, reduces CDI-induced intestinal damage by inhibiting neutrophil recruitment and IL-1β secretion, while promoting Th1 cell differentiation and IFN-γ secretion, which in turn enhances goblet cell production and mucin secretion to protect the intestinal mucosa. T.mu can actively metabolize arginine, not only influencing the host's arginine-ornithine metabolic pathway, but also shaping the metabolic environment for the microbial community in the host's intestinal lumen. This leads to a relatively low ornithine state in the intestinal lumen in C. difficile-infected mice. These changes modulate C. difficile's virulence and the host intestinal immune response, and thus collectively alleviating CDI. These findings strongly suggest interactions between an intestinal commensal eukaryote, a pathogenic bacterium, and the host immune system via inter-related arginine-ornithine metabolism in the regulation of pathogenesis and provide further insights for treating CDI.}, } @article {pmid38565398, year = {2024}, author = {Zhang, L and Yin, Z and Liu, X and Jin, G and Wang, Y and He, L and Li, M and Pang, X and Yan, B and Jia, Z and Ma, J and Wei, J and Cheng, F and Li, D and Wang, L and Han, Z and Liu, Q and Chen, F and Cao, H and Lei, P}, title = {Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2024.03.052}, pmid = {38565398}, issn = {1090-2139}, abstract = {Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.}, } @article {pmid38560650, year = {2024}, author = {Quan, YX and Lao, YD and Wu, HY and He, XX and Wu, LH}, title = {Beneficial effects of the first case of washed microbiota transplantation for postorgasmic illness syndrome: a case report.}, journal = {Sexual medicine}, volume = {12}, number = {2}, pages = {qfae015}, pmid = {38560650}, issn = {2050-1161}, abstract = {INTRODUCTION: Postorgasmic illness syndrome (POIS) is characterized by allergic symptoms and flu-like illness after ejaculation. There are still no effective treatments for POIS.

AIM: To report the first case of washed microbiota transplantation (WMT) to treat patient with POIS.

METHODS: Data were collected from a patient with POIS who had received 3 courses of WMT: self-rating scale of POIS symptoms, Self-rating Anxiety Scale, Self-rating Depression Scale, and Symptom Checklist 90. The patient's stool samples for 16sDNA sequencing were collected 1 month after WMT.

RESULTS: POIS symptoms improved after WMT. Scores decreased from baseline after WMT: self-rating scale of POIS symptoms (before WMT, 16; after first, 16; after second, 8; after third, 9), Self-rating Anxiety Scale (45, 42.5, 37.5, 45), Self-rating Depression Scale (63.75, 58.75, 47.5, 50), and Symptom Checklist 90 (143, 140, 109, 149). Characteristics of the patient's gut microbiota changed. At the genus level, the relative abundance of beneficial bacteria increased, and some opportunistic pathogenic bacteria decreased.

CONCLUSION: WMT may be an effective and safe choice for the treatment of patients with POIS by changing the gut microbiota of the host.}, } @article {pmid38558912, year = {2024}, author = {Lee, KE and Tu, VY and Faye, AS}, title = {Optimal Management of Refractory Crohn's Disease: Current Landscape and Future Direction.}, journal = {Clinical and experimental gastroenterology}, volume = {17}, number = {}, pages = {75-86}, pmid = {38558912}, issn = {1178-7023}, abstract = {Refractory Crohn's disease, defined as ongoing inflammation despite the trial of multiple advanced therapies, impacts a number of individuals with Crohn's disease, and leads to significant burden in quality of life and cost. Interventions such as early implementation of advanced therapies, optimization of current therapies prior to switching to an alternative, as well as understanding the overlapping pathophysiology between immune-mediated disorders, however, can help shift the current landscape and reduce the number of patients with refractory disease. As such, in this review we summarize the key takeaways of the latest research in the management of moderate-to-severe Crohn's disease, focusing on maximization of our currently available medications, while also exploring topics such as combination advanced therapies. We also describe evidence for emerging and alternative therapeutic modalities, including fecal microbiota transplant, exclusive enteral feeding, hyperbaric oxygen, stem cell therapy, bone marrow transplant, and posaconazole, with a focus on both the potential impact and specific indications for each.}, } @article {pmid38558090, year = {2024}, author = {Bolia, R and Goel, A and Thapar, N}, title = {Transanal irrigation in children with functional constipation: A systematic review and meta-analysis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.12200}, pmid = {38558090}, issn = {1536-4801}, support = {//None/ ; }, abstract = {OBJECTIVES: Refractory functional constipation is a challenging condition to manage in children. The use of transanal irrigation (TAI) is well reported in children with neurological disorders as well as anorectal malformations but less so in children with functional disorders of defecation. The objective of our study was to evaluate the effectiveness, safety and outcomes of TAI in children with functional constipation.

METHODS: PubMed, Scopus and Google Scholar were searched for publications related to the use of TAI in functional constipation. Data regarding the study design, sample size, patient characteristics, investigator-reported response to TAI and adverse effects were extracted from studies that met the selection criteria. The inverse variance heterogeneity model was used for ascertaining the summary effect in this meta-analysis.

RESULTS: The search strategy yielded 279 articles of which five studies were included in the final review. The studies were from the United Kingdom (n = 2), Netherlands (n = 2) and Denmark (n = 1). These studies included 192 children with a median age ranging from 7 to 12.2 years old. The TAI systems used in these studies were: Peristeen (n = 2), Peristeen or Qufora (n = 1), Alterna (n = 1) and Navina (n = 1). The follow-up duration ranged from 5.5 months to 3 years. Eleven (5.7%) children did not tolerate TAI and withdrew from treatment soon after initiation. The pooled investigator-reported success of TAI was 62% (95% CI: 52%-71%). The most common adverse event was pain which was experienced by 21.7% of children. A total of 27 (14%) were successfully weaned off TAI at the last follow-up.

CONCLUSIONS: TAI is reported to be successful in 62% of children with refractory functional constipation. There is a need for well-designed prospective trials to evaluate this treatment option in children with refractory functional constipation.}, } @article {pmid38556088, year = {2024}, author = {Vega-Abellaneda, S and Dopazo, C and Yañez, F and Soler, Z and Xie, Z and Canalda Baltrons, A and Pons, M and Bilbao, I and Manichanh, C}, title = {Microbiome Composition Recovery after Liver Transplantation Correlates with Initial Liver Disease Severity and Antibiotics Treatment.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajt.2024.03.038}, pmid = {38556088}, issn = {1600-6143}, abstract = {Liver transplantation (LT) is crucial for end-stage liver disease, but it is linked to infection risks. Pathobionts, microorganisms potentially harmful under specific conditions, can cause complications post-transplant. Monitoring such pathogens in fecal samples can be challenging and therefore remains underexplored post-LT. This study aimed to analyze the gut microbiome before and after LT, tracking pathobionts and correlating clinical data. The study involved 17 liver transplant recipients, 17 healthy relatives (spouses), and 13 donors. Gut samples collected pre- and post-transplantation underwent bacterial and fungal profiling through DNA sequencing. Quantitative PCR was used to assess microbial load. Statistical analyses included alpha and beta diversity measures, differential abundance analysis, and correlation tests between microbiome and clinical parameters. Microbiome analysis revealed dynamic changes in diversity post-transplant. Notably, high-severity patients showed persistent and greater dysbiosis during the first months post-LT compared to low-severity patients, partly due to an antibiotic treatment pre-LT. The analysis identified a higher proportion of pathogens such as Escherichia coli/Shigella flexneri in high-severity cases post-transplant. Furthermore, butyrate producers including Roseburia intestinalis, Anaerostipes hadrus and Eubacterium coprostanoligenes were positively correlated with levels of albumin. This study offers valuable insights into post-LT microbiome changes, shedding light on the need for tailored prophylactic treatment post-LT.}, } @article {pmid38555945, year = {2024}, author = {Tu, Y and Luo, L and Zhou, Q and Ni, J and Tang, Q}, title = {Fecal Microbiota Transplantation Repairs Radiation Enteritis Through Modulating the Gut Microbiota-Mediated Tryptophan Metabolism.}, journal = {Radiation research}, volume = {}, number = {}, pages = {}, doi = {10.1667/RADE-23-00189.1}, pmid = {38555945}, issn = {1938-5404}, abstract = {Radiation enteritis is a common complication of abdominal and pelvic radiotherapy. Several previous studies showed that fecal microbiota transplantation (FMT) could alleviate radiation enteritis. In this study, we investigated the efficacy of FMT in alleviating radiation enteritis and explored the mechanisms by multi-omics approaches. Briefly, C57BL/6J mice were subjected to 9 Gy irradiation to the localized abdominal field, and randomized received FMT from healthy donor mice or saline. H&E staining of harvested small intestine showed FMT decreased epithelial injury. Radiation-induced microbiota dysbiosis, characterized by a decrease in beneficial bacteria Lactobacillaceae and Lachnospiraceae, while these bacteria were restored by FMT. Fecal metabolomics analysis revealed that FMT modulated metabolic dysregulation. Two tryptophan pathway metabolites, indole-3-acetaldehyde and N-Acetyl-5-hydroxytryptamine were decreased after irradiation, whereas these metabolites showed a pronounced recovery in mice receiving FMT. Proteomics analysis of small intestine indicated that radiation enteritis triggered immune-inflammatory responses, which were potentially mitigated by FMT. In 21 patients receiving pelvic radiotherapy for cervical cancer, those who developed enteritis (n = 15) had higher abundance in Lachnospiraceae. Moreover, Indole-3-acetaldehyde was reduced after irradiation. These findings provide insights into the therapeutic effects of FMT in radiation enteritis and highlight Lachnospiraceae and the tryptophan metabolite, Indole-3-acetaldehyde may protect against radiation enteritis.}, } @article {pmid38555499, year = {2024}, author = {Heston, SM and Young, RR and Jenkins, K and Martin, PL and Stokhuyzen, A and Ward, DV and Bhattarai, SK and Bucci, V and Arshad, M and Chao, NJ and Seed, PC and Kelly, MS}, title = {The effects of antibiotic exposures on the gut resistome during hematopoietic cell transplantation in children.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2333748}, pmid = {38555499}, issn = {1949-0984}, mesh = {Child ; Humans ; Anti-Bacterial Agents/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/genetics ; Bacteria/genetics ; Fluoroquinolones/pharmacology ; *Hematopoietic Stem Cell Transplantation ; }, abstract = {Antibiotic resistance is a global threat driven primarily by antibiotic use. We evaluated the effects of antibiotic exposures on the gut microbiomes and resistomes of children at high risk of colonization by antibiotic-resistant bacteria. We performed shotgun metagenomic sequencing of 691 serially collected fecal samples from 80 children (<18 years) undergoing hematopoietic cell transplantation. We evaluated the effects of aerobic (cefepime, vancomycin, fluoroquinolones, aminoglycosides, macrolides, and trimethoprim-sulfamethoxazole) and anaerobic (piperacillin-tazobactam, carbapenems, metronidazole, and clindamycin) antibiotic exposures on the diversity and composition of the gut microbiome and resistome. We identified 372 unique antibiotic resistance genes (ARGs); the most frequent ARGs identified encode resistance to tetracyclines (n = 88), beta-lactams (n = 84), and fluoroquinolones (n = 79). Both aerobic and anaerobic antibiotic exposures were associated with a decrease in the number of bacterial species (aerobic, β = 0.71, 95% CI: 0.64, 0.79; anaerobic, β = 0.66, 95% CI: 0.53, 0.82) and the number of unique ARGs (aerobic, β = 0.81, 95% CI: 0.74, 0.90; anaerobic, β = 0.73, 95% CI: 0.61, 0.88) within the gut metagenome. However, only antibiotic regimens that included anaerobic activity were associated with an increase in acquisition of new ARGs (anaerobic, β = 1.50; 95% CI: 1.12, 2.01) and an increase in the relative abundance of ARGs in the gut resistome (anaerobic, β = 1.62; 95% CI: 1.15, 2.27). Specific antibiotic exposures were associated with distinct changes in the number and abundance of ARGs for individual antibiotic classes. Our findings detail the impact of antibiotics on the gut microbiome and resistome and demonstrate that anaerobic antibiotics are particularly likely to promote acquisition and expansion of antibiotic-resistant bacteria.}, } @article {pmid38555356, year = {2024}, author = {Dörner, PJ and Anandakumar, H and Röwekamp, I and Fiocca Vernengo, F and Millet Pascual-Leone, B and Krzanowski, M and Sellmaier, J and Brüning, U and Fritsche-Guenther, R and Pfannkuch, L and Kurth, F and Milek, M and Igbokwe, V and Löber, U and Gutbier, B and Holstein, M and Heinz, GA and Mashreghi, MF and Schulte, LN and Klatt, AB and Caesar, S and Wienhold, SM and Offermanns, S and Mack, M and Witzenrath, M and Jordan, S and Beule, D and Kirwan, JA and Forslund, SK and Wilck, N and Bartolomaeus, H and Heimesaat, MM and Opitz, B}, title = {Clinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2788}, pmid = {38555356}, issn = {2041-1723}, support = {OP 86/12-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; OP 86/13-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB-TR84 A5//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB 1449 B02//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB-TR84 A5//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Humans ; Mice ; Animals ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Monocytes ; *Anti-Infective Agents/pharmacology ; Klebsiella pneumoniae ; Lung ; }, abstract = {Hospital-acquired pneumonia (HAP) is associated with high mortality and costs, and frequently caused by multidrug-resistant (MDR) bacteria. Although prior antimicrobial therapy is a major risk factor for HAP, the underlying mechanism remains incompletely understood. Here, we demonstrate that antibiotic therapy in hospitalized patients is associated with decreased diversity of the gut microbiome and depletion of short-chain fatty acid (SCFA) producers. Infection experiments with mice transplanted with patient fecal material reveal that these antibiotic-induced microbiota perturbations impair pulmonary defense against MDR Klebsiella pneumoniae. This is dependent on inflammatory monocytes (IMs), whose fatty acid receptor (FFAR)2/3-controlled and phagolysosome-dependent antibacterial activity is compromized in mice transplanted with antibiotic-associated patient microbiota. Collectively, we characterize how clinically relevant antibiotics affect antimicrobial defense in the context of human microbiota, and reveal a critical impairment of IM´s antimicrobial activity. Our study provides additional arguments for the rational use of antibiotics and offers mechanistic insights for the development of novel prophylactic strategies to protect high-risk patients from HAP.}, } @article {pmid38554422, year = {2024}, author = {Paraschiv, AC and Vacaras, V and Nistor, C and Vacaras, C and Nistor, DT and Vesa, SC and Ilut, S and Muresanu, DF}, title = {Dysbiosis in Multiple Sclerosis: Can Immunoglobulin Y Supplements Help?.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {33}, number = {1}, pages = {115-122}, doi = {10.15403/jgld-5241}, pmid = {38554422}, issn = {1842-1121}, mesh = {Humans ; *Multiple Sclerosis/therapy ; Dysbiosis/microbiology/therapy ; Dietary Supplements/adverse effects ; *Probiotics/therapeutic use ; Inflammation ; *Autoimmune Diseases ; *Immunoglobulins ; }, abstract = {The role of gut microbiota in autoimmune disorders like multiple sclerosis is gaining attention. Multiple sclerosis is characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Alterations in gut microbiota have been linked to multiple sclerosis development, with decreased beneficial bacteria and increased harmful species. The gut-brain axis is a complex interface influencing bidirectional interactions between the gut and the brain. Dysbiosis, an imbalance in gut microbiota, has been associated with autoimmune diseases. The influence of gut microbiota in multiple sclerosis is reversible, making it a potential therapeutic target. Probiotics, prebiotics, and fecal microbiota transplantation have shown promise in multiple sclerosis treatment, with positive effects on inflammation and immune regulation. Immunoglobulin Y (IgY) supplements derived from chicken egg yolk have potential as nutraceuticals or dietary supplements. IgY technology has been effective against various infections, and studies have highlighted its role in modulating gut microbiota and immune responses. Clinical trials using IgY supplements in multiple sclerosis are limited but have shown positive outcomes, including reduced symptoms, and altered immune responses. Future research directions involve understanding the mechanisms of IgY's interaction with gut microbiota, optimal dosage determination, and long-term safety assessments. Combining IgY therapy with other interventions and investigating correlations between microbiota changes and clinical outcomes are potential avenues for advancing multiple sclerosis treatment with IgY supplements.}, } @article {pmid38441806, year = {2024}, author = {Blair, HA}, title = {SER-109 (VOWST[™]): A Review in the Prevention of Recurrent Clostridioides difficile Infection.}, journal = {Drugs}, volume = {84}, number = {3}, pages = {329-336}, pmid = {38441806}, issn = {1179-1950}, mesh = {Adult ; Humans ; Adolescent ; Quality of Life ; *Clostridioides difficile ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy/prevention & control ; Gastrointestinal Tract ; Recurrence ; Fecal Microbiota Transplantation ; }, abstract = {SER-109 (VOWST[™]; fecal microbiota spores, live-brpk) is a live biotherapeutic product indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in patients 18 years of age and older following standard of care (SOC) antibacterial treatment for recurrent CDI. It is a purified bacterial spore suspension sourced from healthy donors. As the first oral faecal microbiota product approved for prevention of recurrent CDI, SER-109 is administered as four capsules once daily for three consecutive days. In a well-designed, placebo-controlled, phase III trial (ECOSPOR III), SER-109 significantly reduced the risk of recurrent CDI at 8 weeks post-treatment, with a durable response seen at 6 months post-treatment. Treatment with SER-109 was also associated with rapid and steady improvement in health-related quality of life compared with placebo. SER-109 was generally well tolerated, with a safety profile similar to that of placebo. The most common adverse events were of mild to moderate severity and generally gastrointestinal in nature. Thus, with the convenience of oral administration and lack of necessity for cold storage, SER-109 is a valuable option for preventing further CDI recurrence in adults following antibacterial treatment for recurrent CDI.}, } @article {pmid38550860, year = {2024}, author = {Zhu, X and Zhou, Z and Pan, X}, title = {Research reviews and prospects of gut microbiota in liver cirrhosis: a bibliometric analysis (2001-2023).}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1342356}, pmid = {38550860}, issn = {1664-302X}, abstract = {INTRODUCTION: The gut-liver axis has emerged as a focal point in chronic liver disorders, prompting more research into the role of the gut microbiota in liver cirrhosis. In individuals with liver cirrhosis, changes in the structure and function of the gut microbiota are closely tied to clinical prognosis. However, there is a scarcity of bibliometric evaluations conducted in this particular field.

METHODS: This study is aiming to conduct a complete analysis of the knowledge structure and centers pertaining to gut microbiota in liver cirrhosis using bibliometric methods. Publications on gut microbiota and liver cirrhosis from 2001 to 2023 are sourced from the Web of Science Core Collection. For the bibliometric analysis, we employ VOSviewer, CiteSpace, and the R package "bibliometrix".

RESULTS: Our study encompasses a comprehensive collection of 3109 articles originating from 96 countries, with notable contributions from leading nations such as the United States and China. The quantity of publications concerning the gut microbiota of liver cirrhosis rises annually. The University of California San Diego, Virginia Commonwealth University, Zhejiang University are the primary research institutions. World Journal of Gastroenterology publishes the most papers in this field, while hepatology is the most frequently co-cited journal. These publications come from a total of 15,965 authors, and the most prolific authors are Bajaj Jasmohan S., Schnabl Bernd and Gillevet Patrick M., while the most co-cited authors are Bajaj Jasmohan S., Younossi Zobair M., and Reiner Wiest. In addition, "dysbiosis", "gut microbiota", "intestinal barrier", "fecal microbiota transplantation", and "complement-system" are the primary keywords of research trends in recent years.

DISCUSSION: This study offering a comprehensive insight into the research dynamics surrounding gut microbiota in patients with liver cirrhosis. It delineates the current research frontiers and hotspots, serving as a valuable guide for scholars.}, } @article {pmid38548771, year = {2024}, author = {Jiang, L and Ye, Y and Han, Y and Wang, Q and Lu, H and Li, J and Qian, W and Zeng, X and Zhang, Z and Zhao, Y and Shi, J and Luo, Y and Qiu, Y and Sun, J and Sheng, J and Huang, H and Qian, P}, title = {Microplastics dampen the self-renewal of hematopoietic stem cells by disrupting the gut microbiota-hypoxanthine-Wnt axis.}, journal = {Cell discovery}, volume = {10}, number = {1}, pages = {35}, pmid = {38548771}, issn = {2056-5968}, support = {82222003//National Natural Science Foundation of China (National Science Foundation of China)/ ; 92268117//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82370105//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82000149//National Natural Science Foundation of China (National Science Foundation of China)/ ; Z24H080001//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; LQ21H180006//Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)/ ; 2021M702853//China Postdoctoral Science Foundation/ ; }, abstract = {Microplastics (MPs) are contaminants ubiquitously found in the global biosphere that enter the body through inhalation or ingestion, posing significant risks to human health. Recent studies emerge that MPs are present in the bone marrow and damage the hematopoietic system. However, it remains largely elusive about the specific mechanisms by which MPs affect hematopoietic stem cells (HSCs) and their clinical relevance in HSC transplantation (HSCT). Here, we established a long-term MPs intake mouse model and found that MPs caused severe damage to the hematopoietic system. Oral gavage administration of MPs or fecal transplantation of microbiota from MPs-treated mice markedly undermined the self-renewal and reconstitution capacities of HSCs. Mechanistically, MPs did not directly kill HSCs but disrupted gut structure and permeability, which eventually ameliorated the abundance of Rikenellaceae and hypoxanthine in the intestine and inactivated the HPRT-Wnt signaling in bone marrow HSCs. Furthermore, administration of Rikenellaceae or hypoxanthine in mice as well as treatment of WNT10A in the culture system substantially rescued the MPs-induced HSC defects. Finally, we validated in a cohort of human patients receiving allogenic HSCT from healthy donors, and revealed that the survival time of patients was negatively correlated with levels of MPs, while positively with the abundance of Rikenellaceae, and hypoxanthine in the HSC donors' feces and blood. Overall, our study unleashes the detrimental roles and mechanisms of MPs in HSCs, which provides potential strategies to prevent hematopoietic damage from MPs and serves as a fundamental critique for selecting suitable donors for HSCT in clinical practice.}, } @article {pmid38548441, year = {2024}, author = {Singh, J and Ibrahim, B and Han, SH}, title = {Nontraditional Treatment of Hepatic Encephalopathy.}, journal = {Clinics in liver disease}, volume = {28}, number = {2}, pages = {297-315}, doi = {10.1016/j.cld.2024.01.007}, pmid = {38548441}, issn = {1557-8224}, mesh = {Humans ; *Hepatic Encephalopathy/therapy/drug therapy ; Gastrointestinal Agents/therapeutic use ; *Rifamycins/therapeutic use ; Rifaximin/therapeutic use ; Lactulose/therapeutic use ; }, abstract = {The pathophysiology of hepatic encephalopathy (HE) is complex, with hyperammonemia playing a central role in its development. Traditional therapies for HE have targeted ammonia and include medications such as lactulose and rifaximin. Although these agents are considered standard of care, nontraditional treatments seek to affect other factors in the pathogenesis of HE. Finally, procedural therapies include albumin dialysis, shunt closure, and the ultimate cure for HE, which is liver transplant. The treatments discussed provide alternative options for patients who have failed standard of care. However, more high-quality studies are needed to routinely recommend many of these agents.}, } @article {pmid38548440, year = {2024}, author = {Khalessi, A and Pyrsopoulos, NT}, title = {Pharmacologic Management of Hepatic Encephalopathy.}, journal = {Clinics in liver disease}, volume = {28}, number = {2}, pages = {287-296}, doi = {10.1016/j.cld.2024.01.006}, pmid = {38548440}, issn = {1557-8224}, abstract = {Hepatic encephalopathy is a common cause of morbidity and mortality among patients with decompensated liver cirrhosis. In this article, we review the history, mechanism, and evidence for first-line pharmacologic therapies for hepatic encephalopathy including nonabsorbable disaccharides, antibiotics, and electrolyte management. We also review newer, second-line therapies including polyethylene glycol, albumin, branched-chain amino acids, probiotics and fecal microbiota transplant, zinc, and l-ornithine-l-aspartate.}, } @article {pmid38547865, year = {2024}, author = {Yousefi, Y and Baines, KJ and Maleki Vareki, S}, title = {Microbiome bacterial influencers of host immunity and response to immunotherapy.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {101487}, doi = {10.1016/j.xcrm.2024.101487}, pmid = {38547865}, issn = {2666-3791}, abstract = {The gut microbiota influences anti-tumor immunity and can induce or inhibit response to immune checkpoint inhibitors (ICIs). Therefore, microbiome features are being studied as predictive/prognostic biomarkers of patient response to ICIs, and microbiome-based interventions are attractive adjuvant treatments in combination with ICIs. Specific gut-resident bacteria can influence the effectiveness of immunotherapy; however, the mechanism of action on how these bacteria affect anti-tumor immunity and response to ICIs is not fully understood. Nevertheless, early bacterial-based therapeutic strategies have demonstrated that targeting the gut microbiome through various methods can enhance the effectiveness of ICIs, resulting in improved clinical responses in patients with a diverse range of cancers. Therefore, understanding the microbiota-driven mechanisms of response to immunotherapy can augment the success of these interventions, particularly in patients with treatment-refractory cancers.}, } @article {pmid38546675, year = {2024}, author = {Pötgens, SA and Havelange, V and Lecop, S and Li, F and Neyrinck, AM and Bindels, F and Neveux, N and Demoulin, JB and Moors, I and Kerre, T and Maertens, J and Walter, J and Schoemans, H and Delzenne, NM and Bindels, LB}, title = {Gut microbiome alterations at acute myeloid leukemia diagnosis are associated with muscle weakness and anorexia.}, journal = {Haematologica}, volume = {}, number = {}, pages = {}, doi = {10.3324/haematol.2023.284138}, pmid = {38546675}, issn = {1592-8721}, abstract = {The gut microbiota makes critical contributions to host homeostasis, and its role in the treatment of acute myeloid leukaemia (AML) has attracted attention. We investigated whether the gut microbiome is affected by AML, and whether such changes are associated with cachectic hallmarks. Biological samples and clinical data were collected from 30 antibiotic-free AML patients at diagnosis and matched volunteers (1:1) in a multicenter cross-sectional prospective study. The composition and functional potential of the faecal microbiota were analyzed using shotgun metagenomics. Faecal, blood, and urine metabolomics analyses were performed. AML patients displayed muscle weakness, anorexia, signs of altered gut function, and glycaemic disorders. The composition of the faecal microbiota differed between patients with AML and control subjects, with an increase in oral bacteria. Alterations in bacterial functions and faecal metabolome support an altered redox status in the gut microbiota, which may contribute to the altered redox status observed in patients with AML. Eubacterium eligens, reduced 3-fold in AML patients, was strongly correlated with muscle strength and citrulline, a marker of enterocyte mass and function. Blautia and Parabacteroides, increased in patients with AML, were correlated with anorexia. Several bacterial taxa and metabolites (e.g. Blautia, Prevotella, phenylacetate, and hippurate) previously associated with glycaemic disorders were altered. Our work revealed important perturbations in the gut microbiome of AML patients at diagnosis, which are associated with muscle strength, altered redox status, and anorexia. These findings pave the way for future mechanistic work to explore the function and therapeutic potential of the bacteria identified in this study.}, } @article {pmid38546138, year = {2024}, author = {Pettit, NN and Shaeer, KM and Chahine, EB}, title = {Live Biotherapeutic Products for the Prevention of Recurrent Clostridioides difficile Infection.}, journal = {The Annals of pharmacotherapy}, volume = {}, number = {}, pages = {10600280241239685}, doi = {10.1177/10600280241239685}, pmid = {38546138}, issn = {1542-6270}, abstract = {OBJECTIVE: To review the efficacy, safety, and role of live biotherapeutic products (LBPs) in the prevention of recurrent Clostridioides difficile infection (rCDI).

DATA SOURCES: A literature search was performed using PubMed and Google Scholar (through February 2024) with search terms RBX2660, SER-109, and fecal microbiota. Other resources included abstracts presented at recent conferences, national clinical practice guidelines, and manufacturers' websites.

All relevant studies, trial updates, conference abstracts, and guidelines in the English language were included.

DATA SYNTHESIS: Two LBPs were recently approved by the Food and Drug Administration for the prevention of recurrence in adults following antibiotic treatment for rCDI. Fecal microbiota, live-jslm is administered rectally as a retention enema, whereas fecal microbiota spores, live-brpk is given orally after bowel preparation. Several phase 2 and phase 3 clinical trials have established the safety and efficacy of these LBPs in reducing rates of rCDI compared with placebo. Patients with severe immunosuppression and those with inflammatory bowel disease were largely excluded from these trials.

Live biotherapeutic products offer a similar mechanism to conventional fecal microbiota transplant (FMT) in preventing rCDI through microbiota restoration. The primary advantages of LBPs over FMT are their standardized composition and donor stool screening processes for transmissible pathogens. Bezlotoxumab is also available for the prevention of Clostridioides difficile infection; however, there are no clinical data available to compare the efficacy of LBPs with bezlotoxumab, and the benefit of simultaneous use of these preventative therapies is unclear.

CONCLUSIONS: Live biotherapeutic products provide a safe and effective option for the prevention of rCDI and represent an improvement over conventional FMT. Additional studies are needed to further determine their place in therapy relative to bezlotoxumab and in the setting of immunosuppression and inflammatory bowel disease.}, } @article {pmid38545472, year = {2024}, author = {Patel, RK and Cardeiro, M and Frankel, L and Kim, E and Takabe, K and Rashid, OM}, title = {Incidence of Colorectal Cancer After Intestinal Infection Due to Clostridioides difficile.}, journal = {World journal of oncology}, volume = {15}, number = {2}, pages = {279-286}, pmid = {38545472}, issn = {1920-454X}, abstract = {BACKGROUND: Clostridioides difficile (C. difficile or C. diff) is a toxin-producing bacteria that is notorious for causing life-threatening diarrhea. Recent literature has investigated various effects of Clostridioides difficile infection (CDI) in cancer patients, but research into the impact of CDI on the development of cancer and its effects on the microbiome is limited. CDI predominately affects the colon, which urges consideration into the sequalae of infection. This study investigated the correlation between CDI and the incidence of colorectal carcinoma (CRC).

METHODS: A retrospective study (2010 - 2020) was conducted using a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. The International Classification of Disease ninth and 10th Codes (ICD-9, ICD-10), Current Procedural Terminology (CPT), and National Drug Codes were used to identify CRC diagnosis, CDI, and matching or control parameters. Patients were matched for age, sex, Charlson Comorbidity Index (CCI), region of residence, and CDI treatment. An additional, but separate, query was executed to include obese patients with and without CDI, who were similarly matched and assessed for CRC. Statistical analyses were implemented to assess significance and estimate odds ratios (ORs).

RESULTS: CDI was associated with a decreased incidence of CRC (OR = 0.59, 95% confidence interval (CI): 0.55 - 0.63), and the difference was statistically significant (P < 2.2 × 10[-16]). CDI treatment, including appropriate antibiotics and fecal microbiota transplant (FMT), was controlled for in both infected and noninfected populations. Patients with a prior CDI who received relevant treatment were compared to patients with no history of CDI and received analogous treatment. Both populations subsequently developed CRC. Results remained statistically significant (P < 2.2 × 10[-16]) with a relative risk (RR) of 0.57 (95% CI: 0.54 - 0.60). Obesity was explored as a controlled variable in relation to CRC development in patients with and without prior CDI. Obese patients without a history of CDI were found to have a decreased risk of developing CRC. Results were statistically significant (P < 4.3 × 10[-13]) with an OR of 0.70 (95% CI: 0.63 - 0.77).

CONCLUSIONS: This study shows a statistically significant correlation between CDI and decreased incidence of CRC. Additionally, there is a statistically significant correlation between obese patients with CDI and an increased incidence of CRC. Further research is needed to explore the mechanism of this striking relationship and the implications of CDIs on the microbiome.}, } @article {pmid38544906, year = {2024}, author = {Marshall, DA and MacDonald, KV and Kao, D and Bernstein, CN and Kaplan, GG and Jijon, H and Hazlewood, G and Panaccione, R and Nasser, Y and Raman, M and Moayyedi, P}, title = {Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.}, journal = {Therapeutic advances in chronic disease}, volume = {15}, number = {}, pages = {20406223241239168}, pmid = {38544906}, issn = {2040-6223}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising treatment for active ulcerative colitis (UC). Understanding patient preferences can identify treatment features that may impact treatment decisions, improve shared decision-making, and contribute to patient-centered care, which is especially important in the context of novel treatments like FMT.

OBJECTIVES: We aimed to quantify preferences for active UC treatments, specifically FMT and biologics, and identify patient characteristics associated with different preference patterns.

DESIGN: This is a cross-sectional survey study.

METHODS: We administered a discrete choice experiment (DCE) survey to elicit preferences in a sample of Canadian adults with UC. DCE data were analyzed using a main-effects mixed logit model and used to predict uptake of hypothetical scenarios reflecting alternative combinations of treatment features. Latent class modeling identified heterogeneity in patient preference patterns.

RESULTS: Participants' (n = 201) mean age was 47.1 years (SD: 14.5 years), 58% were female, and most (84%) had at least some post-secondary education. Almost half were willing to undergo FMT. When considering treatments for active UC, the most important attributes were chance of remission and severity of rare unknown side effects. All else equal, participants were most likely to uptake treatment that involves oral capsules/pills. Participants in the class with the highest utility for chance of remission were younger, had more severe disease, and 58% indicated that they would be willing to undergo FMT.

CONCLUSION: We identified characteristics of UC patients who are more likely to be interested in FMT using preference elicitation methods. Patient-centered care can be enhanced by knowing which patients are more likely to be interested in FMT, potentially improving satisfaction with and adherence to treatments for active UC to maximize the effectiveness of treatment while considering heterogeneity in patient preferences.}, } @article {pmid38544348, year = {2024}, author = {Soukupova, H and Rehorova, V and Cibulkova, I and Duska, F}, title = {Assessment of Faecal Microbiota Transplant Stability in Deep-Freeze Conditions: A 12-Month Ex Vivo Viability Analysis.}, journal = {Journal of clinical laboratory analysis}, volume = {}, number = {}, pages = {e25023}, doi = {10.1002/jcla.25023}, pmid = {38544348}, issn = {1098-2825}, support = {//Univerzita Karlova v Praze/ ; //Donatio Intensivistam Endowement Fund/ ; //FNKV University Hospital/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an established treatment for Clostridioides difficile infection and is under investigation for other conditions. The availability of suitable donors and the logistics of fresh stool preparation present challenges, making frozen, biobanked stools an attractive alternative.

AIMS: This study aimed to evaluate the long-term viability of bacterial populations in faecal samples stored at -80°C for up to 12 months, supporting the feasibility of using frozen grafts for FMT.

METHODS: Fifteen faecal samples from nine healthy donors were processed, mixed with cryoprotectants and stored at -80°C. Samples were assessed at baseline and after 3, 6 and 12 months using quantitative culturing methods to determine the concentration of live bacteria.

RESULTS: Quantitative analysis showed no significant decrease in bacterial viability over the 12-month period for both aerobic and anaerobic cultures (p = 0.09). At all timepoints, the coefficients of variability in colony-forming unit (CFU) counts were greater between samples (102 ± 21% and 100 ± 13% for aerobic and anaerobic cultures, respectively) than the variability between measurements of the same sample (30 ± 22% and 30 ± 19%).

CONCLUSIONS: The study confirmed that faecal microbiota can be preserved with high viability in deep-freeze storage for up to a year, making allogenic FMT from biobanked samples a viable and safer option for patients. However, a multidonor approach may be beneficial to mitigate the risk of viability loss in any single donor sample.}, } @article {pmid38543535, year = {2024}, author = {Yadav, D and Sainatham, C and Filippov, E and Kanagala, SG and Ishaq, SM and Jayakrishnan, T}, title = {Gut Microbiome-Colorectal Cancer Relationship.}, journal = {Microorganisms}, volume = {12}, number = {3}, pages = {}, doi = {10.3390/microorganisms12030484}, pmid = {38543535}, issn = {2076-2607}, abstract = {Traditionally, the role of gut dysbiosis was thought to be limited to pathologies like Clostridioides difficile infection, but studies have shown its role in other intestinal and extraintestinal pathologies. Similarly, recent studies have surfaced showing the strong potential role of the gut microbiome in colorectal cancer, which was traditionally attributed mainly to sporadic or germline mutations. Given that it is the third most common cancer and the second most common cause of cancer-related mortality, 78 grants totaling more than USD 28 million have been granted to improve colon cancer management since 2019. Concerted efforts by several of these studies have identified specific bacterial consortia inducing a proinflammatory environment and promoting genotoxin production, causing the induction or progression of colorectal cancer. In addition, changes in the gut microbiome have also been shown to alter the response to cancer chemotherapy and immunotherapy, thus changing cancer prognosis. Certain bacteria have been identified as biomarkers to predict the efficacy of antineoplastic medications. Given these discoveries, efforts have been made to alter the gut microbiome to promote a favorable diversity to improve cancer progression and the response to therapy. In this review, we expand on the gut microbiome, its association with colorectal cancer, and antineoplastic medications. We also discuss the evolving paradigm of fecal microbiota transplantation in the context of colorectal cancer management.}, } @article {pmid38542753, year = {2024}, author = {Shi, Y and Chen, J and Qu, D and Sun, Q and Yu, Y and Zhang, H and Liu, Z and Sha, J and Sun, Y}, title = {Ginsenoside Rg5 Activates the LKB1/AMPK/mTOR Signaling Pathway and Modifies the Gut Microbiota to Alleviate Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet.}, journal = {Nutrients}, volume = {16}, number = {6}, pages = {}, doi = {10.3390/nu16060842}, pmid = {38542753}, issn = {2072-6643}, support = {2023YFD1601600//National Key Research and Development Program/ ; 2023QN16//Jilin Provincial Department of Human Resources and Social Security/ ; 202301ZYTS352//Jilin Province Science and Technology Development Program/ ; }, abstract = {The primary objective of this investigation was to elucidate the manner in which ginsenoside Rg5 (Rg5) ameliorates nonalcoholic fatty liver disease (NAFLD) via the modulation of the gut microbiota milieu. We administered either a standard diet (ND) or a high-fat diet (HFD), coupled with 12-week treatment employing two distinct doses of Rg5 (50 and 100 mg/kg/d), to male C57BL/6J mice. In comparison to the HFD cohort, the Rg5-treated group demonstrated significant enhancements in biochemical parameters, exemplified by a substantial decrease in lipid concentrations, as well as the reduced expression of markers indicative of oxidative stress and liver injury. This signifies a mitigation of hepatic dysfunction induced by an HFD. Simultaneously, Rg5 demonstrates the capacity to activate the LKB1/AMPK/mTOR signaling pathway, instigating energy metabolism and consequently hindering the progression of NAFLD. Furthermore, we underscored the role of Rg5 in the treatment of NAFLD within the gut-microbiota-liver axis. Analysis via 16S rRNA sequencing unveiled that Rg5 intervention induced alterations in gut microbiota composition, fostering an increase in beneficial bacteria, such as Bacteroides and Akkermansia, while concurrently reducing the relative abundance of detrimental bacteria, exemplified by Olsenella. Furthermore, employing fecal microbiota transplantation (FMT) experiments, we observed analogous outcomes in mice subjected to fecal bacterial transplants, providing additional verification of the capacity of Rg5 to mitigate NAFLD in mice by actively participating in the restoration of gut microbiota via FMT. Drawing from these data, the regulation of the gut microbiota is recognized as an innovative strategy for treating or preventing NAFLD and metabolic syndrome. Consequently, these research findings suggest that Rg5 holds promise as a potential therapeutic agent for NAFLD management.}, } @article {pmid38541242, year = {2024}, author = {Choi, SY and Choi, JH}, title = {Ovarian Cancer and the Microbiome: Connecting the Dots for Early Diagnosis and Therapeutic Innovations-A Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {3}, pages = {}, doi = {10.3390/medicina60030516}, pmid = {38541242}, issn = {1648-9144}, support = {NRF-2017R1A5A2014768 and 2022R1A2C1003498//National Research Foundation of Korea/ ; }, abstract = {Ovarian cancer, which ranks eighth among global female cancers and fifth in fatality, poses a significant health challenge owing to its asymptomatic early stages. Understanding the pathogenesis requires extensive research. Recent studies have emphasized the role of the gut and cervicovaginal microbiota in ovarian cancer. This review explores the current understanding of the relationship between the microbiome and ovarian cancer, considering the potential of biomarkers in the serum and various tissues. Insights into the influence of the microbiome on treatments, including surgery and chemotherapy, open doors to innovative approaches, such as fecal microbiome transplantation. This synthesis of recent findings provides crucial insights into the intricate interplay between the microbiome and ovarian cancer, thereby shaping diagnostic and treatment strategies.}, } @article {pmid38535842, year = {2024}, author = {Jessop, E and Li, L and Renaud, DL and Verbrugghe, A and Macnicol, J and Gamsjäger, L and Gomez, DE}, title = {Neonatal Calf Diarrhea and Gastrointestinal Microbiota: Etiologic Agents and Microbiota Manipulation for Treatment and Prevention of Diarrhea.}, journal = {Veterinary sciences}, volume = {11}, number = {3}, pages = {}, doi = {10.3390/vetsci11030108}, pmid = {38535842}, issn = {2306-7381}, abstract = {Neonatal calf diarrhea is the leading cause of neonatal morbidity and mortality globally. The changes associated with the gastrointestinal microbiota in neonatal calves experiencing diarrhea and its etiology are not fully understood or completely defined in the literature. Several studies have demonstrated that the fecal microbiota of calves that experience diarrhea substantially deviates from that of healthy age-matched calves. However, one key question remains: whether the changes observed in the bacterial communities (also known as dysbiosis) are a predisposing factor for, or the consequence of, gastrointestinal inflammation caused by the pathogens associated with calf diarrhea. The first objective of this literature review is to present the current information regarding the changes in the fecal microbiota of diarrheic calves and the impact of the pathogens associated with diarrhea on fecal microbiota. Modulation of the gastrointestinal microbiota using pre- and probiotics, colostrum feeding, and fecal microbiota transplantation (FMT) has been used to treat and prevent gastrointestinal diseases in humans and dogs. Although information regarding the use of probiotics for the prevention of diarrhea is available in cattle, little information is available regarding the use of these strategies for treating calf diarrhea and the use of prebiotics or FMT to prevent diarrhea. The second objective of this literature review is to summarize the current knowledge regarding the impact of prebiotics, probiotics, synbiotics, colostrum feeding, and FMT for the treatment and prevention of calf diarrhea.}, } @article {pmid38534216, year = {2024}, author = {Clarke, LM and Allegretti, JR}, title = {The epidemiology and management of Clostridioides difficile infection-A clinical update.}, journal = {Alimentary pharmacology & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.17975}, pmid = {38534216}, issn = {1365-2036}, abstract = {BACKGROUND: Clostridioides difficile is the most common cause of healthcare-associated infection, and severe cases can result in significant complications. While anti-microbial therapy is central to infection management, adjunctive therapies may be utilised as preventative strategies.

AIM: This article aims to review updates in the epidemiology, diagnosis, and management, including treatment and prevention, of C. difficile infections.

METHODS: A narrative review was performed to evaluate the current literature between 1986 and 2023.

RESULTS: The incidence of C. difficile infection remains significantly high in both hospital and community settings, though with an overall decline in recent years and similar surveillance estimates globally. Vancomycin and fidaxomicin remain the first line antibiotics for treatment of non-severe C. difficile infection, though due to lower recurrence rates, infectious disease society guidelines now favour use of fidaxomicin. Faecal microbiota transplantation should still be considered to prevent recurrent C. difficile infection. However, in the past year the field has had a significant advancement with the approval of the first two live biotherapeutic products-faecal microbiota spores-live brpk, an oral capsule preparation, and faecal microbiota live-jslm-both indicated for the prevention of recurrent C. difficile infection, with additional therapies on the horizon.

CONCLUSION: Although the prevalence of C. difficile infection remains high, there have been significant advances in the development of novel therapeutics and preventative measures following changes in recent practice guidelines, and will continue to evolve in the future.}, } @article {pmid38533674, year = {2024}, author = {Cui, J and Wang, S and Zhai, Z and Song, X and Qiu, T and Yu, L and Zhai, Q and Zhang, H}, title = {Induction of autism-related behavior in male mice by early-life vitamin D deficiency: association with disruption of the gut microbial composition and homeostasis.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo00279b}, pmid = {38533674}, issn = {2042-650X}, abstract = {Vitamin D deficiency (VDD) during early life emerges as a potential risk factor for autism spectrum disorder (ASD). Individuals with autism commonly exhibit lower vitamin D (VD) levels compared to the general population, and VD deficiency is prevalent during pregnancy and lactation. Moreover, gastrointestinal comorbidity, prevalent in ASD patients, correlates closely with disruptions in the gut microbiota and altered intestinal permeability. Therefore, it is fascinating and significant to explore the effects of maternal VD deficiency during pregnancy and lactation on the maturation of the gut microbiota of the offspring and its relevance to autism spectrum disorders. In this study, we established maternal pregnancy and lactation VD-deficient mouse models, employed shotgun macrogenomic sequencing to unveil alterations in the gut microbiome of offspring mice, and observed autism-related behaviours. Furthermore, fecal microbial transplantation (FMT) reversed repetitive and anxious behaviours and alleviated social deficits in offspring mice by modulating the gut microbiota and increasing short-chain fatty acid levels in the cecum, along with influencing the concentrations of claudin-1 and occludin in the colon. Our findings confirm that VDD during pregnancy and lactation is a risk factor for autism in the offspring, with disturbances in the structure and function of the offspring's gut microbiota contributing at least part of the effect. The study emphasises the importance of nutrition and gut health early in life. Simultaneously, this study further demonstrates the effect of VDD on ASD and provides potential ideas for early prevention and intervention of ASD.}, } @article {pmid38532703, year = {2024}, author = {Sheikh, IA and Bianchi-Smak, J and Laubitz, D and Schiro, G and Midura-Kiela, MT and Besselsen, DG and Vedantam, G and Jarmakiewicz, S and Filip, R and Ghishan, FK and Gao, N and Kiela, PR}, title = {Transplant of microbiota from Crohn's disease patients to germ-free mice results in colitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2333483}, doi = {10.1080/19490976.2024.2333483}, pmid = {38532703}, issn = {1949-0984}, mesh = {Humans ; Mice ; Animals ; *Crohn Disease/microbiology ; *Clostridioides difficile ; *Gastrointestinal Microbiome ; *Colitis ; *Microbiota ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology ; }, abstract = {Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn's disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn's ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis. We observed a markedly reduced engraftment of CD_L3 microbiome compared to healthy control microbiota. FMT from CD_L3 patients did not lead to ileitis but resulted in colitis with features consistent with CD: a discontinued pattern of colitis, more proximal colonic localization, enlarged isolated lymphoid follicles and/or tertiary lymphoid organ neogenesis, and a transcriptomic pattern consistent with epithelial reprograming and promotion of the Paneth cell-like signature in the proximal colon and immune dysregulation characteristic of CD. The observed inflammatory response was associated with persistently increased abundance of Ruminococcus gnavus, Erysipelatoclostridium ramosum, Faecalimonas umbilicate, Blautia hominis, Clostridium butyricum, and C. paraputrificum and unexpected growth of toxigenic C. difficile, which was below the detection level in the community used for inoculation. Our study provides the first evidence that the transfer of a dysbiotic community from CD patients can lead to spontaneous inflammatory changes in the colon of xGF mice and identifies a signature microbial community capable of promoting colonization of pathogenic and conditionally pathogenic bacteria.}, } @article {pmid38532577, year = {2024}, author = {Chang, M and Chang, KT and Chang, F}, title = {Just a gut feeling: Faecal microbiota transplant for treatment of depression - A mini-review.}, journal = {Journal of psychopharmacology (Oxford, England)}, volume = {}, number = {}, pages = {2698811241240308}, doi = {10.1177/02698811241240308}, pmid = {38532577}, issn = {1461-7285}, abstract = {BACKGROUND: The microbiota-gut-brain axis (MGBA) allows bidirectional crosstalk between the brain and gut microbiota (GM) and is believed to contribute to regulating mood/cognition/behaviour/metabolism/health and homeostasis. Manipulation of GM through faecal microbiota transplant (FMT) is a new, exciting and promising treatment for major depressive disorder (MDD).

AIMS: This mini-review examines current research into GM and FMT as a therapy for depression.

METHODS: Original research articles published in Medline/Cochrane Library/PubMed/EMBASE/PsycINFO databases/National Institute of Health website Clinicaltrials.gov/controlled-trials.com were searched. Full articles included in reference lists were evaluated. We summarise current data on GM and depression and discuss communication through the MGBA and the interaction of antidepressants and GM through this. We review compositions of dysbiosis in depressed cohorts, focusing on future directions in the treatment of MDD.

RESULTS: Studies have demonstrated significant gut dysbiosis in depressed patients compared to healthy cohorts, with overgrowth of pro-inflammatory microbiota, reduction in anti-inflammatory species and reduced overall stability and taxonomic richness. FMT allows the introduction of healthy microbiota into the gastrointestinal tract, facilitating the restoration of eubiosis.

CONCLUSION: The GM plays an integral role in human health and disease through its communication with the rest of the body via the MGBA. FMT may provide a means to transfer the healthy phenotype into the recipient and this concept in humans is attracting enormous attention as a prospective treatment for psychopathologies, such as MDD, in the future. It may be possible to manipulate the GM in a number of ways, but further research is needed to determine the exact likelihood and profiles involved in the development and amelioration of MDD in humans, as well as the long-term effects and potential risks of this procedure.}, } @article {pmid38531874, year = {2024}, author = {Luu, LDW and Pandey, A and Paramsothy, S and Ngo, C and Castaño-Rodríguez, N and Liu, C and Kamm, MA and Borody, TJ and Man, SM and Kaakoush, NO}, title = {Profiling the colonic mucosal response to fecal microbiota transplantation identifies a role for GBP5 in colitis in humans and mice.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {2645}, pmid = {38531874}, issn = {2041-1723}, support = {APP2011047//Department of Health | National Health and Medical Research Council (NHMRC)/ ; APP2002686//Department of Health | National Health and Medical Research Council (NHMRC)/ ; IBD-0391R//Crohn's and Colitis Foundation (Crohn's & Colitis Foundation)/ ; 988415//Crohn's and Colitis Foundation (Crohn's & Colitis Foundation)/ ; }, mesh = {Humans ; Female ; Mice ; Animals ; *Fecal Microbiota Transplantation ; Feces ; *Colitis, Ulcerative ; Intestinal Mucosa ; Treatment Outcome ; GTP-Binding Proteins ; }, abstract = {Host molecular responses to fecal microbiota transplantation (FMT) in ulcerative colitis are not well understood. Here, we profile the human colonic mucosal transcriptome prior to and following FMT or placebo to identify molecules regulated during disease remission. FMT alters the transcriptome above the effect of placebo (n = 75 vs 3 genes, q < 0.05), including modulation of structural, metabolic and inflammatory pathways. This response is attributed to responders with no consistency observed in non-responders. Regulated pathways in responders include tight junctions, calcium signalling and xenobiotic metabolism. Genes significantly regulated longitudinally in responders post-FMT could discriminate them from responders and non-responders at baseline and non-responders post-FMT, with GBP5 and IRF4 downregulation being associated with remission. Female mice with a deletion of GBP5 are more resistant to developing colitis than their wild-type littermates, showing higher colonic IRF4 phosphorylation. The colonic mucosal response discriminates UC remission following FMT, with GBP5 playing a detrimental role in colitis.}, } @article {pmid38531144, year = {2024}, author = {Yu, H and Yang, WM and Chen, YH and Guo, L and Li, R and Xue, F and Tan, QR and Peng, ZW}, title = {The gut microbiome from middle-aged women with depression modulates depressive-like behaviors and plasma fatty acid metabolism in female middle-aged mice.}, journal = {Journal of psychiatric research}, volume = {173}, number = {}, pages = {139-150}, doi = {10.1016/j.jpsychires.2024.03.023}, pmid = {38531144}, issn = {1879-1379}, abstract = {BACKGROUND: Intestinal dysbacteriosis has frequently been involved in the context of depression. Nonetheless, only scant information is available about the features and functional changes of gut microbiota in female middle-aged depression (MAD).

OBJECTIVE: This study aims to explore whether there are characteristic changes in the gut microbes of female MAD and whether these changes are associated with depressive-like behaviors. Meanwhile, this study observed alterations in the lipid metabolism function of gut microbes and further examined changes in plasma medium- and long-chain fatty acids (MLCFAs) in mice that underwent fecal microbiota transplantation (FMT).

METHODS: Stool samples obtained from 31 MAD, along with 24 healthy individuals (HC) were analyzed by 16 S rRNA gene sequencing. Meanwhile, 14-month-old female C57BL/6J mice received antibiotic cocktails and then oral gavage of the microbiota suspension of MAD or HC for 3 weeks to reconstruct gut microbiota. The subsequent depressive-like behaviors, the composition of gut microbiota, as well as MLCFAs in the plasma were evaluated.

RESULTS: A noteworthy disruption in gut microbial composition in MAD individuals compared to HC was observed. Several distinct bacterial taxa, including Dorea, Butyricicoccus, and Blautia, demonstrated associations with the demographic variables. A particular microbial panel encompassing 49 genera effectively differentiated MAD patients from HC (AUC = 0.82). Fecal microbiome transplantation from MAD subjects led to depressive-like behaviors and dysfunction of plasma MLCFAs in mice.

CONCLUSIONS: These findings suggest that microbial dysbiosis is linked to the pathogenesis of MAD, and its role may be associated with the regulation of MLCFAs metabolism.}, } @article {pmid38530054, year = {2024}, author = {Gurung, M and Schlegel, BT and Rajasundaram, D and Fox, R and Bode, L and Yao, T and Lindemann, SR and LeRoith, T and Read, QD and Simecka, C and Carroll, L and Andres, A and Yeruva, L}, title = {Microbiota from human infants consuming secretors or non-secretors mothers' milk impacts the gut and immune system in mice.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0029424}, doi = {10.1128/msystems.00294-24}, pmid = {38530054}, issn = {2379-5077}, abstract = {UNLABELLED: Maternal secretor status is one of the determinants of human milk oligosaccharides (HMOs) composition, which, in turn, influences the gut microbiota composition of infants. To understand if this change in gut microbiota impacts immune cell composition, intestinal morphology, and gene expression, 21-day-old germ-free C57BL/6 mice were transplanted with fecal microbiota from infants whose mothers were either secretors (SMM) or non-secretors (NSM) or from infants consuming dairy-based formula (MFM). For each group, one set of mice was supplemented with HMOs. HMO supplementation did not significantly impact the microbiota diversity; however, SMM mice had a higher abundance of genus Bacteroides, Bifidobacterium, and Blautia, whereas, in the NSM group, there was a higher abundance of Akkermansia, Enterocloster, and Klebsiella. In MFM, gut microbiota was represented mainly by Parabacteroides, Ruminococcaceae_unclassified, and Clostrodium_sensu_stricto. In mesenteric lymph node, Foxp3+ T cells and innate lymphoid cells type 2 were increased in MFM mice supplemented with HMOs, while in the spleen, they were increased in SMM + HMOs mice. Similarly, serum immunoglobulin A was also elevated in MFM + HMOs group. Distinct global gene expression of the gut was observed in each microbiota group, which was enhanced with HMOs supplementation. Overall, our data show that distinct infant gut microbiota due to maternal secretor status or consumption of dairy-based formula and HMO supplementation impacts immune cell composition, antibody response, and intestinal gene expression in a mouse model.

IMPORTANCE: Early life factors like neonatal diet modulate gut microbiota, which is important for the optimal gut and immune function. One such factor, human milk oligosaccharides (HMOs), the composition of which is determined by maternal secretor status, has a profound effect on infant gut microbiota. However, how the infant gut microbiota composition determined by maternal secretor status or consumption of infant formula devoid of HMOs impacts infant intestinal ammorphology, gene expression, and immune signature is not well explored. This study provides insights into the differential establishment of infant microbiota derived from infants fed by secretor or non-secretor mothers milk or those consuming infant formula and demonstrates that the secretor status of mothers promotes Bifidobacteria and Bacteroides sps. establishment. This study also shows that supplementation of pooled HMOs in mice changed immune cell composition in the spleen and mesenteric lymph nodes and immunoglobulins in circulation. Hence, this study highlights that maternal secretor status has a role in infant gut microbiota composition, and this, in turn, can impact host gut and immune system.}, } @article {pmid38529272, year = {2024}, author = {Yang, Y and Ma, Q and Wang, Q and Zhao, L and Liu, H and Chen, Y}, title = {Mannose enhances intestinal immune barrier function and dextran sulfate sodium salt-induced colitis in mice by regulating intestinal microbiota.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1365457}, pmid = {38529272}, issn = {1664-3224}, mesh = {Mice ; Humans ; Animals ; *Gastrointestinal Microbiome ; Mannose ; Dextran Sulfate/toxicity ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Occludin/genetics ; Quality of Life ; *Colitis/chemically induced/therapy/metabolism ; *Inflammatory Bowel Diseases ; Sodium Chloride ; Sodium Chloride, Dietary ; Body Weight ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) greatly affects human quality of life. Mannose has been reported to be used to treat IBD, but the mechanism is currently unknown.

METHODS: C57/BL mice were used as research subjects, and the mouse acute colitis model was induced using dextran sulfate sodium salt (DSS). After oral administration of mannose, the body weights and disease activity index (DAI) scores of the mice were observed. The colon lengths, histopathological sections, fecal content microbial sequencing, colon epithelial inflammatory genes, and tight junction protein Occludin-1 expression levels were measured. We further used the feces of mice that had been orally administered mannose to perform fecal bacterial transplantation on the mice with DSS-induced colitis and detected the colitis-related indicators.

RESULTS: Oral administration of mannose increased body weights and colon lengths and reduced DAI scores in mice with DSS-induced colitis. In addition, it reduced the expression of colon inflammatory genes and the levels of serum inflammatory factors (TNF-α, IL-6, and IL-1β), further enhancing the expression level of the colonic Occludin-1 protein and alleviating the toxic response of DSS to the intestinal epithelium of the mice. In addition, gut microbial sequencing revealed that mannose increased the abundance and diversity of intestinal flora. Additionally, after using the feces of the mannose-treated mice to perform fecal bacterial transplantation on the mice with DSS-induced colitis, they showed the same phenotype as the mannose-treated mice, and both of them alleviated the intestinal toxic reaction induced by the DSS. It also reduced the expression of intestinal inflammatory genes (TNF-α, IL-6, and IL-1β) and enhanced the expression level of the colonic Occludin-1 protein.

CONCLUSION: Mannose can treat DSS-induced colitis in mice, possibly by regulating intestinal microorganisms to enhance the intestinal immune barrier function and reduce the intestinal inflammatory response.}, } @article {pmid38528541, year = {2024}, author = {Yu, F and Hu, X and Ren, H and Wang, X and Shi, R and Guo, J and Chang, J and Zhou, X and Jin, Y and Li, Y and Liu, Z and Hu, P}, title = {Protective effect of synbiotic combination of Lactobacillus plantarum SC-5 and olive oil extract tyrosol in a murine model of ulcerative colitis.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {308}, pmid = {38528541}, issn = {1479-5876}, support = {JLUXKJC2021ZY08//Interdisciplinary Integration and Innovation Project of JLU/ ; 419080520415//the Excellent Young Teachers Training Plan of Jilin University/ ; }, mesh = {Animals ; Mice ; *Colitis, Ulcerative/drug therapy ; *Lactobacillus plantarum ; Olive Oil ; NF-kappa B ; *Synbiotics ; Occludin ; Disease Models, Animal ; *Colitis/chemically induced ; Inflammation/complications/drug therapy ; Colon ; Anti-Inflammatory Agents/pharmacology/therapeutic use ; *Inflammatory Bowel Diseases/drug therapy ; Dextran Sulfate/adverse effects ; Mice, Inbred C57BL ; Phenylethyl Alcohol/*analogs & derivatives ; }, abstract = {BACKGROUND: Ulcerative colitisis (UC) classified as a form of inflammatory bowel diseases (IBD) characterized by chronic, nonspecific, and recurrent symptoms with a poor prognosis. Common clinical manifestations of UC include diarrhea, fecal bleeding, and abdominal pain. Even though anti-inflammatory drugs can help alleviate symptoms of IBD, their long-term use is limited due to potential side effects. Therefore, alternative approaches for the treatment and prevention of inflammation in UC are crucial.

METHODS: This study investigated the synergistic mechanism of Lactobacillus plantarum SC-5 (SC-5) and tyrosol (TY) combination (TS) in murine colitis, specifically exploring their regulatory activity on the dextran sulfate sodium (DSS)-induced inflammatory pathways (NF-κB and MAPK) and key molecular targets (tight junction protein). The effectiveness of 1 week of treatment with SC-5, TY, or TS was evaluated in a DSS-induced colitis mice model by assessing colitis morbidity and colonic mucosal injury (n = 9). To validate these findings, fecal microbiota transplantation (FMT) was performed by inoculating DSS-treated mice with the microbiota of TS-administered mice (n = 9).

RESULTS: The results demonstrated that all three treatments effectively reduced colitis morbidity and protected against DSS-induced UC. The combination treatment, TS, exhibited inhibitory effects on the DSS-induced activation of mitogen-activated protein kinase (MAPK) and negatively regulated NF-κB. Furthermore, TS maintained the integrity of the tight junction (TJ) structure by regulating the expression of zona-occludin-1 (ZO-1), Occludin, and Claudin-3 (p < 0.05). Analysis of the intestinal microbiota revealed significant differences, including a decrease in Proteus and an increase in Lactobacillus, Bifidobacterium, and Akkermansia, which supported the protective effect of TS (p < 0.05). An increase in the number of Aspergillus bacteria can cause inflammation in the intestines and lead to the formation of ulcers. Bifidobacterium and Lactobacillus can regulate the micro-ecological balance of the intestinal tract, replenish normal physiological bacteria and inhibit harmful intestinal bacteria, which can alleviate the symptoms of UC. The relative abundance of Akkermansia has been shown to be negatively associated with IBD. The FMT group exhibited alleviated colitis, excellent anti-inflammatory effects, improved colonic barrier integrity, and enrichment of bacteria such as Akkermansia (p < 0.05). These results further supported the gut microbiota-dependent mechanism of TS in ameliorating colonic inflammation.

CONCLUSION: In conclusion, the TS demonstrated a remission of colitis and amelioration of colonic inflammation in a gut microbiota-dependent manner. The findings suggest that TS could be a potential natural medicine for the protection of UC health. The above results suggest that TS can be used as a potential therapeutic agent for the clinical regulation of UC.}, } @article {pmid38527650, year = {2024}, author = {Costa, DVS and Pham, NV and Loureiro, AV and Yang, SE and Behm, BW and Warren, CA}, title = {Clostridioides difficile infection promotes gastrointestinal dysfunction in human and mice post-acute phase of the disease.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {102837}, doi = {10.1016/j.anaerobe.2024.102837}, pmid = {38527650}, issn = {1095-8274}, abstract = {OBJECTIVES: In the US, Clostridioides difficile (C. difficile) infection (CDI) is the 8th leading cause for hospital readmission and 7th for mortality among all gastrointestinal (GI) disorders. Here, we investigated GI dysfunction post-CDI in human and mice post-acute infection.

MATERIALS AND METHODS: From March 2020 to July 2021, we reviewed the clinical records of 67 patients referred to the UVA Complicated C. difficile clinic for fecal microbiota transplantation (FMT) eligibility. In vivo, C57BL/6 mice were infected with C. difficile and clinical scores were determined daily. Stool samples from mice were collected to measure the shedding of C. difficile and myeloperoxidase (MPO) levels. On day 21 post-infection, Evans's blue and FITC-70kDa method were performed to evaluate GI motility in mice.

RESULTS: Of the 67 patients evaluated at the C. difficile clinic, 40 patients (59.7%) were confirmed to have CDI, and 22 patients (32.8%) with post-CDI IBS (diarrhea-type, constipation-type, and mixed-type). In infected mice, levels of MPO in stools and clinical score were higher on day 3. On day 21, mice have recovered from body weight loss induced by CDI, and fecal MPO was undetectable. The total GI transit time (TGITT) and FITC-70kDa levels on proximal colon were increased in infected mice (p = 0.002), suggesting a constipation phenotype post-acute phase of CDI. A positive correlation on intestinal inflammation on day 3 and TGITT on day 21 was observed.

CONCLUSION: In conclusion, post-infection intestinal dysfunction occurs in humans and mice post-CDI. Importantly, we have validated in the mouse model that CDI causes abnormal GI transit in the recovery phase of the disease, indicating the potential utility of the model in exploring the underlying mechanisms of post-infectious IBS in humans.}, } @article {pmid38527453, year = {2024}, author = {Maccauro, V and Fianchi, F and Gasbarrini, A and Ponziani, FR}, title = {GUT MICROBIOTA IN PRIMARY SCLEROSING CHOLANGITIS: FROM PROGNOSTIC ROLE TO THERAPEUTIC IMPLICATIONS.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {}, number = {}, pages = {}, doi = {10.1159/000538493}, pmid = {38527453}, issn = {1421-9875}, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease of unknown etiology characterized by biliary inflammation and periductal fibrosis. The gut microbiota plays a crucial role in the pathogenesis of PSC by regulating bile acids metabolism, inflammation and immune response. On the other hand, liver disease progression affects the composition of the gut microbiota, fostering these mechanisms in a mutual detrimental way.

SUMMARY: Recent evidences described a specific pro-inflammatory microbial signature in PSC patients, with an overall reduced bacterial diversity and the loss of beneficial metabolites such as short-chain fatty acids. As effective therapies for PSC are still lacking, targeting the gut microbiota offers a new perspective in the management of this disease. To date, antibiotics, fecal microbiota transplantation and probiotics are the most studied gut microbiota-targeted intervention in PSC, but new potential strategies such as vaccines and bacteriophages represent possible future therapeutic horizons.

KEY MESSAGES: In this review, we focus on the role of the gut microbiota in PSC, considering its pathogenetic and prognostic role, and the therapeutic implications.}, } @article {pmid38527267, year = {2024}, author = {Fletcher, KA and Johnson, DB}, title = {Investigational Approaches for Treatment of Melanoma Patients Progressing After Standard of Care.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {30}, number = {2}, pages = {126-131}, doi = {10.1097/PPO.0000000000000702}, pmid = {38527267}, issn = {1540-336X}, mesh = {Humans ; *Melanoma/therapy ; Standard of Care ; Immunotherapy ; Proto-Oncogene Proteins B-raf ; }, abstract = {The advent of effective immunotherapy, specifically cytotoxic T-lymphocyte associated protein 4 and programmed cell death 1 inhibitors, as well as targeted therapy including BRAF/MEK inhibitors, has dramatically changed the prognosis for metastatic melanoma patients. Up to 50% of patients may experience long-term survival currently. Despite these advances in melanoma treatment, many patients still progress and die of their disease. As such, there are many studies aimed at providing new treatment options for this population. Therapies currently under investigation include, but are not limited to, novel immunotherapies, targeted therapies, tumor-infiltrating lymphocytes and other cellular therapies, oncolytic viral therapy and other injectables, and fecal microbiota transplant. In this review, we discuss the emerging treatment options for metastatic melanoma patients who have progressed on standard of care treatments.}, } @article {pmid38524669, year = {2024}, author = {D'Amico, F and Rinaldi, M and Pascale, R and Fabbrini, M and Morelli, MC and Siniscalchi, A and Laici, C and Coladonato, S and Ravaioli, M and Cescon, M and Ambretti, S and Viale, P and Brigidi, P and Turroni, S and Giannella, M}, title = {Gut microbiome dynamics and Enterobacterales infection in liver transplant recipients: A prospective observational study.}, journal = {JHEP reports : innovation in hepatology}, volume = {6}, number = {4}, pages = {101039}, pmid = {38524669}, issn = {2589-5559}, abstract = {BACKGROUND & AIMS: The aim of this study was to investigate gut microbiome (GM) dynamics in relation to carbapenem-resistant Enterobacterales (CRE) colonization, CRE infection, and non-CRE infection development within 2 months after liver transplant (LT).

METHODS: A single-center, prospective study was performed in patients undergoing LT from November 2018 to January 2020. The GM was profiled through 16S rRNA amplicon sequencing of a rectal swab taken on the day of transplantation, and fecal samples were collected weekly until 1 month after LT. A subset of samples was subjected to shotgun metagenomics, including resistome dynamics. The primary endpoint was to explore changes in the GM in the following groups: (1) CRE carriers developing CRE infection (CRE_I); (2) CRE carriers not developing infection (CRE_UI); (3) non-CRE carriers developing microbial infection (INF); and (4) non-CRE carriers not developing infection (NEG).

RESULTS: Overall, 97 patients were enrolled, and 91 provided fecal samples. Of these, five, nine, 22, and 55 patients were classified as CRE_I, CRE_UI, INF, and NEG, respectively. CRE_I patients showed an immediate and sustained post-LT decrease in alpha diversity, with depletion of the GM structure and gradual over-representation of Klebsiella and Enterococcus. The proportions of Klebsiella were significantly higher in CRE_I patients than in NEG patients even before LT, serving as an early marker of subsequent CRE infection. CRE_UI patients had a more stable and diverse GM, whose compositional dynamics tended to overlap with those of NEG patients.

CONCLUSIONS: GM profiling before LT could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.

IMPACT AND IMPLICATIONS: Little is known about the temporal dynamics of gut microbiome (GM) in liver transplant recipients associated with carbapenem-resistant Enterobacterales (CRE) colonization and infection. The GM structure and functionality of patients colonized with CRE and developing infection appeared to be distinct compared with CRE carriers without infection or patients with other microbial infection or no infection and CRE colonization. Higher proportions of antimicrobial-resistant pathogens and poor representation of bacteria and metabolic pathways capable of promoting overall host health were observed in CRE carriers who developed infection, even before liver transplant. Therefore, pretransplant GM profiling could improve patient stratification and risk prediction and guide early GM-based intervention strategies to reduce infectious complications and improve overall prognosis.}, } @article {pmid38521337, year = {2024}, author = {Wan, L and Qian, C and Yang, C and Peng, S and Dong, G and Cheng, P and Zong, G and Han, H and Shao, M and Gong, G and Deng, Z and Pan, H and Wang, H and Liu, X and Wang, G and Lu, Y and Zhao, Y and Jiang, Z}, title = {Ginseng polysaccharides ameliorate ulcerative colitis via regulating gut microbiota and tryptophan metabolism.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {130822}, doi = {10.1016/j.ijbiomac.2024.130822}, pmid = {38521337}, issn = {1879-0003}, abstract = {Ulcerative colitis (UC) is regarded as a recurring inflammatory disorder of the gastrointestinal tract, for which treatment approaches remain notably limited. In this study, we demonstrated that ginseng polysaccharides (GPs) could alleviate the development of dextran sulfate sodium (DSS)-induced UC as reflected by the ameliorated pathological lesions in the colon. GPs strikingly suppressed the expression levels of multiple inflammatory cytokines, as well as significantly inhibited the infiltration of inflammatory cells. Microbiota-dependent investigations by virtue of 16S rRNA gene sequencing, antibiotic treatment and fecal microbiota transplantation illustrated that GPs treatment prominently restored intestinal microbial balance predominantly through modulating the relative abundance of Lactobacillus. Additionally, GPs remarkably influenced the levels of microbial tryptophan metabolites, diminished the intestinal permeability and strengthened intestinal barrier integrity via inhibiting the 5-HT/HTR3A signaling pathway. Taken together, the promising therapeutic potential of GPs on the development of UC predominantly hinges on the capacity to suppress the expression of inflammatory cytokines as well as to influence Lactobacillus and microbial tryptophan metabolites.}, } @article {pmid38521227, year = {2024}, author = {Moreau, GB and Naz, F and Petri, WA}, title = {Fecal microbiota transplantation stimulates type 2 and tolerogenic immune responses in a mouse model.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {102841}, doi = {10.1016/j.anaerobe.2024.102841}, pmid = {38521227}, issn = {1095-8274}, abstract = {OBJECTIVES: Clostridioides difficile infection (CDI) is the leading hospital-acquired infection in North America. While previous work on fecal microbiota transplantation (FMT), a highly effective treatment for CDI, has focused on colonization resistance mounted against C. difficile by FMT-delivered commensals, the effects of FMT on host gene expression are relatively unexplored. This study aims to identify transcriptional changes associated with FMT, particularly changes associated with protective immune responses.

METHODS: Gene expression was assessed on day 2 and day 7 after FMT in mice after antibiotic-induced dysbiosis. Flow cytometry was also performed on colon and mesenteric lymph nodes at day 7 to investigate changes in immune cell populations.

RESULTS: FMT administration after antibiotic-induced dysbiosis successfully restored microbial alpha diversity to levels of donor mice by day 7 post-FMT. Bulk RNA sequencing of cecal tissue at day 2 identified immune genes, including both pro-inflammatory and Type 2 immune pathways as upregulated after FMT. RNA sequencing was repeated on day 7 post-FMT, and expression of these immune genes was decreased along with upregulation of genes associated with restoration of intestinal homeostasis. Immunoprofiling on day 7 identified increased colonic CD45[+] immune cells that exhibited dampened Type 1 and heightened regulatory and Type 2 responses. These include an increased abundance of eosinophils, alternatively activated macrophages, Th2, and T regulatory cell populations.

CONCLUSION: These results highlight the impact of FMT on host gene expression, providing evidence that FMT restores intestinal homeostasis after antibiotic treatment and facilitates tolerogenic and Type 2 immune responses.}, } @article {pmid38519447, year = {2024}, author = {Stone, CB and Rudinsky, AJ and Urion, RJ and March, SB and Winston, JA}, title = {Gastrointestinal release site for delayed release and gelatin capsules in healthy dogs.}, journal = {Journal of veterinary pharmacology and therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/jvp.13439}, pmid = {38519447}, issn = {1365-2885}, support = {//T-35 grant (2T35OD010977)/ ; }, abstract = {Gelatin capsules deliver their contents to the stomach, while delayed-release (DR) capsules are designed to allow delivery to the small intestine. This study evaluated the gastrointestinal release site of DR capsules in six healthy adult dogs compared to gelatin capsules. Both gelatin and DR capsules were filled with barium-impregnated polyethylene spheres (BIPS™), and following enteral administration, release site was assessed using abdominal radiographs at baseline, immediately after ingestion, 15 min post-ingestion, 30 min post-ingestion, and then every 30 min thereafter. The evaluated phases included fasted conditions (phase 1, n = 6), increased meal size (phase 2, n = 2), double encapsulation (phase 3, n = 2), and altered capsule size (phase 4, n = 1). The released site was the stomach in all phases for both capsule types. In phase 1, DR capsules had a significantly prolonged time (median 60 min, range 60-90) to release BIPS™ compared to gelatin capsules (15 min, range 15-30; p = .03). In phase 2 (full meal size), 3 (double encapsulation), and 4 (smaller capsule size) pilot studies, release time was prolonged but still occurred in the stomach. This is similar to the release site for gelatin capsules but differs from the release site for DR capsules in people. This has implications for pharmacologic outcomes for products that are affected by gastric physiology (e.g. fecal microbiota transplantation). Based on this pilot data, clinicians and researchers should not assume DR capsules will allow for intestinal delivery of contents in dogs. Future studies should be conducted on larger and varied populations of dogs.}, } @article {pmid38518650, year = {2024}, author = {Zhang, HJ and Fu, J and Yu, H and Xu, H and Hu, JC and Lu, JY and Bu, MM and Zhai, Z and Wang, JY and Ye, ML and Zuo, HT and Song, JY and Zhao, Y and Jiang, JD and Wang, Y}, title = {Berberine promotes the degradation of phenylacetic acid to prevent thrombosis by modulating gut microbiota.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {128}, number = {}, pages = {155517}, doi = {10.1016/j.phymed.2024.155517}, pmid = {38518650}, issn = {1618-095X}, abstract = {BACKGROUND: Berberine is the main bioactive constituent of Coptis chinensis, a quaternary ammonium alkaloid. While berberine's cardiovascular benefits are well-documented, its impact on thrombosis remains not fully understood.

PURPOSE: This study investigates the potential of intestinal microbiota as a novel target for preventing thrombosis, with a focus on berberine, a natural compound known for its effectiveness in managing cardiovascular conditions.

METHODS: Intraperitoneal injection of carrageenan induces the secretion of chemical mediators such as histamine and serotonin from mast cells to promote thrombosis. This model can directly and visually observe the progression of thrombosis in a time-dependent manner. Thrombosis was induced by intravenous injection of 1 % carrageenan solution (20 mg/kg) to all mice except the vehicle control group. Quantitative analysis of gut microbiota metabolites through LC/MS. Then, the gut microbiota of mice was analyzed using 16S rRNA sequencing to assess the changes. Finally, the effects of gut microbiota on thrombosis were explored by fecal microbiota transplantation.

RESULTS: Our research shows that berberine inhibits thrombosis by altering intestinal microbiota composition and related metabolites. Notably, berberine curtails the biosynthesis of phenylacetylglycine, a thrombosis-promoting coproduct of the host-intestinal microbiota, by promoting phenylacetic acid degradation. This research underscores the significance of phenylacetylglycine as a thrombosis-promoting risk factor, as evidenced by the ability of intraperitoneal phenylacetylglycine injection to reverse berberine's efficacy. Fecal microbiota transplantation experiment confirms the crucial role of intestinal microbiota in thrombus formation.

CONCLUSION: Initiating our investigation from the perspective of the gut microbiota, we have, for the first time, unveiled that berberine inhibits thrombus formation by promoting the degradation of phenylacetic acid, consequently suppressing the biosynthesis of PAG. This discovery further substantiates the intricate interplay between the gut microbiota and thrombosis. Our study advances the understanding that intestinal microbiota plays a crucial role in thrombosis development and highlights berberine-mediated intestinal microbiota modulation as a promising therapeutic approach for thrombosis prevention.}, } @article {pmid38518435, year = {2024}, author = {Belotserkovsky, I and Stabryla, LM and Hunter, M and Allegretti, J and Callahan, BJ and Carlson, PE and Daschner, PJ and Goudarzi, M and Guyard, C and Jackson, SA and Rao, K and Servetas, SL and Sokol, H and Wargo, JA and Novick, S}, title = {Standards for fecal microbiota transplant: Tools and therapeutic advances.}, journal = {Biologicals : journal of the International Association of Biological Standardization}, volume = {86}, number = {}, pages = {101758}, doi = {10.1016/j.biologicals.2024.101758}, pmid = {38518435}, issn = {1095-8320}, abstract = {Fecal microbiota transplantation (FMT) has been demonstrated to be efficacious in preventing recurrent Clostridioides difficile (C. difficile) infections, and is being investigated for treatment of several other diseases including inflammatory bowel disease, cancer, obesity, liver disease, and diabetes. To speed up the translation of FMT into clinical practice as a safe and standardized therapeutic intervention, additional evidence-based technical and regulatory guidance is needed. To this end in May of 2022, the International Alliance for Biological Standardization (IABS) and the BIOASTER Microbiology Technology Institute hosted a second webinar to discuss key issues still impeding the advancement and standardization of FMT. The goal of this two-day webinar was to provide a forum for scientific experts to share and discuss data and key challenges with one another. Discussion included a focus on the evaluation of safety, efficacy, clinical trial design, reproducibility and accuracy in obtained microbiome measurements and data reporting, and the potential for standardization across these areas. It also focused on increasing the application potential and visibility of FMT beyond treating C. difficile infections.}, } @article {pmid38516869, year = {2024}, author = {Dong, S and Zeng, Q and He, W and Cheng, W and Zhang, L and Zhong, R and He, W and Fang, X and Wei, H}, title = {Effect of Lactobacillus plantarum BFS1243 on a female frailty model induced by fecal microbiota transplantation in germ-free mice.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo05282f}, pmid = {38516869}, issn = {2042-650X}, abstract = {Frailty, a complex geriatric syndrome, significantly impedes the goal of achieving 'healthy aging'. Increasing evidence suggests a connection between gut microbiota, systemic inflammation, and disease. However, it remains to be determined whether interventions targeting the intestinal flora can effectively ameliorate frailty. Our research involved fecal microbiota transplantation (FMT) experiments on germ-free (GF) mice, dividing these mice into three groups: a group receiving transplants from healthy elderly individuals (HF group), a group of frailty patients (FF group), and the FF group supplemented with Lactobacillus plantarum BFS1243 (FFL group). Our findings indicated a significant shift in the gut microbiota of the FF group, in contrast to the HF group, characterized by decreased Akkermansia and increased Enterocloster, Parabacteroides, and Eisenbergiella. Concurrently, there was a reduction in amino acids and SCFAs, with BFS1243 partially mitigating these changes. The FF group exhibited an upregulation of inflammatory markers, including PGE2, CRP, and TNF-α, and a downregulation of irisin, all of which were moderated by BFS1243 treatment. Furthermore, BFS1243 improved intestinal barrier integrity and physical endurance in the FF mice. Correlation analysis revealed a negative association between SCFA-producing species and metabolites like lysine and butyric acid with pro-inflammatory factors. In conclusion, our study conclusively demonstrated that alterations in the gut microbiota of elderly individuals can lead to physical frailty, likely due to detrimental effects on the intestinal barrier and a pro-inflammatory state. These findings underscore the potential of gut microbiome modulation as a clinical strategy for treating frailty.}, } @article {pmid38516478, year = {2024}, author = {Vidal-Gallardo, A and Méndez Benítez, JE and Flores Rios, L and Ochoa Meza, LF and Mata Pérez, RA and Martínez Romero, E and Vargas Beltran, AM and Beltran Hernandez, JL and Banegas, D and Perez, B and Martinez Ramirez, M}, title = {The Role of Gut Microbiome in the Pathogenesis and the Treatment of Inflammatory Bowel Diseases.}, journal = {Cureus}, volume = {16}, number = {2}, pages = {e54569}, pmid = {38516478}, issn = {2168-8184}, abstract = {Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic condition characterized by inflammation of the gastrointestinal tract. Its exact cause is unknown, but it's thought to result from a dysregulated immune response influenced by various factors, including changes in the intestinal microbiota, diet, lifestyle, and genetics. The gut microbiome, consisting of diverse microorganisms, plays a crucial role in maintaining physiological balance, with its disruption leading to inflammatory responses typical of IBD. Treatments primarily aim at symptom control, employing immunomodulators, corticosteroids, and newer approaches like probiotics, prebiotics, fecal transplants, and dietary modifications, all focusing on leveraging the microbiota's potential in disease management. These strategies aim to restore the delicate balance of the gut microbiome, typically altered in IBD, marked by a decrease in beneficial bacteria and an increase in harmful pathogens. This review underscores the importance of the gut microbiome in the pathogenesis and treatment of IBD, highlighting the shift towards personalized medicine and the necessity for further research in understanding the complex interactions between the gut microbiota, immune system, and genetics in IBD. It points to the potential of emerging treatments and the importance of a multifaceted approach in managing this complex and challenging disease.}, } @article {pmid38516317, year = {2024}, author = {Caputi, V and Hill, L and Figueiredo, M and Popov, J and Hartung, E and Margolis, KG and Baskaran, K and Joharapurkar, P and Moshkovich, M and Pai, N}, title = {Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1341656}, pmid = {38516317}, issn = {1662-4548}, abstract = {INTRODUCTION: Critical phases of neurodevelopment and gut microbiota diversification occur in early life and both processes are impacted by genetic and environmental factors. Recent studies have shown the presence of gut microbiota alterations in neurodevelopmental disorders. Here we performed a systematic review of alterations of the intestinal microbiota composition and function in pediatric and adult patients affected by autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Rett syndrome (RETT).

METHODS: We searched selected keywords in the online databases of PubMed, Cochrane, and OVID (January 1980 to December 2021) with secondary review of references of eligible articles. Two reviewers independently performed critical appraisals on the included articles using the Critical Appraisal Skills Program for each study design.

RESULTS: Our systematic review identified 18, 7, and 3 original articles describing intestinal microbiota profiles in ASD, ADHD, and RETT, respectively. Decreased Firmicutes and increased Bacteroidetes were observed in the gut microbiota of individuals affected by ASD and ADHD. Proinflammatory cytokines, short-chain fatty acids and neurotransmitter levels were altered in ASD and RETT. Constipation and visceral pain were related to changes in the gut microbiota in patients affected by ASD and RETT. Hyperactivity and impulsivity were negatively correlated with Faecalibacterium (phylum Firmicutes) and positively correlated with Bacteroides sp. (phylum Bacteroidetes) in ADHD subjects. Five studies explored microbiota-or diet-targeted interventions in ASD and ADHD. Probiotic treatments with Lactobacillus sp. and fecal microbiota transplantation from healthy donors reduced constipation and ameliorated ASD symptoms in affected children. Perinatal administration of Lactobacillus sp. prevented the onset of Asperger and ADHD symptoms in adolescence. Micronutrient supplementation improved disease symptomatology in ADHD without causing significant changes in microbiota communities' composition.

DISCUSSION: Several discrepancies were found among the included studies, primarily due to sample size, variations in dietary practices, and a high prevalence of functional gastrointestinal symptoms. Further studies employing longitudinal study designs, larger sample sizes and multi-omics technologies are warranted to identify the functional contribution of the intestinal microbiota in developmental trajectories of the human brain and neurobehavior.

https://clinicaltrials.gov/, CRD42020158734.}, } @article {pmid38516241, year = {2024}, author = {Qiu, XX and Cheng, SL and Liu, YH and Li, Y and Zhang, R and Li, NN and Li, Z}, title = {Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease: Mechanism, clinical evidence, and prospect.}, journal = {World journal of gastroenterology}, volume = {30}, number = {8}, pages = {833-842}, pmid = {38516241}, issn = {2219-2840}, abstract = {The population of non-alcoholic fatty liver disease (NAFLD) patients along with relevant advanced liver disease is projected to continue growing, because currently no medications are approved for treatment. Fecal microbiota transplantation (FMT) is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease. There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment, however, existing findings diverge on its effects. Herein, we briefly summarized the mechanism of FMT for NAFLD treatment, reviewed randomized controlled trials for evaluating its efficacy in NAFLD, and proposed the prospect of future trials on FMT.}, } @article {pmid38513881, year = {2024}, author = {Xu, J and Lu, L and Jiang, S and Qin, Z and Huang, J and Huang, M and Jin, J}, title = {Paeoniflorin ameliorates oxaliplatin-induced peripheral neuropathy via inhibiting neuroinflammation through influence on gut microbiota.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {176516}, doi = {10.1016/j.ejphar.2024.176516}, pmid = {38513881}, issn = {1879-0712}, abstract = {Oxaliplatin (OXA)-induced peripheral neuropathy (OIPN) is a severe side effect that greatly limits OXA clinical use and threatens patients' life and health. Paeoniflorin exhibits extensive anti-inflammatory and neuroprotective effects, but whether it can protect against OIPN and the underlying mechanisms remain unclear. This study aimed to investigate the effects of paeoniflorin on OIPN and probe into the underlying mechanisms. The OIPN model was established through oxaliplatin injection in rats. The ameliorative effects of paeoniflorin on OIPN was assessed by nociceptive hypersensitivities through pain behavioral methods. Neuroinflammation were examined by measuring the levels of inflammatory cytokines and immune cells infiltration. The signaling pathway of TLR4/MyD88/NF-κB was evaluated by Western blotting. Gut microbial changes were detected by 16S rDNA sequencing technology. In addition, antibiotics-induced microbiota eradication and fecal microbial transplantation (FMT) were applied for exploring the function of gut microbiota in the protective effects of paeoniflorin. The results revealed that paeoniflorin significantly alleviated mechanical and cold hypersensitivity, mitigated neuroinflammation and influenced gut microbial composition in OIPN rats. Fecal microbiota transplantation further verified that gut microbiota was required for paeoniflorin ameliorating OIPN and that the underlying mechanism involved downregulation of TLR4/MyD88/NF-κB signaling. Specifically, Akkermansia, Dubosiella and Corynebacterium might serve as crucial genera regulated by paeoniflorin in the treatment of OIPN. In summary, our investigations delineate paeoniflorin's ameliorative effects on OIPN by alleviating neuroinflammation through regulations of gut microbiota. This suggests that paeoniflorin may serve as a new potential strategy for treatment of OIPN in clinical practice.}, } @article {pmid38513836, year = {2024}, author = {Liu, D and Hu, L and Yang, Y and Wang, Y and Li, Y and Su, J and Wang, G and Gong, S}, title = {Saccharomyces boulardii alleviates allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.}, journal = {Immunology letters}, volume = {}, number = {}, pages = {106853}, doi = {10.1016/j.imlet.2024.106853}, pmid = {38513836}, issn = {1879-0542}, abstract = {BACKGROUND: Allergic asthma is a heterogeneous disease and new strategies are needed to prevent or treat this disease. Studies have shown that probiotic interventions are effective in preventing asthma. Here, we investigated the impact of Saccharomyces boulardii (S. boulardii) on ovalbumin (OVA)-induced allergic asthma in mice, as well as the underlying mechanisms.

METHODS: First, we constructed a mouse asthma model using OVA and given S. boulardii intervention. Next, we measured N6-methyladenosine (m6A) levels in lung injury tissues. 16s rRNA was employed to identify different gut microbiota in fecal samples. The analysis of differential metabolites in feces was performed by non-targeted metabolomics. Pearson correlation coefficient was utilized to analyze correlation between gut microbiota, metabolites and methyltransferase-like 3 (METTL3). Finally, we collected mouse feces treated by OVA and S. boulardii intervention for fecal microbiota transplantation (FMT) and interfered with METTL3.

RESULTS: S. boulardii improved inflammation and oxidative stress and alleviated lung damage in asthmatic mice. In addition, S. boulardii regulated m6A modification levels in asthmatic mice. 16s rRNA sequencing showed that S. boulardii remodeled gut microbiota homeostasis in asthmatic mice. Non-targeted metabolomics analysis showed S. boulardii restored metabolic homeostasis in asthmatic mice. There was a correlation between gut microbiota, differential metabolites, and METTL3 analyzed by Pearson correlation. Additionally, through FMT and interference of METTL3, we found that gut microbiota mediated the up-regulation of METTL3 by S. boulardii improved inflammation and oxidative stress in asthmatic mice, and alleviated lung injury.

CONCLUSIONS: S. boulardii alleviated allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.}, } @article {pmid38513657, year = {2024}, author = {Zhu, X and Huang, X and Hu, M and Sun, R and Li, J and Wang, H and Pan, X and Ma, Y and Ning, L and Tong, T and Zhou, Y and Ding, J and Zhao, Y and Xuan, B and Fang, JY and Hong, J and Hon Wong, JW and Zhang, Y and Chen, H}, title = {A specific enterotype derived from gut microbiome of older individuals enables favorable responses to immune checkpoint blockade therapy.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2024.03.002}, pmid = {38513657}, issn = {1934-6069}, abstract = {Immunotherapy has revolutionized cancer treatment, but inconsistent responses persist. Our study delves into the intriguing phenomenon of enhanced immunotherapy sensitivity in older individuals with cancers. Through a meta-analysis encompassing 25 small-to-mid-sized trials of immune checkpoint blockade (ICB), we demonstrate that older individuals exhibit heightened responsiveness to ICB therapy. To understand the underlying mechanism, we reanalyze single-cell RNA sequencing (scRNA-seq) data from multiple studies and unveil distinct upregulation of exhausted and cytotoxic T cell markers within the tumor microenvironment (TME) of older patients. Recognizing the potential role of gut microbiota in modulating the efficacy of immunotherapy, we identify an aging-enriched enterotype linked to improved immunotherapy outcomes in older patients. Fecal microbiota transplantation experiments in mice confirm the therapeutic potential of the aging-enriched enterotype, enhancing treatment sensitivity and reshaping the TME. Our discoveries confront the prevailing paradox and provide encouraging paths for tailoring cancer immunotherapy strategies according to an individual's gut microbiome profile.}, } @article {pmid38512763, year = {2024}, author = {Benedé-Ubieto, R and Cubero, FJ and Nevzorova, YA}, title = {Breaking the barriers: the role of gut homeostasis in Metabolic-Associated Steatotic Liver Disease (MASLD).}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2331460}, doi = {10.1080/19490976.2024.2331460}, pmid = {38512763}, issn = {1949-0984}, abstract = {Obesity, insulin resistance (IR), and the gut microbiome intricately interplay in Metabolic-associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease (NAFLD), a growing health concern. The complex progression of MASLD extends beyond the liver, driven by "gut-liver axis," where diet, genetics, and gut-liver interactions influence disease development. The pathophysiology of MASLD involves excessive liver fat accumulation, hepatocyte dysfunction, inflammation, and fibrosis, with subsequent risk of hepatocellular carcinoma (HCC). The gut, a tripartite barrier, with mechanical, immune, and microbial components, engages in a constant communication with the liver. Recent evidence links dysbiosis and disrupted barriers to systemic inflammation and disease progression. Toll-like receptors (TLRs) mediate immunological crosstalk between the gut and liver, recognizing microbial structures and triggering immune responses. The "multiple hit model" of MASLD development involves factors like fat accumulation, insulin resistance, gut dysbiosis, and genetics/environmental elements disrupting the gut-liver axis, leading to impaired intestinal barrier function and increased gut permeability. Clinical management strategies encompass dietary interventions, physical exercise, pharmacotherapy targeting bile acid (BA) metabolism, and microbiome modulation approaches through prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). This review underscores the complex interactions between diet, metabolism, microbiome, and their impact on MASLD pathophysiology and therapeutic prospects.}, } @article {pmid38509104, year = {2024}, author = {Faraci, M and Bonaretti, C and Dell'Orso, G and Pierri, F and Giardino, S and Angiero, F and Blasi, S and Farronato, G and Di Marco, E and Trevisiol, A and Olcese, E and Rufino, L and Squillario, M and Biassoni, R}, title = {Association between oral and fecal microbiome dysbiosis and treatment complications in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {6708}, pmid = {38509104}, issn = {2045-2322}, mesh = {Humans ; Child ; *Mucositis/etiology ; Dysbiosis/etiology ; Prospective Studies ; *Microbiota ; *Graft vs Host Disease ; Bacteria ; *Hematopoietic Stem Cell Transplantation/adverse effects ; }, abstract = {The oral and gastrointestinal mucosae represent the main targets of the toxic effect of chemo and/or radiotherapy administered during the conditioning regimen before hematopoietic stem cell transplant (HSCT). These harmful consequences and the immunological complications that may occur after the transplant (such as Graft versus Host Disease, GvHD) are responsible for the clinical symptoms associated with mucositis during the aplasia phase, like pain, nausea, vomiting, and diarrhea. These toxicities could play a critical role in the oral and gastrointestinal microbiomes during the post-transplant phase, and the degree of microbial dysbiosis and dysregulation among different bacterial species could also be crucial in intestinal mucosa homeostasis, altering the host's innate and adaptive immune responses and favoring abnormal immune responses responsible for the occurrence of GvHD. This prospective pediatric study aims to analyze longitudinally oral and gut microbiomes in 17 pediatric patients who received allogeneic HSCT for malignant and non-malignant diseases. The oral mucositis was mainly associated with an increased relative abundance of Fusobacteria, and Prevotella species, while Streptococcus descendants showed a negative correlation. The fecal microbiome of subjects affected by cutaneous acute GvHD (aGvHD) correlated with Proteobacteria. Oral mucosal microbiota undergoes changes after HSCT, Fusobacteria, and Prevotella represent bacterial species associated with mucositis and they could be the target for future therapeutic approaches, while fecal microbiome in patients with acute GvHD (aGvHD) revealed an increase of different class of Proteobacteria (Alphaproteobacteria and Deltaproteobacteria) and a negative correlation with the class of Gammaproteobacteria.}, } @article {pmid38509085, year = {2024}, author = {Fu, Y and Chen, YS and Xia, DY and Luo, XD and Luo, HT and Pan, J and Ma, WQ and Li, JZ and Mo, QY and Tu, Q and Li, MM and Zhao, Y and Li, Y and Huang, YT and Chen, ZX and Li, ZJ and Bernard, L and Dione, M and Zhang, YM and Miao, K and Chen, JY and Zhu, SS and Ren, J and Zhou, LJ and Jiang, XZ and Chen, J and Lin, ZP and Chen, JP and Ye, H and Cao, QY and Zhu, YW and Yang, L and Wang, X and Wang, WC}, title = {Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {25}, pmid = {38509085}, issn = {2055-5008}, mesh = {Humans ; *Lacticaseibacillus rhamnosus ; *Hyperuricemia/therapy ; Nucleosides ; Lactobacillus ; Proline ; Purines ; }, abstract = {Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.}, } @article {pmid38508446, year = {2024}, author = {Tao, S and Fan, J and Li, J and Wu, Z and Yao, Y and Wang, Z and Wu, Y and Liu, X and Xiao, Y and Wei, H}, title = {Extracellular vesicles derived from Lactobacillus johnsonii promote gut barrier homeostasis by enhancing M2 macrophage polarization.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.03.011}, pmid = {38508446}, issn = {2090-1224}, abstract = {INTRODUCTION: Diarrheic disease is a common intestinal health problem worldwide, causing great suffering to humans and animals. Precise manipulation strategies based on probiotics to combat diarrheic diseases have not been fully developed.

OBJECTIVES: The aim of this study was to investigate the molecular mechanisms by which probiotics manipulate macrophage against diarrheic disease.

METHODS: Metagenome reveals gut microbiome profiles of healthy and diarrheic piglets. Fecal microbial transplantation (FMT) was employed to explore the causal relationship between gut microbes and diarrhea. The protective role of probiotics and their derived extracellular vesicles (EVs) was investigated in ETEC K88-infected mice. Macrophage depletion was performed to assess the role of macrophages in EVs against diarrhea. Execution of in vitro cell co-culture and transcriptome analyses elucidated the molecular mechanisms by which EVs modulate the macrophage and intestinal epithelial barrier.

RESULTS: Escherichia coli was enriched in weaned diarrheic piglets, while Lactobacillus johnsonii (L. john) showed a negative correlation with Escherichia coli. The transmission of diarrheic illness symptoms was achieved by transferring fecal microbiota, but not metabolites, from diarrheic pigs to germ-free (GF) mice. L. john's intervention prevented the transmission of disease phenotypes from diarrheic piglets to GF mice. L. john also reduces the gut inflammation induced by ETEC K88. The EVs secreted by L. john demonstrated enhanced efficacy in mitigating the adverse impacts induced by ETEC K88 through the modulation of macrophage phenotype. In vitro experiments have revealed that EVs activate M2 macrophages in a manner that shuts down ERK, thereby inhibiting NLRP3 activation in intestinal epithelial cells.

CONCLUSION: Our results reveal that intestinal microbiota drives the onset of diarrheic disease and that probiotic-derived EVs ameliorate diarrheic disease symptoms by modulating macrophage phenotypes. These findings can enhance the advancement of innovative therapeutic approaches for diarrheic conditions based on probiotic-derived EVs.}, } @article {pmid38508330, year = {2024}, author = {Cymbal, M and Chatterjee, A and Baggott, B and Auron, M}, title = {Management of Clostridioides difficile infection: Diagnosis, Treatment, and Future Perspectives.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2024.03.024}, pmid = {38508330}, issn = {1555-7162}, abstract = {Clostridioides difficile infection is the most common healthcare-associated infection in the United States, with potential life-threatening complications and significant impact in the costs of care. Antibiotic stewardship as well as discontinuation of chronic acid suppressive therapy are key for its prevention and treatment. Effective infection management requires appropriate interpretation of diagnostic tests, as well as the use of vancomycin and fidaxomicin as first-line treatment. Novel treatments as Bezlotoxumab, fecal microbiota transplant and live biotherapeutic products are proven effective in recurrent C. difficile infection and addresses dysbiosis.}, } @article {pmid38506871, year = {2023}, author = {Rojo Gutiérrez, MI and Ballesteros González, D and Ortiz Durán, AK}, title = {[Non-IgE-mediated food allergy].}, journal = {Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993)}, volume = {70}, number = {4}, pages = {269-279}, doi = {10.29262/ram.v70i4.1338}, pmid = {38506871}, issn = {2448-9190}, mesh = {Adult ; Child ; Infant, Newborn ; Humans ; *Proctocolitis/etiology/therapy ; *Food Hypersensitivity/complications/therapy ; Food ; *Enterocolitis/etiology/therapy ; Inflammation ; }, abstract = {Food allergy is an immune response to proteins in food. It usually affects 8% of children and 2% of adults in Western countries. Non-IgE-mediated food allergy mainly affects the gastrointestinal tract. Gastrointestinal food allergies are classified, by their underlying pathogenesis, as: IgE-mediated, non-IgE-mediated, or mixed. The symptoms of patients with food protein-induced allergic proctocolitis originate from local inflammation of the distal colon, which causes hematochezia in neonates. It can affect the entire gastrointestinal tract and cause symptoms of intractable emesis, with subsequent metabolic disorders and hypovolemic shock. Food protein-induced enterocolitis syndrome is a non-IgE-mediated allergy that usually appears in childhood, with prolonged repetitive vomiting, starting 1 to 4 hours after ingestion of food. The manifestation in adults is usually triggered by the consumption of shellfish. Atopic diseases affect 40-60% of patients with food protein- induced enterocolitis syndrome, including 40-50% of those with food protein-induced enteropathy and proctocolitis. Probiotics (Lactobacillus GG) can alleviate the symptoms of allergic proctocolitis induced by food proteins, by altering the composition of the intestinal microbiota. Fecal microbiota transplantation (FMT) can change intestinal microecology efficiently compared to food or probiotics.}, } @article {pmid38503933, year = {2024}, author = {Böttger, TW and Turina, M and Ensle, F and Mihic-Probst, D and Meier, CA and Ersözlü, S}, title = {Episodic Abdominal Pain-An Unexpected Cause for a Common Clinical Problem.}, journal = {Journal of general internal medicine}, volume = {}, number = {}, pages = {}, pmid = {38503933}, issn = {1525-1497}, abstract = {A previously healthy 55-year-old male patient presented repeatedly to the emergency department with severe episodic periumbilical abdominal pain. After an extensive diagnostic work-up and subsequent clinical deterioration, appendiceal diverticulitis was diagnosed. We identified a correlation of white blood cell counts and possibly faecal calprotectin with the clinical presentation. We suggest that appendiceal diverticulitis should be considered in middle-aged patients with recurrent episodes of abdominal pain that correlate with laboratory markers of inflammation.}, } @article {pmid38502145, year = {2024}, author = {Xu, B and Fu, Y and Yin, N and Qin, W and Huang, Z and Xiao, W and Huang, H and Mei, Q and Fan, J and Zeng, Y and Huang, C}, title = {Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii served as key components of fecal microbiota transplantation to alleviate colitis.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00303.2023}, pmid = {38502145}, issn = {1522-1547}, support = {NO. 81970555//MOST | National Natural Science Foundation of China (NSFC)/ ; NO. 82270671//MOST | National Natural Science Foundation of China (NSFC)/ ; 22SJKGGG28//Songjiang Science and Technology Committee/ ; KY-2023-03-02//Shanghai Jiao Tong University School of Medicine, Digestive Institute/ ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising therapy for inflammatory bowel disease (IBD) via rectifying gut microbiota. The aim of this study was to identify a mechanism of how specific bacteria-associated immune response contributes to alleviated colitis. 40 donors were divided into high (donor-H) and low (donor-L) groups according to diversity and the abundance of Bacteroides and Faecalibacterium by 16S rRNA sequencing. FMT was performed on dextran sulfate sodium (DSS)-induced colitis in mice. Mice with colitis showed significant improvement in intestinal injury and immune imbalance after FMT with group donor-H (p <0.05). Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii were identified as targeted strains in donor feces by real-time PCR and droplet digital PCR. Mice with colitis were treated with mono- or dual-bacterial gavage therapy. Dual-bacterial therapy significantly ameliorated intestinal injury compared with mono-bacterial therapy (p <0.05). Dual-bacterial therapy increased the M2/M1 macrophage polarization and improved the Th17/Treg imbalance and elevated IL-10 production by Tregs compared with the DSS group (p <0.05). Metabolomics showed increased abundance of lecithin in the glycerophospholipid metabolism pathway. In conclusion, B. thetaiotaomicron and F. prausnitzii, as the key bacteria in donor feces, alleviate colitis in mice. The mechanism may involve increasing lecithin and regulating IL-10 production of intestinal Tregs.}, } @article {pmid38501942, year = {2024}, author = {Tan, Z and Wang, Z and Zeng, Q and Liu, X and Zhang, Y and Li, S and Huang, J and Zeng, Y and Huang, Z and Jin, C and Fu, N and Zhao, Q and Mu, Y and Wang, Z and Xiao, J and Yang, H and Ke, G}, title = {Natural intestinal metabolite xylitol reduces BRD4 levels to mitigate renal fibrosis.}, journal = {Clinical and translational science}, volume = {17}, number = {3}, pages = {e13770}, pmid = {38501942}, issn = {1752-8062}, support = {82060131//National Natural Science Foundation of China/ ; 82360154//National Natural Science Foundation of China/ ; 81871551//National Natural Science Foundation of China/ ; 2023A1515012474//Guangdong Basic and Applied Basic Research Foundation/ ; 2021YFS0159//Sichuan Science and Technology Program/ ; 2023A03J0344//Guangzhou City Science and Technology Project/ ; 2023A03J0342//Guangzhou City Science and Technology Project/ ; 202201020508//Guangzhou City Science and Technology Project/ ; }, mesh = {Humans ; *Nuclear Proteins ; Xylitol ; Molecular Docking Simulation ; Transcription Factors ; *Renal Insufficiency, Chronic/drug therapy ; Fibrosis ; Transforming Growth Factor beta ; Bromodomain Containing Proteins ; Cell Cycle Proteins ; }, abstract = {Renal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end-stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the "gut-kidney axis," therefore, although clinical intervention to modulate the "gut-kidney axis" imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non-absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD-triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain-containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor-β (TGF-β) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4-regulated TGF-β pathway.}, } @article {pmid38501667, year = {2024}, author = {Allegretti, JR and Axelrad, J and Dalal, RS and Kelly, CR and Grinspan, A and Fischer, M}, title = {Outcomes after Fecal Microbiota Transplantation in combination with Bezlotoxumab for Inflammatory Bowel Disease and Recurrent C . difficile Infection.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000002770}, pmid = {38501667}, issn = {1572-0241}, support = {//Merck/ ; }, abstract = {Fecal microbiota transplantation (FMT) prevents recurrent C. difficile infections (rCDI) in IBD. Patients. Bezlotoxumab is also indicated to prevent rCDI. We assess the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI. We conducted a multicenter randomized placebo-controlled trial. All received a single colonoscopic FMT. Patients were randomized 1:1 to receive bezlotoxumab or placebo. Sixty-one patients were enrolled (30 received treatment and 31 placebo. Overall, 5 participants (8%) experienced a CDI recurrence; 4 in the treatment arm, 1 in placebo (13% vs 3%, p=0.15). There was no clear benefit to the combination approach compared to FMT alone.}, } @article {pmid38501427, year = {2024}, author = {Li, X and Liu, Y and Deng, K and Hu, Y}, title = {[Modulating gut microbiota improves neurological function and depressive symptoms in rats with post-stroke depression].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {44}, number = {2}, pages = {405-410}, doi = {10.12122/j.issn.1673-4254.2024.02.24}, pmid = {38501427}, issn = {1673-4254}, mesh = {Rats ; Animals ; *Depression/etiology/therapy/metabolism ; Rats, Sprague-Dawley ; Fluoxetine ; *Gastrointestinal Microbiome ; Occludin ; Anti-Bacterial Agents ; Water ; Sugars ; Immunoglobulin G ; *Methylamines ; }, abstract = {OBJECTIVE: To evaluate the effect of modulating gut microbiota for improving brain injury in rats with post-stroke depression.

METHODS: Adult SD rats were randomized into normal control, middle cerebral artery occlusion (MCAO), post-stroke depression (PSD), PSD with fecal transplantation, PSD with antibiotics (rifaximin), PSD with probiotics (lactobacilli), and PSD with fluoxetine treatment groups (n=9). Neurological function scores of the rats were determined, and the changes in sugar water preference and immobility time in forced swimming test were observed; plasma levels of trimethylamine N-oxide (TMAO) and hydrogen sulfide (H2S) were detected with ELISA, Occludin, and the expressions of occludin, caudin-5 and IgG proteins Ⅰ the brain tissues were determined using Western blotting.

RESULTS: Compared with those in the control group, the rats in MCAO and PSD groups had significantly increased neurological function scores, TMAO level, the ratio of TMAO/H2S, and immobility time in forced swimming test with a lowered level of H2S (P < 0.05). These changes were more obvious in PSD rats, which also exhibited a reduced sugar water preference with increased IgG protein and decreased occluding and caudin-5 expressions in the brain tissue (P < 0.05). TMAO/H2S ratio in PSD rats was positively correlated with neurological function score (R[2]=0.3235, P=0.0269) and immobility time in swimming (R[2]=0.6290, P=0.0004) and negatively with sugar water preference (R[2]=-0.4534, P=0.0059). Treatment with fecal transplantation, antibiotics, probiotics and fluoxetine all significantly reduced neurological function scores, immobility time in forced swimming, TMAO/H2S ratio, and IgG protein expression and increased sugar water preference and brain occludin and caudin-5 expressions of the PSD rats (P < 0.05).

CONCLUSION: In PSD rats, TMAO/H2S ratio is correlated with neurological function score, immobility time in forced swimming and sugar water preference, and modulating intestinal flora can improve neurological function and depressive symptoms and improve the integrity of the blood-brain barrier.}, } @article {pmid38500273, year = {2024}, author = {Andriolo, IRL and Longo, B and Melo, DM and Souza, MM and Prediger, RD and Silva, LMD}, title = {Gastrointestinal Issues in Depression, Anxiety, and Neurodegenerative Diseases: A Systematic Review on Pathways and Clinical Targets Implications.}, journal = {CNS & neurological disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715273289138240306050532}, pmid = {38500273}, issn = {1996-3181}, abstract = {INTRODUCTION: Multiple illnesses commonly involve both the Central Nervous System (CNS) and the Gastrointestinal Tract (GI) simultaneously. Consistent evidence suggests that neurological disorders impair GI tract function and worsen the symptomatology and pathophysiology of digestive disorders. On the other hand, it has been proposed that early functional changes in the GI tract contribute to the genesis of several CNS illnesses. Additionally, the role played by the gut in these diseases can be seen as a paradigm for how the gut and the brain interact.

METHODS: We mentioned significant GI symptoms and discussed how the GI tract affects central nervous system illnesses, including depression, anxiety, Alzheimer's disease, and Parkinson's disease in this study. We also explored potential pathophysiological underpinnings and novel targets for the creation of future therapies targeted at gut-brain connections.

RESULTS & DISCUSSION: In this situation, modulating the gut microbiota through the administration of fecal microbiota transplants or probiotics may represent a new therapeutic option for this population, not only to treat GI problems but also behavioral problems, given the role that dysbiosis and leaky gut play in many neurological disorders.

CONCLUSION: Accurate diagnosis and treatment of co-existing illnesses also require coordination between psychiatrists, neurologists, gastroenterologists, and other specialties, as well as a thorough history and thorough physical examination.}, } @article {pmid38499070, year = {2024}, author = {Baske, MM and Timmerman, KC and Garmo, LG and Freitas, MN and McCollum, KA and Ren, TY}, title = {Fecal microbiota transplant on Escherichia-Shigella gut composition and its potential role in the treatment of generalized anxiety disorder: A systematic review.}, journal = {Journal of affective disorders}, volume = {354}, number = {}, pages = {309-317}, doi = {10.1016/j.jad.2024.03.088}, pmid = {38499070}, issn = {1573-2517}, abstract = {BACKGROUND: The gut-brain-axis has a role in mental health disorders. In people with generalized anxiety disorder, GAD,[1] normal flora Escherichia-Shigella, are significantly elevated. Fecal microbiota transplant, FMT,[2] has been used to alter the gut composition in unhealthy individuals. There may be a role for FMT in the treatment of GAD to improve the gut-brain-axis.

METHODS: A systematic review of literature was conducted on articles published in PubMed, CINAHL Plus, Scopus, Cochrane Library, and Wed of Science from 2000 to 2022 that analyzed FMT as a modality to alter the gut microbiome in which Escherichia-Shigella levels were quantified and reported.

RESULTS: Of 1916 studies identified, 14 fit criteria and were included. Recipients undergoing FMT procedures had at least one enteric diagnosis and increased percentages of Escherichia-Shigella pre-FMT. Five studies on recurrent Clostridioides difficile infection, three irritable bowel syndrome, two ulcerative colitis, one ulcerative colitis and recurrent Clostridioides difficile infection, one acute intestinal and chronic graft-vs-host disease, one pouchitis, and one slow transit constipation. 10 articles (71.4 %) showed decreased levels of Escherichia-Shigella post-FMT compared to pre-FMT. Four studies claimed the results were significant (40 %).

LIMITATIONS: Limitations include potential bias in study selection, study methods of analysis, and generalization of results.

CONCLUSIONS: The gut-brain-axis has a role in GAD. Those with GAD have significantly higher Escherichia-Shigella compared to those without GAD. FMT has the potential to decrease Escherichia-Shigella in patients with GAD to positively alter the gut-brain-axis as a potential for future GAD treatment.}, } @article {pmid38497338, year = {2024}, author = {Das, S and Preethi, B and Kushwaha, S and Shrivastava, R}, title = {Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management.}, journal = {Histology and histopathology}, volume = {}, number = {}, pages = {18730}, doi = {10.14670/HH-18-730}, pmid = {38497338}, issn = {1699-5848}, abstract = {Sarcopenia is a progressive and generalized loss of skeletal muscle and functions associated with ageing with currently no definitive treatment. Alterations in gut microbial composition have emerged as a significant contributor to the pathophysiology of multiple diseases. Recently, its association with muscle health has pointed to its potential role in mediating sarcopenia. The current review focuses on the association of gut microbiota and mediators of muscle health, connecting the dots between the influence of gut microbiota and their metabolites on biomarkers of sarcopenia. It further delineates the mechanism by which the gut microbiota affects muscle health with progressing age, aiding the formulation of a multi-modal treatment plan involving nutritional supplements and pharmacological interventions along with lifestyle changes compiled in the review. Nutritional supplements containing proteins, vitamin D, omega-3 fatty acids, creatine, curcumin, kefir, and ursolic acid positively impact the gut microbiome. Dietary fibres foster a conducive environment for the growth of beneficial microbes such as Bifidobacterium, Faecalibacterium, Ruminococcus, and Lactobacillus. Probiotics and prebiotics act by protecting against reactive oxygen species (ROS) and inflammatory cytokines. They also increase the production of gut microbiota metabolites like short-chain fatty acids (SCFAs), which aid in improving muscle health. Foods rich in polyphenols are anti-inflammatory and have an antioxidant effect, contributing to a healthier gut. Pharmacological interventions like faecal microbiota transplantation (FMT), non-steroidal anti-inflammatory drugs (NSAIDs), ghrelin mimetics, angiotensin-converting enzyme inhibitors (ACEIs), and butyrate precursors lead to the production of anti-inflammatory fatty acids and regulate appetite, gut motility, and microbial impact on gut health. Further research is warranted to deepen our understanding of the interaction between gut microbiota and muscle health for developing therapeutic strategies for ameliorating sarcopenic muscle loss.}, } @article {pmid38496183, year = {2024}, author = {Basra, M and Patel, H and Stern-Harbutte, A and Lee, D and Gregg, RK and Waters, HB and Potter, AK}, title = {A Narrative Review on the Viability of Osteopathic Manipulative Medicine in Treating Irritable Bowel Syndrome With Constipation (IBS-C).}, journal = {Cureus}, volume = {16}, number = {2}, pages = {e54180}, pmid = {38496183}, issn = {2168-8184}, abstract = {Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal pain and alterations in bowel habits, with global prevalence. The etiology of the disease is likely multifactorial; however, autonomic nervous system (ANS) dysfunction and immune-mediated inflammation may contribute the most to the hallmark symptoms of abdominal pain and altered motility of the gut. Current pharmacological therapies operate to modulate intestinal transit, alter the composition of the gut flora and control pain. Non-pharmacological approaches include dietary changes, increased physical activity, or fecal microbiota transplants. None of these therapies can modulate ANS dysfunction or impact the underlying inflammation that is likely perpetuating the symptoms of IBS. Osteopathic Manipulative Medicine (OMM) is a clinical approach focused on physical manipulation of the body's soft tissues to correct somatic dysfunctions. OMM can directly target the pathophysiology of IBS through many approaches such as ANS modulation and lymphatic techniques to modify the inflammatory mechanisms within the body. Particular OMM techniques of use are lymphatic manipulation, myofascial release, sympathetic ganglia treatment, sacral rocking, counterstrain, and viscerosomatic treatment. The aim of this study is to identify OMM treatments that can be used to potentially reduce the inflammation and ANS dysfunction associated with IBS symptoms, thereby providing a new non-pharmacological targeted approach for treating the disease.}, } @article {pmid38495755, year = {2024}, author = {Zou, X and Zou, G and Zou, X and Wang, K and Chen, Z}, title = {Gut microbiota and its metabolites in Alzheimer's disease: from pathogenesis to treatment.}, journal = {PeerJ}, volume = {12}, number = {}, pages = {e17061}, pmid = {38495755}, issn = {2167-8359}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Alzheimer Disease/therapy ; *Microbiota ; Brain-Gut Axis ; Brain ; }, abstract = {INTRODUCTION: An increasing number of studies have demonstrated that altered microbial diversity and function (such as metabolites), or ecological disorders, regulate bowel-brain axis involvement in the pathophysiologic processes in Alzheimer's disease (AD). The dysregulation of microbes and their metabolites can be a double-edged sword in AD, presenting the possibility of microbiome-based treatment options. This review describes the link between ecological imbalances and AD, the interactions between AD treatment modalities and the microbiota, and the potential of interventions such as prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and dietary interventions as complementary therapeutic strategies targeting AD pathogenesis and progression.

SURVEY METHODOLOGY: Articles from PubMed and china.com on intestinal flora and AD were summarized to analyze the data and conclusions carefully to ensure the comprehensiveness, completeness, and accuracy of this review.

CONCLUSIONS: Regulating the gut flora ecological balance upregulates neurotrophic factor expression, regulates the microbiota-gut-brain (MGB) axis, and suppresses the inflammatory responses. Based on emerging research, this review explored novel directions for future AD research and clinical interventions, injecting new vitality into microbiota research development.}, } @article {pmid38495146, year = {2024}, author = {Xue, Y and Zhang, YN and Wang, M and Fu, HY and Mao, YC and Hu, M and Sun, MT and Guo, HG and Cao, L and Feng, CZ}, title = {Prolonged oral intake of green tea polyphenols attenuates delirium-like behaviors in mice induced by anesthesia/surgery.}, journal = {Heliyon}, volume = {10}, number = {5}, pages = {e26200}, pmid = {38495146}, issn = {2405-8440}, abstract = {Postoperative delirium (POD) is a severe postoperative complication characterized by delirium-like symptoms. So far, no effective preventable strategy for POD prevention has been identified. Reports show that the consumption of green tea polyphenols (GTP) is associated with better cognitive function by modulating the composition of gut microbiota. Whether GTP also play a role in alleviating POD through gut microbiota is unknown. Herein, we studied the effect of prolonged (eight weeks) GTP intake on postoperative delirium in C57BL/6 mice with laparotomies under isoflurane anesthesia (anesthesia/surgery). We subsequently investigated anesthesia/surgery caused behavioral changes and increased the expression of malondialdehyde (MAD), an oxidative stress marker, and the activities of superoxide dismutase (SOD), an antioxidant marker, in the mice at 6 h after anesthesia/surgery. However, GTP administration reversed these changes and alleviated anesthesia/surgery-induced decrease in the abundance of gut bacterial genera, Roseburia. Further, fecal microbiota transplant demonstrated that compared with mice in the control group, treatment of C57BL/6 mice with feces from GTP-treated mice had a slight effect on the behavioral changes of mice. These data suggest that daily consumption of GTP could protect against anesthesia/surgery-induced behavioral changes, which is closely associated with gut microbiota modification by GTP.}, } @article {pmid38493312, year = {2024}, author = {Kalam, N and Balasubramaniam, VRMT}, title = {Crosstalk between COVID-19 and the gut-brain axis: a gut feeling.}, journal = {Postgraduate medical journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/postmj/qgae030}, pmid = {38493312}, issn = {1469-0756}, support = {STG-000131//School Strategic Grants/ ; //Jeffrey Cheah School of Medicine & Health Sciences/ ; //Monash University Malaysia/ ; }, abstract = {The microbes in the gut are crucial for maintaining the body's immune system and overall gut health. However, it is not fully understood how an unstable gut environment can lead to more severe cases of SARS-CoV-2 infection. The gut microbiota also plays a role in the gut-brain axis and interacts with the central nervous system through metabolic and neuroendocrine pathways. The interaction between the microbiota and the host's body involves hormonal, immune, and neural pathways, and any disruption in the balance of gut bacteria can lead to dysbiosis, which contributes to pathogen growth. In this context, we discuss how dysbiosis could contribute to comorbidities that increase susceptibility to SARS-CoV-2. Probiotics and fecal microbiota transplantation have successfully treated infectious and non-infectious inflammatory-related diseases, the most common comorbidities. These treatments could be adjuvant therapies for COVID-19 infection by restoring gut homeostasis and balancing the gut microbiota.}, } @article {pmid38492132, year = {2024}, author = {Maharshi, S and Sharma, BC}, title = {Prophylaxis of hepatic encephalopathy: current and future drug targets.}, journal = {Hepatology international}, volume = {}, number = {}, pages = {}, pmid = {38492132}, issn = {1936-0541}, abstract = {Hepatic encephalopathy is described by a broad spectrum of neurological and psychiatric aberrations resulting due to advanced liver dysfunction. It is a neurological disorder due to hepatic insufficiency and/or portosystemic shunts. Its clinical presentation includes neuropsychiatric dysfunction ranging from subclinical changes to comatose state. It is a sign of poor prognosis in cirrhotics with a high 1-year mortality. Each episode of hepatic encephalopathy leads to high hospitalization rate, poor prognosis and raised burden of healthcare. Primary prophylaxis is prevention of initial occurrence and secondary prophylaxis is prevention of reappearance of hepatic encephalopathy in subjects who had prior history. Early detection and management of triggers is very important in the treatment of hepatic encephalopathy. The initial choice of treatment is still lactulose, as it is effective in minimal, overt, and recurrent hepatic encephalopathy. Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated. Branch chain amino acids are beneficial in subjects who are protein intolerant. L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy. Rifaximin along with lactulose is effective in managing overt and recurrent hepatic encephalopathy. Large portosystemic shunts embolization and liver transplant is efficacious in certain group of patients. Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy.}, } @article {pmid38488837, year = {2024}, author = {Wang, F and Liu, X and Huang, F and Zhou, Y and Wang, X and Song, Z and Wang, S and Wang, X and Shi, D and Ruan, G and Ji, X and Zhang, E and Tan, Z and Ye, Y and Wang, C and Zhu, J and Wang, W}, title = {Gut microbiota-derived gamma-aminobutyric acid from metformin treatment reduces hepatic ischemia/reperfusion injury through inhibiting ferroptosis.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {38488837}, issn = {2050-084X}, support = {2022R413C074//Zhejiang University Student Science and Technology Innovation Activity Plan/ ; LGF22H030011//Zhejiang Province Public Welfare Technology Application Research Project/ ; KJHX2212//Suzhou Inhale Pharma Co, Ltd/ ; KJHX2202//Zhejiang Xiaolun Intelligent Manufacturing Co, Ltd/ ; }, mesh = {Humans ; Mice ; Animals ; *Metformin/pharmacology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; *Ferroptosis ; *Reperfusion Injury/drug therapy/metabolism ; Ischemia ; gamma-Aminobutyric Acid/pharmacology ; }, abstract = {Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was confirmed by the results of fecal microbiota transplantation treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase and putrescine aminotransferase, in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite.}, } @article {pmid38488112, year = {2024}, author = {Frerichs, NM and de Meij, TGJ and Niemarkt, HJ}, title = {Microbiome and its impact on fetal and neonatal brain development: current opinion in pediatrics.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {}, number = {}, pages = {}, pmid = {38488112}, issn = {1473-6519}, abstract = {PURPOSE OF REVIEW: Emerging evidence suggests that the gut microbiota and its metabolites regulate neurodevelopment and cognitive functioning via a bi-directional communication system known as the microbiota-gut-brain axis (MGBA).

RECENT FINDINGS: The MGBA influences brain development and function via the hypothalamic-pituitary axis, the vagal nerve, immune signaling, bacterial production of neurotransmitters, and microbial metabolites like short-chain fatty acids, tryptophan derivatives, and bile acids. Animal studies show fetal neurodevelopment is mediated by maternal microbiota derivatives, immune activation, and diet. Furthermore, manipulation of the microbiota during critical windows of development, like antibiotic exposure and fecal microbiota transplantation, can affect cognitive functioning and behavior in mice. Evidence from human studies, particularly in preterm infants, also suggests that a disrupted gut microbiota colonization may negatively affect neurodevelopment. Early microbial signatures were linked to favorable and adverse neurodevelopmental outcomes.

SUMMARY: The link between the gut microbiota and the brain is evident. Future studies, including experimental studies, larger participant cohort studies with longitudinal analyses of microbes, their metabolites, and neurotransmitters, and randomized controlled trials are warranted to further elucidate the mechanisms of the MGBA. Identification of early, predictive microbial markers could pave the way for the development of novel early microbiota-based intervention strategies, such as targeted probiotics, and vaginal or fecal microbiota transplantation, aimed at improving infant neurodevelopment.}, } @article {pmid38485738, year = {2024}, author = {Di, Y and Song, Y and Xu, K and Wang, Q and Zhang, L and Liu, Q and Zhang, M and Liu, X and Wang, Y}, title = {Chicoric Acid Alleviates Colitis via Targeting the Gut Microbiota Accompanied by Maintaining Intestinal Barrier Integrity and Inhibiting Inflammatory Responses.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c08363}, pmid = {38485738}, issn = {1520-5118}, abstract = {Polyphenols have shown great potential to prevent ulcerative colitis. As a natural plant polyphenol, chicoric acid (CA) has antioxidant and anti-inflammatory properties. This study explored the intervention effects and potential mechanism of CA on dextran sodium sulfate (DSS)-induced colitis mice. The results showed that CA alleviated the symptoms of colitis and maintained the intestinal barrier integrity. CA significantly downregulated the mRNA expression levels of inflammatory factors including IL-6, IL-1β, TNF-α, IFN-γ, COX-2, and iNOS. In addition, CA modulated the gut microbiota by improving the microbial diversity, reducing the abundance of Gammaproteobacteriaand Clostridium_XI and increasing the abundance ofBarnesiellaandLachnospiraceae. Further fecal microbiota transplantation experiments showed that FM from CA donor mice significantly alleviated the symptoms of colitis, verifying the key role of gut microbiota. These results indicate that CA effectively relieves DSS-induced colitis via targeting gut microbiota along with preserving intestinal barrier function and suppressing inflammatory responses.}, } @article {pmid38485702, year = {2024}, author = {Li, L and Huang, X and Chen, H}, title = {Unveiling the hidden players: exploring the role of gut mycobiome in cancer development and treatment dynamics.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2328868}, doi = {10.1080/19490976.2024.2328868}, pmid = {38485702}, issn = {1949-0984}, mesh = {Humans ; *Mycobiome ; *Gastrointestinal Microbiome ; Fungi/genetics ; Carcinogenesis ; Cell Transformation, Neoplastic ; }, abstract = {The role of gut fungal species in tumor-related processes remains largely unexplored, with most studies still focusing on fungal infections. This review examines the accumulating evidence suggesting the involvement of commensal and pathogenic fungi in cancer biological process, including oncogenesis, progression, and treatment response. Mechanisms explored include fungal influence on host immunity, secretion of bioactive toxins/metabolites, interaction with bacterial commensals, and migration to other tissues in certain types of cancers. Attempts to utilize fungal molecular signatures for cancer diagnosis and fungal-derived products for treatment are discussed. A few studies highlight fungi's impact on the responsiveness and sensitivity to chemotherapy, radiotherapy, immunotherapy, and fecal microbiota transplant. Given the limited understanding and techniques in fungal research, the studies on gut fungi are still facing great challenges, despite having great potentials.}, } @article {pmid38484559, year = {2024}, author = {Wang, S and Li, X and Zhang, B and Li, Y and Chen, K and Qi, H and Gao, M and Rong, J and Liu, L and Wan, Y and Dong, X and Yan, M and Ma, L and Li, P and Zhao, T}, title = {Tangshen formula targets the gut microbiota to treat non-alcoholic fatty liver disease in HFD mice: A 16S rRNA and non-targeted metabolomics analyses.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {173}, number = {}, pages = {116405}, doi = {10.1016/j.biopha.2024.116405}, pmid = {38484559}, issn = {1950-6007}, abstract = {BACKGROUND: Tangshen formula (TSF) has an ameliorative effect on hepatic lipid metabolism in non-alcoholic fatty liver disease (NAFLD), but the role played by the gut microbiota in this process is unknown.

METHOD: We conducted three batches of experiments to explore the role played by the gut microbiota: TSF administration, antibiotic treatment, and fecal microbial transplantation. NAFLD mice were induced with a high-fat diet to investigate the ameliorative effects of TSF on NAFLD features and intestinal barrier function. 16S rRNA sequencing and serum untargeted metabolomics were performed to further investigate the modulatory effects of TSF on the gut microbiota and metabolic dysregulation in the body.

RESULTS: TSF ameliorated insulin resistance, hypercholesterolemia, lipid metabolism disorders, inflammation, and impairment of intestinal barrier function. 16S rRNA sequencing analysis revealed that TSF regulated the composition of the gut microbiota and increased the abundance of beneficial bacteria. Antibiotic treatment and fecal microbiota transplantation confirmed the importance of the gut microbiota in the treatment of NAFLD with TSF. Subsequently, untargeted metabolomics identified 172 differential metabolites due to the treatment of TSF. Functional predictions suggest that metabolisms of choline, glycerophospholipid, linoleic acid, alpha-linolenic acid, and arachidonic acid are the key metabolic pathways by which TSF ameliorates NAFLD and this may be influenced by the gut microbiota.

CONCLUSION: TSF treats the NAFLD phenotype by remodeling the gut microbiota and improving metabolic profile, suggesting that TSF is a functional gut microbial and metabolic modulator for the treatment of NAFLD.}, } @article {pmid38484370, year = {2024}, author = {Yao, Y and Wang, X and Li, D and Chen, S and Li, C and Guan, H and Wang, D and Nie, X}, title = {Cyclocarya paliurus leaves alleviate high-sucrose diet-induced obesity by improving intestinal metabolic disorders.}, journal = {Aging}, volume = {16}, number = {}, pages = {}, doi = {10.18632/aging.205657}, pmid = {38484370}, issn = {1945-4589}, abstract = {High-sucrose diets are common in daily life but harmful to human health. Cyclocarya paliurus leaves (CPL) are a kind of tea used to alleviate metabolic diseases and are widely used in China. However, the effects of CPL on high-sucrose-induced obesity are unknown. This study aimed to describe the changes in gut metabolism induced by a high-sucrose diet and to reveal the potential mechanisms through which CPL alleviate high-sucrose diet-induced obesity. A high-sucrose-induced obesity model was generated in C57BL/6J and KM mice. The effects of CPL on obese mice were evaluated, and changes in the gut microbiota and intestinal metabolites induced by CPL treatment were observed. Furthermore, the fecal microbiota transplantation (FMT) method was used to prove that the effects of CPL on high-sucrose induced obesity depend on the changes of gut microbiota. The results of the C57BL/6J mouse experiment revealed that high-sucrose intake induced fat deposition and altered the gut microbiota. CPL treatment decreased fat deposition and alleviated disorders of the gut microbiota. Furthermore, CPL treatment increased the utilization of amnio acids, long fatty acids and saccharides and produced more bile acids, indole derivatives and less trimethylamine (TMA). A confirmatory experiment in KM mice also revealed that CPL can alleviate obesity, ameliorate intestinal metabolic disorders, and upregulate the expression of tight junction proteins in the intestinal mucosa. These results demonstrated that CPL could prevent high sucrose-induced obesity and generate more beneficial intestinal microbial metabolites but less harmful intestinal microbial metabolites.}, } @article {pmid38479921, year = {2024}, author = {Peddinti, V and Avaghade, MM and Suthar, SU and Rout, B and Gomte, SS and Agnihotri, TG and Jain, A}, title = {Gut instincts: Unveiling the connection between gut microbiota and Alzheimer's disease.}, journal = {Clinical nutrition ESPEN}, volume = {60}, number = {}, pages = {266-280}, doi = {10.1016/j.clnesp.2024.02.019}, pmid = {38479921}, issn = {2405-4577}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Alzheimer Disease ; Dysbiosis ; Instinct ; Neuroinflammatory Diseases ; }, abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder marked by neuroinflammation and gradual cognitive decline. Recent research has revealed that the gut microbiota (GM) plays an important role in the pathogenesis of AD through the microbiota-gut-brain axis. However, the mechanism by which GM and microbial metabolites alter brain function is not clearly understood. GM dysbiosis increases the permeability of the intestine, alters the blood-brain barrier permeability, and elevates proinflammatory mediators causing neurodegeneration. This review article introduced us to the composition and functions of GM along with its repercussions of dysbiosis in relation to AD. We also discussed the importance of the gut-brain axis and its role in communication. Later we focused on the mechanism behind gut dysbiosis and the progression of AD including neuroinflammation, oxidative stress, and changes in neurotransmitter levels. Furthermore, we highlighted recent developments in AD management, such as microbiota-based therapy, dietary interventions like prebiotics, probiotics, and fecal microbiota transplantation. Finally, we concluded with challenges and future directions in AD research based on GM.}, } @article {pmid38479258, year = {2024}, author = {Wang, H and Zhu, W and Hong, Y and Wei, W and Zheng, N and He, X and Bao, Y and Gao, X and Huang, W and Sheng, L and Li, M and Li, H}, title = {Astragalus polysaccharides attenuate chemotherapy-induced immune injury by modulating gut microbiota and polyunsaturated fatty acid metabolism.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {128}, number = {}, pages = {155492}, doi = {10.1016/j.phymed.2024.155492}, pmid = {38479258}, issn = {1618-095X}, abstract = {BACKGROUND: The damage of chemotherapy drugs to immune function and intestinal mucosa is a common side effect during chemotherapy. Astragalus polysaccharides (APS) exhibit immunomodulatory properties and are recognized for preserving the integrity of the human intestinal barrier. Nevertheless, their application and mechanisms of action in chemotherapy-induced immune damage and intestinal barrier disruption remain insufficiently explored.

PURPOSE: This study delved into investigating how APS mitigates chemotherapy-induced immune dysfunction and intestinal mucosal injury, while also providing deeper insights into the underlying mechanisms.

METHODS: In a chemotherapy mice model induced by 5-fluorouracil (5-Fu), the assessment of APS's efficacy encompassed evaluations of immune organ weight, body weight, colon length, and histopathology. The regulation of different immune cells in spleen was detected by flow cytometry. 16S rRNA gene sequencings, ex vivo microbiome assay, fecal microbiota transplantation (FMT), and targeted metabolomics analysis were applied to explore the mechanisms of APS effected on chemotherapy-induced mice.

RESULTS: APS ameliorated chemotherapy-induced damage to immune organs and regulated immune cell differentiation disorders, including CD4[+]T, CD8[+]T, CD19[+]B, F4/80[+]CD11B[+] macrophages. APS also alleviated colon shortening and upregulated the expression of intestinal barrier proteins. Furthermore, APS significantly restored structure of gut microbiota following chemotherapy intervention. Ex vivo microbiome assays further demonstrated the capacity of APS to improve 5-Fu-induced microbiota growth inhibition and compositional change. FMT demonstrated that the regulation of gut microbiota by APS could promote the recovery of immune functions and alleviate shortening of the colon length. Remarkably, APS significantly ameliorated the imbalance of linoleic acid (LA) and α-linolenic acid in polyunsaturated fatty acid (PUFA) metabolism. Further in vitro experiments showed that LA could promote splenic lymphocyte proliferation. In addition, both LA and DGLA down-regulated the secretion of NO and partially up-regulated the percentage of F4/80[+]CD11B[+]CD206[+] cells.

CONCLUSION: APS can effectively ameliorate chemotherapy-induced immune damage and intestinal mucosal disruption by regulating the composition of the gut microbiota and further restoring PUFA metabolism. These findings indicate that APS can serve as an adjuvant to improve the side effects such as intestinal and immune damage caused by chemotherapy.}, } @article {pmid38478462, year = {2024}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Kazadi, D and Halaweish, H and Khan, MH and Hoeschen, A and Cao, Q and Luo, X and Kabage, AJ and Lopez, S and Holtan, SG and Weisdorf, DJ and Liu, C and Ishii, S and Khoruts, A and Staley, C}, title = {Long- and short-term effects of fecal microbiota transplantation on antibiotic resistance genes: results from a randomized placebo-controlled trial.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2327442}, pmid = {38478462}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Anti-Bacterial Agents/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/genetics ; Treatment Outcome ; Drug Resistance, Microbial ; Feces ; }, abstract = {In small series, third-party fecal microbiota transplantation (FMT) has been successful in decolonizing the gut from clinically relevant antibiotic resistance genes (ARGs). Less is known about the short- and long-term effects of FMT on larger panels of ARGs. We analyzed 226 pre- and post-treatment stool samples from a randomized placebo-controlled trial of FMT in 100 patients undergoing allogeneic hematopoietic cell transplantation or receiving anti-leukemia induction chemotherapy for 47 ARGs. These patients have heavy antibiotic exposure and a high incidence of colonization with multidrug-resistant organisms. Samples from each patient spanned a period of up to 9 months, allowing us to describe both short- and long-term effects of FMT on ARGs, while the randomized design allowed us to distinguish between spontaneous changes vs. FMT effect. We find an overall bimodal pattern. In the first phase (days to weeks after FMT), low-level transfer of ARGs largely associated with commensal healthy donor microbiota occurs. This phase is followed by long-term resistance to new ARGs as stable communities with colonization resistance are formed after FMT. The clinical implications of these findings are likely context-dependent and require further research. In the setting of cancer and intensive therapy, long-term ARG decolonization could translate into fewer downstream infections.}, } @article {pmid38475913, year = {2024}, author = {Sangiorgio, M and Middleton, C and Wilson, M and Osler, W and Patwardan, A}, title = {A case of fulminant severe Clostridioides difficile colitis managed with faecal microbial transplantation.}, journal = {Internal medicine journal}, volume = {54}, number = {3}, pages = {518-520}, doi = {10.1111/imj.16354}, pmid = {38475913}, issn = {1445-5994}, mesh = {Humans ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Clostridium Infections ; *Colitis ; }, } @article {pmid38473999, year = {2024}, author = {Jang, JH and Jang, SY and Ahn, S and Oh, JY and Yeom, M and Ko, SJ and Park, JW and Kwon, SK and Kim, K and Lee, IS and Hahm, DH and Park, HJ}, title = {Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38473999}, issn = {1422-0067}, support = {NRF-2021R1A2C2006818//National Research Foundation of Korea/ ; 2022M3A9B6017813//National Research Foundation of Korea/ ; }, mesh = {Humans ; Animals ; Mice ; *Irritable Bowel Syndrome ; *Dermatitis, Atopic ; Dysbiosis ; *Gastrointestinal Microbiome/physiology ; Feces ; Fecal Microbiota Transplantation ; Inflammation ; }, abstract = {Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.}, } @article {pmid38473913, year = {2024}, author = {Teschke, R}, title = {Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38473913}, issn = {1422-0067}, mesh = {Humans ; *Hemochromatosis/genetics ; Hepcidins/metabolism ; Reactive Oxygen Species/metabolism ; *Alcoholism/complications ; *Ferroptosis ; Artificial Intelligence ; *Gastrointestinal Microbiome ; Confounding Factors, Epidemiologic ; Histocompatibility Antigens Class I/genetics ; Hemochromatosis Protein/metabolism ; Membrane Proteins/metabolism ; Iron/metabolism ; *Iron Overload/genetics ; Ferritins ; Ethanol ; *Liver Neoplasms/complications ; }, abstract = {Hemochromatosis represents clinically one of the most important genetic storage diseases of the liver caused by iron overload, which is to be differentiated from hepatic iron overload due to excessive iron release from erythrocytes in patients with genetic hemolytic disorders. This disorder is under recent mechanistic discussion regarding ferroptosis, reactive oxygen species (ROS), the gut microbiome, and alcohol abuse as a risk factor, which are all topics of this review article. Triggered by released intracellular free iron from ferritin via the autophagic process of ferritinophagy, ferroptosis is involved in hemochromatosis as a specific form of iron-dependent regulated cell death. This develops in the course of mitochondrial injury associated with additional iron accumulation, followed by excessive production of ROS and lipid peroxidation. A low fecal iron content during therapeutic iron depletion reduces colonic inflammation and oxidative stress. In clinical terms, iron is an essential trace element required for human health. Humans cannot synthesize iron and must take it up from iron-containing foods and beverages. Under physiological conditions, healthy individuals allow for iron homeostasis by restricting the extent of intestinal iron depending on realistic demand, avoiding uptake of iron in excess. For this condition, the human body has no chance to adequately compensate through removal. In patients with hemochromatosis, the molecular finetuning of intestinal iron uptake is set off due to mutations in the high-FE[2+] (HFE) genes that lead to a lack of hepcidin or resistance on the part of ferroportin to hepcidin binding. This is the major mechanism for the increased iron stores in the body. Hepcidin is a liver-derived peptide, which impairs the release of iron from enterocytes and macrophages by interacting with ferroportin. As a result, iron accumulates in various organs including the liver, which is severely injured and causes the clinically important hemochromatosis. This diagnosis is difficult to establish due to uncharacteristic features. Among these are asthenia, joint pain, arthritis, chondrocalcinosis, diabetes mellitus, hypopituitarism, hypogonadotropic hypogonadism, and cardiopathy. Diagnosis is initially suspected by increased serum levels of ferritin, a non-specific parameter also elevated in inflammatory diseases that must be excluded to be on the safer diagnostic side. Diagnosis is facilitated if ferritin is combined with elevated fasting transferrin saturation, genetic testing, and family screening. Various diagnostic attempts were published as algorithms. However, none of these were based on evidence or quantitative results derived from scored key features as opposed to other known complex diseases. Among these are autoimmune hepatitis (AIH) or drug-induced liver injury (DILI). For both diseases, the scored diagnostic algorithms are used in line with artificial intelligence (AI) principles to ascertain the diagnosis. The first-line therapy of hemochromatosis involves regular and life-long phlebotomy to remove iron from the blood, which improves the prognosis and may prevent the development of end-stage liver disease such as cirrhosis and hepatocellular carcinoma. Liver transplantation is rarely performed, confined to acute liver failure. In conclusion, ferroptosis, ROS, the gut microbiome, and concomitant alcohol abuse play a major contributing role in the development and clinical course of genetic hemochromatosis, which requires early diagnosis and therapy initiation through phlebotomy as a first-line treatment.}, } @article {pmid38473143, year = {2024}, author = {Boucher, L and Leduc, L and Leclère, M and Costa, MC}, title = {Current Understanding of Equine Gut Dysbiosis and Microbiota Manipulation Techniques: Comparison with Current Knowledge in Other Species.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {5}, pages = {}, pmid = {38473143}, issn = {2076-2615}, abstract = {Understanding the importance of intestinal microbiota in horses and the factors influencing its composition have been the focus of many studies over the past few years. Factors such as age, diet, antibiotic administration, and geographic location can affect the gut microbiota. The intra- and inter-individual variability of fecal microbiota in horses complicates its interpretation and has hindered the establishment of a clear definition for dysbiosis. Although a definitive causal relationship between gut dysbiosis in horses and diseases has not been clearly identified, recent research suggests that dysbiosis may play a role in the pathogenesis of various conditions, such as colitis and asthma. Prebiotics, probiotics, and fecal microbiota transplantation to modulate the horse's gastrointestinal tract may eventually be considered a valuable tool for preventing or treating diseases, such as antibiotic-induced colitis. This article aims to summarize the current knowledge on the importance of intestinal microbiota in horses and factors influencing its composition, and also to review the published literature on methods for detecting dysbiosis while discussing the efficacy of gut microbiota manipulation in horses.}, } @article {pmid38472547, year = {2024}, author = {Homma, Y and Mimura, T and Koinuma, K and Horie, H and Sata, N}, title = {Incidence of low anterior resection syndrome and its association with the quality of life in patients with lower rectal tumors.}, journal = {Surgery today}, volume = {}, number = {}, pages = {}, pmid = {38472547}, issn = {1436-2813}, abstract = {PURPOSE: Low anterior resection syndrome (LARS) causes devastating symptoms and impairs the quality of life (QOL). This study investigated the incidence and risk factors of LARS and their association with the QOL in patients with lower rectal tumors.

METHODS: Patients who underwent anus-preserving surgery for lower rectal tumors between 2014 and 2019 and who had anal defecation between 2020 and 2021 were surveyed. The LARS score measured severity, and the QOL was evaluated using the Japanese version of the Fecal Incontinence Quality-of-Life Scale (JFIQL). The primary endpoint was the incidence of Major LARS, and the secondary endpoints were risk factors and association with the JFIQL.

RESULTS: Of 107 eligible patients, 82 (76.6%) completed the LARS survey. The incidence of Major LARS was 48%. Independent risk factors included neoadjuvant chemoradiotherapy (CRT) and a short interval (< 24 months after surgery; odds ratio, 4.6; 95% confidence interval: 1.1-19, both). The LARS score was moderately correlated with the JFIQL generic score (correlation coefficient: - 0.54). The JFIQL scores were significantly worse in the Minor and Major LARS groups than in the No LARS group.

CONCLUSIONS: Major LARS was found in 48% of lower rectal tumors, and independent risk factors include neoadjuvant CRT and a short interval. The QOL was significantly impaired in patients with both Minor and Major LARS.}, } @article {pmid38472186, year = {2024}, author = {Zhu, J and Bao, Z and Hu, Z and Wu, S and Tian, C and Zhou, Y and Ding, Z and Tan, X}, title = {Myricetin alleviates diabetic cardiomyopathy by regulating gut microbiota and their metabolites.}, journal = {Nutrition & diabetes}, volume = {14}, number = {1}, pages = {10}, pmid = {38472186}, issn = {2044-4052}, support = {No. 2023A1515011969, 2019A1515011817//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; No. 81900347//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {BACKGROUND: The gut microbiota is involved in the pathogenesis of diabetic cardiomyopathy (DCM). Myricetin protects cardiac function in DCM. However, the low bioavailability of myricetin fails to explain its pharmacological mechanisms thoroughly. Research has shown that myricetin has a positive effect on the gut microbiota. We hypothesize that myricetin improves the development of DCM via regulating gut microbiota.

METHODS: DCM mice were induced with streptozotocin and fed a high-fat diet, and then treated with myricetin by gavage and high-fat diet for 16 weeks. Indexes related to gut microbiota composition, cardiac structure, cardiac function, intestinal barrier function, and inflammation were detected. Moreover, the gut contents were transplanted to DCM mice, and the effect of fecal microbiota transplantation (FMT) on DCM mice was assessed.

RESULTS: Myricetin could improve cardiac function in DCM mice by decreasing cardiomyocyte hypertrophy and interstitial fibrosis. The composition of gut microbiota, especially for short-chain fatty acid-producing bacteria involving Roseburia, Faecalibaculum, and Bifidobacterium, was more abundant by myricetin treatment in DCM mice. Myricetin increased occludin expression and the number of goblet cells in DCM mice. Compared with DCM mice unfed with gut content, the cardiac function, number of goblet cells, and expression of occludin in DCM mice fed by gut contents were elevated, while cardiomyocyte hypertrophy and TLR4/MyD88 pathway-related proteins were decreased.

CONCLUSIONS: Myricetin can prevent DCM development by increasing the abundance of beneficial gut microbiota and restoring the gut barrier function.}, } @article {pmid38471063, year = {2024}, author = {DeFilipp, Z and Damania, AV and Kim, HT and Chia-Chi, C and El-Jawahri, A and McAfee, SL and Bottoms, AS and Toncheva, V and Smith, MM and Dolaher, M and Perry, LS and White, M and Diana, B and Connolly, S and Dey, BR and Frigault, MJ and Newcomb, RA and O'Donnell, PV and Spitzer, TR and Mansour, MK and Weber, D and Ajami, NJ and Hohmann, E and Jenq, RR and Chen, YB}, title = {Third-party fecal microbiota transplantation for high-risk treatment-naïve acute GVHD of the lower GI tract.}, journal = {Blood advances}, volume = {}, number = {}, pages = {}, doi = {10.1182/bloodadvances.2024012556}, pmid = {38471063}, issn = {2473-9537}, abstract = {Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study (NCT04139577), third-party, single donor FMT was administered in combination with systemic corticosteroids to participants with high-risk acute LGI GVHD, with a focus on treatment-naïve cases. Participants were scheduled to receive one induction dose (15 capsules/day for 2 consecutive days), followed by 3 weekly maintenance doses, consisting of 15 capsules/dose. The primary endpoint of the study was feasibility, which would be achieved if ≥80% of participants able to swallow ≥40 of the 75 scheduled capsules. Ten participants (9 treatment-naïve; 1 steroid-refractory) were enrolled and treated. The study met the primary endpoint, with 9 of 10 participants completing all eligible doses. Organ-specific LGI complete response rate at Day 28 was 70%. Initial clinical response was observed within 1 week for all responders and clinical responses were durable, without recurrent LGI GVHD in complete responders. Exploratory analyses suggest that alpha diversity increased following FMT. While recipient microbiome composition never achieved a high degree of donor similarity, expansion of donor-derived species and increases in tryptophan metabolites and short-chain fatty acids were observed within the first 7 days after FMT. Investigation into the use of microbiome-targeted interventions earlier in the treatment paradigm for acute LGI GVHD is warranted.}, } @article {pmid38471012, year = {2024}, author = {Jiang, Y and Yang, J and Xia, L and Wei, T and Cui, X and Wang, D and Jin, Z and Lin, X and Li, F and Yang, K and Lang, S and Liu, Y and Hang, J and Zhang, Z and Hong, T and Wei, R}, title = {Gut microbiota-tryptophan metabolism-GLP-1 axis participates in β-cell regeneration induced by dapagliflozin.}, journal = {Diabetes}, volume = {}, number = {}, pages = {}, doi = {10.2337/db23-0553}, pmid = {38471012}, issn = {1939-327X}, abstract = {Sodium-glucose co-transporter 2 (SGLT2) inhibitor, an efficacious anti-diabetic agent, which has cardiovascular and renal benefits, can promote pancreatic β-cell regeneration in type 2 diabetic mice. However, the underlying mechanism remains unclear. In this study, we aimed to use multi-omics to identify the mediators involved in β-cell regeneration induced by dapagliflozin. We showed that dapagliflozin lowered blood glucose level, upregulated plasma insulin level, and increased islet area in db/db mice. Dapagliflozin reshaped gut microbiota, and modulated microbiotic and plasmatic metabolites related to tryptophan metabolism, especially L-tryptophan, in the diabetic mice. Notably, L-tryptophan upregulated the mRNA level of GLP-1 production-related genes (Gcg and Pcsk1) expression and promoted GLP-1 secretion in cultured mouse intestinal L-cells, and it increased supernatant insulin level in primary human islets, which was eliminated by GPR142 antagonist. Transplantation of fecal microbiota from dapagliflozin-treated mice, supplementation of L-tryptophan or treatment with dapagliflozin upregulated L-tryptophan, GLP-1, and insulin or C-peptide level, and promoted β-cell regeneration in db/db mice. Addition of exendin 9-39, a GLP-1 receptor (GLP-1R) antagonist, or pancreatic Glp1r knockout diminished these beneficial effects. In summary, treatment with dapagliflozin in type 2 diabetic mice promotes β-cell regeneration by upregulating GLP-1 production, which is mediated via gut microbiota and tryptophan metabolism.}, } @article {pmid38470843, year = {2024}, author = {Chen, H and Ye, L and Wang, Y and Chen, J and Wang, J and Li, X and Lei, H and Liu, Y}, title = {Aflatoxin B1 exposure causes splenic pyroptosis by disturbing the gut microbiota-immune axis.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo04717b}, pmid = {38470843}, issn = {2042-650X}, abstract = {Aflatoxin B1 (AFB1) causes serious immunotoxicity and has attracted considerable attention owing to its high sensitivity and common chemical-viral interactions in living organisms. However, the sensitivity of different species to AFB1 widely varies, which cannot be explained by the different metabolism in species. The gut microbiota plays a crucial role in the immune system, but the interaction of the microbiota with AFB1-induced immunotoxicity still needs to be determined. Our results indicated that AFB1 exposure disrupted the structure of the gut microbiota and damaged the gut barrier, which caused translocation of microbiota metabolites, lipopolysaccharides, to the spleen. Subsequently, pyroptosis of the spleen was activated. Interestingly, AFB1 exposure had little effect on the splenic pyroptosis of pseudo-germfree mice (antibiotic mixtures eliminated their gut microbiota, ABX). Then, fecal microbiota transplant (FMT) and sterile fecal filtrate (SFF) were employed to validate the function of the gut microbiota and its metabolites in AFB1-induced splenic pyroptosis. The AFB1-disrupted microbiota and its metabolites significantly promoted splenic pyroptosis, which was worse than that in control mice. Overall, AFB1-induced splenic pyroptosis is associated with the gut microbiota and its metabolites, which was further demonstrated by FMT and SFF. The mechanism of AFB1-induced splenic pyroptosis was explored for the first time, which paves a new way for preventing and treating the immunotoxicity from mycotoxins by regulating the gut microbiota.}, } @article {pmid38470061, year = {2024}, author = {Hunt, A and Drwiega, E and Wang, Y and Danziger, L}, title = {A review of fecal microbiota, live-jslm for the prevention of recurrent Clostridioides difficile infection.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {}, number = {}, pages = {}, doi = {10.1093/ajhp/zxae066}, pmid = {38470061}, issn = {1535-2900}, abstract = {DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: To review the composition, preparation, proposed mechanism of action, safety, efficacy, and current place in therapy of Rebyota (fecal microbiota, live-jslm).

SUMMARY: As the first agent in a new class of drugs, live biotherapeutic products (LBPs), fecal microbiota, live-jslm offers another therapeutic approach for the prevention of recurrent Clostridioides difficile infection (rCDI). LBPs are given following antibiotic therapy for C. difficile to reintroduce certain bacteria present in the normal microbiome, as a means to reconstitute the microbiome of infected individuals. This review provides a summary of phase 2 and 3 clinical trials, product information, discussion of data limitations, and recommendations for place in therapy. High efficacy rates compared to placebo with sustained response up to 24 months after administration have been reported. The majority of adverse events identified were mild to moderate without significant safety signals.

CONCLUSION: Fecal microbiota, live-jslm has consistently been shown in randomized trials to be safe and effective in reducing rCDI. Its approval marks the culmination of decades of work to identify, characterize, and refine the intestinal microbiome to create pharmaceutical products.}, } @article {pmid38467249, year = {2024}, author = {Mullish, BH and Bak, A and Merrick, B and Quraishi, MN and Goldenberg, SD and Williams, HRT}, title = {Overview of the second edition of the joint British Society of Gastroenterology and Healthcare Infection Society faecal microbiota transplant guidelines, 2024.}, journal = {The Journal of hospital infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhin.2024.02.021}, pmid = {38467249}, issn = {1532-2939}, } @article {pmid38466881, year = {2024}, author = {Yang, H and Liu, Q and Liu, H and Kang, X and Tian, H and Kang, Y and Li, L and Yang, X and Ren, P and Kuang, X and Wang, X and Guo, L and Tong, M and Ma, J and Fan, W}, title = {Berberine alleviates concanavalin A-induced autoimmune hepatitis in mice by modulating the gut microbiota.}, journal = {Hepatology communications}, volume = {8}, number = {4}, pages = {}, pmid = {38466881}, issn = {2471-254X}, mesh = {Mice ; Animals ; *Hepatitis, Autoimmune/drug therapy/etiology ; *Berberine/pharmacology/therapeutic use ; Concanavalin A/pharmacology ; Lipopolysaccharides/pharmacology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; *Hepatitis A ; }, abstract = {BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored.

METHODS: BBR was orally administered at doses of 100 mg⋅kg-1⋅d-1 for 7 days to mice before concanavalin A-induced AIH model establishment. Histopathological, immunohistochemical, immunofluorescence, western blotting, ELISA, 16S rRNA analysis, flow cytometry, real-time quantitative PCR, and fecal microbiota transplantation studies were performed to ascertain BBR effects and mechanisms in AIH mice.

RESULTS: We found that liver necrosis and apoptosis were decreased upon BBR administration; the levels of serum transaminase, serum lipopolysaccharide, liver proinflammatory factors TNF-α, interferon-γ, IL-1β, and IL-17A, and the proportion of Th17 cells in spleen cells were all reduced, while the anti-inflammatory factor IL-10 and regulatory T cell proportions were increased. Moreover, BBR treatment increased beneficial and reduced harmful bacteria in the gut. BBR also strengthened ileal barrier function by increasing the expression of the tight junction proteins zonula occludens-1 and occludin, thereby blocking lipopolysaccharide translocation, preventing lipopolysaccharide/toll-like receptor 4 (TLR4)/ NF-κB pathway activation, and inhibiting inflammatory factor production in the liver. Fecal microbiota transplantation from BBR to model mice also showed that BBR potentially alleviated AIH by altering the gut microbiota.

CONCLUSIONS: BBR alleviated concanavalin A-induced AIH by modulating the gut microbiota and related immune regulation. These results shed more light on potential BBR therapeutic strategies for AIH.}, } @article {pmid38464968, year = {2024}, author = {Lazar, L and Eshel, A and Moadi, L and Yackobovitch-Gavan, M and Bar-Maisels, M and Shtaif, B and Nevo, M and Phillip, M and Turjeman, S and Koren, O and Gat-Yablonski, G}, title = {Children with idiopathic short stature have significantly different gut microbiota than their normal height siblings: a case-control study.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1343337}, pmid = {38464968}, issn = {1664-2392}, mesh = {Child ; Humans ; Mice ; Animals ; *Siblings ; Case-Control Studies ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Growth Disorders/etiology ; }, abstract = {OBJECTIVES: To investigate the role of gut microbiota (GM) in pathogenesis of idiopathic short stature (ISS) by comparing GM of ISS children to their normal-height siblings.

METHODS: This case-control study, conducted at the Schneider Children's Medical Center's Institute for Endocrinology and Diabetes between 4/2018-11/2020, involved 30 pairs of healthy pre-pubertal siblings aged 3-10 years, each comprising one sibling with ISS and one with normal height. Outcome measures from fecal analysis of both siblings included GM composition analyzed by 16S rRNA sequencing, fecal metabolomics, and monitoring the growth of germ-free (GF) mice after fecal transplantation.

RESULTS: Fecal analysis of ISS children identified higher predicted levels of genes encoding enzymes for pyrimidine, purine, flavin, coenzyme B, and thiamine biosynthesis, lower levels of several amino acids, and a significantly higher prevalence of the phylum Euryarchaeota compared to their normal-height siblings (p<0.001). ISS children with higher levels of Methanobrevibacter, the dominant species in the archaeal gut community, were significantly shorter in stature than those with lower levels (p=0.022). Mice receiving fecal transplants from ISS children did not experience stunted growth, probably due to the eradication of Methanobrevibacter caused by exposure to oxygen during fecal collection.

DISCUSSION: Our findings suggest that different characteristics in the GM may explain variations in linear growth. The varying levels of Methanobrevibacter demonstrated within the ISS group reflect the multifactorial nature of ISS and the potential ability of the GM to partially explain growth variations. The targeting of specific microbiota could provide personalized therapies to improve growth in children with ISS.}, } @article {pmid38464791, year = {2024}, author = {Bai, X and Fu, R and Liu, Y and Deng, J and Fei, Q and Duan, Z and Zhu, C and Fan, D}, title = {Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis.}, journal = {Journal of pharmaceutical analysis}, volume = {14}, number = {2}, pages = {259-275}, pmid = {38464791}, issn = {2214-0883}, abstract = {The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer (CRC). However, the effect of ginsenoside Rk3 (Rk3) on CRC and gut microbiota remains unclear. Therefore, the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation. Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors, repairs intestinal barrier damage, and regulates the gut microbiota imbalance caused by CRC, including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis, and clearance of pathogenic Desulfovibrio. Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids, particularly by upregulating glutamine, which has the potential to regulate the immune response. Furthermore, we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells (ILC3s) and T helper 17 (Th17) signaling pathways, which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signaling pathway. These results indicate that Rk3 modulates gut microbiota, regulates ILC3s immune response, and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors. More importantly, the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota. In summary, these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.}, } @article {pmid38464781, year = {2024}, author = {Hui, H and Wang, Z and Zhao, X and Xu, L and Yin, L and Wang, F and Qu, L and Peng, J}, title = {Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata (Desv.) Spring against inflammatory bowel disease.}, journal = {Journal of pharmaceutical analysis}, volume = {14}, number = {2}, pages = {177-195}, pmid = {38464781}, issn = {2214-0883}, abstract = {Inflammatory bowel disease (IBD) is a serious disorder, and exploration of active compounds to treat it is necessary. An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata (Desv.) Spring, which contained galacturonic acid, galactose, xylose, arabinose, and rhamnose with the main chain structure of →4)-α-d-GalAp-(1→ and →6)-β-d-Galp-(1→ and the branched structure of →5)-α-l-Araf-(1→ . Animal experiments showed that compared with Model group, SUSP-4 significantly improved body weight status, disease activity index (DAI), colonic shortening, and histopathological damage, and elevated occludin and zonula occludens protein 1 (ZO-1) expression in mice induced by dextran sulfate sodium salt (DSS). 16S ribosomal RNA (rRNA) sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes. Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism, which was further confirmed by a targeted metabolism study. Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice. A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B (p-NF-κB) and cyclooxygenase-2 (COX-2) and elevating NF-E2-related factor 2 (Nrf2) levels compared with Model group. In conclusion, SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD. This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD, showing great potential for in-depth research and development applications.}, } @article {pmid38461664, year = {2024}, author = {Wang, Y and Gao, C and Niu, W and Han, S and Qin, M and Tian, Z and Zuo, W and Xia, X and Wang, H and Li, Y}, title = {Polystyrene microplastics promote intestinal colonization of Aeromonas veronii through inducing intestinal microbiota dysbiosis.}, journal = {Journal of hazardous materials}, volume = {469}, number = {}, pages = {133976}, doi = {10.1016/j.jhazmat.2024.133976}, pmid = {38461664}, issn = {1873-3336}, abstract = {The premise that pathogen colonized microplastics (MPs) can promote the spread of pathogens has been widely recognized, however, their role in the colonization of pathogens in a host intestine has not been fully elucidated. Here, we investigated the effect of polystyrene MPs (PS-MPs) on the colonization levels of Aeromonas veronii, a typical aquatic pathogen, in the loach (Misgurnus anguillicaudatus) intestine. Multiple types of MPs were observed to promote the intestinal colonization of A. veronii, among which PS-MPs exhibited the most significant stimulating effect (67.18% increase in A. veronii colonization). PS-MPs inflicted serious damage to the intestinal tracts of loaches and induced intestinal microbiota dysbiosis. The abundance of certain intestinal bacteria with resistance against A. veronii colonization decreased, with Lactococcus sp. showing the strongest colonization resistance (73.64% decline in A. veronii colonization). Fecal microbiota transplantation was performed, which revealed that PS-MPs induced intestinal microbiota dysbiosis was responsible for the increased colonization of A. veronii in the intestine. It was determined that PS-MPs reshaped the intestinal microbiota community to attenuate the colonization resistance against A. veronii colonization, resulting in an elevated intestinal colonization levels of A. veronii.}, } @article {pmid38460630, year = {2024}, author = {Huang, X and Hu, X and Li, S and Li, T}, title = {Vitexin-rhamnoside encapsulated with zein-pectin nanoparticles relieved high-fat diet induced lipid metabolism disorders in mice by altering the gut microbiota.}, journal = {International journal of biological macromolecules}, volume = {264}, number = {Pt 2}, pages = {130704}, doi = {10.1016/j.ijbiomac.2024.130704}, pmid = {38460630}, issn = {1879-0003}, abstract = {This study aimed to investigate the modulatory effects of Vitexin-rhamnoside (VR) and Zein-VR-pectin nanoparticles (VRN) on lipid metabolism disorders induced by high-fat diet (HFD). The ingestion of VR or VRN attenuated dyslipidemia and fat accumulation in HFD mice, and improved intestinal dysbiosis by regulating the relative abundance of dominant bacteria, alleviating chronic inflammation and hepatic injury in HFD mice. The intervention effect of VRN was significantly higher than that of VR. After fecal microbiota transplantation (FMT) treatment, the fecal microbiota of VRN-treated donor mice significantly attenuated the symptoms associated with hyperlipidemia, confirming that VRN ameliorates HFD-induced disorders of lipid metabolism by modulating the gut microbiota, especially increasing the abundance of Rombousia and Faecalibaculum. Overall, VRN can regulate the gut microbiota and thus improve lipid metabolism. The present study provided new evidence that nanoparticles enhance the bioavailability of food bioactive ingredients.}, } @article {pmid38459479, year = {2024}, author = {Wang, Q and He, Z and Zhu, J and Hu, M and Yang, L and Yang, H}, title = {Polyphyllin B inhibited STAT3/NCOA4 pathway and restored gut microbiota to ameliorate lung tissue injury in cigarette smoke-induced mice.}, journal = {BMC biotechnology}, volume = {24}, number = {1}, pages = {13}, pmid = {38459479}, issn = {1472-6750}, support = {20C1591//Scientific Research Project of Hunan Provincial Department of Education/ ; kq2202044//Science and Technology Program Foundation of Changsha/ ; 202203022887//Scientific Research Project of Hunan Provincial Health Commission/ ; }, mesh = {Animals ; Mice ; *Lung Injury/complications/metabolism/pathology ; *Cigarette Smoking/adverse effects ; *Gastrointestinal Microbiome ; STAT3 Transcription Factor/genetics/metabolism/therapeutic use ; Lipopolysaccharides/adverse effects ; Molecular Docking Simulation ; RNA, Ribosomal, 16S ; Cell Line ; Lung ; *Pulmonary Disease, Chronic Obstructive/therapy/drug therapy ; Nicotiana ; Inflammation/pathology ; Ferritins/adverse effects/metabolism ; }, abstract = {OBJECTIVE: Smoking was a major risk factor for chronic obstructive pulmonary disease (COPD). This study plan to explore the mechanism of Polyphyllin B in lung injury induced by cigarette smoke (CSE) in COPD.

METHODS: Network pharmacology and molecular docking were applied to analyze the potential binding targets for Polyphyllin B and COPD. Commercial unfiltered CSE and LPS were used to construct BEAS-2B cell injury in vitro and COPD mouse models in vivo, respectively, which were treated with Polyphyllin B or fecal microbiota transplantation (FMT). CCK8, LDH and calcein-AM were used to detect the cell proliferation, LDH level and labile iron pool. Lung histopathology, Fe[3+] deposition and mitochondrial morphology were observed by hematoxylin-eosin, Prussian blue staining and transmission electron microscope, respectively. ELISA was used to measure inflammation and oxidative stress levels in cells and lung tissues. Immunohistochemistry and immunofluorescence were applied to analyze the 4-HNE, LC3 and Ferritin expression. RT-qPCR was used to detect the expression of FcRn, pIgR, STAT3 and NCOA4. Western blot was used to detect the expression of Ferritin, p-STAT3/STAT3, NCOA4, GPX4, TLR2, TLR4 and P65 proteins. 16S rRNA gene sequencing was applied to detect the gut microbiota.

RESULTS: Polyphyllin B had a good binding affinity with STAT3 protein, which as a target gene in COPD. Polyphyllin B inhibited CS-induced oxidative stress, inflammation, mitochondrial damage, and ferritinophagy in COPD mice. 16S rRNA sequencing and FMT confirmed that Akkermansia and Escherichia_Shigella might be the potential microbiota for Polyphyllin B and FMT to improve CSE and LPS-induced COPD, which were exhausted by the antibiotics in C + L and C + L + P mice. CSE and LPS induced the decrease of cell viability and the ferritin and LC3 expression, and the increase of NCOA4 and p-STAT3 expression in BEAS-2B cells, which were inhibited by Polyphyllin B. Polyphyllin B promoted ferritin and LC3II/I expression, and inhibited p-STAT3 and NCOA4 expression in CSE + LPS-induced BEAS-2B cells.

CONCLUSION: Polyphyllin B improved gut microbiota disorder and inhibited STAT3/NCOA4 pathway to ameliorate lung tissue injury in CSE and LPS-induced mice.}, } @article {pmid38457473, year = {2024}, author = {Ji, K and Zhang, M and Du, L and Wang, J and Liu, Y and Xu, C and He, N and Wang, Q and Gu, Y and Song, H and Wang, Y and Liu, Q}, title = {Exploring the Role of Inulin in Targeting the Gut Microbiota: An Innovative Strategy for Alleviating Colonic Fibrosis Induced By Irradiation.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c03432}, pmid = {38457473}, issn = {1520-5118}, abstract = {The use of radiation therapy to treat pelvic and abdominal cancers can lead to the development of either acute or chronic radiation enteropathy. Radiation-induced chronic colonic fibrosis is a common gastrointestinal disorder resulting from the above radiation therapy. In this study, we establish the efficacy of inulin supplements in safeguarding against colonic fibrosis caused by irradiation therapy. Studies have demonstrated that inulin supplements enhance the proliferation of bacteria responsible to produce short-chain fatty acids (SCFAs) and elevate the levels of SCFAs in feces. In a mouse model of chronic radiation enteropathy, the transplantation of gut microbiota and its metabolites from feces of inulin-treated mice were found to reduce colonic fibrosis in validation experiments. Administering inulin-derived metabolites from gut microbiota led to a notable decrease in the expression of genes linked to fibrosis and collagen production in mouse embryonic fibroblast cell line NIH/3T3. In the cell line, inulin-derived metabolites also suppressed the expression of genes linked to the extracellular matrix synthesis pathway. The results indicate a novel and practical approach to safeguarding against chronic radiation-induced colonic fibrosis.}, } @article {pmid38457257, year = {2024}, author = {Liu, X and Li, Y and Gu, M and Xu, T and Wang, C and Chang, P}, title = {Radiation enteropathy-related depression: A neglectable course of disease by gut bacterial dysbiosis.}, journal = {Cancer medicine}, volume = {13}, number = {4}, pages = {e6865}, pmid = {38457257}, issn = {2045-7634}, support = {20200201400JC//Scientific and Technological Developing Scheme Foundation of Jilin Province/ ; 82272738//National Natural Science Foundation of China/ ; 81874254//National Natural Science Foundation of China/ ; JLSWSRCZX2020-00931//Special Foundation to Health Professionals of Jilin Province/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; Depression/etiology ; *Inflammatory Bowel Diseases ; Bacteria ; }, abstract = {Radiation enteropathy (RE) is common in patients treated with radiotherapy for pelvic-abdominal cancers. Accumulating data indicate that gut commensal bacteria determine intestinal radiosensitivity. Radiotherapy can result in gut bacterial dysbiosis. Gut bacterial dysbiosis contributes to the pathogenesis of RE. Mild to moderate depressive symptoms can be observed in patients with RE in clinical settings; however, the rate of these symptoms has not been reported. Studies have demonstrated that gut bacterial dysbiosis induces depression. In the state of comorbidity, RE and depression may be understood as local and abscopal manifestations of gut bacterial disorders. The ability of comorbid depression to worsen inflammatory bowel disease (IBD) has long been demonstrated and is associated with dysfunction of cholinergic neural anti-inflammatory pathways. There is a lack of direct evidence for RE comorbid with depression. It is widely accepted that RE shares similar pathophysiologic mechanisms with IBD. Therefore, we may be able to draw on the findings of the relationship between IBD and depression. This review will explore the relationship between gut bacteria, RE, and depression in light of the available evidence and indicate a method for investigating the mechanisms of RE combined with depression. We will also describe new developments in the treatment of RE with probiotics, prebiotics, and fecal microbial transplantation.}, } @article {pmid38457115, year = {2024}, author = {Sadowsky, MJ and Matson, M and Mathai, PP and Pho, M and Staley, C and Evert, C and Weldy, M and Khoruts, A}, title = {Successful Treatment of Recurrent Clostridioides difficile Infection Using a Novel, Drinkable, Oral Formulation of Fecal Microbiota.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {38457115}, issn = {1573-2568}, abstract = {BACKGROUND: Fecal microbiota transplants can be administered orally in encapsulated form or require invasive procedures to administer liquid formulations. There is a need for an oral liquid formulation of fecal microbiota for patients who are unable to swallow capsules, especially if they require multiple, repeated administrations.

AIMS: These studies were conducted to develop a protocol to manufacture an organoleptically acceptable powdered fecal microbiota formulation that can be suspended in a liquid carrier and used for fecal microbiota transplantation.

METHODS: Several processing steps were investigated, including extra washes of microbiota prior to lyophilization and an addition of a flavoring agent. The viability of bacteria in the transplant formulation was tested using live/dead microscopy staining and engraftment into antibiotic-treated mice. After development of a clinical protocol for suspension of the powdered microbiota, the new formulation was tested in three elderly patients with recurrent Clostridioides difficile infections and who have difficulties in swallowing capsules. Changes in the microbial community structure in one of the patients were characterized using 16S rRNA gene profiling and engraftment analysis.

RESULTS: The processing steps used to produce an organoleptically acceptable suspension of powdered fecal microbiota did not result in loss of its viability. The powder could be easily suspended in a liquid carrier. The use of the new formulation was associated with abrogation of the cycle of C. difficile infection recurrences in the three patients.

CONCLUSION: We developed a novel organoleptically acceptable liquid formulation of fecal microbiota that is suitable for use in clinical trials for patients with difficulties in swallowing capsules.}, } @article {pmid38454984, year = {2024}, author = {Lwin, MW and Cheng, CY and Calderazzo, S and Schramm, C and Schlander, M}, title = {Would initiating colorectal cancer screening from age of 45 be cost-effective in Germany? An individual-level simulation analysis.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1307427}, pmid = {38454984}, issn = {2296-2565}, mesh = {Humans ; Middle Aged ; Young Adult ; Adult ; *Cost-Effectiveness Analysis ; Cost-Benefit Analysis ; Early Detection of Cancer/methods ; *Colorectal Neoplasms/diagnosis/prevention & control ; Colonoscopy ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) screening has been shown to be effective and cost-saving. However, the trend of rising incidence of early-onset CRC challenges the current national screening program solely for people ≥50 years in Germany, where extending the screening to those 45-49 years might be justified. This study aims to evaluate the cost-effectiveness of CRC screening strategies starting at 45 years in Germany.

METHOD: DECAS, an individual-level simulation model accounting for both adenoma and serrated pathways of CRC development and validated with German CRC epidemiology and screening effects, was used for the cost-effectiveness analysis. Four CRC screening strategies starting at age 45, including 10-yearly colonoscopy (COL), annual/biennial fecal immunochemical test (FIT), or the combination of the two, were compared with the current screening offer starting at age 50 years in Germany. Three adherence scenarios were considered: perfect adherence, current adherence, and high screening adherence. For each strategy, a cohort of 100,000 individuals with average CRC risk was simulated from age 20 until 90 or death. Outcomes included CRC cases averted, prevented death, quality-adjusted life-years gained (QALYG), and total incremental costs considering both CRC treatment and screening costs. A 3% discount rate was applied and costs were in 2023 Euro.

RESULT: Initiating 10-yearly colonoscopy-only or combined FIT + COL strategies at age 45 resulted in incremental gains of 7-28 QALYs with incremental costs of €28,360-€71,759 per 1,000 individuals, compared to the current strategy. The ICER varied from €1,029 to €9,763 per QALYG, and the additional number needed for colonoscopy ranged from 129 to 885 per 1,000 individuals. Among the alternatives, a three times colonoscopy strategy starting at 45 years of age proves to be the most effective, while the FIT-only strategy was dominated by the currently implemented strategy. The findings remained consistent across probabilistic sensitivity analyses.

CONCLUSION: The cost-effectiveness findings support initiating CRC screening at age 45 with either colonoscopy alone or combined with FIT, demonstrating substantial gains in quality-adjusted life-years with a modest increase in costs. Our findings emphasize the importance of implementing CRC screening 5 years earlier than the current practice to achieve more significant health and economic benefits.}, } @article {pmid38454775, year = {2024}, author = {Mortezaee, K and Majidpoor, J}, title = {Immunotherapy of Human Melanoma: Past, Present, Future.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0109298673283943240227104122}, pmid = {38454775}, issn = {1875-533X}, abstract = {Immunotherapy with immune checkpoint inhibitors (ICIs) is a promising therapeutic schedule in advanced solid cancers. In this review, clinical trials from highly reputable journals are interpreted for safety and efficacy evaluation of the common anti-programmed death-1 (PD-1) inhibitor nivolumab and/or the most known anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitor ipilimumab in advanced melanoma. Current progress in the field of melanoma immunotherapy is the focus of this review. Solo nivolumab and combo nivolumab-ipilimumab show higher responses compared to solo ipilimumab or chemotherapy. BRAF and programmed death-ligand 1 (PDL1) expression states are seemingly not reliable biomarkers of response to ICI therapy in melanoma. Solo ipilimumab and particularly a combination of nivolumab-ipilimumab show higher adverse events (AEs) compared with solo nivolumab or chemotherapy. Besides, ICI therapy is safer in mucosal melanoma, but its efficacy is higher in the cutaneous subtype. Patients receiving combination regimens who are experiencing serious AEs can discontinue such regimens until recovery and still maintain clinical benefits. To conclude, combo nivolumab-ipilimumab represents more therapeutic advantages compared with solo nivolumab or ipilimumab, but the rate of AEs is higher for combination regimens. Resistance to combo nivolumab-ipilimumab demands the application of novel approaches to go with ICIs in melanoma immunotherapy. Immunogenic agents, alternative immune checkpoints, vaccination, oncolytic viruses, extracellular vesicles (EVs) and fecal microbiome transplantation (FMT) are novel strategies in patients developing ICI resistance.}, } @article {pmid38454425, year = {2024}, author = {Zeng, F and Su, X and Liang, X and Liao, M and Zhong, H and Xu, J and Gou, W and Zhang, X and Shen, L and Zheng, JS and Chen, YM}, title = {Gut microbiome features and metabolites in non-alcoholic fatty liver disease among community-dwelling middle-aged and older adults.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {104}, pmid = {38454425}, issn = {1741-7015}, support = {2023A1515030155//Guangdong Basic and Applied Basic Research Foundation/ ; 81602853//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82073546//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 82073529//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 2007032//the 5010 Program for Clinical Researches/ ; }, abstract = {BACKGROUND: The specific microbiota and associated metabolites linked to non-alcoholic fatty liver disease (NAFLD) are still controversial. Thus, we aimed to understand how the core gut microbiota and metabolites impact NAFLD.

METHODS: The data for the discovery cohort were collected from the Guangzhou Nutrition and Health Study (GNHS) follow-up conducted between 2014 and 2018. We collected 272 metadata points from 1546 individuals. The metadata were input into four interpretable machine learning models to identify important gut microbiota associated with NAFLD. These models were subsequently applied to two validation cohorts [the internal validation cohort (n = 377), and the prospective validation cohort (n = 749)] to assess generalizability. We constructed an individual microbiome risk score (MRS) based on the identified gut microbiota and conducted animal faecal microbiome transplantation experiment using faecal samples from individuals with different levels of MRS to determine the relationship between MRS and NAFLD. Additionally, we conducted targeted metabolomic sequencing of faecal samples to analyse potential metabolites.

RESULTS: Among the four machine learning models used, the lightGBM algorithm achieved the best performance. A total of 12 taxa-related features of the microbiota were selected by the lightGBM algorithm and further used to calculate the MRS. Increased MRS was positively associated with the presence of NAFLD, with odds ratio (OR) of 1.86 (1.72, 2.02) per 1-unit increase in MRS. An elevated abundance of the faecal microbiota (f__veillonellaceae) was associated with increased NAFLD risk, whereas f__rikenellaceae, f__barnesiellaceae, and s__adolescentis were associated with a decreased presence of NAFLD. Higher levels of specific gut microbiota-derived metabolites of bile acids (taurocholic acid) might be positively associated with both a higher MRS and NAFLD risk. FMT in mice further confirmed a causal association between a higher MRS and the development of NAFLD.

CONCLUSIONS: We confirmed that an alteration in the composition of the core gut microbiota might be biologically relevant to NAFLD development. Our work demonstrated the role of the microbiota in the development of NAFLD.}, } @article {pmid38454297, year = {2024}, author = {Buldukoglu, OC and Ocal, S and Cekin, AH}, title = {Fecal microbiota transplantation as an early therapeutic option in treatment refractory Clostridioides difficile infection.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16535}, pmid = {38454297}, issn = {1440-1746}, } @article {pmid38453435, year = {2024}, author = {Zhuang, B and Gan, L and Liu, B and Yuan, W and Shi, M and Peng, A and Wang, L and Chen, X and Liu, T and Zhang, S and Wang, S and Gao, Q and Wang, B and Zheng, H and Liu, C and Luo, Y and Ye, H and Lin, H and Li, Y and He, Q and Zheng, F and Luo, P and Long, G and Lu, W and Li, K and Yang, J and Liu, YC and Zhang, Z and Li, X and Zhang, W and Zuo, L}, title = {Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301).}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {}, number = {}, pages = {}, doi = {10.1093/ndt/gfae053}, pmid = {38453435}, issn = {1460-2385}, abstract = {BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD).

METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus.

RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation.

CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.}, } @article {pmid38452932, year = {2024}, author = {Zhang, D and Lv, W and Xu, Y and Zhang, Z and Zeng, S and Zhang, W and Gong, L and Shao, L and Zhang, M and He, T and Liu, Y and Wang, Y and Liu, L and Hu, X}, title = {Microbial bile acid metabolite ameliorates mycophenolate mofetil-induced gastrointestinal toxicity through vitamin D3 receptor.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ajt.2024.02.029}, pmid = {38452932}, issn = {1600-6143}, abstract = {Mycophenolate mofetil (MMF) is one of the most used immunosuppressive drugs in organ transplantation, but frequent gastrointestinal (GI) side effects through unknown mechanisms limit its clinical use. Gut microbiota and its metabolites were recently reported to play a vital role in MMF-induced GI toxicity, but the specific mechanism of how they interact with the human body is still unclear. Here, we found that secondary bile acids (BAs), as bacterial metabolites, were significantly reduced by MMF administration in the gut of mice. Microbiome data and fecal microbiota transfer model supported a microbiota-dependent effect on the reduction of secondary BAs. Supplementation of the secondary BA lithocholic acid (LCA) alleviated MMF-induced weight loss, colonic inflammation, and oxidative phosphorylation damage. Genetic deletion of the vitamin D3 receptor (VDR), which serves as a primary colonic BA receptor, in colonic epithelial cells (VDR[ΔIEC]) abolished the therapeutic effect of LCA on MMF-induced GI toxicity. Impressively, we discovered that paricalcitol, an FDA-approved VDR agonist that has been used in clinics for years, could effectively alleviate MMF-induced GI toxicity. Our study reveals a previously unrecognized mechanism of gut microbiota, BAs, and VDR signaling in MMF-induced GI side effects, offering potential therapeutic strategies for clinics.}, } @article {pmid38449863, year = {2024}, author = {Hediyal, TA and Vichitra, C and Anand, N and Bhaskaran, M and Essa, SM and Kumar, P and Qoronfleh, MW and Akbar, M and Kaul-Ghanekar, R and Mahalakshmi, AM and Yang, J and Song, BJ and Monaghan, TM and Sakharkar, MK and Chidambaram, SB}, title = {Protective effects of fecal microbiota transplantation against ischemic stroke and other neurological disorders: an update.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1324018}, pmid = {38449863}, issn = {1664-3224}, mesh = {Humans ; *Ischemic Stroke ; Fecal Microbiota Transplantation ; *Nervous System Diseases/therapy ; *Stroke/therapy ; *Parkinson Disease ; }, abstract = {The bidirectional communication between the gut and brain or gut-brain axis is regulated by several gut microbes and microbial derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide, and lipopolysaccharides. The Gut microbiota (GM) produce neuroactives, specifically neurotransmitters that modulates local and central neuronal brain functions. An imbalance between intestinal commensals and pathobionts leads to a disruption in the gut microbiota or dysbiosis, which affects intestinal barrier integrity and gut-immune and neuroimmune systems. Currently, fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection. FMT elicits its action by ameliorating inflammatory responses through the restoration of microbial composition and functionality. Thus, FMT may be a potential therapeutic option in suppressing neuroinflammation in post-stroke conditions and other neurological disorders involving the neuroimmune axis. Specifically, FMT protects against ischemic injury by decreasing IL-17, IFN-γ, Bax, and increasing Bcl-2 expression. Interestingly, FMT improves cognitive function by lowering amyloid-β accumulation and upregulating synaptic marker (PSD-95, synapsin-1) expression in Alzheimer's disease. In Parkinson's disease, FMT was shown to inhibit the expression of TLR4 and NF-κB. In this review article, we have summarized the potential sources and methods of administration of FMT and its impact on neuroimmune and cognitive functions. We also provide a comprehensive update on the beneficial effects of FMT in various neurological disorders by undertaking a detailed interrogation of the preclinical and clinical published literature.}, } @article {pmid38449416, year = {2024}, author = {Yuki, H and Okazaki, M and Katano, K and Sugita, A and Tokoro, T and Gabata, R and Takada, S and Nakanuma, S and Makino, I and Yagi, S}, title = {[Two Cases of Portal Vein Stent Placement for Portal Vein Stenosis Due to Recurrence of Pancreatic Cancer].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {2}, pages = {211-213}, pmid = {38449416}, issn = {0385-0684}, mesh = {Female ; Humans ; Aged ; Portal Vein/surgery ; Constriction, Pathologic/etiology/surgery ; *Pancreatic Neoplasms/complications/surgery ; Pancreas ; Melena ; *Anemia ; }, abstract = {We report 2 cases of portal vein stent placement for malignant portal stenosis due to recurrence of pancreatic cancer with symptoms of portal hypertension. Case 1: The patient was a 68-year-old female. Five years ago, a mass was found around the aorta on a computerized tomography(CT)scan taken after a residual pancreatectomy for pancreatic cancer. It was diagnosed as lymph node recurrence and S-1 therapy was started. As further tumor enlargement led to portal vein compression, venostasis around the ascending jejunum, anemia, and black stools, a portal vein stent was placed. The portal vein blood flow was improved, the collateral vessels disappeared, and the patient no longer experienced anemia or black stool. Case 2: A 75-year-old female patient underwent a subtotal gastric-sparing pancreaticoduodenectomy and combined resection of the portal vein for pancreas head cancer. On a postoperative CT scan taken 6 months later, a mass compressing the portal vein appeared, which was diagnosed as a local recurrence. As thrombocytopenia was observed, a portal vein stent was placed before starting chemotherapy. The portal vein blood flow and the platelet count improved. Portal vein stenting is an effective procedure for malignant portal stenosis, improving portal blood flow and clinical symptoms.}, } @article {pmid38447617, year = {2024}, author = {Cai, J and Zhu, Z and Li, Y and Li, Q and Tian, T and Meng, Q and Wang, T and Ma, Y and Wu, J}, title = {Artemisia capillaris thunb. Polysaccharide alleviates cholestatic liver injury through gut microbiota modulation and Nrf2 signaling pathway activation in mice.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {118009}, doi = {10.1016/j.jep.2024.118009}, pmid = {38447617}, issn = {1872-7573}, abstract = {According to traditional Chinese medicine (TCM) theory, cholestasis belongs to category of jaundice. Artemisia capillaris Thunb. has been widely used for the treatment of jaundice in TCM. The polysaccharides are the one of main active components of the herb, but its effects on cholestasis remain unclear.

AIM OF THE STUDY: To investigate the protective effect and mechanism of Artemisia capillaris Thunb. polysaccharide (APS) on cholestasis and liver injury.

MATERIALS AND METHODS: The amelioration of APS on cholestasis was evaluated in an alpha-naphthyl isothiocyanate (ANIT)-induced mice model. Then nuclear Nrf2 knockout mice, mass spectrometry, 16s rDNA sequencing, metabolomics, and molecular biotechnology methods were used to elucidate the associated mechanisms of APS against cholestatic liver injury.

RESULTS: Treatment with low and high doses of APS markedly decreased cholestatic liver injury of mice. Mechanistically, APS promoted nuclear translocation of hepatic nuclear factor erythroid 2-related factor (Nrf2), upregulated downstream bile acid (BA) efflux transporters and detoxifying enzymes expression, improved BA homeostasis, and attenuated oxidative liver injury; however, these effects were annulled in Nrf2 knock-out mice. Furthermore, APS ameliorated the microbiota dysbiosis of cholestatic mice and selectively increased short-chain fatty acid (SCFA)-producing bacteria growth. Fecal microbiota transplantation of APS also promoted hepatic Nrf2 activation, increased BA efflux transporters and detoxifying enzymes expression, ameliorated intrahepatic BA accumulation and cholestatic liver injury. Non-targeted metabolomics and in vitro microbiota culture confirmed that APS significantly increased the production of a microbiota-derived SCFA (butyric acid), which is also able to upregulate Nrf2 expression.

CONCLUSIONS: These findings indicate that APS can ameliorate cholestasis by modulating gut microbiota and activating the Nrf2 pathway, representing a novel therapeutic approach for cholestatic liver disease.}, } @article {pmid38446328, year = {2024}, author = {Olejnik, P and Buczma, K and Cudnoch-Jędrzejewska, A and Kasarełło, K}, title = {Involvement of gut microbiota in multiple sclerosis-review of a new pathophysiological hypothesis and potential treatment target.}, journal = {Immunologic research}, volume = {}, number = {}, pages = {}, pmid = {38446328}, issn = {1559-0755}, abstract = {Multiple sclerosis (MS) is a chronic inflammatory disease that leads to demyelination and damage to the central nervous system. It is well known, the significance of the involvement and influence of the immune system in the development and course of MS. Nowadays, more and more studies are demonstrating that an important factor that affects the action of the immune system is the gut microbiota. Changes in the composition and interrelationships in the gut microbiota have a significant impact on the course of MS. Dysbiosis affects the disease course mainly by influencing the immune system directly but also by modifying the secreted metabolites and increasing mucosal permeability. The essential metabolites affecting the course of MS are short-chain fatty acids, which alter pro- and anti-inflammatory responses in the immune system but also increase the permeability of the intestinal wall and the blood-brain barrier. Dietary modification alone can have a significant impact on MS. Based on these interactions, new treatments for MS are being developed, including probiotics administration, supplementation of bacterial metabolites, fecal microbiota transplantation, and dietary changes. Further studies may serve to develop new drugs and therapeutic approaches for MS.}, } @article {pmid38446309, year = {2024}, author = {El-Salhy, M and Hatlebakk, JG}, title = {Factors Underlying the Difference in Response to Fecal Microbiota Transplantation Between IBS Patients with Severe and Moderate Symptoms.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {38446309}, issn = {1573-2568}, abstract = {BACKGROUND: Previous studies showed that patients with Severe IBS respond better to fecal microbiota transplantation (FMT) than do those with Moderate IBS.

AIMS: The present study aimed to determine the effects of the transplant dose, route of administering it and repeating FMT on this difference.

METHODS: This study included 186 patients with IBS randomized 1:1:1 into groups with a 90-g transplant administered once to the colon (LI), once to the duodenum (SI), or twice to the distal duodenum twice (repeated SI). The patients provided a fecal sample and were asked to complete three questionnaires at baseline and at 3, 6, and 12 months after FMT. The fecal bacteria composition and Dysbiosis index were analyzed using 16 S rRNA gene PCR DNA amplification/probe hybridization covering regions V3-V9.

RESULTS: There was no difference in the response rates between severe IBS and moderate IBS for SI and repeated SI at all observation intervals after FMT. In the LI group, the response rate at 3 months after FMT was higher for moderate IBS than for severe IBS. The levels of Dorea spp. were higher and those of Streptococcus salivarius subsp. Thermophilus, Alistipes spp., Bacteroides and Prevotella spp., Parabacteroides johnsoni and Parabacteroides spp. were lower in moderate IBS than in severe IBS.

CONCLUSIONS: There was no difference in the response to FMT between severe and moderate IBS when a 90-g transplant was administered to the small intestine. The difference in the bacterial profile between severe and moderate IBS may explain the difference in symptoms between these patients. (www.

CLINICALTRIALS: gov : NCT04236843).}, } @article {pmid38444807, year = {2024}, author = {Ye, W and Fan, J and Wu, W and Chen, Z and Huang, Q and Qian, L}, title = {Effects of fecal microbiota transplantation on metabolic health of DBA mice.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1352555}, pmid = {38444807}, issn = {1664-302X}, abstract = {INTRODUCTION: Numerous studies have demonstrated that C57BL/6 mice exhibit superior growth rates and overall growth performance compared to DBA mice. To investigate whether this discrepancy in growth performance is linked to the composition of gut microorganisms, we conducted fecal microbiome transplantation (FMT) experiments.

METHODS: Specifically, we transplanted fecal fluids from adult C57BL/6 mice, high-fat C57BL/6 mice, and Wistar rats into weaned DBA mice (0.2mL/d), and subsequently analyzed their gut contents and gene expression through 16S rRNA sequencing and transcriptome sequencing. During the test period, C57BL/6 mice and Wistar rats were provided with a normal diet, and high-fat C57BL/6 mice were provided with a high-fat diet.

RESULTS: The results of our study revealed that mice receiving FMT from all three donor groups exhibited significantly higher daily weight gain and serum triglyceride (TG) levels compared to mice of CK group. 16S rRNA sequensing unveiled substantial differences in the abundance and function of the gut microbiota between the FMT groups and the CK group. Transcriptome analysis revealed a total of 988 differential genes, consisting of 759 up-regulated genes and 187 down-regulated genes, between the three experimental groups and the CK group. Functional Gene Ontology (GO) annotation suggested that these genes were primarily linked to lipid metabolism, coagulation, and immunity. Pearson correlation analysis was performed on the differential genes and clusters, and it revealed significant correlations, mainly related to processes such as fatty acid metabolism, fat digestion and absorption, and cholesterol metabolism.

DISCUSSION: In summary, FMT from dominant strains improved the growth performance of DBA mice, including body weight gain, institutional growth, and immune performance. This change may be due to the increase of probiotic content in the intestinal tract by FMT and subsequent alteration of intestinal gene expression. However, the effects of cross-species fecal transplantation on the intestinal flora and gene expression of recipient mice were not significant.}, } @article {pmid38441196, year = {2024}, author = {Oldereid, TS and Jiang, X and Nordhus, KS and Ponzetta, A and Bjørnholt, JV and Björkström, NK and Melum, E and Rasmussen, H}, title = {Role of bacteria and microbial metabolites in immune modulation during early life.}, journal = {Scandinavian journal of immunology}, volume = {99}, number = {2}, pages = {e13336}, doi = {10.1111/sji.13336}, pmid = {38441196}, issn = {1365-3083}, support = {//Helse Sør-Øst RHF/ ; //Norwegian PSC Research Center/ ; //Research Support Services, Oslo University Hospital/ ; }, mesh = {Animals ; Mice ; *Sodium Chloride ; Administration, Oral ; *B-Lymphocytes ; Bacteria ; Feces ; }, abstract = {Host-microbiome interplay from birth is essential for immune imprinting and tuning. Live gut microbes and microbial-derived metabolites regulate the development and modulation of the immune system, but whether microbial metabolites solely are sufficient to induce immune maturation remains unclear. Sterile faecal filtrates (FFT) were generated from murine gut contents. Newborn germ-free (GF) mice were treated twice daily with FFT (GF-FFT) or saline (GF-NaCl) from post-natal day 5 until 4 weeks of age. A third group of GF neonates were conventionalized by the transfer of caecal microbiota with live gut microbes. Host immune compartments were comprehensively immunophenotyped and systemically analysed in all available immune-related organs using flow cytometry. Oral FFT was associated with reduced survival among neonates (n = 7/19; 36.8% mortality), while saline treatment was well tolerated (n = 1/17, 5.9% mortality). Four-week-old FFT-treated pups were comparable in body weight to GF-NaCl, and the major B-cell, conventional T-cell and unconventional T-cell subsets were unchanged from saline-treated mice. Live bacteria administered during early life induced clear changes in proportions of B cells, T cells and T-cell subsets in all mucosal tissues and secondary lymphoid organs compared to GF-FFT, including restoration of intestinal natural killer T (NKT) cells with characteristics similar to conventional pups. Our findings show that oral administration of a FFT made of microbial metabolites, antigens and bacteriophages alone is insufficient to induce normal immune development elicited by the presence of live bacteria. Reduced survival during neonatal FFT treatment suggests a potential bioactive attribute of sterile faecal filtrates.}, } @article {pmid38439546, year = {2024}, author = {Madhav, A and Bousfield, R and Pereira-Dias, J and Cormie, C and Forrest, S and Keane, J and Kermack, L and Higginson, E and Dougan, G and Spiers, H and Massey, D and Sharkey, L and Rutter, C and Woodward, J and Russell, N and Amin, I and Butler, A and Atkinson, K and Dymond, T and Bartholdson Scott, J and Baker, S and Gkrania-Klotsas, E}, title = {A metagenomic prospective cohort study on gut microbiome composition and clinical infection in small bowel transplantation.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2323232}, doi = {10.1080/19490976.2024.2323232}, pmid = {38439546}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Metagenome ; Prospective Studies ; *Sepsis ; *Microbiota ; }, abstract = {Two-thirds of small-bowel transplantation (SBT) recipients develop bacteremia, with the majority of infections occurring within 3 months post-transplant. Sepsis-related mortality occurs in 31% of patients and is commonly caused by bacteria of gut origin, which are thought to translocate across the implanted organ. Serial post-transplant surveillance endoscopies provide an opportunity to study whether the composition of the ileal and colonic microbiota can predict the emergence as well as the pathogen of subsequent clinical infections in the SBT patient population. Five participants serially underwent aspiration of ileal and colonic bowel effluents at transplantation and during follow-up endoscopy either until death or for up to 3 months post-SBT. We performed whole-metagenome sequencing (WMS) of 40 bowel effluent samples and compared the results with clinical infection episodes. Microbiome composition was concordant between participants and timepoint-matched ileal and colonic samples. Four out of five (4/5) participants had clinically significant infections thought to be of gut origin. Bacterial translocation from the gut was observed in 3/5 patients with bacterial infectious etiologies. In all three cases, the pathogens had demonstrably colonized the gut between 1-10 days prior to invasive clinical infection. Recipients with better outcomes received donor grafts with higher alpha diversity. There was an increase in the number of antimicrobial resistance genes associated with longer hospital stay for all participants. This metagenomic study provides preliminary evidence to support the pathogen translocation hypothesis of gut-origin sepsis in the SBT cohort. Ileal and colonic microbiome compositions were concordant; therefore, fecal metagenomic analysis could be a useful surveillance tool for impeding infection with specific gut-residing pathogens.}, } @article {pmid38436067, year = {2024}, author = {Zhang, L and Liu, Z and Zhang, W and Wang, J and Kang, H and Jing, J and Han, L and Gao, A}, title = {Gut microbiota-palmitoleic acid-interleukin-5 axis orchestrates benzene-induced hematopoietic toxicity.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2323227}, pmid = {38436067}, issn = {1949-0984}, mesh = {Animals ; Mice ; Mice, Inbred C57BL ; *Interleukin-5 ; Benzene/toxicity ; *Gastrointestinal Microbiome ; Fatty Acids ; Inflammation ; *Fatty Acids, Monounsaturated ; }, abstract = {Due to the annual increase in its production and consumption in occupational environments, the adverse blood outcomes caused by benzene are of concern. However, the mechanism of benzene-induced hematopoietic damage remains elusive. Here, we report that benzene exposure causes hematopoietic damage in a dose-dependent manner and is associated with disturbances in gut microbiota-long chain fatty acids (LCFAs)-inflammation axis. C57BL/6J mice exposed to benzene for 45 days were found to have a significant reduction in whole blood cells and the suppression of hematopoiesis, an increase in Bacteroides acidifaciens and a decrease in Lactobacillus murinus. Recipient mice transplanted with fecal microbiota from benzene-exposed mice showed potential for hematopoietic disruption, LCFAs, and interleukin-5 (IL-5) elevation. Abnormally elevated plasma LCFAs, especially palmitoleic acid (POA) exacerbated benzene-induced immune-inflammation and hematopoietic damage via carnitine palmitoyltransferase 2 (CPT2)-mediated disorder of fatty acid oxidation. Notably, oral administration of probiotics protects the mice against benzene-induced hematopoietic toxicity. In summary, our data reveal that the gut microbiota-POA-IL-5 axis is engaged in benzene-induced hematopoietic damage. Probiotics might be a promising candidate to prevent hematopoietic abnormalities from benzene exposure.}, } @article {pmid38435309, year = {2024}, author = {Tang, F and Deng, M and Xu, C and Yang, R and Ji, X and Hao, M and Wang, Y and Tian, M and Geng, Y and Miao, J}, title = {Unraveling the microbial puzzle: exploring the intricate role of gut microbiota in endometriosis pathogenesis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1328419}, pmid = {38435309}, issn = {2235-2988}, mesh = {Female ; Humans ; *Gastrointestinal Microbiome ; *Endometriosis/etiology ; *Microbiota ; Estrogens ; Inflammation ; }, abstract = {Endometriosis (EMs) is a prevalent gynecological disorder characterized by the growth of uterine tissue outside the uterine cavity, causing debilitating symptoms and infertility. Despite its prevalence, the exact mechanisms behind EMs development remain incompletely understood. This article presents a comprehensive overview of the relationship between gut microbiota imbalance and EMs pathogenesis. Recent research indicates that gut microbiota plays a pivotal role in various aspects of EMs, including immune regulation, generation of inflammatory factors, angiopoietin release, hormonal regulation, and endotoxin production. Dysbiosis of gut microbiota can disrupt immune responses, leading to inflammation and impaired immune clearance of endometrial fragments, resulting in the development of endometriotic lesions. The dysregulated microbiota can contribute to the release of lipopolysaccharide (LPS), triggering chronic inflammation and promoting ectopic endometrial adhesion, invasion, and angiogenesis. Furthermore, gut microbiota involvement in estrogen metabolism affects estrogen levels, which are directly related to EMs development. The review also highlights the potential of gut microbiota as a diagnostic tool and therapeutic target for EMs. Interventions such as fecal microbiota transplantation (FMT) and the use of gut microbiota preparations have demonstrated promising effects in reducing EMs symptoms. Despite the progress made, further research is needed to unravel the intricate interactions between gut microbiota and EMs, paving the way for more effective prevention and treatment strategies for this challenging condition.}, } @article {pmid38216845, year = {2024}, author = {Cintron, M and Jani, K and Madhavappallil, J and Kamboj, M and Babady, NE}, title = {Prevalence of astrovirus and sapovirus among adult oncology patients with acute gastroenteritis using a multiplexed gastrointestinal pathogen PCR panel.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {43}, number = {3}, pages = {525-531}, pmid = {38216845}, issn = {1435-4373}, mesh = {Adult ; Humans ; Infant ; *Sapovirus/genetics ; Prevalence ; Retrospective Studies ; *Norovirus/genetics ; *Gastroenteritis/diagnosis ; Diarrhea/epidemiology ; *Neoplasms/complications ; Feces ; Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Multiplex syndromic gastrointestinal panels (GIPCR) have streamlined the diagnosis of infectious diarrhea. Additionally, they have expanded the number of pathogens that can be routinely evaluated, allowing further understanding of the prevalence of enteric pathogens in various patient populations. The goal of this study was to investigate the prevalence and clinical presentation of astrovirus and sapovirus gastroenteritis in adult oncology patients as detected by the FilmArray GIPCR.

METHODS: All GIPCR panel results from December 2017 to June 2021 were retrospectively reviewed to determine the prevalence of astrovirus and sapovirus in adult oncology patients. Medical records were also reviewed to obtain clinical information. Repeat GIPCR positivity and symptom duration were used to estimate prolonged viral shedding.

RESULTS: A total of 18,014 panels were performed on samples collected from 9303 adults. Overall, astrovirus and sapovirus were detected in 0.35% (33/9303) and 0.45% (42/9303) GIPCRs respectively. At least one viral target was detected in 424 (4.4%) patients. Astrovirus accounted for 7.8% (33/424) and sapovirus 9.9% (42/424) of patients. Diarrhea was the most common symptom documented. A subset of transplant patients had protracted viral detection with a median of ~27 days (range 23-43 days) for astrovirus and 97 days (range 11-495) for sapovirus. No clusters or outbreaks were identified during the study period.

CONCLUSION: In oncology patients with viral gastroenteritis, astrovirus and sapovirus were the causative agents in 18% of the cases. Both viruses were associated with mild disease. Prolonged diarrhea and viral shedding were observed in a few transplant patients.}, } @article {pmid38431789, year = {2024}, author = {Hendrickx, T and Peetermans, M and D'Hoore, A and Claes, K and Van Hootegem, A and Sabino, J}, title = {STEC colitis mimicking acute severe colitis with life-threatening consequences: a case report.}, journal = {Acta gastro-enterologica Belgica}, volume = {87}, number = {1}, pages = {37-39}, doi = {10.51821/87.1.11652}, pmid = {38431789}, issn = {1784-3227}, mesh = {Humans ; *Shiga-Toxigenic Escherichia coli ; *Escherichia coli Infections/complications/diagnosis ; *Colitis, Ulcerative/complications/diagnosis ; *Hemolytic-Uremic Syndrome/diagnosis/complications ; *Colitis/diagnosis ; }, abstract = {Acute colitis is a common feature of infection with Shiga-toxin producing Escherichia coli (STEC) and can mimic acute severe ulcerative colitis. Early recognition is important as there is a risk of developing Shiga toxin-induced haemolytic uremic syndrome (STEC-HUS), defined by the triad of microangiopathic haemolytic anemia, thrombocytopenia and organ damage. In severe cases STEC-HUS can cause severe neurological complications and can be fatal. We present a patient with a medical history of refractory ulcerative colitis, where making the diagnosis of STEC-HUS was challenging since the initial clinical presentation was difficult to differentiate from a flare of ulcerative colitis. This case illustrates that STEC induced colitis can mimic acute severe ulcerative colitis. This finding is of utmost clinical importance because of the potential life-threatening complications of STEC-HUS. Therefore it should be excluded promptly in patients with acute severe ulcerative colitis by using multiplex-PCR assay on a faecal sample.}, } @article {pmid38430889, year = {2024}, author = {Wang, W and Fan, J and Zhang, C and Huang, Y and Chen, Y and Fu, S and Wu, J}, title = {Targeted modulation of gut and intra-tumor microbiota to improve the quality of immune checkpoint inhibitor responses.}, journal = {Microbiological research}, volume = {282}, number = {}, pages = {127668}, doi = {10.1016/j.micres.2024.127668}, pmid = {38430889}, issn = {1618-0623}, abstract = {Immune checkpoint inhibitor (ICI) therapies, such as those blocking the interaction of PD-1 with its ligands, can restore the immune-killing function of T cells. However, ICI therapy is clinically beneficial in only a small number of patients, and it is difficult to predict post-treatment outcomes, thereby limiting its widespread clinical use. Research suggests that gut microbiota can regulate the host immune system and affect cancer progression and treatment. Moreover, the effectiveness of immunotherapy is related to the composition of the patient's gut microbiota; different gut microbial strains can either activate or inhibit the immune response. However, the importance of the microbial composition within the tumor has not been explored until recently. This study describes recent advances in the crosstalk between microbes in tumors and gut microbiota, which can modulate the tumor microbiome by directly translocating into the tumor and altering the tumor microenvironment. This study focused on the potential manipulation of the tumor and gut microbiota using fecal microbiota transplantation (FMT), probiotics, antimicrobials, prebiotics, and postbiotics to enrich immune-boosting bacteria while decreasing unfavorable bacteria to proactively improve the efficacy of ICI treatments. In addition, the use of genetic technologies and nanomaterials to modify microorganisms can largely optimize tumor immunotherapy and advance personalized and precise cancer treatment.}, } @article {pmid38428658, year = {2024}, author = {Hu, Y and Tang, J and Xie, Y and Xu, W and Zhu, W and Xia, L and Fang, J and Yu, D and Liu, J and Zheng, Z and Zhou, Q and Shou, Q and Zhang, W}, title = {Gegen Qinlian decoction ameliorates TNBS-induced ulcerative colitis by regulating Th2/Th1 and Tregs/Th17 cells balance, inhibiting NLRP3 inflammasome activation and reshaping gut microbiota.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {117956}, doi = {10.1016/j.jep.2024.117956}, pmid = {38428658}, issn = {1872-7573}, abstract = {Chinese herbal medicine Gegen Qinlian Decoction (GQD) has been clinically shown to be an effective treatment of ulcerative colitis (UC) in China. However, the underlying mechanism of GQD's anti-ulcerative colitis properties and its effect on gut microbiota still deserve further exploration.

AIM OF THE STUDY: This study observed the regulatory effects of GQD on Th2/Th1 and Tregs/Th17 cells balance, the NOD-like receptor family pyrin domain containing 3 (NLRP3) infammasome and gut microbiota in TNBS-induced UC in BALB/c mice.

MATERIALS AND METHODS: 61 main chemical compounds in the GQD were determined by UPLC-Q-TOF/MS. The UC BALB/c model was established by intrarectal administration of trinitrobenzene sulfonic acid (TNBS), and GQD was orally administered at low and high dosages of 2.93 and 11.71 g/kg/day, respectively. The anti-inflammatory effects of GQD for ulcerative colitis were evaluated by survival rate, body weight, disease activity index (DAI) score, colonic weight and index, spleen index, hematoxylin-eosin (HE) staining and histopathological scores. Flow cytometry was used to detect the percentage of CD4, Th1, Th2, Th17 and Tregs cells. The levels of Th1-/Th2-/Th17-/Tregs-related inflammatory cytokines and additional proinflammatory cytokines (IL-1β, IL-18) were detected by CBA, ELISA, and RT-PCR. The expressions of GATA3, T-bet, NLRP3, Caspase-1, IL-Iβ, Occludin and Zonula occludens-1 (ZO-1) on colon tissues were detected by Western blot and RT-PCR. Transcriptome sequencing was performed using colon tissue and 16S rRNA gene sequencing was performed on intestinal contents. Fecal microbiota transplantation (FMT) was employed to assess the contribution of intestinal microbiota and its correlation with CD4 T cells and the NLRP3 inflammasome.

RESULTS: GQD increased the survival rate of TNBS-induced UC in BALB/c mice, and significantly improved their body weight, DAI score, colonic weight and index, spleen index, and histological characteristics. The intestinal barrier dysfunction was repaired after GQD administration through promoting the expression of tight junction proteins (Occludin and ZO-1). GQD restored the balance of Th2/Th1 and Tregs/Th17 cells immune response of colitis mice, primarily inhibiting the increase in Th2/Th1 ratio and their transcription factor production (GATA3 and T-bet). Morever, GQD changed the secretion of Th1-/Th2-/Th17-/Tregs-related cytokines (IL-2, IL-12, IL-5, IL-13, IL-6, IL-10, and IL-17A) and reduced the expressions of IL-1β, IL-18. Transcriptome results suggested that GQD could also remodel the immune inflammatory response of colitis by inhibiting NOD-like receptor signaling pathway, and Western blot, immunohistochemistry and RT-PCR further revealed that GQD exerted anti-inflammatory effects by inhibiting the NLRP3 inflammasome, such as down-regulating the expression of NLRP3, Caspase-1 and IL-1β. More interestingly, GQD regulated gut microbiota dysbiosis, suppressed the overgrowth of conditional pathogenic gut bacteria like Helicobacter, Proteobacteria, and Mucispirillum, while the probiotic gut microbiota, such as Lactobacillus, Muribaculaceae, Ruminiclostridium_6, Akkermansia, and Ruminococcaceae_unclassified were increased. We further confirmed that GQD-treated gut microbiota was sufficient to relieve TNBS-induced colitis by FMT, involving the modulation of Th2/Th1 and Tregs/Th17 balance, inhibition of NLRP3 inflammasome activation, and enhancement of colonic barrier function.

CONCLUSIONS: GQD might alleviate TNBS-induced UC via regulating Th2/Th1 and Tregs/Th17; cells Balance, inhibiting NLRP3 inflammasome and reshaping gut microbiota, which may provide a novel strategy for patients with colitis.}, } @article {pmid38428648, year = {2024}, author = {Ma, X and Kim, JK and Shin, YJ and Park, HS and Lee, DY and Yim, SV and Kim, DH}, title = {Lipopolysaccharide-producing Veillonella infantium and Escherichia fergusonii cause vagus nerve-mediated cognitive impairment in mice.}, journal = {Brain, behavior, and immunity}, volume = {118}, number = {}, pages = {136-148}, doi = {10.1016/j.bbi.2024.02.031}, pmid = {38428648}, issn = {1090-2139}, abstract = {Gut microbiota communicates bidirectionally with the brain through the nervous, immune, and endocrine systems of the gut. In our preliminary study, the fecal microbiota of volunteers with mild cognitive impairment (Fmci) exhibited a higher abundance of Escherichia fergusonii (NK2001), Veillonella infantium (NK2002), and Enterococcus faecium (NK2003) populations compared with those of healthy volunteers. Therefore, we examined the effects of Fmci, NK2001 (gram-negative), NK2002 (gram-negative-like), and NK2003 (gram-positive) on cognitive impairment-like behavior, neuroinflammation, and colitis in mice with or without antibiotics. Fmci transplantation increased cognitive impairment-like behavior, hippocampal tumor necrosis factor (TNF)-α expression, and the size of toll-like receptor (TLR)4[+]Iba1[+], TLR2[+]Iba1[+], and NF-κB[+]Iba1[+] cell populations independent of antibiotic treatment. Oral gavage of NK2001, NK2002, or NK2003, which induced TNF-α expression in Caco-2 cells, significantly increased cognitive impairment-like behavior and hippocampal TNF-α expression and Iba1-positive cell populations and decreased brain-derived neurotrophic factor (BDNF) expression in mice. Celiac vagotomy significantly decreased NK2001- or NK2002-induced cognitive impairment-like behavior and hippocampal Iba1[+] cell population and TNF-α expression and increased NK2001- or NK2002-suppressed hippocampal BDNF expression. However, NK2003-induced cognitive impairment-like behavior and hippocampal Iba1[+] cell population and TNF-α expression were partially, but not significantly, attenuated by celiac vagotomy. Furthermore, celiac vagotomy did not affect NK2001-, NK2002-, or NK2003-induced lipopolysaccharide (LPS) levels in the blood and feces and TNF-α expression and NF-κB-positive cell population in the colon. In conclusion, LPS-producing NK2001 and NK2002 and LPS-nonproducing NK2003 may induce NF-κB-mediated neuroinflammation through the translocation of byproducts such as LPS and peptidoglycan into the brain through gut-blood/vagus nerve-brain and gut-blood-brain pathways, respectively, resulting in cognitive impairment.}, } @article {pmid38428570, year = {2024}, author = {Ran, X and Hu, G and Guo, W and Li, K and Wang, X and Liu, J and Fu, S}, title = {Hesperetin regulates the intestinal flora and inhibits the TLR4/NF-κB signaling axis to protect the blood-milk barrier and prevent mastitis.}, journal = {Life sciences}, volume = {342}, number = {}, pages = {122533}, doi = {10.1016/j.lfs.2024.122533}, pmid = {38428570}, issn = {1879-0631}, abstract = {The World Health Organization recommends breastfeeding for 6 months, but mastitis, a common disease during lactation, presents a major obstacle to fulfilling this recommendation. Maternal nutrient intake during lactation has been shown to be related to mastitis. Therefore, this study aimed to explore the effect of hesperetin, a phytonutrient, on mastitis. The oral administration of hesperetin to lipopolysaccharide (LPS)-induced mastitis mice alleviated their pathological damage, reduced the secretion of pro-inflammatory cytokines, and maintained the integrity of their blood-milk barrier. Moreover, our results showed that oral administration of hesperetin regulates the composition of the intestinal flora of mice. Fecal microbial transplantation (FMT) from the mice of hesperetin group alleviated LPS-induced mastitis in recipient mice. In additional, hesperetin attenuated the inflammatory response and increased the expression of tight junction proteins (TJs) in LPS-stimulated mouse mammary epithelial cells (mMECs). Through network pharmacological analysis and further research, we demonstrated hesperetin inhibits the expression of TLR4 and the activation of NF-κB signaling. In conclusion, hesperetin protects the blood-milk barrier and improve mastitis by regulating intestinal flora and inhibiting the activation of TLR4/NF-κB signaling axis. This study provides a theoretical basis for lactating females to consume hesperetin as a supplement to prevent mastitis and maintain mammary health.}, } @article {pmid38427251, year = {2024}, author = {Niccolai, E and Martinelli, I and Quaranta, G and Nannini, G and Zucchi, E and De Maio, F and Gianferrari, G and Bibbò, S and Cammarota, G and Mandrioli, J and Masucci, L and Amedei, A}, title = {Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis: Clinical Protocol and Evaluation of Microbiota Immunity Axis.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2761}, number = {}, pages = {373-396}, pmid = {38427251}, issn = {1940-6029}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Amyotrophic Lateral Sclerosis/therapy ; *Microbiota ; *Gastrointestinal Microbiome/physiology ; Clinical Protocols ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; }, abstract = {The fecal microbial transplantation (FMT) is a therapeutic transplant of fecal microbiota from healthy donors to patients. This practice is aimed at restoring eubiosis and rebalancing the enteric and systemic immune responses, and then eliminating pathogenic triggers of multiple disease, including neurodegenerative diseases. Alterations of gut microbiota (GM) affect the central nervous system (CNS) health, impacting neuro-immune interactions, synaptic plasticity, myelination, and skeletal muscle function. T-regulatory lymphocytes (Treg) are among the most important players in the pathogenesis of amyotrophic lateral sclerosis (ALS), altering the disease course. Along with circulating neuropeptides, other immune cells, and the gut-brain axis, the GM influences immunological tolerance and controls Treg's number and suppressive functions. A double-blind, controlled, multicenter study on FMT in ALS patients has been designed to evaluate if FMT can modulate neuroinflammation, by restoring Treg number, thus modifying disease activity and progression.}, } @article {pmid38423412, year = {2024}, author = {Luo, Y and Fu, S and Liu, Y and Kong, S and Liao, Q and Lin, L and Li, H}, title = {Banxia Xiexin decoction modulates gut microbiota and gut microbiota metabolism to alleviate DSS-induced ulcerative colitis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {117990}, doi = {10.1016/j.jep.2024.117990}, pmid = {38423412}, issn = {1872-7573}, abstract = {Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine prescription for treating ulcerative colitis (UC). However, its potential mechanism of action is still unclear.

AIM OF THE STUDY: Reveal the correlation between the beneficial impacts of BXD on UC and the composition of the gut microbiota.

MATERIALS AND METHODS: The major constituents of BXD were identified using the HPLC-DAD technique. An experimental model of UC was induced in male C57BL/6 mice by administering dextran sodium sulfate (DSS). A total of 48 mice were divided into different groups, including control, model, high-dose BXD treatment, medium-dose BXD treatment, low-dose BXD treatment, and a group treated with 5-amino acid salicylic acid (5-ASA). Body weight changes and disease activity index (DAI) scores were documented; colon length, colon index, spleen index, and thymus index scores were determined; myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) activities were assessed; and histological staining with hematoxylin-eosin and alcian blue/phosphate Schiff was performed. The immunofluorescence technique was employed to examine the presence of ZO-1 and occludin in the colon tissue. 16S rRNA sequencing was employed to assess the gut microbiota's diversity and metabolomics was utilized to examine alterations in metabolites within the gut microbiota. The impact of BXD on the gut microbiota was confirmed through fecal microbiota transplantation (FMT).

RESULTS: BXD exhibited a positive impact on UC mice, particularly in the high-dose BXD treatment group. The BXD group experienced weight recovery, decreased DAI scores, improved colon length, and restored of spleen and thymus index scores compared to the DSS group. Additionally, BXD alleviated colon damage and the inflammatory response while restoring intestinal barrier function. FMT in BXD-treated mice also showed therapeutic effects in UC mice. At the phylum level, the relative abundance of Desulfobacterota, Deferribacterota and Actinobacteriota increased; at the genus level, g__norank__f__Muribaculaceae, Dubosiella, Akkermansia, and Lactobacillus increased, whereas Faecalibaculum, Alloprevotella, Turicibacter, and g_Paraprevotella decreased. g__norank_f__Muribaculaceae was positively correlated with body weight and colon length and negatively with colon index scores, splenic index scores, and MPO levels; Alloprevotella was positively correlated with splenic index scores, histological scores, and TNF-α levels and negatively with thymus index scores and thymus index scores. Faecalibaculum was positively correlated with colon index scores and MPO levels. Metabolic investigations revealed 58 potential indicators, primarily associated with the metabolism of amino acids, purines, and lipids. Alloprevotella, g_Paraprevotella, and Bifidobacterium were strongly associated with metabolic pathways.

CONCLUSION: BXD showed beneficial therapeutic effects in UC mice. The mechanism may be by promoting the balance and variety of gut microbiota, as well as regulating the metabolism of amino acids, purines, and lipids.}, } @article {pmid38419010, year = {2024}, author = {Nooij, S and Vendrik, KEW and Zwittink, RD and Ducarmon, QR and Keller, JJ and Kuijper, EJ and Terveer, EM and , }, title = {Long-term beneficial effect of faecal microbiota transplantation on colonisation of multidrug-resistant bacteria and resistome abundance in patients with recurrent Clostridioides difficile infection.}, journal = {Genome medicine}, volume = {16}, number = {1}, pages = {37}, pmid = {38419010}, issn = {1756-994X}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Clostridioides difficile/genetics ; Feces/microbiology ; *Microbiota ; *Clostridium Infections/therapy/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases.

METHODS: We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1-3 years), combining culture methods and faecal metagenomics.

RESULTS: Based on MDR culture (n = 87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 3 weeks after FMT). Metagenomic sequencing of patient stool samples (n = 63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n = 11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n = 22 patients), the recipients' resistomes are still donor-like, suggesting the effect of FMT may last for years.

CONCLUSIONS: Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes.}, } @article {pmid38417315, year = {2024}, author = {Chen, X and Zhu, D and Ge, R and Bao, Z}, title = {Fecal transplantation of young mouse donors effectively improves enterotoxicity in elderly recipients exposed to triphenyltin.}, journal = {Ecotoxicology and environmental safety}, volume = {273}, number = {}, pages = {116140}, doi = {10.1016/j.ecoenv.2024.116140}, pmid = {38417315}, issn = {1090-2414}, abstract = {Triphenyltin (TPT) is a widely used biocide known for its high toxicity to various organisms, including humans, and its potential contribution to environmental pollution. The aging process leads to progressive deterioration of physiological functions in the elderly, making them more susceptible to the toxic effects of environmental pollutants. This study aimed to investigate the mitigating effect of fecal transplantation in young mice on the toxicological impairment caused by TPT exposure. For the study, 18-month-old mice were divided into four groups with six replicates each. The control group was fed a basal diet, the TPT group was exposed to 3.75 mg/Kg TPT, the feces group received fecal transplantation from 8-week-old young mice, and the combined group was exposed to 3.75 mg/Kg TPT after receiving fecal transplantation. Compared with the elderly control group, TPT induced significant upregulation of mRNA expression of pro-inflammatory factors (IL-1β, IL-6, TNF-α), while the anti-inflammatory factor gene IL-10 was significantly suppressed. The mRNA expression of intestinal barrier proteins (Claudin, Occludin, Muc2) was also significantly downregulated. However, fecal transplantation in young mice alleviated TPT-induced changes in inflammatory factors, ameliorated oxidative stress, and increased the activities of antioxidant enzymes (including SOD, CAT, GSH-Px). Further analysis using 16 s RNA showed that exposure to TPT led to changes in the composition of the intestinal flora. Untargeted metabolomics observations of feces from older mice revealed that exposure to TPT resulted in altered fecal metabolites. Fecal transplantation in young mice altered the microbiota of TPT-exposed older mice, especially by enhancing the levels of core probiotics. Similar beneficial effects were observed through untargeted metabolomics. Overall, this study highlights the potential benefits of young fecal transplantation in protecting the elderly from the toxicity of TPT, offering a promising approach to improve healthy aging.}, } @article {pmid38417203, year = {2024}, author = {Zhu, X and Zhao, L and Lei, L and Zhu, Y and Xu, J and Liu, L}, title = {Fecal microbiota transplantation ameliorates abdominal obesity through inhibiting microbiota-mediated intestinal barrier damage and inflammation in mice.}, journal = {Microbiological research}, volume = {282}, number = {}, pages = {127654}, doi = {10.1016/j.micres.2024.127654}, pmid = {38417203}, issn = {1618-0623}, abstract = {Abdominal obesity (AO), characterized by the excessive abdominal fat accumulation, has emerged as a significant public health concern due to its metabolic complications and escalating prevalence worldwide, posing a more pronounced threat to human health than general obesity. While certain studies have indicated that intestinal flora contributed to diet-induced general obesity, the precise involvement of gut microbiota in the development of AO, specifically the accumulation of abdominal fat, remains inadequately explored. In this study, the 16 S rDNA sequencing was employed to analyze gut flora alterations, and the intestinal microbiota dysbiosis characterized by a vanishing decline of Akkermansia was found in the AO group. Along with notable gut microbiota changes, the intestinal mucosal barrier damage and metabolic inflammation were detected, which collectively promoted metabolic dysregulation in AO. Furthermore, the metabolic inflammation and AO were ameliorated after the intestinal microbiota depletion with antibiotics (ABX) drinking, underscoring a significant involvement of gut microbiota dysbiosis in the progression of AO. More importantly, our findings demonstrated that the transplantation of healthy intestinal flora successfully reversed the gut microbiota dysbiosis, particularly the decline of Akkermansia in the AO group. The gut flora reshaping has led to the repair of gut barrier damage and mitigation of metabolic inflammation, which ultimately ameliorated abdominal fat deposition. Our study established the role of interactions between gut flora, mucus barrier, and metabolic inflammation in the development of AO, thereby offering a theoretical foundation for the clinical application of fecal microbiota transplantation (FMT) as a treatment for AO.}, } @article {pmid38414441, year = {2024}, author = {Wang, N and Huo, Y and Gao, X and Li, Y and Cheng, F and Zhang, Z}, title = {Lead exposure exacerbates liver injury in high-fat diet-fed mice by disrupting the gut microbiota and related metabolites.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo05148j}, pmid = {38414441}, issn = {2042-650X}, abstract = {Lead (Pb) is a widespread toxic endocrine disruptor that could cause liver damage and gut microbiota dysbiosis. However, the causal relationship and underlying mechanisms between the gut microbiota and Pb-induced liver injury are unclear. In this study, we investigated the metabolic toxicity caused by Pb exposure in normal chow (Chow) and high-fat diet (HFD) mice and confirmed the causal relationship by fecal microbial transplantation (FMT) and antibiotic cocktail experiments. The results showed that Pb exposure exacerbated HFD-induced hepatic lipid deposition, fibrosis, and inflammation, but it had no significant effect on Chow mice. Pb increased serum lipopolysaccharide (LPS) levels and induced intestinal inflammation and barrier damage by activating TLR4/NFκB/MLCK in HFD mice. Furthermore, Pb exposure disrupted the gut microbiota, reduced short-chain fatty acid (SCFA) concentrations and the colonic SCFA receptors, G protein-coupled receptor (GPR) 41/43/109A, in HFD mice. Additionally, Pb significantly inhibited the hepatic GPR109A-mediated adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway, resulting in hepatic lipid accumulation. FMT from Pb-exposed HFD mice exacerbated liver damage, disturbed lipid metabolic pathways, impaired intestinal barriers, and altered the gut microbiota and metabolites in recipient mice. However, mice exposed to HFD + Pb and HFD mice had similar levels of these biomarkers in microbiota depleted by antibiotics. In conclusion, our study provides new insights into gut microbiota dysbiosis as a potential novel mechanism for human health related to liver function impairment caused by Pb exposure.}, } @article {pmid38414430, year = {2024}, author = {Moinul, D and Hao, C and Dimitropoulos, G and Taylor, VH}, title = {Patient Perceptions of Microbiome-Based Therapies as Novel Treatments for Mood Disorders: A Mixed Methods Study.}, journal = {Canadian journal of psychiatry. Revue canadienne de psychiatrie}, volume = {}, number = {}, pages = {7067437241234954}, doi = {10.1177/07067437241234954}, pmid = {38414430}, issn = {1497-0015}, abstract = {OBJECTIVE: Medications are critical for treating major depressive disorder (MDD) and bipolar disorder (BD). Unfortunately, 30% to 40% of individuals do not respond well to current pharmacotherapy. Given the compelling growing body of research on the gut-brain axis, this study aims to assess patient perspectives regarding microbiome-based therapies (MBT) such as probiotics, prebiotics, dietary changes, or fecal microbiota transplantation (FMT) in the management of MDD and BD.

METHODS: This single-centred observational study used quantitative and qualitative assessments to examine patient perceptions of MBT. Participants diagnosed with MDD or BD completed an anonymous questionnaire obtaining demographics, prior medication history, and symptom burden. Self-assessment questionnaires specific to each diagnosis were also used: Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), Altman Self-Rating Mania Scale (ASRM), and General Anxiety Disorder Questionnaire (GAD-7). A logistic regression model analysed the association of MBT acceptance with disorder type, QIDS-SR, and GAD-7 scores. A bootstrap method assessed the proportion of MBT acceptance. The qualitative assessment consisted of 30-minute interviews to elicit perceptions and attitudes towards MBT.

RESULTS: The qualitative assessment achieved information power with n = 20. Results from the 63-item MBT questionnaire (n = 43) showed probiotics (37.2%) as the top choice, followed by FMT (32.6%), dietary change (25.6%), and prebiotics (4.6%). A majority of participants (72.1%) expressed willingness to try MBT for their mood disorder, however, logistic regression analysis did not identify statistically significant predictors for MBT acceptance among disorder type, QIDS-SR, and GAD-7.

CONCLUSION: There is an increased focus on the gut microbiota's role in mood disorders' etiology and treatment. Promising research and patient interest underscore the necessity for exploring and educating on patient perspectives and the factors influencing attitudes towards MBT.}, } @article {pmid38414054, year = {2024}, author = {Ma, YY and Li, X and Yu, JT and Wang, YJ}, title = {Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside.}, journal = {Translational neurodegeneration}, volume = {13}, number = {1}, pages = {12}, pmid = {38414054}, issn = {2047-9158}, support = {92249305//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Amyotrophic Lateral Sclerosis ; *Alzheimer Disease ; *Parkinson Disease/therapy ; }, abstract = {The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), are complex and multifaceted. A growing body of evidence suggests that the gut microbiome plays crucial roles in the development and progression of neurodegenerative diseases. Clinicians have come to realize that therapeutics targeting the gut microbiome have the potential to halt the progression of neurodegenerative diseases. This narrative review examines the alterations in the gut microbiome in AD, PD, ALS and HD, highlighting the close relationship between the gut microbiome and the brain in neurodegenerative diseases. Processes that mediate the gut microbiome-brain communication in neurodegenerative diseases, including the immunological, vagus nerve and circulatory pathways, are evaluated. Furthermore, we summarize potential therapeutics for neurodegenerative diseases that modify the gut microbiome and its metabolites, including diets, probiotics and prebiotics, microbial metabolites, antibacterials and faecal microbiome transplantation. Finally, current challenges and future directions are discussed.}, } @article {pmid38413211, year = {2024}, author = {Yau, YK and Su, Q and Xu, Z and Tang, W and Ching, JYL and Cheung, CP and Fung, M and Ip, M and Chan, PKS and Chan, FKL and Ng, SC}, title = {Faecal microbiota transplantation for patients with irritable bowel syndrome: abridged secondary publication.}, journal = {Hong Kong medical journal = Xianggang yi xue za zhi}, volume = {30 Suppl 1}, number = {1}, pages = {34-38}, pmid = {38413211}, issn = {1024-2708}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Irritable Bowel Syndrome/therapy ; Feces ; *Microbiota ; }, } @article {pmid38412097, year = {2024}, author = {Dong, J and Wang, B and Xiao, Y and Liu, J and Wang, Q and Xiao, H and Jin, Y and Liu, Z and Chen, Z and Li, Y and Fan, S and Li, Y and Cui, M}, title = {Roseburia intestinalis sensitizes colorectal cancer to radiotherapy through the butyrate/OR51E1/RALB axis.}, journal = {Cell reports}, volume = {43}, number = {3}, pages = {113846}, doi = {10.1016/j.celrep.2024.113846}, pmid = {38412097}, issn = {2211-1247}, abstract = {The radioresistant signature of colorectal cancer (CRC) hampers the clinical utility of radiotherapy. Here, we find that fecal microbiota transplantation (FMT) potentiates the tumoricidal effects of radiation and degrades the intertwined adverse events in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC mice. FMT cumulates Roseburia intestinalis (R. intestinalis) in the gastrointestinal tract. Oral gavage of R. intestinalis assembles at the CRC site and synthetizes butyrate, sensitizing CRC to radiation and alleviating intestinal toxicity in primary and CRC hepatic metastasis mouse models. R. intestinalis-derived butyrate activates OR51E1, a G-protein-coupled receptor overexpressing in patients with rectal cancer, facilitating radiogenic autophagy in CRC cells. OR51E1 shows a positive correlation with RALB in clinical rectal cancer tissues and CRC mouse model. Blockage of OR51E1/RALB signaling restrains butyrate-elicited autophagy in irradiated CRC cells. Our findings highlight that the gut commensal bacteria R. intestinalis motivates radiation-induced autophagy to accelerate CRC cell death through the butyrate/OR51E1/RALB axis and provide a promising radiosensitizer for CRC in a pre-clinical setting.}, } @article {pmid38412095, year = {2024}, author = {Hu, J and He, K and Yang, Y and Huang, C and Dou, Y and Wang, H and Zhang, G and Wang, J and Niu, C and Bi, G and Zhang, L and Zhu, S}, title = {Amino acid formula induces microbiota dysbiosis and depressive-like behavior in mice.}, journal = {Cell reports}, volume = {43}, number = {3}, pages = {113817}, doi = {10.1016/j.celrep.2024.113817}, pmid = {38412095}, issn = {2211-1247}, abstract = {Amino acid formula (AAF) is increasingly consumed in infants with cow's milk protein allergy; however, the long-term influences on health are less described. In this study, we established a mouse model by subjecting neonatal mice to an amino acid diet (AAD) to mimic the feeding regimen of infants on AAF. Surprisingly, AAD-fed mice exhibited dysbiotic microbiota and increased neuronal activity in both the intestine and brain, as well as gastrointestinal peristalsis disorders and depressive-like behavior. Furthermore, fecal microbiota transplantation from AAD-fed mice or AAF-fed infants to recipient mice led to elevated neuronal activations and exacerbated depressive-like behaviors compared to that from normal chow-fed mice or cow's-milk-formula-fed infants, respectively. Our findings highlight the necessity to avoid the excessive use of AAF, which may influence the neuronal development and mental health of children.}, } @article {pmid38411876, year = {2024}, author = {Mascaretti, F and Haider, S and Amoroso, C and Caprioli, F and Ramai, D and Ghidini, M}, title = {Role of the Microbiome in the Diagnosis and Management of Gastroesophageal Cancers.}, journal = {Journal of gastrointestinal cancer}, volume = {}, number = {}, pages = {}, pmid = {38411876}, issn = {1941-6636}, abstract = {PURPOSE: Stomach and esophageal cancers are among the highest mortality from cancers worldwide. Microbiota has an interplaying role within the human gastrointestinal (GI) tract. Dysbiosis occurs when a disruption of the balance between the microbiota and the host happens. With this narrative review, we discuss the main alterations in the microbiome of gastroesophageal cancer, revealing its potential role in the pathogenesis, early detection, and treatment.

RESULTS: Helicobacter pylori plays a major role the development of a cascade of preneoplastic conditions ranging from atrophic gastritis to metaplasia and dysplasia, ultimately culminating in gastric cancer, while other pathogenic agents are Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli, and Lactobacillus. Campylobacter species (spp.)'s role in the progression of esophageal adenocarcinoma may parallel that of Helicobacter pylori in the context of gastric cancer, with other esophageal carcinogenic agents being Escherichia coli, Bacteroides fragilis, and Fusobacterium nucleatum. Moreover, gut microbiome could significantly alter the outcomes of chemotherapy and immunotherapy. The gut microbiome can be modulated through interventions such as antibiotics, probiotics, or prebiotics intake. Fecal microbiota transplantation has emerged as a therapeutic strategy as well.

CONCLUSIONS: Nowadays, it is widely accepted that changes in the normal gut microbiome causing dysbiosis and immune dysregulation play a role gastroesophageal cancer. Different interventions, including probiotics and prebiotics intake are being developed to improve therapeutic outcomes and mitigate toxicities associated with anticancer treatment. Further studies are required in order to introduce the microbiome among the available tools of precision medicine in the field of anticancer treatment.}, } @article {pmid38411457, year = {2024}, author = {Vieujean, S and Gillard, R and Delanaye, P and Seidel, L and Bequet, E and Salée, C and Meuwis, MA and Massot, C and Pierre, N and Meunier, P and Cavalier, E and Louis, E}, title = {Matrix gla protein, a potential marker of tissue remodelling and physiological ageing of the gut in crohn's disease.}, journal = {Scandinavian journal of gastroenterology}, volume = {59}, number = {3}, pages = {296-303}, doi = {10.1080/00365521.2023.2286913}, pmid = {38411457}, issn = {1502-7708}, mesh = {Female ; Humans ; *Crohn Disease ; Matrix Gla Protein ; Constriction, Pathologic ; Aging ; Leukocyte L1 Antigen Complex ; }, abstract = {BACKGROUND: The inactive dephosphorylated and uncarboxylated form of the matrix Gla protein (dp-ucMGP) has been shown to be increased in plasma of inflammatory bowel disease (IBD) patients. Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity, presence of strictures and cumulative structural bowel damage in Crohn's disease (CD) patients.

METHODS: The plasmatic level of dp-ucMGP was measured in a monocentric cohort of prospectively recruited patients. The analysis was done by chemiluminescent immunoassay on blood samples collected the day of a planned ileocolonoscopy. In addition to classical clinical data (gender, age, body mass index (BMI), disease duration, current treatment), endoscopic data (disease location, Crohn's Disease Endoscopic Index of Severity (CDEIS), mucosal healing (MH), presence of 9 CD lesion types) and biological markers (faecal calprotectin and C-reactive protein (CRP)) were collected. The association between dp-ucMGP level and Lémann index was also investigated. Univariate linear regression was used to investigate the relationship between dp-ucMGP level and different parameters collected.

RESULTS: A total of 82 ileocolonoscopies and dp-ucMGP assays were performed in 75 CD patients (45 females; 37 ileocolonic, 19 ileal and 19 colonic diseases) between October 2012 and November 2019. A total of 24 patients (29.3%) showed MH. The dp-ucMGP levels were not associated with MH, CDEIS, faecal calprotectin or CRP levels. Plasmatic dp-ucMGP levels increased significantly with age (p = 0.0032), disease duration (p = 0.0033), corticosteroids use (p = 0.019) and tended to increase in patients with intestinal strictures (p = 0.086) but not with the Lémann index.

CONCLUSION: The significant increase of plasmatic dp-ucMGP levels with age, disease duration and the trend observed in patients with non-ulcerated strictures may suggest that this extracellular matrix protein could be a marker of tissue remodelling and physiological ageing of the gut.}, } @article {pmid38410824, year = {2023}, author = {Pasam, T and Dandekar, MP}, title = {Fecal microbiota transplantation unveils sex-specific differences in a controlled cortical impact injury mouse model.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1336537}, pmid = {38410824}, issn = {1664-302X}, abstract = {INTRODUCTION: Contusion type of traumatic brain injury (TBI) is a major cause of locomotor disability and mortality worldwide. While post-TBI deleterious consequences are influenced by gender and gut dysbiosis, the sex-specific importance of commensal gut microbiota is underexplored after TBI. In this study, we investigated the impact of controlled cortical impact (CCI) injury on gut microbiota signature in a sex-specific manner in mice.

METHODS: We depleted the gut microflora of male and female C57BL/6 mice using antibiotic treatment. Thereafter, male mice were colonized by the gut microbiota of female mice and vice versa, employing the fecal microbiota transplantation (FMT) method. CCI surgery was executed using a stereotaxic impactor (Impact One™). For the 16S rRNA gene amplicon study, fecal boli of mice were collected at 3 days post-CCI (dpi).

RESULTS AND DISCUSSION: CCI-operated male and female mice exhibited a significant alteration in the genera of Akkermansia, Alistipes, Bacteroides, Clostridium, Lactobacillus, Prevotella, and Ruminococcus. At the species level, less abundance of Lactobacillus helveticus and Lactobacillus hamsteri was observed in female mice, implicating the importance of sex-specific bacteriotherapy in CCI-induced neurological deficits. FMT from female donor mice to male mice displayed an increase in genera of Alistipes, Lactobacillus, and Ruminococcus and species of Bacteroides acidifaciens and Ruminococcus gnavus. Female FMT-recipient mice from male donors showed an upsurge in the genus Lactobacillus and species of Lactobacillus helveticus, Lactobacillus hamsteri, and Prevotella copri. These results suggest that the post-CCI neurological complications may be influenced by the differential gut microbiota perturbation in male and female mice.}, } @article {pmid38410679, year = {2024}, author = {Chen, S and Li, M and Tong, C and Wang, Y and He, J and Shao, Q and Liu, Y and Wu, Y and Song, Y}, title = {Regulation of miRNA expression in the prefrontal cortex by fecal microbiota transplantation in anxiety-like mice.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1323801}, pmid = {38410679}, issn = {1664-0640}, abstract = {BACKGROUND: The gut-brain axis and gut microbiota have emerged as key players in emotional disorders. Recent studies suggest that alterations in gut microbiota may impact psychiatric symptoms through brain miRNA along the gut-brain axis. However, direct evidence linking gut microbiota to the pathophysiology of generalized anxiety disorder (GAD) via brain miRNA is limited. In this study, we explored the effects of fecal microbiota transplantation (FMT) from GAD donors on gut microbiota and prefrontal cortex miRNA in recipient mice, aiming to understand the relationship between these two factors.

METHODS: Anxiety scores and gut microbiota composition were assessed in GAD patients, and their fecal samples were utilized for FMT in C57BL/6J mice. Anxiety-like behavior in mice was evaluated using open field and elevated plus maze tests. High-throughput sequencing of gut microbiota 16S rRNA and prefrontal cortex miRNA was performed.

RESULTS: The fecal microbiota of GAD patients exhibited a distinct microbial structure compared to the healthy group, characterized by a significant decrease in Verrucomicrobia and Akkermansia, and a significant increase in Actinobacteria and Bacteroides. Subsequent FMT from GAD patients to mice induced anxiety-like behavior in recipients. Detailed analysis of gut microbiota composition revealed lower abundances of Verrucomicrobia, Akkermansia, Bifidobacterium, and Butyricimonas, and higher abundances of Deferribacteres, Allobaculum, Bacteroides, and Clostridium in mice that received FMT from GAD patients. MiRNA analysis identified five key miRNAs affecting GAD pathogenesis, including mmu-miR-10a-5p, mmu-miR-1224-5p, mmu-miR-218-5p, mmu-miR-10b-5p, and mmu-miR-488-3p. Notably, mmu-miR-488-3p showed a strong negative correlation with Verrucomicrobia and Akkermansia.

CONCLUSION: This study demonstrates that anxiety-like behavior induced by human FMT can be transmitted through gut microbiota and is associated with miRNA expression in the prefrontal cortex. It is inferred that the reduction of Akkermansia caused by FMT from GAD patients leads to the upregulation of mmu-miR-488-3p expression, resulting in the downregulation of its downstream target gene Creb1 and interference with its related signaling pathway. These findings highlight the gut microbiota's crucial role in the GAD pathophysiology.}, } @article {pmid38409485, year = {2024}, author = {Yadav, A and Yadav, R and Sharma, V and Dutta, U}, title = {A comprehensive guide to assess gut mycobiome and its role in pathogenesis and treatment of inflammatory bowel disease.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {38409485}, issn = {0975-0711}, abstract = {Inflammatory bowel disease (IBD) is an immune mediated chronic inflammatory disorder of gastrointestinal tract, which has underlying multifactorial pathogenic determinants such as environmental factors, susceptibility genes, gut microbial dysbiosis and a dysregulated immune response. Human gut is a frequent inhabitant of complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi and other microorganisms that have an undisputable role in maintaining balanced homeostasis. All of these microbes interact with immune system and affect human gut physiology either directly or indirectly with interaction of each other. Intestinal fungi represent a smaller but crucial component of the human gut microbiome. Besides interaction with bacteriome and virome, it helps in balancing homoeostasis between pathophysiological and physiological processes, which is often dysregulated in patients with IBD. Understanding of gut mycobiome and its clinical implications are still in in its infancy as opposed to bacterial component of gut microbiome, which is more often focused. Modulation of gut mycobiome represents a novel and promising strategy in the management of patients with IBD. Emerging mycobiome-based therapies such as diet interventions, fecal microbiota transplantation (FMT), probiotics (both fungal and bacterial strains) and antifungals exhibit substantial effects in calibrating the gut mycobiome and restoring dysbalanced immune homeostasis by restoring the core gut mycobiome. In this review, we summarized compositional and functional diversity of the gut mycobiome in healthy individuals and patients with IBD, gut mycobiome dysbiosis in patients with IBD, host immune-fungal interactions and therapeutic role of modulation of intestinal fungi in patients with IBD.}, } @article {pmid38409241, year = {2024}, author = {Kasahara, N and Teratani, T and Yokota, S and Sakuma, Y and Sasanuma, H and Fujimoto, Y and Ijichi, T and Urahashi, T and Yoshitomi, H and Kitayama, J and Sata, N}, title = {Dietary polyamines promote intestinal adaptation in an experimental model of short bowel syndrome.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4605}, pmid = {38409241}, issn = {2045-2322}, support = {JP26461926//JSPS KAKENHI/ ; }, abstract = {Intestinal adaptation does not necessarily recover absorptive capacity in short bowel syndrome (SBS), sometimes resulting in intestinal failure-associated liver disease (IFALD). Additionally, its therapeutic options remain limited. Polyamines (spermidine and spermine) are known as one of the autophagy inducers and play important roles in promoting the weaning process; however, their impact on intestinal adaptation is unknown. The aim of this study was to investigate the impact of polyamines ingestion on adaptation and hepatic lipid metabolism in SBS. We performed resection of two-thirds of the small intestine in male Lewis rats as an SBS model. They were allocated into three groups and fed different polyamine content diets (0%, 0.01%, 0.1%) for 30 days. Polyamines were confirmed to distribute to remnant intestine, whole blood, and liver. Villous height and number of Ki-67-positive cells in the crypt area increased with the high polyamine diet. Polyamines increased secretory IgA and mucin content in feces, and enhanced tissue Claudin-3 expression. In contrast, polyamines augmented albumin synthesis, mitochondrial DNA copy number, and ATP storage in the liver. Moreover, polyamines promoted autophagy flux and activated AMP-activated protein kinase with suppression of lipogenic gene expression. Polyamines ingestion may provide a new therapeutic option for SBS with IFALD.}, } @article {pmid38408636, year = {2024}, author = {Yousef, M and Rob, M and Varghese, S and Rao, S and Zamir, F and Paul, P and Chaari, A}, title = {The effect of microbiome therapy on COVID-19-induced gut dysbiosis: A narrative and systematic review.}, journal = {Life sciences}, volume = {}, number = {}, pages = {122535}, doi = {10.1016/j.lfs.2024.122535}, pmid = {38408636}, issn = {1879-0631}, abstract = {AIMS: Emerging evidence highlights the role of COVID-19 in instigating gut dysbiosis, with repercussions on disease severity and bidirectional gut-organ communication involving the lung, heart, brain, and liver. This study aims to evaluate the efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) in addressing gut dysbiosis associated with COVID-19, as well as their impact on related disease severity and clinical outcomes.

MATERIALS AND METHODS: We systematically review 27 studies exploring the efficacy of different microbiome-modulating therapies: probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as potential interventions for COVID-19.

KEY FINDINGS: The probiotics and synbiotics investigated encompassed a spectrum of eight bacterial and fungal genera, namely Lactobacillus, Bifidobacterium, Streptococcus, Enterococcus, Pediococcus, Bacillus, Saccharomyces, and Kluyveromyces. Noteworthy prebiotics employed in these studies included chestnut tannin, galactooligosaccharides, fructooligosaccharides, xylooligosaccharide, and resistant dextrin. The majority of the investigated biotics exhibited positive effects on COVID-19 patients, manifesting in symptom alleviation, inflammation reduction, and notable decreases in mortality rates. Five studies reported death rates, showing an average mortality ranging from 0 % to 11 % in the intervention groups, as compared to 3 % to 30 % in the control groups. Specifically, probiotics, prebiotics, and synbiotics demonstrated efficacy in diminishing the duration and severity of symptoms while significantly accelerating viral and symptomatic remission. FMT emerged as a particularly effective strategy, successfully restoring gut microbiota and ameliorating gastrointestinal disorders.

SIGNIFICANCE: The insights gleaned from this review significantly contribute to our broader comprehension of the therapeutic potential of biotics in addressing COVID-19-related gut dysbiosis and mitigating secondary multi-organ complications.}, } @article {pmid38407390, year = {2024}, author = {Tian, B and Pan, Y and Zhou, X and Jiang, Y and Zhang, X and Luo, X and Yang, K}, title = {Yellow leaf green tea modulates AMPK/ACC/SREBP1c signaling pathway and gut microbiota in high-fat diet-induced mice to alleviate obesity.}, journal = {Journal of the science of food and agriculture}, volume = {}, number = {}, pages = {}, doi = {10.1002/jsfa.13413}, pmid = {38407390}, issn = {1097-0010}, abstract = {BACKGROUND: Yellow leaf green tea (YLGT) is a new variety of Camellia sinensis (L.) O. Ktze, which has yellow leaves and the unique qualities of 'three green through three yellow'. This study aimed to investigate the anti-obesity effect of YLGT in mice fed a high-fat diet (HFD) and to explore the potential mechanisms by regulating the AMPK/ACC/SREBP1c signaling pathways and gut microbiota.

RESULTS: The results showed that YLGT aqueous extract reduced body weight, hepatic inflammation, fat accumulation and hyperlipidemia in HFD-induced C57BL/6J mice, and accelerated energy metabolism, reduced fat synthesis, and suppressed obesity by activating the AMPK/CPT-1α signaling pathway and inhibiting the FAS/ACC/SREBP-1c signaling pathway. Fecal microbiota transplantation experiment further confirmed that the alteration of gut microbiota, e.g., increasing unclassified_Muribaculaceae and decreasing Colidextribacter, might be an important cause of YLGT water extract inhibiting obesity.

CONCLUSION: In conclusion, YLGT has a broad application prospect in the treatment of obesity and the development of anti-obesity function beverages. This article is protected by copyright. All rights reserved.}, } @article {pmid38407164, year = {2024}, author = {Mena, CJ and Garófalo, MP and Perazzo, J and Epelbaum, C and Castro, G and Sicilia, P and Barnes, A and Guasconi, L and Burstein, VL and Beccacece, I and Almeida, MA and Cervi, L and Santin, M and Chiapello, LS}, title = {Enterocytozoon bieneusi Infection after Hematopoietic Stem Cell Transplant in Child, Argentina.}, journal = {Emerging infectious diseases}, volume = {30}, number = {3}, pages = {613-616}, doi = {10.3201/eid3003.231580}, pmid = {38407164}, issn = {1080-6059}, mesh = {Humans ; Child ; Argentina/epidemiology ; *Enterocytozoon/genetics ; Transplant Recipients ; Feces ; *Hematopoietic Stem Cell Transplantation/adverse effects ; }, abstract = {We report a case of Enterocytozoon bieneusi infection in a pediatric hematopoietic stem cell transplant recipient in Argentina. Spores were visualized in feces using Calcofluor White and modified trichrome stainings. PCR and sequencing identified E. bieneusi genotype D in fecal samples and liver samples, confirming extraintestinal dissemination of the parasite.}, } @article {pmid38405608, year = {2024}, author = {Lu, X and Yang, R and Chen, Y and Chen, D}, title = {NAD metabolic therapy in metabolic dysfunction-associated steatotic liver disease: Possible roles of gut microbiota.}, journal = {iScience}, volume = {27}, number = {3}, pages = {109174}, pmid = {38405608}, issn = {2589-0042}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly named non-alcoholic fatty liver disease (NAFLD), is induced by alterations of hepatic metabolism. As a critical metabolites function regulator, nicotinamide adenine dinucleotide (NAD) nowadays has been validated to be effective in the treatment of diet-induced murine model of MASLD. Additionally, gut microbiota has been reported to have the potential to prevent MASLD by dietary NAD precursors metabolizing together with mammals. However, the underlying mechanism remains unclear. In this review, we hypothesized that NAD enhancing mitochondrial activity might reshape a specific microbiota signature, and improve MASLD progression demonstrated by fecal microbiota transplantation. Here, this review especially focused on the mechanism of Microbiota-Gut-Liver Axis together with NAD metabolism for the MASLD progress. Notably, we found significant changes in Prevotella associated with NAD in a gut microbiome signature of certain MASLD patients. With the recent researches, we also inferred that Prevotella can not only regulate the level of NAD pool by boosting the carbon metabolism, but also play a vital part in regulating the branched-chain amino acid (BCAA)-related fatty acid metabolism pathway. Altogether, our results support the notion that the gut microbiota contribute to the dietary NAD precursors metabolism in MASLD development and the dietary NAD precursors together with certain gut microbiota may be a preventive or therapeutic strategy in MASLD management.}, } @article {pmid38405047, year = {2024}, author = {Kopera, AF and Khiew, YC and Amer Alsamman, M and Mattar, MC and Olsen, RS and Doman, DB}, title = {Depression and the Aberrant Intestinal Microbiome.}, journal = {Gastroenterology & hepatology}, volume = {20}, number = {1}, pages = {30-40}, pmid = {38405047}, issn = {1554-7914}, abstract = {Depression is one of the most common mental health disorders affecting adults in the United States. The current treatment is the combination of pharmacotherapy and psychotherapy. Recently, the evidence linking gut microbiome dysregulation to the development of depression has grown. The pathophysiology is currently poorly understood, although leading hypotheses include involvement of the hypothalamic-pituitary-adrenal axis, a bidirectional relationship between the gut microbiome and the central nervous system, and production of signaling molecules by the gut microbiome. Available and emerging treatments of the aberrant microbiome include antidepressants, antibiotics, diet modification, probiotics, and fecal microbiota transplant. This article explores the interconnectivity of gut microbiota and depression and treatments targeted toward the gut, reviews the gastroenterologist's potential role in managing gut dysbiosis in patients with depression, and highlights research topics to be addressed to create evidence-based guidelines.}, } @article {pmid38404132, year = {2024}, author = {Joo, MK and Lee, JW and Woo, JH and Kim, HJ and Kim, DH and Choi, JH}, title = {Regulation of colonic neuropeptide Y expression by the gut microbiome in patients with ulcerative colitis and its association with anxiety- and depression-like behavior in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2319844}, doi = {10.1080/19490976.2024.2319844}, pmid = {38404132}, issn = {1949-0984}, mesh = {Humans ; *Colitis, Ulcerative/microbiology ; *Gastrointestinal Microbiome ; Neuropeptide Y/genetics ; Depression ; Fecal Microbiota Transplantation ; Feces/microbiology ; Anxiety ; }, abstract = {Patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC), show an increased incidence of anxiety and depression; however, the association between UC-associated psychiatric disorders and the gut microbiota is unclear. This study aimed to examine whether gut microbiota from patients with UC can alter colonic gene expression, leading to anxiety- and depression-like behavior in mice receiving fecal microbiota transplantation (FMT). RNA sequencing transcriptome analyses revealed a difference in colonic gene expression between mice receiving FMT from patients with UC (UC-FMT mice) and those receiving FMT from healthy controls (HC-FMT mice). Gene ontology analysis revealed the downregulation of neuropeptide signaling pathways, including neuropeptide Y (NPY) expression, in the colons of UC-FMT mice. The protein levels of NPY also decreased in the colon and plasma of UC-FMT mice compared to those in HC-FMT mice. The oral administration of Enterococcus mundtii (EM), a bacterium isolated from the feces of patients with UC, reduced NPY expression in the colons of mice and induced intestinal inflammation, anxiety, and depression-like behavior. Reduced NPY protein levels were also observed in the plasma and hippocampus of EM-treated mice. Intraperitoneal administration of NPY significantly alleviated anxiety- and depressive-like behaviors induced by EM in mice. Capsular polysaccharide in EM was associated with EM-induced NPY downregulation in the colon. Analysis of Gene Expression Omnibus datasets showed markedly reduced NPY expression in the inflamed colons of patients with UC compared with that in the colons of healthy controls. In summary, EM-induced reduction in the colonic expression of NPY may be associated with a decrease in hippocampal NPY and anxiety- and depression-like behavior in mice.}, } @article {pmid38402605, year = {2024}, author = {Ijeomah, IM and Temitope, FOC and Lander, C and Sheriff, AT and Uwem, GE and Bernard, OA and Oluseyi, OA and Elijah, OI and Toluwani, AG and Arthur, OO and Toluwanimi, AE and Bolutife, PO and Damilola, OG and Titilola, OO and Oluwadamilola, GA and Muhammad, AI and Omotosho, KI and Johnson, AA and Jelle, M and Olubusuyi, AM}, title = {Classic human astrovirus 4, 8, MLB-3, and likely new genotype 5 sublineage in stool samples of children in Nigeria.}, journal = {Journal of medical virology}, volume = {96}, number = {3}, pages = {e29489}, doi = {10.1002/jmv.29489}, pmid = {38402605}, issn = {1096-9071}, mesh = {Child ; Humans ; Aged ; *Mamastrovirus/genetics ; Phylogeny ; Nigeria/epidemiology ; *Astroviridae Infections/epidemiology ; Feces ; Genotype ; }, abstract = {Human astrovirus (HAstV) is a nonenveloped RNA virus and has been implicated in acute gastroenteritis among children and elderly. However, there exists a substantial dearth of information on HAstV strains circulating in Nigeria. Viral-like particles were purified from archived 254 stool samples of children with acute flaccid paralysis between January and December 2020 from five states in Nigeria, using the NetoVIR protocol. Extracted viral RNA and DNA were subjected to a reverse transcription step and subsequent random polymerase chain reaction amplification. Library preparation and Illumina sequencing were performed. Using the virome paired-end reads pipeline, raw reads were processed into genomic contigs. Phylogenetic and pairwise identity analysis of the recovered HAstV genomes was performed. Six near-complete genome sequences of HAstV were identified and classified as HAstV4 (n = 1), HAstV5 (n = 1), HAstV8 (n = 1), and MLB-3 (n = 3). The HAstV5 belonged to a yet unclassified sublineage, which we tentatively named HAstV-5d. Phylogenetic analysis of open reading frames 1a, 1b, and 2 suggested recombination events inside the MAstV1 species. Furthermore, phylogenetic analysis implied a geographic linkage between the HAstV5 strain from this study with two strains from Cameroon across all the genomic regions. We report for the first time the circulation of HAstV genotypes 4, 8, and MLB-3 in Nigeria and present data suggestive for the existence of a new sublineage of HAstV5. To further understand the burden, diversity, and evolution of HAstV, increased research interest as well as robust HAstV surveillance in Nigeria is essential.}, } @article {pmid38402460, year = {2024}, author = {Zhu, Y and He, H and Sun, W and Wu, J and Xiao, Y and Peng, Y and Hu, P and Jin, M and Liu, P and Zhang, D and Wu, J and Xie, T and Huang, L and He, W and Wei, M and Wang, L and Xu, X and Tang, Y}, title = {IgA nephropathy: gut microbiome regulates the production of hypoglycosilated IgA1via the TLR4 signaling pathway.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {}, number = {}, pages = {}, doi = {10.1093/ndt/gfae052}, pmid = {38402460}, issn = {1460-2385}, abstract = {BACKGROUND: IgA nephropathy (IgAN) is a major cause of primary glomerulonephritis characterized by mesangial deposits of galactose-deficient IgA1 (Gd-IgA1). Toll-like receptors (TLRs), particularly TLR4 are involved in the pathogenesis of IgAN. The role of gut microbiota on IgAN patients was recently investigated. However, whether gut microbial modifications of Gd-IgA1 through TLR4 play a role in IgAN remains unclear.

METHODS: We recruited subjects into four groups, including 48 patients with untreated IgAN, 22 treated IgAN patients (IgANIT), 22 primary membranous nephropathy (MN), and 31 healthy controls (HCs). Fecal samples were collected to analyze changes in gut microbiome. Gd-IgA1 levels, expression of TLR4, B-cell stimulators, and intestinal barrier function were evaluated in all subjects. C57BL/6 mice were treated with a broad-spectrum antibiotic cocktail to deplete the gut microbiota and then gavaged with fecal microbiota transplanted fromclinical subjects of every group. Gd-IgA1 and TLR4 pathway were detected in peripheral blood mononuclear cells (PBMCs) from IgAN and HCs co-incubated with Lipopolysaccharide (LPS) and TLR4 inhibitor.

RESULTS: Compared with other three groups, different compositions and decreased diversity demonstrated gut dysbiosis in un-treated IgAN, especially the enrichment of Escherichia -Shigella. Elevated Gd-IgA1 levels were found in un-treated IgAN patients and correlated with gut dysbiosis, TLR4, B-cell stimulators, indexes of intestinal barrier damage, and proinflammatory cytokines. In vivo, mice colonized with gut microbiota from IgAN and IgANIT patients, copied the IgAN phenotype with the activation of TLR4/MyD88/NF-κB pathway, B-cell stimulators in the intestine, and complied with enhanced proinflammatory cytokines. In vitro, LPS activated TLR4/MyD88/NF-κB pathway, B-cell stimulators and proinflammatory cytokines in the PBMCs from IgAN patients, which resulted in overproduction of Gd-IgA1 and inhibited by TLR4 inhibitor.

CONCLUSIONS: Our results illustrated that gut-kidney axis was involved in the pathogenesis of IgAN. Gut dysbiosis could stimulate the overproduction of Gd-IgA1 by TLR4 signaling pathway production and B-cell stimulators.}, } @article {pmid38400885, year = {2024}, author = {Chen, X and Wang, G and Qin, L and Hu, B and Li, J}, title = {Intestinal Microbiota Modulates the Antitumor Effect of Oncolytic Virus Vaccines in Colorectal Cancer.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {38400885}, issn = {1573-2568}, support = {22NSFCS1601//Department of Science and Technology of Sichuan Province/ ; }, abstract = {BACKGROUND: Immunotherapies, such as oncolytic viruses, have become powerful cancer treatments, but only some patients with cancer can benefit from them, especially those with advanced-stage cancer, and new therapeutic strategies are needed to facilitate extended survival. The intestinal microbiota may contribute to colorectal cancer (CRC) carcinogenesis and the response to immunotherapy. However, whether and how the intestinal microbiota modulates the effects of oncolytic virus vaccines (OVVs) in CRC remain to be investigated.

METHODS: We generated an MC38-gp33 CRC mouse model and treated it with OVV-gp33 in early and advanced stages. Probiotics, fecal microbiota transplantation (FMT), and antibiotics (ABX) were administered to regulate the microbial composition of CRC mice at an advanced stage. The tumor growth rate and survival time of the mice were recorded; 16S rDNA sequencing was used to analyze the microbial composition and flow cytometry was used to detect T-cell subset activity.

RESULTS: OVV-gp33 treatment inhibited tumor growth and prolonged survival in the early stage of CRC but did not have a significant effect on the advanced stage of CRC. Moreover, 16S rDNA sequence analysis and flow cytometry showed significant differences in intestinal microbiota composition, microbial metabolites, and T-cell subsets in early and advanced-stage CRC. Probiotic and FMT treatment significantly enhanced the antitumor effect of OVV in the advanced stage of CRC with an increased abundance of activated CD8[+] T cells and a decreased ratio of Treg cells, while depletion of the microbiota by ABX eliminated the antitumor activity of OVV with decreased CD8[+] T-cell activation and upregulated Treg cells.

CONCLUSIONS: These results indicate that the intestinal microbiota and microbial metabolites play an important role in the antitumor effect of OVV in CRC. Furthermore, altering the intestinal microbiota composition can modulate the antitumor and immunomodulatory effects of OVV in CRC.}, } @article {pmid38400752, year = {2024}, author = {He, Z and Xie, H and Xu, H and Wu, J and Zeng, W and He, Q and Jobin, C and Jin, S and Lan, P}, title = {Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2319511}, doi = {10.1080/19490976.2024.2319511}, pmid = {38400752}, issn = {1949-0984}, mesh = {Humans ; Mice ; Animals ; Oxaliplatin/toxicity ; Interleukin-10/genetics ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Macrophages ; *Probiotics/pharmacology/therapeutic use ; *Antineoplastic Agents/adverse effects ; }, abstract = {The gut microbiota has been shown to influence the efficacy and toxicity of chemotherapy, thereby affecting treatment outcomes. Understanding the mechanism by which microbiota affects chemotherapeutic toxicity would have a profound impact on cancer management. In this study, we report that fecal microbiota transplantation from oxaliplatin-exposed mice promotes toxicity in recipient mice. Splenic RNA sequencing and macrophage depletion experiment showed that the microbiota-induced toxicity of oxaliplatin in mice was dependent on macrophages. Furthermore, oxaliplatin-mediated toxicity was exacerbated in Il10[-/-] mice, but not attenuated in Rag1[-/-] mice. Adoptive transfer of macrophage into Il10[-/-] mice confirmed the role of macrophage-derived IL-10 in the improvement of oxaliplatin-induced toxicity. Depletion of fecal Lactobacillus and Bifidobacterium was associated with the exacerbation of oxaliplatin-mediated toxicity, whereas supplementation with these probiotics alleviated chemotherapy-induced toxicity. Importantly, IL-10 administration and probiotics supplementation did not attenuate the antitumor efficacy of chemotherapy. Clinically, patients with colorectal cancer exposed to oxaliplatin exhibited downregulation of peripheral CD45[+]IL-10[+] cells. Collectively, our findings indicate that microbiota-mediated IL-10 production influences tolerance to chemotherapy, and thus represents a potential clinical target.}, } @article {pmid38400709, year = {2024}, author = {de Wit, S and Geerlings, L and Shi, C and Dronkers, J and Schouten, EM and Blancke, G and Andries, V and Yntema, T and Meijers, WC and Koonen, DPY and Vereecke, L and Silljé, HHW and Aboumsallem, JP and de Boer, RA}, title = {Heart failure-induced microbial dysbiosis contributes to colonic tumour formation in mice.}, journal = {Cardiovascular research}, volume = {}, number = {}, pages = {}, doi = {10.1093/cvr/cvae038}, pmid = {38400709}, issn = {1755-3245}, abstract = {INTRODUCTION: Heart failure (HF) and cancer are the leading causes of death worldwide. Epidemiological studies revealed that HF patients are prone to develop cancer. Preclinical studies provided some insights into this connection, but the exact mechanisms remain elusive. In colorectal cancer (CRC), gut microbial dysbiosis is linked to cancer progression and recent studies have shown that HF patients display microbial dysbiosis.

AIM: This current study focussed on the effects of HF-induced microbial dysbiosis on colonic tumour formation.

METHODS AND RESULTS: C57BL/6J mice were subjected to myocardial infarction (MI), with sham surgery as control. After six weeks faeces were collected, processed for 16s rRNA sequencing, and pooled for faecal microbiota transplantation. CRC tumour growth was provoked in germ-free mice by treating them with Azoxymethane/Dextran sodium sulphate. The CRC mice were transplanted with faeces from MI or sham mice. MI-induced HF resulted in microbial dysbiosis, characterized by a decreased α-diversity and microbial alterations on the genus level, several of which have been associated with CRC. We then performed, faecal microbiota transplantation with faeces from HF mice in CRC mice, which resulted in a higher endoscopic disease score and an increase in the number of tumours in CRC mice.

CONCLUSION: We demonstrated that MI-induced HF contributes to colonic tumour formation by altering the gut microbiota composition, providing a mechanistic explanation for the observed association between HF and increased risk for cancer. Targeting the microbiome may present as a tool to mitigate HF-associated co-morbidities, especially cancer.}, } @article {pmid38399665, year = {2024}, author = {Raymo, G and Ali, A and Ahmed, RO and Salem, M}, title = {Early-Life Fecal Transplantation from High Muscle Yield Rainbow Trout to Low Muscle Yield Recipients Accelerates Somatic Growth through Respiratory and Mitochondrial Efficiency Modulation.}, journal = {Microorganisms}, volume = {12}, number = {2}, pages = {}, pmid = {38399665}, issn = {2076-2607}, support = {2023-67015-39742//National Institute of Food and Agriculture/ ; }, abstract = {Previous studies conducted in our lab revealed microbial assemblages to vary significantly between high (ARS-FY-H) and low fillet yield (ARS-FY-L) genetic lines in adult rainbow trout. We hypothesized that a high ARS-FY-H donor microbiome can accelerate somatic growth in microbiome-depleted rainbow trout larvae of the ARS-FY-L line. Germ-depleted larvae of low ARS-FY-L line trout reared in sterile environments were exposed to high- or low-fillet yield-derived microbiomes starting at first feeding for 27 weeks. Despite weight-normalized diets, somatic mass was significantly increased in larvae receiving high fillet yield microbiome cocktails at 27 weeks post-hatch. RNA-seq from fish tails reveals enrichment in NADH dehydrogenase activity, oxygen carrier, hemoglobin complex, gas transport, and respiratory pathways in high fillet yield recolonized larvae. Transcriptome interrogation suggests a relationship between electron transport chain inputs and body weight assimilation, mediated by the gut microbiome. These findings suggest that microbiome payload originating from high fillet yield adult donors primarily accelerates juvenile somatic mass assimilation through respiratory and mitochondrial input modulation. Further microbiome studies are warranted to assess how increasing beneficial microbial taxa could be a basis for formulating appropriate pre-, pro-, or post-biotics in the form of feed additives and lead to fecal transplantation protocols for accelerated feed conversion and fillet yield in aquaculture.}, } @article {pmid38399561, year = {2024}, author = {Di Leo, V and Annese, F and Papadia, F and Russo, MS and Giliberti, M and Sallustio, F and Gesualdo, L}, title = {Refractory IgA Nephropathy: A Challenge for Future Nephrologists.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {2}, pages = {}, pmid = {38399561}, issn = {1648-9144}, mesh = {Humans ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; *Glomerulonephritis, IGA/drug therapy ; Angiotensin Receptor Antagonists/therapeutic use ; Nephrologists ; Antihypertensive Agents/therapeutic use ; *Kidney Failure, Chronic/therapy ; Steroids/therapeutic use ; Immunosuppressive Agents/therapeutic use ; }, abstract = {IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.}, } @article {pmid38398873, year = {2024}, author = {Suprunowicz, M and Tomaszek, N and Urbaniak, A and Zackiewicz, K and Modzelewski, S and Waszkiewicz, N}, title = {Between Dysbiosis, Maternal Immune Activation and Autism: Is There a Common Pathway?.}, journal = {Nutrients}, volume = {16}, number = {4}, pages = {}, pmid = {38398873}, issn = {2072-6643}, mesh = {Child ; Humans ; *Autism Spectrum Disorder/etiology/metabolism ; *Autistic Disorder/etiology ; Dysbiosis/complications ; *Gastrointestinal Microbiome/physiology ; Family ; Bacteria ; }, abstract = {Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother's obesity as potentially environmental factors of ASD. The purpose of this review is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.}, } @article {pmid38397562, year = {2024}, author = {Cheng, N and Wang, X and Zhou, Y and Zhao, X and Chen, M and Zhao, H and Cao, W}, title = {Schisandra chinensis Bee Pollen Ameliorates Colitis in Mice by Modulating Gut Microbiota and Regulating Treg/Th17 Balance.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {4}, pages = {}, pmid = {38397562}, issn = {2304-8158}, support = {2022YFD1600205//the National Key Research and Development Program of China/ ; No. 32372428//the National Natural Science Foundation of China/ ; TZ0389//the Shaanxi high-level talent special support plan/ ; 23KGDW0010-2023//the Xi'an Science& Technology Project/ ; }, abstract = {Colitis is a chronic disease associated with alterations in the composition of gut microbiota. Schisandra chinensis bee pollen extract (SCPE) has been proved to be rich in phenolic compounds and effective in modulating gut microbiota, but its effect on colitis and the underlying mechanism remains unclear. This study investigates the relationship between colitis amelioration and the gut microbiota regulation of SCPE via fecal microbial transplantation (FMT). The results showed that administration of 20.4 g/kg BW of SCPE could primely ameliorate colitis induced by dextran sulfate sodium (DSS) in mice, showing as more integration of colon tissue structure and the colonic epithelial barrier, as well as lower oxidative stress and inflammation levels compared with colitis mice. Moreover, SCPE supplement restored the balance of T regulatory (Treg) cells and T helper 17 (Th17) cells. Gut microbiota analysis showed SCPE treatment could reshape the gut microbiota balance and improve the abundance of gut microbiota, especially the beneficial bacteria (Akkermansia and Lactobacillus) related to the production of short-chain fatty acids and the regulation of immunity. Most importantly, the protection of 20.4 g/kg BW of SCPE on colitis can be perfectly transmitted by fecal microbiota. Therefore, the gut microbiota-SCFAS-Treg/Th17 axis can be the main mechanism for SCPE to ameliorate colitis. This study suggests that SCPE can be a new promising functional food for prevention and treatment of colitis by reshaping gut microbiota and regulating gut immunity.}, } @article {pmid38395525, year = {2024}, author = {Peery, AF and Kelly, CR and Kao, D and Vaughn, BP and Lebwohl, B and Singh, S and Imdad, A and Altayar, O and , }, title = {AGA Clinical Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases.}, journal = {Gastroenterology}, volume = {166}, number = {3}, pages = {409-434}, doi = {10.1053/j.gastro.2024.01.008}, pmid = {38395525}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Fecal microbiota-based therapies include conventional fecal microbiota transplant and US Food and Drug Administration-approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal microbiota-based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome.

METHODS: The guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of fecal microbiota-based therapies in the specified gastrointestinal conditions and provided implementation considerations for clinical practice.

RESULTS: The guideline panel made 7 recommendations. In immunocompetent adults with recurrent C difficile infection, the AGA suggests select use of fecal microbiota-based therapies on completion of standard of care antibiotics to prevent recurrence. In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests select use of conventional fecal microbiota transplant. In severely immunocompromised adults, the AGA suggests against the use of any fecal microbiota-based therapies to prevent recurrent C difficile. In adults hospitalized with severe or fulminant C difficile not responding to standard of care antibiotics, the AGA suggests select use of conventional fecal microbiota transplant. The AGA suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials.

CONCLUSIONS: Fecal microbiota-based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.}, } @article {pmid38392196, year = {2024}, author = {Tao, W and Fan, Q and Wei, J}, title = {Gut-Liver Axis as a Therapeutic Target for Drug-Induced Liver Injury.}, journal = {Current issues in molecular biology}, volume = {46}, number = {2}, pages = {1219-1236}, pmid = {38392196}, issn = {1467-3045}, support = {2021-620-000-001-021//Hubei Innovation Center of Agricultural Science and Technology/ ; 2024NKYJJ17//Youth Foundation of Hubei Academy of Agricultural Sciences/ ; }, abstract = {Drug-induced liver injury (DILI) is a liver disease that remains difficult to predict and diagnose, and the underlying mechanisms are yet to be fully clarified. The gut-liver axis refers to the reciprocal interactions between the gut and the liver, and its homeostasis plays a prominent role in maintaining liver health. It has been recently reported that patients and animals with DILI have a disrupted gut-liver axis, involving altered gut microbiota composition, increased intestinal permeability and lipopolysaccharide translocation, decreased short-chain fatty acids production, and impaired bile acid metabolism homeostasis. The present review will summarize the evidence from both clinical and preclinical studies about the role of the gut-liver axis in the pathogenesis of DILI. Moreover, we will focus attention on the potential therapeutic strategies for DILI based on improving gut-liver axis function, including herbs and phytochemicals, probiotics, fecal microbial transplantation, postbiotics, bile acids, and Farnesoid X receptor agonists.}, } @article {pmid38391047, year = {2024}, author = {Lauwers, E and Sabino, J and Hoffman, I and van Hoeve, K}, title = {Faecal microbiota transplantation in children: A systematic review.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {}, number = {}, pages = {}, doi = {10.1111/apa.17167}, pmid = {38391047}, issn = {1651-2227}, support = {//Fonds Wetenschappelijk Onderzoek/ ; //Viatris/ ; }, abstract = {AIM: Novel technologies offer insights into the potential role of the intestinal microbiota in human health and disease. Dysbiosis has been associated with several diseases, and it is thought to play a role in the pathogenesis of different gastrointestinal diseases. Faecal microbiota transplantation (FMT) is emerging as a method to modulate the gastrointestinal microbial ecosystem. While recurrent Clostridioides difficile infection is the recognised FMT indication, exploration of other therapeutic uses is ongoing.

METHODS: Following PRISMA guidelines, we conducted a systematic review, extracting 583 articles from Embase and PubMed (index date to October 2022).

RESULTS: The search yielded 58 studies for full review, with 50 included in the systematic review. Articles were categorised by FMT indication, study design, efficacy, adverse events, donor selection and administration route. FMT appears safe and effective for recurrent Clostridioides difficile infection, although severe adverse events are reported in children. However, there are currently insufficient data to support the use of FMT for other potential therapeutic indications (such as irritable or inflammatory bowel disease or obesity), beside the potential to decolonise multi-drug resistant organisms.

CONCLUSION: This underscores the need for randomised, controlled, prospective cohort studies in children to assess FMT effectiveness in diverse conditions and counteract publication bias.}, } @article {pmid38390942, year = {2024}, author = {Jirillo, E and Palmirotta, R and Colella, M and Santacroce, L}, title = {A Bird's-Eye View of the Pathophysiologic Role of the Human Urobiota in Health and Disease: Can We Modulate It?.}, journal = {Pathophysiology : the official journal of the International Society for Pathophysiology}, volume = {31}, number = {1}, pages = {52-67}, pmid = {38390942}, issn = {1873-149X}, abstract = {For a long time, urine has been considered sterile in physiological conditions, thanks to the particular structure of the urinary tract and the production of uromodulin or Tamm-Horsfall protein (THP) by it. More recently, thanks to the development and use of new technologies, i.e., next-generation sequencing and expanded urine culture, the identification of a microbial community in the urine, the so-called urobiota, became possible. Major phyla detected in the urine are represented by Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Particularly, the female urobiota is largely represented by Lactobacillus spp., which are very active against urinary pathogenic Escherichia (E.) coli (UPEC) strains via the generation of lactic acid and hydrogen peroxide. Gut dysbiosis accounts for recurrent urinary tract infections (UTIs), so-called gut-bladder axis syndrome with the formation of intracellular bacterial communities in the course of acute cystitis. However, other chronic urinary tract infections are caused by bacterial strains of intestinal derivation. Monomicrobial and polymicrobial infections account for the outcome of acute and chronic UTIs, even including prostatitis and chronic pelvic pain. E. coli isolates have been shown to be more invasive and resistant to antibiotics. Probiotics, fecal microbial transplantation, phage therapy, antimicrobial peptides, and immune-mediated therapies, even including vaccines for the treatment of UTIs, will be described.}, } @article {pmid38389631, year = {2024}, author = {Franco, CD and Sagar, RS and Bokhari, SFH}, title = {From Microbes to Memories: Challenges and Future Perspectives Regarding the Gut-Brain Axis for Improved Cognitive Health in Alzheimer's.}, journal = {Cureus}, volume = {16}, number = {1}, pages = {e52795}, pmid = {38389631}, issn = {2168-8184}, abstract = {The gut-brain axis, a bidirectional communication network between the gastrointestinal tract and the central nervous system, regulates various physiological processes crucial for health, including immune response, metabolism, and neurotransmitter production. In the context of neurodegenerative diseases, especially Alzheimer's disease (AD), understanding the intricate connection of the gut-brain axis has gained significance. Disturbances along this axis have been implicated in neurodegenerative diseases, emphasizing its role in AD pathogenesis. Microbiota dysbiosis, influenced by diet, lifestyle, and genetics, contributes to altered gut permeability, leading to protein dyshomeostasis, astroglial activation, neuroinflammation, and cognitive decline. Understanding these mechanisms is crucial for developing interventions to restore a healthy gut microbiota and potentially mitigate AD-related cognitive decline. The bidirectional communication along the gut-brain axis involves microbial metabolites, influencing oxidative stress, protein aggregation, and other pathways linked to neuroprotection. Modulating the gut microbiota through dietary changes, prebiotics, probiotics, or fecal microbiota transplantation emerges as a promising approach to target cognitive decline in AD. Despite progress, challenges persist, including the correlational nature of studies, the complexity of the gut microbiome, and variations in methodologies. Standardization is essential for reliable findings and the identification of biomarkers associated with AD. Unanswered questions warrant further exploration, particularly in understanding specific mechanisms, the temporal dynamics of microbiota changes, and the influence of diet and lifestyle on the gut-brain axis in AD. Future perspectives involve promising therapeutic interventions targeting the gut-brain axis, emphasizing personalized medicine to optimize outcomes based on individual variations in the gut-brain axis characteristics.}, } @article {pmid38389170, year = {2024}, author = {Lyu, X and Zhang, TT and Ye, Z and Chen, C}, title = {Astragaloside IV Mitigated Diabetic Nephropathy by Restructuring Intestinal Microflora and Ferroptosis.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2300734}, doi = {10.1002/mnfr.202300734}, pmid = {38389170}, issn = {1613-4133}, support = {Q202147//Jiangsu Provincial Pharmaceutical Society-Tianqing Hospital Pharmacy Fund/ ; }, abstract = {SCOPE: To investigate the underlying mechanism of Astragaloside IV (AS-IV) in ameliorating diabetic nephropathy (DN) by regulating intestinal microbiota ecology and intestinal mucosal barrier.

METHODS AND RESULTS: Genetically db/db mice are used to establish DN mouse model to monitor the therapeutic effects of AS-IV and fecal microbiota transplantation (FMT) against DN. Supplementation with AS-IV dramatically attenuates several clinical indicators of DN in db/db mice. In addition, AS-IV markedly improves intestinal barrier function, modifies intestinal permeability, and reduces inflammation. Moreover, AS-IV treatment remarkably improves intestinal dysbiosis in db/db mice, characterized by an elevated abundance of Akkermansia, Ligilactobacillus, and Lactobacillus, indicating the fundamental role of the microbiome in DN progression. Furthermore, FMT derived from AS-IV-treated db/db mice is potentially efficient in antagonizing renal dysfunction, rebalancing gut microbiota, and improving intestinal permeability in recipient db/db mice. AS-IV-enriched Akkermansia muciniphila dramatically alleviates DN and intestinal mucosal barrier dysfunction in db/db mice. Intriguingly, AS-IV intervention dramatically diminishes ferroptosis in the kidney and colon tissues. CONCLUSION : Intestinal microbiome alterations and ferroptosis modulation by AS-IV may play instrumental roles in this mechanism, providing compelling evidence for the role of the gut-renal axis in DN.}, } @article {pmid38388538, year = {2024}, author = {Cao, Z and Fan, D and Sun, Y and Huang, Z and Li, Y and Su, R and Zhang, F and Li, Q and Yang, H and Zhang, F and Miao, Y and Lan, P and Wu, X and Zuo, T}, title = {The gut ileal mucosal virome is disturbed in patients with Crohn's disease and exacerbates intestinal inflammation in mice.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {1638}, pmid = {38388538}, issn = {2041-1723}, support = {82172323//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32100134//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82060107//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn's disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.}, } @article {pmid38388458, year = {2024}, author = {Yang, J and Liu, W and Han, X and Hao, X and Yao, Q and Du, W}, title = {Gut microbiota modulation enhances the immune capacity of lizards under climate warming.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {37}, pmid = {38388458}, issn = {2049-2618}, support = {32301304//National Natural Science Foundation of China/ ; 31821001//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Host-microbial interactions are expected to affect species' adaptability to climate change but have rarely been explored in ectothermic animals. Some studies have shown that short-term warming reduced gut microbial diversity that could hamper host functional performance.

RESULTS: However, our longitudinal experiments in semi-natural conditions demonstrated that warming decreased gut microbiota diversity at 2 months, but increased diversity at 13 and 27 months in a desert lizard (Eremias multiocellata). Simultaneously, long-term warming significantly increased the antibacterial activity of serum, immune responses (higher expression of intestinal immune-related genes), and the concentration of short-chain fatty acids (thereby intestinal barrier and immunity) in the lizard. Fecal microbiota transplant experiments further revealed that increased diversity of gut microbiota significantly enhanced antibacterial activity and the immune response of lizards. More specifically, the enhanced immunity is likely due to the higher relative abundance of Bacteroides in warming lizards, given that the bacteria of Bacteroides fragilis regulated IFN-β expression to increase the immune response of lizards under a warming climate.

CONCLUSIONS: Our study suggests that gut microbiota can help ectotherms cope with climate warming by enhancing host immune response, and highlights the importance of long-term studies on host-microbial interactions and their biological impacts.}, } @article {pmid38382594, year = {2024}, author = {Wu, JJ and Zheng, X and Wu, C and Ma, W and Wang, Y and Wang, J and Wei, Y and Zeng, X and Zhang, S and Guan, W and Chen, F}, title = {Melatonin alleviates high temperature exposure induced fetal growth restriction via the gut-placenta-fetus axis in pregnant mice.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.02.014}, pmid = {38382594}, issn = {2090-1224}, abstract = {INTRODUCTION: Global warming augments the risk of adverse pregnancy outcomes in vulnerable expectant mothers. Pioneering investigations into heat stress (HS) have predominantly centered on its direct impact on reproductive functions, while the potential roles of gut microbiota, despite its significant influence on distant tissues, remain largely unexplored. Our understanding of deleterious mechanisms of HS and the development of effective intervention strategies to mitigate the detrimental impacts are still limited.

OBJECTIVES: In this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment.

METHODS: We firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment.

RESULTS: Melatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS- challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight.

CONCLUSION: Melatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.}, } @article {pmid38380023, year = {2024}, author = {Chen, L and Xie, L and Tan, J and Li, N and Luo, Y and Li, M and Zhang, S and Wang, Z}, title = {The gut microbiota regulates the depressive-type behaviors and inflammatory processes after severe burn injuries in mice.}, journal = {Heliyon}, volume = {10}, number = {4}, pages = {e25617}, pmid = {38380023}, issn = {2405-8440}, abstract = {An emerging number of studies have recently revealed the correlation between burn injuries and psychological disorders. Gut microbiota and inflammatory factors may play a vital role in this process. Nevertheless, there are few studies conducted to disclose the potential mechanism of the gut microbiota between depression and burn injuries. In this study, we constructed a burn model of C57BL/6 mice, which showed that the symptom of depression became more and more severe with the burn of mice lasted longer. Meanwhile, there are significant differences of composition of gut microbiota among mice before and after burn. Then, we tested the inflammatory factors in the brain and peripheral blood, which showed an increased expression of Iba1, VWF, TNF-α and IL-6, and a decreased expression of IL-10 in burn mice. In addition, the expression of zonula occludens-1 (ZO-1) in cecum showed a down-regulation in burn mice, which indicated impaired intestinal barrier function. Lastly, the crossing fecal microbiota transplantation (FMT) and cohousing experiment were conducted to determine the functions of cross-transplantation of fecal microbiota on the depressive-type behaviours in burned mice. According to the score of Tail suspension test (TST), the burn mice were divided into two groups: Resilient mice (no-depressed mice) and Abnormal mice (depressed mice). After abnormal mice were transplanted with fecal microbiota of resilient mice, the symptom of depression was improved, and the expression of TNF-α, IL-6 and IL-10 return to normal levels (P < 0.05). On the contrary, after resilient mice were transplanted with fecal microbiota of abnormal mice both the TST scores and inflammatory factor developed depressive-type changes. In conclusion, our study demonstrated the changes of gut microbiota and inflammatory factors in depressed burn mice and non-depressed burn mice. The gut microbiota dysbiosis could impaired intestinal barrier function and lead to neuroinflammation, and this phenomenon could be significantly mitigated by FMT.}, } @article {pmid38378622, year = {2024}, author = {Hao, W and Ma, Q and Wang, L and Yuan, N and Gan, H and He, L and Li, X and Huang, J and Chen, J}, title = {Gut dysbiosis induces the development of depression-like behavior through abnormal synapse pruning in microglia-mediated by complement C3.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {34}, pmid = {38378622}, issn = {2049-2618}, support = {2023M741396//China Postdoctoral Science Foundation/ ; 2021A1515010869; 2022A1515011699//the Guangdong Basic and Applied Basic Research Foundation/ ; 2021A1515010869; 2022A1515011699//the Guangdong Basic and Applied Basic Research Foundation/ ; 82074300, 82174278//National Natural Science Foundation of China/ ; 82074300, 82174278//National Natural Science Foundation of China/ ; 2020B1111100001//Key-Area Research and Development Program of Guangdong Province/ ; 2020B1111100001//Key-Area Research and Development Program of Guangdong Province/ ; 2021B1212040007//Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization/ ; 2021B1212040007//Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization/ ; 202201020052//Science and Technology Program of Guangzhou/ ; 202102010014//the Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine/ ; 202102010014//the Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine/ ; 201911//the Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University/ ; }, mesh = {Animals ; Mice ; Complement C3 ; *Depression/microbiology ; Dysbiosis ; *Microglia/physiology ; Synapses/physiology ; }, abstract = {BACKGROUND: Remodeling eubiosis of the gut microenvironment may contribute to preventing the occurrence and development of depression. Mounting experimental evidence has shown that complement C3 signaling is associated with the pathogenesis of depression, and disruption of the gut microbiota may be an underlying cause of complement system activation. However, the mechanism by which complement C3 participates in gut-brain crosstalk in the pathogenesis of depression remains unknown.

RESULTS: In the present study, we found that chronic unpredictable mild stress (CUMS)-induced mice exhibited obvious depression-like behavior as well as cognitive impairment, which was associated with significant gut dysbiosis, especially enrichment of Proteobacteria and elevation of microbiota-derived lipopolysaccharides (LPS). In addition, peripheral and central complement C3 activation and central C3/CR3-mediated aberrant synaptic pruning in microglia have also been observed. Transplantation of gut microbiota from CUMS-induced depression model mice into specific pathogen-free and germ-free mice induced depression-like behavior and concomitant cognitive impairment in the recipient mice, accompanied by increased activation of the complement C3/CR3 pathway in the prefrontal cortex and abnormalities in microglia-mediated synaptic pruning. Conversely, antidepressants and fecal microbiota transplantation from antidepressant-treated donors improved depression-like behaviors and restored gut microbiome disturbances in depressed mice. Concurrently, inhibition of the complement C3/CR3 pathway, amelioration of abnormal microglia-mediated synaptic pruning, and increased expression of the synapsin and postsynaptic density protein 95 were observed. Collectively, our results revealed that gut dysbiosis induces the development of depression-like behaviors through abnormal synapse pruning in microglia-mediated by complement C3, and the inhibition of abnormal synaptic pruning is the key to targeting microbes to treat depression.

CONCLUSIONS: Our findings provide novel insights into the involvement of complement C3/CR3 signaling and aberrant synaptic pruning of chemotactic microglia in gut-brain crosstalk in the pathogenesis of depression. Video Abstract.}, } @article {pmid38376627, year = {2024}, author = {Isali, I and Helstrom, EK and Uzzo, N and Lakshmanan, A and Nandwana, D and Valentine, H and Sindhani, M and Abbosh, P and Bukavina, L}, title = {Current Trends and Challenges of Microbiome Research in Bladder Cancer.}, journal = {Current oncology reports}, volume = {}, number = {}, pages = {}, pmid = {38376627}, issn = {1534-6269}, abstract = {PURPOSE OF THE REVIEW: Microbiome research has provided valuable insights into the associations between microbial communities and bladder cancer. However, this field faces significant challenges that hinder the interpretation, generalization, and translation of findings into clinical practice. This review aims to elucidate these challenges and highlight the importance of addressing them for the advancement of microbiome research in bladder cancer.

RECENT FINDINGS: Recent findings underscore the complexities involved in microbiome research, particularly in the context of bladder cancer. Challenges include low microbial biomass in urine samples, potential contamination issues during collection and processing, variability in sequencing methods and primer selection, and the difficulty of establishing causality between microbiota and bladder cancer. Studies have shown the impact of sample storage conditions and DNA isolation kits on microbiome analysis, emphasizing the need for standardization. Additionally, variations in urine collection methods can introduce contamination and affect results. The choice of 16S rRNA gene amplicon sequencing or shotgun metagenomic sequencing introduces technical challenges, including primer selection and sequencing read length. Establishing causality between the microbiota and bladder cancer requires experimental methods like fecal microbiota transplantation and human microbiota-associated murine models, which face their own set of challenges. Translating microbiome research into therapeutic applications is hindered by methodological variability, incomplete understanding of bioactive molecules, imperfect animal models, and the inherent heterogeneity of microbiome communities among individuals. Microbiome research in bladder cancer presents significant challenges stemming from technical and conceptual complexities. Addressing these challenges through standardization, improved experimental models, and advanced analytical approaches is essential for advancing our understanding of the microbiome's role in bladder cancer and its potential clinical applications. Achieving this goal can lead to improved patient outcomes and novel therapeutic strategies in the future.}, } @article {pmid38375101, year = {2024}, author = {Monday, L and Tillotson, G and Chopra, T}, title = {Microbiota-Based Live Biotherapeutic Products for Clostridioides Difficile Infection- The Devil is in the Details.}, journal = {Infection and drug resistance}, volume = {17}, number = {}, pages = {623-639}, pmid = {38375101}, issn = {1178-6973}, abstract = {Clostridioides difficile infection (CDI) remains a significant contributor to healthcare costs and morbidity due to high rates of recurrence. Currently, available antibiotic treatment strategies further disrupt the fecal microbiome and do not address the alterations in commensal flora (dysbiosis) that set the stage for CDI. Advances in microbiome-based research have resulted in the development of new agents, classified as live biotherapeutic products (LBPs), for preventing recurrent CDI (rCDI) by restoring eubiosis. Prior to the LBPs, fecal microbiota transplantation (FMT) was available for this purpose; however, lack of large-scale availability and safety concerns have remained barriers to its widespread use. The LBPs are an exciting development, but questions remain. Some are derived directly from human stool while other developmental products contain a defined microbial consortium manufactured ex vivo, and they may be composed of either living bacteria or their spores, making it difficult to compare members of this heterogenous drug class to one another. None have been studied head-to head or against FMT in preventing rCDI. As a class, they have considerable variability in their biologic composition, biopharmaceutic science, route of administration, stages of development, and clinical trial data. This review will start by explaining the role of dysbiosis in CDI, then give the details of the biopharmaceutical components for the LBPs which are approved or in development including how they differ from FMT and from one another. We then discuss the clinical trials of the LBPs currently approved for rCDI and end with the future clinical directions of LBPs beyond C. difficile.}, } @article {pmid38370838, year = {2024}, author = {McMillan, AS and Zhang, G and Dougherty, MK and McGill, SK and Gulati, AS and Baker, ES and Theriot, CM}, title = {Metagenomic, metabolomic, and lipidomic shifts associated with fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.02.07.579219}, pmid = {38370838}, abstract = {Recurrent C. difficile infection (rCDI) is an urgent public health threat for which the last resort and lifesaving treatment is a fecal microbiota transplant (FMT). However, the exact mechanisms which mediate a successful FMT are not well understood. Here we use longitudinal stool samples collected from patients undergoing FMT to evaluate changes in the microbiome, metabolome, and lipidome after successful FMTs. We show changes in the abundance of many lipids, specifically acylcarnitines and bile acids, in response to FMT. These changes correlate with Enterobacteriaceae, which encode carnitine metabolism genes, and Lachnospiraceae, which encode bile salt hydrolases and baiA genes. LC-IMS-MS revealed a shift from microbial conjugation of primary bile acids pre-FMT to secondary bile acids post-FMT. Here we define the structural and functional changes in successful FMTs. This information will help guide targeted Live Biotherapeutic Product development for the treatment of rCDI and other intestinal diseases.}, } @article {pmid38051896, year = {2024}, author = {Huang, Q and Wei, M and Feng, X and Luo, Y and Liu, Y and Xia, J}, title = {Hemorrhagic transformation in patients with large-artery atherosclerotic stroke is associated with the gut microbiota and lipopolysaccharide.}, journal = {Neural regeneration research}, volume = {19}, number = {7}, pages = {1532-1540}, pmid = {38051896}, issn = {1673-5374}, abstract = {Hemorrhagic transformation is a major complication of large-artery atherosclerotic stroke (a major ischemic stroke subtype) that worsens outcomes and increases mortality. Disruption of the gut microbiota is an important feature of stroke, and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation pathogenesis. We aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in large-artery atherosclerotic stroke. An observational retrospective study was conducted. From May 2020 to September 2021, blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy, as well as 16 healthy controls. Patients with stroke who developed hemorrhagic transformation (n = 15) were compared to those who did not develop hemorrhagic transformation (n = 17) and with healthy controls. The gut microbiota was assessed through 16S ribosomal ribonucleic acid sequencing. We also examined key components of the lipopolysaccharide pathway: lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14. We observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transformation group compared with the healthy controls. The patients with ischemic stroke who developed hemorrhagic transformation exhibited altered gut microbiota composition, in particular an increase in the relative abundance and diversity of members belonging to the Enterobacteriaceae family. Plasma lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transformation group. lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14 concentrations were associated with increased abundance of Enterobacteriaceae. Next, the role of the gut microbiota in hemorrhagic transformation was evaluated using an experimental stroke rat model. In this model, transplantation of the gut microbiota from hemorrhagic transformation rats into the recipient rats triggered higher plasma levels of lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14. Taken together, our findings demonstrate a noticeable change in the gut microbiota and lipopolysaccharide-related inflammatory response in stroke patients with hemorrhagic transformation. This suggests that maintaining a balanced gut microbiota may be an important factor in preventing hemorrhagic transformation after stroke.}, } @article {pmid38369241, year = {2024}, author = {Meroni, M and Longo, M and Paolini, E and Dongiovanni, P}, title = {A narrative review about cognitive impairment in metabolic Dysfunction-Associated liver disease (MASLD): Another matter to face through a holistic approach.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.02.007}, pmid = {38369241}, issn = {2090-1224}, abstract = {BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic hepatic disorder worldwide in both adults and children. It is well established that MASLD represents the hepatic manifestation of the metabolic syndrome whose definition includes the presence of obesity, type 2 diabetes (T2D), dyslipidemia, hypertension and hypercoagulability. All these conditions contribute to a chronic inflammatory status which may impact on blood brain barrier (BBB) integrity leading to an impaired function of central nervous system (CNS).

AIM OF REVIEW: Since the mechanisms underlying the brain-liver-gut axis derangement are still inconclusive, the present narrative review aims to make a roundup of the most recent studies regarding the cognitive decline in MASLD also highlighting possible therapeutic strategies to reach a holistic advantage for the patients.

Due to its ever-growing prevalence, the MASLD-related mental dysfunction represents an enormous socio-economic burden since it largely impacts on the quality of life of patients as well as on their working productivity. Indeed, cognitive decline in MASLD translates in low concentration and processing speed, reduced memory, sleepiness but also anxiety and depression. Chronic systemic inflammation, hyperammonemia, genetic background and intestinal dysbiosis possibly contribute to the cognitive decline in MASLD patients. However, its diagnosis is still underestimated since the leading mechanisms are multi-faceted and unexplained and do not exist standardized diagnostic tools or cognitive test strategies. In this scenario, nutritional and lifestyle interventions as well as intestinal microbiota manipulation (probiotics, fecal transplantation) may represent new approaches to counteract mental impairment in these subjects. In sum, to face the "mental aspect" of this multifactorial disease which is almost unexplored, cognitive tools should be introduced in the management of MASLD patients.}, } @article {pmid38367807, year = {2024}, author = {Xu, H and Li, O and Kim, D and Yang, F and Bao, Z}, title = {Age-related gut microbiota transplantation disrupts myocardial energy homeostasis and induces oxidative damage.}, journal = {The Journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tjnut.2024.02.011}, pmid = {38367807}, issn = {1541-6100}, abstract = {BACKGROUND: Aging-related energy homeostasis significantly affects normal heart function and disease development. The relationship between the gut microbiota and host energy metabolism has been well established. However, the influence of an aged microbiota on energy metabolism in the heart remains unclear.

OBJECTIVE: To explore the effects of age-related microbiota composition on energy metabolism in the heart METHODS: In this study, we used the fecal microbiota transplantation (FMT) method. The fecal microbiota from young (2-3 months) and aged (18-22 months) donor mice were transplanted into separate groups of young (2-3 months) recipient mice. The analysis utilized whole 16S rRNA sequencing and plasma metabolomics to assess changes in the gut microbiota composition and metabolic potential. Energy changes were monitored by performing an oral glucose tolerance test (OGTT), biochemical testing, body composition analysis, and metabolic cage measurements. Metabolic markers and markers of DNA damage were assessed in heart samples.

RESULTS: FMT of an aged microbiota changed the composition of the recipient's gut microbiota, leading to an elevated Firmicutes-to-Bacteroidetes (F/B) ratio. It also affected overall energy metabolism, resulting in elevated plasma glucose levels, impaired glucose tolerance, and epididymal fat accumulation. Notably, FMT of an aged microbiota increased the heart weight and promoted cardiac hypertrophy. Furthermore, there were significant associations between heart weight and cardiac hypertrophy indicators, epididymal fat weight, and fasting glucose levels. Mechanistically, FMT of an aged microbiota modulated the glucose metabolic pathway and induced myocardial oxidative damage.

CONCLUSIONS: Our findings suggested that an aged microbiota can modulate metabolism and induce cardiac injury. This highlights the possible role of the gut microbiota in age-related metabolic disorders and cardiac dysfunction.}, } @article {pmid38367621, year = {2024}, author = {Chen, Q and Wu, C and Xu, J and Ye, C and Chen, X and Tian, H and Zong, N and Zhang, S and Li, L and Gao, Y and Zhao, D and Lv, X and Yang, Q and Wang, L and Cui, J and Lin, Z and Lu, J and Yang, R and Yin, F and Qin, N and Li, N and Xu, Q and Qin, H}, title = {Donor-recipient intermicrobial interactions impact transfer of subspecies and fecal microbiota transplantation outcome.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2024.01.013}, pmid = {38367621}, issn = {1934-6069}, abstract = {Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906). We found that interactions between donor and recipient microbes, which were overwhelmingly phylogenetically divergent, were important for subspecies transfer and positive clinical outcomes. Additionally, a donor-recipient SGB match was indicative of a high likelihood of strain transfer. Importantly, these ecodynamics were shared across FMT datasets encompassing multiple diseases. Collectively, these findings provide detailed insight into specific microbial interactions and dynamics that determine FMT success.}, } @article {pmid38365257, year = {2024}, author = {Dong, Q and Hua, D and Wang, X and Jiao, Y and Liu, L and Deng, Q and Wu, T and Zou, H and Zhao, C and Wang, C and Reng, J and Ding, L and Hu, S and Shi, J and Wang, Y and Zhang, H and Sheng, Y and Sun, W and Shen, Y and Tang, L and Kong, X and Chen, L}, title = {Temporal colonization and metabolic regulation of the gut microbiome in neonatal oxen at single nucleotide resolution.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {38365257}, issn = {1751-7370}, support = {32394052//National Natural Science Foundation of China/ ; JSSCBS20221815//Jiangsu Shuangchuang Project/ ; BK20220709//Natural Science Foundation of Jiangsu/ ; C2022204247//Natural Science Foundation of Hebei/ ; CMCM202204//Nanjing Medical University/ ; //Development of Jiangsu Higher Education Institutions Priority Academic Program/ ; }, mesh = {Infant, Newborn ; Humans ; Female ; *Gastrointestinal Microbiome/physiology ; Nucleotides ; Levodopa ; *Microbiota ; Feces ; Metagenomics/methods ; }, abstract = {The colonization of microbes in the gut is key to establishing a healthy host-microbiome symbiosis for newborns. We longitudinally profiled the gut microbiome in a model consisting of 36 neonatal oxen from birth up to 2 months postpartum and carried out microbial transplantation to reshape their gut microbiome. Genomic reconstruction of deeply sequenced fecal samples resulted in a total of 3931 metagenomic-assembled genomes from 472 representative species, of which 184 were identified as new species when compared with existing databases of oxen. Single nucleotide level metagenomic profiling shows a rapid influx of microbes after birth, followed by dynamic shifts during the first few weeks of life. Microbial transplantation was found to reshape the genetic makeup of 33 metagenomic-assembled genomes (FDR < 0.05), mainly from Prevotella and Bacteroides species. We further linked over 20 million microbial single nucleotide variations to 736 plasma metabolites, which enabled us to characterize 24 study-wide significant associations (P < 4.4 × 10-9) that identify the potential microbial genetic regulation of host immune and neuro-related metabolites, including glutathione and L-dopa. Our integration analyses further revealed that microbial genetic variations may influence the health status and growth performance by modulating metabolites via structural regulation of their encoded proteins. For instance, we found that the albumin levels and total antioxidant capacity were correlated with L-dopa, which was determined by single nucleotide variations via structural regulations of metabolic enzymes. The current results indicate that temporal colonization and transplantation-driven strain replacement are crucial for newborn gut development, offering insights for enhancing newborn health and growth.}, } @article {pmid38363696, year = {2024}, author = {Weber, AT and Lichtenstein, GR}, title = {Evidence-Based Approach to Chronic Antibiotic Refractory Pouchitis: A Review.}, journal = {Diseases of the colon and rectum}, volume = {}, number = {}, pages = {}, doi = {10.1097/DCR.0000000000003207}, pmid = {38363696}, issn = {1530-0358}, abstract = {BACKGROUND: Chronic antibiotic refractory pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis, characterized by at least 4 weeks of pouchitis symptoms that have not responded to standard antibiotic therapy, presents a therapeutic challenge for patients and healthcare providers.

OBJECTIVE: The aim of this narrative review was to summarize the current evidence regarding management of chronic antibiotic refractory pouchitis.

DATA SOURCES: Studies were identified through search of PubMed database from the National Library of Medicine.

STUDY SELECTION: We included case series, cohort studies, randomized-controlled trials, and systematic reviews with meta-analyses that addressed chronic antibiotic refractory pouchitis management, with prioritization of data published within the last 3-5 years.

INTERVENTION: Studies examining pharmacologic and select non-pharmacologic interventions were included.

MAIN OUTCOME MEASURE: Outcomes measures included clinical, endoscopic, and histologic endpoints.

RESULTS: Mesalamine has demonstrated efficacy in symptom improvement but no improvement in quality of life. Budesonide has demonstrated high rates of clinical remission that have mostly been sustained in a small number of patients. Anti-tumor necrosis factor alpha therapies have demonstrated efficacy in reaching clinical and even endoscopic endpoints, although rates of treatment discontinuation were not insignificant. Limited evidence is encouraging for use of ustekinumab in achieving clinical response. Data for vedolizumab are favorable across clinical, endoscopic, and histologic endpoints, including one of the only randomized, placebo-controlled trials. Non-medication therapies including hyperbaric oxygen therapy and fecal microbiota transplant have undergone limited evaluation and concerns about ultimate accessibility of these therapies remain.

LIMITATIONS: Overall, studies assessing therapeutic options for chronic antibiotic refractory pouchitis are mostly limited to case series and retrospective studies with small sample sizes.

CONCLUSIONS: Biologic therapies have demonstrated efficacy in the management of chronic antibiotic refractory pouchitis and offer a steroid-sparing option for refractory disease. Non-pharmacologic therapies, including hyperbaric oxygen and fecal microbiota transplant, require further exploration. See video.}, } @article {pmid38362864, year = {2024}, author = {Schöler, D and Schnabl, B}, title = {The role of the microbiome in liver disease.}, journal = {Current opinion in gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MOG.0000000000001013}, pmid = {38362864}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: The intestinal microbiome and the gut-liver axis play a major role in health and disease. The human gut harbors trillions of microbes and a disruption of the gut homeostasis can contribute to liver disease. In this review, the progress in the field within the last 3 years is summarized, focusing on metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), autoimmune liver disease (AILD), and hepatocellular carcinoma (HCC).

RECENT FINDINGS: Changes in the fecal virome and fungal mycobiome have been described in patients with various liver diseases. Several microbial derived metabolites including endogenous ethanol produced by bacteria, have been mechanistically linked to liver disease such as MASLD. Virulence factors encoded by gut bacteria contribute to ALD, AILD and HCC. Novel therapeutic approaches focused on the microbiome including phages, pre- and postbiotics have been successfully used in preclinical models. Fecal microbiota transplantation has been effective in attenuating liver disease. Probiotics are safe in patients with alcohol-associated hepatitis and improve liver disease and alcohol addiction.

SUMMARY: The gut-liver axis plays a key role in the pathophysiology of liver diseases. Understanding the microbiota in liver disease can help to develop precise microbiota centered therapies.}, } @article {pmid38361239, year = {2024}, author = {Mohamed, ME and Saqr, A and Staley, C and Onyeaghala, G and Teigen, L and Dorr, CR and Remmel, RP and Guan, W and Oetting, WS and Matas, AJ and Israni, AK and Jacobson, PA}, title = {Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation.}, journal = {Transplantation}, volume = {}, number = {}, pages = {}, pmid = {38361239}, issn = {1534-6080}, abstract = {The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug-microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.}, } @article {pmid38360862, year = {2024}, author = {Loh, JS and Mak, WQ and Tan, LKS and Ng, CX and Chan, HH and Yeow, SH and Foo, JB and Ong, YS and How, CW and Khaw, KY}, title = {Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases.}, journal = {Signal transduction and targeted therapy}, volume = {9}, number = {1}, pages = {37}, pmid = {38360862}, issn = {2059-3635}, mesh = {Humans ; Brain/metabolism ; *Neurodegenerative Diseases/therapy/metabolism ; Brain-Gut Axis ; *Probiotics/therapeutic use ; Prebiotics ; }, abstract = {The human gastrointestinal tract is populated with a diverse microbial community. The vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect of human biology, including health maintenance, development, aging, and disease. The advent of new sequencing technologies and culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations to shed light on microbiome-host interactions. Evidence has unveiled the bidirectional communication between the gut microbiome and the central nervous system, referred to as the "microbiota-gut-brain axis". The microbiota-gut-brain axis represents an important regulator of glial functions, making it an actionable target to ameliorate the development and progression of neurodegenerative diseases. In this review, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases. As the gut microbiome provides essential cues to microglia, astrocytes, and oligodendrocytes, we examine the communications between gut microbiota and these glial cells during healthy states and neurodegenerative diseases. Subsequently, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases using a metabolite-centric approach, while also examining the role of gut microbiota-related neurotransmitters and gut hormones. Next, we examine the potential of targeting the intestinal barrier, blood-brain barrier, meninges, and peripheral immune system to counteract glial dysfunction in neurodegeneration. Finally, we conclude by assessing the pre-clinical and clinical evidence of probiotics, prebiotics, and fecal microbiota transplantation in neurodegenerative diseases. A thorough comprehension of the microbiota-gut-brain axis will foster the development of effective therapeutic interventions for the management of neurodegenerative diseases.}, } @article {pmid37106038, year = {2024}, author = {Maghini, DG and Dvorak, M and Dahlen, A and Roos, M and Kuersten, S and Bhatt, AS}, title = {Quantifying bias introduced by sample collection in relative and absolute microbiome measurements.}, journal = {Nature biotechnology}, volume = {42}, number = {2}, pages = {328-338}, pmid = {37106038}, issn = {1546-1696}, support = {Lieberman Fellowship//Stanford University (SU)/ ; T32GM007276//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30CA124435//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 1S10OD02014101//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI14862302//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01AI14375702//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; }, mesh = {Feces ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; Metagenome ; DNA ; }, abstract = {To gain insight into the accuracy of microbial measurements, it is important to evaluate sources of bias related to sample condition, preservative method and bioinformatic analyses. There is increasing evidence that measurement of the total count and concentration of microbes in the gut, or 'absolute abundance', provides a richer source of information than relative abundance and can correct some conclusions drawn from relative abundance data. However, little is known about how preservative choice can affect these measurements. In this study, we investigated how two common preservatives and short-term storage conditions impact relative and absolute microbial measurements. OMNIgene GUT OMR-200 yields lower metagenomic taxonomic variation between different storage temperatures, whereas Zymo DNA/RNA Shield yields lower metatranscriptomic taxonomic variation. Absolute abundance quantification reveals two different causes of variable Bacteroidetes:Firmicutes ratios across preservatives. Based on these results, we recommend OMNIgene GUT OMR-200 preservative for field studies and Zymo DNA/RNA Shield for metatranscriptomics studies, and we strongly encourage absolute quantification for microbial measurements.}, } @article {pmid38357521, year = {2024}, author = {Kriz, J and Hysperska, V and Bebrova, E and Roznetinska, M}, title = {Faecal microbiota transplantation for multidrug-resistant organism decolonization in spinal cord injury patients: a case series.}, journal = {Infection prevention in practice}, volume = {6}, number = {1}, pages = {100340}, pmid = {38357521}, issn = {2590-0889}, abstract = {INTRODUCTION: The increase of multidrug-resistant (MDR) bacteria in healthcare settings is a worldwide concern. Isolation precautions must be implemented to control the significant risk of transmitting these pathogens among patients. Antibiotic decolonization is not recommended because of the threat of increasing antibiotic resistance. However, restoring gut microflora through faecal microbiota transplantation (FMT) is a hopeful solution.

PATIENTS AND METHOD: In 2019-2022, FMT was indicated in seven patients of the Spinal Cord Unit at University Hospital Motol who were colonized with MDR bacterial strains. Five patients tested positive for carriage of carbapenemase-producing Enterobacteriaceae, and two were carriers of vancomycin-resistant enterococci. Isolation measures were implemented in all patients. Donor faeces were obtained from healthy, young, screened volunteers. According to local protocol, 200-300 ml of suspension was applied through a nasoduodenal tube.

RESULTS: The mean age of the patients was 43 years. The mean length of previous hospital stay was 93.2 days. All patients were treated with broad-spectrum antibiotics for infectious complications before detecting colonisation with MDR bacteria. MDR organism decolonization was achieved in five patients, and consequently, isolation measures could be removed. Colonization persisted in two patients, one of whom remained colonized even after a third FMT. No adverse events were reported after FMT.

CONCLUSION: FMT is a safe and effective strategy to eradicate MDR bacteria, even in spinal cord injured patients. FMT can allow relaxation of isolation facilitates, the participation of patients in a complete rehabilitation program, their social integration, and transfer to follow-up rehabilitation centres.}, } @article {pmid38357210, year = {2023}, author = {Zhang, H and Dong, M and Zheng, J and Yang, Y and He, J and Liu, T and Wei, H}, title = {Fecal bacteria-free filtrate transplantation is proved as an effective way for the recovery of radiation-induced individuals in mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1343752}, pmid = {38357210}, issn = {2235-2988}, mesh = {Mice ; Animals ; Fecal Microbiota Transplantation/methods ; Dysbiosis/therapy/microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Microbiota ; }, abstract = {BACKGROUND: Ionizing radiation can cause intestinal microecological dysbiosis, resulting in changes in the composition and function of gut microbiota. Altered gut microbiota is closely related to the development and progression of radiation-induced intestinal damage. Although microbiota-oriented therapeutic options such as fecal microbiota transplantation (FMT) have shown some efficacy in treating radiation toxicity, safety concerns endure. Therefore, fecal bacteria-free filtrate transplantation (FFT), which has the potential to become a possible alternative therapy, is well worth investigating. Herein, we performed FFT in a mouse model of radiation exposure and monitored its effects on radiation damage phenotypes, gut microbiota, and metabolomic profiles to assess the effectiveness of FFT as an alternative therapy to FMT safety concerns.

RESULTS: FFT treatment conferred radioprotection against radiation-induced toxicity, representing as better intestinal integrity, robust proinflammatory and anti-inflammatory cytokines homeostasis, and accompanied by significant shifts in gut microbiome. The bacterial compartment of recipients following FFT was characterized by an enrichment of radioprotective microorganisms (members of family Lachnospiraceae). Furthermore, metabolome data revealed increased levels of microbially generated short-chain fatty acids (SCFAs) in the feces of FFT mice.

CONCLUSIONS: FFT improves radiation-induced intestinal microecological dysbiosis by reshaping intestinal mucosal barrier function, gut microbiota configurations, and host metabolic profiles, highlighting FFT regimen as a promising safe alternative therapy for FMT is effective in the treatment of radiation intestinal injury.}, } @article {pmid38356049, year = {2024}, author = {van Bergeijk, DA and Augustijn, HE and Elsayed, SS and Willemse, J and Carrión, VJ and Du, C and Urem, M and Grigoreva, LV and Cheprasov, MY and Grigoriev, S and Jansen, H and Wintermans, B and Budding, AE and Spaink, HP and Medema, MH and van Wezel, GP}, title = {Taxonomic and metabolic diversity of Actinomycetota isolated from faeces of a 28,000-year-old mammoth.}, journal = {Environmental microbiology}, volume = {26}, number = {2}, pages = {e16589}, doi = {10.1111/1462-2920.16589}, pmid = {38356049}, issn = {1462-2920}, support = {//Universiteit Leiden/ ; 101055020-COMMUNITY//European Research Council/International ; 948770-DECIPHER//European Research Council/International ; }, mesh = {Animals ; Phylogeny ; *Mammoths ; Genomics ; *Streptomyces/genetics ; *Actinomycetales ; Feces ; }, abstract = {Ancient environmental samples, including permafrost soils and frozen animal remains, represent an archive with microbial communities that have barely been explored. This yet unexplored microbial world is a genetic resource that may provide us with new evolutionary insights into recent genomic changes, as well as novel metabolic pathways and chemistry. Here, we describe Actinomycetota Micromonospora, Oerskovia, Saccharopolyspora, Sanguibacter and Streptomyces species were successfully revived and their genome sequences resolved. Surprisingly, the genomes of these bacteria from an ancient source show a large phylogenetic distance to known strains and harbour many novel biosynthetic gene clusters that may well represent uncharacterised biosynthetic potential. Metabolic profiles of the strains display the production of known molecules like antimycin, conglobatin and macrotetrolides, but the majority of the mass features could not be dereplicated. Our work provides insights into Actinomycetota isolated from an ancient source, yielding unexplored genomic information that is not yet present in current databases.}, } @article {pmid38353638, year = {2024}, author = {Liu, B and Fan, L and Wang, Y and Wang, H and Yan, Y and Chen, S and Hung, I and Liu, C and Wei, H and Ge, L and Ren, W}, title = {Gut microbiota regulates host melatonin production through epithelial cell MyD88.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2313769}, pmid = {38353638}, issn = {1949-0984}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Escherichia coli ; *Melatonin ; Myeloid Differentiation Factor 88/genetics ; Adaptor Proteins, Signal Transducing ; Epithelial Cells ; }, abstract = {Melatonin has various physiological effects, such as the maintenance of circadian rhythms, anti-inflammatory functions, and regulation of intestinal barriers. The regulatory functions of melatonin in gut microbiota remodeling have also been well clarified; however, the role of gut microbiota in regulating host melatonin production remains poorly understood. To address this, we studied the contribution of gut microbiota to host melatonin production using gut microbiota-perturbed models. We demonstrated that antibiotic-treated and germ-free mice possessed diminished melatonin levels in the serum and elevated melatonin levels in the colon. The influence of the intestinal microbiota on host melatonin production was further confirmed by fecal microbiota transplantation. Notably, Lactobacillus reuteri (L. R) and Escherichia coli (E. coli) recapitulated the effects of gut microbiota on host melatonin production. Mechanistically, L. R and E. coli activated the TLR2/4/MyD88/NF-κB signaling pathway to promote expression of arylalkylamine N-acetyltransferase (AANAT, a rate-limiting enzyme for melatonin production), and MyD88 deficiency in colonic epithelial cells abolished the influence of intestinal microbiota on colonic melatonin production. Collectively, we revealed a specific underlying mechanism of gut microbiota to modulate host melatonin production, which might provide novel therapeutic ideas for melatonin-related diseases.}, } @article {pmid38352546, year = {2024}, author = {Kellogg, TD and Ceglia, S and Mortzfeld, BM and Zeamer, AL and Foley, SE and Ward, DV and Bhattarai, SK and McCormick, BA and Reboldi, A and Bucci, V}, title = {Microbiota encoded fatty-acid metabolism expands tuft cells to protect tissues homeostasis during Clostridioides difficile infection in the large intestine.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.29.574039}, pmid = {38352546}, abstract = {Metabolic byproducts of the intestinal microbiota are crucial in maintaining host immune tone and shaping inter-species ecological dynamics. Among these metabolites, succinate is a driver of tuft cell (TC) differentiation and consequent type 2 immunity-dependent protection against invading parasites in the small intestine. Succinate is also a growth enhancer of the nosocomial pathogen Clostridioides difficile in the large intestine. To date, no research has shown the role of succinate in modulating TC dynamics in the large intestine, or the relevance of this immune pathway to C. difficile pathophysiology. Here we reveal the existence of a three-way circuit between commensal microbes, C. difficile and host epithelial cells which centers around succinate. Through selective microbiota depletion experiments we demonstrate higher levels of type 2 cytokines leading to expansion of TCs in the colon. We then demonstrate the causal role of the microbiome in modulating colonic TC abundance and subsequent type 2 cytokine induction using rational supplementation experiments with fecal transplants and microbial consortia of succinate-producing bacteria. We show that administration of a succinate-deficient Bacteroides thetaiotaomicron knockout (Δfrd) significantly reduces the enhanced type 2 immunity in mono-colonized mice. Finally, we demonstrate that mice prophylactically administered with the consortium of succinate-producing bacteria show reduced C. difficile -induced morbidity and mortality compared to mice administered with heat-killed bacteria or the vehicle. This effect is reduced in a partial tuft cell knockout mouse, Pou2f3 [+/-] , and nullified in the tuft cell knockout mouse, Pou2f3 [-/-] , confirming that the observed protection occurs via the TC pathway. Succinate is an intermediary metabolite of the production of short-chain fatty acids, and its concentration often increases during dysbiosis. The first barrier to enteric pathogens alike is the intestinal epithelial barrier, and host maintenance and strengthening of barrier integrity is vital to homeostasis. Considering our data, we propose that activation of TC by the microbiota-produced succinate in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by intestinal pathogens.}, } @article {pmid38351748, year = {2024}, author = {Wang, J and Gao, Y and Ren, S and Li, J and Chen, S and Feng, J and He, B and Zhou, Y and Xuan, R}, title = {Gut microbiota-derived trimethylamine N-Oxide: a novel target for the treatment of preeclampsia.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2311888}, pmid = {38351748}, issn = {1949-0984}, mesh = {Female ; Pregnancy ; Child ; Humans ; Mice ; Animals ; *Pre-Eclampsia/therapy ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Cohort Studies ; Endothelial Cells/metabolism ; Methylamines/metabolism ; }, abstract = {Pre-eclampsia (PE) is the most common complication of pregnancy and seriously threatens the health and safety of the mother and child. Studies have shown that an imbalance in gut microbiota can affect the progression of PE. Trimethylamine N-oxide (TMAO) is an intestinal microbiota-derived metabolite that is thought to be involved in the occurrence of PE; however, its causal relationship and mechanism remain unclear. In this clinical cohort study, including 28 patients with eclampsia and 39 matched healthy controls, fecal samples were collected for 16S rRNA gene sequencing, and serum was collected for targeted metabolomics research. The results showed that the level of TMAO and the abundance of its source bacteria had significantly increased in patients with PE, and were positively correlated with the clinical progression of PE. Fecal microbiota transplantation (FMT) was applied to an antibiotic-depleted-treated mouse model and targeted inhibition of TMAO. The results of the FMT experiment revealed that mice that received fecal microbiota transplantation from patients with PE developed typical PE symptoms and increased oxidative stress and inflammatory damage, both of which were reversed by 3,3-Dimethyl-1-butanol (DMB), a TMAO inhibitor, which also improved pregnancy outcomes in the model mice. Similar results were obtained in the classical NG-Nitroarginine methyl ester (L-NAME) induced PE mouse model. Mechanistically, TMAO promotes the progression of PE by regulating inflammatory and oxidative stress-related signaling pathways, affecting the migration and angiogenesis of vascular endothelial cells, as well as the migration and invasion of trophoblast cells. Our results reveal the role and mechanism of gut microbiota and TMAO in the progression of PE, provides new ideas for exploring the pathogenesis and therapeutic targets of PE, and determines the potential application value of TMAO as a target for PE intervention.}, } @article {pmid38350484, year = {2023}, author = {Yin, S and Liao, Y and Ma, Y and Han, X and Yang, Z and Fang, J and Alahmadi, RM and Hatamleh, AA and Duraipandiyan, V and Gurusunathan, VR and Arokiyaraj, S and Liu, G}, title = {Lactiplantibacillus plantarum and faecal microbiota transplantation can improve colitis in mice by affecting gut microbiota and metabolomics.}, journal = {Beneficial microbes}, volume = {14}, number = {6}, pages = {609-622}, doi = {10.1163/18762891-20230046}, pmid = {38350484}, issn = {1876-2891}, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Fecal Microbiota Transplantation ; RNA, Ribosomal, 16S/genetics ; *Probiotics/analysis ; *Colitis/chemically induced/therapy ; *Inflammatory Bowel Diseases/therapy ; *Lactobacillus plantarum/physiology ; Dextran Sulfate ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Gut microbiota may have therapeutic effects on inflammatory bowel disease (IBD). Regulating intestinal microbiota through Lactiplantibacillus plantarum (L. plantarum) and faecal microbiota transplantation (FMT) is a novel approach to treating IBD. This study aimed to explore the effect of L. plantarum and FMT pretreatment in alleviating colitis in mice. Five groups of mice (n = 6 per group) were included: CON group, DSS group (dextran sodium sulphate-induced colitis mice), LP-DSS pretreatment group (colitis mice were given strain L. plantarum and 5% DSS), DSS-FMT group (mice pretreated with faecal microbiota transplantation were given 5% DSS), and LP-FMT pretreatment group (mice pretreated with faecal microbiota transplantation and L. plantarum were given 5% DSS). Serum metabolites and intestinal microbiota were analysed by 16S rRNA sequencing liquid chromatography-mass spectrometry (LC-MS). The results demonstrated that L. plantarum and FMT improved gut microbiota in mice by increasing Firmicutes and decreasing the Bacteroidetes. In the serum metabolomics analysis, there were 11 differential metabolites in the DSS-FMT and LP-FMT pretreatment groups, and these differential metabolites were mainly glycerophospholipids and sphingolipids. It is worth noting that Lachnospira and Lactobacillus were positively associated with 8 differential metabolites. These results suggest that L. plantarum and FMT can regulate intestinal microorganisms and serum metabolomics to alleviate inflammation.}, } @article {pmid38347911, year = {2024}, author = {Zhou, X and Chen, R and Cai, Y and Chen, Q}, title = {Fecal Microbiota Transplantation: A Prospective Treatment for Type 2 Diabetes Mellitus.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {17}, number = {}, pages = {647-659}, pmid = {38347911}, issn = {1178-7007}, abstract = {PURPOSE OF REVIEW: The aim of this review is to summarize the role of gastrointestinal microbiome (GM) in the development of type 2 diabetes mellitus (T2DM). Besides, we discuss the feasibility of applying FMT in the treatment of T2DM and propose a series of processes to refine the use of FMT in the treatment of T2DM.

RECENT FINDINGS: T2DM is a metabolic disease which is connected with the GM. According to many researches, GM can produce a variety of metabolites such as bile acid, short chain fatty acids, lipopolysaccharides and trimethylamine oxide which play an important role in metabolism. FMT is a method to regulate GM and has been observed to be effective in the treatment of metabolic diseases such as T2DM in some mouse models and people. However, there is still a lack of direct evidence for the use of FMT in the treatment of T2DM, and the process of FMT is not standardized.

SUMMARY: Dysregulation of GM is closely related to the development of T2DM. Promoting the conversion of GM in T2DM patients to normal population through FMT can reduce insulin resistance and lower their blood glucose level, which is an optional treatment for T2DM patients in the future. At present, the feasibility and limitations of applying FMT to the treatment of T2DM need to be further studied.}, } @article {pmid38347627, year = {2024}, author = {Behling, AH and Wilson, BC and Ho, D and Cutfield, WS and Vatanen, T and O'Sullivan, JM}, title = {Horizontal gene transfer after faecal microbiota transplantation in adolescents with obesity.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {26}, pmid = {38347627}, issn = {2049-2618}, mesh = {Adolescent ; Humans ; Fecal Microbiota Transplantation/methods ; Gene Transfer, Horizontal ; *Pediatric Obesity ; *Microbiota ; *Gastrointestinal Microbiome/genetics ; Bacteria/genetics ; Feces/microbiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Horizontal gene transfer (HGT) describes the transmission of DNA outside of direct ancestral lineages. The process is best characterised within the bacterial kingdom and can enable the acquisition of genetic traits that support bacterial adaptation to novel niches. The adaptation of bacteria to novel niches has particular relevance for faecal microbiota transplantation (FMT), a therapeutic procedure which aims to resolve gut-related health conditions of individuals, through transplanted gut microbiota from healthy donors.

RESULTS: Three hundred eighty-one stool metagenomic samples from a placebo-controlled FMT trial for obese adolescents (the Gut Bugs Trial) were analysed for HGT, using two complementary methodologies. First, all putative HGT events, including historical HGT signatures, were quantified using the bioinformatics application WAAFLE. Second, metagenomic assembly and gene clustering were used to assess and quantify donor-specific genes transferred to recipients following the intervention. Both methodologies found no difference between the level of putative HGT events in the gut microbiomes of FMT and placebo recipients, post-intervention. HGT events facilitated by engrafted donor species in the FMT recipient gut at 6 weeks post-intervention were identified and characterised. Bacterial strains contributing to this subset of HGT events predominantly belonged to the phylum Bacteroidetes. Engraftment-dependent horizontally transferred genes were retained within recipient microbiomes at 12 and 26 weeks post-intervention.

CONCLUSION: Our study suggests that novel microorganisms introduced into the recipient gut following FMT have no impact on the basal rate of HGT within the human gut microbiome. Analyses of further FMT studies are required to assess the generalisability of this conclusion across different FMT study designs and for the treatment of different gut-related conditions. Video Abstract.}, } @article {pmid38346843, year = {2024}, author = {}, title = {Correction: Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial.}, journal = {RMD open}, volume = {10}, number = {1}, pages = {}, doi = {10.1136/rmdopen-2023-003750corr1}, pmid = {38346843}, issn = {2056-5933}, } @article {pmid38345223, year = {2024}, author = {Pett, N and Hunter, M and Carranza García, NA and Seo, JH and Collins, SR and Rohwer, F and Osborne, LC and Tropini, C}, title = {T4 Bacteriophage and E. coli Interaction in the Murine Intestine: A Prototypical Model for Studying Host-Bacteriophage Dynamics In Vivo.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {203}, pages = {}, doi = {10.3791/65906}, pmid = {38345223}, issn = {1940-087X}, mesh = {Humans ; Mice ; Animals ; *Bacteriophages/physiology ; Bacteriophage T4 ; Escherichia coli ; Gastrointestinal Tract/microbiology ; Intestines ; *Microbiota ; Bacteria ; }, abstract = {Bacteriophages (phages) are viruses that infect bacteria with species- and strain-level specificity and are the most abundant biological entities across all known ecosystems. Within bacterial communities, such as those found in the gut microbiota, phages are implicated in regulating microbiota population dynamics and driving bacterial evolution. There has been renewed interest in phage research in the last decade, in part due to the host-specific killing capabilities of lytic phages, which offer a promising tool to counter the increasing threat of antimicrobial resistant bacteria. Furthermore, recent studies demonstrating that phages adhere to intestinal mucus suggest they may have a protective role in preventing bacterial invasion into the underlying epithelium. Importantly, like bacterial microbiomes, disrupted phageomes have been associated with worsened outcomes in diseases such as inflammatory bowel disease. Previous studies have demonstrated that phages can modulate the microbiome of animals and humans through fecal filtrate transplants, benefiting the host's health. With this recent wave of research comes the necessity to establish and standardize protocols for studying phages in the context of the gut microbiome. This protocol provides a set of procedures to study isolated T4 phages and their bacterial host, Escherichia coli, in the context of the murine gastrointestinal tract. The methods described here outline how to start from a phage lysate, administer it to mice and assess effects on bacterial host and phage levels. This protocol can be modified and applied to other phage-bacterial pairs and provides a starting point for studying host-phage dynamics in vivo.}, } @article {pmid38344334, year = {2024}, author = {Deac, IŞ and Ofrim, AM and Fărcaş, RA and Grad, S and Popa, ŞL and Dumitraşcu, DL}, title = {The management of Clostridioides difficile infection: from empirism to evidence.}, journal = {Medicine and pharmacy reports}, volume = {97}, number = {1}, pages = {5-11}, pmid = {38344334}, issn = {2668-0572}, abstract = {Clostridioides difficile infection (CDI) in clinical practice represents a challenge for its management and also prevention of recurrence. Even though there are updated guidelines for infection prevention, control and treatment, CDI remains a leading cause of healthcare acquired diarrhea with increasing incidence in the community. We present here a synthesis of the most recent international guidelines on the management of CDI. In 2021 updated guidelines on the treatment of CDI in adults were published by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA), American College of Gastroenterology (ACG) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). These guidelines focused on CDI management in adults, including new data on the clinical efficacy of Fidaxomicin (FDX) and Bezlotoxumab. The 2017 publication of IDSA and SHEA - Clinical Practice Guidelines for Clostridium difficile infection also included pediatric treatment recommendations that are not a part of the 2021 update. Vancomycin (VAN) treatment for an initial CDI episode remains an acceptable alternative to FDX, considering the monetary and logistical challenge of acquiring FDX. There is growing literature on fecal microbiota transplantation (FMT) and the 2021 guidelines describe its role in severe complicated refractory CDI cases and for which surgical management is not feasible. Moreover, there are new data on the secondary prophylaxis with VAN in refractory CDI in patients with risk factors who receive broad spectrum antibiotics.}, } @article {pmid38344171, year = {2024}, author = {Zhu, H and Wang, W and Li, Y}, title = {The interplay between microbiota and brain-gut axis in epilepsy treatment.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1276551}, pmid = {38344171}, issn = {1663-9812}, abstract = {The brain-gut axis plays a vital role in connecting the cognitive and emotional centers of the brain with the intricate workings of the intestines. An imbalance in the microbiota-mediated brain-gut axis extends far beyond conditions like Irritable Bowel Syndrome (IBS) and obesity, playing a critical role in the development and progression of various neurological disorders, including epilepsy, depression, Alzheimer's disease (AD), and Parkinson's disease (PD). Epilepsy, a brain disorder characterized by unprovoked seizures, affects approximately 50 million people worldwide. Accumulating evidence suggests that rebuilding the gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and ketogenic diets (KD) can benefit drug-resistant epilepsy. The disturbances in the gut microbiota could contribute to the toxic side effects of antiepileptic drugs and the development of drug resistance in epilepsy patients. These findings imply the potential impact of the gut microbiota on epilepsy and suggest that interventions targeting the microbiota, such as the KD, hold promise for managing and treating epilepsy. However, the full extent of the importance of microbiota in epilepsy treatment is not yet fully understood, and many aspects of this field remain unclear. Therefore, this article aims to provide an overview of the clinical and animal evidence supporting the regulatory role of gut microbiota in epilepsy, and of potential pathways within the brain-gut axis that may be influenced by the gut microbiota in epilepsy. Furthermore, we will discuss the recent advancements in epilepsy treatment, including the KD, fecal microbiota transplantation, and antiseizure drugs, all from the perspective of the gut microbiota.}, } @article {pmid38320845, year = {2024}, author = {Tweedie-Cullen, RY and Leong, K and Wilson, BC and Derraik, JGB and Albert, BB and Monk, R and Vatanen, T and Creagh, C and Depczynski, M and Edwards, T and Beck, K and Thabrew, H and O'Sullivan, JM and Cutfield, WS}, title = {Protocol for the Gut Bugs in Autism Trial: a double-blind randomised placebo-controlled trial of faecal microbiome transfer for the treatment of gastrointestinal symptoms in autistic adolescents and adults.}, journal = {BMJ open}, volume = {14}, number = {2}, pages = {e074625}, pmid = {38320845}, issn = {2044-6055}, mesh = {Adult ; Humans ; Adolescent ; *Autistic Disorder/therapy ; *Autism Spectrum Disorder/therapy ; Fecal Microbiota Transplantation/methods ; Quality of Life ; *Gastrointestinal Diseases/therapy ; Double-Blind Method ; *Gastrointestinal Microbiome ; Treatment Outcome ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Autism (formally autism spectrum disorder) encompasses a group of complex neurodevelopmental conditions, characterised by differences in communication and social interactions. Co-occurring chronic gastrointestinal symptoms are common among autistic individuals and can adversely affect their quality of life. This study aims to evaluate the efficacy of oral encapsulated faecal microbiome transfer (FMT) in improving gastrointestinal symptoms and well-being among autistic adolescents and adults.

METHODS AND ANALYSIS: This double-blind, randomised, placebo-controlled trial will recruit 100 autistic adolescents and adults aged 16-45 years, who have mild to severe gastrointestinal symptoms (Gastrointestinal Symptoms Rating Scale (GSRS) score ≥2.0). We will also recruit eight healthy donors aged 18-32 years, who will undergo extensive clinical screening. Recipients will be randomised 1:1 to receive FMT or placebo, stratified by biological sex. Capsules will be administered over two consecutive days following an overnight bowel cleanse with follow-up assessments at 6, 12 and 26 weeks post-treatment. The primary outcome is GSRS score at 6 weeks. Other assessments include anthropometry, body composition, hair cortisol concentration, gut microbiome profile, urine/plasma gut-derived metabolites, plasma markers of gut inflammation/permeability and questionnaires on general well-being, sleep quality, physical activity, food diversity and treatment tolerability. Adverse events will be recorded and reviewed by an independent data monitoring committee.

ETHICS AND DISSEMINATION: Ethics approval for the study was granted by the Central Health and Disability Ethics Committee on 24 August 2021 (reference number: 21/CEN/211). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences.

TRIAL REGISTRATION NUMBER: ACTRN12622000015741.}, } @article {pmid38343539, year = {2024}, author = {Luqman, A and Hassan, A and Ullah, M and Naseem, S and Ullah, M and Zhang, L and Din, AU and Ullah, K and Ahmad, W and Wang, G}, title = {Role of the intestinal microbiome and its therapeutic intervention in cardiovascular disorder.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1321395}, pmid = {38343539}, issn = {1664-3224}, abstract = {The gut microbiome is a heterogeneous population of microbes comprising viruses, bacteria, fungi, and protozoa. Such a microbiome is essential for sustaining host equilibrium, and its impact on human health can be altered by a variety of factors such as external variables, social behavior, age, nutrition, and genetics. Gut microbes' imbalances are related to a variety of chronic diseases including cancer, obesity, and digestive disorders. Globally, recent findings show that intestinal microbes have a significant role in the formation of cardiovascular disease (CVD), which is still the primary cause of fatalities. Atherosclerosis, hypertension, diabetes, inflammation, and some inherited variables are all cardiovascular risk variables. However, studies found correlations between metabolism, intestinal flora, and dietary intake. Variations in the diversity of gut microbes and changes in their activity are thought to influence CVD etiology. Furthermore, the gut microbiota acts as an endocrine organ, producing bioactive metabolites such as TMA (trimethylamine)/TMAO (trimethylamine N-oxide), SCFA (short-chain fatty acids), and bile acids, which have a substantial impact on host wellness and disease by multiple mechanisms. The purpose of this overview is to compile current evidence highlighting the intricate links between gut microbiota, metabolites, and the development of CVD. It focuses on how intestinal dysbiosis promotes CVD risk factors such as heart failure, hypertension, and atherosclerosis. This review explores the normal physiology of intestinal microbes and potential techniques for targeting gut bacteria for CVD treatment using various microbial metabolites. It also examines the significance of gut bacteria in disease treatment, including supplements, prebiotics, probiotics, antibiotic therapies, and fecal transplantation, which is an innovative approach to the management of CVD. As a result, gut bacteria and metabolic pathways become increasingly attractive as potential targets for CVD intervention.}, } @article {pmid38340564, year = {2024}, author = {Sun, H and Yang, B and Zhu, X and Li, Q and Song, E and Song, Y}, title = {Oral exposure of polystyrene microplastics and doxycycline affects mice neurological function via gut microbiota disruption: The orchestrating role of fecal microbiota transplantation.}, journal = {Journal of hazardous materials}, volume = {467}, number = {}, pages = {133714}, doi = {10.1016/j.jhazmat.2024.133714}, pmid = {38340564}, issn = {1873-3336}, abstract = {The debris of plastics with a size < 5 mm, called microplastics, possess long-lived legacies of plastic pollution and a growing threat to human beings. The adverse effects and corresponding molecular mechanisms of microplastics are still largely unknown and must be prioritized. Antibiotics commonly co-existed with microplastics; the current study investigated the syngenetic toxic effect of doxycycline (Dox) and polystyrene microplastics (PS). Specifically, we found that Dox combined with PS exposure perturbed gut microbiota homeostasis in mice, which mediated brain lesions and inflammation with a concomitant decline in learning and memory behaviors through the gut-brain axis. Of note, PS exposure resulted in intestinal damage and structural change, but Dox did not accelerate the disruption of intestinal barrier integrity in PS-treated mice. Interestingly, fecal microbiota transplantation (FMT) can reverse neurological impairment caused by combined PS and Dox exposure via compensating gut microbes; therefore, the learning and memory abilities of mice were also recovered. This work not only provides insights into the syngenetic effect of microplastics and antibiotics and highlights their distal neurotoxicity through the gut-brain axis but also offers a promising strategy against their combined toxicity.}, } @article {pmid38339251, year = {2024}, author = {Vongsavath, T and Rahmani, R and Tun, KM and Manne, V}, title = {The Use of Fecal Microbiota Transplant in Overcoming and Modulating Resistance to Anti-PD-1 Therapy in Patients with Skin Cancer.}, journal = {Cancers}, volume = {16}, number = {3}, pages = {}, pmid = {38339251}, issn = {2072-6694}, abstract = {While immune checkpoint inhibitors have evolved into the standard of care for advanced melanoma, 40-50% of melanoma cases progress while on therapies. The relationship between bacterium and carcinogenesis is well founded, such as in H. pylori in gastric cancers, and Fusobacterium in colorectal cancers. This interplay between dysbiosis and carcinogenesis questions whether changes in the microbiome could affect treatment. Thus, FMT may find utility in modifying the efficacy of anti-PD-1. This review aims to examine the use of FMT in treatment-resistant melanoma. A literature search was performed using the keywords "fecal microbiota transplant" and "skin cancer". Studies were reviewed for inclusion criteria and quality and in the final stage, and three studies were included. Overall objective responses were reported in 65% of patients who were able to achieve CR, and 45% who achieved PR. Clinical benefit rate of combined CR/PR with stable disease greater or equal to 6 months was 75%. Reported objective responses found durable stable disease lasting 12 months. Overall survival was 7 months, and overall PRS was 3 months. As for the evaluation of safety, many patients reported grade 1-2 FMT related AE. Only following the administration of anti-PD-1 therapy were there a grade 3 or higher AE.}, } @article {pmid38339169, year = {2024}, author = {Chechushkov, A and Desyukevich, P and Yakovlev, T and Al Allaf, L and Shrainer, E and Morozov, V and Tikunova, N}, title = {Sterile Fecal Microbiota Transplantation Boosts Anti-Inflammatory T-Cell Response in Ulcerative Colitis Patients.}, journal = {International journal of molecular sciences}, volume = {25}, number = {3}, pages = {}, pmid = {38339169}, issn = {1422-0067}, support = {21-14-00360//Russian Science Foundation/ ; }, abstract = {Ulcerative colitis is a chronic immune-mediated disease of unclear etiology, affecting people of different ages and significantly reducing the quality of life. Modern methods of therapy are mainly represented by anti-inflammatory drugs and are not aimed at a specific pathogenetic factor. In this study, we investigated the effect of transplantation of sterile stool filtrate from healthy donors on the induction of anti-inflammatory immune mechanisms. It was shown that performing such a procedure in patients with ulcerative colitis caused the appearance of T helper cells in the blood, which reacted to the content of sterile stool filtrates in an antigen-specific manner and produced IL-10. At the same time, cells of the same patients before therapy in response to the addition of sterile stool filtrates were less reactive and predominantly produced IL-4, indicating its pro-inflammatory skewing. The obtained data demonstrated the effect of an anti-inflammatory shift in the T-helper response after transplantation of sterile stool filtrate, which increased and persisted for at least three months after the procedure.}, } @article {pmid38334893, year = {2024}, author = {Singh, A and Midha, V and Chauhan, NS and Sood, A}, title = {Current perspectives on fecal microbiota transplantation in inflammatory bowel disease.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {38334893}, issn = {0975-0711}, abstract = {Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic modality within the domain of inflammatory bowel disease (IBD). While FMT has secured approval and demonstrated efficacy in addressing recurrent and refractory Clostridioides difficile infection, its application in IBD remains an area of active exploration and research. The current status of FMT in IBD reflects a nuanced landscape, with ongoing investigations delving into its effectiveness, safety and optimal implementation. Early-stage clinical trials and observational studies have provided insights into the potential of FMT to modulate the dysbiotic gut microbiota associated with IBD, aiming to mitigate inflammation and promote mucosal healing. However, considerable complexities persist, including variations in donor selection, treatment protocols and outcome assessments. Challenges in standardizing FMT protocols for IBD treatment are compounded by the dynamic nature of the gut microbiome and the heterogeneity of IBD itself. Despite these challenges, enthusiasm for FMT in IBD emanates from its capacity to address gut microbial dysbiosis, signifying a paradigm shift towards more comprehensive approaches in IBD management. As ongoing research progresses, an enhanced understanding of FMT's role in IBD therapy is anticipated. This article synthesizes the current status of FMT in IBD, elucidating the attendant challenges and aspiring towards the refinement of its application for improved patient outcomes.}, } @article {pmid38334013, year = {2024}, author = {Liu, Y and Li, Z and Sun, T and Li, Z and Manyande, A and Xiang, H and He, Z}, title = {Gut microbiota regulates hepatic ischemia-reperfusion injury-induced cognitive dysfunction via the HDAC2-ACSS2 axis in mice.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {2}, pages = {e14610}, pmid = {38334013}, issn = {1755-5949}, support = {81670240//National Natural Science Foundation of China/ ; 81873467//National Natural Science Foundation of China/ ; }, abstract = {AIMS: Hepatic ischemia-reperfusion injury (HIRI) resulting from hepatic inflow occlusion, which is a common procedure in liver surgery is inevitable. Previous research has confirmed that the cognitive dysfunction induced by HIRI is closely related to dysbiosis of the gut microbiota. This research aims to investigate the mechanisms underlying this complication.

METHODS: C57BL/6 mice underwent hepatic ischemia experimentally through the occlusion of the left hepatic artery and portal vein. To assess the HDAC2-ACSS2 axis, gut microbiota transplantation. Enzyme-linked immunosorbent assay and LC/MS short-chain fatty acid detection were utilized.

RESULTS: The findings indicated a notable decline in ACSS2 expression in the hippocampus of mice experiencing hepatic ischemia-reperfusion injury, emphasizing the compromised acetate metabolism in this particular area. Furthermore, the cognitive impairment phenotype and the dysregulation of the HDAC2-ACSS2 axis could also be transmitted to germ-free mice via fecal microbial transplantation. Enzyme-linked immunosorbent assay revealed reduced Acetyl-coenzyme A (acetyl-CoA) and Acetylated lysine levels in the hippocampus.

CONCLUSION: These findings suggest that acetate metabolism is impaired in the hippocampus of HIRI-induced cognitive impairment mice and related to dysbiosis, leading to compromised histone acetylation.}, } @article {pmid38332676, year = {2024}, author = {Jiang, Y and Wang, X and Chen, J and Zhang, Y and Hashimoto, K and Yang, JJ and Zhou, Z}, title = {Repeated (S)-ketamine administration ameliorates the spatial working memory impairment in mice with chronic pain: role of the gut microbiota-brain axis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2310603}, doi = {10.1080/19490976.2024.2310603}, pmid = {38332676}, issn = {1949-0984}, abstract = {Chronic pain is commonly linked with diminished working memory. This study explores the impact of the anesthetic (S)-ketamine on spatial working memory in a chronic constriction injury (CCI) mouse model, focusing on gut microbiome. We found that multiple doses of (S)-ketamine, unlike a single dose, counteracted the reduced spontaneous alteration percentage (%SA) in the Y-maze spatial working memory test, without affecting mechanical or thermal pain sensitivity. Additionally, repeated (S)-ketamine treatments improved the abnormal composition of the gut microbiome (β-diversity), as indicated by fecal 16S rRNA analysis, and increased levels of butyrate, a key gut - brain axis mediator. Protein analysis showed that these treatments also corrected the upregulated histone deacetylase 2 (HDAC2) and downregulated brain-derived neurotrophic factor (BDNF) in the hippocampi of CCI mice. Remarkably, fecal microbiota transplantation from mice treated repeatedly with (S)-ketamine to CCI mice restored %SA and hippocampal BDNF levels in CCI mice. Butyrate supplementation alone also improved %SA, BDNF, and HDAC2 levels in CCI mice. Furthermore, the TrkB receptor antagonist ANA-12 negated the beneficial effects of repeated (S)-ketamine on spatial working memory impairment in CCI mice. These results indicate that repeated (S)-ketamine administration ameliorates spatial working memory impairment in CCI mice, mediated by a gut microbiota - brain axis, primarily through the enhancement of hippocampal BDNF - TrkB signaling by butyrate.}, } @article {pmid38331095, year = {2024}, author = {Lin, Q and Kuypers, M and Baglaenko, Y and Cao, E and Hezaveh, K and Despot, T and de Amat Herbozo, C and Cruz Tleugabulova, M and Mauricio Umaña, J and McGaha, TL and Philpott, DJ and Mallevaey, T}, title = {The intestinal microbiota modulates the transcriptional landscape of iNKT cells at steady-state and following antigen exposure.}, journal = {Mucosal immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.mucimm.2024.02.002}, pmid = {38331095}, issn = {1935-3456}, abstract = {Invariant Natural Killer T (iNKT) cells are unconventional T cells that respond to microbe-derived glycolipid antigens. iNKT cells exert fast innate effector functions that regulate immune responses in a variety of contexts, including during infection, cancer, or inflammation. The roles these unconventional T cells play in intestinal inflammation remain poorly defined and vary based on the disease model and species. Our previous work suggested that the gut microbiota influenced iNKT cell functions during dextran sulfate sodium-induced colitis in mice. In this study, we show that iNKT cell homeostasis and response following activation are altered in germ-free mice. Using prenatal fecal transplant in specific pathogen-free mice, we show that the transcriptional signatures of iNKT cells at steady state and following αGC-mediated activation in vivo are modulated by the microbiota. Our data suggest that iNKT cells sense the microbiota at homeostasis independently of their TCR. Finally, iNKT cell transcriptional signatures are different in male and female mice. Collectively, our findings suggest that sex and the intestinal microbiota are important factors that regulate iNKT cell homeostasis and responses. A deeper understanding of microbiota-iNKT cell interactions and the impact of sex could improve the development of iNKT cell-based immunotherapies.}, } @article {pmid38329942, year = {2024}, author = {Zhan, K and Wu, H and Xu, Y and Rao, K and Zheng, H and Qin, S and Yang, Y and Jia, R and Chen, W and Huang, S}, title = {The function of the gut microbiota-bile acid-TGR5 axis in diarrhea-predominant irritable bowel syndrome.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0129923}, doi = {10.1128/msystems.01299-23}, pmid = {38329942}, issn = {2379-5077}, abstract = {Imbalanced gut microbiota (GM) and abnormal fecal bile acid (BA) are thought to be the key factors for diarrhea-predominant irritable bowel syndrome (IBS-D), but the underlying mechanism remains unclear. Herein, we explore the influence of the GM-BA-Takeda G-protein-coupled receptor 5 (TGR5) axis on IBS-D. Twenty-five IBS-D patients and fifteen healthy controls were recruited to perform BA-related metabolic and metagenomic analyses. Further, the microbiota-humanized IBS-D rat model was established by fecal microbial transplantation (FMT) to investigate the GM-BA-TGR5 axis effects on the colonic barrier and visceral hypersensitivity (VH) in IBS-D. Finally, we used chenodeoxycholic acid (CDCA), an important BA screened out by metabolome, to evaluate whether it affected diarrhea and VH via the TGR5 pathway. Clinical research showed that GM associated with bile salt hydrolase (BSH) activity such as Bacteroides ovatus was markedly reduced in the GM of IBS-D, accompanied by elevated total and primary BA levels. Moreover, we found that CDCA not only was increased as the most important primary BA in IBS-D patients but also could induce VH through upregulating TGR5 in the colon and ileum of normal rats. TGR5 inhibitor could reverse the phenotype, depression-like behaviors, pathological change, and level of fecal BSH in a microbiota-humanized IBS-D rat model. Our findings proved that human-associated FMT could successfully induce the IBS-D rat model, and the imbalanced GM-BA-TGR5 axis may promote colonic mucosal barrier dysfunction and enhance VH in IBS-D. IMPORTANCE Visceral hypersensitivity and intestinal mucosal barrier damage are important factors that cause abnormal brain-gut interaction in diarrhea-predominant irritable bowel syndrome (IBS-D). Recently, it was found that the imbalance of the gut microbiota-bile acid axis is closely related to them. Therefore, understanding the structure and function of the gut microbiota and bile acids and the underlying mechanisms by which they shape visceral hypersensitivity and mucosal barrier damage in IBS-D is critical. An examination of intestinal feces from IBS-D patients revealed that alterations in gut microbiota and bile acid metabolism underlie IBS-D and symptom onset. We also expanded beyond existing knowledge of well-studied gut microbiota and bile acid and found that Bacteroides ovatus and chenodeoxycholic acid may be potential bacteria and bile acid involved in the pathogenesis of IBS-D. Moreover, our data integration reveals the influence of the microbiota-bile acid-TGR5 axis on barrier function and visceral hypersensitivity.}, } @article {pmid38329115, year = {2024}, author = {Kesh, K and Tao, J and Ghosh, N and Jalodia, R and Singh, S and Dawra, R and Roy, S}, title = {Prescription opioids induced microbial dysbiosis worsens severity of chronic pancreatitis and drives pain hypersensitivity.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2310291}, pmid = {38329115}, issn = {1949-0984}, abstract = {Opioids, such as morphine and oxycodone, are widely used for pain management associated with chronic pancreatitis (CP); however, their impact on the progression and pain sensitivity of CP has never been evaluated. This report investigates the impact of opioid use on the severity of CP, pain sensitivity, and the gut microbiome. C57BL/6 mice were divided into control, CP, CP with morphine/oxycodone, and either morphine or oxycodone alone groups. CP was induced by administration of caerulein (50ug/kg/h, i.p. hourly x7, twice a week for 10 weeks). The mouse-to-pancreas weight ratio, histology, and Sirius red staining were performed to measure CP severity. Tail flick and paw pressure assays were used to measure thermal and mechanical pain. DNA was extracted from the fecal samples and subjected to whole-genome shotgun sequencing. Germ-free mice were used to validate the role of gut microbiome in sensitizing acute pancreatic inflammation. Opioid treatment exacerbates CP by increasing pancreatic necrosis, fibrosis, and immune-cell infiltration. Opioid-treated CP mice exhibited enhanced pain hypersensitivity and showed distinct clustering of the gut microbiome compared to untreated CP mice, with severely compromised gut barrier integrity. Fecal microbiota transplantation (FMT) from opioid-treated CP mice into germ-free mice resulted in pancreatic inflammation in response to a suboptimal caerulein dose. Together, these analyses revealed that opioids worsen the severity of CP and induce significant alterations in pain sensitivity and the gut microbiome in a caerulein CP mouse model. Microbial dysbiosis plays an important role in sensitizing the host to pancreatic inflammation.}, } @article {pmid38328082, year = {2024}, author = {Gray, SM and Moss, AD and Herzog, JW and Kashiwagi, S and Liu, B and Young, JB and Sun, S and Bhatt, A and Fodor, AA and Sartor, RB}, title = {Mouse Adaptation of Human Inflammatory Bowel Diseases Microbiota Enhances Colonization Efficiency and Alters Microbiome Aggressiveness Depending on Recipient Colonic Inflammatory Environment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.23.576862}, pmid = {38328082}, abstract = {Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis. Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10 [-/-] mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10 [-/-] mice. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10 [-/-] host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10 [-/-] mice than the distinct microbiota reassembled in non-inflamed WT hosts. Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer.}, } @article {pmid38328040, year = {2024}, author = {Bauer, KC and Trehan, R and Ruf, B and Myojin, Y and Benmebarek, MR and Ma, C and Seifert, M and Nur, A and Qi, J and Huang, P and Soliman, M and Green, BL and Wabitsch, S and Springer, DA and Rodriguez-Matos, FJ and Ghabra, S and Gregory, SN and Matta, J and Dawson, B and Golino, J and Xie, C and Dzutsev, A and Trinchieri, G and Korangy, F and Greten, TF}, title = {The Gut Microbiome Controls Liver Tumors via the Vagus Nerve.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.23.576951}, pmid = {38328040}, abstract = {Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8 [+] T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.}, } @article {pmid38325336, year = {2024}, author = {She, J and Tuerhongjiang, G and Guo, M and Liu, J and Hao, X and Guo, L and Liu, N and Xi, W and Zheng, T and Du, B and Lou, B and Gao, X and Yuan, X and Yu, Y and Zhang, Y and Gao, F and Zhuo, X and Xiong, Y and Zhang, X and Yu, J and Yuan, Z and Wu, Y}, title = {Statins aggravate insulin resistance through reduced blood glucagon-like peptide-1 levels in a microbiota-dependent manner.}, journal = {Cell metabolism}, volume = {36}, number = {2}, pages = {408-421.e5}, doi = {10.1016/j.cmet.2023.12.027}, pmid = {38325336}, issn = {1932-7420}, mesh = {Humans ; Animals ; *Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/therapeutic use ; *Insulin Resistance ; Atorvastatin/pharmacology/therapeutic use ; Glucagon-Like Peptide 1 ; *Glucose Intolerance/drug therapy ; Bile Acids and Salts ; Ursodeoxycholic Acid/pharmacology/therapeutic use ; *Microbiota ; }, abstract = {Statins are currently the most common cholesterol-lowering drug, but the underlying mechanism of statin-induced hyperglycemia is unclear. To investigate whether the gut microbiome and its metabolites contribute to statin-associated glucose intolerance, we recruited 30 patients with atorvastatin and 10 controls, followed up for 16 weeks, and found a decreased abundance of the genus Clostridium in feces and altered serum and fecal bile acid profiles among patients with atorvastatin therapy. Animal experiments validated that statin could induce glucose intolerance, and transplantation of Clostridium sp. and supplementation of ursodeoxycholic acid (UDCA) could ameliorate statin-induced glucose intolerance. Furthermore, oral UDCA administration in humans alleviated the glucose intolerance without impairing the lipid-lowering effect. Our study demonstrated that the statin-induced hyperglycemic effect was attributed to the Clostridium sp.-bile acids axis and provided important insights into adjuvant therapy of UDCA to lower the adverse risk of statin therapy.}, } @article {pmid38324560, year = {2024}, author = {Barko, P and Nguyen-Edquilang, J and Williams, DA and Gal, A}, title = {Fecal microbiome composition and diversity of cryopreserved canine stool at different duration and storage conditions.}, journal = {PloS one}, volume = {19}, number = {2}, pages = {e0294730}, doi = {10.1371/journal.pone.0294730}, pmid = {38324560}, issn = {1932-6203}, mesh = {Humans ; Dogs ; Animals ; *Specimen Handling ; Feces/microbiology ; *Microbiota ; Cryopreservation/veterinary ; Gastrointestinal Tract ; Bacteria/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Fresh-frozen stool banks intended for humans with gastrointestinal and metabolic disorders have been recently established and there are ongoing efforts to establish the first veterinary fresh-frozen stool bank. Fresh frozen stored feces provide an advantage of increased availability and accessibility to high-quality optimal donor fecal material. The stability of frozen canine feces regarding fecal microbiome composition and diversity has not been reported in dogs, providing the basis for this study. We hypothesized that fecal microbial composition and diversity of healthy dogs would remain stable when stored at -20°C and -80°C for up to 12 months compared to baseline samples evaluated before freezing. Stool samples were collected from 20 apparently healthy dogs, manually homogenized, cryopreserved in 20% glycerol and aliquoted, frozen in liquid nitrogen and stored at -20°C or -80°C for 3, 6, 9, and 12 months. At baseline and after period of storage, aliquots were thawed and treated with propidium monoazide before fecal DNA extraction. Following long-read 16S-rRNA amplicon sequencing, bacterial community composition and diversity were compared among treatment groups. We demonstrated that fresh-frozen canine stools collected from 20 apparently healthy dogs could be stored for up to 12 months at -80°C with minimal change in microbial community composition and diversity and that storage at -80°C is superior to storage at -20°C. We also found that differences between dogs had the largest effect on community composition and diversity. Relative abundances of certain bacterial taxa, including those known to be short-chain fatty acid producers, varied significantly with specific storage temperatures and duration. Further work is required to ascertain whether fecal donor material that differs in bacterial community composition and diversity across storage conditions and duration could lead to differences in clinical efficacy for specific clinical indications of fecal microbiota transplantation.}, } @article {pmid38323255, year = {2024}, author = {Prayag, PS and Patwardhan, SA and Ajapuje, PS and Melinkeri, S and Gadhikar, H and Palnitkar, S and Simbasivam, R and Joshi, RS and Baheti, A and Sheth, US and Prayag, AP}, title = {Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India.}, journal = {Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine}, volume = {28}, number = {2}, pages = {106-110}, doi = {10.5005/jp-journals-10071-24607}, pmid = {38323255}, issn = {0972-5229}, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is an emerging option for recurrent or refractory Clostridium difficile-associated diarrhea (CDAD). We describe a single-center experience of FMT in hematopoietic stem cell transplant (HSCT) recipients with CDAD in India.

METHODS: A prospective observational study of HSCT recipients with CDAD who received FMT in our center.

RESULTS: A total of 13 patients were included. All the patients were allogenic HSCT recipients; FMT was performed in seven patients due to refractory CDAD, in five patients due to the presence of both CDAD and graft vs host disease (GVHD), and in 1 patient due to recurrent CDAD. The approach to FMT was colonoscopic in 10 (77%) patients. Only one patient reported bacteremia and one patient had candidemia, both of which were unrelated to FMT. Of the 10 patients who had complete resolution of CDAD, only one patient presented with a recurrence of CDAD within 8 weeks post-FMT.

CONCLUSION: This is the first study from India using FMT as a therapeutic modality for CDAD in the setting of HSCT. Here we demonstrate that FMT in India is an effective option, especially when patients have refractory CDAD, recurrent CDAD, or both GVHD and CDAD. Further studies should explore the efficacy and feasibility of FMT in India.

HOW TO CITE THIS ARTICLE: Prayag PS, Patwardhan SA, Ajapuje PS, Melinkeri S, Gadhikar H, Palnitkar S, et al. Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India. Indian J Crit Care Med 2024;28(2):106-110.}, } @article {pmid38323251, year = {2024}, author = {Gopal, PB}, title = {Lurking Danger: Emerging Evidence.}, journal = {Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine}, volume = {28}, number = {2}, pages = {93-94}, doi = {10.5005/jp-journals-10071-24644}, pmid = {38323251}, issn = {0972-5229}, abstract = {How to cite this article: Gopal PB. Lurking Danger: Emerging Evidence. Indian J Crit Care Med 2024;28(2):93-94.}, } @article {pmid38322428, year = {2024}, author = {Wolstenholme, JT and Duong, NK and Brocato, ER and Bajaj, JS}, title = {Gut-Liver-Brain Axis and Alcohol Use Disorder: Treatment Potential of Fecal Microbiota Transplantation.}, journal = {Alcohol research : current reviews}, volume = {44}, number = {1}, pages = {01}, doi = {10.35946/arcr.v44.1.01}, pmid = {38322428}, issn = {2169-4796}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Alcoholism ; *Non-alcoholic Fatty Liver Disease/therapy ; *Liver Diseases, Alcoholic/therapy ; Alcohol Drinking ; }, abstract = {PURPOSE: Chronic alcohol use is a major cause of liver damage and death. In the United States, multiple factors have led to low utilization of pharmacotherapy for alcohol use disorder (AUD), including lack of provider knowledge and comfort in prescribing medications for AUD. Alcohol consumption has direct effects on the gut microbiota, altering the diversity of bacteria and leading to bacterial overgrowth. Growing evidence suggests that alcohol's effects on the gut microbiome may contribute to increased alcohol consumption and progression of alcohol-associated liver disease (ALD). This article reviews human and preclinical studies investigating the role of fecal microbiota transplantation (FMT) in ameliorating alcohol-associated alterations to the liver, gut, and brain resulting in altered behavior; it also discusses the therapeutic potential of FMT.

SEARCH METHODS: For this narrative review, a literature search was conducted in September 2022 of PubMed, Web of Science Core Collection, and Google Scholar to identify studies published between January 2012 and September 2022. Search terms used included "fecal microbiota transplantation" and "alcohol."

SEARCH RESULTS: Most results of the literature search were review articles or articles on nonalcoholic fatty liver disease; these were excluded. Of the remaining empirical manuscripts, very few described clinical or preclinical studies that were directly investigating the effects of FMT on alcohol drinking or related behaviors. Ultimately, 16 studies were included in the review.

DISCUSSION AND CONCLUSIONS: The literature search identified only a few studies that were directly investigating the effect of FMT on ALD or alcohol drinking and related behaviors. Largely proof-of-concept studies, these findings demonstrate that alcohol can alter the gut microbiome and that the microbiome can be transferred between humans and rodents to alter affective behaviors frequently associated with increased alcohol use. Other studies have shown promise of FMT or other probiotic supplementation in alleviating some of the symptoms associated with ALD and drinking. These results show that the implementation of FMT as a therapeutic approach is still in the investigatory stages.}, } @article {pmid38322318, year = {2024}, author = {Feng, P and Xue, X and Bukhari, I and Qiu, C and Li, Y and Zheng, P and Mi, Y}, title = {Gut microbiota and its therapeutic implications in tumor microenvironment interactions.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1287077}, doi = {10.3389/fmicb.2024.1287077}, pmid = {38322318}, issn = {1664-302X}, abstract = {The development of cancer is not just the growth and proliferation of a single transformed cell, but its tumor microenvironment (TME) also coevolves with it, which is primarily involved in tumor initiation, development, metastasis, and therapeutic responses. Recent years, TME has been emerged as a potential target for cancer diagnosis and treatment. However, the clinical efficacy of treatments targeting the TME, especially its specific components, remains insufficient. In parallel, the gut microbiome is an essential TME component that is crucial in cancer immunotherapy. Thus, assessing and constructing frameworks between the gut microbiota and the TME can significantly enhance the exploration of effective treatment strategies for various tumors. In this review the role of the gut microbiota in human cancers, including its function and relationship with various tumors was summarized. In addition, the interaction between the gut microbiota and the TME as well as its potential applications in cancer therapeutics was described. Furthermore, it was summarized that fecal microbiota transplantation, dietary adjustments, and synthetic biology to introduce gut microbiota-based medical technologies for cancer treatment. This review provides a comprehensive summary for uncovering the mechanism underlying the effects of the gut microbiota on the TME and lays a foundation for the development of personalized medicine in further studies.}, } @article {pmid38319728, year = {2024}, author = {Yu, X and Ou, J and Wang, L and Li, Z and Ren, Y and Xie, L and Chen, Z and Liang, J and Shen, G and Zou, Z and Zhao, C and Li, G and Hu, Y}, title = {Gut microbiota modulate CD8[+] T cell immunity in gastric cancer through Butyrate/GPR109A/HOPX.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2307542}, doi = {10.1080/19490976.2024.2307542}, pmid = {38319728}, issn = {1949-0984}, mesh = {Humans ; Mice ; Animals ; Butyrates/metabolism ; *Gastrointestinal Microbiome/physiology ; CD8-Positive T-Lymphocytes ; *Stomach Neoplasms ; Fatty Acids, Volatile/metabolism ; Butyric Acid ; Claudins ; }, abstract = {The gut microbiota and Short-chain fatty acids (SCFAs) can influence the progression of diseases, yet the role of these factors on gastric cancer (GC) remains uncertain. In this work, the analysis of the gut microbiota composition and SCFA content in the blood and feces of both healthy individuals and GC patients indicated that significant reductions in the abundance of intestinal bacteria involved in SCFA production were observed in GC patients compared with the controls. ABX mice transplanted with fecal microbiota from GC patients developed more tumors during the induction of GC and had lower levels of butyric acid. Supplementation of butyrate during the induction of gastric cancer along with H. pylori and N-methyl-N-nitrosourea (MNU) in WT in GPR109A[-/-]mice resulted in fewer tumors and more IFN-γ[+] CD8[+] T cells, but this effect was significantly weakened after knockout of GPR109A. Furthermore, In vitro GC cells and co-cultured CD8[+] T cells or CAR-Claudin 18.2[+] CD8[+] T cells, as well as in vivo tumor-bearing studies, have indicated that butyrate enhanced the killing function of CD8[+] T cells or CAR-Claudin 18.2[+] CD8[+] T cells against GC cells through G protein-coupled receptor 109A (GPR109A) and homologous domain protein homologous box (HOPX). Together, these data highlighted that the restoration of gut microbial butyrate enhanced CD8[+] T cell cytotoxicity via GPR109A/HOPX, thus inhibiting GC carcinogenesis, which suggests a novel theoretical foundation for GC management against GC.}, } @article {pmid38319686, year = {2024}, author = {Martini, S and Zaccaria, T and Gasbarrini, A and Cammarota, G and Romagnoli, R and Ianiro, G}, title = {Fecal microbiota transplantation before liver transplant in patient colonized with New Delhi metallo-beta-lactamase: Are we ready for a sequential approach?.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e14248}, doi = {10.1111/tid.14248}, pmid = {38319686}, issn = {1399-3062}, support = {GR-2018-12365734//Ricerca Finalizzata Giovani Ricercatori 2018 of the Italian Ministry of Health/ ; FIS_00001711//Fondo Italiano per la Scienza 2021 of the Italian Ministry of University and Research/ ; //BIOMIS grant of the Italian Ministry of Research/ ; }, } @article {pmid38317780, year = {2024}, author = {He, H and He, H and Mo, L and Yuan, Q and Xiao, C and Ma, Q and Yi, S and Zhou, T and You, Z and Zhang, J}, title = {Gut microbiota regulate stress resistance by influencing microglia-neuron interactions in the hippocampus.}, journal = {Brain, behavior, & immunity - health}, volume = {36}, number = {}, pages = {100729}, pmid = {38317780}, issn = {2666-3546}, abstract = {Communication among the brain, gut and microbiota in the gut is known to affect the susceptibility to stress, but the mechanisms involved are unclear. Here we demonstrated that stress resistance in mice was associated with more abundant Lactobacillus and Akkermansia in the gut, but less abundant Bacteroides, Alloprevotella, Helicobacter, Lachnoclostridium, Blautia, Roseburia, Colidextibacter and Lachnospiraceae NK4A136. Stress-sensitive animals showed higher permeability and stronger immune responses in their colon, as well as higher levels of pro-inflammatory cytokines in serum. Their hippocampus also showed more extensive microglial activation, abnormal interactions between microglia and neurons, and lower synaptic plasticity. Transplanting fecal microbiota from stress-sensitive mice into naïve ones perturbed microglia-neuron interactions and impaired synaptic plasticity in the hippocampus, translating to more depression-like behavior after stress exposure. Conversely, transplanting fecal microbiota from stress-resistant mice into naïve ones protected microglia from activation and preserved synaptic plasticity in the hippocampus, leading to less depression-like behavior after stress exposure. These results suggested that gut microbiota may influence resilience to chronic psychological stress by regulating microglia-neuron interactions in the hippocampus.}, } @article {pmid38317473, year = {2024}, author = {Chowdhury, M and Raj Chaudhary, N and Kaur, P and Goyal, A and Sahu, SK}, title = {Different Strategies Targeting Gut Microbiota for the Management of Several Disorders: A Sustainable Approach.}, journal = {Infectious disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715265267536231121095634}, pmid = {38317473}, issn = {2212-3989}, abstract = {BACKGROUND: A potential limelight is flashed on the Gut Microbiota (GM) in the human body, which confers additional psychological as well as physiological attributes to health. Other than just occupying a wide portion of the gastrointestinal tract, it also plays numerous functions in the systems of the body. Gut Microbiota is largely responsible for a considerably vast array of conditions such as obesity, diabetes ,other metabolic disorders, and cardiovascular disorders. Strategies targeting the gut microbiota have been proposed as a promising approach for the management of these disorders.

OBJECTIVE: This review aims to summarize the different strategies targeting the gut microbiota for the management of several disorders and to highlight the importance of a sustainable approach.

METHODS: A comprehensive literature search was conducted using various databases between 2008 and 2022 that focused on the use of prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation, dietary interventions, and antibiotics.

RESULTS: Different strategies targeting the gut microbiota for the management of several disorders were identified, including probiotics, prebiotics, synbiotics, postbiotics, fecal microbiota transplantation, and dietary interventions. Modification in diet and lifestyle, allowing favorable microbiota growth in the stomach, intake of prebiotics and probiotics, and fecal microbiota transplantation are amongst the widely accepted recent approaches allowing the application of GM in the field of treatment.

CONCLUSION: Although considerable steps in enhancing and understanding the mechanism of treatment with the help of gut microbiota are under progress, much diversified and elaborate research must be conducted in order to enhance and implement the use of GM with high effectiveness.}, } @article {pmid38317217, year = {2024}, author = {Xing, JH and Niu, TM and Zou, BS and Yang, GL and Shi, CW and Yan, QS and Sun, MJ and Yu, T and Zhang, SM and Feng, XZ and Fan, SH and Huang, HB and Wang, JH and Li, MH and Jiang, YL and Wang, JZ and Cao, X and Wang, N and Zeng, Y and Hu, JT and Zhang, D and Sun, WS and Yang, WT and Wang, CF}, title = {Gut microbiota-derived LCA mediates the protective effect of PEDV infection in piglets.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {20}, pmid = {38317217}, issn = {2049-2618}, support = {U21A20261， 721 32202819, 31941018, 31972696 and 32072888//National Natural Science Foundation of China/ ; CARS-35//China Agriculture Research System of MOF 722 and MARA/ ; 20190301042NY, YDZJ202102CXJD029, and 20210202102NC//Science and Technology Development Program of Jilin Province/ ; }, mesh = {Animals ; Swine ; *Gastrointestinal Microbiome ; *Porcine epidemic diarrhea virus ; *Coronavirus Infections/prevention & control/veterinary ; *Swine Diseases/prevention & control ; Disease Resistance ; }, abstract = {BACKGROUND: The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics.

RESULTS: Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids' deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8[+] CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8[+] CTLs to exert antiviral effects.

CONCLUSIONS: Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract.}, } @article {pmid38316929, year = {2024}, author = {Ritz, NL and Draper, LA and Bastiaanssen, TFS and Turkington, CJR and Peterson, VL and van de Wouw, M and Vlckova, K and Fülling, C and Guzzetta, KE and Burokas, A and Harris, H and Dalmasso, M and Crispie, F and Cotter, PD and Shkoporov, AN and Moloney, GM and Dinan, TG and Hill, C and Cryan, JF}, title = {The gut virome is associated with stress-induced changes in behaviour and immune responses in mice.}, journal = {Nature microbiology}, volume = {9}, number = {2}, pages = {359-376}, pmid = {38316929}, issn = {2058-5276}, support = {12/RC/2273_P2//Science Foundation Ireland (SFI)/ ; }, abstract = {The microbiota-gut-brain axis has been shown to play an important role in the stress response, but previous work has focused primarily on the role of the bacteriome. The gut virome constitutes a major portion of the microbiome, with bacteriophages having the potential to remodel bacteriome structure and activity. Here we use a mouse model of chronic social stress, and employ 16S rRNA and whole metagenomic sequencing on faecal pellets to determine how the virome is modulated by and contributes to the effects of stress. We found that chronic stress led to behavioural, immune and bacteriome alterations in mice that were associated with changes in the bacteriophage class Caudoviricetes and unassigned viral taxa. To determine whether these changes were causally related to stress-associated behavioural or physiological outcomes, we conducted a faecal virome transplant from mice before stress and autochthonously transferred it to mice undergoing chronic social stress. The transfer of the faecal virome protected against stress-associated behaviour sequelae and restored stress-induced changes in select circulating immune cell populations, cytokine release, bacteriome alterations and gene expression in the amygdala. These data provide evidence that the virome plays a role in the modulation of the microbiota-gut-brain axis during stress, indicating that these viral populations should be considered when designing future microbiome-directed therapies.}, } @article {pmid38316805, year = {2024}, author = {Prakash, A and Rubin, N and Staley, C and Onyeaghala, G and Wen, YF and Shaukat, A and Milne, G and Straka, RJ and Church, TR and Prizment, A}, title = {Effect of ginger supplementation on the fecal microbiome in subjects with prior colorectal adenoma.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {2988}, pmid = {38316805}, issn = {2045-2322}, mesh = {Adult ; Humans ; *Zingiber officinale ; RNA, Ribosomal, 16S/genetics/analysis ; *Colorectal Neoplasms/pathology ; Feces/chemistry ; *Microbiota ; *Adenoma/drug therapy ; Dietary Supplements ; }, abstract = {Ginger has been associated with a decreased incidence of colorectal cancer (CRC) through reduction in inflammatory pathways and inhibition of tumor growth. Recent pre-clinical models have implicated changes in the gut microbiome as a possible mediator of the ginger effect on CRC. We hypothesized that, in adults previously diagnosed with a colorectal adenoma, ginger supplementation would alter the fecal microbiome in the direction consistent with its CRC-inhibitory effect. Sixty-eight adults were randomized to take either ginger or placebo daily for 6 weeks, with a 6-week washout and longitudinal stool collection throughout. We performed 16S rRNA sequencing and evaluated changes in overall microbial diversity and the relative abundances of pre-specified CRC-associated taxa using mixed-effects logistic regression. Ginger supplementation showed no significant effect on microbial community structure through alpha or beta diversity. Of 10 pre-specified CRC-associated taxa, there were significant decreases in the relative abundances of the genera Akkermansia (p < 0.001), Bacteroides (p = 0.018), and Ruminococcus (p = 0.013) after 6-week treatment with ginger compared to placebo. Ginger supplementation led to decreased abundances of Akkermansia and Bacteroides, which suggests that ginger may have an inhibitory effect on CRC-associated taxa. Overall, ginger supplementation appears to have a limited effect on gut microbiome in patients with colorectal adenomas.}, } @article {pmid38316265, year = {2024}, author = {Qu, L and Ma, X and Wang, F}, title = {The roles of gut microbiome and metabolites associated with skin photoaging in mice by intestinal flora sequencing and metabolomics.}, journal = {Life sciences}, volume = {}, number = {}, pages = {122487}, doi = {10.1016/j.lfs.2024.122487}, pmid = {38316265}, issn = {1879-0631}, abstract = {Photoaging of skin, a chronic disease, can produce the appearance changes and cancer lesions of skin. Therefore, it is of great significance to investigate the mechanisms and explore effective methods to treat the disorder. Gut microbiota and intestinal metabolisms have critical roles in a variety of diseases. However, their roles on photoaging of skin were not well tested. In the present work, the results showed that compared with control group, the levels of MDA, SOD and CAT associated with oxidative stress, the levels of COL I, CER, and HA associated with skin function, and the mRNA levels of IL-1β, IL-6, TNF-α associated with inflammation after long-term exposure to ultraviolet radiation in mice were significantly changed. Skin pathological tissue was also seriously damaged. The protein levels of AQP3 and FLG were significantly decreased. Ultraviolet exposure also promoted skin photoaging by activating TNFR1/TRAF2-mediated MAPK pathway, in which the protein levels of P38/P-P38, c-FOS/P-c-FOS, MMP1, TNFR1 and TRAF2 were significantly increased in model mice compared with control group. In fecal microbiota transplantation (FMT) experiment, we found that the intestinal microbiome of control mice alleviated skin photoaging via adjusting the protein levels of P38/P-P38, c-FOS/P-c-FOS, MMP1, TNFR1 and TRAF2. 16S rRNA sequencing found that 1639 intestinal bacteria were found, in which 15 bacteria including norank_f_Ruminococcaceae, Lachnospirac -eae_NK4A136_group, Lachnoclostridium, etc., were significantly different at the genus level. Untargeted GC-TOF/MS and UHPLC-MS/MS metabolomics showed 72 and 188 metabolites including taurine, ornithine, L-arginine, L-histidine, sucrose with significant differences compared with control group. Then, amino acid targeting assay showed 10 amino acids including L-ornithine, L-arginine and L-citrulline with higher levels in control group compared with model group. In addition, we also found that the variation of Lachnoclostridium abundance may regulate L-arginine metabolism to affect skin photoaging. Some intestinal bacteria and metabolites including amino acids may be closely related to skin photoaging, which should provide new methods to treat skin photoaging in the future.}, } @article {pmid38314929, year = {2024}, author = {Diaz-Marugan, L and Rutsch, A and Kaindl, AM and Ronchi, F}, title = {The impact of microbiota and ketogenic diet interventions in the management of drug-resistant epilepsy.}, journal = {Acta physiologica (Oxford, England)}, volume = {}, number = {}, pages = {e14104}, doi = {10.1111/apha.14104}, pmid = {38314929}, issn = {1748-1716}, support = {//Helmut Horten Foundation/ ; 2020/R-Single/029//FISM-Fondazione Italiana Sclerosi Multipla-Cod/ ; //Biostime Institute Nutrition & Care (BINC)-Geneva/ ; //the Spanish Ministry of Universities (University of Barcelona)/ ; }, abstract = {AIM: Drug-resistant epilepsy (DRE) is a neurological disorder characterized by uncontrolled seizures. It affects between 10%-40% of the patients with epilepsy worldwide. Drug-resistant patients have been reported to have a different microbiota composition compared to drug-sensitive patients and healthy controls. Importantly, fecal microbiota transplantations (FMTs), probiotic and dietary interventions have been shown to be able to reduce seizure frequency and improve the quality of life in drug-resistant patients. The classic ketogenic diet (KD) and its modifications may reduce seizures in DRE in some patients, whereas in others they do not. The mechanisms mediating the dietary effects remain elusive, although it is known that gut microbes play an important role in transmitting dietary effects to the host. Indeed, specific commensal microbes differ even between responders and non-responders to KD treatment.

METHODS: In this narrative mini-review, we summarize what is known about the gut microbiota changes and ketogenic diets with special focus on patients with DRE.

RESULTS AND CONCLUSIONS: By highlighting unanswered questions and by suggesting future research directions, we map the route towards future improvement of successful DRE therapy.}, } @article {pmid38314132, year = {2024}, author = {Yuan, XY and Chen, YS and Liu, Z}, title = {Relationship among Parkinson's disease, constipation, microbes, and microbiological therapy.}, journal = {World journal of gastroenterology}, volume = {30}, number = {3}, pages = {225-237}, doi = {10.3748/wjg.v30.i3.225}, pmid = {38314132}, issn = {2219-2840}, mesh = {Humans ; *Parkinson Disease/complications/therapy/microbiology ; Constipation/etiology/therapy ; Fecal Microbiota Transplantation/adverse effects ; Prebiotics ; *Probiotics/therapeutic use ; }, abstract = {This comprehensive review elucidates the complex interplay between gut microbiota and constipation in Parkinson's disease (PD), a prevalent non-motor symptom contributing significantly to patients' morbidity. A marked alteration in the gut microbiota, predominantly an increase in the abundance of Proteobacteria and Bacteroidetes, is observed in PD-related constipation. Conventional treatments, although safe, have failed to effectively alleviate symptoms, thereby necessitating the development of novel therapeutic strategies. Microbiological interventions such as prebiotics, probiotics, and fecal microbiota transplantation (FMT) hold therapeutic potential. While prebiotics improve bowel movements, probiotics are effective in enhancing stool consistency and alleviating abdominal discomfort. FMT shows potential for significantly alleviating constipation symptoms by restoring gut microbiota balance in patients with PD. Despite promising developments, the causal relationship between changes in gut microbiota and PD-related constipation remains elusive, highlighting the need for further research in this expanding field.}, } @article {pmid38313244, year = {2024}, author = {Shah, YR and Ali, H and Tiwari, A and Guevara-Lazo, D and Nombera-Aznaran, N and Pinnam, BSM and Gangwani, MK and Gopakumar, H and Sohail, AH and Kanumilli, S and Calderon-Martinez, E and Krishnamoorthy, G and Thakral, N and Dahiya, DS}, title = {Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions.}, journal = {World journal of hepatology}, volume = {16}, number = {1}, pages = {17-32}, doi = {10.4254/wjh.v16.i1.17}, pmid = {38313244}, issn = {1948-5182}, abstract = {Fecal microbiota transplantation (FMT) offers a potential treatment avenue for hepatic encephalopathy (HE) by leveraging beneficial bacterial displacement to restore a balanced gut microbiome. The prevalence of HE varies with liver disease severity and comorbidities. HE pathogenesis involves ammonia toxicity, gut-brain communication disruption, and inflammation. FMT aims to restore gut microbiota balance, addressing these factors. FMT's efficacy has been explored in various conditions, including HE. Studies suggest that FMT can modulate gut microbiota, reduce ammonia levels, and alleviate inflammation. FMT has shown promise in alcohol-associated, hepatitis B and C-associated, and non-alcoholic fatty liver disease. Benefits include improved liver function, cognitive function, and the slowing of disease progression. However, larger, controlled studies are needed to validate its effectiveness in these contexts. Studies have shown cognitive improvements through FMT, with potential benefits in cirrhotic patients. Notably, trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care. Although evidence is promising, challenges remain: Limited patient numbers, varied dosages, administration routes, and donor profiles. Further large-scale, controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy. While FMT holds potential for HE management, ongoing research is needed to address these challenges, optimize protocols, and expand its availability as a therapeutic option for diverse hepatic conditions.}, } @article {pmid38312240, year = {2024}, author = {Huang, H and Jiang, J and Wang, X and Jiang, K and Cao, H}, title = {Exposure to prescribed medication in early life and impacts on gut microbiota and disease development.}, journal = {EClinicalMedicine}, volume = {68}, number = {}, pages = {102428}, doi = {10.1016/j.eclinm.2024.102428}, pmid = {38312240}, issn = {2589-5370}, abstract = {The gut microbiota during early life plays a crucial role in infant development. This microbial-host interaction is also essential for metabolism, immunity, and overall human health in later life. Early-life pharmaceutical exposure, mainly referring to exposure during pregnancy, childbirth, and infancy, may change the structure and function of gut microbiota and affect later human health. In this Review, we describe how healthy gut microbiota is established in early life. We summarise the commonly prescribed medications during early life, including antibiotics, acid suppressant medications and other medications such as antidepressants, analgesics and steroid hormones, and discuss how these medication-induced changes in gut microbiota are involved in the pathological process of diseases, including infections, inflammatory bowel disease, metabolic diseases, allergic diseases and neurodevelopmental disorders. Finally, we review some critical methods such as dietary therapy, probiotics, prebiotics, faecal microbiota transplantation, genetically engineered phages, and vagus nerve stimulation in early life, aiming to provide a new strategy for the prevention of adverse health outcomes caused by prescribed medications exposure in early life.}, } @article {pmid38309391, year = {2024}, author = {Zheng, YZ and Chen, QR and Yang, HM and Zhao, JA and Ren, LZ and Wu, YQ and Long, YL and Li, TM and Yu, Y}, title = {Modulation of gut microbiota by crude mulberry polysaccharide attenuates knee osteoarthritis progression in rats.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {129936}, doi = {10.1016/j.ijbiomac.2024.129936}, pmid = {38309391}, issn = {1879-0003}, abstract = {Mulberry (Morus alba L.), a kind of common fruits widely cultivated worldwide, has been proven various biological activities. However, its potential role in the progression of knee osteoarthritis (KOA) remains unclear. This study aims to investigate the potential protective effects of crude polysaccharide extracted from mulberry fruit, referred to as a complex blend of polysaccharides and other unidentified extracted impurities, on KOA progression. The KOA rats were established by injection of 1 mg sodium monoiodoacetate into knee, and administrated with crude mulberry polysaccharide (Mup) by gastric gavage for 4 weeks. Furthermore, intestinal bacteria clearance assay (IBCA) and fecal microbiota transplantation were conducted for the evaluation of the effect of gut microbiota (GM) on KOA. Our findings demonstrated that Mup, particularly at a dosage of 200 mg/kg, effectively improved abnormal gait patterns, reduced the level of inflammation, mitigated subchondral bone loss, restored compromised joint surfaces, alleviated cartilage destruction, and positively modulated the dysregulated profile of GM in KOA rats. Moreover, IBCA compromised the protective effects of Mup, while transplantation of fecal bacteria from Mup-treated rats facilitated KOA recovery. Collectively, our study suggested that Mup had the potential to ameliorate the progression of KOA, potentially through its modulation of GM profile.}, } @article {pmid38309340, year = {2024}, author = {Yu, K and Song, Y and Wang, N and Yu, X and Sun, T and Yu, H and Ruan, Z and Qiu, Y}, title = {Exposure of Danio rerio to environmental sulfamethoxazole may contribute to neurobehavioral abnormalities via gut microbiome disturbance.}, journal = {The Science of the total environment}, volume = {}, number = {}, pages = {170546}, doi = {10.1016/j.scitotenv.2024.170546}, pmid = {38309340}, issn = {1879-1026}, abstract = {The neurotoxic effects and mechanisms of low-dose and long-term sulfamethoxazole (SMZ) exposure remain unknown. This study exposed zebrafish to environmental SMZ concentrations and observed behavioral outcomes. SMZ exposure increased hyperactivity and altered the transcript levels of 17 genes associated with neurological function. It impaired intestinal function by reducing the number of intestinal goblet cells and lipid content. Metabolomic results indicated that the contents of several lipids and amino acids in the gut were altered, which might affect the expression levels of neurological function-related genes. Metagenomic results demonstrated that SMZ exposure substantially altered the composition of the gut microbiome. Zebrafish receiving a transplanted fecal microbiome from the SMZ group were also found to exhibit abnormal behavior, suggesting that the gut microbiome is an important target for SMZ exposure-induced neurobehavioral abnormalities. Multi-omics correlation analysis revealed that gut micrometabolic function was related to differential gut metabolite levels, which may affect neurological function through the gut-brain-axis. Reduced abundance of Lefsonia and Microbacterium was strongly correlated with intestinal metabolic function and may be the key bacterial genera in neurobehavioral changes. This study confirms for the first time that SMZ-induced neurotoxicity in zebrafish is closely mediated by alterations in the gut microbiome.}, } @article {pmid38306142, year = {2024}, author = {Natarelli, N and Aflatooni, S and Boby, A and Krenitsky, A and Grichnik, J}, title = {The Gastrointestinal Microbiome and Immune Checkpoint Inhibitors: A Review of Human Interventional Studies Among Melanoma Patients.}, journal = {Journal of drugs in dermatology : JDD}, volume = {23}, number = {2}, pages = {78-84}, doi = {10.36849/JDD.7674}, pmid = {38306142}, issn = {1545-9616}, mesh = {Humans ; *Colitis ; *Gastrointestinal Microbiome ; Immune Checkpoint Inhibitors/adverse effects ; *Melanoma/therapy ; Remission Induction ; }, abstract = {Immune checkpoint inhibitors (ICI) are widely utilized for the treatment of malignant melanoma. Interestingly, gastrointestinal microbiome composition has emerged as a predictive biomarker of immunotherapy outcomes. This review seeks to assess the effect of microbiota-modulatory interventions on the clinical and immunological response of metastatic melanoma treated with ICIs. A systematic search was performed to retrieve studies and cases involving any microbiota-modulating intervention. Three studies assessed the effect of fecal microbiota transplantation (FMT) on ICI efficacy, and one case report assessed its effect on clearance of ICI-associated colitis. Overall, 37.5% of melanoma patients who had been previously refractory to ICI immunotherapy demonstrated complete or partial response following FMT and subsequent immunotherapy. 65% of immunotherapy-na&iuml;ve melanoma patients demonstrated an objective response. No severe FMT-associated adverse events were reported, and FMT depicted efficacy in the remission of ICI-associated colitis. The results suggest that FMT may be a safe and moderately effective microbiota-modulating intervention to improve the efficacy of therapy in ICI-treated melanoma patients. Large, randomized, controlled trials are needed to determine optimal FMT donors and assess other microbiota-modulating interventions, such as pre- and probiotics, in melanoma patients.&nbsp; J Drugs Dermatol. 2024;23(2):78-84.&nbsp; &nbsp;&nbsp; doi:10.36849/JDD.7674.}, } @article {pmid38305096, year = {2024}, author = {Linnehan, BK and Kodera, SM and Allard, SM and Brodie, EC and Allaband, C and Knight, R and Lutz, HL and Carroll, MC and Meegan, JM and Jensen, ED and Gilbert, JA}, title = {Evaluation of the safety and efficacy of fecal microbiota transplantations in bottlenose dolphins (Tursiops truncatus) using metagenomic sequencing.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jambio/lxae026}, pmid = {38305096}, issn = {1365-2672}, abstract = {AIMS: Gastrointestinal disease is a leading cause of morbidity in bottlenose dolphins (Tursiops truncatus) under managed care. Fecal microbiota transplantation (FMT) holds promise as a therapeutic tool to restore gut microbiota without antibiotic use. This prospective clinical study aimed to develop a screening protocol for FMT donors to ensure safety, determine an effective FMT administration protocol for managed dolphins, and evaluate the FMT's efficacy in four recipient dolphins.

METHODS AND RESULTS: Comprehensive health monitoring was performed on donor and recipient dolphins. Fecal samples were collected before, during, and after FMT therapy. Screening of donor and recipient fecal samples was accomplished by in-house and reference lab diagnostic tests. Shotgun metagenomics was used for sequencing. Following FMT treatment, all four recipient communities experienced engraftment of novel microbial species from donor communities. Engraftment coincided with resolution of clinical signs and a sustained increase in alpha diversity.

CONCLUSION: The donor screening protocol proved to be safe in this study and no adverse effects were observed in four recipient dolphins. Treatment coincided with improvement in clinical signs.}, } @article {pmid38302438, year = {2024}, author = {Eberhart, T and Stanley, FU and Ricci, L and Chirico, T and Ferrarese, R and Sisti, S and Scagliola, A and Baj, A and Badurek, S and Sommer, A and Culp-Hill, R and Dzieciatkowska, M and Shokry, E and Sumpton, D and D'Alessandro, A and Clementi, N and Mancini, N and Cardaci, S}, title = {ACOD1 deficiency offers protection in a mouse model of diet-induced obesity by maintaining a healthy gut microbiota.}, journal = {Cell death & disease}, volume = {15}, number = {2}, pages = {105}, pmid = {38302438}, issn = {2041-4889}, support = {Start-Up 2017 - ID. 20464 project//Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)/ ; GR-2018-12365954//Ministero della Salute (Ministry of Health, Italy)/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Ecosystem ; Obesity/metabolism ; Diet, High-Fat/adverse effects ; Mice, Inbred C57BL ; *Succinates ; }, abstract = {Aconitate decarboxylase 1 (ACOD1) is the enzyme synthesizing itaconate, an immuno-regulatory metabolite tuning host-pathogen interactions. Such functions are achieved by affecting metabolic pathways regulating inflammation and microbe survival. However, at the whole-body level, metabolic roles of itaconate remain largely unresolved. By using multiomics-integrated approaches, here we show that ACOD1 responds to high-fat diet consumption in mice by promoting gut microbiota alterations supporting metabolic disease. Genetic disruption of itaconate biosynthesis protects mice against obesity, alterations in glucose homeostasis and liver metabolic dysfunctions by decreasing meta-inflammatory responses to dietary lipid overload. Mechanistically, fecal metagenomics and microbiota transplantation experiments demonstrate such effects are dependent on an amelioration of the intestinal ecosystem composition, skewed by high-fat diet feeding towards obesogenic phenotype. In particular, unbiased fecal microbiota profiling and axenic culture experiments point towards a primary role for itaconate in inhibiting growth of Bacteroidaceae and Bacteroides, family and genus of Bacteroidetes phylum, the major gut microbial taxon associated with metabolic health. Specularly to the effects imposed by Acod1 deficiency on fecal microbiota, oral itaconate consumption enhances diet-induced gut dysbiosis and associated obesogenic responses in mice. Unveiling an unrecognized role of itaconate, either endogenously produced or exogenously administered, in supporting microbiota alterations underlying diet-induced obesity in mice, our study points ACOD1 as a target against inflammatory consequences of overnutrition.}, } @article {pmid38301301, year = {2024}, author = {Yan, M and Zhao, Y and Man, S and Dai, Y and Ma, L and Gao, W}, title = {Diosgenin as a substitute for cholesterol alleviates NAFLD by affecting CYP7A1 and NPC1L1-related pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {125}, number = {}, pages = {155299}, doi = {10.1016/j.phymed.2023.155299}, pmid = {38301301}, issn = {1618-095X}, abstract = {BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) rapidly becomes the leading cause of end-stage liver disease or liver transplantation. Nowadays, there has no approved drug for NAFLD treatment. Diosgenin as the structural analogue of cholesterol attenuates hypercholesterolemia by inhibiting cholesterol metabolism, which is an important pathogenesis in NAFLD progression. However, there has been no few report concerning its effects on NAFLD so far.

METHODS: Using a high-fat diet & 10% fructose-feeding mice, we evaluated the anti-NAFLD effects of diosgenin. Transcriptome sequencing, LC/MS analysis, molecular docking simulation, molecular dynamics simulations and Luci fluorescent reporter gene analysis were used to evaluate pathways related to cholesterol metabolism.

RESULTS: Diosgenin treatment ameliorated hepatic dysfunction and inhibited NAFLD formation including lipid accumulation, inflammation aggregation and fibrosis formation through regulating cholesterol metabolism. For the first time, diosgenin was structurally similar to cholesterol, down-regulated expression of CYP7A1 and regulated cholesterol metabolism in the liver (p < 0.01) and further affecting bile acids like CDCA, CA and TCA in the liver and feces. Besides, diosgenin decreased expression of NPC1L1 and suppressed cholesterol transport (p < 0.05). Molecular docking and molecular dynamics further proved that diosgenin was more strongly bound to CYP7A1. Luci fluorescent reporter gene analysis revealed that diosgenin concentration-dependently inhibited the enzymes activity of CYP7A1.

CONCLUSION: Our findings demonstrated that diosgenin was identified as a specific regulator of cholesterol metabolism, which pave way for the design of novel clinical therapeutic strategies.}, } @article {pmid38300802, year = {2024}, author = {Kirk, D and Costeira, R and Visconti, A and Khan Mirzaei, M and Deng, L and Valdes, AM and Menni, C}, title = {Bacteriophages, gut bacteria, and microbial pathways interplay in cardiometabolic health.}, journal = {Cell reports}, volume = {43}, number = {2}, pages = {113728}, doi = {10.1016/j.celrep.2024.113728}, pmid = {38300802}, issn = {2211-1247}, abstract = {Cardiometabolic diseases are leading causes of mortality in Western countries. Well-established risk factors include host genetics, lifestyle, diet, and the gut microbiome. Moreover, gut bacterial communities and their activities can be altered by bacteriophages (also known simply as phages), bacteria-infecting viruses, making these biological entities key regulators of human cardiometabolic health. The manipulation of bacterial populations by phages enables the possibility of using phages in the treatment of cardiometabolic diseases through phage therapy and fecal viral transplants. First, however, a deeper understanding of the role of the phageome in cardiometabolic diseases is required. In this review, we first introduce the phageome as a component of the gut microbiome and discuss fecal viral transplants and phage therapy in relation to cardiometabolic diseases. We then summarize the current state of phageome research in cardiometabolic diseases and propose how the phageome might indirectly influence cardiometabolic health through gut bacteria and their metabolites.}, } @article {pmid38071977, year = {2024}, author = {Zhao, H and Li, W and Zhou, X and Pan, L and Feng, Y and Gao, P and Ji, J and Zhang, H and Zhao, K and Wang, C and Lu, Z}, title = {C-X-C Motif Chemokine Ligand 1 Promotes Colitis by Modulating the Gut Microbiota.}, journal = {Journal of innate immunity}, volume = {16}, number = {1}, pages = {33-44}, pmid = {38071977}, issn = {1662-8128}, abstract = {INTRODUCTION: C-X-C motif chemokine ligand 1 (CXCL1) is a potent neutrophil chemoattractant that plays a pivotal role in recruiting neutrophils during inflammatory conditions. This study explored the role of CXCL1 in modulating the gut microbiota, influencing neutrophil infiltration, and contributing to the development of colitis.

METHODS: We employed quantitative PCR to assess CXCL1 expression in colon samples. A mouse model of dextran sulfate sodium (DSS)-induced colitis was utilized to explore the progression of colitis in wild-type (WT) and CXCL1-deficient (CXCL1-/-) mice.

RESULTS: Colitis attenuation was evident in CXCL1-/- mice. Significant alterations were observed in the gut microbiome, as revealed by 16S rRNA gene sequencing. Furthermore, CXCL1-/- mice exhibited reduced gut permeability and diminished endotoxin levels in peripheral blood following DSS treatment compared to WT mice. In response to DSS treatment, WT mice showed a clear increase in neutrophil infiltration, while CXCL1-/- mice exhibited lower levels of infiltration. Fecal microbiota transplantation (FMT) using stools from CXCL1-/- mice alleviated DSS-induced colitis. Interestingly, FMT from patients with colitis increased CXCL1 and Ly6G expression in the colons of gut-sterilized mice. Clinical data analysis revealed elevated CXCL1 and CD15 expression in patients with colitis, with a positive correlation between the severity of colitis and the expression of CXCL1 and CD15.

CONCLUSION: These findings shed light on the pivotal role of CXCL1 in promoting colitis by modulating the gut microbiota.}, } @article {pmid38299844, year = {2024}, author = {Zhang, Z and Huang, J and Li, C and Zhao, Z and Cui, Y and Yuan, X and Wang, X and Liu, Y and Zhou, Y and Zhu, Z}, title = {The gut microbiota contributes to the infection of bovine viral diarrhea virus in mice.}, journal = {Journal of virology}, volume = {}, number = {}, pages = {e0203523}, doi = {10.1128/jvi.02035-23}, pmid = {38299844}, issn = {1098-5514}, abstract = {Bovine viral diarrhea virus (BVDV) is prevalent worldwide and causes significant economic losses. Gut microbiota is a large microbial community and has a variety of biological functions. However, whether there is a correlation between gut microbiota and BVDV infection and what kind of relation between them have not been reported. Here, we found that gut microbiota composition changed in normal mice after infecting with BVDV, but mainly the low abundance microbe was affected. Interestingly, BVDV infection significantly reduced the diversity of gut microbiota and changed its composition in gut microbiota-dysbiosis mice. Furthermore, compared with normal mice of BVDV infection, there were more viral loads in the duodenum, jejunum, spleen, and liver of the gut microbiota-dysbiosis mice. However, feces microbiota transplantation (FMT) reversed these effects. The data above indicated that the dysbiosis of gut microbiota was a key factor in the high infection rate of BVDV. It is found that the IFN-I signal was involved by investigating the underlying mechanisms. The inhibition of the proliferation and increase in the apoptosis of peripheral blood lymphocytes (PBL) were also observed. However, FMT treatment reversed these changes by regulating PI3K/Akt, ERK, and Caspase-9/Caspase-3 pathways. Furthermore, the involvement of butyrate in the pathogenesis of BVDV was also further confirmed. Our results showed for the first time that gut microbiota acts as a key endogenous defense mechanism against BVDV infection; moreover, targeting regulation of gut microbiota structure and abundance may serve as a new strategy to prevent and control the disease.IMPORTANCEWhether the high infection rate of BVDV is related to gut microbiota has not been reported. In addition, most studies on BVDV focus on in vitro experiments, which limits the study of its prevention and control strategy and its pathogenic mechanism. In this study, we successfully confirmed the causal relationship between gut microbiota and BVDV infection as well as the potential molecular mechanism based on a mouse model of BVDV infection and a mouse model of gut microbiota dysbiosis. Meanwhile, a mouse model which is more susceptible to BVDV provided in this study lays an important foundation for further research on prevention and control strategy of BVDV and its pathogenesis. In addition, the antiviral effect of butyrate, the metabolites of butyrate-producing bacteria, has been further revealed. Overall, our findings provide a promising prevention and control strategy to treat this infectious disease which is distributed worldwide.}, } @article {pmid38296309, year = {2024}, author = {Kragsnaes, MS and Jensen, JRB and Nilsson, AC and Malik, MI and Munk, HL and Pedersen, JK and Horn, HC and Kruhøffer, M and Kristiansen, K and Mullish, BH and Marchesi, JR and Kjeldsen, J and Röttger, R and Ellingsen, T}, title = {Dynamics of inflammation-associated plasma proteins following faecal microbiota transplantation in patients with psoriatic arthritis and healthy controls: exploratory findings from the FLORA trial.}, journal = {RMD open}, volume = {10}, number = {1}, pages = {}, pmid = {38296309}, issn = {2056-5933}, abstract = {OBJECTIVES: The gut microbiota can mediate both pro and anti-inflammatory responses. In patients with psoriatic arthritis (PsA), we investigated the impact of faecal microbiota transplantation (FMT), relative to sham transplantation, on 92 inflammation-associated plasma proteins.

METHODS: This study relates to the FLORA trial cohort, where 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate treatment, were included in a 26-week, double-blind, randomised, sham-controlled trial. Participants were allocated to receive either one gastroscopic-guided healthy donor FMT (n=15) or sham (n=16). Patient plasma samples were collected at baseline, week 4, 12 and 26 while samples from 31 age-matched and sex-matched healthy controls (HC) were collected at baseline. Samples were analysed using proximity extension assay technology (Olink Target-96 Inflammation panel).

RESULTS: Levels of 26 proteins differed significantly between PsA and HC pre-FMT (adjusted p<0.05), of which 10 proteins were elevated in PsA: IL-6, CCL20, CCL19, CDCP1, FGF-21, HGF, interferon-γ (IFN-γ), IL-18R1, monocyte chemotactic protein 3, and IL-2. In the FMT group, levels of 12 proteins changed significantly across all timepoints (tumour necrosis factor (TNF), CDCP1, IFN-γ, TWEAK, signalling lymphocytic activation molecule (SLAMF1), CD8A, CD5, Flt3L, CCL25, FGF-23, CD6, caspase-8). Significant differences in protein levels between FMT and sham-treated patients were observed for TNF (p=0.002), IFN-γ (p=0.011), stem cell factor (p=0.024), matrix metalloproteinase-1 (p=0.038), and SLAMF1 (p=0.042). FMT had the largest positive effect on IFN-γ, Axin-1 and CCL25 and the largest negative effect on CCL19 and IL-6.

CONCLUSIONS: Patients with active PsA have a distinct immunological plasma protein signature compared with HC pre-FMT. FMT affects several of these disease markers, including sustained elevation of IFN-γ.

TRIAL REGISTRATION NUMBER: NCT03058900.}, } @article {pmid38296308, year = {2024}, author = {Gilbert, BTP and Tadeo, RYT and Lamacchia, C and Studer, O and Courvoisier, D and Raes, J and Finckh, A}, title = {Gut microbiome and intestinal inflammation in preclinical stages of rheumatoid arthritis.}, journal = {RMD open}, volume = {10}, number = {1}, pages = {}, doi = {10.1136/rmdopen-2023-003589}, pmid = {38296308}, issn = {2056-5933}, abstract = {BACKGROUND: Faecal Prevotellaceae, and other microbes, have been associated with rheumatoid arthritis (RA) and preclinical RA. We have performed a quantitative microbiome profiling study in preclinical stages of RA.

METHODS: First-degree relatives of patients with RA (RA-FDRs) from the SCREEN-RA cohort were categorised into four groups: controls, healthy asymptomatic RA-FDRs; high genetic risk, asymptomatic RA-FDRs with two copies of the shared epitope; autoimmunity, asymptomatic RA-FDRs with RA-associated autoimmunity; and symptomatic, clinically suspect arthralgias or untreated new-onset RA.Faecal samples were collected and frozen. 16S sequencing was performed, processed with DADA2 pipeline and Silva database. Cell counts (cytometry) and faecal calprotectin (enzyme-linked immunosorbent assay, ELISA) were also obtained. Microbial community analyses were conducted using non-parametric tests, such as permutational multivariate analysis of variance (PERMANOVA), Wilcoxon and Kruskal-Wallis, or Aldex2.

RESULTS: A total of 371 individuals were included and categorised according to their preclinical stage of the disease. Groups had similar age, gender and body mass index. We found no significant differences in the quantitative microbiome profiles by preclinical stages (PERMANOVA, R2=0.00798, p=0.56) and, in particular, no group differences in Prevotellaceae abundance. Results were similar when using relative microbiome profiling data (PERMANOVA, R2=0.0073, p=0.83) or Aldex2 on 16S sequence counts. Regarding faecal calprotectin, we found no differences between groups (p=0.3).

CONCLUSIONS: We could not identify microbiome profiles associated with preclinical stages of RA. Only in a subgroup of individuals with the most pronounced phenotypes did we modestly retrieve the previously reported associations.}, } @article {pmid38296019, year = {2024}, author = {Wei, J and Wang, G and Lai, M and Zhang, Y and Li, F and Wang, Y and Tan, Y}, title = {Faecal Microbiota Transplantation Alleviates Ferroptosis after Ischaemic Stroke.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2024.01.021}, pmid = {38296019}, issn = {1873-7544}, abstract = {Ischaemic stroke can induce changes in the abundance of gut microbiota constituents, and the outcome of stroke may also be influenced by the gut microbiota. This study aimed to determine whether gut microbiota transplantation could rescue changes in the gut microbiota and reduce ferroptosis after stroke in rats. Male Sprague-Dawley rats (6 weeks of age) were subjected to ischaemic stroke by middle cerebral artery occlusion (MCAO). Fecal samples were collected for 16S ribosomal RNA (rRNA) sequencing to analyze the effects of FMT on the gut microbiota. Neurological deficits were evaluated using the Longa score. triphenyl tetrazolium chloride (TTC) staining was performed in the brain, and kits were used to measure malondialdehyde (MDA), iron, and glutathione (GSH) levels in the ipsilateral brain of rats. Western blotting was used to detect the protein expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and the transferrin receptor 2 (TFR2) in the ipsilateral brain of rats. Stroke induced significant changes in the gut microbiota, and FMT ameliorated these changes. TTC staining results showed that FMT reduced cerebral infarct volume. In addition, FMT diminished MDA and iron levels and elevated GSH levels in the ipsilateral brain. Western blot analysis showed that FMT increased GPX4 and SLC7A11 protein expression and decreased TFR2 protein expression in the ipsilateral brain after stroke. FMT can reverse gut microbiota dysbiosis, reduce cerebellar infarct volume, and decrease ferroptosis after stroke.}, } @article {pmid38294580, year = {2024}, author = {Dong, L and Tang, Y and Wen, S and He, Y and Li, F and Deng, Y and Tao, Z}, title = {Fecal Microbiota Transplantation Alleviates Allergic Rhinitis via CD4[+] T Cell Modulation Through Gut Microbiota Restoration.}, journal = {Inflammation}, volume = {}, number = {}, pages = {}, pmid = {38294580}, issn = {1573-2576}, support = {81970860//National Natural Science Foundation of China/ ; }, abstract = {Allergic rhinitis (AR) is an allergic condition of the upper respiratory tract with a complex pathogenesis, including epithelial barrier disruption, immune regulation, and gut microbiota, which is not yet fully understood. Gut microbiota is closely linked to allergic diseases, including AR. Fecal microbiota transplantation (FMT) has recently been recognized as a potentially effective therapy for allergic diseases. However, the efficacy and mechanism of action of FMT in AR remain unknown. Herein, we aimed to observe the implications of gut microbiota on epithelial barrier function and T cell homeostasis, as well as the effect of FMT in AR, using the ovalbumin (OVA)-induced AR mice. The intestinal microbiota of recipient mice was cleared using an antibiotic cocktail; thereafter, FMT was performed. Subsequently, the nasal symptom scores and histopathological features of colon and nasal mucosa tissues of mice were monitored, and serum OVA-sIgE and cytokines of IL-4, IFNγ, IL-17A, and IL-10 cytokine concentrations were examined. Thereafter, tight junction protein and CD4[+] T cell-related transcription factor and cytokine expressions were observed in the colon and nasal mucosa, and changes in the expression of PI3K/AKT/mTOR and NFκB signaling pathway were detected by WB assay in each group. Fecal DNA was extracted from the four mice groups for high-throughput 16S rRNA sequencing. FMT ameliorated nasal symptoms and reduced nasal mucosal inflammation in AR mice. Moreover, according to 16S rRNA sequencing, FMT restored the disordered gut microbiota in AR mice. Following FMT, ZO-1 and claudin-1 and Th1/Th2/Th17-related transcription factor and cytokine expressions were upregulated, whereas Treg cell-related Foxp3 and IL-10 expressions were downregulated. Mechanistic studies have revealed that FMT also inhibited PI3K/AKT/mTOR and NF-κB pathway protein phosphorylation in AR mouse tissues. FMT alleviates allergic inflammation in AR by repairing the epithelial barrier and modulating CD4[+] T cell balance and exerts anti-inflammatory effects through the PI3K/AKT/mTOR and NF-κB signaling pathways. Moreover, gut microbiota disorders are involved in AR pathogenesis. Disturbed gut microbiota causes an altered immune-inflammatory state in mice and increases susceptibility to AR. This study suggested the regulatory role of the gut-nose axis in the pathogenesis of AR is an emerging field, which provides novel directions and ideas for the treatment of AR.}, } @article {pmid38293097, year = {2024}, author = {Ma, L and Ge, Y and Brown, J and Choi, SC and Elshikha, A and Kanda, N and Terrell, M and Six, N and Garcia, A and Mohamadzadeh, M and Silverman, G and Morel, L}, title = {Dietary tryptophan and genetic susceptibility expand gut microbiota that promote systemic autoimmune activation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.16.575942}, pmid = {38293097}, abstract = {Tryptophan modulates disease activity and the composition of microbiota in the B6. Sle1.Sle2.Sle3 (TC) mouse model of lupus. To directly test the effect of tryptophan on the gut microbiome, we transplanted fecal samples from TC and B6 control mice into germ-free or antibiotic-treated non-autoimmune B6 mice that were fed with a high or low tryptophan diet. The recipient mice with TC microbiota and high tryptophan diet had higher levels of immune activation, autoantibody production and intestinal inflammation. A bloom of Ruminococcus gnavus (Rg), a bacterium associated with disease flares in lupus patients, only emerged in the recipients of TC microbiota fed with high tryptophan. Rg depletion in TC mice decreased autoantibody production and increased the frequency of regulatory T cells. Conversely, TC mice colonized with Rg showed higher autoimmune activation. Overall, these results suggest that the interplay of genetic and tryptophan can influence the pathogenesis of lupus through the gut microbiota.}, } @article {pmid38292634, year = {2024}, author = {Xu, TC and Liu, Y and Yu, Z and Xu, B}, title = {Gut-targeted therapies for type 2 diabetes mellitus: A review.}, journal = {World journal of clinical cases}, volume = {12}, number = {1}, pages = {1-8}, pmid = {38292634}, issn = {2307-8960}, abstract = {Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance. The global prevalence of T2DM has reached epidemic proportions, affecting approximately 463 million adults worldwide in 2019. Current treatments for T2DM include lifestyle modifications, oral antidiabetic agents, and insulin therapy. However, these therapies may carry side effects and fail to achieve optimal glycemic control in some patients. Therefore, there is a growing interest in the role of gut microbiota and more gut-targeted therapies in the management of T2DM. The gut microbiota, which refers to the community of microorganisms that inhabit the human gut, has been shown to play a crucial role in the regulation of glucose metabolism and insulin sensitivity. Alterations in gut microbiota composition and diversity have been observed in T2DM patients, with a reduction in beneficial bacteria and an increase in pathogenic bacteria. This dysbiosis may contribute to the pathogenesis of the disease by promoting inflammation and impairing gut barrier function. Several gut-targeted therapies have been developed to modulate the gut microbiota and improve glycemic control in T2DM. One potential approach is the use of probiotics, which are live microorganisms that confer health benefits to the host when administered in adequate amounts. Several randomized controlled trials have demonstrated that certain probiotics, such as Lactobacillus and Bifidobacterium species, can improve glycemic control and insulin sensitivity in T2DM patients. Mechanisms may include the production of short-chain fatty acids, the improvement of gut barrier function, and the reduction of inflammation. Another gut-targeted therapy is fecal microbiota transplantation (FMT), which involves the transfer of fecal material from a healthy donor to a recipient. FMT has been used successfully in the treatment of Clostridioides difficile infection and is now being investigated as a potential therapy for T2DM. A recent randomized controlled trial showed that FMT from lean donors improved glucose metabolism and insulin sensitivity in T2DM patients with obesity. However, FMT carries potential risks, including transmission of infectious agents and alterations in the recipient's gut microbiota that may be undesirable. In addition to probiotics and FMT, other gut-targeted therapies are being investigated for the management of T2DM, such as prebiotics, synbiotics, and postbiotics. Prebiotics are dietary fibers that promote the growth of beneficial gut bacteria, while synbiotics combine probiotics and prebiotics. Postbiotics refer to the metabolic products of probiotics that may have beneficial effects on the host. The NIH SPARC program, or the Stimulating Peripheral Activity to Relieve Conditions, is a research initiative aimed at developing new therapies for a variety of health conditions, including T2DM. The SPARC program focuses on using electrical stimulation to activate peripheral nerves and organs, in order to regulate glucose levels in the body. The goal of this approach is to develop targeted, non-invasive therapies that can help patients better manage their diabetes. One promising area of research within the SPARC program is the use of electrical stimulation to activate the vagus nerve, which plays an important role in regulating glucose metabolism. Studies have shown that vagus nerve stimulation can improve insulin sensitivity and lower blood glucose levels in patients with T2DM. Gut-targeted therapies, such as probiotics and FMT, have shown potential for improving glycemic control and insulin sensitivity in T2DM patients. However, further research is needed to determine the optimal dose, duration, and safety of these therapies.}, } @article {pmid38292322, year = {2024}, author = {Huang, T and Lv, Y and Wang, W and Chen, Y and Fan, L and Teng, Z and Zhou, X and Shen, H and Fu, G}, title = {Case Report: Fecal Microbiota Transplantation for the Treatment of Generalized Eczema Occurring After COVID-19 Vaccination.}, journal = {Clinical, cosmetic and investigational dermatology}, volume = {17}, number = {}, pages = {229-235}, pmid = {38292322}, issn = {1178-7015}, abstract = {Adverse skin reactions caused by the COVID-19 vaccine have attracted considerable attention. As we all know, the development mechanism of some skin diseases is related to the gut and skin microbiome. A 78-year-old male patient who received the COVID-19 vaccine developed generalized eczema with multiple dense black patches over the body, a widespread rash, erosion, and scabs on his limbs, as well as facial edema. The patient experienced recurrent flare-ups after conventional treatment, but then recovered well without recurrence after undergoing three fecal microbial transplantation (FMT) treatments. This rare case is reported for the first time in this study. This report demonstrates the possible potential of FMT in targeting refractory skin diseases, such as eczema, as well as diseases associated with gut microbiota disturbance after vaccination.}, } @article {pmid38288791, year = {2024}, author = {Bahmani, M and Mehrtabar, S and Jafarizadeh, A and Zoghi, S and Heravi, FS and Abbasi, A and Sanaie, S and Rahnemayan, S and Leylabadlo, HE}, title = {The Gut Microbiota and Major Depressive Disorder: Current Understanding and Novel Therapeutic Strategies.}, journal = {Current pharmaceutical biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113892010281892240116081031}, pmid = {38288791}, issn = {1873-4316}, abstract = {Major depressive disorder (MDD) is a common neuropsychiatric challenge that primarily targets young females. MDD as a global disorder has a multifactorial etiology related to the environment and genetic background. A balanced gut microbiota is one of the most important environmental factors involved in human physiological health. The interaction of gut microbiota components and metabolic products with the hypothalamic-pituitary-adrenal system and immune mediators can reverse depression phenotypes in vulnerable individuals. Therefore, abnormalities in the quantitative and qualitative structure of the gut microbiota may lead to the progression of MDD. In this review, we have presented an overview of the bidirectional relationship between gut microbiota and MDD, and the effect of pre-treatments and microbiomebased approaches, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and a new generation of microbial alternatives, on the improvement of unstable clinical conditions caused by MDD.}, } @article {pmid38287975, year = {2023}, author = {Wetzel, S and Müller, A and Kohnert, E and Mehrbarzin, N and Huber, R and Häcker, G and Kreutz, C and Lederer, AK and Badr, MT}, title = {Longitudinal dynamics of gut bacteriome and mycobiome interactions pre- and post-visceral surgery in Crohn's disease.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1275405}, pmid = {38287975}, issn = {2235-2988}, mesh = {Humans ; *Mycobiome ; *Crohn Disease/surgery ; RNA, Ribosomal, 16S/genetics ; Prospective Studies ; Bacteria/genetics ; *Digestive System Surgical Procedures ; Fungi/genetics ; }, abstract = {INTRODUCTION: Alterations of the gut microbiome are involved in the pathogenesis of Crohn's disease (CD). The role of fungi in this context is unclear. This study aimed to determine postoperative changes in the bacterial and fungal gut communities of CD patients undergoing intestinal resection, and to evaluate interactions between the bacteriome and mycobiome and their impact on the patients' outcome.

METHODS: We report a subgroup analysis of a prospective cohort study, focusing on 10 CD patients whose fecal samples were collected for bacterial 16S rRNA and fungal ITS2 genes next-generation sequencing the day before surgery and on the 5th or 6th postoperative day.

RESULTS: No significant differences in bacterial and fungal diversity were observed between preoperative and postoperative stool samples. By in-depth analysis, significant postoperative abundance changes of bacteria and fungi and 17 interkingdom correlations were detected. Network analysis identified 13 microbial clusters in the perioperative gut communities, revealing symbiotic and competitive interactions. Relevant factors were gender, age, BMI, lifestyle habits (smoking, alcohol consumption) and surgical technique. Postoperative abundance changes and identified clusters were associated with clinical outcomes (length of hospital stay, complications) and levels of inflammatory markers.

CONCLUSIONS: Our findings highlight the importance of dissecting the interactions of gut bacterial and fungal communities in CD patients and their potential influence on postoperative and disease outcomes.}, } @article {pmid38287961, year = {2023}, author = {Li, H and Lv, N and Li, D and Qian, Y and Si, X and Hua, Y and Wang, Y and Han, X and Xu, T}, title = {Tongbian decoction restores intestinal microbiota and activates 5-hydroxytryptamine signaling: implication in slow transit constipation.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1296163}, pmid = {38287961}, issn = {1664-302X}, abstract = {INTRODUCTION: Slow transit constipation (STC) is a type of functional constipation. The detailed mechanism of STC, for which there is currently no effective treatment, is unknown as of yet. Tongbian decoction (TBD), a traditional Chinese medicinal formula, is commonly used to treat STC in clinical settings. However, the potential impact of TBD on the management of STC via modulation of the gut microbiota remains unclear.

METHODS: Pseudo-germ-free rats were constructed after 6 days of treatment with bacitracin, neomycin, and streptomycin (abbreviated as ABX forthwith). Based on the successful construction of pseudo-germ-free rats, the STC model (ABX + STC) was induced using loperamide hydrochloride. After successful modeling, based on the different sources of donor rat microbiota, the ABX + STC rats were randomly divided into three groups: Control → ABX + STC, STC → ABX + STC, and STC + TBD → ABX + STC for fecal microbiota transplant (FMT). Body weight, fecal water content, and charcoal power propelling rate of the rats were recorded. Intestinal microbiota was detected by 16S rRNA sequencing, and the 5-hydroxytryptamine (5-HT) signaling pathway was examined by western blots, immunofluorescence, and immunohistochemical analysis.

RESULTS: After treatment with fecal bacterial solutions derived from rats treated with Tongbian decoction (TBD), there was an increase in body weight, fecal water content, and the rate of charcoal propulsion in the rats. Additionally, activation of the 5-hydroxytryptamine (5-HT) signaling pathway was observed. The 16S rRNA sequencing results showed that the fecal bacterial solution from TBD-treated rats affected the intestinal microbiota of STC rats by increasing the proliferation of beneficial bacteria and suppressing the expansion of harmful bacteria.

CONCLUSION: Our study showed that TBD alleviated constipation in STC rats by modulating the structure of the intestinal microbiota.}, } @article {pmid38283489, year = {2023}, author = {Sinnathamby, ES and Mason, JW and Flanagan, CJ and Pearl, NZ and Burroughs, CR and De Witt, AJ and Wenger, DM and Klapper, VG and Ahmadzadeh, S and Varrassi, G and Shekoohi, S and Kaye, AD}, title = {Clostridioides difficile Infection: A Clinical Review of Pathogenesis, Clinical Considerations, and Treatment Strategies.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e51167}, pmid = {38283489}, issn = {2168-8184}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is a common nosocomial infection. Risk factors for developing CDI include prior hospitalization, being older than 65 years old, antibiotic use, and chronic disease. It is linked with diarrhea and colitis and can vary in severity. It is a major cause of increased morbidity and mortality among hospitalized patients. However, community-acquired CDI is also increasing. Proper diagnosis and determination of severity are crucial for the treatment of CDI. Depending on how severe the CDI is, the patient may endorse different symptoms and physical exam findings. The severity of CDI will determine how aggressively it is treated. Management and treatment: Laboratory studies can be helpful in the diagnosis of CDI. In this regard, common labs include complete blood count, stool assays, and, in certain cases, radiography and endoscopy. Mild-to-moderate colitis is treated with antibiotics, but severe colitis requires a different approach, which may include surgery. Several alternative therapies for CDI exist and have shown promising results. This review will touch upon these therapies, which include fecal transplants, intravenous immunoglobulin, and the use of cholestyramine and tigecycline.

CONCLUSION: Prevention of CDI can be achieved by proper hygiene, vaccinations, and detecting the infection early. Proper hygiene is indeed noted to be one of the best ways to prevent CDI in the hospital setting. Overprescribing antibiotics is also another huge reason why CDI occurs. Proper prescription of antibiotics can also help reduce the chances of acquiring CDI.}, } @article {pmid38281930, year = {2024}, author = {Sabbaghian, M and Gheitasi, H and Shekarchi, AA and Tavakoli, A and Poortahmasebi, V}, title = {The mysterious anelloviruses: investigating its role in human diseases.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {40}, pmid = {38281930}, issn = {1471-2180}, mesh = {Humans ; *Anelloviridae/genetics ; *DNA Virus Infections/epidemiology ; *Torque teno virus/genetics ; *Body Fluids ; Liver ; DNA, Viral ; }, abstract = {Anelloviruses (AVs) that infect the human population are members of the Anelloviridae family. They are widely distributed in human populations worldwide. Torque teno virus (TTV) was the first virus of this family to be identified and is estimated to be found in the serum of 80-90% of the human population. Sometime after the identification of TTV, Torque teno mini virus (TTMV) and Torque teno midi virus (TTMDV) were also identified and classified in this family. Since identifying these viruses, have been detected in various types of biological fluids of the human body, including blood and urine, as well as vital organs such as the liver and kidney. They can be transmitted from person to person through blood transfusions, fecal-oral contact, and possibly sexual intercourse. Recent studies on these newly introduced viruses show that although they are not directly related to human disease, they may be indirectly involved in initiating or exacerbating some human population-related diseases and viral infections. Among these diseases, we can mention various types of cancers, immune system diseases, viral infections, hepatitis, and AIDS. Also, they likely use the microRNAs (miRNAs) they encode to fulfill this cooperative role. Also, in recent years, the role of proliferation and their viral load, especially TTV, has been highlighted to indicate the immune system status of immunocompromised people or people who undergo organ transplants. Here, we review the possible role of these viruses in diseases that target humans and highlight them as important viruses that require further study. This review can provide new insights to researchers.}, } @article {pmid38281337, year = {2024}, author = {Ren, P and Yue, H and Tang, Q and Wang, Y and Xue, C}, title = {Astaxanthin exerts an adjunctive anti-cancer effect through the modulation of gut microbiota and mucosal immunity.}, journal = {International immunopharmacology}, volume = {128}, number = {}, pages = {111553}, doi = {10.1016/j.intimp.2024.111553}, pmid = {38281337}, issn = {1878-1705}, abstract = {This study aimed to investigate the function of gut microbiota in astaxanthin's adjuvant anticancer effects. Our prior research demonstrated that astaxanthin enhanced the antitumor effects of sorafenib by enhancing the body's antitumor immune response; astaxanthin also regulated the intestinal flora composition of tumor-bearing mice. However, it is presently unknown whether this beneficial effect is dependent on the gut microbiota. We first used broad-spectrum antibiotics to eradicate gut microbiota of tumor-bearing mice, followed by the transplantation of fecal microbiota. The results of this study indicate that the beneficial effects of astaxanthin when combined with molecular targeting are dependent on the presence of intestinal microbiota. Astaxanthin facilitates the infiltration of CD8+ T lymphocytes into the tumor microenvironment and increases Granzyme B production by modulating the intestinal flora. Therefore, it strengthens the body's anti-tumor immune response and synergistically boosts the therapeutic efficacy of drugs. Astaxanthin stimulates the production of cuprocytes and mucus in the intestines by promoting the proliferation of Akkermansia. In addition, astaxanthin enhances the intestinal mucosal immunological function. Our research supports the unique ability of astaxanthin to sustain intestinal flora homeostasis and its function as a dietary immune booster for individuals with tumors.}, } @article {pmid38280701, year = {2024}, author = {Liu, M and Ma, J and Xu, J and Huangfu, W and Zhang, Y and Ali, Q and Liu, B and Li, D and Cui, Y and Wang, Z and Sun, H and Zhu, X and Ma, S and Shi, Y}, title = {Fecal microbiota transplantation alleviates intestinal inflammatory diarrhea caused by oxidative stress and pyroptosis via reducing gut microbiota-derived lipopolysaccharides.}, journal = {International journal of biological macromolecules}, volume = {261}, number = {Pt 1}, pages = {129696}, doi = {10.1016/j.ijbiomac.2024.129696}, pmid = {38280701}, issn = {1879-0003}, abstract = {Infancy is a critical period in the maturation of the gut microbiota and a phase of susceptibility to gut microbiota dysbiosis. Early disturbances in the gut microbiota can have long-lasting effects on host physiology, including intestinal injury and diarrhea. Fecal microbiota transplantation (FMT) can remodel gut microbiota and may be an effective way to treat infant diarrhea. However, limited research has been conducted on the mechanisms of infant diarrhea and the regulation of gut microbiota balance through FMT, primarily due to ethical challenges in testing on human infants. Our study demonstrated that elevated Lipopolysaccharides (LPS) levels in piglets with diarrhea were associated with colon microbiota dysbiosis induced by early weaning. Additionally, LPS upregulated NLRP3 levels by activating TLR4 and inducing ROS production, resulting in pyroptosis, disruption of the intestinal barrier, bacterial translocation, and subsequent inflammation, ultimately leading to diarrhea in piglets. Through microbiota regulation, FMT modulated β-PBD-2 secretion in the colon by increasing butyric acid levels. This modulation alleviated gut microbiota dysbiosis, reduced LPS levels, attenuated oxidative stress and pyroptosis, inhibited the inflammatory response, maintained the integrity of the intestinal barrier, and ultimately reduced diarrhea in piglets caused by colitis. These findings present a novel perspective on the pathogenesis, pathophysiology, prevention, and treatment of diarrhea diseases, underscoring the significance of the interaction between FMT and the gut microbiota as a critical strategy for treating diarrhea and intestinal diseases in infants and farm animals.}, } @article {pmid38172339, year = {2024}, author = {Thiele Orberg, E and Meedt, E and Hiergeist, A and Xue, J and Heinrich, P and Ru, J and Ghimire, S and Miltiadous, O and Lindner, S and Tiefgraber, M and Göldel, S and Eismann, T and Schwarz, A and Göttert, S and Jarosch, S and Steiger, K and Schulz, C and Gigl, M and Fischer, JC and Janssen, KP and Quante, M and Heidegger, S and Herhaus, P and Verbeek, M and Ruland, J and van den Brink, MRM and Weber, D and Edinger, M and Wolff, D and Busch, DH and Kleigrewe, K and Herr, W and Bassermann, F and Gessner, A and Deng, L and Holler, E and Poeck, H}, title = {Bacteria and bacteriophage consortia are associated with protective intestinal metabolites in patients receiving stem cell transplantation.}, journal = {Nature cancer}, volume = {5}, number = {1}, pages = {187-208}, pmid = {38172339}, issn = {2662-1347}, support = {395357507//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 360372040//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; BA 2851/6-1, 360372040//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; DE 2360/6-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; DE 2360/1-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 464797012//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 324392634, 395357507//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 360372040, 395357507, 324392634//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; R01-HL123340, R01-HL147584//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; DJCLS 01 GvHD/2016//Jos& Carreras Leuk&mie-Stiftung (Deutsche Jos& Carreras Leuk&mie-Stiftung)/ ; 70114547//Deutsche Krebshilfe (German Cancer Aid)/ ; 2021.040.1//Wilhelm Sander-Stiftung (Wilhelm Sander Foundation)/ ; }, mesh = {Humans ; *Bacteriophages/genetics ; Feces/microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Bacteria/genetics/metabolism ; Butyric Acid/metabolism ; }, abstract = {The microbiome is a predictor of clinical outcome in patients receiving allogeneic hematopoietic stem cell transplantation (allo-SCT). Microbiota-derived metabolites can modulate these outcomes. How bacteria, fungi and viruses contribute to the production of intestinal metabolites is still unclear. We combined amplicon sequencing, viral metagenomics and targeted metabolomics from stool samples of patients receiving allo-SCT (n = 78) and uncovered a microbiome signature of Lachnospiraceae and Oscillospiraceae and their associated bacteriophages, correlating with the production of immunomodulatory metabolites (IMMs). Moreover, we established the IMM risk index (IMM-RI), which was associated with improved survival and reduced relapse. A high abundance of short-chain fatty acid-biosynthesis pathways, specifically butyric acid via butyryl-coenzyme A (CoA):acetate CoA-transferase (BCoAT, which catalyzes EC 2.8.3.8) was detected in IMM-RI low-risk patients, and virome genome assembly identified two bacteriophages encoding BCoAT as an auxiliary metabolic gene. In conclusion, our study identifies a microbiome signature associated with protective IMMs and provides a rationale for considering metabolite-producing consortia and metabolite formulations as microbiome-based therapies.}, } @article {pmid38280329, year = {2024}, author = {Hu, L and Feng, X and Lan, Y and Zhang, J and Nie, P and Xu, H}, title = {Co-exposure with cadmium elevates the toxicity of microplastics: Trojan horse effect from the perspective of intestinal barrier.}, journal = {Journal of hazardous materials}, volume = {466}, number = {}, pages = {133587}, doi = {10.1016/j.jhazmat.2024.133587}, pmid = {38280329}, issn = {1873-3336}, abstract = {Microplastics (MPs) have been shown to adsorb heavy metals and serve as vehicles for their environmental transport. To date, insufficient studies have focused on enterohepatic injury in mice co-exposed to both MPs and cadmium (Cd). Here, we report that Cd adsorption increased the surface roughness and decreased the monodispersity of PS-MPs. Furthermore, exposure to both PS-MPs and Cd resulted in a more severe toxic effect compared to single exposure, with decreased body weight gain, shortened colon length, and increased colonic and hepatic inflammatory response observed. This can be attributed to an elevated accumulation of Cd resulting from increased gut permeability, coupled with the superimposed effects of oxidative stress. In addition, using 16 S sequencing and fecal microbiota transplantation, it was demonstrated that gut microbiota dysbiosis plays an essential role in the synergistic toxicity induced by PS-MPs and Cd in mice. This study showed that combined exposure to MPs and Cd induced more severe intestinal and liver damage in mice compared to individual exposure, and provided a new perspective for a more systematic risk assessment process related to MPs exposure.}, } @article {pmid38276546, year = {2024}, author = {Czarnik, W and Fularski, P and Gajewska, A and Jakubowska, P and Uszok, Z and Młynarska, E and Rysz, J and Franczyk, B}, title = {The Role of Intestinal Microbiota and Diet as Modulating Factors in the Course of Alzheimer's and Parkinson's Diseases.}, journal = {Nutrients}, volume = {16}, number = {2}, pages = {}, pmid = {38276546}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Parkinson Disease/therapy ; *Alzheimer Disease ; Diet ; *Microbiota ; Dysbiosis ; Brain ; }, abstract = {Many researchers propose manipulating microbiota to prevent and treat related diseases. The brain-gut axis is an object that remains the target of modern research, and it is not without reason that many researchers enrich it with microbiota and diet in its name. Numerous connections and mutual correlations have become the basis for seeking answers to many questions related to pathology as well as human physiology. Disorders of this homeostasis as well as dysbiosis itself accompany neurodegenerative diseases such as Alzheimer's and Parkinson's. Heavily dependent on external factors, modulation of the gut microbiome represents an opportunity to advance the treatment of neurodegenerative diseases. Probiotic interventions, synbiotic interventions, or fecal transplantation can undoubtedly support the biotherapeutic process. A special role is played by diet, which provides metabolites that directly affect the body and the microbiota. A holistic view of the human organism is therefore essential.}, } @article {pmid38276309, year = {2024}, author = {Gurung, B and Stricklin, M and Wang, S}, title = {Gut Microbiota-Gut Metabolites and Clostridioides difficile Infection: Approaching Sustainable Solutions for Therapy.}, journal = {Metabolites}, volume = {14}, number = {1}, pages = {}, pmid = {38276309}, issn = {2218-1989}, support = {19168-20-4250002//Start-up funding and RSAC (Research and Scholarly Awards Committee) pilot grant support from Ohio University Heritage College of Osteopathic Medicine/ ; }, abstract = {Clostridioides difficile (C. difficile) infection (CDI) is the most common hospital-acquired infection. With the combination of a high rate of antibiotic resistance and recurrence, it has proven to be a debilitating public health threat. Current treatments for CDI include antibiotics and fecal microbiota transplantation, which contribute to recurrent CDIs and potential risks. Therefore, there is an ongoing need to develop new preventative treatment strategies for CDI. Notably, gut microbiota dysbiosis is the primary risk factor for CDI and provides a promising target for developing novel CDI therapy approaches. Along with gut microbiota dysbiosis, a reduction in important gut metabolites like secondary bile acids and short-chain fatty acids (SCFAs) were also seen in patients suffering from CDI. In this review study, we investigated the roles and mechanisms of gut microbiota and gut microbiota-derived gut metabolites, especially secondary bile acids and SCFAs in CDI pathogenesis. Moreover, specific signatures of gut microbiota and gut metabolites, as well as different factors that can modulate the gut microbiota, were also discussed, indicating that gut microbiota modulators like probiotics and prebiotics can be a potential therapeutic strategy for CDI as they can help restore gut microbiota and produce gut metabolites necessary for a healthy gut. The understanding of the associations between gut microbiota-gut metabolites and CDI will allow for developing precise and sustainable approaches, distinct from antibiotics and fecal transplant, for mitigating CDI and other gut microbiota dysbiosis-related diseases.}, } @article {pmid38276223, year = {2023}, author = {Suswał, K and Tomaszewski, M and Romaniuk, A and Świechowska-Starek, P and Zygmunt, W and Styczeń, A and Romaniuk-Suswał, M}, title = {Gut-Lung Axis in Focus: Deciphering the Impact of Gut Microbiota on Pulmonary Arterial Hypertension.}, journal = {Journal of personalized medicine}, volume = {14}, number = {1}, pages = {}, pmid = {38276223}, issn = {2075-4426}, support = {DS 640//Polish Society of Cardiology/ ; }, abstract = {Recent advancements in the understanding of pulmonary arterial hypertension (PAH) have highlighted the significant role of the gut microbiota (GM) in its pathogenesis. This comprehensive review delves into the intricate relationship between the GM and PAH, emphasizing the influence of gut microbial composition and the critical metabolites produced. We particularly focus on the dynamic interaction between the gut and lung, examining how microbial dysbiosis contributes to PAH development through inflammation, altered immune responses, and changes in the gut-lung axis. Noteworthy findings include variations in the ratios of key bacterial groups such as Firmicutes and Bacteroidetes in PAH and the pivotal roles of metabolites like trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and serotonin in the disease's progression. Additionally, the review elucidates potential diagnostic biomarkers and novel therapeutic approaches, including the use of probiotics and fecal microbiota transplantation, which leverage the gut microbiota for managing PAH. This review encapsulates the current state of research in this field, offering insights into the potential of gut microbiota modulation as a promising strategy in PAH diagnosing and treatment.}, } @article {pmid38275924, year = {2024}, author = {Rojas, CA and Entrolezo, Z and Jarett, JK and Jospin, G and Martin, A and Ganz, HH}, title = {Microbiome Responses to Oral Fecal Microbiota Transplantation in a Cohort of Domestic Dogs.}, journal = {Veterinary sciences}, volume = {11}, number = {1}, pages = {}, pmid = {38275924}, issn = {2306-7381}, abstract = {Fecal microbiota transplants (FMTs) have been successful at treating digestive and skin conditions in dogs. The degree to which the microbiome is impacted by FMT in a cohort of dogs has not been thoroughly investigated. Using 16S rRNA gene sequencing, we document the changes in the microbiome of fifty-four dogs that took capsules of lyophilized fecal material for their chronic diarrhea, vomiting, or constipation. We found that the relative abundances of five bacterial genera (Butyricicoccus, Faecalibacterium, Fusobacterium, Megamonas, and Sutterella) were higher after FMT than before FMT. Fecal microbiome alpha- and beta-diversity were correlated with kibble and raw food consumption, and prior antibiotic use. On average, 18% of the stool donor's bacterial amplicon sequence variants (ASVs) engrafted in the FMT recipient, with certain bacterial taxa like Bacteroides spp., Fusobacterium spp., and Lachnoclostridium spp. engrafting more frequently than others. Lastly, analyses indicated that the degree of overlap between the donor bacteria and the community of microbes already established in the FMT recipient likely impacts engraftment. Collectively, our work provides further insight into the microbiome and engraftment dynamics of dogs before and after taking oral FMTs.}, } @article {pmid38274729, year = {2023}, author = {Wang, L and Xu, A and Wang, J and Fan, G and Liu, R and Wei, L and Pei, M}, title = {The effect and mechanism of Fushen Granule on gut microbiome in the prevention and treatment of chronic renal failure.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1334213}, pmid = {38274729}, issn = {2235-2988}, abstract = {BACKGROUND: Fushen Granule is an improved granule based on the classic formula Fushen Formula, which is used for the treatment of peritoneal dialysis-related intestinal dysfunction in patients with end-stage renal disease. However, the effect and mechanism of this granule on the prevention and treatment of chronic renal failure have not been fully elucidated.

METHODS: A 5/6 nephrectomy model of CRF was induced and Fushen Granule was administered at low and high doses to observe its effects on renal function, D-lactate, serum endotoxin, and intestinal-derived metabolic toxins. The 16SrRNA sequencing method was used to analyze the abundance and structure of the intestinal flora of CRF rats. A FMT assay was also used to evaluate the effects of transplantation of Fushen Granule fecal bacteria on renal-related functional parameters and metabolic toxins in CRF rats.

RESULTS: Gavage administration of Fushen Granule at low and high doses down-regulated creatinine, urea nitrogen, 24-h urine microalbumin, D-lactate, endotoxin, and the intestinal-derived toxins indophenol sulphateand p-cresol sulphate in CRF rats. Compared with the sham-operated group in the same period, CRF rats had a decreased abundance of the firmicutes phylum and an increased abundance of the bacteroidetes phylum at the phylum level, and a decreasing trend of the lactobacillus genus at the genus level. Fushen Granule intervention increased the abundance of the firmicutes phylum, decreased the abundance of the bacteroidetes phylum, and increased the abundance of the lactobacillus genus. The transplantation of Fushen Granule fecal bacteria significantly reduced creatinine(Cr), blood urea nitrogen(Bun), uric acid(UA), 24-h urinary microalbumin, D-lactate, serum endotoxin, and enterogenic metabolic toxins in CRF rats. Compared with the sham-operated group, the transplantation of Fushen Granule fecal bacteria modulated the Firmicutes and Bacteroidetes phyla and the Lactobacillus genus.

CONCLUSION: Fushen Granule improved renal function and intestinal barrier function by regulating intestinal flora, inhibiting renal fibrosis, and delaying the progression of chronic renal failure.}, } @article {pmid38273106, year = {2024}, author = {Zhang, YD and Shi, DD and Liao, BB and Li, Y and Zhang, S and Gao, J and Lin, LJ and Wang, Z}, title = {Human microbiota from drug-naive patients with obsessive-compulsive disorder drives behavioral symptoms and neuroinflammation via succinic acid in mice.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {38273106}, issn = {1476-5578}, support = {82071518//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32271066//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2021-01-07-00-02-E0086//Shanghai Municipal Education Commission/ ; }, abstract = {Emerging evidence suggests that the gut microbiota is closely related to psychiatric disorders. However, little is known about the role of the gut microbiota in the development of obsessive-compulsive disorder (OCD). Here, to investigate the contribution of gut microbiota to the pathogenesis of OCD, we transplanted fecal microbiota from first-episode, drug-naive OCD patients or demographically matched healthy individuals into antibiotic-treated specific pathogen-free (SPF) mice and showed that colonization with OCD microbiota is sufficient to induce core behavioral deficits, including abnormal anxiety-like and compulsive-like behaviors. The fecal microbiota was analyzed using 16 S rRNA full-length sequencing, and the results demonstrated a clear separation of the fecal microbiota of mice colonized with OCD and control microbiota. Notably, microbiota from OCD-colonized mice resulted in injured neuronal morphology and function in the mPFC, with inflammation in the mPFC and colon. Unbiased metabolomic analyses of the serum and mPFC region revealed the accumulation of succinic acid (SA) in OCD-colonized mice. SA impeded neuronal activity and induced an inflammatory response in both the colon and mPFC, impacting intestinal permeability and brain function, which act as vital signal mediators in gut microbiota-brain-immune crosstalk. Manipulations of dimethyl malonate (DM) have been reported to exert neuroprotective effects by suppressing the oxidation of accumulated succinic acid, attenuating the downstream inflammatory response and neuronal damage, and can help to partly improve abnormal behavior and reduce neuroinflammation and intestinal inflammation in OCD-colonized mice. We propose that the gut microbiota likely regulates brain function and behaviors in mice via succinic acid signaling, which contributes to the pathophysiology of OCD through gut-brain crosstalk and may provide new insights into the treatment of this disorder.}, } @article {pmid38272165, year = {2024}, author = {Do Nascimento, J and Ladeiro, MP and Bonnard, I and Gantzer, C and Boudaud, N and Lopes, C and Geffard, A}, title = {Assessing viral freshwater hazard using a toxicokinetic model and Dreissena polymorpha.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {}, number = {}, pages = {123420}, doi = {10.1016/j.envpol.2024.123420}, pmid = {38272165}, issn = {1873-6424}, abstract = {The detection all pathogenic enteric viruses in water is expensive, time-consuming, and limited by numerous technical difficulties. Consequently, using reliable indicators such as F-specific RNA phages (FRNAPH) can be well adapted to assess the risk of viral contamination of fecal origin in surface waters. However, the variability of results inherent to the water matrix makes it difficult to use them routinely and to interpret viral risk. Spatial and temporal variability of surface waters can lead to underestimate this risk, in particular in the case of low loading. The use of bivalve molluscs as accumulating systems appears as a promising alternative, as recently highlighted with the freshwater mussel Dreissena polymorpha, but its capacity to accumulate and depurate FRNAPH needs to be better understood and described. The purpose of this study is to characterise the kinetics of accumulation and elimination of infectious FRNAPH by D. polymorpha in laboratory conditions, formalised by a toxico-kinetic (TK) mechanistic model. Accumulation and depuration experiments were performed at a laboratory scale to determine the relationship between the concentration of infectious FRNAPH in water and the concentration accumulated by D. polymorpha. The mussels accumulated infectious FRNAPH (3-5.4 × 10[4] PFU/g) in a fast and concentration-dependent way in only 48 h, as already recently demonstrated. The second exposure demonstrated that the kinetics of infectious FRNAPH depuration by D. polymorpha was independent to the exposure dose, with a T90 (time required to depurate 90 % of the accumulated concentration) of approximately 6 days. These results highlight the capacities of D. polymorpha to detect and reflect the viral pollution in an integrative way and over time, which is not possible with point water sampling. Different TK models were fitted based on the concentrations measured in the digestive tissues (DT) of D. polymorpha. The model has been developed to formalise the kinetics of phage accumulation in mussels tissues through the simultaneous estimation of accumulation and depuration rates. This model showed that accumulation depended on the exposure concentration, while depuration did not. Standardized D. polymorpha could be easily transplanted to the environment to predict viral concentrations using the TK model defined in the present study to predict the level of contamination of bodies of water on the basis of the level of phages accumulated by the organisms. It will be also provide a better understanding of the dynamics of the virus in continental waters at different time and spatial scales, and thereby contribute to the protection of freshwater resources.}, } @article {pmid38268839, year = {2024}, author = {Wu, J and Deng, X and Sun, Y and Li, J and Dai, H and Qi, S and Huang, Y and Sun, W}, title = {Aged oolong tea alleviates dextran sulfate sodium-induced colitis in mice by modulating the gut microbiota and its metabolites.}, journal = {Food chemistry: X}, volume = {21}, number = {}, pages = {101102}, pmid = {38268839}, issn = {2590-1575}, abstract = {In this study, the mechanism of aged oolong tea (AOT) to alleviate colitis was investigated in terms of microbiome, metabolome, and fecal microbiota transplantation (FMT). AOT storage period could alleviate colitis in mice and there were some differences in AOT between storage periods, especially AOT-10. AOT improves UC by modulating oxidative stress and inflammatory factors and upregulating intestinal tight junction protein expression (Occludin, Claudin-1, ZO-1 and MUC2), which is associated with the recovery of gut microbiota. FMT and targeted metabolomics further demonstrate that the anti-inflammatory effects of AOT can reshape the gut microbiota through faecal bacterial transfer. Anti-inflammatory effects are exerted through the stimulation of metabolic pathways associated with amino acid, fatty acid and bile acid metabolites. Importantly, the study identified key bacteria (e.g., Sutterella, Clostridiaceae_Clostridium, Mucispirillum, Oscillospira and Ruminococcus) for the development and remission of inflammation. Conclusively, AOT may have great potential in the future adjuvant treatment of colitis.}, } @article {pmid38266859, year = {2024}, author = {Hu, H and Sun, W and Zhang, L and Zhang, Y and Kuang, T and Qu, D and Lian, S and Hu, S and Cheng, M and Xu, Y and Liu, S and Qian, Y and Lu, Y and He, L and Cheng, Y and Si, H}, title = {Carboxymethylated Abrus cantoniensis polysaccharide prevents CTX-induced immunosuppression and intestinal damage by regulating intestinal flora and butyric acid content.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {129590}, doi = {10.1016/j.ijbiomac.2024.129590}, pmid = {38266859}, issn = {1879-0003}, abstract = {As a Chinese folk health product, Abrus cantoniensis exhibits good immunomodulatory activity because of its polysaccharide components (ACP), and carboxymethylation of polysaccharides can often further improve the biological activity of polysaccharides. In this study, we explored the impact of prophylactic administration of carboxymethylated Abrus cantoniensis polysaccharide (CM-ACP) on immunosuppression and intestinal damage induced by cyclophosphamide (CTX) in mice. Our findings demonstrated that CM-ACP exhibited a more potent immunomodulatory activity compared to ACP. Additionally, CM-ACP effectively enhanced the abundance of short-chain fatty acid (SCFA)-producing bacteria in immunosuppressed mice and regulated the gene expression of STAT6 and STAT3 mediated pathway signals. In order to further explore the relationship among polysaccharides, intestinal immunity and intestinal flora, we performed a pseudo-sterile mouse validation experiment and fecal microbiota transplantation (FMT) experiment. The findings suggest that CM-FMT and butyrate attenuate CTX-induced immunosuppression and intestinal injury. CM-FMT and butyrate show superior immunomodulatory ability, and may effectively regulate intestinal cell metabolism and repair the damaged intestine by activating STAT6 and STAT3-mediated pathways. These findings offer new insights into the mechanisms by which CM-ACP functions as functional food or drug, facilitating immune response regulation and maintaining intestinal health.}, } @article {pmid38260901, year = {2023}, author = {Song, J and Luo, C and Liu, Z and Liu, J and Xie, L and Zhang, X and Xie, Z and Li, X and Ma, Z and Ding, J and Li, H and Xiang, H}, title = {Early fecal microbiota transplantation from high abdominal fat chickens affects recipient cecal microbiome and metabolism.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1332230}, pmid = {38260901}, issn = {1664-302X}, abstract = {Abdominal fat deposition (AFD) in chickens is closely related to the gut microecological balance. In this study, the gut microbiota from high-AFD chickens was transplanted into the same strain of 0-day-old chicks via fecal microbiota transplantation (FMT). The FTM from chickens with high AFD had no obvious effects on growth traits, adult body weight, carcass weight, abdominal fat weight, and abdominal fat percentage, but did reduce the coefficient of variation of AFD traits. FMT significantly decreased cecal microbiome richness, changed the microbiota structure, and regulated the biological functions associated with energy metabolism and fat synthesis. Additionally, the cecal metabolite composition and metabolic function of FMT recipient chickens were also significantly altered from those of the controls. Transplantation of high-AFD chicken gut microbiota promoted fatty acid elongation and biosynthesis and reduced the metabolism of vitamins, steroids, and carbohydrates in the cecum. These findings provide insights into the mechanisms by which chicken gut microbiota affect host metabolic profiles and fat deposition.}, } @article {pmid38260539, year = {2024}, author = {Liu, C and Cyphert, EL and Stephen, SJ and Wang, B and Morales, AL and Nixon, JC and Natsoulas, NR and Garcia, M and Blazquez Carmona, P and Vill, AC and Donnelly, EL and Brito, IL and Vashishth, D and Hernandez, CJ}, title = {Microbiome-induced Increases and Decreases in Bone Tissue Strength can be Initiated After Skeletal Maturity.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.01.03.574074}, pmid = {38260539}, abstract = {Recent studies in mice have indicated that the gut microbiome can regulate bone tissue strength. However, prior work involved modifications to the gut microbiome in growing animals and it is unclear if the same changes in the microbiome, applied later in life, would change matrix strength. Here we changed the composition of the gut microbiome before and/or after skeletal maturity (16 weeks of age) using oral antibiotics (ampicillin + neomycin). Male and female mice (n=143 total, n=12-17/group/sex) were allocated into five study groups:1) Unaltered, 2) Continuous (dosing 4-24 weeks of age), 3) Delayed (dosing only 16-24 weeks of age), 4) Initial (dosing 4-16 weeks of age, suspended at 16 weeks), and 5) Reconstituted (dosing from 4-16 weeks following by fecal microbiota transplant from Unaltered donors). Animals were euthanized at 24 weeks of age. In males, bone matrix strength in the femur was 25-35% less than expected from geometry in mice from the Continuous (p= 0.001), Delayed (p= 0.005), and Initial (p=0.040) groups as compared to Unaltered. Reconstitution of the gut microbiota, however, led to a bone matrix strength similar to Unaltered animals (p=0.929). In females, microbiome-induced changes in bone matrix strength followed the same trend as males but were not significantly different, demonstrating sex-related differences in the response of bone matrix to the gut microbiota. Minor differences in chemical composition of bone matrix were observed (Raman spectroscopy). Our findings indicate that microbiome-induced impairment of bone matrix in males can be initiated and/or reversed after skeletal maturity. The portion of the femoral cortical bone formed after skeletal maturity (16 weeks) is small; however, this suggests that microbiome-induced changes in bone matrix occur without osteoblast/osteoclast turnover using an, as of yet unidentified mechanism. These findings add to evidence that the mechanical properties of bone matrix can be altered in the adult skeleton.}, } @article {pmid38260015, year = {2023}, author = {Mogi, K and Akiyama, U and Futagawa, N and Tamura, K and Kamiya, M and Mizuta, M and Yamaoka, M and Kamimura, I and Kuze-Arata, S and Kikusui, T}, title = {Intergenerational transmission of maternal behavioral traits in mice: involvement of the gut microbiota.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1302841}, pmid = {38260015}, issn = {1662-4548}, abstract = {The matrilineal transmission of maternal behavior has been reported in several species. Studies, primarily on rats, have suggested the importance of postnatal experience and the involvement of epigenetic mechanisms in mediating these transmissions. This study aims to determine whether the matrilineal transmission of maternal behavior occurs in mice and whether the microbiota is involved. We first observed that early weaned (EW) female mice showed lower levels of maternal behavior, particularly licking/grooming (LG) of their own pups, than normally weaned (NW) female mice. This difference in maternal behavioral traits was also observed in the second generation, even though all mice were weaned normally. In the subsequent cross-fostering experiment, the levels of LG were influenced by the nurturing mother but not the biological mother. Finally, we transplanted the fecal microbiota from EW or NW mice into germ-free (GF) mice raising pups. The maternal behaviors that the pups exhibited toward their own offspring after growth were analyzed, and the levels of LG in GF mice colonized with microbiota from EW mice were lower than those in GF mice colonized with microbiota from NW mice. These results clearly indicate that, among maternal behavioral traits, LG is intergenerationally transmitted in mice and suggest that the vertical transmission of microbiota is involved in this process. This study demonstrates the universality of the intergenerational transmission of maternal behavioral traits and provides new insights into the role of microbiota.}, } @article {pmid38259389, year = {2023}, author = {Ghazanfar, H and Kandhi, S and Acherjee, T and Qureshi, ZA and Shaban, M and Yordanka, DS and Cordero, D and Chinta, S and Jyala, A and Patel, H}, title = {Role of Fecal Microbiota Transplantation in Managing Clostridium Difficile Infection and Inflammatory Bowel Disease: A Narrative Review.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e51004}, pmid = {38259389}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) has been emerging as an alternate treatment modality in the management of patients with dysbiosis by restoring abnormal gut microbiota composition through the transplantation of normal fecal microbiota from healthy donors. This technique has lately gained a lot of attention in the treatment of recurrent or refractory Clostridium difficile infection (CDI) owing to its high success rates combined with its favorable safety profile. FMT has also been attracting the interest of clinicians as a new treatment option for inflammatory bowel diseases (IBD). Here, we reviewed most of the recent advancements in the use of FMT for CDI as well as its use in the treatment of IBD.}, } @article {pmid38257851, year = {2023}, author = {Ciernikova, S and Sevcikova, A and Mladosievicova, B and Mego, M}, title = {Microbiome in Cancer Development and Treatment.}, journal = {Microorganisms}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/microorganisms12010024}, pmid = {38257851}, issn = {2076-2607}, support = {No. 2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; No. 1/0738/21//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, abstract = {Targeting the microbiome, microbiota-derived metabolites, and related pathways represents a significant challenge in oncology. Microbiome analyses have confirmed the negative impact of cancer treatment on gut homeostasis, resulting in acute dysbiosis and severe complications, including massive inflammatory immune response, mucosal barrier disruption, and bacterial translocation across the gut epithelium. Moreover, recent studies revealed the relationship between an imbalance in the gut microbiome and treatment-related toxicity. In this review, we provide current insights into the role of the microbiome in tumor development and the impact of gut and tumor microbiomes on chemo- and immunotherapy efficacy, as well as treatment-induced late effects, including cognitive impairment and cardiotoxicity. As discussed, microbiota modulation via probiotic supplementation and fecal microbiota transplantation represents a new trend in cancer patient care, aiming to increase bacterial diversity, alleviate acute and long-term treatment-induced toxicity, and improve the response to various treatment modalities. However, a more detailed understanding of the complex relationship between the microbiome and host can significantly contribute to integrating a microbiome-based approach into clinical practice. Determination of causal correlations might lead to the identification of clinically relevant diagnostic and prognostic microbial biomarkers. Notably, restoration of intestinal homeostasis could contribute to optimizing treatment efficacy and improving cancer patient outcomes.}, } @article {pmid38256945, year = {2024}, author = {Kim, SJ and Park, M and Choi, A and Yoo, S}, title = {Microbiome and Prostate Cancer: Emerging Diagnostic and Therapeutic Opportunities.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {17}, number = {1}, pages = {}, doi = {10.3390/ph17010112}, pmid = {38256945}, issn = {1424-8247}, support = {Project No: 20016285//Technology Innovation Pro-398 gram funded by the Ministry of Trade, Industry and Energy (MOTIE)/ ; 2022RIS-005//"Regional Innovation Strategy (RIS)" through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) in 2023/ ; }, abstract = {This review systematically addresses the correlation between the microbiome and prostate cancer and explores its diagnostic and therapeutic implications. Recent research has indicated an association between the urinary and gut microbiome composition and prostate cancer incidence and progression. Specifically, the urinary microbiome is a potential non-invasive biomarker for early detection and risk evaluation, with altered microbial profiles in prostate cancer patients. This represents an advancement in non-invasive diagnostic approaches to prostate cancer. The role of the gut microbiome in the efficacy of various cancer therapies has recently gained attention. Gut microbiota variations can affect the metabolism and effectiveness of standard treatment modalities, including chemotherapy, immunotherapy, and hormone therapy. This review explores the potential of gut microbiome modification through dietary interventions, prebiotics, probiotics, and fecal microbiota transplantation for improving the treatment response and mitigating adverse effects. Moreover, this review discusses the potential of microbiome profiling for patient stratification and personalized treatment strategies. While the current research identifies the pivotal role of the microbiome in prostate cancer, it also highlights the necessity for further investigations to fully understand these complex interactions and their practical applications in improving patient outcomes in prostate cancer management.}, } @article {pmid37647637, year = {2024}, author = {Brothers, AW and Pak, DJ and Poole, NM and Kronman, MP and Bettinger, B and Wilkes, JJ and Carpenter, PA and Englund, JA and Weissman, SJ}, title = {Individualized Antibiotic Plans as a Quality Improvement Initiative to Reduce Carbapenem Use for Hematopoietic Cell Transplant Patients at a Freestanding Pediatric Hospital.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {78}, number = {1}, pages = {15-23}, doi = {10.1093/cid/ciad518}, pmid = {37647637}, issn = {1537-6591}, abstract = {BACKGROUND: Providers must balance effective empiric therapy against toxicity risks and collateral damage when selecting antibiotic therapy for patients receiving hematopoietic cell transplant (HCT). Antimicrobial stewardship interventions during HCT are often challenging due to concern for undertreating potential infections.

METHODS: In an effort to decrease unnecessary carbapenem exposure for patients undergoing HCT at our pediatric center, we implemented individualized antibiotic plans (IAPs) to provide recommendations for preengraftment neutropenia prophylaxis, empiric treatment of febrile neutropenia, and empiric treatment for hemodynamic instability. We compared monthly antibiotic days of therapy (DOT) adjusted per 1000 patient-days for carbapenems, antipseudomonal cephalosporins, and all antibiotics during two 3-year periods immediately before and after the implementation of IAPs to measure the impact of IAP on prescribing behavior. Bloodstream infection (BSIs) and Clostridioides difficile (CD) positivity test rates were also compared between cohorts. Last, providers were surveyed to assess their experience of using IAPs in antibiotic decision making.

RESULTS: Overall antibiotic use decreased after the implementation of IAPs (monthly reduction of 19.6 DOT/1000 patient-days; P = .004), with carbapenems showing a continuing decline after IAP implementation. BSI and CD positivity rates were unchanged. More than 90% of providers found IAPs to be either extremely or very valuable for their practice.

CONCLUSIONS: Implementation of IAPs in this high-risk HCT population led to reduction in overall antibiotic use without increase in rate of BSI or CD test positivity. The program was well received by providers.}, } @article {pmid38255326, year = {2024}, author = {Clemente-Suárez, VJ and Redondo-Flórez, L and Rubio-Zarapuz, A and Martín-Rodríguez, A and Tornero-Aguilera, JF}, title = {Microbiota Implications in Endocrine-Related Diseases: From Development to Novel Therapeutic Approaches.}, journal = {Biomedicines}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/biomedicines12010221}, pmid = {38255326}, issn = {2227-9059}, abstract = {This comprehensive review article delves into the critical role of the human microbiota in the development and management of endocrine-related diseases. We explore the complex interactions between the microbiota and the endocrine system, emphasizing the implications of microbiota dysbiosis for the onset and progression of various endocrine disorders. The review aims to synthesize current knowledge, highlighting recent advancements and the potential of novel therapeutic approaches targeting microbiota-endocrine interactions. Key topics include the impact of microbiota on hormone regulation, its role in endocrine pathologies, and the promising avenues of microbiota modulation through diet, probiotics, prebiotics, and fecal microbiota transplantation. We underscore the importance of this research in advancing personalized medicine, offering insights for more tailored and effective treatments for endocrine-related diseases.}, } @article {pmid38255161, year = {2023}, author = {Li, J and Liu, Y and Li, Y and Sun, T and Xiang, H and He, Z}, title = {The Role of Gut Microbiota and Circadian Rhythm Oscillation of Hepatic Ischemia-Reperfusion Injury in Diabetic Mice.}, journal = {Biomedicines}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/biomedicines12010054}, pmid = {38255161}, issn = {2227-9059}, support = {82070302,81873467//National Natural Science Foundation of China/ ; }, abstract = {Circadian rhythm oscillation and the gut microbiota play important roles in several physiological functions and pathology regulations. In this study, we aimed to elucidate the characteristics of diabetic hepatic ischemia-reperfusion injury (HIRI) and the role of the intestinal microbiota in diabetic mice with HIRI. Hepatic ischemia-reperfusion injury surgery was performed at ZT0 or ZT12. The liver pathological score and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed to evaluate liver injury. We conducted an FMT experiment to examine the role of intestinal microbiota in diabetic mice with HIRI. The 16S rRNA gene sequencing of fecal samples was performed for microbial analysis. Our results showed that hyperglycemia aggravated HIRI in diabetic mice, but there was no diurnal variation seen in diabetic HIRI. We also demonstrated that there were significant alterations in the gut microbiota composition between the diabetic and control mice and that gut microbiota transplantation from diabetic mice had obvious harmful effects on HIRI. These findings provide some useful information for the future research of diabetic mice with HIRI.}, } @article {pmid38255150, year = {2023}, author = {Lauko, S and Gancarcikova, S and Hrckova, G and Hajduckova, V and Andrejcakova, Z and Fecskeova, LK and Bertkova, I and Hijova, E and Kamlarova, A and Janicko, M and Ambro, L and Kvakova, M and Gulasova, Z and Strojny, L and Strkolcova, G and Mudronova, D and Madar, M and Demeckova, V and Nemetova, D and Pacuta, I and Sopkova, D}, title = {Beneficial Effect of Faecal Microbiota Transplantation on Mild, Moderate and Severe Dextran Sodium Sulphate-Induced Ulcerative Colitis in a Pseudo Germ-Free Animal Model.}, journal = {Biomedicines}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/biomedicines12010043}, pmid = {38255150}, issn = {2227-9059}, support = {APVV-16-0176//Slovak Research and Development Agency/ ; VEGA 1/0015/21//Ministry of Education of SR/ ; }, abstract = {Transplantation of faecal microbiota (FMT) is generally considered a safe therapeutic procedure with few adverse effects. The main factors that limit the spread of the use of FMT therapy for idiopathic inflammatory bowel disease (IBD) are the necessity of minimising the risk of infection and transfer of another disease. Obtaining the animal model of UC (ulcerative colitis) by exposure to DSS (dextran sodium sulphate) depends on many factors that significantly affect the result. Per os intake of DSS with water is individual for each animal and results in the development of a range of various forms of induced UC. For this reason, the aim of our study was to evaluate the modulation and regenerative effects of FMT on the clinical and histopathological responses and the changes in the bowel microenvironment in pseudo germ-free (PGF) mice of the BALB/c line subjected to chemical induction of mild, moderate and serious forms of UC. The goal was to obtain new data related to the safety and effectiveness of FMT that can contribute to its improved and optimised use. The animals with mild and moderate forms of UC subjected to FMT treatment exhibited lower severity of the disease and markedly lower damage to the colon, including reduced clinical and histological disease index and decreased inflammatory response of colon mucosa. However, FMT treatment failed to achieve the expected therapeutic effect in animals with the serious form of UC activity. The results of our study indicated a potential safety risk involving development of bacteraemia and also translocation of non-pathogenic representatives of bowel microbiota associated with FMT treatment of animals with a diagnosed serious form of UC.}, } @article {pmid38254757, year = {2024}, author = {Oberhoff, G and Schooren, L and Vondran, F and Kroh, A and Koch, A and Bednarsch, J and Neumann, UP and Schmitz, SM and Alizai, PH}, title = {Impairment of Nutritional Status and Quality of Life Following Minimal-Invasive Esophagectomy-A Prospective Cohort Analysis.}, journal = {Cancers}, volume = {16}, number = {2}, pages = {}, doi = {10.3390/cancers16020266}, pmid = {38254757}, issn = {2072-6694}, support = {START Grant//Universitätsklinikum Aachen/ ; }, abstract = {Minimal-invasive resection of the esophagus for esophageal cancer has led to a relevant decrease in postoperative morbidity. Postoperatively, patients still suffer from surgical and adjuvant therapy-related symptoms impairing nutrition and quality of life. The aim of this study was to evaluate the nutritional status and associated symptoms six months after esophagectomy. Patients who attended follow-up examination six months after minimal-invasive esophagectomy were included. Blood and fecal tests, quality of life surveys (QLQ-C30 and QLQ-OG25) and nutritional risk screening (NRS) were performed. Twenty-four patients participated. The mean weight loss was 11 kg. A significant decrease in vitamin B12 (737 to 467 pg/mL; p = 0.033), ferritin (302 to 126 ng/mL; p = 0.012) and haptoglobin (227 to 152 mg/dL; p = 0.025) was found. In total, 47% of the patients had an impaired pancreatic function (fecal elastase < 500 µg/g). Physical (72 to 58; p = 0.034) and social functioning (67 to 40; p = 0.022) was significantly diminished, while self-reported global health status remained stable (52 to 54). The number of patients screened and found to be in need of nutritional support according to NRS score decreased slightly (59% to 52%). After MIE, patients should be meticulously monitored for nutritional status after surgery.}, } @article {pmid38254421, year = {2024}, author = {Leduc, L and Costa, M and Leclère, M}, title = {The Microbiota and Equine Asthma: An Integrative View of the Gut-Lung Axis.}, journal = {Animals : an open access journal from MDPI}, volume = {14}, number = {2}, pages = {}, doi = {10.3390/ani14020253}, pmid = {38254421}, issn = {2076-2615}, abstract = {Both microbe-microbe and host-microbe interactions can have effects beyond the local environment and influence immunological responses in remote organs such as the lungs. The crosstalk between the gut and the lungs, which is supported by complex connections and intricate pathways, is defined as the gut-lung axis. This review aimed to report on the potential role of the gut-lung gut-lung axis in the development and persistence of equine asthma. We summarized significant determinants in the development of asthma in horses and humans. The article discusses the gut-lung axis and proposes an integrative view of the relationship between gut microbiota and asthma. It also explores therapies for modulating the gut microbiota in horses with asthma. Improving our understanding of the horse gut-lung axis could lead to the development of techniques such as fecal microbiota transplants, probiotics, or prebiotics to manipulate the gut microbiota specifically for improving the management of asthma in horses.}, } @article {pmid38253409, year = {2024}, author = {Zong, Y and Mao, T and Yao, P and Liang, J and Lai, Y and Chen, Z and Chen, S and Huang, L and Guo, Y and Zhu, M and Zhao, J and Liu, Y and Li, Y and Guo, K and Tang, H and Ke, X and Zhou, Y}, title = {Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jambio/lxae016}, pmid = {38253409}, issn = {1365-2672}, abstract = {BACKGROUND: Recent studies have suggested an association between the dysregulation of gut microbiota and its metabolites and menopausal hot flashes. It has been demonstrated that the Guizhi and Erxian Decoction (GED) has efficacy in managing hot flashes but the precise relationship between the hot flashes and the gut microbiota, as well as the specific mechanism by which GED alleviates hot flashes, remains unclear.

OBJECTIVE: To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes.

METHODS: 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota.

RESULTS: GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing L(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase (eNOS) and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition.

CONCLUSIONS: Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.}, } @article {pmid38250691, year = {2024}, author = {Homma, Y and Mimura, T and Koinuma, K and Horie, H and Lefor, AK and Sata, N}, title = {Low anterior resection syndrome: Incidence and association with quality of life.}, journal = {Annals of gastroenterological surgery}, volume = {8}, number = {1}, pages = {114-123}, pmid = {38250691}, issn = {2475-0328}, abstract = {AIM: Low anterior resection syndrome (LARS) causes devastating symptoms and impairs quality of life (QOL). Although its incidence and risk factors have been reported, these data are scarce in Japan. This study aimed to elucidate the incidence and risk factors of LARS as well as to evaluate its association with QOL in Japanese patients.

METHOD: Patients with anal defecation at the time of the survey between November 2020 and April 2021 were included, among those who underwent anus-preserving surgery for rectal tumors between 2014 and 2019 in tertiary referral university hospital. The severity of LARS and QOL were evaluated with the LARS score and the Japanese version of the fecal incontinence quality of life scale (JFIQL), respectively. Primary endpoint was the incidence of major LARS. Secondary endpoints were risk factors and association with JFIQL.

RESULTS: Of 332 eligible patients, 238 (71.7%) answered the LARS survey completely. The incidence of major LARS was 22% overall, and 48% when limited to lower tumors. Independent risk factors included lower tumors (OR: 7.0, 95% CI: 2.1-23.1, p = 0.001) and surgical procedures with lower anastomoses (OR: 4.6, 95% CI: 1.2-18.5, p = 0.03). The JFIQL generic score correlated moderately with the LARS score (correlation coefficient of -0.65). The JFIQL generic score was also significantly lower in lower tumors.

CONCLUSIONS: The incidence of major LARS is 22% in Japanese patients, and independent risk factors include lower tumors and surgical procedures with lower anastomoses. More severe LARS is associated with worse QOL which is significantly more impaired in patients with lower tumors.}, } @article {pmid38250318, year = {2024}, author = {Kim, JS and Park, H and Lee, JH and Shin, J and Cha, B and Kwon, KS and Shin, YW and Kim, Y and Kim, Y and Bae, JS and Lee, JH and Choi, SJ and Kim, TJ and Ko, SB and Park, SH}, title = {Effect of altered gene expression in lipid metabolism on cognitive improvement in patients with Alzheimer's dementia following fecal microbiota transplantation: a preliminary study.}, journal = {Therapeutic advances in neurological disorders}, volume = {17}, number = {}, pages = {17562864231218181}, pmid = {38250318}, issn = {1756-2856}, abstract = {BACKGROUND: The brain-gut axis has emerged as a potential target in neurodegenerative diseases, including dementia, as individuals with dementia exhibit distinct gut microbiota compositions. Fecal microbiota transplantation (FMT), the transfer of fecal solution from a healthy donor to a patient, has shown promise in restoring homeostasis and cognitive enhancement.

OBJECTIVE: This study aimed to explore the effects of FMT on specific cognitive performance measures in Alzheimer's dementia (AD) patients and investigate the relationship between cognition and the gut microbiota by evaluating changes in gene expression following FMT.

METHODS: Five AD patients underwent FMT, and their cognitive function [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)] was assessed before and after FMT. The patients' fecal samples were analyzed with 16S rRNA to compare the composition of their gut microbiota. We also assessed modifications in the serum mRNA expression of patients' genes related to lipid metabolism using serum RNA sequencing and quantitative real-time polymerase chain reaction.

RESULTS: Significant improvements in cognitive function, as measured by the MMSE (pre- and post-FMT was 13.00 and 18.00) and MoCA were seen. The MoCA scores at 3 months post-FMT (21.0) were the highest (12.0). The CDR-SOB scores at pre- and post-FMT were 10.00 and 5.50, respectively. Analysis of the gut microbiome composition revealed changes via 16S rRNA sequencing with an increase in Bacteroidaceae and a decrease in Enterococcaceae. Gene expression analysis identified alterations in lipid metabolism-related genes after FMT.

CONCLUSION: These findings suggest a link between alterations in the gut microbiome, gene expression related to lipid metabolism, and cognitive function. The study highlights the importance of gut microbiota in cognitive function and provides insights into potential biomarkers for cognitive decline progression. FMT could complement existing therapies and show potential as a therapeutic intervention to mitigate cognitive decline in AD.}, } @article {pmid38249807, year = {2024}, author = {Jiang, H and Zhang, Q}, title = {Gut microbiota influences the efficiency of immune checkpoint inhibitors by modulating the immune system (Review).}, journal = {Oncology letters}, volume = {27}, number = {2}, pages = {87}, pmid = {38249807}, issn = {1792-1082}, abstract = {Immune checkpoint inhibitors (ICIs) are commonly utilized in tumor treatment. However, they still have limitations, including insufficient effectiveness and unavoidable adverse events. It has been demonstrated that gut microbiota can influence the effectiveness of ICIs, although the precise mechanism remains unclear. Gut microbiota plays a crucial role in the formation and development of the immune system. Gut microbiota and their associated metabolites play a regulatory role in immune balance. Tumor occurrence and development are linked to their ability to evade recognition and destruction by the immune system. The purpose of ICIs treatment is to reinitiate the immune system's elimination of tumor cells. Thus, the immune system acts as a communication bridge between gut microbiota and ICIs. Varied composition and characteristics of gut microbiota result in diverse outcomes in ICIs treatment. Certain gut microbiota-related metabolites also influence the therapeutic efficacy of ICIs to some extent. The administration of antibiotics before or during ICIs treatment can diminish treatment effectiveness. The utilization of probiotics and fecal transplantation can partially alter the outcome of ICIs treatment. The present review synthesized previous studies to examine the association between gut microbiota and ICIs, elucidated the role of gut microbiota and its associated factors in ICIs treatment, and offered direction for future research.}, } @article {pmid38249454, year = {2023}, author = {Li, D and Liang, W and Zhang, W and Huang, Z and Liang, H and Liu, Q}, title = {Fecal microbiota transplantation repairs intestinal permeability and regulates the expression of 5-HT to influence alcohol-induced depression-like behaviors in C57BL/6J mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1241309}, pmid = {38249454}, issn = {1664-302X}, abstract = {The epidemic of alcohol abuse affects millions of people worldwide. Relevant evidence supports the notion that the gut microbiota (GM) plays a crucial role in central nervous system (CNS) function, and its composition undergoes changes following alcohol consumption. Therefore, the purpose of this study was to investigate the effect of reconstructing the gut microbiota by fecal microbiota transplantation (FMT) on alcohol dependence. Here, we established an alcohol dependence model with C57BL/6J mice and proved that FMT treatment improved anxiety-like behavior and alcohol-seeking behavior in alcohol-dependent mice. Additionally, we found that the expression of the intestinal intercellular tight junction structure proteins ZO-1 and occludin was significantly increased after FMT. FMT repaired intestinal permeability in alcohol-dependent mice and decreased the levels of lipopolysaccharide (LPS) and proinflammatory factors. Moreover, the serotonin (5-hydroxytryptamine, 5-HT) content was significantly increased in alcohol-dependent mouse intestinal and brain tissues after receiving the fecal microbiome from healthy mice. 16S rRNA sequencing demonstrated that FMT markedly reshaped the composition of the gut microbiota and elicited changes in the intestinal barrier and 5-HT levels. Collectively, our results revealed that FMT has a palliative effect on alcohol dependence and explored the underlying mechanisms, which provides new strategies for the treatment of alcohol dependence.}, } @article {pmid38249228, year = {2023}, author = {Bhattacharjee, P and Karim, KA and Khan, Z}, title = {Harnessing the Microbiome: A Comprehensive Review on Advancing Therapeutic Strategies for Rheumatic Diseases.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50964}, pmid = {38249228}, issn = {2168-8184}, abstract = {Rheumatic diseases are a group of disorders that affect the joints, muscles, and bones. These diseases, such as rheumatoid arthritis, lupus, and psoriatic arthritis, can cause pain, stiffness, and swelling, leading to reduced mobility and disability. Recent studies have identified the microbiome, the diverse community of microorganisms that live in and on the human body, as a potential factor in the development and progression of rheumatic diseases. Harnessing the microbiome offers a promising new avenue for developing therapeutic strategies for these debilitating conditions. There is growing interest in the role of oral and gut microbiomes in the management of rheumatoid arthritis and other autoimmune disease. Microbial metabolites have immunomodulatory properties that could be exploited for rheumatic disorders. A wide range of microorganisms are present in the oral cavity and are found to be vulnerable to the effects of the environment. The physiology and ecology of the microbiota become intimately connected with those of the host, and they critically influence the promotion of health or progression toward disease. This article aims to provide a comprehensive overview of the current state of knowledge on oral and gut microbiome and its potential future role in the management of rheumatic diseases. This article will also discuss newer treatment strategies such as bioinformatic analyses and fecal transplantation.}, } @article {pmid38247148, year = {2024}, author = {Taha, AS}, title = {Editorial: The microbiome and gastric mucosal protection in aspirin users.}, journal = {Alimentary pharmacology & therapeutics}, volume = {59}, number = {4}, pages = {575-576}, doi = {10.1111/apt.17821}, pmid = {38247148}, issn = {1365-2036}, mesh = {Humans ; *Microbiota ; }, } @article {pmid38244075, year = {2024}, author = {Yuan, L and Li, Y and Chen, M and Xue, L and Wang, J and Ding, Y and Gu, Q and Zhang, J and Zhao, H and Xie, X and Wu, Q}, title = {Therapeutic applications of gut microbes in cardiometabolic diseases: current state and perspectives.}, journal = {Applied microbiology and biotechnology}, volume = {108}, number = {1}, pages = {156}, pmid = {38244075}, issn = {1432-0614}, support = {2021YFA0910200//Guangdong Province National key research and development project/ ; 2022B1111070006//Guangdong Province key research and development project/ ; 2020GDASYL20200102003//Innovation Development Project of Guangdong Academy of Sciences/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/therapy ; Diet ; *Microbiota ; *Heart Failure ; }, abstract = {Cardiometabolic disease (CMD) encompasses a range of diseases such as hypertension, atherosclerosis, heart failure, obesity, and type 2 diabetes. Recent findings about CMD's interaction with gut microbiota have broadened our understanding of how diet and nutrition drive microbes to influence CMD. However, the translation of basic research into the clinic has not been smooth, and dietary nutrition and probiotic supplementation have yet to show significant evidence of the therapeutic benefits of CMD. In addition, the published reviews do not suggest the core microbiota or metabolite classes that influence CMD, and systematically elucidate the causal relationship between host disease phenotypes-microbiome. The aim of this review is to highlight the complex interaction of the gut microbiota and their metabolites with CMD progression and to further centralize and conceptualize the mechanisms of action between microbial and host disease phenotypes. We also discuss the potential of targeting modulations of gut microbes and metabolites as new targets for prevention and treatment of CMD, including the use of emerging technologies such as fecal microbiota transplantation and nanomedicine. KEY POINTS: • To highlight the complex interaction of the gut microbiota and their metabolites with CMD progression and to further centralize and conceptualize the mechanisms of action between microbial and host disease phenotypes. • We also discuss the potential of targeting modulations of gut microbes and metabolites as new targets for prevention and treatment of CMD, including the use of emerging technologies such as FMT and nanomedicine. • Our study provides insight into identification-specific microbiomes and metabolites involved in CMD, and microbial-host changes and physiological factors as disease phenotypes develop, which will help to map the microbiome individually and capture pathogenic mechanisms as a whole.}, } @article {pmid38243335, year = {2024}, author = {Han, Y and Zeng, X and Hua, L and Quan, X and Chen, Y and Zhou, M and Chuang, Y and Li, Y and Wang, S and Shen, X and Wei, L and Yuan, Z and Zhao, Y}, title = {The fusion of multi-omics profile and multimodal EEG data contributes to the personalized diagnostic strategy for neurocognitive disorders.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {12}, pmid = {38243335}, issn = {2049-2618}, support = {0106/2019/A2//Science and Technology Development Fund, Macau SAR/ ; MYRG-CRG2022-00011-ICMS//University of Macau/ ; }, mesh = {Humans ; Animals ; Mice ; Aged ; *Multiomics ; *Proteomics/methods ; Metagenomics/methods ; Metabolomics/methods ; Electroencephalography/methods ; }, abstract = {BACKGROUND: The increasing prevalence of neurocognitive disorders (NCDs) in the aging population worldwide has become a significant concern due to subjectivity of evaluations and the lack of precise diagnostic methods and specific indicators. Developing personalized diagnostic strategies for NCDs has therefore become a priority.

RESULTS: Multimodal electroencephalography (EEG) data of a matched cohort of normal aging (NA) and NCDs seniors were recorded, and their faecal samples and urine exosomes were collected to identify multi-omics signatures and metabolic pathways in NCDs by integrating metagenomics, proteomics, and metabolomics analysis. Additionally, experimental verification of multi-omics signatures was carried out in aged mice using faecal microbiota transplantation (FMT). We found that NCDs seniors had low EEG power spectral density and identified specific microbiota, including Ruminococcus gnavus, Enterocloster bolteae, Lachnoclostridium sp. YL 32, and metabolites, including L-tryptophan, L-glutamic acid, gamma-aminobutyric acid (GABA), and fatty acid esters of hydroxy fatty acids (FAHFAs), as well as disturbed biosynthesis of aromatic amino acids and TCA cycle dysfunction, validated in aged mice. Finally, we employed a support vector machine (SVM) algorithm to construct a machine learning model to classify NA and NCDs groups based on the fusion of EEG data and multi-omics profiles and the model demonstrated 92.69% accuracy in classifying NA and NCDs groups.

CONCLUSIONS: Our study highlights the potential of multi-omics profiling and EEG data fusion in personalized diagnosis of NCDs, with the potential to improve diagnostic precision and provide insights into the underlying mechanisms of NCDs. Video Abstract.}, } @article {pmid38242462, year = {2024}, author = {Feng, Y and Wu, H and Feng, L and Zhang, R and Feng, X and Wang, W and Xu, H and Fu, F}, title = {Maternal F-53B exposure during pregnancy and lactation induced glucolipid metabolism disorders and adverse pregnancy outcomes by disturbing gut microbiota in mice.}, journal = {The Science of the total environment}, volume = {915}, number = {}, pages = {170130}, doi = {10.1016/j.scitotenv.2024.170130}, pmid = {38242462}, issn = {1879-1026}, abstract = {In the metal plating industry, F-53B has been widely used for almost half a century as a replacement for perfluorooctane sulfonate. However, F-53B can reach the food chain and affect human health. Pregnant women have distinct physiological characteristics and may thus be more sensitive to the toxicity of F-53B. In the present study, F-53B was added to the drinking water of pregnant mice during gestation and lactation at doses of 0 mg/L (Ctrl), 0.57 mg/L (L-F), and 5.7 mg/L (H-F). The aim was to explore the potential effects of F-53B on glucolipid metabolism and pregnancy outcomes in dams. Results showed that F-53B induced disordered glucolipid metabolism, adverse pregnancy outcomes, hepatic inflammation, oxidative stress and substantially altered related biochemical parameters in maternal mice. Moreover, F-53B induced remarkable gut barrier damage and gut microbiota perturbation. Correlation analysis revealed that gut microbiota is associated with glucolipid metabolism disorders and hepatic inflammation. The fecal microbiota transplant experiment demonstrated that altered gut microbiota induced by F-53B caused metabolic disorders, adverse pregnancy outcomes, and gut barrier damage. These results suggested that maternal mice exposed to F-53B during gestation and lactation had an increased risk of developing metabolic disorders and adverse pregnancy outcomes and highlighted the crucial role of the gut microbiota in this process, offering novel insights into the risk of F-53B to health.}, } @article {pmid38241975, year = {2024}, author = {Yang, Y and An, Y and Dong, Y and Chu, Q and Wei, J and Wang, B and Cao, H}, title = {Fecal microbiota transplantation: no longer cinderella in tumour immunotherapy.}, journal = {EBioMedicine}, volume = {100}, number = {}, pages = {104967}, doi = {10.1016/j.ebiom.2024.104967}, pmid = {38241975}, issn = {2352-3964}, abstract = {The incidence of cancer has shown a great increase during the past decades and poses tough challenges to cancer treatment. Anti-tumour immunotherapy, represented by immune checkpoint inhibitors (ICIs), possesses favorable remission in unrestricted spectrum of cancer types. However, its efficacy seems to be heterogeneous among accumulating studies. Emerging evidences suggest that gut microbiota can modulate anti-tumour immuno-response and predict clinical prognosis. Therefore, remodeling microbiota characteristics with fecal microbiota transplantation (FMT) may be capable of reinforcing host ICIs performance by regulating immune-tumour cell interactions and altering microbial metabolites, thereby imperceptibly shifting the tumour microenvironment. However, the long-term safety of FMT is under concern, which calls for more rigorous screening. In this review, we examine current experimental and clinical evidences supporting the FMT efficacy in boosting anti-tumour immuno-response and lessening tumour-related complications. Moreover, we discuss the challenges in FMT and propose feasible resolutions, which may offer crucial guidance for future clinical operations.}, } @article {pmid38241896, year = {2024}, author = {Tyszka, M and Maciejewska-Markiewicz, D and Styburski, D and Biliński, J and Tomaszewska, A and Stachowska, E and Basak, GW}, title = {Altered lipid metabolism in patients with acute graft-versus-host disease after allogeneic hematopoietic cell transplantation.}, journal = {Leukemia research}, volume = {137}, number = {}, pages = {107435}, doi = {10.1016/j.leukres.2024.107435}, pmid = {38241896}, issn = {1873-5835}, abstract = {Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for many hematological malignancies and other diseases. Nevertheless, its application is limited due to the risk of life-threatening complications, mainly graft-versus-host disease (GVHD). Currently, in clinical practice, the risk of developing GVHD is estimated for every patient based on factors related to the donor and the host. In our prospective, observational study, we analyzed serum from 38 patients undergoing allo-HCT at our institution. We compared the metabolic profiles of patients who developed acute GVHD (aGVHD) with those without such complication by identification and comparison of metabolites masses on the XCMS platform. We observed that patients diagnosed with aGVHD had different metabolic profiles compared to the remaining patients and this alteration was noticeable already 7 days before the procedure. We identified dysregulated metabolites involved in bile acid transformation and cholesterol synthesis. Our study of the untargeted metabolome in allo-HCT recipients has revealed a potential link between lipid metabolism, specifically involving bile acid transformation and cholesterol synthesis, and the development of aGVHD. This finding might be an important indication for future research focused on understanding GVHD development, discovering prediction models, and investigating possible prophylactic interventions.}, } @article {pmid38238900, year = {2024}, author = {Yan, H and Zhang, Y and Lin, X and Huang, J and Zhang, F and Chen, C and Ren, H and Zheng, S and Yang, J and Hui, S}, title = {Resveratrol improves diabetic kidney disease by modulating the gut microbiota-short chain fatty acids axis in db/db mice.}, journal = {International journal of food sciences and nutrition}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/09637486.2024.2303041}, pmid = {38238900}, issn = {1465-3478}, abstract = {Diabetic kidney disease is associated with the dysbiosis of the gut microbiota and its metabolites. db/db mice were fed chow diet with or without 0.4% resveratrol for 12 weeks, after which the gut microbiota, faecal short-chain fatty acids (SCFAs), and renal fibrosis were analysed. Resveratrol ameliorated the progression of diabetic kidney disease and alleviated tubulointerstitial fibrosis. Further studies showed that gut microbiota dysbiosis was modulated by resveratrol, characterised by the expansion of SCFAs-producing bacteria Faecalibaculum and Lactobacillus, which increased the concentrations of SCFAs (especially acetic acid) in the faeces. Moreover, microbiota transplantation experiments found that alteration of the gut microbiota contributed to the prevention of diabetic kidney disease. Acetate treatment ameliorated proteinuria, glomerulosclerosis and tubulointerstitial fibrosis in db/db mice. Overall, resveratrol improved the progression of diabetic kidney disease by suppressing tubulointerstitial fibrosis, which may be involved, at least in part, in the regulation of the gut microbiota-SCFAs axis.}, } @article {pmid38237167, year = {2024}, author = {Guo, L and Liu, Q and Yin, X}, title = {Gut Microbiota Protects Listeria monocytogenes-Infected Mice by Reducing the Inflammatory Cytokines Storm and Cell Apoptosis.}, journal = {Foodborne pathogens and disease}, volume = {}, number = {}, pages = {}, doi = {10.1089/fpd.2023.0121}, pmid = {38237167}, issn = {1556-7125}, abstract = {Gut microbiota (GM) has been proven to resist pathogenic infection through nutritional competition, colonization resistance and promotion of the host immune response. However, in clinical practice, GM is mainly used in intestinal diseases, such as Clostridium difficile infection, and there are few reports on its application in the treatment of pathogenic bacterial infections. In this study, GM from healthy mice was transplanted into mice infected with Listeria monocytogenes using fecal microbiota transplantation (FMT) and the effects were observed. We found that GM from healthy mice could reduce the mortality of infected mice and decrease the counts of L. monocytogenes in their liver and spleen. In addition, FMT inhibited the expression of inflammatory factors in the liver and spleen of infected mice. In vitro cell experiments revealed that GM can reduce the count of L. monocytogenes invading Caco-2 cells and inhibit the L. monocytogenes-caused apoptosis. These results indicate that GM can be used to protect mice infected with L. monocytogenes by eliminating the amount of L. monocytogenes in the host and inhibiting the overexpression of inflammatory factors. Hence, this method can potentially replace antibiotics in the treatment of L. monocytogenes infection.}, } @article {pmid38232140, year = {2024}, author = {Bhattarai, SK and Du, M and Zeamer, AL and M Morzfeld, B and Kellogg, TD and Firat, K and Benjamin, A and Bean, JM and Zimmerman, M and Mardi, G and Vilbrun, SC and Walsh, KF and Fitzgerald, DW and Glickman, MS and Bucci, V}, title = {Commensal antimicrobial resistance mediates microbiome resilience to antibiotic disruption.}, journal = {Science translational medicine}, volume = {16}, number = {730}, pages = {eadi9711}, doi = {10.1126/scitranslmed.adi9711}, pmid = {38232140}, issn = {1946-6242}, mesh = {Humans ; Animals ; Mice ; Anti-Bacterial Agents/pharmacology/therapeutic use ; *Resilience, Psychological ; Drug Resistance, Bacterial/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {Despite their therapeutic benefits, antibiotics exert collateral damage on the microbiome and promote antimicrobial resistance. However, the mechanisms governing microbiome recovery from antibiotics are poorly understood. Treatment of Mycobacterium tuberculosis, the world's most common infection, represents the longest antimicrobial exposure in humans. Here, we investigate gut microbiome dynamics over 20 months of multidrug-resistant tuberculosis (TB) and 6 months of drug-sensitive TB treatment in humans. We find that gut microbiome dynamics and TB clearance are shared predictive cofactors of the resolution of TB-driven inflammation. The initial severe taxonomic and functional microbiome disruption, pathobiont domination, and enhancement of antibiotic resistance that initially accompanied long-term antibiotics were countered by later recovery of commensals. This resilience was driven by the competing evolution of antimicrobial resistance mutations in pathobionts and commensals, with commensal strains with resistance mutations reestablishing dominance. Fecal-microbiota transplantation of the antibiotic-resistant commensal microbiome in mice recapitulated resistance to further antibiotic disruption. These findings demonstrate that antimicrobial resistance mutations in commensals can have paradoxically beneficial effects by promoting microbiome resilience to antimicrobials and identify microbiome dynamics as a predictor of disease resolution in antibiotic therapy of a chronic infection.}, } @article {pmid38231673, year = {2024}, author = {Sung, C and Park, CG and Maienschein-Cline, M and Chlipala, G and Green, S and Doorenbos, A and Fink, A and Bronas, U and Lockwood, M}, title = {Associations Between Gut Microbial Features and Sickness Symptoms in Kidney Transplant Recipients.}, journal = {Biological research for nursing}, volume = {}, number = {}, pages = {10998004241227560}, doi = {10.1177/10998004241227560}, pmid = {38231673}, issn = {1552-4175}, abstract = {PURPOSE: The study investigated the relationship of gut microbiome features and sickness symptoms in kidney transplant recipients.

METHODS: Employing a prospective, longitudinal design, we collected data from 19 participants who had undergone living-donor kidney transplant at three timepoints (pre-transplant and 1 week and 3 months post-transplant). Sickness symptom data and fecal specimens were collected at each timepoint. Participants were grouped either as high or low sickness symptom severity at baseline. Shotgun metagenomics sequencing characterized gut microbial structure and functional gene content. Fecal microbial features, including alpha (evenness and richness within samples) and beta (dissimilarities between samples) diversity and relative abundances, were analyzed using R statistical packages. Cross-sectional and longitudinal analyses examined relationships between gut microbial features and sickness symptoms.

RESULTS: Although our exploratory findings revealed no significant differences in alpha and beta diversity between groups, the high-severity group showed lower microbial richness and evenness than the low-severity group. The high-severity group had enriched relative abundance of bacteria from the genera Citrobacter and Enterobacter and reduced relative abundance of bacteria from the genus Akkermansia across timepoints. No functional genes differed significantly between groups or timepoints.

CONCLUSIONS: Kidney transplant recipients with high symptom burden displayed increased putative proinflammatory bacteria and decreased beneficial bacteria. This study provides an effect size that future large cohort studies can employ to confirm associations between gut microbial features and sickness symptom experiences in the kidney transplant population. The study findings also have implications for future interventional studies aiming to alleviate the sickness symptom burden in this population.}, } @article {pmid38228976, year = {2024}, author = {Babu, A and Devi Rajeswari, V and Ganesh, V and Das, S and Dhanasekaran, S and Usha Rani, G and Ramanathan, G}, title = {Gut Microbiome and Polycystic Ovary Syndrome: Interplay of Associated Microbial-Metabolite Pathways and Therapeutic Strategies.}, journal = {Reproductive sciences (Thousand Oaks, Calif.)}, volume = {}, number = {}, pages = {}, pmid = {38228976}, issn = {1933-7205}, abstract = {Polycystic ovary syndrome (PCOS) is a multifaceted disease with an intricate etiology affecting reproductive-aged women. Despite attempts to unravel the pathophysiology, the molecular mechanism of PCOS remains unknown. There are no effective or suitable therapeutic strategies available to ameliorate PCOS; however, the symptoms can be managed. In recent years, a strong association has been found between the gut microbiome and PCOS, leading to the formulation of novel ideas on the genesis and pathological processes of PCOS. Further, gut microbiome dysbiosis involving microbial metabolites may trigger PCOS symptoms via many mechanistic pathways including those associated with carbohydrates, short-chain fatty acids, lipopolysaccharides, bile acids, and gut-brain axis. We present the mechanistic pathways of PCOS-related microbial metabolites and therapeutic opportunities available to treat PCOS, such as prebiotics, probiotics, and fecal microbiota therapy. In addition, the current review highlights the emerging treatment strategies available to alleviate the symptoms of PCOS.}, } @article {pmid38227935, year = {2024}, author = {Renga, G and Nunzi, E and Stincardini, C and Pariano, M and Puccetti, M and Pieraccini, G and Di Serio, C and Fraziano, M and Poerio, N and Oikonomou, V and Mosci, P and Garaci, E and Fianchi, L and Pagano, L and Romani, L}, title = {CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance and immune homeostasis.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2023021380}, pmid = {38227935}, issn = {1528-0020}, abstract = {CPX-351, a liposomal combination of cytarabine plus daunorubicin, has been approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukaemia (t-AML) or AML with myelodysplasia-related changes as it improves survival and outcome of haematopoietic stem cell transplanted patients as compared to the continuous infusion of cytarabine plus daunorubicin (referred to as "7+3" combination). Because gut dysbiosis occurring in patients with AML during induction chemotherapy heavily impacts on the subsequent phases of therapy, we have assessed whether the superior activity of CPX-351 versus "7+3" combination in the real-life setting implicates an action on and by the intestinal microbiota. To this purpose, we have evaluated the impact of CPX-351 and "7+3" combination on mucosal barrier function, gut microbial composition and function and antifungal colonization resistance in preclinical models of intestinal damage in vitro and in vivo and fecal microbiota transplantation. We found that CPX-351, at variance with "7+3" combination, protected from gut dysbiosis, mucosal damage and gut morbidity while increasing antifungal resistance. Mechanistically, the protective effect of CPX-351 occurred through pathways involving both the host and the intestinal microbiota, namely via the activation of the aryl hydrocarbon receptor-IL-22-IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes. This study reveals how the gut microbiota may contribute to the good safety profile, with a low infection-related mortality, of CPX-351 and highlights how a better understanding of the host-microbiota dialogue may contribute to pave the way for precision medicine in AML.}, } @article {pmid38227850, year = {2024}, author = {Marasco, G and Cremon, C and Barbaro, MR and Stanghellini, V and Barbara, G}, title = {Management of Irritable Bowel Syndrome With Diarrhea.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {38227850}, issn = {1539-2031}, abstract = {Irritable bowel syndrome (IBS) with diarrhea (IBS-D) affects ~1% of the general population and is characterized by abdominal pain associated with diarrhea. IBS-D symptoms significantly impact the quality of life of patients. Major uncertainties remain regarding the optimal management of these patients. Several therapies have been investigated over the years for the treatment of IBS-D. In the initial management, commonly prescribed approaches with an effect on global IBS symptoms include a low Fermentable Oligo-, Di-, Mono-Saccharides and Polyols diet and probiotics, while antispasmodics are used for targeting abdominal pain and loperamide for diarrhea only. Additional therapeutic options for the relief of global IBS symptoms include rifaximin, 5-HT3 antagonists, gut-directed psychological therapies, and eluxadoline, while tricyclic antidepressants can target abdominal pain and bile acid sequestrants diarrhea. Promising evidence exists for the use of mesalazine and fecal microbiota transplantation in IBS-D, although further evidence is needed for definitive conclusions regarding their efficacy.}, } @article {pmid38227539, year = {2024}, author = {Fang, X and Liu, S and Muhammad, B and Zheng, M and Ge, X and Xu, Y and Kan, S and Zhang, Y and Yu, Y and Zheng, K and Geng, D and Liu, CF}, title = {Gut microbiota dysbiosis contributes to α-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson's disease.}, journal = {Neural regeneration research}, volume = {19}, number = {9}, pages = {2081-2088}, doi = {10.4103/1673-5374.391191}, pmid = {38227539}, issn = {1673-5374}, abstract = {JOURNAL/nrgr/04.03/01300535-202409000-00042/figure1/v/2024-01-16T170235Z/r/image-tiff Parkinson's disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction. Gastrointestinal dysfunction can precede the onset of motor symptoms by several years. Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson's disease, whether it plays a causal role in motor dysfunction, and the mechanism underlying this potential effect, remain unknown. CCAAT/enhancer binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling, activated by bacterial endotoxin, can promote α-synuclein transcription, thereby contributing to Parkinson's disease pathology. In this study, we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling, α-synuclein-related pathology, and motor symptoms using a rotenone-induced mouse model of Parkinson's disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation. We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier, as well as activation of the C/EBP/AEP pathway, α-synuclein aggregation, and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits. However, treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics. Importantly, we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits, intestinal inflammation, and endotoxemia. Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits, intestinal inflammation, endotoxemia, and intestinal barrier impairment. These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits, C/EBPβ/AEP signaling activation, and α-synuclein-related pathology in a rotenone-induced mouse model of Parkinson's disease. Additionally, our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson's disease.}, } @article {pmid38226811, year = {2024}, author = {Zhang, Q and Guan, G and Liu, J and Hu, W and Jin, P}, title = {Gut microbiota dysbiosis and decreased levels of acetic and propionic acid participate in glucocorticoid-induced glycolipid metabolism disorder.}, journal = {mBio}, volume = {}, number = {}, pages = {e0294323}, doi = {10.1128/mbio.02943-23}, pmid = {38226811}, issn = {2150-7511}, abstract = {The role of the gut microbiota in glucocorticoid (GC)-induced glycolipid metabolism disorder remains unclear. In our study, gut microbiota dysbiosis characterized by an increased abundance of Proteobacteria/Parasuttrerella and a decreased abundance of Lachnospiraceae_NK4A136_group was observed in mice with GC-induced glycolipid metabolism disorder. Some bacteria were shared in our previous study in patients with endogenous hypercortisolism and the mouse model used in the study. Furthermore, the depletion of the gut microbiota and fecal bacteria transplantation with control bacteria could alleviate GC-induced glycolipid metabolism disorder. Plasma acetic acid, propionic acid, and GLP-1 and the mRNA expression of the GPR41 receptor and Pcsk1 in the colon were decreased significantly in mice with GC-induced glycolipid metabolism disorder, which indicated that the gut microbiota/SCFA/GPR41/GLP-1 axis may participate in GC-induced glycolipid metabolism disorder. Our findings indicate that the gut microbiota may serve as a novel therapeutic target for GC-related metabolic disorders.}, } @article {pmid38224464, year = {2024}, author = {Bu, L and Wang, C and Bai, J and Song, J and Zhang, Y and Chen, H and Suo, H}, title = {Gut microbiome-based therapies for alleviating cognitive impairment: state of the field, limitations, and future perspectives.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo02307a}, pmid = {38224464}, issn = {2042-650X}, abstract = {Cognitive impairment (CI) is a multifaceted neurological condition that can trigger negative emotions and a range of concurrent symptoms, imposing significant public health and economic burdens on society. Therefore, it is imperative to discover a remedy for CI. Nevertheless, the mechanisms behind the onset of this disease are multifactorial, which makes the search for effective amelioration difficult and complex, hindering the search for effective measures. Intriguingly, preclinical research indicates that gut microbiota by influencing brain function, plays an important role in the progression of CI. Furthermore, numerous preclinical studies have highlighted the potential of probiotics, prebiotics, fecal microbiota transplantation (FMT), and diet in modulating the gut microbiota, thereby ameliorating CI symptoms. This review provides a comprehensive evaluation of CI pathogenesis, emphasizing the contribution of gut microbiota disorders to CI development. It also summarizes and discusses current strategies and mechanisms centered on the synergistic role of gut microbiota modulation in the microbiota-gut-brain axis in CI development. Finally, problems with existing approaches are contemplated and the development of microbial modulation strategies as therapeutic approaches to promote and restore brain cognition is discussed. Further research considerations and directions are highlighted to provide ideas for future CI prevention and treatment strategies.}, } @article {pmid38223927, year = {2024}, author = {Wu, H and Zhang, P and Zhou, J and Hu, S and Hao, J and Zhong, Z and Yu, H and Yang, J and Guo, H and Chi, J}, title = {Paeoniflorin confers ferroptosis resistance by regulating the gut microbiota and its metabolites in diabetic cardiomyopathy.}, journal = {American journal of physiology. Cell physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpcell.00565.2023}, pmid = {38223927}, issn = {1522-1563}, support = {82174204//MOST | National Natural Science Foundation of China (NSFC)/ ; 81873120//MOST | National Natural Science Foundation of China (NSFC)/ ; }, abstract = {Diabetic cardiomyopathy (DCM) is closely related to ferroptosis, a new type of cell death that mainly manifests as intracellular iron accumulation and lipid peroxidation. Paeoniflorin (PA) helps improve impaired glucose tolerance and affects intestinal flora distributiona and induce significant resistance to ferroptosis in various models . In this study,we found PA improved cardiac dysfunction in mice with DCM by alleviating myocardial damage, resisting oxidative stress and ferroptosis, and changing the community composition and structure of the intestinal microbiota. Metabolomic analysis revealed that PA-treated fecal microbiota transplantation affected metabolites in DCM mice. Based on in vivo and in vitro experiments, 11,12-EET may serve as the main effector species in the intestinal flora that mediates the cardioprotective and anti-ferroptotic effects of PA-treated FMT in DCM mice.}, } @article {pmid38223735, year = {2024}, author = {Zhou, Y and Liu, X and Gao, W and Luo, X and Lv, J and Wang, Y and Liu, D}, title = {The role of intestinal flora on tumor immunotherapy: recent progress and treatment implications.}, journal = {Heliyon}, volume = {10}, number = {1}, pages = {e23919}, pmid = {38223735}, issn = {2405-8440}, abstract = {Immunotherapy, specifically immune checkpoint inhibitors, has emerged as a promising approach for treating malignant tumors. The gut, housing approximately 70 % of the body's immune cells, is abundantly populated with gut bacteria that actively interact with the host's immune system. Different bacterial species within the intestinal flora are in a delicate equilibrium and mutually regulate each other. However, when this balance is disrupted, pathogenic microorganisms can dominate, adversely affecting the host's metabolism and immunity, ultimately promoting the development of disease. Emerging researches highlight the potential of interventions such as fecal microflora transplantation (FMT) to improve antitumor immune response and reduce the toxicity of immunotherapy. These remarkable findings suggest the major role of intestinal flora in the development of cancer immunotherapy and led us to the hypothesis that intestinal flora transplantation may be a new breakthrough in modifying immunotherapy side effects.}, } @article {pmid38223452, year = {2023}, author = {Qu, C and Xu, QQ and Yang, W and Zhong, M and Yuan, Q and Xian, YF and Lin, ZX}, title = {Gut dysbiosis aggravates cognitive deficits, amyloid pathology and lipid metabolism dysregulation in a transgenic mouse model of Alzheimer's disease.}, journal = {Journal of pharmaceutical analysis}, volume = {13}, number = {12}, pages = {1526-1547}, pmid = {38223452}, issn = {2214-0883}, abstract = {Gut dysbiosis, a well-known risk factor to triggers the progression of Alzheimer's disease (AD), is strongly associated with metabolic disturbance. Trimethylamine N-oxide (TMAO), produced in the dietary choline metabolism, has been found to accelerate neurodegeneration in AD pathology. In this study, the cognitive function and gut microbiota of TgCRND8 (Tg) mice of different ages were evaluated by Morris water maze task (MWMT) and 16S rRNA sequencing, respectively. Young pseudo germ-free (PGF) Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type (WT) mice were selected to determine the role of the gut microbiota in the process of neuropathology. Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions. Our results showed that gut dysbiosis, neuroinflammation response, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and cyclin-dependent kinase 5 (CDK5)/transcription 3 (STAT3) activation occurred in Tg mice age-dependently. Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice, with the activation of CDK5/STAT3 signaling in the brains. On the contrary, faecal microbiota transplantation from WT mice alleviated the cognitive deficits, attenuated neuroinflammation, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice. Moreover, excessive choline treatment was also shown to aggravate the cognitive deficits, Aβ deposition, neuroinflammation and CDK5/STAT3 pathway activation. These findings provide a novel insight into the interaction between gut dysbiosis and AD progression, clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.}, } @article {pmid38216353, year = {2023}, author = {Powell-Brett, S and Halle-Smith, JM and Hall, LA and Hodson, J and Phillips, ME and Roberts, KJ}, title = {Comprehensive, long-term evaluation of pancreatic exocrine insufficiency after pancreatoduodenectomy.}, journal = {Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pan.2023.11.016}, pmid = {38216353}, issn = {1424-3911}, abstract = {AIMS: Treatment of pancreatic exocrine insufficiency (PEI) following pancreatoduodenectomy (PD) improves quality of life, clinical outcomes, and survival. However, diagnosing PEI following PD is challenging owing to the difficulties with current tests and often non-specific symptoms. This work aims to quantify the true rate of long-term PEI in patients following a PD.

METHODS: Patients underwent a PEI screen approximately one to two years following PD for oncologic indication, including the [13]C Mixed triglyceride breath test ([13]CMTGT), faecal elastase 1 (FE-1) and the PEI Questionnaire (PEI-Q). Four reviewers with expertise in PEI reviewed the results blinded to other decisions to classify PEI status; disagreements were resolved on consensus.

RESULTS: 26 patients were recruited. Of those with valid test results, these were indicative of PEI based on pre-specified thresholds for 60 % (15/25) for the [13]CMTGT, 82 % (18/22) for FE-1, and 88 % (22/25) for the PEI-Q. After discussion between reviewers, the consensus PEI prevalence was 81 % (95 % CI: 61-93 %; 21/26), with 50 % (N = 13) classified as having severe, 23 % (N = 6) moderate, and 8 % (N = 2) mild PEI.

DISCUSSION: Since no ideal test exists for PEI, this collation of diagnostic modalities and blinded expert review was designed to ascertain the true rate of long-term PEI following PD. This required our cohort to survive a year, travel to hospital, and undergo a period of starvation and PERT hold, and therefore there is likely to be recruitment bias towards fitter, younger patients with less aggressive pathology. Despite this, over 80 % were deemed to have PEI, with over 90 % of these being considered moderate or severe.}, } @article {pmid38214604, year = {2024}, author = {Hartikainen, AK and Khan, I and Karjalainen, EK and Renkonen-Sinisalo, L and Arkkila, P and Jalanka, J and Lepistö, AH and Satokari, R}, title = {Microbiota and mucosal gene expression of fecal microbiota transplantation or placebo treated patients with chronic pouchitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2295445}, doi = {10.1080/19490976.2023.2295445}, pmid = {38214604}, issn = {1949-0984}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Pouchitis/therapy/metabolism ; *Colitis, Ulcerative/therapy ; *Gastrointestinal Microbiome ; *Microbiota ; Gene Expression ; Feces ; }, abstract = {Altered microbiota and impaired host immune function have been linked to the pathogenesis of pouchitis. We used 16S rRNA gene sequencing and RNA sequencing data from a previous randomized clinical trial (RCT) on fecal microbiota transplantation (FMT) therapy in 26 chronic pouchitis patients with one-year follow-up. We analyzed changes in both luminal and mucosal microbiota composition, as well as in host mucosal gene expression to gain insights into the host-microbiota interactions possibly underlying clinical outcomes of the patients. Antibiotic type and pattern of use were significant drivers of the luminal microbiota at baseline. Differential gene expression analysis indicated transition from ileal to colonic gene expression in the pouch, and upregulation in inflammation- and immune system-related pathways in the pouch. At 4 weeks, the non-relapsed FMT patients had a lower microbiota dissimilarity to the donor than the non-relapsed placebo patients (p = .02). While two FMT-treated patients showed a shift toward the donor's microbiota during the one-year follow-up, the overall FMT microbiota modulation effect was low. Patient's luminal and mucosal microbiota profiles were unstable in both FMT and placebo groups. Expression of the chemokine receptor CXCR4 was downregulated at 52 weeks compared to the baseline in the non-relapsed patients in both FMT and placebo groups. Microbiota modulation by FMT seems to be low in this patient group. The microbiota composition or alterations did not explain the relapse status of the patients. Some evidence for remission-related host gene expression pattern was found; specifically, CXCR4 expression may have a role in sustained remission.}, } @article {pmid38213259, year = {2024}, author = {Yunqi, X and Junxiang, LI and Yali, Y and Tangyou, M}, title = {The combination of gut microbiota-depleted treatment and fecal microbiota transplantation is an important strategy to verify the efficacy of Traditional Chinese Medicine though modulation of gut dysbiosis.}, journal = {Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan}, volume = {44}, number = {1}, pages = {222-223}, pmid = {38213259}, issn = {2589-451X}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Medicine, Chinese Traditional ; Dysbiosis/therapy ; Feces ; }, } @article {pmid38212672, year = {2024}, author = {Youngster, I and Eshel, A and Geva, M and Danylesko, I and Henig, I and Zuckerman, T and Fried, S and Yerushalmi, R and Shem-Tov, N and Fein, JA and Bomze, D and Shimoni, A and Koren, O and Shouval, R and Nagler, A}, title = {Fecal microbiota transplantation in capsules for the treatment of steroid refractory and steroid dependent acute graft vs. host disease: a pilot study.}, journal = {Bone marrow transplantation}, volume = {}, number = {}, pages = {}, pmid = {38212672}, issn = {1476-5365}, support = {K08CA282987//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; }, abstract = {Acute graft-versus-host disease (aGvHD) is a serious complication of allogeneic hematopoietic stem-cell transplantation with limited treatment options. The gut microbiome plays a critical role in aGvHD pathogenesis. Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach to restore gut microbial diversity. In this prospective pilot study, 21 patients with steroid-resistant or steroid-dependent lower gastrointestinal aGvHD received FMT in capsule form. At 28 days after the first FMT, the overall response rate was 52.4%, with 23.8% complete and 28.6% partial responses. However, sustained responses were infrequent, with only one patient remaining aGvHD-free long-term. FMT was generally well-tolerated. Microbiome analysis revealed dysbiosis in pre-FMT patient stool samples, with distinct microbial characteristics compared to donors. Following FMT, there was an increase in beneficial Clostridiales and a decrease in pathogenic Enterobacteriales. These findings highlight the potential of FMT as a treatment option for steroid-resistant aGvHD. Trial registration number NCT #03214289.}, } @article {pmid38203833, year = {2024}, author = {Ahn, JS and Koo, BC and Choi, YJ and Jung, WW and Kim, HS and Lee, SJ and Hong, ST and Chung, HJ}, title = {Identification of Muscle Strength-Related Gut Microbes through Human Fecal Microbiome Transplantation.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203833}, issn = {1422-0067}, support = {C380300//Korea Basic Science Institute/ ; C320000//Korea Basic Science Institute/ ; C330340//Korea Basic Science Institute/ ; HV22C0171//Korea Health Industry Development Institute/Republic of Korea ; RS-2023-00224099//National Research Foundation of Korea/ ; }, mesh = {Humans ; Animals ; Mice ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Microbiota ; Feces ; Muscle Strength ; }, abstract = {The gut microbiome is well known for its influence on human physiology and aging. Therefore, we speculate that the gut microbiome may affect muscle strength in the same way as the host's own genes. To demonstrate candidates for gut microbes affecting muscle strength, we remodeled the original gut microbiome of mice into human intestinal microbiome through fecal microbiome transplantation (FMT), using human feces and compared the changes in muscle strength in the same mice before and three months after FMT. After comparing before and after FMT, the mice were divided into three groups based on the observed changes in muscle strength: positive, none, and negative changes in muscle strength. As a result of analyzing the α-diversity, β-diversity, and co-occurrence network of the intestinal microbial community before and after FMT, it was observed that a more diverse intestinal microbial community was established after FMT in all groups. In particular, the group with increased muscle strength had more gut microbiome species and communities than the other groups. Fold-change comparison showed that Eisenbergiella massiliensis and Anaeroplasma abactoclasticum from the gut microbiome had positive contributions to muscle strength, while Ileibacterium valens and Ethanoligenens harbinense had negative effects. This study identifies candidates for the gut microbiome that contribute positively and those that contribute negatively to muscle strength.}, } @article {pmid38203771, year = {2024}, author = {Feješ, A and Belvončíková, P and Porcel Sanchis, D and Borbélyová, V and Celec, P and Džunková, M and Gardlík, R}, title = {The Effect of Cross-Sex Fecal Microbiota Transplantation on Metabolism and Hormonal Status in Adult Rats.}, journal = {International journal of molecular sciences}, volume = {25}, number = {1}, pages = {}, pmid = {38203771}, issn = {1422-0067}, support = {APVV-21-0370//Slovak Research and Development Agency/ ; VEGA 1/0649/21//Ministry of Education, Science, Research and Sport of the Slovak Republic/ ; VEGA 1/0398/24//Ministry of Education, Science, Research and Sport of the Slovak Republic/ ; CDEIGENT/2021/008//Generalitat Valenciana/ ; CIACIF/2022/070//Generalitat Valenciana/ ; }, mesh = {Animals ; Female ; Male ; Rats ; *Fecal Microbiota Transplantation ; Lipid Metabolism ; Rats, Wistar ; Testosterone/blood ; }, abstract = {Increasing evidence of sexual dimorphism in the pathophysiology of metabolic complications caused by sex steroids is under investigation. The gut microbiota represents a complex microbial ecosystem involved in energy metabolism, immune response, nutrition acquisition, and the health of host organisms. Gender-specific differences in composition are present between females and males. The purpose of this study was to use cross-sex fecal microbiota transplantation (FMT) for the detection of sex-dependent metabolic, hormonal, and gut microbiota changes in female and male recipients. Healthy non-obese female and male Wistar rats were divided into donor, same-sex, and cross-sex recipient groups. After a 30-day period of FMT administration, biochemical markers (glucose and lipid metabolism) and sex hormones were measured, and the gut microbiota was analyzed. The cross-sex male recipients displayed a significantly lower testosterone concentration compared to the males that received same-sex FMT. Sex-dependent changes caused by cross-sex FMT were detected, while several bacterial taxa correlated with plasma testosterone levels. This study represents the first to study the effect of cross-sex changes in the gut microbiome concerning metabolic and hormonal changes/status in adult non-obese Wistar rats. Herein, we present cross-sex FMT as a potential tool to modify sex-specific pathologies.}, } @article {pmid38202028, year = {2023}, author = {Friis, KH and Thomsen, KL and Laleman, W and Montagnese, S and Vilstrup, H and Lauridsen, MM}, title = {Post-Transjugular Intrahepatic Portosystemic Shunt (TIPS) Hepatic Encephalopathy-A Review of the Past Decade's Literature Focusing on Incidence, Risk Factors, and Prophylaxis.}, journal = {Journal of clinical medicine}, volume = {13}, number = {1}, pages = {}, pmid = {38202028}, issn = {2077-0383}, abstract = {Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for portal hypertension and its' complications in liver cirrhosis, yet the development of hepatic encephalopathy (HE) remains a significant concern. This review covers the reported incidence, risk factors, and management strategies for post-TIPS HE over the past decade. Incidence varies widely (7-61%), with factors like age, liver function, hyponatremia, and spontaneous portosystemic shunts influencing risk. Procedural aspects, including TIPS timing, indication, and stent characteristics, also contribute. Pharmacological prophylaxis with lactulose and rifaximin shows promise, but current evidence is inconclusive. Procedural preventive measures, such as shunt embolization and monitoring portal pressure gradients, are explored. Treatment involves pharmacological options like lactulose and rifaximin, and procedural interventions like stent diameter reduction. Ongoing studies on novel predictive markers and emerging treatments, such as faecal microbiota transplant, reflect the evolving landscape in post-TIPS HE management. This concise review provides clinicians with insights into the multifaceted nature of post-TIPS HE, aiding in improved risk assessment, prophylaxis, and management for patients undergoing TIPS procedures.}, } @article {pmid38201921, year = {2023}, author = {Poto, R and Fusco, W and Rinninella, E and Cintoni, M and Kaitsas, F and Raoul, P and Caruso, C and Mele, MC and Varricchi, G and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {The Role of Gut Microbiota and Leaky Gut in the Pathogenesis of Food Allergy.}, journal = {Nutrients}, volume = {16}, number = {1}, pages = {}, pmid = {38201921}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Food Hypersensitivity/prevention & control ; Fecal Microbiota Transplantation ; Health Status ; Intestinal Barrier Function ; }, abstract = {Food allergy (FA) is a growing public health concern, with an increasing prevalence in Western countries. Increasing evidence suggests that the balance of human gut microbiota and the integrity of our intestinal barrier may play roles in the development of FA. Environmental factors, including industrialization and consumption of highly processed food, can contribute to altering the gut microbiota and the intestinal barrier, increasing the susceptibility to allergic sensitization. Compositional and functional alterations to the gut microbiome have also been associated with FA. In addition, increased permeability of the gut barrier allows the translocation of allergenic molecules, triggering Th2 immune responses. Preclinical and clinical studies have highlighted the potential of probiotics, prebiotics, and postbiotics in the prevention and treatment of FA through enhancing gut barrier function and promoting the restoration of healthy gut microbiota. Finally, fecal microbiota transplantation (FMT) is now being explored as a promising therapeutic strategy to prevent FA in both experimental and clinical studies. In this review article, we aim to explore the complex interplay between intestinal permeability and gut microbiota in the development of FA, as well as depict potential therapeutic strategies.}, } @article {pmid38197171, year = {2024}, author = {Huang, Y and Ge, R and Qian, J and Lu, J and Qiao, D and Chen, R and Jiang, H and Cui, D and Zhang, T and Wang, N and He, S and Wang, M and Yan, F}, title = {Lacticaseibacillus rhamnosus GG Improves Periodontal Bone Repair via Gut-Blood Axis in Hyperlipidemia.}, journal = {Journal of dental research}, volume = {}, number = {}, pages = {220345231217402}, doi = {10.1177/00220345231217402}, pmid = {38197171}, issn = {1544-0591}, abstract = {Periodontal bone regeneration remains a clinical challenge, and hyperlipidemia can aggravate alveolar bone resorption. Probiotics have recently been reported to improve bone mass. We aimed to determine the role of Lacticaseibacillus rhamnosus GG (LGG) in periodontal bone regeneration improvement within the context of periodontitis with hyperlipidemia. A Sprague Dawley rat model for periodontitis, hyperlipidemia, and periodontal fenestration defect was constructed (n = 36) and administered LGG gavage for 6 wk (the rats were subsequently sacrificed). Fecal microbiota from donor rats 3 wk after LGG gavage was transplanted into recipient rats to evaluate the role of LGG-modulated gut microbiota in periodontal bone regeneration. Regenerated bone mass was detected using micro-computerized tomography and hematoxylin and eosin stain. Gut microbiota was analyzed using 16S ribosomal RNA sequencing. Serum metabolites were detected by liquid chromatography-mass spectrometry (6 wk after LGG gavage). The pro-osteogenic effects of screened serum metabolite were verified in vitro on bone marrow mesenchymal stem cells (BMMSCs). We found that the bone mineral density, bone volume (BV), trabecular bone volume fraction (BV/TV), and trabecular thickness of the regenerated periodontal bone increased after LGG gavage (P < 0.05) but had little effect on oral flora. After LGG gavage, Staphylococcus, Corynebacterium, and Collinsella in the gut of donors were significantly changed, and these differences were maintained in recipients, who also showed increased trabecular thickness of the regenerated periodontal bone (P < 0.05). These key genera were correlated with BV/TV and BV (P < 0.05). In addition, LGG gavage significantly regulated bone-related blood metabolites, of which selenomethionine promoted BMMSC osteogenesis. Notably, selenomethionine was associated with key gut genera (P < 0.05). Collectively, LGG improved periodontal bone regeneration in the context of periodontitis with hyperlipidemia by modulating gut microbiota and increasing pro-osteogenic metabolites in the blood. These results reveal new insights into the use of probiotics to promote periodontal bone regeneration via the gut-blood-bone axis.}, } @article {pmid38195483, year = {2024}, author = {Zhao, T and Yu, Z}, title = {Modified Gexia-Zhuyu Tang inhibits gastric cancer progression by restoring gut microbiota and regulating pyroptosis.}, journal = {Cancer cell international}, volume = {24}, number = {1}, pages = {21}, pmid = {38195483}, issn = {1475-2867}, abstract = {BACKGROUND: Gexia-Zhuyu Tang (GZT), a traditional Chinese medicine formula, is used to treat a variety of diseases. However, its roles in gastric cancer (GC) remain unclear.

OBJECTIVE: The aim of this study was to explore the roles and underlying molecular mechanisms of modified GZT in GC.

METHODS: The effects of modified GZT on GC were investigated by constructing mouse xenograft models with MFC cell line. The fecal samples from low-dose, high-dose, and without modified GZT treatment groups were collected for the 16S rRNA gene sequencing and fecal microbiota transplantation (FMT). Histopathological alterations of mice were evaluated using the hematoxylin-eosin (HE). Immunohistochemical (IHC) analysis with Ki67 and GSDMD was performed to measure tissue cell proliferation and pyroptosis, respectively. Proteins associated with pyroptosis, invasion, and metastasis were detected by Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to assess inflammation-related factors levels.

RESULTS: Modified GZT inhibited GC tumor growth and reduced metastasis and invasion-related proteins expression levels, including CD147, VEGF, and MMP-9. Furthermore, it notably promoted caspase-1-dependent pyroptosis, as evidenced by a dose-dependent increase in TNF-α, IL-1β, IL-18, and LDH levels, along with elevated protein expression of NLRP3, ASC, and caspase-1. Additionally, modified GZT increased species abundance and diversity of the intestinal flora. FMT assay identified that modified GZT inhibited GC tumor progression through regulation of intestinal flora.

CONCLUSIONS: Modified GZT treatment may promote pyroptosis by modulating gut microbiota in GC. This study identifies a new potential approach for the GC clinical treatment.}, } @article {pmid38195358, year = {2024}, author = {Andary, CM and Al, KF and Chmiel, JA and Gibbons, S and Daisley, BA and Parvathy, SN and Maleki Vareki, S and Bowdish, DME and Silverman, MS and Burton, JP}, title = {Dissecting mechanisms of fecal microbiota transplantation efficacy in disease.}, journal = {Trends in molecular medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.molmed.2023.12.005}, pmid = {38195358}, issn = {1471-499X}, abstract = {Fecal microbiota transplantation (FMT) has emerged as an alternative or adjunct experimental therapy for microbiome-associated diseases following its success in the treatment of recurrent Clostridioides difficile infections (rCDIs). However, the mechanisms of action involved remain relatively unknown. The term 'dysbiosis' has been used to describe microbial imbalances in relation to disease, but this traditional definition fails to consider the complex cross-feeding networks that define the stability of the microbiome. Emerging research transitions toward the targeted restoration of microbial functional networks in treating different diseases. In this review, we explore potential mechanisms responsible for the efficacy of FMT and future therapeutic applications, while revisiting definitions of 'dysbiosis' in favor of functional network restoration in rCDI, inflammatory bowel diseases (IBDs), metabolic diseases, and cancer.}, } @article {pmid38195204, year = {2024}, author = {Trøseid, M and Molinaro, A and Gelpi, M and Vestad, B and Kofoed, KF and Fuchs, A and Køber, L and Holm, K and Benfield, T and Ueland, PM and Hov, JR and Nielsen, SD and Knudsen, AD}, title = {Gut Microbiota Alterations and Circulating Imidazole Propionate Levels are Associated with Obstructive Coronary Artery Disease in People Living with HIV.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiad604}, pmid = {38195204}, issn = {1537-6613}, abstract = {BACKGROUND: The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with HIV is unknown. Emerging evidence suggests that imidazole propionate (ImP), a microbial metabolite, is linked with cardio-metabolic diseases.

METHODS: Fecal samples from participants of the Copenhagen Comorbidity in HIV infection (COCOMO) study were processed for 16S rRNA sequencing and ImP measured with liquid chromatography-tandem mass spectrometry. CAD severity was investigated by coronary CT-angiography, and participants grouped according to obstructive CAD (n=60), non-obstructive CAD (n=80), or no CAD (N=114).

RESULTS: Participants with obstructive CAD had a gut microbiota with lower diversity and distinct compositional shift, with increased abundance of Rumiococcus gnavus and Veillonella, known producers of ImP. ImP plasma levels were associated with this dysbiosis, and significantly elevated in participants with obstructive CAD. However, gut dysbiosis but not plasma ImP was independently associated with obstructive CAD after adjustment for traditional and HIV-related risk factors (adjusted odds ratio 2.7 [1.1-7.2, 95% confidence interval], p=0.048).

CONCLUSION: PLWH with obstructive CAD displays a distinct gut microbiota profile and increased circulating ImP plasma levels. Future studies should determine whether gut dysbiosis and related metabolites such as ImP are predictive of incident cardiovascular events.}, } @article {pmid38194829, year = {2023}, author = {Liu, X and Wang, C and Li, Y and Wang, Y and Sun, X and Wang, Q and Luo, J and Lv, W and Yang, X and Liu, Y}, title = {Fecal microbiota transplantation revealed the function of folic acid on reducing abdominal fat deposition in broiler chickens mediated by gut microbiota.}, journal = {Poultry science}, volume = {103}, number = {3}, pages = {103392}, doi = {10.1016/j.psj.2023.103392}, pmid = {38194829}, issn = {1525-3171}, abstract = {Excess abdominal fat reduces carcass yield and feed conversion ratio, thereby resulting in significant economic losses in the poultry industry. Our previous study demonstrated that dietary addition of folic acid reduced fat deposition and changed gut microbiota and short-chain fatty acid. However, whether folic acid regulating abdominal fat deposition was mediated by gut microbiota was unclear. A total of 210 one-day-old broiler chickens were divided into 3 groups including the control (CON), folic acid (FA), and fecal microbiota transplantation (FMT) groups. From 14th day, broiler chickens in CON and FA groups were given perfusion administration with 1 mL diluent daily, while 1 mL fecal microbiota transplantation suspension from FA group prepared before was perfusion in FMT group receiving control diets. The result showed that abdominal fat percentage was significantly lower in FA and FMT groups when compared with CON group (P < 0.05). Morphology analysis revealed that the villus height of jejunum and ileum were significantly higher in FMT group (P < 0.05), and the villus height of jejunum was also significantly higher in FA group (P < 0.05), while the diameter and cross-sectional area (CSA) of adipocytes were significantly decreased in FA and FMT groups when compared with CON group (P < 0.05). Western blot results indicated that the expression levels of FOXO1 and PLIN1 in FMT group were significantly increased (P < 0.05), whereas the expression levels of PPARγ, C/EBPα, and FABP4 were significantly decreased (P < 0.05). Additionally, the Chao1, Observed-species, Shannon and Simpson indexes in FA and FMT groups were significantly higher (P < 0.05), but the microbiota were similar between FMT and FA groups (P < 0.05). LEfSe analysis determined that Lactobacillus, Clostridium and Dehalobacterium were found to be predominant in FA group, while Oscillospira, Shigella, and Streptococcus were the dominant microflora in FMT group. Furthermore, these cecal microbiota were mostly involved in infectious disease, cellular community prokaryotes, cell motility and signal transduction in FA group (P < 0.05), whereas functional capacities involved in signal transduction, cell motility, infectious disease and environment adaptation were enriched significantly of cecal microbiota in FMT group (P < 0.05). In summary, both fecal microbiota transplantation from the broiler chickens of dietary added folic acid and dietary folic acid addition effectively reduced abdominal fat deposition, indicating that the regulatory effect of folic acid on abdominal fat deposition was mediated partly by gut microbiota in broiler chickens.}, } @article {pmid38194333, year = {2024}, author = {Birn, FH and Wester, SR and Andreasen, SE and Hvas, CL and Bager, P}, title = {Quality of life among older patients receiving faecal microbiota transplant for Clostridioides difficile infection.}, journal = {British journal of nursing (Mark Allen Publishing)}, volume = {33}, number = {1}, pages = {8-14}, doi = {10.12968/bjon.2024.33.1.8}, pmid = {38194333}, issn = {0966-0461}, mesh = {Humans ; Aged ; *Quality of Life ; Fecal Microbiota Transplantation ; *Clostridium Infections/therapy ; Health Personnel ; Patients ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has mainly been studied in quantitative research to investigate effect rates. However, there is a lack of qualitative studies to explore patient perspectives.

AIM: To explore perceptions of quality of life in older patients with Clostridioides difficile infection (CDI) at least 1 week after receiving FMT.

METHOD: A qualitative study examining quality of life for patients treated with FMT.

FINDINGS: Patients with a permanent or transient treatment effect experienced an increase in quality of life in the physical, psychological and social domains. However, patients who did not respond to the treatment experienced negative impacts on their psychological, physical, and social domains. Although patients found the content unappealing, none had reservations about receiving the treatment.

CONCLUSION: This study highlights the importance of considering the psychological, social and physical wellbeing of patients when assessing the efficacy of FMT as a treatment option for patients with CDI. It further emphasises the importance of health professionals identifying patients' individual ways of handling the disease and everyday life to improve their quality of life.}, } @article {pmid38193712, year = {2024}, author = {Guo, H and Cui, J and Li, Q and Liang, X and Li, J and Yang, B and Kalds, P and Chen, Y and Yang, Y}, title = {A multi-omic assessment of the mechanisms of intestinal microbes used to treat diarrhea in early-weaned lambs.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0095323}, doi = {10.1128/msystems.00953-23}, pmid = {38193712}, issn = {2379-5077}, abstract = {Before weaning, the digestive system of lambs is not well developed; hence, its resistance to infectious diseases is weak. Under intensive feeding systems, lambs can easily be stressed and the risk of bacterial infection is high, which causes diarrhea, which in turn may cause mortality and significant economic losses to the livestock industry. With the elimination of antibiotics in animal feed, the incidence of mortality due to intestinal illnesses in lambs has gradually increased. There are several types of probiotics routinely used in young animals, but the effects and processes of their usage have only been assessed in monogastric animals. The lack of data on ruminants, particularly sheep, has severely hampered the process of efficient and healthy sheep breeding. Therefore, there is an urgent need to identify effective and safe functional supplements for lambs.}, } @article {pmid38193707, year = {2024}, author = {Ghosh, S and Erickson, D and Chua, MJ and Collins, J and Jala, VR}, title = {The microbial metabolite urolithin A reduces Clostridioides difficile toxin expression and toxin-induced epithelial damage.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0125523}, doi = {10.1128/msystems.01255-23}, pmid = {38193707}, issn = {2379-5077}, abstract = {Therapy for Clostridioides difficile infections includes the use of antibiotics, immunosuppressors, and fecal microbiota transplantation. However, these treatments have several drawbacks, including the loss of colonization resistance, the promotion of autoimmune disorders, and the potential for unknown pathogens in donor samples. To date, the potential benefits of microbial metabolites in CDI-induced colitis have not been fully investigated. Here, we report for the first time that the microbial metabolite urolithin A has the potential to block toxin production from C. difficile and enhance gut barrier function to mitigate CDI-induced colitis.}, } @article {pmid38193259, year = {2024}, author = {De Paepe, E and Plekhova, V and Vangeenderhuysen, P and Baeck, N and Bullens, D and Claeys, T and De Graeve, M and Kamoen, K and Notebaert, A and Van de Wiele, T and Van Den Broeck, W and Vanlede, K and Van Winckel, M and Vereecke, L and Elliott, C and Cox, E and Vanhaecke, L}, title = {Integrated gut metabolome and microbiome fingerprinting reveals that dysbiosis precedes allergic inflammation in IgE-mediated pediatric cow's milk allergy.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.16005}, pmid = {38193259}, issn = {1398-9995}, support = {//Fonds Wetenschappelijk Onderzoek/ ; //Bijzonder Onderzoeksfonds UGent/ ; }, abstract = {BACKGROUND: IgE-mediated cow's milk allergy (IgE-CMA) is one of the first allergies to arise in early childhood and may result from exposure to various milk allergens, of which β-lactoglobulin (BLG) and casein are the most important. Understanding the underlying mechanisms behind IgE-CMA is imperative for the discovery of novel biomarkers and the design of innovative treatment and prevention strategies.

METHODS: We report a longitudinal in vivo murine model, in which two mice strains (BALB/c and C57Bl/6) were sensitized to BLG using either cholera toxin or an oil emulsion (n = 6 per group). After sensitization, mice were challenged orally, their clinical signs monitored, antibody (IgE and IgG1) and cytokine levels (IL-4 and IFN-γ) measured, and fecal samples subjected to metabolomics. The results of the murine models were further extrapolated to fecal microbiome-metabolome data from our population of IgE-CMA (n = 22) and healthy (n = 23) children (Trial: NCT04249973), on which polar metabolomics, lipidomics and 16S rRNA metasequencing were performed. In vitro gastrointestinal digestions and multi-omics corroborated the microbial origin of proposed metabolic changes.

RESULTS: During mice sensitization, we observed multiple microbially derived metabolic alterations, most importantly bile acid, energy and tryptophan metabolites, that preceded allergic inflammation. We confirmed microbial dysbiosis, and its associated effect on metabolic alterations in our patient cohort, through in vitro digestions and multi-omics, which was accompanied by metabolic signatures of low-grade inflammation.

CONCLUSION: Our results indicate that gut dysbiosis precedes allergic inflammation and nurtures a chronic low-grade inflammation in children on elimination diets, opening important new opportunities for future prevention and treatment strategies.}, } @article {pmid38193161, year = {2024}, author = {Margalit-Yehuda, R and Maradey-Romero, C and Davidov, Y and Ram, E and Carter, D}, title = {Comparison of etiologic and physiologic characteristics of fecal incontinence in men and women.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00113.2023}, pmid = {38193161}, issn = {1522-1547}, abstract = {BACKGROUND AND AIMS: Fecal incontinence (FI) is often underreported and underestimated in men. Our aims were to clarify the causes and the physiologic characteristics of FI in men and to underline the differences between etiological and physiological factors in men and women diagnosed with FI.

METHODS: The study cohort encompassed 200 men and 200 women that underwent anatomical and physiological evaluation for FI in a tertiary referral center specializing in pelvic floor disorders. All patients underwent endoanal ultrasound and anorectal manometry. Evacuation proctography was performed in some patients. Demographic, medical, anatomic and physiologic parameters were compared between the 2 study groups.

RESULTS: Urge incontinence was the most frequent type of FI in both genders. In men, anal fistula, history of anal surgeries, rectal tumors and pelvic radiotherapy were common etiologic factors, while history of pelvic surgeries was more common in women. Associated urinary incontinence was reported more frequently by women. External anal sphincter defects, usually anterior, were more common in women (M:1.5%,W:24%,p<0.0001), while Internal anal sphincter defects prevalence was similar in men and women (M:16%,W12%,p=0.19). Decreased resting and squeeze pressures were less common in men (M:29%,W:46%,p<0.0001: M:44%,W:66%,p<0.0001). The incidence of rectal hyposensitivity was higher in men (M:33%,W:18%,p<0.0001), while rectal hypersensitivity was higher in women (M:29%,W:49%,p<0.0001). Anorectal dyssynergia was more common in men (M:66%,W:37%,p<0.0001).

CONCLUSIONS: Significantly different etiologic factors and physiologic characteristics for FI were found in men. Acknowledging these differences is significant and may yield better treatment options.}, } @article {pmid38192292, year = {2023}, author = {Dai, W and Cai, D and Zhou, S and Li, A and Xie, J and Zhang, J}, title = {Uncovering a causal connection between the Lachnoclostridium genus in fecal microbiota and non-alcoholic fatty liver disease: a two-sample Mendelian randomization analysis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1276790}, pmid = {38192292}, issn = {1664-302X}, abstract = {BACKGROUND: Previous observational studies have indicated that an imbalance in gut microbiota may contribute to non-alcoholic fatty liver disease (NAFLD). However, given the inevitable bias and unmeasured confounders in observational studies, the causal relationship between gut microbiota and NAFLD cannot be deduced. Therefore, we employed a two-sample Mendelian randomization (TSMR) study to assess the causality between gut microbiota and NAFLD.

METHODS: The gut microbiota-related genome-wide association study (GWAS) data of 18,340 individuals were collected from the International MiBioGen consortium. The GWAS summary data for NAFLD from the Anstee cohort (1,483 cases and 17,781 controls) and the FinnGen consortium (894 cases and 217,898 controls) were utilized in the discovery and verification phases, respectively. The inverse variance weighted (IVW) method was used as the principal method in our Mendelian randomization (MR) study, with sensitivity analyses using the MR-Egger, weighted median, simple mode, and weighted mode methods. The MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy. Moreover, a fixed-effect meta-analysis was conducted to verify the robustness of the results.

RESULTS: The gene prediction results showed that at the genus level, four gut microbiota were causally associated with NAFLD in the GWAS conducted by Anstee et al. The relative abundance of Intestinimonas (OR: 0.694, 95%CI: 0.533-0.903, p = 0.006, IVW), Lachnoclostridium (OR: 0.420, 95%CI: 0.245-0.719, p = 0.002, IVW), and Senegalimassilia (OR: 0.596, 95%CI: 0.363-0.978, p = 0.041, IVW) was negatively associated with NAFLD. The relative abundance of Ruminococcus1 (OR: 1.852, 95%CI: 1.179-2.908, p = 0.007, IVW) was positively correlated with NAFLD. Among them, the Lachnoclostridium genus was validated in FinnGen GWAS (OR: 0.53, 95%CI: 0.304-0.928, p = 0.026, IVW). The Lachnoclostridium genus was also significantly associated with NAFLD risk in the meta-analyses (OR: 0.470, 95%CI: 0.319-0.692, p = 0.0001, IVW). No heterogeneity or pleiotropy was observed.

CONCLUSION: This study provided new evidence of the relationship between the Lachnoclostridium genus and NAFLD, suggesting that augmentation of the relative abundance of the Lachnoclostridium genus through the oral administration of probiotics or fecal microbiota transplantation could be an effective way to reduce the risk of NAFLD.}, } @article {pmid38191517, year = {2024}, author = {Ichikawa, M and Okada, H and Nakamoto, N and Taniki, N and Chu, PS and Kanai, T}, title = {The gut-liver axis in hepatobiliary diseases.}, journal = {Inflammation and regeneration}, volume = {44}, number = {1}, pages = {2}, pmid = {38191517}, issn = {1880-9693}, support = {JP21ek0109416//Japan Agency for Medical Research and Development/ ; }, abstract = {Recent advances in the analysis of intestinal bacteria have led to reports of variations in intestinal bacterial levels among hepatobiliary diseases. The mechanisms behind the changes in intestinal bacteria in various hepatobiliary diseases include the abnormal composition of intestinal bacteria, weakening of the intestinal barrier, and bacterial translocation outside the intestinal tract, along with their metabolites, but many aspects remain unresolved. Further research employing clinical studies and animal models is expected to clarify the direct relationship between intestinal bacteria and hepatobiliary diseases and to validate the utility of intestinal bacteria as a diagnostic biomarker and potential therapeutic target. This review summarizes the involvement of the microbiota in the pathogenesis of hepatobiliary diseases via the gut-liver axis.}, } @article {pmid38191281, year = {2024}, author = {Tariq, R and Loftus, EV and Pardi, D and Khanna, S}, title = {Durability and outcomes of fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with moderate to severe inflammatory bowel disease.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2023.00100}, pmid = {38191281}, issn = {1598-9100}, } @article {pmid38190716, year = {2024}, author = {Cao, Q and Zhao, M and Su, Y and Liu, S and Lin, Y and Da, H and Yue, C and Liu, Y and Jing, D and Zhao, Q and Liu, N and Du, J and Zuo, Z and Fu, Y and Chen, A and Birnbaumer, L and Yang, Y and Dai, B and Gao, X}, title = {Chronic stress dampens Lactobacillus johnsonii-mediated tumor suppression to enhance colorectal cancer progression.}, journal = {Cancer research}, volume = {}, number = {}, pages = {}, doi = {10.1158/0008-5472.CAN-22-3705}, pmid = {38190716}, issn = {1538-7445}, abstract = {Colorectal cancer (CRC) development and outcome are impacted by modifiable risk factors, including psychological stress. The gut microbiota has also been shown to be linked to psychological factors. Here, we found a marked deteriorative effect of chronic stress in multiple CRC models, including chemically-induced (AOM/DSS), genetically engineered (APCmin/+), and xenograft tumor mouse models. RNA-seq data from colon tissues revealed that expression of stemness-related genes was upregulated in the stressed CRC group by activated β-catenin signaling, which was further confirmed by results from ex vivo organoid analyses as well as in vitro and in vivo cell tumorigenicity assays. 16S rRNA sequencing of the gut microbiota showed that chronic stress disrupted gut microbes, and antibiotic treatment and fecal microbiota transplantation abolished the stimulatory effects of chronic stress on CRC progression. Stressed CRC mice displayed a significant decrease in Lactobacillus johnsonii (L. johnsonii) abundance, which was inversely correlated with tumor load. Moreover, protocatechuic acid (PCA) was identified as a beneficial metabolite produced by L. johnsonii based on metabolome sequencing and LC‒MS/MS analysis. Replenishment of L. johnsonii or PCA blocked chronic stress-induced CRC progression by decreasing β-catenin expression. Furthermore, PCA activated the cGMP pathway, and the cGMP agonist sildenafil abolished the effects of chronic stress on CRC. Altogether, these data identify that stress impacts the gut microbiome to support CRC progression.}, } @article {pmid38188335, year = {2023}, author = {Hu, Y and Hu, C and Jiang, J and Zhang, J and Li, Y and Peng, Z}, title = {Clostridioides difficile infection after extracorporeal membrane oxygenation support for acute myocardial infarction: a case report.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1333209}, pmid = {38188335}, issn = {2296-858X}, abstract = {INTRODUCTION: Restored cardiopulmonary function is efficiently achieved by utilizing extracorporeal membrane oxygenation (ECMO). Nevertheless, the incidence of Clostridioides difficile infection (CDI) associated with ECMO is relatively uncommon.

CASE PRESENTATION: In this report, we present the case of a 59-year-old male with severe chest pain due to acute myocardial infarction, subsequently necessitating ECMO support. During the first day of hospitalization, pulmonary infections were observed, and piperacillin-tazobactam was prescribed for 7 days at low dosages. However, the patient developed severe diarrhea 4 days later. After ruling out common pathogens, we suspected the occurrence of CDI and performed genetic testing for C. difficile toxin, confirming our diagnosis. The prescription of vancomycin resulted in slight improvement, while fecal microbiota transplantation (FMT) proved to be more effective.

CONCLUSION: In this case, temporary application of ECMO was applied, and the anti-infective treatment relied on the use of antibiotics at short-term, low-dose, and low CDI risk. Hence, the occurrence of CDI was considered an uncommon event, which may serve as a reference for future cases.}, } @article {pmid38187130, year = {2023}, author = {Zhang, R and Qiu, W and Sun, X and Li, J and Geng, X and Yu, S and Liu, Y and Huang, H and Li, M and Fan, Z and Li, M and Lv, G}, title = {Gut microbiota dynamics in a 1-year follow-up after adult liver transplantation in Northeast China.}, journal = {Frontiers in physiology}, volume = {14}, number = {}, pages = {1266635}, pmid = {38187130}, issn = {1664-042X}, abstract = {Background: Liver transplantation (LTx) is the most effective treatment for end-stage liver diseases. Gut microorganisms influence the host physiology. We aim to profile the dynamics of gut microbiota in the perioperative period and a 1-year follow-up of LTx recipients in Northeast China. Methods: A total of 257 fecal samples were longitudinally collected from 85 LTx patients using anal swabs from pre-LTx to 1-year post-LTx. A total of 48 fecal samples from end-stage liver disease patients without LTx served as the control. 16S rRNA sequencing was used to analyze gut microbiota diversity, bacterial genera, phenotype classification, and metabolic pathways. Results: The diversity of gut microbiota decreased significantly after transplantation, accompanied by a profound change in the microbial structure, which is characterized by increased abundance of facultative anaerobic bacteria dominated by g_Enterococcus and reduced anaerobic bacteria composition. Predicted functional analysis also revealed disturbances in the metabolic pathway of the gut microbiota. After LTx, the diversity of microbiota gradually recovered but to a less preoperative level after 1 year of recovery. Compared with pre-transplantation, the microbiome structure was characterized by an increase in Acidaminococcus and Acidithiobacillus after 1 year of transplantation. Conclusion: LTx and perioperative treatment triggered gut microbial dysbiosis. The gut microbiota was restructured after LTx to near to but significantly differed from that of pre-LTx.}, } @article {pmid38184271, year = {2024}, author = {Yang, T and Qin, N and Liu, F and Zhao, Y and Liu, W and Fan, D}, title = {Berberine regulates intestinal microbiome and metabolism homeostasis to treat ulcerative colitis.}, journal = {Life sciences}, volume = {}, number = {}, pages = {122385}, doi = {10.1016/j.lfs.2023.122385}, pmid = {38184271}, issn = {1879-0631}, abstract = {AIMS: This study aims to investigate the effects of berberine (BBR) on the intestinal microbiome (IM) and serum metabolome in ulcerative colitis (UC). Furthermore, the underlying molecular mechanisms of BBR in treating UC also will be explored systematically.

MATERIALS AND METHODS: A multi-omics approach that integrates the 16s rDNA, serum metabolome, transcriptomics and bioinformatics was profiled to investigate the potential effects of BBR on the IM, serum metabolites and metabolic pathways, and gene expression. In addition, BBR-induced fecal microbiota transplantation (BBR_FMT) was conducted in pseudo germ-free mice combined with the UC model to explore the effects of the IM on metabolic pathways and gene expression. The results of the transcriptomics and metabolic pathway-related genes were further examined by real-time PCR and western blot.

KEY FINDINGS: BBR ameliorated the community of IM and significantly promoted the abundance of f__Muribaculaceae, Bacteroides, Dubosiella, Allobaculum and Akkermansia. The metabolic profiles in UC mice were significantly modulated by BBR treatment. Furthermore, the inflammation-related metabolites and metabolic pathways in serum were negatively correlated with the abundance of Bacteroides and Akkermansia, which were induced by BBR treatment. BBR_FMT significantly inhibited the arachidonic acid (AA) metabolism pathway and its multiple markers with the mediation of the IM.

SIGNIFICANCE: BBR ameliorated serum metabolic homeostasis by regulating the IM. The inhibition of the AA metabolism pathway and its multiple markers was one of the mechanisms of BBR in the treatment of UC.}, } @article {pmid38184214, year = {2024}, author = {Ji, H and Feng, S and Liu, Y and Cao, Y and Lou, H and Li, Z}, title = {Effect of GVHD on the gut and intestinal microflora.}, journal = {Transplant immunology}, volume = {}, number = {}, pages = {101977}, doi = {10.1016/j.trim.2023.101977}, pmid = {38184214}, issn = {1878-5492}, abstract = {Graft-versus-host disease (GVHD) is one of the most important cause of death in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). The gastrointestinal tract is one of the most common sites affected by GVHD. However, there is no gold standard clinical practice for diagnosing gastrointestinal GVHD (GI-GVHD), and it is mainly diagnosed by the patient's clinical symptoms and related histological changes. Additionally, GI-GVHD causes intestinal immune system disorders, damages intestinal epithelial tissue such as intestinal epithelial cells((IEC), goblet, Paneth, and intestinal stem cells, and disrupts the intestinal epithelium's physical and chemical mucosal barriers. The use of antibiotics and diet alterations significantly reduces intestinal microbial diversity, further reducing bacterial metabolites such as short-chain fatty acids and indole, aggravating infection, and GI-GVHD. gut microbe diversity can be restored by fecal microbiota transplantation (FMT) to treat refractory GI-GVHD. This review article focuses on the clinical diagnosis of GI-GVHD and the effect of GVHD on intestinal flora and its metabolites.}, } @article {pmid37924444, year = {2024}, author = {Rubio-Mora, E and Carrascoso, GR and Rodríguez, JG}, title = {Sapovirus infection as another cause of persistent viral diarrhea: case series and review of the literature.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {43}, number = {1}, pages = {55-59}, pmid = {37924444}, issn = {1435-4373}, mesh = {Humans ; Child ; Infant ; *Sapovirus/genetics ; Retrospective Studies ; *Caliciviridae Infections/diagnosis ; *Gastroenteritis/diagnosis ; Diarrhea/diagnosis ; *Adenovirus Infections, Human ; *Enterovirus Infections ; Immunosuppressive Agents ; Feces ; }, abstract = {Human sapovirus (HuSaV) is a common cause of gastroenteritis worldwide and is responsible for approximately 4% of acute gastroenteritis episodes in Europe. As reported with norovirus, patients with immunocompromised states are at increased risk of developing HuSaV infection, which can lead to persistent diarrhea and chronic viral shedding in some individuals. Chronic infections are incompletely investigated in these patients, and, due to the lack of specific treatment for HuSaV infection, different clinical approaches were carried out in order to provide further evidence on clinical evolution of these patients with different treatments. In this retrospective study, we report five immunocompromised pediatric patients with recurrent diarrhea caused by HuSaV and long-term viral shedding. Stool samples were analyzed by real-time PCR and tested for enteropathogenic viruses and bacteria and protozoa. Among transplant recipients, reduction of immunosuppressant therapy led to clinical improvement and relief of symptoms, maintaining a balance between managing the infection and preventing graft rejection. Nitazoxanide for 14 days was only used in one of these patients, showing to be an effective therapy to achieve reduction in time to resolution of symptoms. Neither nitazoxanide nor modification of immunosuppressant therapy could avoid recurrences. Further investigations are needed to develop new approaches that can both clear the infection and avoid persistent diarrhea in these patients.}, } @article {pmid38184015, year = {2024}, author = {Wang, Y and Zhang, X and Yao, Y and Hu, S and Wang, W and Wang, D and Huang, C and Liu, H and Zhang, Q and He, T and Wang, S and Wu, Z and Jiang, R and Yang, C}, title = {Inferior social hierarchy is vulnerable to anxiety-like behavior in chronic pain mice: Potential role of gut microbiota and metabolites.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {106402}, doi = {10.1016/j.nbd.2024.106402}, pmid = {38184015}, issn = {1095-953X}, abstract = {Social dominance is a universal phenomenon among grouped animals that profoundly affects survival, health, and reproductive success by determining access to resources, and exerting a powerful influence on subsequent behavior. However, the understanding of pain and anxiety comorbidities in dominant or subordinate animals suffering from chronic pain is not well-defined. Here, we provide evidence that subordinate mice are more susceptible to pain-induced anxiety compared to dominant mice. We propose that the gut microbiota may play a mediating role in this mechanism. Our findings demonstrate that transplantation of fecal microbiota from subordinate mice with chronic inflammatory pain, but not dominant mice, into antibiotics-treated pseudo-germ-free mice significantly amplifies anxiety-like phenotypes, highlighting the critical involvement of gut microbiota in this behavioral response. Using chronic inflammatory pain model, we carried out 16S rRNA sequencing and untargeted metabolomic analyses to explore the relationship between microbiota and metabolites in a stable social hierarchy of mice. Interestingly, anxiety-like behaviors were directly associated with some microbial genera and metabolites, especially bile acid metabolism. Overall, we have demonstrated a close relationship between social status and anxiety susceptibility, highlighting the contributions of gut microbiota and the associated metabolites in the high-anxiety state of subordinate mice with chronic inflammatory pain.}, } @article {pmid38183474, year = {2024}, author = {Lin, QY and Du, JJ and Xu, H and Lv, MK and Xu, L and Li, J and Cao, ZH}, title = {Effects of fecal microbial transplantation on police performance and transportation stress in Kunming police dogs.}, journal = {Applied microbiology and biotechnology}, volume = {108}, number = {1}, pages = {1-13}, pmid = {38183474}, issn = {1432-0614}, support = {202305AC160040//Yunnan Provincial Middle-Young Academic and Technical Leader Candidate/ ; YNWR-QNBJ-2018-137//Young Top-notch Talent of Yunnan Xingdian Support Project for High Level Talents/ ; }, mesh = {Dogs ; Animals ; *Fecal Microbiota Transplantation ; *Working Dogs ; Feces ; Bifidobacterium ; Diarrhea ; }, abstract = {Fecal microbiota transplantation (FMT) has been shown to improve gut dysbiosis in dogs; however, it has not completely been understood in police dogs. This study aimed to investigate the effects of FMT on performance and gut microflora in Kunming police dogs. Twenty Wolf Cyan dogs were randomly assigned to receive physiological saline or fecal suspension at low, medium, or high doses through oral gavage for 14 days. Growth performance, police performance, serum biochemical profiling, and gut microflora were determined 2-week post-FMT. Dogs after FMT treatment were also subjected to an hour road transportation and then were evaluated for serum stress indicators. Overall, FMT enhanced the growth performance and alleviated diarrhea rate in Kunming dogs with the greatest effects occurring in the low dose FMT (KML) group. The improvement of FMT on police performance was also determined. These above alterations were accompanied by changed serum biochemical parameters as indicated by elevated total protein and albumin and reduced total cholesterol and glycerol. Furthermore, the serum stress indicators after road transportation in dog post-FMT significantly decreased. Increased bacterial diversity and modified bacterial composition were found in the feces of dogs receiving FMT. The fecal samples from FMT dogs were characterized by higher abundances of the genera Lactobacillus, Prevotella, and Fusobacterium and lower concentrations of Cetobacterium, Allobaculum, Bifidobacterium, and Streptococcus. The present study supports a potential benefit of FMT on police performance in Kunming dogs. KEY POINTS: • FMT improves the growth performance and reduces diarrhea rates in Kunming police dogs. • FMT alleviates the serum stress profiles after road transportation in Kunming police dogs. • FMT modifies the gut microbiota composition of Kunming police dogs.}, } @article {pmid38183010, year = {2024}, author = {Pourali, G and Kazemi, D and Chadeganipour, AS and Arastonejad, M and Kashani, SN and Pourali, R and Maftooh, M and Akbarzade, H and Fiuji, H and Hassanian, SM and Ghayour-Mobarhan, M and Ferns, GA and Khazaei, M and Avan, A}, title = {Microbiome as a biomarker and therapeutic target in pancreatic cancer.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {16}, pmid = {38183010}, issn = {1471-2180}, mesh = {Humans ; *Pancreatic Neoplasms/diagnosis/therapy ; Biomarkers ; *Microbiota ; Anti-Bacterial Agents ; Dysbiosis/therapy ; Tumor Microenvironment ; }, abstract = {Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.}, } @article {pmid38181823, year = {2024}, author = {Zheng, C and Wang, L and Zou, T and Lian, S and Luo, J and Lu, Y and Hao, H and Xu, Y and Xiang, Y and Zhang, X and Xu, G and Zou, X and Jiang, R}, title = {Ileitis promotes MASLD progression via bile acid modulation and enhanced TGR5 signaling in ileal CD8+ T cells.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2023.12.024}, pmid = {38181823}, issn = {1600-0641}, abstract = {BACKGROUND: Clinical evidence substantiates a link between inflammatory bowel disease (IBD), particularly Crohn's disease (CD), and metabolic dysfunction associated steatotic liver disease (MASLD). This study aims to explore the underlying molecular mechanisms responsible for this association.

METHODS: MASLD was induced by administering high-fat and western diets, while IBD was induced using dextran sulfate sodium salt (DSS) and the Il10 KO mice model. The investigation into the role of secondary bile acids (SBA) in ileitis involved employing metagenomic sequencing, conducting metabolomics detection, performing fecal bacterial transplantation, and constructing CD8[+] T cell specific gene knockout mice.

RESULTS: In MASLD+DSS and Il10 KO MASLD mice, we observed ileitis characterized by T cell infiltration and activation in the terminal ileum. This condition resulted in decreased bile acid levels in the portal vein and liver, inhibited hepatic Farnesol X receptor (FXR) activation, and exacerbated MASLD. Metagenomic and metabolomic analysis of ileum contents revealed increased Clostridium proliferation and elevated SBA levels in MASLD-associated ileitis. Experiments using germ-free mice and fecal microbiota transplantation suggested an association between SBA and MASLD-related ileitis. In vitro, SBA promoted CD8[+] T cell activation via the TGR5, mTOR, and Oxidative Phosphorylation (OXPHOS) pathways. In vivo, TGR5 knockout in CD8[+] T cells effectively alleviated ileitis and worsened the MASLD phenotype. Clinical data further supported these findings, demonstrating a positive correlation ileitis and MASLD.

CONCLUSION: MASLD-induced changes in intestinal flora result in elevated levels of SBA in the ileum. In the presence of compromised intestinal barrier, this leads to severe CD8[+] T cell-mediated ileitis through the TGR5/mTOR/OXPHOS signaling pathway. Ileitis-induced tissue damage impairs enterohepatic circulation, inhibits hepatic FXR activation, and exacerbates the MASLD phenotype.

IMPACT AND IMPLICATIONS: Our study provides a comprehensive investigation of the interplay and underlying mechanisms connecting ileitis and MASLD. SBA produced by intestinal bacteria, as the critical link between MASLD and ileitis. This compound exerts its influence by disrupting liver lipid metabolism through the promotion of CD8[+] T cell-mediated ileitis. In future endeavors to prevent and treat MASLD, it is essential to thoroughly account for the impact of the intestinal tract, especially the ileum, on liver function via the enterohepatic circulation.}, } @article {pmid38180642, year = {2024}, author = {Theofilis, P and Vlachakis, PK and Oikonomou, E and Tsioufis, K and Tousoulis, D}, title = {Targeting the Gut Microbiome to Treat Cardiometabolic Disease.}, journal = {Current atherosclerosis reports}, volume = {}, number = {}, pages = {}, pmid = {38180642}, issn = {1534-6242}, abstract = {PURPOSE OF REVIEW: Cardiometabolic diseases, which include obesity, type 2 diabetes, and cardiovascular diseases, constitute a worldwide health crisis of unparalleled proportions. The human gut microbiota has emerged as a prominent topic of inquiry in the search for novel treatment techniques. This review summarizes current research on the potential of addressing the gut microbiota to treat cardiometabolic disease.

RECENT FINDINGS: Recent studies have highlighted a complex link between the gut microbiota and host physiology, shedding light on the several processes through which gut microorganisms impact metabolic health, inflammation, and cardiovascular function. Furthermore, a growing corpus of research is available on microbiome-based therapies such as dietary interventions, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. These therapies show promise as methods for reshaping the gut microbiota and, as a result, improving cardiometabolic outcomes. However, hurdles remain, ranging from the intricacies of microbiome research to the necessity for tailored treatments that take individual microbial variations into consideration, emphasizing the significance of furthering research to bridge the gap between microbiome science and clinical practice. The gut microbiome is a beacon of hope for improving the management of cardiometabolic disease in the age of precision medicine, since its association with their pathophysiology is constantly being unraveled and strengthened. Available studies point to the potential of gut microbiome-based therapeutics, which remains to be tested in appropriately designed clinical trials. Further preclinical research is, however, essential to provide answers to the existing obstacles, with the ultimate goal of enhancing patient care.}, } @article {pmid37216694, year = {2023}, author = {Strassmann, V and Silva-Alvarenga, E and Emile, SH and Garoufalia, Z and DaSilva, G and Wexner, SD}, title = {Gracilis Muscle Interposition: A Valuable Tool for the Treatment of Failed Repair of Post-partum Rectovaginal Fistulas-A Single-Center Experience.}, journal = {The American surgeon}, volume = {89}, number = {12}, pages = {6366-6369}, doi = {10.1177/00031348231175481}, pmid = {37216694}, issn = {1555-9823}, mesh = {Female ; Humans ; Adult ; Rectovaginal Fistula/etiology/surgery ; Retrospective Studies ; *Gracilis Muscle/transplantation ; Surgical Flaps/transplantation ; *Rectal Fistula/surgery ; Postoperative Complications/surgery ; Postpartum Period ; Treatment Outcome ; }, abstract = {INTRODUCTION: Rectovaginal fistulas (RVFs) account for approximately 40% of anorectal complications from obstetrical trauma. Treatment can be challenging requiring multiple surgical repairs. Interposition of healthy transposed tissue (lotus or Martius flap or gracilis muscle) has been used for recurrent RVF. We aimed to review our experience with gracilis muscle interposition (GMI) for post-partum RVF.

METHODS: A retrospective analysis of patients who underwent GMI for post-partum RVF from February 1995 to December 2019 was undertaken. Patient demographics, number of prior treatments, comorbidities, tobacco use, postoperative complications, additional procedures, and outcome were assessed. Success was defined as absence of leakage from the repair site after stoma reversal.

RESULTS: Six of 119 patients who underwent GMI did so for recurrent post-partum RVF. Median age was 34.2 (28-48) years. All patients had at least 1 previously failed procedure [median: 3 (1-7)] including endorectal advancement flap, fistulotomy, vaginoplasty, mesh interposition, and sphincteroplasty. All patients underwent fecal diversion prior to or at initial procedure. Success was achieved in 4/6 (66.7%) patients; 2 underwent further procedures (1 fistulotomy and 1 rectal flap advancement) for a final 100% success rate as all ileostomies were reversed. Morbidity was reported in 3 (50%) patients, including wound dehiscence, delayed rectoperineal fistula, and granuloma formation in one each, all managed without surgery. There was no morbidity related to stoma closure.

CONCLUSIONS: Gracilis muscle interposition is a valuable tool for recurrent post-partum RVF. Our ultimate success rate in this very small series was 100% with a relatively low morbidity rate.}, } @article {pmid38176929, year = {2023}, author = {Zhang, W and Ye, Y and Song, J and Sang, T and Xia, T and Xie, L and Qiu, X and Zeng, Q and Luo, X}, title = {Research Progress of Microbiota-Gut-Brain Axis in Parkinson's Disease.}, journal = {Journal of integrative neuroscience}, volume = {22}, number = {6}, pages = {157}, doi = {10.31083/j.jin2206157}, pmid = {38176929}, issn = {0219-6352}, abstract = {Parkinson's disease (PD) is a common neurodegenerative disorder characterized by misfolding of α-synuclein. Clinical manifestations include slowly developing resting tremor, muscle rigidity, bradykinesia and abnormal gait. The pathological mechanisms underlying PD are complex and yet to be fully elucidated. Clinical studies suggest that the onset of gastrointestinal symptoms may precede motor symptoms in PD patients. The microbiota-gut-brain axis plays a bidirectional communication role between the enteric nervous system and the central nervous system. This bidirectional communication between the brain and gut is influenced by the neural, immune and endocrine systems related to the gut microbiome. A growing body of evidence indicates a strong link between dysregulation of the gut microbiota and PD. In this review, we present recent progress in understanding the relationship between the microbiota-gut-brain axis and PD. We focus on the role of the gut microbiota, the unique changes observed in the microbiome of PD patients, and the impact of these changes on the progression of PD. Finally, we evaluate the role of current treatment strategies for PD, including probiotics, fecal microbial transplants, dietary modifications, and related drug therapies.}, } @article {pmid38176570, year = {2024}, author = {He, H and Zhao, Z and Xiao, C and Li, L and Liu, YE and Fu, J and Liao, H and Zhou, T and Zhang, J}, title = {Gut microbiome promotes mice recovery from stress-induced depression by rescuing hippocampal neurogenesis.}, journal = {Neurobiology of disease}, volume = {}, number = {}, pages = {106396}, doi = {10.1016/j.nbd.2023.106396}, pmid = {38176570}, issn = {1095-953X}, abstract = {Studies from rodents to primates and humans indicate that individuals vary in how resilient they are to stress, and understanding the basis of these variations may help improve treatments for depression. Here we explored the potential contribution of the gut microbiome to such variation. Mice were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks then allowed to recover for 3 weeks, after which they were subjected to behavioral tests and categorized as showing low or high stress resilience. The two types of mouse were compared in terms of hippocampal gene expression using RNA sequencing, fecal microbiomes using 16S RNA sequencing, and extent of neurogenesis in the hippocampus using immunostaining of brain sections. Fecal microbiota were transplanted from either type of mouse into previously stress-exposed and stress-naïve animals, and the effects of the transplantation on stress-induced behaviors and neurogenesis in the hippocampus were examined. Finally, we blocked neurogenesis using temozolomide to explore the role of neurogenesis promoted by fecal microbiota transplantation in enhancing resilience to stress. Results showed that highly stress-resilient mice, but not those with low resilience, improved significantly on measures of anhedonia, behavioral despair, and anxiety after 3-week recovery from CUMS. Their feces showed greater abundance of Lactobacillus, Bifidobacterium and Romboutsia than feces from mice with low stress resilience, as well as lower abundance of Staphylococcus, Psychrobacter and Corynebacterium. Similarly, highly stress-resilient mice showed greater neurogenesis in hippocampus than animals with low stress resilience. Transplanting fecal microbiota from mice with high stress resilience into previously CUMS-exposed recipients rescued neurogenesis in hippocampus, facilitating recovery from stress-induced depression and cognitive decline. Blockade of neurogenesis with temozolomide abolished recovery of recipients from CUMS-induced depression and cognitive decline in mice transplanted with fecal microbiota from mice with high stress resilience. In conclusion, our results suggested that remodeling of the gut microbiome after stress may reverse stress-induced impairment of hippocampal neurogenesis and thereby promote recovery from stress-induced depression.}, } @article {pmid38175474, year = {2024}, author = {Campidelli, C and Bruxelle, JF and Collignon, A and Péchiné, S}, title = {Immunization Strategies Against Clostridioides difficile.}, journal = {Advances in experimental medicine and biology}, volume = {1435}, number = {}, pages = {117-150}, pmid = {38175474}, issn = {0065-2598}, mesh = {Animals ; Humans ; *Clostridioides difficile ; Immunization ; Vaccination ; Immunization, Passive ; Virulence Factors ; }, abstract = {Clostridioides difficile (C. difficile) infection (CDI) is an important healthcare but also a community-associated disease. CDI is considered a public health threat and an economic burden. A major problem is the high rate of recurrences. Besides classical antibiotic treatments, new therapeutic strategies are needed to prevent infection, to treat patients, and to prevent recurrences. If fecal transplantation has been recommended to treat recurrences, another key approach is to elicit immunity against C. difficile and its virulence factors. Here, after a summary concerning the virulence factors, the host immune response against C. difficile, and its role in the outcome of disease, we review the different approaches of passive immunotherapies and vaccines developed against CDI. Passive immunization strategies are designed in function of the target antigen, the antibody-based product, and its administration route. Similarly, for active immunization strategies, vaccine antigens can target toxins or surface proteins, and immunization can be performed by parenteral or mucosal routes. For passive immunization and vaccination as well, we first present immunization assays performed in animal models and second in humans and associated clinical trials. The different studies are presented according to the mode of administration either parenteral or mucosal and the target antigens and either toxins or colonization factors.}, } @article {pmid38175472, year = {2024}, author = {Porcari, S and Maida, M and Bibbò, S and McIlroy, J and Ianiro, G and Cammarota, G}, title = {Fecal Microbiota Transplantation as Emerging Treatment in European Countries 2.0.}, journal = {Advances in experimental medicine and biology}, volume = {1435}, number = {}, pages = {85-99}, pmid = {38175472}, issn = {0065-2598}, mesh = {Humans ; Fecal Microbiota Transplantation ; Feces ; Anti-Bacterial Agents ; *Cross Infection ; *Inflammatory Bowel Diseases/therapy ; }, abstract = {Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections and one of the leading causes of morbidity and mortality in hospitalized patients in the world. Although several antibiotics effectively treat CDI, some individuals may not respond to these drugs and may be cured by transplanting stool from healthy donors. FMT has demonstrated extraordinary cure rates for the cure of CDI recurrences.Moreover, FMT has also been investigated in other disorders associated with the alteration of gut microbiota, such as inflammatory bowel disease (IBD), where the alterations of the gut microbiota ecology have been theorized to play a causative role. Although FMT is currently not recommended to cure IBD patients in clinical practice, several studies have been recently carried out with the ultimate goal to search new therapeutic options to patients.This review summarizes data on the use of FMT for the treatment of both CDI and IBD, with a special attention to highlight studies conducted in European countries.}, } @article {pmid38175471, year = {2024}, author = {Fitzpatrick, F and Brennan, R and van Prehn, J and Skally, M and Brady, M and Burns, K and Rooney, C and Wilcox, MH}, title = {European Practice for CDI Treatment.}, journal = {Advances in experimental medicine and biology}, volume = {1435}, number = {}, pages = {57-84}, pmid = {38175471}, issn = {0065-2598}, mesh = {Humans ; Fidaxomicin ; *Metronidazole ; Vancomycin ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy ; }, abstract = {Clostridioides difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) management guidance for CDI were updated in 2021. This guidance document outlines the treatment options for a variety of CDI clinical scenarios and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). One of the main changes is that metronidazole is no longer recommended as first-line CDI treatment. Rather, fidaxomicin is preferred on the basis of reduced recurrence rates with vancomycin as an acceptable alternative. Recommended options for recurrent CDI now include bezlotoxumab as well as FMT.A 2017 survey of 20 European countries highlighted variation internationally in CDI management strategies. A variety of restrictions were in place in 65% countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. This survey was repeated in November 2022 to assess the current landscape of CDI management practices in Europe. Of 64 respondents from 17 countries, national CDI guidelines existed in 14 countries, and 11 have already/plan to incorporate the ESCMID 2021 CDI guidance, though implementation has not been surveyed in 6. Vancomycin is the most commonly used first-line agent for the treatment of CDI (n = 42, 66%), followed by fidaxomicin (n = 30, 47%). Six (9%) respondents use metronidazole as first-line agent for CDI treatment, whereas 22 (34%) only in selected low-risk patient groups. Fidaxomicin is more likely to be used in high-risk patient groups. Availability of anti-CDI therapy influenced prescribing in six respondents (9%). Approval pre-prescription was required before vancomycin (n = 3, 5%), fidaxomicin (n = 10, 6%), bezlotoxumab (n = 11, 17%) and FMT (n = 10, 6%). Implementation of CDI guidelines is rarely audited.Novel anti-CDI agents are being evaluated; it is not yet clear what will be the roles of these agents. The treatment of recurrent CDI is particularly troublesome, and several different live biotherapeutics are being developed, in addition to FMT.}, } @article {pmid38174845, year = {2024}, author = {Liu, YH and Chen, J and Chen, X and Liu, H}, title = {Factors of faecal microbiota transplantation applied to cancer management.}, journal = {Journal of drug targeting}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/1061186X.2023.2299724}, pmid = {38174845}, issn = {1029-2330}, abstract = {The homeostasis of the microbiota is essential for human health. In particular, the gut microbiota plays a critical role in the regulation of the immune system. Thus, faecal microbiota transplantation (FMT), a technology that has rapidly developed in the last decade, has specifically been utilised for the treatment of intestinal inflammation and has recently been found to be able to treat tumours in combination with immunotherapy. FMT has become a breakthrough in enhancing the response rate to immunotherapy in cancer patients by altering the composition of the patient's gut microbiota. This review discusses the mechanisms of faecal microorganism effects on tumour development, drug treatment efficacy, and adverse effects and describes the recent clinical research trials on FMT. Moreover, the factors influencing the efficacy and safety of FMT are described. We summarise the possibilities of faecal transplantation in the treatment of tumours and its complications and propose directions to explore the development of FMT.}, } @article {pmid38173790, year = {2023}, author = {Jia, X and Chen, Q and Zhang, Y and Asakawa, T}, title = {Multidirectional associations between the gut microbiota and Parkinson's disease, updated information from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1296713}, pmid = {38173790}, issn = {2235-2988}, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome ; Ecosystem ; *Parkinson Disease ; Dysbiosis ; Fecal Microbiota Transplantation ; }, abstract = {The human gastrointestinal tract is inhabited by a diverse range of microorganisms, collectively known as the gut microbiota, which form a vast and complex ecosystem. It has been reported that the microbiota-gut-brain axis plays a crucial role in regulating host neuroprotective function. Studies have shown that patients with Parkinson's disease (PD) have dysbiosis of the gut microbiota, and experiments involving germ-free mice and fecal microbiota transplantation from PD patients have revealed the pathogenic role of the gut microbiota in PD. Interventions targeting the gut microbiota in PD, including the use of prebiotics, probiotics, and fecal microbiota transplantation, have also shown efficacy in treating PD. However, the causal relationship between the gut microbiota and Parkinson's disease remains intricate. This study reviewed the association between the microbiota-gut-brain axis and PD from the perspectives of humoral pathway, cellular immune pathway and neuronal pathway. We found that the interactions among gut microbiota and PD are very complex, which should be "multidirectional", rather than conventionally regarded "bidirectional". To realize application of the gut microbiota-related mechanisms in the clinical setting, we propose several problems which should be addressed in the future study.}, } @article {pmid38170622, year = {2024}, author = {Huang, F and Cao, Y and Liang, J and Tang, R and Wu, S and Zhang, P and Chen, R}, title = {The influence of the gut microbiome on ovarian aging.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2295394}, doi = {10.1080/19490976.2023.2295394}, pmid = {38170622}, issn = {1949-0984}, abstract = {Ovarian aging occurs prior to the aging of other organ systems and acts as the pacemaker of the aging process of multiple organs. As life expectancy has increased, preventing ovarian aging has become an essential goal for promoting extended reproductive function and improving bone and genitourinary conditions related to ovarian aging in women. An improved understanding of ovarian aging may ultimately provide tools for the prediction and mitigation of this process. Recent studies have suggested a connection between ovarian aging and the gut microbiota, and alterations in the composition and functional profile of the gut microbiota have profound consequences on ovarian function. The interaction between the gut microbiota and the ovaries is bidirectional. In this review, we examine current knowledge on ovary-gut microbiota crosstalk and further discuss the potential role of gut microbiota in anti-aging interventions. Microbiota-based manipulation is an appealing approach that may offer new therapeutic strategies to delay or reverse ovarian aging.}, } @article {pmid38169417, year = {2024}, author = {Cheng, S and Yu, J and Cui, M and Su, H and Cao, Y}, title = {Changes in the composition of the fecal metabolome and gut microbiota contribute to intervertebral disk degeneration in a rabbit model.}, journal = {Journal of orthopaedic surgery and research}, volume = {19}, number = {1}, pages = {6}, pmid = {38169417}, issn = {1749-799X}, abstract = {PURPOSE: Lower back pain (LBP), mainly caused by intervertebral disk (IVD) degeneration (IDD), is widely prevalent worldwide and is a serious socioeconomic burden. Numerous factors may trigger this degenerative process, and microbial dysbiosis has recently been implicated as one of the likely causes. However, the exact relationship between IDD and the microbiome remains obscure. In this study, we investigated the gut microbiota composition and fecal metabolic phenotype and discussed the possible influences of microbiome dysbiosis on IDD.

METHODS: Fecal DNA was extracted from 16 fecal samples (eight rabbit models with IDD and eight sex- and age-matched healthy controls) and analyzed by high-throughput 16S rDNA sequencing. The fecal samples were also analyzed by liquid chromatography-mass spectrometry-based metabolomics. Multivariate analyses were conducted for the relationship between the omics data and IDD, linear discriminant analysis effect size was employed for biomarker discovery. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the differential metabolites. The potential correlation between differential gut microbiota and metabolites was then assessed.

RESULTS: The 16S rDNA sequencing results showed that the β-diversity of the gut microbiota was significantly different between the IDD and control groups, with distinct abundance levels of dominant genera. Moreover, 59 metabolites were significantly upregulated and 91 were downregulated in IDD rabbits versus the controls. The KEGG enrichment analysis revealed that the top pathways remarkably impacted by IDD were tyrosine metabolism, amino sugar and nucleotide sugar metabolism, benzoate degradation, ABC transporters, ascorbate and aldarate metabolism, pantothenate and CoA biosynthesis, and pyrimidine metabolism. The correlation analysis revealed that DL-tyrosine and N-acetylmuramic acid were associated with multiple differential bacterial genera, including Helicobacter and Vibrio, which may play important roles in the process of IVD degeneration.

CONCLUSION: Our findings revealed that IDD altered gut microbiota and fecal metabolites in a rabbit model. The correlation analysis of microbiota and metabolome provides a deeper understanding of IDD and its possible etiopathogenesis. These results also provide a direction and theoretical basis for the clinical application of fecal transplantation, probiotics, and other methods to regulate gut microbiota in the treatment of LBP caused by IDD.}, } @article {pmid38168034, year = {2024}, author = {Zhu, L and Jian, X and Zhou, B and Liu, R and Muñoz, M and Sun, W and Xie, L and Chen, X and Peng, C and Maurer, M and Li, J}, title = {Gut microbiota facilitate chronic spontaneous urticaria.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {112}, pmid = {38168034}, issn = {2041-1723}, support = {81974476//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82173424//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82073458//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81830096//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Chronic spontaneous urticaria (CSU) comes with gut dysbiosis, but its relevance remains elusive. Here we use metagenomics sequencing and short-chain fatty acids metabolomics and assess the effects of human CSU fecal microbial transplantation, Klebsiella pneumoniae, Roseburia hominis, and metabolites in vivo. CSU gut microbiota displays low diversity and short-chain fatty acids production, but high gut Klebsiella pneumoniae levels, negatively correlates with blood short-chain fatty acids levels and links to high disease activity. Blood lipopolysaccharide levels are elevated, link to rapid disease relapse, and high gut levels of conditional pathogenic bacteria. CSU microbiome transfer and Klebsiella pneumoniae transplantation facilitate IgE-mediated mast cell(MC)-driven skin inflammatory responses and increase intestinal permeability and blood lipopolysaccharide accumulation in recipient mice. Transplantation of Roseburia hominis and caproate administration protect recipient mice from MC-driven skin inflammation. Here, we show gut microbiome alterations, in CSU, may reduce short-chain fatty acids and increase lipopolysaccharide levels, respectively, and facilitate MC-driven skin inflammation.}, } @article {pmid38164399, year = {2023}, author = {Shayya, NW and Bandick, R and Busmann, LV and Mousavi, S and Bereswill, S and Heimesaat, MM}, title = {Metabolomic signatures of intestinal colonization resistance against Campylobacter jejuni in mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1331114}, pmid = {38164399}, issn = {1664-302X}, abstract = {INTRODUCTION: Campylobacter jejuni stands out as one of the leading causes of bacterial enteritis. In contrast to humans, specific pathogen-free (SPF) laboratory mice display strict intestinal colonization resistance (CR) against C. jejuni, orchestrated by the specific murine intestinal microbiota, as shown by fecal microbiota transplantation (FMT) earlier.

METHODS: Murine infection models, comprising SPF, SAB, hma, and mma mice were employed. FMT and microbiota depletion were confirmed by culture and culture-independent analyses. Targeted metabolome analyses of fecal samples provided insights into the associated metabolomic signatures.

RESULTS: In comparison to hma mice, the murine intestinal microbiota of mma and SPF mice (with CR against C. jejuni) contained significantly elevated numbers of lactobacilli, and Mouse Intestinal Bacteroides, whereas numbers of enterobacteria, enterococci, and Clostridium coccoides group were reduced. Targeted metabolome analysis revealed that fecal samples from mice with CR contained increased levels of secondary bile acids and fatty acids with known antimicrobial activities, but reduced concentrations of amino acids essential for C. jejuni growth as compared to control animals without CR.

DISCUSSION: The findings highlight the role of microbiota-mediated nutrient competition and antibacterial activities of intestinal metabolites in driving murine CR against C. jejuni. The study underscores the complex dynamics of host-microbiota-pathogen interactions and sets the stage for further investigations into the mechanisms driving CR against enteric infections.}, } @article {pmid38163440, year = {2023}, author = {Lu, X and Yang, R and Chen, Y and Chen, D}, title = {Evaluating the Therapeutic Efficacy of NAD Supplementation in Management of MASLD: Key Considerations.}, journal = {Clinical and molecular hepatology}, volume = {}, number = {}, pages = {}, doi = {10.3350/cmh.2023.0555}, pmid = {38163440}, issn = {2287-285X}, } @article {pmid38162858, year = {2023}, author = {Toshida, K and Itoh, S and Kosai-Fujimoto, Y and Ishikawa, T and Nakayama, Y and Tsutsui, Y and Iseda, N and Izumi, T and Bekki, Y and Yoshiya, S and Toshima, T and Nakamuta, M and Yoshizumi, T}, title = {Association of gut microbiota with portal vein pressure in patients with liver cirrhosis undergoing living donor liver transplantation.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {12}, pages = {982-989}, pmid = {38162858}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: Many recent studies have shown a relationship between various systemic diseases and the gut microbiota (GM), with the gut-liver axis receiving particular attention. In contrast, no report has comprehensively shown the effects of GM on the pathophysiology of patients undergoing living donor liver transplantation (LDLT).

METHOD: We enrolled 16 recipients who underwent LDLT for liver cirrhosis, and 17 donors constituted the reference group. We examined the differences in GM between recipients and donors. We also examined the relationships between GM, short-chain fatty acids, and portal vein pressure (PVP) in recipients.

RESULTS: There was no significant difference in alpha-diversity between the recipients and donors, but there was variation in beta-diversity among the recipients. The abundance of the phylum Bacteroidetes was significantly higher in recipients than in donors (P = 0.016), and it was positively correlated with PVP (r = 0.511, P = 0.043). Propionic acid, which is a component of short-chain fatty acids, was positively correlated with PVP (r = 0.544, P = 0.0295), the phylum Bacteroidetes (r = 0.677, P = 0.004), and total bilirubin concentration (r = 0.501, P = 0.048). Propionic acid was negatively correlated with serum albumin concentration (r = -0.482, P = 0.043).

CONCLUSION: Our findings suggest relationships between fecal Bacteroidetes levels, propionic acid concentrations, and PVP in patients with liver cirrhosis undergoing LDLT.}, } @article {pmid38158466, year = {2023}, author = {Terra, DAA and de Oliveira Carvalho, RD and da Silva, TF and Dos Santos Freitas, A and Góes-Neto, A and Amarante, VS and Azevedo, V and Vilela, EG and Coelho, LGV and Silva, ROS}, title = {Bacterial microbiome changes after fecal transplantation for recurrent Clostridioides difficile infection in the Brazilian center.}, journal = {Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]}, volume = {}, number = {}, pages = {}, pmid = {38158466}, issn = {1678-4405}, support = {FAPEMIG RED-00132-16//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; }, abstract = {Clostridioides difficile infection (CDI) poses a significant global health threat owing to its substantial morbidity and associated healthcare costs. A key challenge in controlling CDI is the risk of multiple recurrences, which can affect up to 30% of patients. In such instances, fecal microbiota transplantation (FMT) is increasingly recognized as the optimal treatment. However, few related studies have been conducted in developing countries, and the microbiota composition of Brazilian patients and its dynamic modification post-FMT remain largely unexplored. This study aimed to evaluate the changes in the bacterial gut microbiome in Brazilian patients with recurrent CDI post-FMT. Ten patients underwent FMT, and the primary and overall CDI resolution rates were 80% and 90% after the first and second FMT, respectively. FMT was associated with an early increase in Shannon's diversity, evident as soon as 1 week post-FMT and persisting for at least 25 days post-treatment. Post-treatment, the abundance of Firmicutes increased and that of Proteobacteria decreased. Specifically, the abundance of the genera Ruminococcus, Faecalibacterium, Lachnospira, and Roseburia of the Firmicutes phylum was significantly higher 1 week post-transplantation, with Ruminococcus and Faecalibacterium remaining enriched 25 days post-transplantation. This study is the first of its kind in Brazil to evaluate the microbiota of a donor and patients undergoing FMT. Our findings suggest that FMT can induce remarkable changes in the gut microbiota, characterized by an early and sustained increase in diversity lasting at least 25 days. FMT also promotes enrichment of genera such as Ruminococcus spp., Faecalibacterium spp., and Roseburia spp., essential for therapeutic success.}, } @article {pmid38157106, year = {2023}, author = {Chen, S and Huang, L and Liu, B and Duan, H and Li, Z and Liu, Y and Li, H and Fu, X and Lin, J and Xu, Y and Liu, L and Wan, D and Yin, Y and Xie, L}, title = {Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {38157106}, issn = {1869-1889}, abstract = {The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions, such as developing and preserving the skeletal muscle system. However, the interplay between gut microbiota/metabolites and the regulation of satellite cell (SC) homeostasis, particularly during aging, remains elusive. We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development, regeneration, and aging process. Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice, leads to the activation of SCs or a significant reduction in the total number. Furthermore, employing multi-omics (e.g., RNA-seq, 16S rRNA gene sequencing, and metabolomics) and bioinformatic analysis, we demonstrate that the reduced butyrate levels, alongside the gut microbial dysbiosis, could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging. Meanwhile, butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota, potentially by inhibiting the proliferation and differentiation of SCs/myoblasts. The butyrate effect is likely facilitated through the monocarboxylate transporter 1 (Mct1), a lactate transporter enriched on membranes of SCs and myoblasts. As a result, butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging. Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.}, } @article {pmid38156008, year = {2023}, author = {He, KY and Lei, XY and Zhang, L and Wu, DH and Li, JQ and Lu, LY and Laila, UE and Cui, CY and Xu, ZX and Jian, YP}, title = {Development and management of gastrointestinal symptoms in long-term COVID-19.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1278479}, pmid = {38156008}, issn = {1664-302X}, abstract = {BACKGROUND: Emerging evidence reveals that SARS-CoV-2 possesses the capability to disrupt the gastrointestinal (GI) homeostasis, resulting in the long-term symptoms such as loss of appetite, diarrhea, gastroesophageal reflux, and nausea. In the current review, we summarized recent reports regarding the long-term effects of COVID-19 (long COVID) on the gastrointestine.

OBJECTIVE: To provide a narrative review of abundant clinical evidence regarding the development and management of long-term GI symptoms in COVID-19 patients.

RESULTS: Long-term persistent digestive symptoms are exhibited in a majority of long-COVID patients. SARS-CoV-2 infection of intestinal epithelial cells, cytokine storm, gut dysbiosis, therapeutic drugs, psychological factors and exacerbation of primary underlying diseases lead to long-term GI symptoms in COVID-19 patients. Interventions like probiotics, prebiotics, fecal microbiota transplantation, and antibiotics are proved to be beneficial in preserving intestinal microecological homeostasis and alleviating GI symptoms.

CONCLUSION: Timely diagnosis and treatment of GI symptoms in long-COVID patients hold great significance as they may contribute to the mitigation of severe conditions and ultimately lead to the improvement of outcomes of the patients.}, } @article {pmid38155743, year = {2023}, author = {Sun, X and Zhou, X and He, W and Sun, W and Xu, Z}, title = {Co-Housing and Fecal Microbiota Transplantation: Technical Support for TCM Herbal Treatment of Extra-Intestinal Diseases Based on Gut Microbial Ecosystem Remodeling.}, journal = {Drug design, development and therapy}, volume = {17}, number = {}, pages = {3803-3831}, pmid = {38155743}, issn = {1177-8881}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Ecosystem ; Housing ; *Intestinal Diseases/drug therapy ; }, abstract = {Dysregulation of the gut microbial ecosystem (GME) (eg, alterations in the gut microbiota, gut-derived metabolites, and gut barrier) may contribute to the onset and progression of extra-intestinal diseases. Previous studies have found that Traditional Chinese Medicine herbs (TCMs) play an important role in manipulating the GME, but a prominent obstacle in current TCM research is the causal relationship between GME and disease amelioration. Encouragingly, co-housing and fecal microbiota transplantation (FMT) provide evidence-based support for TCMs to treat extra-intestinal diseases by targeting GME. In this review, we documented the principles, operational procedures, applications and limitations of the key technologies (ie, co-housing and FMT); furthermore, we provided evidence that TCM works through the GME, especially the gut microbiota (eg, SCFA- and BSH-producing bacteria), the gut-derived metabolites (eg, IS, pCS, and SCFAs), and intestinal barrier to alleviate extra-intestinal diseases. This will be beneficial in constructing microecological pathways for TCM treatment of extra-intestinal diseases in the future.}, } @article {pmid38154268, year = {2023}, author = {Dong, P and Wang, H and Li, Y and Yu, J and Liu, X and Wang, Y and Dai, L and Wang, S}, title = {Active peptides from Eupolyphaga sinensis walker attenuates experimental hyperlipidemia by regulating the gut microbiota and biomarkers in rats with dyslipidemia.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {170}, number = {}, pages = {116064}, doi = {10.1016/j.biopha.2023.116064}, pmid = {38154268}, issn = {1950-6007}, abstract = {Eupolyphaga sinensis Walker (ESW) is a traditional Chinese medicine formulation used to treat hyperlipidemia. However, the hypolipidemic effect of the active peptides from E. sinensis Walker (APE) is incompletely understood. We studied the hypolipidemic effect of APE and explored the impact of APE on the gut microbiota (GM) in rats suffering from hyperlipidemia. APE was prepared by enzymatic digestion, and its structure was characterized using various methods. The anti-hyperlipidemic activity of APE was assessed using a high-fat diet (HFD)-induced model in zebrafish and rats. In rats, HFD administration caused abnormalities of lipid metabolism and disturbances of the GM and amino acid (AA) profile in plasma. The abundance of bacteria of the phyla Firmicutes and Bacteroides was increased significantly (p < 0.05), and the relative abundance of Lactobacillus species and Clostridium species was decreased significantly (p < 0.05). HFD therapy affected the levels of 12 AAs in vivo: 10 AAs showed increased levels and two AAs had decreased levels (p < 0.05). Similar results were demonstrated in an experiment on fecal microbiota transplantation. APE treatment dose-dependently decreased lipid factors and liver damage (p < 0.05). Sequencing of the 16 S rRNA gene indicated that APE improved the intestinal-flora structure of rats with HL markedly, and increased the relative abundance of Lactobacillus species and Clostridium species. Metabolomics analysis indicated that APE could alter the levels of 10 AAs affected by HFD consumption. Spearman correlation analysis revealed that gamma-aminobutyric acid (GABA) could be a crucial metabolite, and Lactobacillus species and Clostridium species might be important bacteria for the action of APE against hyperlipidemia. We speculate that APE exhibited an anti-hyperlipidemic effect by regulating GABA synthesis in the presence of Lactobacillus species and Clostridium species.}, } @article {pmid38153838, year = {2023}, author = {Yang, CJ and Chang, HC and Sung, PC and Ge, MC and Tang, HY and Cheng, ML and Cheng, HT and Chou, HH and Lin, CY and Lin, WR and Lee, YS and Hsieh, SY}, title = {Oral fecal transplantation enriches Lachnospiraceae and butyrate to mitigate acute liver injury.}, journal = {Cell reports}, volume = {43}, number = {1}, pages = {113591}, doi = {10.1016/j.celrep.2023.113591}, pmid = {38153838}, issn = {2211-1247}, abstract = {While fecal microbiota transplantation (FMT) shows promise in treating human diseases, oral capsule FMT is more accepted and accessible to patients. However, microbe selection in the upper gastrointestinal tract (UGIT) through oral administration remains unclear. Here, we demonstrate that short-term oral fecal gavage (OFG) alleviates acetaminophen-induced acute liver injury (AILI) in mice, regardless of the divergent effects of commensal gut microbes. Pasteurized fecal gavage yields similar therapeutic effects. OFG enriches gut Lachnospiraceae and butyrate compared to donor feces. Butyrate mitigates AILI-induced ferroptosis via AMPK-ULK1-p62 signaling to simultaneously induce mitophagy and Nrf2 antioxidant responses. Combined N-acetylcysteine and butyrate administration significantly improves AILI mouse survival rates. These observations indicate the significance of the UGIT in modulating the implanted fecal microbes through oral administration and its potential biological and clinical impacts. Our findings also highlight a possible strategy for applying microbial metabolites to treat acute liver injury.}, } @article {pmid38153260, year = {2024}, author = {Cross, TL and Simpson, AMR and Lin, CY and Hottmann, NM and Bhatt, AP and Pellock, SJ and Nelson, ER and Loman, BR and Wallig, MA and Vivas, EI and Suchodolski, J and Redinbo, MR and Rey, FE and Swanson, KS}, title = {Gut microbiome responds to alteration in female sex hormone status and exacerbates metabolic dysfunction.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2295429}, doi = {10.1080/19490976.2023.2295429}, pmid = {38153260}, issn = {1949-0984}, mesh = {Humans ; Female ; Mice ; Animals ; *Gastrointestinal Microbiome/physiology ; Obesity/metabolism ; Liver/metabolism ; Diet, High-Fat/adverse effects ; Inflammation/metabolism ; Gonadal Steroid Hormones/metabolism ; Mice, Inbred C57BL ; }, abstract = {Women are at significantly greater risk of metabolic dysfunction after menopause, which subsequently leads to numerous chronic illnesses. The gut microbiome is associated with obesity and metabolic dysfunction, but its interaction with female sex hormone status and the resulting impact on host metabolism remains unclear. Herein, we characterized inflammatory and metabolic phenotypes as well as the gut microbiome associated with ovariectomy and high-fat diet feeding, compared to gonadal intact and low-fat diet controls. We then performed fecal microbiota transplantation (FMT) using gnotobiotic mice to identify the impact of ovariectomy-associated gut microbiome on inflammatory and metabolic outcomes. We demonstrated that ovariectomy led to greater gastrointestinal permeability and inflammation of the gut and metabolic organs, and that a high-fat diet exacerbated these phenotypes. Ovariectomy also led to alteration of the gut microbiome, including greater fecal β-glucuronidase activity. However, differential changes in the gut microbiome only occurred when fed a low-fat diet, not the high-fat diet. Gnotobiotic mice that received the gut microbiome from ovariectomized mice fed the low-fat diet had greater weight gain and hepatic gene expression related to metabolic dysfunction and inflammation than those that received intact sham control-associated microbiome. These results indicate that the gut microbiome responds to alterations in female sex hormone status and contributes to metabolic dysfunction. Identifying and developing gut microbiome-targeted modulators to regulate sex hormones may be useful therapeutically in remediating menopause-related diseases.}, } @article {pmid38153222, year = {2024}, author = {Feuerstadt, P and LaPlante, KL}, title = {Efficacy and Practical Implementation of Fecal Microbiota Spores, Live-BRPK: A Novel Approach for Preventing Recurrent Clostridioides difficile Infection.}, journal = {The American journal of gastroenterology}, volume = {119}, number = {1S}, pages = {S22-S26}, doi = {10.14309/ajg.0000000000002582}, pmid = {38153222}, issn = {1572-0241}, mesh = {Humans ; Spores, Bacterial ; *Clostridium Infections/prevention & control/drug therapy ; *Clostridioides difficile ; *Microbiota ; Fecal Microbiota Transplantation ; Recurrence ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use ; }, } @article {pmid38153221, year = {2024}, author = {Oneto, C and Khanna, S}, title = {Prescription Microbiome Therapeutic for Recurrent Clostridioides difficile Infection: Fecal Microbiota Live-jslm.}, journal = {The American journal of gastroenterology}, volume = {119}, number = {1S}, pages = {S16-S21}, doi = {10.14309/ajg.0000000000002577}, pmid = {38153221}, issn = {1572-0241}, mesh = {Humans ; *Clostridium Infections/drug therapy ; *Microbiota ; Fecal Microbiota Transplantation ; Recurrence ; Treatment Outcome ; }, } @article {pmid38151280, year = {2023}, author = {Hanssen, HM and Fjellstad, MS and Skjevling, L and Johnsen, PH and Kulseng, B and Goll, R and Almå, KH and Valle, PC}, title = {Randomised, placebo-controlled, double-blinded trial of fecal microbiota transplantation in severe obesity: a study protocol.}, journal = {BMJ open}, volume = {13}, number = {12}, pages = {e073242}, doi = {10.1136/bmjopen-2023-073242}, pmid = {38151280}, issn = {2044-6055}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Obesity, Morbid/therapy/etiology ; Obesity/therapy/etiology ; Double-Blind Method ; Weight Loss ; Treatment Outcome ; Randomized Controlled Trials as Topic ; }, abstract = {INTRODUCTION: Obesity is one of the main threats to public health in western countries and increases the risk of several diseases, overall morbidity and mortality. Sustained weight loss will reduce risk factors and improve several obesity comorbidities. Options are conservative treatment such as lifestyle changes, bariatric surgery or medications. Conservative treatment has a low success rate, and bariatric surgery is typically not reversible, with the risk of complications and recurrences. Treatment of obesity with medications has in recent years shown great promise, but the side effects are many, and the long-term effect is unknown. There is also a need for an option for patients where surgery has contraindications and conservative follow-up does not succeed.The research on obesity and gut microbiota has yielded promising results regarding weight reduction and metabolic health, but more research is needed to better understand the relationship between gut microbiota and severe obesity. This study could show proof of concept that gut microbiota from a lean donor could, in addition to lifestyle intervention, contribute to weight reduction in people suffering from severe obesity.

METHOD AND ANALYSIS: This study aims to investigate if a fecal microbiota transplantation (FMT) from a lean donor leads to weight reduction in participants suffering from severe obesity. The study is a single-centre, double-blinded, placebo-controlled, parallel-group study with 60 participants. Participants will be randomised 1:1 for FMT from a lean donor or placebo. FMT or placebo will be delivered once by enema.We will include participants from the outpatient clinic for severe obesity, at the Medical Department, University Hospital of North Norway, Harstad, by invitation only. The study has a follow-up period of 12 months, with study visits of 3, 6 and 12 months post FMT. The primary endpoint is a weight reduction of ≥10%, 12 months after intervention.The results of the study will be published in open access journals. At the end of the study, the participants will receive information on which treatment group they belong to.

ETHICS AND DISSEMINATION: The Regional Ethical Committee in North Norway (REK) approved the study protocol (2017/1655/REK Nord). We plan to present the results from the study at (inter)national conferences and publish in open-access general peer-reviewed journals. The enema method for FMT administration used in this study was developed by our study team.

TRIAL REGISTRATION NUMBER: NCT03273855.}, } @article {pmid38150616, year = {2023}, author = {Huang, X and He, X and Chen, X and Li, Y}, title = {Fecal Microbiota Transplantation Alleviates Severe PD-1 Inhibitor-Associated Colitis Caused by Neoadjuvant Therapy for Esophageal Cancer: A Case Report.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {}, number = {}, pages = {}, doi = {10.1097/SGA.0000000000000794}, pmid = {38150616}, issn = {1538-9766}, abstract = {Surgical resection is the preferred treatment for early-stage esophageal cancer. But most patients with esophageal cancer are diagnosed at advanced stages, making them ineligible for surgery. Therefore, preoperative neoadjuvant therapy has been introduced to help them meet surgical requirements. However, this therapy has been associated with serious complications, such as diarrhea, preventing patients from surgery. During neoadjuvant therapy combined with chemoradiotherapy, a 58-year-old male patient with esophageal cancer was diagnosed with severe immune-related colitis, which seriously affected both cancer treatment and the patient's quality of life. Despite conventional antidiarrheal therapy, the patient remained refractory to treatment. However, after undergoing fecal microbiota transplantation, the frequency of diarrhea was significantly reduced. During e-colonoscopy, no significant ulcers were found in the sigmoid colon. Additionally, successful radical resection of esophageal cancer was performed, resulting in a favorable outcome for the patient. Regular follow-up appointments were scheduled to monitor the patient's progress. Fecal microbiota transplantation effectively relieved severe immune-related diarrhea in a patient undergoing neoadjuvant immunotherapy and chemoradiotherapy for esophageal cancer. This successful treatment ultimately enabled the patient to meet the surgical requirements for radical esophagectomy.}, } @article {pmid38148326, year = {2023}, author = {Song, Y and Lau, HC and Zhang, X and Yu, J}, title = {Bile acids, gut microbiota, and therapeutic insights in hepatocellular carcinoma.}, journal = {Cancer biology & medicine}, volume = {}, number = {}, pages = {}, doi = {10.20892/j.issn.2095-3941.2023.0394}, pmid = {38148326}, issn = {2095-3941}, support = {2020J01122587//Fujian Provincial Natural Science Foundation project/ ; 82103355//National Natural Science Foundation of China/ ; 82102255//National Natural Science Foundation of China/ ; 82222901//National Natural Science Foundation of China/ ; T12-703/19-R//RGC Theme-based Research Scheme/ ; 14117422//Research grants Council-General Research Fund/ ; 14117123//Research grants Council-General Research Fund/ ; }, abstract = {Hepatocellular carcinoma (HCC) is a prevalent and aggressive liver malignancy. The interplay between bile acids (BAs) and the gut microbiota has emerged as a critical factor in HCC development and progression. Under normal conditions, BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs. The gut microbiota plays a critical role in BA metabolism, and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis. Of note, dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis, thereby leading to liver inflammation and fibrosis, and ultimately contributing to HCC development. Therefore, understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis. In this review, we comprehensively explore the roles and functions of BA metabolism, with a focus on the interactions between BAs and gut microorganisms in HCC. Additionally, therapeutic strategies targeting BA metabolism and the gut microbiota are discussed, including the use of BA agonists/antagonists, probiotic/prebiotic and dietary interventions, fecal microbiota transplantation, and engineered bacteria. In summary, understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.}, } @article {pmid38147728, year = {2023}, author = {Feng, H and Xiong, J and Liang, S and Wang, Y and Zhu, Y and Hou, Q and Yang, X and Yang, X}, title = {Fecal virus transplantation has more moderate effect than fecal microbiota transplantation on changing gut microbial structure in broiler chickens.}, journal = {Poultry science}, volume = {103}, number = {2}, pages = {103282}, doi = {10.1016/j.psj.2023.103282}, pmid = {38147728}, issn = {1525-3171}, abstract = {Growing evidence of fecal microbiota transplantation (FMT) and fecal virus transplantation (FVT) provides a possibility to regulate animal health, whereas little is known about the impact of the 2 methods. This study aimed to investigate the effects of gut microbes on jejunal function in healthy broiler chickens, with the objective of establishing a theoretical basis for the application of FMT and FVT. Cecal feces from 28-day-old AA broilers were collected to prepare gavage juice for FMT and FVT. FMT for Group FM, FVT for group FV and PBS gavage for group CON, continuously treated for 6 days start at 5-day-old chicks. Samples were collected at d 11 and d 21. The results showed that the treatment d 2 and the overall fecal score in treatment groups were significantly lower than CON group (P < 0.05). The jejunum morphology showed that FMT increased crypt depth, decreased villus height, V/C (P < 0.05) and FVT increased villus height (P < 0.05) at d 11. At d 21, villus height and crypt depth significantly higher (P < 0.05) in group FM and group FV. The expression of Claudin1, Occludin, ZO2, and Muc2 in the FV group was significantly increased (P < 0.05) at 11-day-old. FMT increased the secretion of sIgA at 11-day-old, and this influence lasted up to 21-day-old (P < 0.05). At 11-day-old, the expression of b[0+]AT of basic amino acid transport carrier and chymotrypsin activity (P < 0.05) had a significant correlation. At 21 d of age, FVT significantly increased the expression of PepT1 and SGLT1 (P < 0.05). At 11-day-old, FM group showed significantly higher faith pd index (P = 0.004) and Shannon index (P = 0.037), and separated from FV and CON according to PCoA. Among differentiating bacteria, Bacteroides significantly enriched (P < 0.05) in group FM, which positively correlated with the expression of ZO2, Muc2, Occludin, and Claudin1; R_Ruminococcus, L_Ruminococcus, Butyricicoccuss significantly enriched (P < 0.05) in group CON, which significantly higher than processing groups, R_Ruminococcus and L_Ruminococcus negatively correlated with the expression of Occludin (P < 0.05), and R_Ruminococcus, Butyricicoccus negatively correlated with the expression of Claudin1 (P < 0.05). At 21-day-old, PCoA based on Bray-Curtis shows that microbes taxa of 3 groups are isolated with each other and treatment groups were significant different with CON group based on Unweighted UniFrac and weighted UniFrac. The expression of PepT1 was significantly negatively (P < 0.05) correlated with Ruminococcus, and the expression of sIgA was significantly negatively (P < 0.05) correlated with Parabacteroides. In conclusion, FMT regulated intestinal flora rapidly, while it had little effect on intestinal function and a higher potential damaging risk on jejunal. FVT regulated intestinal flora structure softer, improved tight junction expression, but the mechanism of action needs further exploration.}, } @article {pmid38147649, year = {2024}, author = {Ritz, NL and Brocka, M and Butler, MI and Cowan, CSM and Barrera-Bugueño, C and Turkington, CJR and Draper, LA and Bastiaanssen, TFS and Turpin, V and Morales, L and Campos, D and Gheorghe, CE and Ratsika, A and Sharma, V and Golubeva, AV and Aburto, MR and Shkoporov, AN and Moloney, GM and Hill, C and Clarke, G and Slattery, DA and Dinan, TG and Cryan, JF}, title = {Social anxiety disorder-associated gut microbiota increases social fear.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {1}, pages = {e2308706120}, doi = {10.1073/pnas.2308706120}, pmid = {38147649}, issn = {1091-6490}, support = {12/RC/2273_P2//Science Foundation Ireland (SFI)/ ; 220646/Z/20/Z//EC | European Research Council (ERC)/ ; }, mesh = {Humans ; Animals ; Mice ; *Phobia, Social ; *Gastrointestinal Microbiome/physiology ; Oxytocin ; RNA, Ribosomal, 16S/genetics ; Fear ; Anxiety/psychology ; }, abstract = {Social anxiety disorder (SAD) is a crippling psychiatric disorder characterized by intense fear or anxiety in social situations and their avoidance. However, the underlying biology of SAD is unclear and better treatments are needed. Recently, the gut microbiota has emerged as a key regulator of both brain and behaviour, especially those related to social function. Moreover, increasing data supports a role for immune function and oxytocin signalling in social responses. To investigate whether the gut microbiota plays a causal role in modulating behaviours relevant to SAD, we transplanted the microbiota from SAD patients, which was identified by 16S rRNA sequencing to be of a differential composition compared to healthy controls, to mice. Although the mice that received the SAD microbiota had normal behaviours across a battery of tests designed to assess depression and general anxiety-like behaviours, they had a specific heightened sensitivity to social fear, a model of SAD. This distinct heightened social fear response was coupled with changes in central and peripheral immune function and oxytocin expression in the bed nucleus of the stria terminalis. This work demonstrates an interkingdom basis for social fear responses and posits the microbiome as a potential therapeutic target for SAD.}, } @article {pmid38143595, year = {2023}, author = {Kamal, FD and Dagar, M and Reza, T and Karim Mandokhail, A and Bakht, D and Shahzad, MW and Silloca-Cabana, EO and Mohsin, SN and Chilla, SP and Bokhari, SFH}, title = {Beyond Diet and Exercise: The Impact of Gut Microbiota on Control of Obesity.}, journal = {Cureus}, volume = {15}, number = {11}, pages = {e49339}, pmid = {38143595}, issn = {2168-8184}, abstract = {Obesity, a widespread health concern characterized by the excessive accumulation of body fat, is a complex condition influenced by genetics, environment, and social determinants. Recent research has increasingly focused on the role of gut microbiota in obesity, highlighting its pivotal involvement in various metabolic processes. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, interacts with the host in a myriad of ways, impacting energy metabolism, appetite regulation, inflammation, and the gut-brain axis. Dietary choices significantly shape the gut microbiota, with diets high in fat and carbohydrates promoting the growth of harmful bacteria while reducing beneficial microbes. Lifestyle factors, like physical activity and smoking, also influence gut microbiota composition. Antibiotics and medications can disrupt microbial diversity, potentially contributing to obesity. Early-life experiences, including maternal obesity during pregnancy, play a vital role in the developmental origins of obesity. Therapeutic interventions targeting the gut microbiota, including prebiotics, probiotics, fecal microbiota transplantation, bacterial consortium therapy, and precision nutrition, offer promising avenues for reshaping the gut microbiota and positively influencing weight regulation and metabolic health. Clinical applications of microbiota-based therapies are on the horizon, with potential implications for personalized treatments and condition-based interventions. Emerging technologies, such as next-generation sequencing and advanced bioinformatics, empower researchers to identify specific target species for microbiota-based therapeutics, opening new possibilities in healthcare. Despite the promising outlook, microbiota-based therapies face challenges related to microbial selection, safety, and regulatory issues. However, with ongoing research and advances in the field, these challenges can be addressed to unlock the full potential of microbiota-based interventions.}, } @article {pmid38138246, year = {2023}, author = {Ilie, OD and Duta, R and Nita, IB and Dobrin, I and Gurzu, IL and Girleanu, I and Huiban, L and Muzica, C and Ciobica, A and Popescu, R and Cianga, P and Stanciu, C and Cimpoesu, D and Trifan, A}, title = {A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {12}, pages = {}, pmid = {38138246}, issn = {1648-9144}, mesh = {Humans ; *Hepatic Encephalopathy/therapy ; Randomized Controlled Trials as Topic ; Lactulose/therapeutic use ; Liver Cirrhosis/complications/drug therapy ; *Probiotics/therapeutic use ; }, abstract = {Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.}, } @article {pmid38138045, year = {2023}, author = {Bosch, B and Hartikainen, A and Ronkainen, A and Scheperjans, F and Arkkila, P and Satokari, R}, title = {Development of a Protocol for Anaerobic Preparation and Banking of Fecal Microbiota Transplantation Material: Evaluation of Bacterial Richness in the Cultivated Fraction.}, journal = {Microorganisms}, volume = {11}, number = {12}, pages = {}, pmid = {38138045}, issn = {2076-2607}, support = {6600A-C1012//Finnish National Agency for Education/ ; 323156//Academy of Finland/ ; TYH2019204//The Hospital District of Helsinki and Uusimaa/ ; }, abstract = {Fecal microbiota transplantation (FMT) has shown highly variable results in indications beyond recurrent Clostridioides difficile infection. Microbiota dysbiosis in many diseases is characterized by the depletion of strictly anaerobic bacteria, which may be crucial for FMT efficacy. We developed a protocol to ensure anaerobic conditions during the entire transplant preparation and banking process, from material collection to administration. The protocol necessitates an anaerobic cabinet, i.e., a non-standard laboratory equipment. We analyzed the population of viable anaerobes by combining cultivation and 16S rRNA gene profiling during the transplant preparation, and after 4, 8, and 12 months of anaerobic or aerobic storage at -80 °C, 78% of fecal species were captured via cultivation. Our findings suggest that strictly anaerobic transplant preparation and storage may preserve species richness better than oxic conditions, but the overall difference was not significant. However, specific anaerobes such as Neglecta and Anaerotruncus were affected by the oxygen exposure. A storage time of up to 12 months did not affect the presence of cultivated taxa. Noteworthy, our analysis focused on the richness of cultivated anaerobes rather than their abundance, which may have been affected. The benefits of the developed anaerobic protocol in FMT for specific indications remain to be demonstrated in clinical trials.}, } @article {pmid38137998, year = {2023}, author = {Li, M and Yang, H and Shao, C and Liu, Y and Wen, S and Tang, L}, title = {Application of Dominant Gut Microbiota Promises to Replace Fecal Microbiota Transplantation as a New Treatment for Alzheimer's Disease.}, journal = {Microorganisms}, volume = {11}, number = {12}, pages = {}, pmid = {38137998}, issn = {2076-2607}, abstract = {Several studies have confirmed that the pathophysiological progression of Alzheimer's disease (AD) is closely related to changes in the intestinal microbiota; thus, modifying the intestinal microbiota has emerged as a new way to treat AD. Effective interventions for gut microbiota include the application of probiotics and other measures such as fecal microbiota transplantation (FMT). However, the application of probiotics ignores that the intestine is a complete microecosystem with competition among microorganisms. FMT also has issues when applied to patient treatment. In a previous study, we found that eight species of bacteria that are isolated with high frequency in the normal intestinal microbiota (i.e., intestinal dominant microbiota) have biological activities consistent with the effects of FMT. In this article, we confirmed that the treatment of intestinal dominant microbiota significantly restored intestinal microbiota abundance and composition to normal levels in APP/PS1 mice; downregulated brain tissue pro-inflammatory cytokines (IL-1β and IL-6) and amyloid precursor protein (APP) and β-site APP cleavage enzyme 1 (BACE1) expression levels; and reduced the area of Aβ plaque deposition in the brain hippocampus. Our study provides a new therapeutic concept for the treatment of AD, adjusting the intestinal microecological balance through dominant intestinal microbiota may be an alternative to FMT.}, } @article {pmid38137984, year = {2023}, author = {Laeeq, T and Vongsavath, T and Tun, KM and Hong, AS}, title = {The Potential Role of Fecal Microbiota Transplant in the Reversal or Stabilization of Multiple Sclerosis Symptoms: A Literature Review on Efficacy and Safety.}, journal = {Microorganisms}, volume = {11}, number = {12}, pages = {}, pmid = {38137984}, issn = {2076-2607}, abstract = {Multiple sclerosis (MS) affects millions of people worldwide, and recent data have identified the potential role of the gut microbiome in inducing autoimmunity in MS patients. To investigate the potential of fecal microbiota transplant (FMT) as a treatment option for MS, we conducted a comprehensive literature search (PubMed/Medline, Embase, Web of Science, Scopus, and Cochrane) and identified five studies that involved 15 adult MS patients who received FMT for gastrointestinal symptoms. The primary outcome of this review was to assess the effect of FMT in reversing and improving motor symptoms in MS patients, while the secondary outcome was to evaluate the safety of FMT in this patient population. Our findings suggest that all 15 patients who received FMT experienced improved and reversed neurological symptoms secondary to MS. This improvement was sustained even in follow-up years, with no adverse effects observed. These results indicate that FMT may hold promise as a treatment option for MS, although further research is necessary to confirm these findings.}, } @article {pmid38137770, year = {2023}, author = {Tikunov, AY and Fedorets, VA and Shrainer, EV and Morozov, VV and Bystrova, VI and Tikunova, NV}, title = {Intestinal Microbiome Changes and Clinical Outcomes of Patients with Ulcerative Colitis after Fecal Microbiota Transplantation.}, journal = {Journal of clinical medicine}, volume = {12}, number = {24}, pages = {}, pmid = {38137770}, issn = {2077-0383}, support = {21-14-00360//Russian Science Foundation/ ; }, abstract = {BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic inflammatory disease that affects many people. One of the possible ways to treat UC is fecal microbiota transplantation (FMT). In this study, changes in the intestinal microbiome and clinical outcomes of 20 patients with UC after FMT were estimated.

METHODS: FMT enemas were administrated ten times, once a day, and fecal microbiota from three donors was used for each enema. The clinical outcomes were assessed after eight weeks and then via a patient survey. The 16S rRNA profiles of the gut microbiota were compared between three samplings: samples from 20 patients with UC before and after FMT and samples from 18 healthy volunteers.

RESULTS: Clinical remission was achieved in 19 (95%) patients at week 8. Adverse events occurred in five patients, including one non-responder. A significant increase in average biodiversity was shown in samples after FMT compared to samples before FMT, as well as a decrease in the proportion of some potentially pathogenic bacteria.

CONCLUSION: The efficacy of FMT for UC treatment was confirmed; however, the duration of remission varied substantially, possibly due to different characteristics of the initial microbiota of patients. Targeted analysis of a patient's microbiome before FMT could increase the treatment efficacy.}, } @article {pmid38137679, year = {2023}, author = {Tsogka, A and Kitsos, DK and Stavrogianni, K and Giannopapas, V and Chasiotis, A and Christouli, N and Tsivgoulis, G and Tzartos, JS and Giannopoulos, S}, title = {Modulating the Gut Microbiome in Multiple Sclerosis Management: A Systematic Review of Current Interventions.}, journal = {Journal of clinical medicine}, volume = {12}, number = {24}, pages = {}, pmid = {38137679}, issn = {2077-0383}, abstract = {This review attempted to explore all recent clinical studies that have investigated the clinical and autoimmune impact of gut microbiota interventions in multiple sclerosis (MS), including dietary protocols, probiotics, fecal microbiota transplantation (FMT), and intermittent fasting (IF). Methods: Thirteen studies were held between 2011 and 2023 this demonstrated interventions in gut microbiome among patients with MS and their impact the clinical parameters of the disease. These included specialized dietary interventions, the supply of probiotic mixtures, FMT, and IF. Results: Dietary interventions positively affected various aspects of MS, including relapse rates, EDSS disability scores, MS-related fatigue, and metabolic features. Probiotic mixtures showed promising results on MS-related fatigue, EDSS parameters, inflammation; meanwhile, FMT-though a limited number of studies was included-indicated some clinical improvement in similar variables. IF showed reductions in EDSS scores and significant improvement in patients' emotional statuses. Conclusions: In dietary protocols, clinical MS parameters, including relapse rate, EDSS, MFIS, FSS, and MSQoL54 scales, were significantly improved through the application of a specific diet each time. Probiotic nutritional mixtures promote a shift in inflammation towards an anti-inflammatory cytokine profile in patients with MS. The administration of such mixtures affected disability, mood levels, and quality of life among patients with MS. FMT protocols possibly demonstrate a therapeutic effect in some case reports. IF protocols were found to ameliorate EDSS and FAMS scores. All interventional means of gut microbiome modulation provided significant conclusions on several clinical aspects of MS and highlight the complexity in the relationship between MS and the gut microbiome.}, } @article {pmid38137495, year = {2023}, author = {Li, A and Bowen, JM and Ball, IA and Wilson, S and Yong, A and Yeung, DT and Lee, CH and Bryant, RV and Costello, SP and Ryan, FJ and Wardill, HR}, title = {Autologous Faecal Microbiota Transplantation to Improve Outcomes of Haematopoietic Stem Cell Transplantation: Results of a Single-Centre Feasibility Study.}, journal = {Biomedicines}, volume = {11}, number = {12}, pages = {}, doi = {10.3390/biomedicines11123274}, pmid = {38137495}, issn = {2227-9059}, support = {APP1140992//National Health and Medical Research Council/ ; 2021/81-QA25313//Hospital Research Foundation/ ; 9766//Royal Adelaide Hospital/ ; }, abstract = {Haematopoietic stem cell transplantation (HSCT) is a curative approach for blood cancers, yet its efficacy is undermined by a range of acute and chronic complications. In light of mounting evidence to suggest that these complications are linked to a dysbiotic gut microbiome, we aimed to evaluate the feasibility of faecal microbiota transplantation (FMT) delivered during the acute phase after HSCT. Of note, this trial opted for FMT prepared using the individual's own stool (autologous FMT) to mitigate the risks of disease transmission from a donor stool. Adults (>18 years) with multiple myeloma were recruited from a single centre. The stool was collected prior to starting first line therapy. Patients who progressed to HSCT were offered FMT via 3 × retention enemas before day +5 (HSCT = day 0). The feasibility was determined by the recruitment rate, number and volume of enemas administered, and the retention time. Longitudinally collected stool samples were also collected to explore the influence of auto-FMT using 16S rRNA gene sequencing. n = 4 (2F:2M) participants received auto-FMT in 12 months. Participants received an average of 2.25 (1-3) enemas 43.67 (25-50) mL total, retained for an average of 60.78 (10-145) min. No adverse events (AEs) attributed to the FMT were identified. Although the minimum requirements were met for the volume and retention of auto-FMT, the recruitment was significantly impacted by the logistical challenges of the pretherapy stool collection. This ultimately undermined the feasibility of this trial and suggests that third party (donor) FMT should be prioritised.}, } @article {pmid38137365, year = {2023}, author = {Świrkosz, G and Szczygieł, A and Logoń, K and Wrześniewska, M and Gomułka, K}, title = {The Role of the Microbiome in the Pathogenesis and Treatment of Ulcerative Colitis-A Literature Review.}, journal = {Biomedicines}, volume = {11}, number = {12}, pages = {}, doi = {10.3390/biomedicines11123144}, pmid = {38137365}, issn = {2227-9059}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum. UC's pathogenesis involves colonic epithelial cell abnormalities and mucosal barrier dysfunction, leading to recurrent mucosal inflammation. The purpose of the article is to show the complex interplay between ulcerative colitis and the microbiome. The literature search was conducted using the PubMed database. After a screening process of studies published before October 2023, a total of 136 articles were selected. It has been discovered that there is a fundamental correlation of a robust intestinal microbiota and the preservation of gastrointestinal health. Dysbiosis poses a grave risk to the host organism. It renders the host susceptible to infections and has been linked to the pathogenesis of chronic diseases, with particular relevance to conditions such as ulcerative colitis. Current therapeutic strategies for UC involve medications such as aminosalicylic acids, glucocorticoids, and immunosuppressive agents, although recent breakthroughs in monoclonal antibody therapies have significantly improved UC treatment. Furthermore, modulating the gut microbiome with specific compounds and probiotics holds potential for inflammation reduction, while fecal microbiota transplantation shows promise for alleviating UC symptoms. This review provides an overview of the gut microbiome's role in UC pathogenesis and treatment, emphasizing areas for further research.}, } @article {pmid38137038, year = {2023}, author = {Nohesara, S and Abdolmaleky, HM and Zhou, JR and Thiagalingam, S}, title = {Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies.}, journal = {Genes}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/genes14122217}, pmid = {38137038}, issn = {2073-4425}, support = {CA138509//National Institute of Health/ ; }, abstract = {Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are complex and include the interaction of genetics with epigenetics and the host immune system. Modifications of the gut microbiome and its metabolites influence stress-related responses and social behavior in patients with depressive disorders by modulating the maturation of immune cells and neurogenesis in the brain mediated by epigenetic modifications. Here, we discuss the potential roles of a leaky gut in the development of depressive disorders via changes in gut microbiota-derived metabolites with epigenetic effects. Next, we will deliberate how altering the gut microbiome composition contributes to the development of depressive disorders via epigenetic alterations. In particular, we focus on how microbiota-derived metabolites such as butyrate as an epigenetic modifier, probiotics, maternal diet, polyphenols, drugs (e.g., antipsychotics, antidepressants, and antibiotics), and fecal microbiota transplantation could positively alleviate depressive-like behaviors by modulating the epigenetic landscape. Finally, we will discuss challenges associated with recent therapeutic approaches for depressive disorders via microbiome-related epigenetic shifts, as well as opportunities to tackle such problems.}, } @article {pmid38134862, year = {2023}, author = {Zhang, Z and Zuo, L and Song, X and Wang, L and Zhang, Y and Cheng, Y and Huang, J and Zhao, T and Yang, Z and Zhang, H and Li, J and Zhang, X and Geng, Z and Wang, Y and Ge, S and Hu, J}, title = {Arjunolic acid protects the intestinal epithelial barrier, ameliorating Crohn's disease-like colitis by restoring gut microbiota composition and inactivating TLR4 signalling.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {123}, number = {}, pages = {155223}, doi = {10.1016/j.phymed.2023.155223}, pmid = {38134862}, issn = {1618-095X}, abstract = {BACKGROUND AND AIMS: Crohn's disease (CD) is characterized by an overabundance of epithelial cell death and an imbalance in microflora, both of which contribute to the dysfunction of the intestinal barrier. Arjunolic acid (AA) has anti-apoptotic effects and regulates microbiota efficacy. The objective of this study was to assess the impact of the treatment on colitis resembling Crohn's disease, along with exploring the potential underlying mechanism.

METHODS: CD animal models were created using Il-10[-/-] mice, and the impact of AA on colitis in mice was evaluated through disease activity index, weight fluctuations, pathological examination, and assessment of intestinal barrier function. To clarify the direct role of AA on intestinal epithelial cell apoptosis, organoids were induced by LPS, and TUNEL staining was performed. To investigate the potential mechanisms of AA in protecting the intestinal barrier, various methods including bioinformatics analysis and FMT experiments were employed.

RESULTS: The treatment for AA enhanced the condition of colitis and the function of the intestinal barrier in Il-10[-/-] mice. This was demonstrated by the amelioration of weight loss, reduction in tissue inflammation score, and improvement in intestinal permeability. Moreover, AA suppressed the apoptosis of intestinal epithelial cells in Il-10[-/-] mice and LPS-induced colon organoids, while also reducing the levels of Bax and C-caspase-3. In terms of mechanism, AA suppressed the activation of TLR4 signaling in Il-10[-/-] mice and colon organoids induced by LPS. In addition, AA increased the abundance of short-chain fatty acid-producing bacteria in the stool of Il-10[-/-] mice, and transplantation of feces from AA-treated mice improved CD-like colitis.

CONCLUSIONS: The results of our study demonstrate that AA has a protective effect on the intestinal barrier in Crohn's disease-like colitis by preventing apoptosis. Additionally, this groundbreaking study reveals the capacity of AA to hinder TLR4 signaling and alter the makeup of the intestinal microbiome. The findings present fresh possibilities for treating individuals diagnosed with Crohn's disease. AA offers a hopeful novel strategy for managing Crohn's disease by obstructing crucial pathways implicated in intestinal inflammation and enhancing the gut microbiota.}, } @article {pmid38134565, year = {2023}, author = {Sah, RK and Nandan, A and Kv, A and S, P and S, S and Jose, A and Venkidasamy, B and Nile, SH}, title = {Decoding the role of the gut microbiome in gut-brain axis, stress-resilience, or stress-susceptibility: A review.}, journal = {Asian journal of psychiatry}, volume = {91}, number = {}, pages = {103861}, doi = {10.1016/j.ajp.2023.103861}, pmid = {38134565}, issn = {1876-2026}, abstract = {Increased exposure to stress is associated with stress-related disorders, including depression, anxiety, and neurodegenerative conditions. However, susceptibility to stress is not seen in every individual exposed to stress, and many of them exhibit resilience. Thus, developing resilience to stress could be a big breakthrough in stress-related disorders, with the potential to replace or act as an alternative to the available therapies. In this article, we have focused on the recent advancements in gut microbiome research and the potential role of the gut-brain axis (GBA) in developing resilience or susceptibility to stress. There might be a complex interaction between the autonomic nervous system (ANS), immune system, endocrine system, microbial metabolites, and bioactive lipids like short-chain fatty acids (SCFAs), neurotransmitters, and their metabolites that regulates the communication between the gut microbiota and the brain. High fiber intake, prebiotics, probiotics, plant supplements, and fecal microbiome transplant (FMT) could be beneficial against gut dysbiosis-associated brain disorders. These could promote the growth of SCFA-producing bacteria, thereby enhancing the gut barrier and reducing the gut inflammatory response, increase the expression of the claudin-2 protein associated with the gut barrier, and maintain the blood-brain barrier integrity by promoting the expression of tight junction proteins such as claudin-5. Their neuroprotective effects might also be related to enhancing the expression of brain-derived neurotrophic factor (BDNF) and glucagon-like peptide (GLP-1). Further investigations are needed in the field of the gut microbiome for the elucidation of the mechanisms by which gut dysbiosis contributes to the pathophysiology of neuropsychiatric disorders.}, } @article {pmid38133764, year = {2023}, author = {Hiltzik, DM and Goodwin, AM and Kurapaty, SS and Inglis, JE and Pagadala, MS and Edelstein, AI and Hsu, WK}, title = {The Role of the Gut Microbiome in Orthopedic Surgery-a Narrative Review.}, journal = {Current reviews in musculoskeletal medicine}, volume = {}, number = {}, pages = {}, pmid = {38133764}, issn = {1935-973X}, abstract = {PURPOSE OF REVIEW: The importance of the gut microbiome has received increasing attention in recent years. New literature has revealed significant associations between gut health and various orthopedic disorders, as well as the potential for interventions targeting the gut microbiome to prevent disease and improve musculoskeletal outcomes. We provide a broad overview of available literature discussing the links between the gut microbiome and pathogenesis and management of orthopedic disorders.

RECENT FINDINGS: Human and animal models have characterized the associations between gut microbiome dysregulation and diseases of the joints, spine, nerves, and muscle, as well as the physiology of bone formation and fracture healing. Interventions such as probiotic supplementation and fecal transplant have shown some promise in ameliorating the symptoms or slowing the progression of these disorders. We aim to aid discussions regarding optimization of patient outcomes in the field of orthopedic surgery by providing a narrative review of the available evidence-based literature involving gut microbiome dysregulation and its effects on orthopedic disease. In general, we believe that the gut microbiome is a viable target for interventions that can augment current management models and lead to significantly improved outcomes for patients under the care of orthopedic surgeons.}, } @article {pmid38133321, year = {2023}, author = {Goloshchapov, OV and Shchukina, OB and Kusakin, AV and Tsai, VV and Kalinin, RS and Eismont, YA and Glotov, OS and Chukhlovin, AB}, title = {Next-Generation Sequencing-Based Monitoring of Intestinal Bacteria and Bacteriophages Following Fecal Microbiota Transplantation in Inflammatory Bowel Diseases.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, pmid = {38133321}, issn = {2076-0817}, support = {22-15-00149//Russian Science Foundation/ ; }, abstract = {Inflammatory bowel diseases (IBD) and acute graft-versus-host disease (GVHD) are associated with persistent intestinal dysfunction preceded by gut bacterial dysbiosis. There are limited data on intestinal bacteriophages in these conditions. The aim of the present work was to detect associations between dominant intestinal bacteria by means of 16S rRNA gene sequencing, and some clinically significant viruses detected with a customized primer panel for NGS-based study. The clinical group included patients with Crohn's disease (IBD, n = 9), or GVHD (n = 6) subjected to fecal microbiota transplantation (FMT) from healthy donors. The stool specimens were taken initially, and 5 times post-FMT until day 120. Using NGS approach, we have found a higher abundance of Proteobacterota phylum in GVHD, especially, at later terms post-FMT. Moreover, we found an early increase of Klebsiella and E. coli/Shigella abundance in GVHD, along with decreased relative content of Faecalibacterium. Upon evaluation of intestinal phageome, the relative amount of Caudoviricetes class was higher in GVHD. A significant correlation was found between Proteobacteria and Caudoviricetes, thus suggesting their association during the post-FMT period. Moreover, the relative amounts of five Caudoviricetes phage species showed distinct correlations with Klebsiella and Enterococcus ratios at different terms of FMT. In conclusion, parallel use of 16S rRNA gene sequencing and targeted NGS viral panel is a feasible and useful option for tracing specific viral strains in fecal microbiota. The developed array of viral primers may be extended to detect other phages infecting the clinically relevant bacteria.}, } @article {pmid38133287, year = {2023}, author = {Avtanski, D and Reddy, V and Stojchevski, R and Hadzi-Petrushev, N and Mladenov, M}, title = {The Microbiome in the Obesity-Breast Cancer Axis: Diagnostic and Therapeutic Potential.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/pathogens12121402}, pmid = {38133287}, issn = {2076-0817}, abstract = {A growing body of evidence has demonstrated a relationship between the microbiome, adiposity, and cancer development. The microbiome is emerging as an important factor in metabolic disease and cancer pathogenesis. This review aimed to highlight the role of the microbiome in obesity and its association with cancer, with a particular focus on breast cancer. This review discusses how microbiota dysbiosis may contribute to obesity and obesity-related diseases, which are linked to breast cancer. It also explores the potential of the gut microbiome to influence systemic immunity, leading to carcinogenesis via the modulation of immune function. This review underscores the potential use of the microbiome profile as a diagnostic tool and treatment target, with strategies including probiotics, fecal microbiota transplantation, and dietary interventions. However, this emphasizes the need for more research to fully understand the complex relationship between the microbiome, metabolic disorders, and breast cancer. Future studies should focus on elucidating the mechanisms underlying the impact of the microbiome on breast cancer and exploring the potential of the microbiota profile as a biomarker and treatment target.}, } @article {pmid38129963, year = {2023}, author = {Cai, J and Cheung, J and Cheung, SWM and Chin, KTC and Leung, RWK and Lam, RST and Sharma, R and Yiu, JHC and Woo, CW}, title = {Butyrate acts as a positive allosteric modulator of serotonin transporter to decrease ileal serotonin availability.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.16305}, pmid = {38129963}, issn = {1476-5381}, abstract = {BACKGROUND AND PURPOSE: Radiation therapy-induced gastrointestinal distress is partly associated with the elimination of gut microbiota. The effectiveness of serotonin receptor blocker to treat radiation therapy-induced emesis suggests the pathophysiological role of serotonin. Peripheral serotonin is derived from intestinal epithelium. We aim to investigate the role of gut microbiota in regulating intestinal serotonin availability.

EXPERIMENTAL APPROACH: A radiation therapy murine model accompanied by faecal microbiota transplantation (FMT) from donors fed different diets was investigated, and mouse ileal organoid was employed for mechanistic study. The clinical relevance was validated by a small-scale human study.

KEY RESULTS: Short-term high-fat diet (HFD) induced gut bacteria to produce butyrate, and the irradiated mice receiving HFD-induced microbiome had the lowest ileal serotonin level compared with other recipients. The treatment with butyrate increased the serotonin uptake in mouse ileal organoids, such process was visualized by the real-time tracking of a fluorescent substrate for monoamine transporters. Silencing serotonin transporter (SERT) in the organoids abolished the butyrate-stimulated serotonin uptake. The competitive tests using different types of selective serotonin reuptake inhibitors suggested that butyrate acted as a positive allosteric modulator of SERT. In human gut microbiota, butyrate production was associated with the interconversion between acetate and butyrate. Faecal contents of both acetate and butyrate were negatively associated with serum serotonin, but only butyrate was positively correlated with BMI in human.

CONCLUSION AND IMPLICATIONS: Short-term HFD may be beneficial for alleviating gastrointestinal reactions by increasing butyrate to suppress local serotonin level and providing energy to cancer patients undergoing radiation.}, } @article {pmid38129926, year = {2023}, author = {Deng, R and Yu, S and Ruan, X and Liu, H and Zong, G and Cheng, P and Tao, R and Chen, W and Wang, A and Zhao, Y and Wei, Z and Lu, Y}, title = {Capsaicin orchestrates metastasis in gastric cancer via modulating expression of TRPV1 channels and driving gut microbiota disorder.}, journal = {Cell communication and signaling : CCS}, volume = {21}, number = {1}, pages = {364}, pmid = {38129926}, issn = {1478-811X}, support = {BK20200154//Natural Science Foundation of Jiangsu Province/ ; 2020M671551//China Postdoctoral Science Foundation/ ; 82004124//National Natural Science Foundation of China/ ; }, abstract = {The association between capsaicin, the major natural pungent compound of chili peppers, and gastric cancer progression has engendered conflicting findings. In this work, we sought to explore the character of a high capsaicin diet in gastric cancer metastasis and its possible mechanism. The impact of high capsaicin consumption on gastric cancer metastasis was investigated in vivo (xenograft mouse and zebrafish models) and in vitro (biochemical and molecular assays). It was demonstrated that high diet of capsaicin gave rise to accelerate tumor metastasis, which was partially mediated by elevating the expression of transient receptor potential vanilloid 1 (TRPV1) in gastric cancer cells. Importantly, we found that genetic depletion of TRPV1 could reduce gastric cancer metastasis by diminishing the motility of tumor cells in vitro, but acted poorly in xenograft mouse model. Considering the distribution of capsaicin in vivo, 16S rRNA sequencing and fecal microbiota transplantation (FMT) were used to appraise whether the gut microbiota involved in the high capsaicin diet induced metastasis. It was demonstrated that the level of Firmicutes and Clostridiales was expressively boosted following the high consumption of capsaicin. This microbial shift contributed to the increased peripheral 5-hydroxytryptamine (5-HT) levels, yielding the aggravated metastatic burden. Collectively, our findings highlighted the potential risk of high capsaicin diet in promoting gastric cancer metastasis by virtue of modulating TRPV1 expression and gut microbiota composition, indicating the importance of controlled consumption of chili peppers for patients with gastric cancer. Video Abstract.}, } @article {pmid38129370, year = {2023}, author = {Chen, Y and Wang, X and Ye, Y and Ren, Q}, title = {Gut microbiota in cancer: insights on microbial metabolites and therapeutic strategies.}, journal = {Medical oncology (Northwood, London, England)}, volume = {41}, number = {1}, pages = {25}, pmid = {38129370}, issn = {1559-131X}, abstract = {In recent years, the role of gut microbiota in cancer treatment has attracted substantial attention. It is now well established that gut microbiota and its metabolites significantly contribute to the incidence, treatment, and prognosis of various cancers. This review provides a comprehensive review on the pivotal role of gut microbiota and their metabolites in cancer initiation and progression. Furthermore, it evaluates the impact of gut microbiota on the efficacy and associated side effects of anticancer therapies, including radiotherapy, chemotherapy, and immunotherapy, thus emphasizing the clinical importance of gut microbiota reconstitution in cancer treatment.}, } @article {pmid38129277, year = {2023}, author = {Bonaz, B}, title = {The gut-brain axis in Parkinson's disease.}, journal = {Revue neurologique}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neurol.2023.11.004}, pmid = {38129277}, issn = {0035-3787}, abstract = {There is a bi-directional communication between the gut, including the microbiota, and the brain through the autonomic nervous system. Accumulating evidence has suggested a bidirectional link between gastrointestinal inflammation and neurodegeneration, in accordance with the concept of the gut-rain axis. An abnormal microbiota-gut-brain interaction contributes to the pathogeny of Parkinson's disease. This supports the hypothesis that Parkinson's disease originates in the gut to spread to the central nervous system, in particular through the vagus nerve. Targeting the gut-to-brain axis with vagus nerve stimulation, fecal microbiota transplantation, gut-selective antibiotics, as well as drugs targeting the leaky gut might be of interest in the management of Parkinson's disease.}, } @article {pmid38128750, year = {2023}, author = {Kim, HN and Cheong, HS and Kim, B and Sohn, W and Cho, YK and Kwon, MJ and Kim, J and Song, Y and Joo, EJ}, title = {Human gut microbiota from hepatitis B virus-infected individuals is associated with reduced triglyceride level in mice: faecal transplantation study.}, journal = {Microbes and infection}, volume = {}, number = {}, pages = {105281}, doi = {10.1016/j.micinf.2023.105281}, pmid = {38128750}, issn = {1769-714X}, abstract = {BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is associated with a reduced risk of dyslipidaemia. Using a human faecal microbiota transplantation (FMT), we compared changes in gut microbiota and lipid profiles in mice transplanted with human faeces from HBV-infected and non-infected individuals.

APPROACH AND RESULTS: A total of 19 mice received human FMT from four HBV-infected individuals and were categorised into the HBV-positive mice group, while 20 mice received FMT from four HBV-non-infected individuals into the HBV-negative one. In the analysis of gut microbiota in FMT mice, we observed a robust increase in alpha diversity and abundance of Akkermansia muciniphila in HBV-positive mice, compared to that in HBV-negative. Functional inference analysis revealed that the pathways involved in glycerolipid metabolism were more enriched in HBV-positive mice. At 5 weeks of FMT, the reduced triglyceride (TG) level was predominantly observed in HBV-positive mice.

CONCLUSIONS: Altered gut microbiota accompanied by HBV infection was associated with a robust increase in alpha diversity and butyrate producers, which resulted in a reduced level of TG at 5 weeks post-FMT. This indicates that the reduced risk of dyslipidaemia in chronic HBV infection may be due to the altered gut microbiota accompanied by HBV infection.}, } @article {pmid38128454, year = {2023}, author = {Wu, D and Liang, S and Du, X and Xiao, J and Feng, H and Ren, Z and Yang, X and Yang, X}, title = {Effects of fecal microbiota transplantation and fecal virome transplantation on LPS-induced intestinal injury in broilers.}, journal = {Poultry science}, volume = {103}, number = {2}, pages = {103316}, doi = {10.1016/j.psj.2023.103316}, pmid = {38128454}, issn = {1525-3171}, abstract = {The interesting roles and efficiencies of fecal microbiota transplantation (FMT) have attracted considerable attention and have been gradually evidenced in specific animal models. While the growing evidence that bacteriophages play roles in FMT efficacy has attracted considerable interest. In this study, we aimed to explore the effects of FMT and fecal virome transplantation (FVT) in improving inflammatory damage and ileal microbiota disorder in broilers. A total of 224 Arbor Acres broilers were selected at 1-day-old and randomly divided into the following 4 groups, with 56 broilers in each group: the CON group (the negative control group, sterile physiological saline injection + sterile phosphate-buffered saline (PBS) solution gavage), LPS group (the positive control group, lipopolysaccharide (LPS) injection + sterile PBS solution gavage), LPS + FMT group (LPS injection + FMT solution gavage), LPS + FVT group (LPS injection + FVT solution gavage). The results showed that: LPS injection significantly upregulated the mRNA expression levels of IFN-γ (P < 0.05) and IL-8 (P < 0.001) in ileal mucosa of broilers at 11th day of age (D11), while LPS + FMT and LPS + FVT did not; LPS injection significantly upregulated the mRNA expression of ZO-1 in ileal mucosa at D11 (P < 0.01), while LPS + FMT and LPS + FVT did not; at D11, compare to CON group, LPS injection and LPS + FMT significantly increased the relative abundance of virulence factor Rab2 interacting conserved protein A-related genes in broiler ileum contents (P < 0.05), while LPS + FVT had no significant difference with CON group (P > 0.05); at D11, LPS injection significantly downregulated the biosynthesis of antibiotics pathway (P < 0.05) in the ileal contents, while LPS + FVT did not. In conclusion, both FMT and FVT could promote the recovery of inflammation caused by LPS. Furthermore, FVT had shown less disadvantage stimulation on the broilers and could reduce the risk of transmission of pathogenic genes, compared to FMT.}, } @article {pmid38126747, year = {2023}, author = {Peng, J and Liu, T and Meng, P and Luo, Y and Zhu, S and Wang, Y and Ma, M and Han, J and Zhou, J and Su, X and Li, S and Ho, C-T and Lu, C}, title = {Gallic acid ameliorates colitis by trapping deleterious metabolite ammonia and improving gut microbiota dysbiosis.}, journal = {mBio}, volume = {}, number = {}, pages = {e0275223}, doi = {10.1128/mbio.02752-23}, pmid = {38126747}, issn = {2150-7511}, abstract = {The dysbiosis of the gut microbiota and its metabolism directly cause the emergence of IBD. In this study, we aimed to clarify the anti-colitis mechanism of GA in sight of gut microbiota and its metabolite ammonia. We discovered that GA directly captured and reduced the harmful metabolite ammonia in vivo to produce the aminated metabolite 4-NH2-GA, while the amination of GA had no adverse effect on its initial anti-colitis activity. In addition, both GA and its aminated metabolite improved the gut microbiota in colitis mice, and the modified gut microbiota, in turn, helped to relieve colitis. Since the GA structure is presented in diverse polyphenols as a common building block, the novel anti-colitis mechanism targeting the symptoms and root causes might also apply to other complex polyphenols.}, } @article {pmid38126116, year = {2023}, author = {Ma, X and Shin, JW and Cho, JH and Han, SW and Kim, DH}, title = {IL-6 expression-suppressing Lactobacillus reuteri strains alleviate gut microbiota-induced anxiety and depression in mice.}, journal = {Letters in applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/lambio/ovad144}, pmid = {38126116}, issn = {1472-765X}, abstract = {Fecal microbiota transplantation from patients with depression/inflammatory bowel disease (PDI) causes depression with gut inflammation in mice. Here, we investigated the effects of six Lactobacillus reuteri strains on BDNF, serotonin, and IL-6 expression in neuronal or macrophage cells and PDI fecal microbiota-cultured microbiota (PcM)-induced depression in mice. Of these strains, L6 most potently increased BDNF and serotonin levels in corticosterone-stimulated SH-SY5Ycells and PC12 cells, followed by L3. L6 most potently decreased IL-6 expression in LPS-stimulated macrophages. When L1 (weakest in vitro), L3, and L6 were orally administered in mice with PcM-induced depression, L6 most potently suppressed depression-like behaviors and hippocampal TNF-α and IL-6 expression and increased hippocampal serotonin, BDNF, 5HT7, GABAARα1, and GABABR1b expression, followed by L3 and L1. L6 also suppressed TNF-α, and IL-6 expression in the colon. BDNF or serotonin levels in corticosterone-stimulated neuronal cells were negatively correlated with depression-related biomarkers in PcM-transplanted mice, while IL-6 levels in LPS-stimulated macrophage were positively correlated. These findings suggest that IL-6 expression-suppressing and BDNF/serotonin expression-inducing LBPs in vitro, particularly L6, may alleviate gut microbiota-involved depression with colitis in vivo.}, } @article {pmid38124157, year = {2023}, author = {Miller, J and Żebrowska-Różańska, P and Czajkowska, A and Szponar, B and Kumala-Ćwikła, A and Chmielarz, M and Łaczmański, Ł}, title = {Faecal microbiota and fatty acids in feline chronic enteropathy.}, journal = {BMC veterinary research}, volume = {19}, number = {1}, pages = {281}, pmid = {38124157}, issn = {1746-6148}, support = {N060/0020/20//Wroclaw University of Environmental and Life Sciences, Wrocław, Poland/ ; N060/0020/20//Wroclaw University of Environmental and Life Sciences, Wrocław, Poland/ ; N060/0020/20//Wroclaw University of Environmental and Life Sciences, Wrocław, Poland/ ; }, abstract = {BACKGROUND: Feline chronic enteropathy is a set of disorders defined as the presence of clinical signs of gastrointestinal disease for at least three weeks. The most common final diagnoses are inflammatory bowel disease and alimentary small cell lymphoma. The etiopathogenesis of these diseases is incompletely understood; however, it is hypothesised that they involve a combination of factors, including altered composition and/or functionality of the intestinal microbiome. An important factor in the interplay of the microbiome and host is the production of short- and branched-chain fatty acids. The aim of this study was to evaluate the possible differences in faecal microbiota diversity, composition and fatty acid production between cats suffering from chronic enteropathy and healthy cats. Sixteen cats suffering from chronic enteropathy and fourteen healthy control cats were enrolled in the study. The microbiota compositions of faecal samples were analysed by using next-generation amplicon sequencing of the V3V4 fragment of the 16S rRNA gene. Fatty acids were evaluated by high-performance liquid chromatography.

RESULTS: Both the alpha and beta diversities were significantly lower in samples obtained from cats with chronic enteropathy. The relative abundance of the phylum Proteobacteria, orders Lactobacillales and Enterobacterales, family Enteriobacteriaceae and genus Escherichia Shigella were higher in diseased cats, whereas the abundance of the phylum Bacteroidota and order Peptococcales were higher in control cats. The faecal concentrations of short-chain fatty acids were higher in cats with chronic enteropathy, with lower propionate proportions and higher butyrate proportions.

CONCLUSION: The study revealed alterations in microbiota compositions and short-chain fatty acid concentration in cats suffering from chronic enteropathy, which is an important finding both for research on the pathogenesis of the disease and for potential therapeutic interventions in the form of faecal microbiota transplantation and/or probiotic supplementation.}, } @article {pmid38124090, year = {2023}, author = {Bleich, RM and Li, C and Sun, S and Ahn, JH and Dogan, B and Barlogio, CJ and Broberg, CA and Franks, AR and Bulik-Sullivan, E and Carroll, IM and Simpson, KW and Fodor, AA and Arthur, JC}, title = {A consortia of clinical E. coli strains with distinct in vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {277}, pmid = {38124090}, issn = {2049-2618}, support = {R21 AI159786/AI/NIAID NIH HHS/United States ; P30DK034987/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in vitro definition fully predicts mucosal colonization in vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis.

RESULTS: Germ-free inflammation-susceptible interleukin-10-deficient (Il10[-/-]) and inflammation-resistant WT mice were colonized with a consortium of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10[-/-] mice. These E. coli expand in Il10[-/-] mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization.

CONCLUSIONS: Our findings establish the in vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in vivo colonization dynamics of patient-derived bacteria in murine models. Video Abstract.}, } @article {pmid38123016, year = {2023}, author = {Gonçalves, CL and Doifode, T and de Rezende, VL and da Costa, MA and Rhoads, JM and Soutullo, CA}, title = {The many faces of microbiota-gut-brain axis in autism spectrum disorder.}, journal = {Life sciences}, volume = {}, number = {}, pages = {122357}, doi = {10.1016/j.lfs.2023.122357}, pmid = {38123016}, issn = {1879-0631}, abstract = {The gut-brain axis is gaining more attention in neurodevelopmental disorders, especially autism spectrum disorder (ASD). Many factors can influence microbiota in early life, including host genetics and perinatal events (infections, mode of birth/delivery, medications, nutritional supply, and environmental stressors). The gut microbiome can influence blood-brain barrier (BBB) permeability, drug bioavailability, and social behaviors. Developing microbiota-based interventions such as probiotics, gastrointestinal (GI) microbiota transplantation, or metabolite supplementation may offer an exciting approach to treating ASD. This review highlights that RNA sequencing, metabolomics, and transcriptomics data are needed to understand how microbial modulators can influence ASD pathophysiology. Due to the substantial clinical heterogeneity of ASD, medical caretakers may be unlikely to develop a broad and effective general gut microbiota modulator. However, dietary modulation followed by administration of microbiota modulators is a promising option for treating ASD-related behavioral and gastrointestinal symptoms. Future work should focus on the accuracy of biomarker tests and developing specific psychobiotic agents tailored towards the gut microbiota seen in ASD patients, which may include developing individualized treatment options.}, } @article {pmid38118419, year = {2023}, author = {Quesada-Vázquez, S and Castells-Nobau, A and Latorre, J and Oliveras-Cañellas, N and Puig-Parnau, I and Tejera, N and Tobajas, Y and Baudin, J and Hildebrand, F and Beraza, N and Burcelin, R and Martinez-Gili, L and Chilloux, J and Dumas, ME and Federici, M and Hoyles, L and Caimari, A and Del Bas, JM and Escoté, X and Fernández-Real, JM and Mayneris-Perxachs, J}, title = {Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity.}, journal = {Cell reports. Medicine}, volume = {4}, number = {12}, pages = {101341}, doi = {10.1016/j.xcrm.2023.101341}, pmid = {38118419}, issn = {2666-3791}, abstract = {The gut microbiota contributes to the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Histidine is a key energy source for the microbiota, scavenging it from the host. Its role in NAFLD is poorly known. Plasma metabolomics, liver transcriptomics, and fecal metagenomics were performed in three human cohorts coupled with hepatocyte, rodent, and Drosophila models. Machine learning analyses identified plasma histidine as being strongly inversely associated with steatosis and linked to a hepatic transcriptomic signature involved in insulin signaling, inflammation, and trace amine-associated receptor 1. Circulating histidine was inversely associated with Proteobacteria and positively with bacteria lacking the histidine utilization (Hut) system. Histidine supplementation improved NAFLD in different animal models (diet-induced NAFLD in mouse and flies, ob/ob mouse, and ovariectomized rats) and reduced de novo lipogenesis. Fecal microbiota transplantation (FMT) from low-histidine donors and mono-colonization of germ-free flies with Enterobacter cloacae increased triglyceride accumulation and reduced histidine content. The interplay among microbiota, histidine catabolism, and NAFLD opens therapeutic opportunities.}, } @article {pmid38118418, year = {2023}, author = {Liu, X and Xu, B and Xu, X and Wang, Z and Luo, Y and Gao, Y and Ling, S and Wang, A and Zhou, Y and Wang, X and Leng, SX and Li, W and Yao, X}, title = {Attenuation of allergen-specific immunotherapy for atopic dermatitis by ectopic colonization of Brevundimonas vesicularis in the intestine.}, journal = {Cell reports. Medicine}, volume = {4}, number = {12}, pages = {101340}, doi = {10.1016/j.xcrm.2023.101340}, pmid = {38118418}, issn = {2666-3791}, abstract = {Allergen-specific immunotherapy (AIT) has shown beneficial effects against atopic dermatitis (AD); however, the mechanisms and parameters underlying the efficacy of AIT remain unclear. Here, we report that the community structure and function of the oral and gut microbiota are changed in patients with AD undergoing AIT. Transplantation of fecal microbiota from patients who respond well to AIT improves AD-like dermatitis in mice. The abundance of Brevundimonas vesicularis in the gut of AD patients has been found to be positively correlated with disease severity and is decreased following AIT. Furthermore, we find that B. vesicularis from the oral cavity might ectopically colonize the gut of AD patients. In AD model mice, meanwhile, B. vesicularis promotes the skewing of the Treg/Th17 balance toward Th17 polarization and attenuates the efficacy of ovalbumin-specific immunotherapy. Our findings provide potential strategies for the optimization of AIT for AD via the modulation of the gut microbiota.}, } @article {pmid38116809, year = {2023}, author = {Ren, P and Yue, H and Tang, Q and Wang, Y and Xue, C}, title = {Astaxanthin slows down skeletal muscle atrophy in H22 tumor-bearing mice during sorafenib treatment by modulating the gut microbiota.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo04633h}, pmid = {38116809}, issn = {2042-650X}, abstract = {Astaxanthin is a carotenoid that is taken orally and has antitumor and anti-inflammatory properties. Our previous research demonstrated that astaxanthin alleviated skeletal muscle atrophy during sorafenib treatment in H22 tumor-bearing mice and altered the intestinal flora composition. However, the relationship between astaxanthin's amelioration of skeletal muscle atrophy in tumor-bearing mice and its ability to regulate intestinal flora is not clear. We used broad-spectrum antibiotics to create pseudo-sterile tumor-bearing mice, which we then used in fecal bacteria transplantation experiments. Our results indicate that the role of astaxanthin in ameliorating skeletal muscle atrophy during molecularly targeted therapy in mice with tumors is dependent on the intestinal flora. Astaxanthin substantially promoted the proliferation of Blautia, Parabacteroides, and Roseburia, altered the levels of metabolites in mouse serum, and primarily affected the amino acid metabolism of mice. Astaxanthin ameliorated skeletal muscle atrophy by promoting the activation of AKT/FOXO3a, which inhibited the expression of ubiquitination-degrading Fbx32 and MuRF1 and promoted myogenesis in skeletal muscle. Our study confirms that the intestinal flora is an important target for astaxanthin to combat skeletal muscle atrophy. Our research supports the use of astaxanthin as a nutritional supplement and intestinal microecological regulator for cancer patients.}, } @article {pmid38115597, year = {2023}, author = {Li, X and Li, J and Ji, J and Li, S and Yao, X and Fan, H and Yao, R}, title = {Gut microbiota modification by diosgenin mediates antiepileptic effects in a mouse model of epilepsy.}, journal = {Journal of neurochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1111/jnc.16033}, pmid = {38115597}, issn = {1471-4159}, support = {KYCX22_2869//Graduate Research and Innovation Projects of Jiangsu Province/ ; BK20221221//Natural Science Foundation of Jiangsu Province/ ; }, abstract = {Diosgenin, a natural steroid saponin, holds promise as a multitarget therapeutic for various diseases, including neurodegenerative conditions. Its efficacy in slowing Alzheimer's disease, Parkinson's disease, multiple sclerosis, and stroke progression has been demonstrated. However, the role of diosgenin in anti-epilepsy and its potential connection to the modulation of the intestinal microbiota remain poorly understood. In this study, exogenous diosgenin significantly mitigated pentylenetetrazole (PTZ)-induced seizures, learning and memory deficits, and hippocampal neuronal injury. 16S ribosomal RNA (16S rRNA) sequencing revealed a reversal in the decrease of Bacteroides and Parabacteroides genera in the PTZ-induced mouse epileptic model following diosgenin treatment. Fecal microbiota transplantation (FMT) experiments illustrated the involvement of diosgenin in modulating gut microbiota and providing neuroprotection against epilepsy. Our results further indicated the repression of enteric glial cells (EGCs) activation and the TLR4-MyD88 pathway, coupled with reduced production of inflammatory cytokines in the colonic lumen, and improved intestinal barrier function in epilepsy mice treated with diosgenin or FMT. This study suggests that diosgenin plays a role in modifying gut microbiota, contributing to the alleviation of intestinal inflammation and neuroinflammation, ultimately inhibiting epilepsy progression in a PTZ-induced mouse model. Diosgenin emerges as a potential therapeutic option for managing epilepsy and its associated comorbidities.}, } @article {pmid38113887, year = {2023}, author = {Zhu, Y and Jian, X and Chen, S and An, G and Jiang, D and Yang, Q and Zhang, J and Hu, J and Qiu, Y and Feng, X and Guo, J and Chen, X and Li, Z and Zhou, R and Hu, C and He, N and Shi, F and Huang, S and Liu, H and Li, X and Xie, L and Zhu, Y and Zhao, L and Jiang, Y and Li, J and Wang, J and Qiu, L and Chen, X and Jia, W and He, Y and Zhou, W}, title = {Targeting gut microbial nitrogen recycling and cellular uptake of ammonium to improve bortezomib resistance in multiple myeloma.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2023.11.019}, pmid = {38113887}, issn = {1932-7420}, abstract = {The gut microbiome has been found to play a crucial role in the treatment of multiple myeloma (MM), which is still considered incurable due to drug resistance. In previous studies, we demonstrated that intestinal nitrogen-recycling bacteria are enriched in patients with MM. However, their role in MM relapse remains unclear. This study highlights the specific enrichment of Citrobacter freundii (C. freundii) in patients with relapsed MM. Through fecal microbial transplantation experiments, we demonstrate that C. freundii plays a critical role in inducing drug resistance in MM by increasing levels of circulating ammonium. The ammonium enters MM cells through the transmembrane channel protein SLC12A2, promoting chromosomal instability and drug resistance by stabilizing the NEK2 protein. We show that furosemide sodium, a loop diuretic, downregulates SLC12A2, thereby inhibiting ammonium uptake by MM cells and improving progression-free survival and curative effect scores. These findings provide new therapeutic targets and strategies for the intervention of MM progression and drug resistance.}, } @article {pmid38113632, year = {2023}, author = {Wang, J and Xin, J and Xu, X and Chen, W and Lv, Y and Wei, Y and Wei, X and Li, Z and Ding, Q and Zhao, H and Wen, Y and Zhang, X and Fang, Y and Zu, X}, title = {Bacopaside I alleviates depressive-like behaviors by modulating the gut microbiome and host metabolism in CUMS-induced mice.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {170}, number = {}, pages = {115679}, doi = {10.1016/j.biopha.2023.115679}, pmid = {38113632}, issn = {1950-6007}, abstract = {Bacopaside I (BSI) is a natural compound that is difficult to absorb orally but has been shown to have antidepressant effects. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of BSI. Therefore, this study aimed to investigate the potential mechanism of BSI in the treatment of depression via the microbiota-gut-brain axis and to validate it in a fecal microbiota transplantation model. The antidepressant effect of BSI was established in CUMS-induced mice using behavioral tests and measurement of changes in hypothalamicpituitaryadrenal (HPA) axis-related hormones. The improvement of stress-induced gut-brain axis damage by BSI was observed by histopathological sections and enzyme-linked immunosorbent assay (ELISA). 16 S rDNA sequencing analysis indicated that BSI could modulate the abundance of gut microbiota and increase the abundance of probiotic bacteria. We also observed an increase in short-chain fatty acids, particularly acetic acid. In addition, BSI could modulate the disruption of lipid metabolism induced by CUMS. Fecal microbiota transplantation further confirmed that disruption of the microbiota-gut-brain axis is closely associated with the development of depression, and that the microbiota regulated by BSI exerts a partial antidepressant effect. In conclusion, BSI exerts antidepressant effects by remodeling gut microbiota, specifically through the Lactobacillus and Streptococcus-acetic acid-neurotrophin signaling pathways. Furthermore, BSI can repair damage to the gut-brain axis, regulate HPA axis dysfunction, and maintain immune homeostasis.}, } @article {pmid38112268, year = {2023}, author = {Chen, C and Liang, ZF and He, YQ and Li, AQ and Gao, Y and Pan, QW and Cao, JS}, title = {Pravastatin promotes type 2 diabetes vascular calcification through activating intestinal Bacteroides fragilis to induce macrophage M1 polarization.}, journal = {Journal of diabetes}, volume = {}, number = {}, pages = {}, doi = {10.1111/1753-0407.13514}, pmid = {38112268}, issn = {1753-0407}, support = {2021JJ40490//Natural Science Foundation of Hunan Province, China/ ; 2021JJ70113//Natural Science Foundation of Hunan Province, China/ ; 22A0292//The Research Foundation of Education Bureau of Hunan Province, China/ ; }, abstract = {BACKGROUND: Pravastatin is an oral lipid-lowering drug, commonly used by patients with diabetes that is positively correlated with the occurrence of vascular calcification (VC), but the mechanism is unclear.

METHODS: In this study, 16S rRNA sequencing and qRT-PCR wereused to detect the differential gut bacteria. Metabolomics and ELISA were used to analyze the differential metabolites. qRT-PCR and western blotting (WB) were used to detect genes expression. Flow cytometry was used to analyze macrophage phenotype. Immunohistochemistry was used to analyze aortic calcification.

RESULTS: We found that gut Bacteroides fragilis (BF) increased significantly in patients who took pravastatin or type 2 diabetes (T2D) mice treated with pravastatin. In vitro experiments showed that pravastatin had little effect on BF but significantly promoted BF proliferation in vivo. Further analysis showed that ArsR was an important gene for pravastatin to regulate the activation of BF, and overexpression of ArsR significantly promoted the secretion of 3,4,5-trimethoxycinnamic acid (TMCA). Importantly, pravastatin significantly promoted BF secretion of TMCA and significantly increased TMCA secretion in T2D patients or T2D mice. TMCA had little effect on vascular smooth muscle cell calcification but significantly promoted macrophage M1 polarization, which we had demonstrated that M1 macrophages promoted T2D VC. In vivo studies found that pravastatin significantly upregulated TMCA levels in the feces and serum of T2D mice transplanted with BF and promoted the macrophage M1 polarization in bone marrow and the osteoblastic differentiation of aortic cells. Similar results were obtained in T2D mice after intravenous infusion of TMCA.

CONCLUSIONS: Promoting intestinal BF to secrete TMCA, which leads to macrophage M1 polarization, is an important mechanism by which pravastatin promotes calcification, and the result will be used for the optimization of clinical medication strategies of pravastatin supplying a theoretical basis and experimental basis.}, } @article {pmid38111204, year = {2023}, author = {Song, Y and Yu, J and Wang, B and Wen, Q and Zhong, Y and Wu, M and Zheng, X}, title = {Effect of Fecal Microbiota Transplantation on Early Intestinal Immune Function and Histomorphology of Immune Organs in Chicks.}, journal = {Letters in applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/lambio/ovad140}, pmid = {38111204}, issn = {1472-765X}, abstract = {The intestinal microbiota drives the maturation of the immune system, which is essential for maintaining lifetime homeostasis. Whether fecal microbiota transplantation can promote the development of the immune system in chicks? On days 1, 3, and 5, the post-hatch Hy-line Brown chicks were treated with fecal suspension from breeding hens. Intestinal length, blood biochemical indicators, the morphology of immune organs, and intestinal immunity-related indicators were focused on days 7 and 14. Short-chain fatty acids were determined by gas chromatography. We discovered that fecal microbial transplantation significantly increased the area of the follicles and medulla from the bursa of fabricius, as well as the area of the medulla, cortex, and both ratios from the thymus on 14 d, the concentration of butyric acid in feces, the levels of immunologically active substances (TGF-β, IL-10, Foxp3, GPR43, IgA, etc.) in serum or the intestine, and the number of goblet cells. Correlation analysis indicated that short-chain fatty acids, as metabolites of the gut microbiota, were correlated with intestinal immunity. In short, fecal microbiota transplantation regulated early intestinal immunity, which provided the possibility for the processing and utilization of gut microbiota as germplasm resources.}, } @article {pmid38110638, year = {2023}, author = {Xie, B and Wang, B and Shang, R and Wang, L and Huang, X and Xie, L}, title = {Blocking MyD88 signaling with MyD88 inhibitor prevents colitis-associated colorectal cancer development by maintaining colonic microbiota homeostasis.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {22552}, pmid = {38110638}, issn = {2045-2322}, support = {2021CFB401//the Hubei Provincial Natural Science Foundation of China/ ; WJ2023M014//the Hubei Province health and family planning scientific research project/ ; 2020QYKF02//Open Project of the Key Laboratory of Organ Transplantation, Ministry of Education, and NHC/ ; 81702817//National Natural Science Foundations for Young Scientists of China/ ; 82273309//National Natural Science Foundations of China/ ; }, mesh = {Mice ; Animals ; Myeloid Differentiation Factor 88/genetics/metabolism ; *Colitis-Associated Neoplasms ; Colon/metabolism ; Signal Transduction ; *Microbiota ; *Colitis/complications/microbiology ; Dextran Sulfate/pharmacology ; Mice, Inbred C57BL ; Disease Models, Animal ; }, abstract = {Certain intestinal microbiota alterations appear to positively correlate with tumorigenesis of CAC due to the disruption of the balance between the host and microorganisms. It is proven that blocking MyD88 signaling can prevent colitis-associated colorectal cancer (CAC) development in mice. We are aim to reveal the role of MyD88 signaling of maintaining colonic microbiota homeostasis for preventing CAC development. We here analyzed the landscape of gut microbiome in the mice model of AOM/DSS-induced CAC with MyD88 inhibitor treatment. PCoA revealed significant reduction in Lactobacillus load and increase in Escherichia load in the mucosal microbial composition of mice with CAC, compared with normal controls (NCs). Inhibitor-treatment led to almost undetectable Proteobacteria (Escherichia) and the retention of the dominance of Firmicutes and Bacteroidota (Muribaculaceae) in the mucosa. RNA sequencing analysis identified genes were up-regulated (Hp, SAA3 and IL-1F9) and down-regulated (CYP3A44, SLC30A10, GPNMB and OTC) in Inhibitor-treated mice (vs. CAC). Meanwhile, Inhibitor-treated mice had higher percentage of MUC2-positive area in colon sections (vs. CAC, which was less than NCs) by IF staining and decreased Escherichia in the mucus layer (vs. CAC) by FISH. And intestinal microbiota from mice with MyD88 inhibitor treatment could lessen the outcome of CAC by fecal microbiota transplantation. The development of CAC was involved in the increasing and ectopic Escherichia in the decreasing colonic mucus layer. MyD88 signaling blockade may maintain the host-microbiota homeostasis by up-regulating MUC2 production, increasing probiotics and their protective effects, and inhibiting the reproduction of Escherichia.}, } @article {pmid38109364, year = {2023}, author = {Pun, CK and Huang, HC and Chang, CC and Hsu, SJ and Huang, YH and Hou, MC and Lee, FY}, title = {Hepatic encephalopathy: From novel pathogenesis mechanism to emerging treatments.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {}, number = {}, pages = {}, doi = {10.1097/JCMA.0000000000001041}, pmid = {38109364}, issn = {1728-7731}, abstract = {Hepatic encephalopathy (HE) is one of the major complications of liver disease and significantly affects the quality of life (QOL) of patients. HE is common and frequently relapses in cirrhotic patients. The management of hepatic encephalopathy is supportive, and precipitating conditions should be eliminated. Most drugs used to treat HE are conventional, and include nonabsorbable disaccharides such as lactulose, and antibiotics such as rifaximin. However, their therapeutic efficacy is still suboptimal and novel therapeutic agents are urgently needed. In addition, the optimal management and diagnosis of minimal HE/covert HE are under debate. In this review, we focus on novel pathogenetic mechanisms such as central nervous system clearance and emerging therapeutic targets of HE such as fecal material transplantation. We also discuss different classifications and etiologies of HE.}, } @article {pmid38108689, year = {2023}, author = {Zhang, JY and Xiao, J and Xie, B and Barba, H and Boachie-Mensah, M and Shah, RN and Nadeem, U and Spedale, M and Dylla, N and Lin, H and Sidebottom, AM and D'Souza, M and Theriault, B and Sulakhe, D and Chang, EB and Skondra, D}, title = {Oral Metformin Inhibits Choroidal Neovascularization by Modulating the Gut-Retina Axis.}, journal = {Investigative ophthalmology & visual science}, volume = {64}, number = {15}, pages = {21}, doi = {10.1167/iovs.64.15.21}, pmid = {38108689}, issn = {1552-5783}, mesh = {Male ; Female ; Animals ; Mice ; Angiogenesis Inhibitors ; RNA, Ribosomal, 16S ; Vascular Endothelial Growth Factor A ; Visual Acuity ; *Wet Macular Degeneration ; Retina ; *Choroidal Neovascularization/prevention & control ; }, abstract = {PURPOSE: Emerging data indicate that metformin may prevent the development of age-related macular degeneration (AMD). Whereas the underlying mechanisms of metformin's anti-aging properties remain undetermined, one proposed avenue is the gut microbiome. Using the laser-induced choroidal neovascularization (CNV) model, we investigate the effects of oral metformin on CNV, retinal pigment epithelium (RPE)/choroid transcriptome, and gut microbiota.

METHODS: Specific pathogen free (SPF) male mice were treated via daily oral gavage of metformin 300 mg/kg or vehicle. Male mice were selected to minimize sex-specific differences to laser induction and response to metformin. Laser-induced CNV size and macrophage/microglial infiltration were assessed by isolectin and Iba1 immunostaining. High-throughput RNA-seq of the RPE/choroid was performed using Illumina. Fecal pellets were analyzed for gut microbiota composition/pathways with 16S rRNA sequencing/shotgun metagenomics, as well as microbial-derived metabolites, including small-chain fatty acids and bile acids. Investigation was repeated in metformin-treated germ-free (GF) mice and antibiotic-treated/GF mice receiving fecal microbiota transplantation (FMT) from metformin-treated SPF mice.

RESULTS: Metformin treatment reduced CNV size (P < 0.01) and decreased Iba1+ macrophage/microglial infiltration (P < 0.005). One hundred forty-five differentially expressed genes were identified in the metformin-treated group (P < 0.05) with a downregulation in pro-angiogenic genes Tie1, Pgf, and Gata2. Furthermore, metformin altered the gut microbiome in favor of Bifidobacterium and Akkermansia, with a significant increase in fecal levels of butyrate, succinate, and cholic acid. Metformin did not suppress CNV in GF mice but colonization of microbiome-depleted mice with metformin-derived FMT suppressed CNV.

CONCLUSIONS: These data suggest that oral metformin suppresses CNV, the hallmark lesion of advanced neovascular AMD, via gut microbiome modulation.}, } @article {pmid38108398, year = {2023}, author = {Elkrief, A and Waters, NR and Smith, N and Dai, A and Slingerland, J and Aleynick, N and Febles, B and Gogia, P and Socci, ND and Lumish, M and Giardina, PA and Chaft, JE and Eng, J and Motzer, RJ and Mendelsohn, RB and Markey, KA and Zhuang, M and Li, Y and Yang, Z and Hollmann, TJ and Rudin, CM and van den Brink, MRM and Shia, J and DeWolf, S and Schoenfeld, AJ and Hellmann, MD and Babady, NE and Faleck, DM and Peled, JU}, title = {Immune-related colitis is associated with fecal microbial dysbiosis and can be mitigated by fecal microbiota transplantation.}, journal = {Cancer immunology research}, volume = {}, number = {}, pages = {}, doi = {10.1158/2326-6066.CIR-23-0498}, pmid = {38108398}, issn = {2326-6074}, abstract = {Colitis induced by treatment with immune checkpoint inhibitors (ICI), termed irColitis, is a substantial cause of morbidity complicating cancer treatment. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset, and that restoring the microbiome with fecal transplant from a healthy donor would mitigate disease severity. Herein, we present fecal microbiota profiles from 18 patients with irColitis from a single center, 5 of whom were treated with healthy donor fecal microbial transplantation (FMT). Although fecal samples collected at onset of irColitis had comparable (?)-diversity to that of comparator groups with gastrointestinal symptoms, irColitis was characterized by fecal microbial dysbiosis. Abundances of Proteobacteria were associated with irColitis in multivariable analyses. Five patients with irColitis refractory to steroids and biologic anti-inflammatory agents received healthy-donor FMT, with initial clinical improvement in irColitis symptoms observed in four of five patients. Two subsequently exhibited recurrence of irColitis symptoms following courses of antibiotics. Both received a second "salvage" FMT that was, again, followed by clinical improvement of irColitis. In summary, we observed distinct microbial community changes that were present at the time of irColitis onset. FMT was followed by clinical improvements in several cases of steroid- and biologic-agent-refractory irColitis. Strategies to restore or prevent microbiome dysbiosis in the context of immunotherapy toxicities should be further explored in prospective clinical trials.}, } @article {pmid38108213, year = {2023}, author = {Li, L and Liu, T and Shi, Y}, title = {Treatment of preterm brain injury via gut-microbiota-metabolite-brain axis.}, journal = {CNS neuroscience & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/cns.14556}, pmid = {38108213}, issn = {1755-5949}, support = {M1392//345 Talent Project of Shengjing Hospital/ ; M1415//345 Talent Project of Shengjing Hospital/ ; 2020JH1/10300001//Key R&D Guidance Plan Project in Liaoning Province/ ; 82171709//National Natural Science Foundation of China/ ; 81801500//National Natural Science Foundation of China/ ; 2022-MS-207//Natural Science Foundation of Liaoning Province/ ; }, abstract = {BACKGROUND: Brain injury in preterm infants potentially disrupts critical structural and functional connective networks in the brain. It is a major cause of neurological sequelae and developmental deficits in preterm infants. Interesting findings suggest that the gut microbiota (GM) and their metabolites contribute to the programming of the central nervous system (CNS) during developmental stages and may exert structural and functional effects throughout the lifespan.

AIM: To summarize the existing knowledge of the potential mechanisms related to immune, endocrine, neural, and blood-brain barrier (BBB) mediated by GM and its metabolites in neural development and function.

METHODS: We review the recent literature and included 150 articles to summarize the mechanisms through which GM and their metabolites work on the nervous system. Potential health benefits and challenges of relevant treatments are also discussed.

RESULTS: This review discusses the direct and indirect ways through which the GM may act on the nervous system. Treatment of preterm brain injury with GM or related derivatives, including probiotics, prebiotics, synbiotics, dietary interventions, and fecal transplants are also included.

CONCLUSION: This review summarizes mechanisms underlying microbiota-gut-brain axis and novel therapeutic opportunities for neurological sequelae in preterm infants. Optimizing the initial colonization and microbiota development in preterm infants may represent a novel therapy to promote brain development and reduce long-term sequelae.}, } @article {pmid38103544, year = {2023}, author = {Lehmann, CJ and Dylla, NP and Odenwald, M and Nayak, R and Khalid, M and Boissiere, J and Cantoral, J and Adler, E and Stutz, MR and Dela Cruz, M and Moran, A and Lin, H and Ramaswamy, R and Sundararajan, A and Sidebottom, AM and Little, J and Pamer, EG and Aronsohn, A and Fung, J and Baker, TB and Kacha, A}, title = {Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2023.11.016}, pmid = {38103544}, issn = {1934-6069}, abstract = {Metabolites produced by the intestinal microbiome modulate mucosal immune defenses and optimize epithelial barrier function. Intestinal dysbiosis, including loss of intestinal microbiome diversity and expansion of antibiotic-resistant pathobionts, is accompanied by changes in fecal metabolite concentrations and increased incidence of systemic infection. Laboratory tests that quantify intestinal dysbiosis, however, have yet to be incorporated into clinical practice. We quantified fecal metabolites in 107 patients undergoing liver transplantation (LT) and correlated these with fecal microbiome compositions, pathobiont expansion, and postoperative infections. Consistent with experimental studies implicating microbiome-derived metabolites with host-mediated antimicrobial defenses, reduced fecal concentrations of short- and branched-chain fatty acids, secondary bile acids, and tryptophan metabolites correlate with compositional microbiome dysbiosis in LT patients and the relative risk of postoperative infection. Our findings demonstrate that fecal metabolite profiling can identify LT patients at increased risk of postoperative infection and may provide guideposts for microbiome-targeted therapies.}, } @article {pmid38103514, year = {2023}, author = {Wu, Y and Feng, X and Li, M and Hu, Z and Zheng, Y and Chen, S and Luo, H}, title = {Gut microbiota associated with appetite suppression in high-temperature and high-humidity environments.}, journal = {EBioMedicine}, volume = {99}, number = {}, pages = {104918}, doi = {10.1016/j.ebiom.2023.104918}, pmid = {38103514}, issn = {2352-3964}, abstract = {BACKGROUND: Food is crucial for maintaining vital human and animal activities. Disorders in appetite control can lead to various metabolic disturbances. Alterations in the gut microbial composition can affect appetite and energy metabolism. While alterations in the gut microbiota have been observed in high-temperature and high-humidity (HTH) environments, the relationship between the gut microbiota during HTH and appetite remains unclear.

METHODS: We utilised an artificial climate box to mimic HTH environments, and established a faecal bacteria transplantation (FMT) mouse model. Mendelian randomisation (MR) analysis was used to further confirm the causal relationship between gut microbiota and appetite or appetite-related hormones.

FINDINGS: We found that, in the eighth week of exposure to HTH environments, mice showed a decrease in food intake and body weight, and there were significant changes in the intestinal microbiota compared to the control group. After FMT, we observed similar changes in food intake, body weight, and gut bacteria. Appetite-related hormones, including ghrelin, glucagon-like peptide-1, and insulin, were reduced in DH (mice exposed to HTH conditions) and DHF (FMT from mice exposed to HTH environments for 8 weeks), while the level of peptide YY initially increased and then decreased in DH and increased after FMT. Moreover, MR analysis further confirmed that these changes in the intestinal microbiota could affect appetite or appetite-related hormones.

INTERPRETATION: Together, our data suggest that the gut microbiota is closely associated with appetite suppression in HTH. These findings provide novel insights into the effects of HTH on appetite.

FUNDING: This work was supported by the National Natural Science Foundation of China and Guangzhou University of Chinese Medicine.}, } @article {pmid38101472, year = {2023}, author = {Benech, N and Barbut, F and Fitzpatrick, F and Krutova, M and Davies, K and Druart, C and Cordaillat-Simmons, M and Heritage, J and Guery, B and Kuijper, E and , }, title = {Update on Microbiota-derived therapies for recurrent Clostridioides difficile infections, 2023.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2023.12.007}, pmid = {38101472}, issn = {1469-0691}, abstract = {BACKGROUND: Fecal Microbiota transplantation (FMT) is the standard treatment for patients with multiple recurrent Clostridioides difficile infection (rCDI). Recently, new commercially developed human microbiota-derived medicinal products have been evaluated and FDA approved with considerable differences in terms of composition, administration, and targeted populations.

OBJECTIVES: To review available data on the different microbiota-derived treatments at the stage of advanced clinical evaluation and research in rCDI in comparison with FMT.

SOURCES: Phase II or III trials evaluating a microbiota-derived medicinal product to prevent rCDI.

CONTENT: Two commercial microbiota-derived medicinal products are approved by the FDA: Rebyota® (RBX2660 Ferring Pharmaceuticals, marketed in the US) and VOWST® (SER-109 -Seres Therapeutics, marketed in the US), whereas VE303 (Vedanta Biosciences Inc.) will be studied in phase III trial. RBX2660 and SER-109 are based on the processing of stools from healthy donors while VE303 consists of a defined bacterial consortium originating from human stools and produced from clonal cell banks. All have proven efficacy to prevent rCDI compared with placebo in patients considered at high risk of recurrence. However, the heterogeneity of the inclusion criteria, and the time between each episode and CDI diagnostics makes direct comparison between trials difficult. The differences regarding the risk of recurrence between the treatment and placebo arms were lower than previously described for FMT (FMT: Δ=50.5%; RBX2660- Phase III: Δ=13.1%; SER-109-Phase III: Δ=28%; high dose VE303- Phase II: Δ=31.7%). All treatments presented a good overall safety profile with mainly mild gastrointestinal symptoms.

IMPLICATIONS: Stool-derived products and bacterial consortia need to be clearly distinguished in terms of product characterization and their associated risks with specific long-term post-marketing evaluation similar to registries used for FMT. Their place in the therapeutic strategy for patients with rCDI requires further studies to determine the most appropriate patient population and administration route to prevent rCDI.}, } @article {pmid38098663, year = {2023}, author = {Zheng, C and Zhong, Y and Xie, J and Wang, Z and Zhang, W and Pi, Y and Zhang, W and Liu, L and Luo, J and Xu, W}, title = {Bacteroides acidifaciens and its derived extracellular vesicles improve DSS-induced colitis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1304232}, pmid = {38098663}, issn = {1664-302X}, abstract = {INTRODUCTION: "Probiotic therapy" to regulate gut microbiota and intervene in intestinal diseases such as inflammatory bowel disease (IBD) has become a research hotspot. Bacteroides acidifaciens, as a new generation of probiotics, has shown beneficial effects on various diseases.

METHODS: In this study, we utilized a mouse colitis model induced by dextran sodium sulfate (DSS) to investigate how B. acidifaciens positively affects IBD. We evaluated the effects ofB. acidifaciens, fecal microbiota transplantation, and bacterial extracellular vesicles (EVs) on DSS-induced colitis in mice. We monitored the phenotype of mouse colitis, detected serum inflammatory factors using ELISA, evaluated intestinal mucosal barrier function using Western blotting and tissue staining, evaluated gut microbiota using 16S rRNA sequencing, and analyzed differences in EVs protein composition derived from B. acidifaciens using proteomics to explore how B. acidifaciens has a positive impact on mouse colitis.

RESULTS: We confirmed that B. acidifaciens has a protective effect on colitis, including alleviating the colitis phenotype, reducing inflammatory response, and improving intestinal barrier function, accompanied by an increase in the relative abundance of B. acidifaciens and Ruminococcus callidus but a decrease in the relative abundance of B. fragilis. Further fecal bacterial transplantation or fecal filtrate transplantation confirmed the protective effect of eosinophil-regulated gut microbiota and metabolites on DSS-induced colitis. Finally, we validated that EVs derived from B. acidifaciens contain rich functional proteins that can contribute to the relief of colitis.

CONCLUSION: Therefore, B. acidifaciens and its derived EVs can alleviate DSS-induced colitis by reducing mucosal damage to colon tissue, reducing inflammatory response, promoting mucosal barrier repair, restoring gut microbiota diversity, and restoring gut microbiota balance in mice. The results of this study provide a theoretical basis for the preclinical application of the new generation of probiotics.}, } @article {pmid38096785, year = {2023}, author = {Rabot, S}, title = {tHIS way to cognitive development.}, journal = {Cell host & microbe}, volume = {31}, number = {12}, pages = {1947-1949}, doi = {10.1016/j.chom.2023.11.018}, pmid = {38096785}, issn = {1934-6069}, mesh = {*Gastrointestinal Microbiome ; *Microbiota ; Fecal Microbiota Transplantation ; Cognition ; }, abstract = {The effect of the microbiota-gut-brain axis on cognitive development in infancy is increasingly being scrutinized. In this issue of Cell Host & Microbe, Cerdó, Ruiz, and colleagues skillfully combine clinical and preclinical analyses, including a fecal transplantation experiment, to reveal associations between microbiota composition, cognitive scores, and histidine metabolism.}, } @article {pmid38096022, year = {2023}, author = {Nita, AF and Chanpong, A and Nikaki, K and Rybak, A and Thapar, N and Borrelli, O}, title = {Recent advances in the treatment of gastrointestinal motility disorders in children.}, journal = {Expert review of gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1080/17474124.2023.2295495}, pmid = {38096022}, issn = {1747-4132}, abstract = {INTRODUCTION: Paediatric gastrointestinal motility disorders represent some of the most challenging clinical conditions with largely undefined pathogenetic pathways and therefore limited therapeutic options. Herein, we provide an overview of the recent advances in treatment options for these disorders and their clinical impact.

AREAS COVERED: PubMed and Medline databases were searched for relevant articles related to treatment of achalasia, esophageal atresia, gastroparesis, PIPO and constipation published between 2017-2022. In this article we review and summarize recent advances in management of gastrointestinal motility disorders in children with a particular focus on emerging therapies as well as novel diagnostic modalities that help guide their application or develop new, more targeted treatments.

EXPERT OPINION: Gastrointestinal motility disorders represent one of the most challenging conundrums in pediatric age and despite significant advances in investigative tools, the palette of treatment options remain limited. Overall, while pharmacological options have failed to bring a curative solution, recent advances in minimal invasive therapeutic and diagnostic techniques have emerged as potential keys to symptom and quality of life improvement such as - ENDOFLIP, POEM, cine-MRI, fecal microbiota transplantation.}, } @article {pmid38095865, year = {2023}, author = {Pang, X and Chen, L and Xu, G}, title = {New Awareness of the Interplay Between the Gut Microbiota and Circadian Rhythms.}, journal = {Polish journal of microbiology}, volume = {72}, number = {4}, pages = {355-363}, pmid = {38095865}, issn = {2544-4646}, abstract = {Circadian rhythms influence various aspects of the biology and physiology of the host, such as food intake and sleep/wake cycles. In recent years, an increasing amount of genetic and epidemiological data has shown that the light/dark cycle is the main cue that regulates circadian rhythms. Other factors, including sleep/wake cycles and food intake, have necessary effects on the composition and rhythms of the gut microbiota. Interestingly, the gut microbiota can affect the circadian rhythm of hosts in turn through contact-dependent and contact-independent mechanisms. Furthermore, the gut microbiota has been shown to regulate the sleep/wake cycles through gut-brain-microbiota interaction. In addition to diabetes, the gut microbiota can also intervene in the progression of neuro- degenerative diseases through the gut-brain-microbiota interaction, and also in other diseases such as hypertension and rheumatoid arthritis, where it is thought to have a spare therapeutic potential. Even though fecal microbiota transplantation has good potential for treating many diseases, the risk of spreading intestinal pathogens should not be ignored.}, } @article {pmid38094621, year = {2023}, author = {Li, SQ and Shen, Y and Zhang, J and Weng, CZ and Wu, SD and Jiang, W}, title = {Immune modulation of gut microbiota and its metabolites in chronic hepatitis B.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1285556}, pmid = {38094621}, issn = {1664-302X}, abstract = {The gut microbiota is a diverse ecosystem consisting of 100 trillion microbiomes. The interaction between the host's gut and distal organs profoundly impacts various functions such as metabolism, immunity, neurology, and nutrition within the human body. The liver, as the primary immune organ, plays a crucial role in maintaining immune homeostasis by receiving a significant influx of gut-derived components and toxins. Perturbations in gut microbiota homeostasis have been linked to a range of liver diseases. The advancements in sequencing technologies, such as 16S rRNA and metagenomics, have opened up new avenues for comprehending the intricate physiological interplay between the liver and the intestine. Metabolites produced by the gut microbiota function as signaling molecules and substrates, influencing both pathological and physiological processes. Establishing a comprehensive host-bacterium-metabolism axis holds tremendous potential for investigating the mechanisms underlying liver diseases. In this review, we have provided a summary of the detrimental effects of the gut-liver axis in chronic liver diseases, primarily focusing on hepatitis B virus-related chronic liver diseases. Moreover, we have explored the potential mechanisms through which the gut microbiota and its derivatives interact with liver immunity, with implications for future clinical therapies.}, } @article {pmid38093327, year = {2023}, author = {Zhong, HJ and Wang, SQ and Zhang, RX and Zhuang, YP and Li, L and Yi, SZ and Li, Y and Wu, L and Ding, Y and Zhang, J and Xie, X and He, XX and Wu, Q}, title = {Supplementation with high-GABA-producing Lactobacillus plantarum L5 ameliorates essential tremor triggered by decreased gut bacteria-derived GABA.}, journal = {Translational neurodegeneration}, volume = {12}, number = {1}, pages = {58}, pmid = {38093327}, issn = {2047-9158}, support = {2022B1111070006//Guangdong Science and Technology Department/ ; 2019QN01N107//Guangdong Science and Technology Department/ ; 2022GDASZH-2022020402-01//Guangdong Academy of Sciences/ ; }, abstract = {BACKGROUND: The γ-aminobutyric acid (GABA) hypothesis posits a role of GABA deficiency in the central nervous system in the pathogenesis and progression of essential tremor (ET). However, the specific causative factor for GABA deficiency is not clear. The gut microbiota in mammals has recently been considered as a significant source of GABA. Furthermore, the GABA-based signals originating from the intestine can be transmitted to the brain through the "enteric nervous system-vagus nerve-brain" axis. However, the plausible contribution of gut microbiota to ET seems inspiring but remains obscure.

METHODS: Fecal samples from patients with ET and healthy controls were examined by metagenomic sequencing to compare the composition of gut microbiota and the expression of genes involved in GABA biosynthesis. The impact of gut microbiota on ET was explored through transplantation of fecal microbiota from patients with ET into the murine ET model. Lactic acid bacteria producing high amounts of GABA were identified through whole-genome sequencing and ultra-performance liquid chromatography-tandem mass spectrometry. Subsequently, mice were treated with the high-GABA-producing strain Lactobacillus plantarum L5. Tremor severity, behavioral tests, pro-inflammatory cytokines, GABA concentration, and gut microbiota composition were examined in these mice.

RESULTS: The gut microbiota of patients with ET demonstrated an impaired GABA-producing capacity and a reduced fecal GABA concentration. Transplantation of the gut microbiota from patients with ET induced an extension of tremor duration and impaired mobility in the murine model of ET. L5 exhibited an augmented GABA-producing capacity, with the De Man-Rogosa-Sharpe culture broth containing 262 mg/l of GABA. In addition, administration of L5 significantly decreased the tremor severity and enhanced the movement capability and grasping ability of ET mice. In vivo mechanistic experiments indicated that L5 reshaped the gut microbial composition, supplemented the mucosa-associated microbiota with GABA-producing capacity, increased the GABA concentrations in the cerebellum, and diminished inflammation in the central nervous system.

CONCLUSIONS: These findings highlight that deficiency of GABA-producing gut microbes plays an essential role in the pathogenesis of ET and that L5 is a promising candidate for treating ET.}, } @article {pmid38090578, year = {2023}, author = {Liu, W and Jiang, H and Liu, X and Zheng, Y and Liu, Y and Pan, F and Yu, F and Li, Z and Gu, M and Du, Q and Li, X and Zhang, H and Han, D}, title = {Altered intestinal microbiota enhances adenoid hypertrophy by disrupting the immune balance.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1277351}, pmid = {38090578}, issn = {1664-3224}, abstract = {INTRODUCTION: Adenoid hypertrophy (AH) is a common upper respiratory disorder in children. Disturbances of gut microbiota have been implicated in AH. However, the interplay of alteration of gut microbiome and enlarged adenoids remains elusive.

METHODS: 119 AH children and 100 healthy controls were recruited, and microbiome profiling of fecal samples in participants was performed using 16S rRNA gene sequencing. Fecal microbiome transplantation (FMT) was conducted to verify the effects of gut microbiota on immune response in mice.

RESULTS: In AH individuals, only a slight decrease of diversity in bacterial community was found, while significant changes of microbial composition were observed between these two groups. Compared with HCs, decreased abundances of Akkermansia, Oscillospiraceae and Eubacterium coprostanoligenes genera and increased abundances of Bacteroides, Faecalibacterium, Ruminococcus gnavus genera were revealed in AH patients. The abundance of Bacteroides remained stable with age in AH children. Notably, a microbial marker panel of 8 OTUs were identified, which discriminated AH from HC individuals with an area under the curve (AUC) of 0.9851 in the discovery set, and verified in the geographically different validation set, achieving an AUC of 0.9782. Furthermore, transfer of mice with fecal microbiota from AH patients dramatically reduced the proportion of Treg subsets within peripheral blood and nasal-associated lymphoid tissue (NALT) and promoted the expansion of Th2 cells in NALT.

CONCLUSION: These findings highlight the effect of the altered gut microbiota in the AH pathogenesis.}, } @article {pmid38088972, year = {2023}, author = {Fang, H and Yao, T and Li, W and Pan, N and Xu, H and Zhao, Q and Su, Y and Xiong, K and Wang, J}, title = {Efficacy and safety of fecal microbiota transplantation for chronic insomnia in adults: a real world study.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1299816}, pmid = {38088972}, issn = {1664-302X}, abstract = {OBJECTIVE: To assess the efficacy and safety of fecal microbiota transplantation (FMT) for adult chronic insomnia.

METHODS: Patients treated with FMT for chronic diseases were divided into chronic insomnia and non-insomnia group. The primary endpoint was the efficacy of FMT for insomnia 4 weeks after treatment, the secondary endpoints included the impacts of FMT on anxiety, depression, health-related quality of life, gut microbiota, and adverse events associated with FMT. Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) were utilized to assess the efficacy of FMT on insomnia, self-rating anxiety/depression scale [Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS)] was employed to evaluate anxiety and depression. Quality of life was evaluated by SF-36. 16S rRNA sequencing was employed to analyze the gut microbiota and correlation analysis was performed.

RESULTS: Forty patients met the inclusion criteria and seven were excluded. 33 patients were enrolled and stratified into chronic insomnia group (N = 17) and non-insomnia group (N = 16). Compared to baseline, FMT significantly ameliorated the ISI (17.31 ± 5.12 vs. 5.38 ± 5.99), PSQI (14.56 ± 2.13 vs. 6.63 ± 4.67), SAS (54.25 ± 8.90 vs. 43.68 ± 10.64) and SDS (57.43 ± 10.96 vs. 50.68 ± 15.27) score and quality of life of chronic insomnia patients. 76.47% (13/17) of insomnia patients achieved the primary endpoints. In chronic insomnia patients, the relative abundance of Eggerthella marked enhanced at baseline, while the relative abundance of Lactobacillus, Bifidobacterium, Turicibacter, Anaerostipes, and Eisenbergiella significantly increased after FMT treatment, the latter positive correlated with the efficacy of FMT. Encouragingly, FMT also improved the sleep quality of non-insomnia patients.

CONCLUSION: Eggerthella may potentially serve as a distinctive genus associated with chronic insomnia. FMT maybe a novel treatment option for adults with chronic insomnia and provide an alternative to traditional treatments for insomnia. The effects were positive correlated with the augmentation of probiotics, such as Bifidobacterium, Lactobacillus, Turicibacter, and Fusobacterium.}, } @article {pmid38088959, year = {2023}, author = {Deng, H and Yu, Y and Sha, Q and Sun, W and Liang, L and Ren, F and Ji, H and Shen, X and Fan, X}, title = {Construction of antibiotic-induced depression mice model and the function of intestinal microbiota.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1093486}, pmid = {38088959}, issn = {1664-302X}, abstract = {Many research studies focus on intestinal microbiota-related depression induced by the usage of antibiotics, but the use of antibiotics is fairly different. To construct an effective antibiotic-induced depression mice model and explore the effect of intestinal microbiota in antibiotic-induced depression, we used several kinds of antibiotic mixtures to induce mice depression and used depression-related behavioral tests and neurobiological factors to evaluate the construction of the antibiotic-induced depression mice model. SPSS statistical software was used to analyze the above data, and the optimal model was selected according to the stability of the results and the simplicity of the modeling methods. Metagenomic analysis and fecal microbiota transplantation (FMT) of intestinal microbiota from antibiotic-induced depression mice were performed to analyze the effect of intestinal microbiota. The results showed that antibiotic mixture A (1.25 μg/mL natamycin, 5 mg/mL neomycin sulfate, and 5 mg/mL bacitracin), antibiotic mixture B (24 mg/mL bacitracin, 24 mg/mL neomycin sulfate, 9.6 mg/mL ampicillin, 4.8 mg/mL meropenem, and 1.47 mg/mL vancomycin), and antibiotic solution D (only containing 5 mg/mL neomycin sulfate) could induce depression-like behavior in mice. By using these antibiotics, the concentrations of norepinephrine (NE), 5-hydroxytryptamine (5-HT), and brain-derived neurotrophic factor (BDNF) in mice hippocampus and prefrontal cortex tissues were significantly decreased. All the above results were consistent with those of chronic unpredictable mild stress (CUMS) depression mice. The FMT results showed that fecal microbiota from antibiotic-induced depressed mice transplanted into normal mice (8 weeks-old male C57BL/6J SPF mice) also could induce depression-like behavior and cause similar changes in neurobiological factors. Metagenomic analysis showed that the community structure of microbiota in the intestinal tract of antibiotic-induced depression mice was significantly different from that in control mice, the intestinal microbiota species diversity in antibiotic-induced depression mice was lower, the lipoic acid metabolism pathway was significantly activated, and the abundance of functional gene lipA was explicitly increased. Quantitative real-time PCR (qPCR) further verified the abundance of enriched bacteria in the intestinal microbiota of antibiotic-induced depression mice. In summary, the specific antibiotic mixtures can induce depression by causing changes in intestinal microbiota in mice. Antibiotic-induced depressed mice show differences in intestinal microbiota abundance, high enrichment of the unique metabolic pathway, and the functional gene.}, } @article {pmid38088183, year = {2023}, author = {Chalif, J and Wang, H and Spakowicz, D and Quick, A and Arthur, EK and O'Malley, D and Chambers, LM}, title = {The microbiome and gynecologic cancer: cellular mechanisms and clinical applications.}, journal = {International journal of gynecological cancer : official journal of the International Gynecological Cancer Society}, volume = {}, number = {}, pages = {}, doi = {10.1136/ijgc-2023-004894}, pmid = {38088183}, issn = {1525-1438}, abstract = {The microbiome plays a vital function in maintaining human health and homeostasis. Each microbiota has unique characteristics, including those of the gastrointestinal and female reproductive tract. Dysbiosis, or alterations to the composition of the microbial communities, impacts the microbiota-host relationship and is linked to diseases, including cancer. In addition, studies have demonstrated that the microbiota can contribute to a pro-carcinogenic state through altered host immunologic response, modulation of cell proliferation, signaling, gene expression, and dysregulated metabolism of nutrients and hormones.In recent years, the microbiota of the gut and female reproductive tracts have been linked to many diseases, including gynecologic cancers. Numerous pre-clinical and clinical studies have demonstrated that specific bacteria or microbial communities may contribute to the development of gynecologic cancers. Further, the microbiota may also impact the toxicity and efficacy of cancer therapies, including chemotherapy, immunotherapy, and radiation therapy in women with gynecologic malignancies. The microbiota is highly dynamic and may be altered through various mechanisms, including diet, exercise, medications, and fecal microbiota transplantation. This review provides an overview of the current literature detailing the relationship between gynecologic cancers and the microbiota of the female reproductive and gastrointestinal tracts, focusing on mechanisms of carcinogenesis and strategies for modulating the microbiota for cancer prevention and treatment. Advancing our understanding of the complex relationship between the microbiota and gynecologic cancer will provide a novel approach for prevention and therapeutic modulation in the future.}, } @article {pmid38088063, year = {2023}, author = {Nohesara, S and Abdolmaleky, HM and Thiagalingam, S and Zhou, JR}, title = {Gut microbiota defined epigenomes of Alzheimer's and Parkinson's diseases reveal novel targets for therapy.}, journal = {Epigenomics}, volume = {}, number = {}, pages = {}, doi = {10.2217/epi-2023-0342}, pmid = {38088063}, issn = {1750-192X}, support = {NIH (CA138509)//Common Fund/ ; }, abstract = {The origins of Alzheimer's disease (AD) and Parkinson's disease (PD) involve genetic mutations, epigenetic changes, neurotoxin exposure and gut microbiota dysregulation. The gut microbiota's dynamic composition and its metabolites influence intestinal and blood-brain barrier integrity, contributing to AD and PD development. This review explores protein misfolding, aggregation and epigenetic links in AD and PD pathogenesis. It also highlights the role of a leaky gut and the microbiota-gut-brain axis in promoting these diseases through inflammation-induced epigenetic alterations. In addition, we investigate the potential of diet, probiotics and microbiota transplantation for preventing and treating AD and PD via epigenetic modifications, along with a discussion related to current challenges and future considerations. These approaches offer promise for translating research findings into practical clinical applications.}, } @article {pmid38087767, year = {2023}, author = {Tabata, K and Ikarashi, N and Shinozaki, Y and Yoshida, R and Kon, R and Sakai, H and Hosoe, T and Kamei, J}, title = {Effect of the gut microbiota on the expression of genes that are important for maintaining skin function: Analysis using aged mice.}, journal = {The Journal of dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1346-8138.17062}, pmid = {38087767}, issn = {1346-8138}, support = {19K08783//Japan Society for the Promotion of Science/ ; }, abstract = {The gut microbiota changes greatly at the onset of disease, and the importance of intestinal bacteria has been highlighted. The gut microbiota also changes greatly with aging. Aging causes skin dryness, but it is not known how changes in the gut microbiota with aging affects the expression of genes that are important for maintaining skin function. In this study, we investigated how age-related changes in gut microbiota affect the expression of genes that regulate skin function. The gut microbiotas from young mice and aged mice were transplanted into germ-free mice (fecal microbiota transplantation [FMT]). These recipient mice were designated FMT-young mice and FMT-old mice respectively, and the expression levels of genes important for maintaining skin function were analyzed. The dermal water content was significantly lower in old mice than that in young mice, indicating dry skin. The gut microbiota significantly differed between old mice and young mice. The water channel aquaporin-3 (Aqp3) expression level in the skin of FMT-old mice was significantly higher than that in FMT-young mice. In addition, among the genes that play an important role in maintaining skin function, the expression levels of those encoding ceramide-degrading enzyme, ceramide synthase, hyaluronic acid-degrading enzyme, and Type I collagen were also significantly higher in FMT-old mice than in FMT-young mice. It was revealed that the gut microbiota, which changes with age, regulates the expression levels of genes related to skin function, including AQP3.}, } @article {pmid38087724, year = {2023}, author = {Pakmehr, A and Mousavi, SM and Ejtahed, HS and Hoseini-Tavassol, Z and Siadat, SD and Hasani-Ranjbar, S and Larijani, B}, title = {The Effect of Fecal Microbiota Transplantation on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis.}, journal = {Clinical therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clinthera.2023.11.015}, pmid = {38087724}, issn = {1879-114X}, abstract = {PURPOSE: Cardiometabolic disease (CMD) is increasing along with its predisposing factors and adverse consequences. As gut microbiota dysbiosis is established in these patients, fecal microbiota transplantation (FMT), which alters the bacterial composition of the intestine, supposedly can help improve cardiometabolic disturbances. We conducted a systematic review and meta-analysis evaluating the impact of FMT on the cardiometabolic parameters and gut microbiota composition of patients experiencing at least one cardiometabolic issue.

METHODS: Eligible studies were searched through the PubMed, Web of Science, and Scopus databases until December 2022. The initial search results underwent duplication removal and screening until each included study was scanned for intended data. The Cochrane risk of bias tool was used to evaluate the methodologic accuracy of studies and the random effects model was used for conducting the meta-analysis.

FINDINGS: Eighteen of the original 2414 articles from the literature search were entered into the systematic review; of these, 11 were included in the meta-analysis. Insulin showed a significant decrease by 24.7 pmol/L (weighted mean difference [WMD], -24.77; 95% CI, -48.704 to -0.848) after short-term follow-up, and HDL increased by 0.1 mmol/l(WMD, 0.106; 95% CI, 0.027 to 0.184) and 0.12 mmol/l(WMD, 0.120; 95% CI, 0.003 to 0.237) in those using a capsule deliver mode and in short-term follow-up, respectively. No significant changes were seen in other lipid profiles, blood glucose, insulin resistance, or anthropometric indices. In addition, multiple studies reported gut microbiota alterations after the intervention, including an increase in butyrate-producing species.

IMPLICATIONS: Although some articles reported the beneficial effects of FMT on metabolic parameters, we failed to find a clinically significant alteration. Also, information regarding proper donors and the best method to induce FMT have not yet been sufficiently investigated, which should be considered along with means to prevent potential damages. PROSPERO identifier: CRD42022380705.}, } @article {pmid38087373, year = {2023}, author = {Yang, J and Liu, S and Zhao, Q and Li, X and Jiang, K}, title = {Gut microbiota-related metabolite alpha-linolenic acid mitigates intestinal inflammation induced by oral infection with Toxoplasma gondii.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {273}, pmid = {38087373}, issn = {2049-2618}, support = {202301BD070001-069//Joint Special Project of Agricultural Basic Research in Yunnan/ ; 202301AU070109//Yunnan Fundamental Research Projects/ ; }, abstract = {BACKGROUND: Oral infection with cysts is the main transmission route of Toxoplasma gondii (T. gondii), which leads to lethal intestinal inflammation. It has been widely recognized that T. gondii infection alters the composition and metabolism of the gut microbiota, thereby affecting the progression of toxoplasmosis. However, the potential mechanisms remain unclear. In our previous study, there was a decrease in the severity of toxoplasmosis after T. gondii α-amylase (α-AMY) was knocked out. Here, we established mouse models of ME49 and Δα-amy cyst infection and then took advantage of 16S rRNA gene sequencing and metabolomics analysis to identify specific gut microbiota-related metabolites that mitigate T. gondii-induced intestinal inflammation and analyzed the underlying mechanism.

RESULTS: There were significant differences in the intestinal inflammation between ME49 cyst- and Δα-amy cyst-infected mice, and transferring feces from mice infected with Δα-amy cysts into antibiotic-treated mice mitigated colitis caused by T. gondii infection. 16S rRNA gene sequencing showed that the relative abundances of gut bacteria, such as Lactobacillus and Bacteroides, Bifidobacterium, [Prevotella], Paraprevotella and Macellibacteroides, were enriched in mice challenged with Δα-amy cysts. Spearman correlation analysis between gut microbiota and metabolites indicated that some fatty acids, including azelaic acid, suberic acid, alpha-linolenic acid (ALA), and citramalic acid, were highly positively correlated with the identified bacterial genera. Both oral administration of ALA and fecal microbiota transplantation (FMT) decreased the expression of pro-inflammatory cytokines and restrained the MyD88/NF-κB pathway, which mitigated colitis and ultimately improved host survival. Furthermore, transferring feces from mice treated with ALA reshaped the colonization of beneficial bacteria, such as Enterobacteriaceae, Proteobacteria, Shigella, Lactobacillus, and Enterococcus.

CONCLUSIONS: The present findings demonstrate that the host gut microbiota is closely associated with the severity of T. gondii infection. We provide the first evidence that ALA can alleviate T. gondii-induced colitis by improving the dysregulation of the host gut microbiota and suppressing the production of pro-inflammatory cytokines via the MyD88/NF-κB pathway. Our study provides new insight into the medical application of ALA for the treatment of lethal intestinal inflammation caused by Toxoplasma infection. Video Abstract.}, } @article {pmid38087164, year = {2023}, author = {Chen, S and Jiao, Y and Han, C and Li, Y and Zou, W and Liu, J}, title = {Drug-Resistant Epilepsy and Gut-Brain Axis: an Overview of a New Strategy for Treatment.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {38087164}, issn = {1559-1182}, support = {2021JH2/10300135//Liaoning Directed project for planning of science and technology/ ; 2112006//Dalian Science and Technology Innovation Fund/ ; 2021RQ028//Dalian High-Level Talent Innovation Program/ ; XLYC1902031//Liaoning Province Excellent Talent Program Project/ ; 2022RG18//Dalian High-level Talent Team Project/ ; CMR-20161129-1003//National Health and Family Planning Commission and Food and Drug Administration/ ; }, abstract = {Drug-resistant epilepsy (DRE), also known as intractable epilepsy or refractory epilepsy, is a disease state with long-term poorly controlled seizures attack. Without effective treatment, patients are at an elevated risk of injury, premature death, mental disorders, and poor quality of life, increasing the need for a fresh perspective on the etiology and treatment of DRE. The gut is known to harbor a wide variety of microorganisms that can regulate the host's response to exogenous signals and participate in various physiological and pathological processes in the human body. Interestingly, emerging evidence has uncovered the changes in gut microbiota in patients with epilepsy, particularly those with DRE. In addition, both dietary interventions and specific antibiotic therapy have been proven to be effective in restoring the microecological environment and, more importantly, reducing seizures. Here, we reviewed recent studies on DRE and the involvement of gut microbiota in it, describing changes in the gut microflora composition in patients with DRE and corresponding animal models. Furthermore, the influence of the ketogenic diet, probiotics, fecal microbiota transplantation (FMT), and antibiotics as microbiome-related factors on seizure control and its possible mechanisms are broadly discussed. Finally, we highlighted the significance of gut microbiome in DRE, in order to provide a new prospect for early identification and individualized treatment of patients with DRE.}, } @article {pmid38087159, year = {2023}, author = {Wu, D and Xiong, W and Ma, S and Luo, J and Ye, H and Huang, S and Li, F and Xiang, X and Chen, Q and Gao, B and Deng, J and Yin, Y and Tan, C}, title = {Konjac flour-mediated gut microbiota alleviates insulin resistance and improves placental angiogenesis of obese sows.}, journal = {AMB Express}, volume = {13}, number = {1}, pages = {143}, pmid = {38087159}, issn = {2191-0855}, support = {2021A1515012116//Natural science foundation of guangdong province/ ; 32272895//national natural science foundation china/ ; 32172744//national natural science foundation china/ ; }, abstract = {Our previous study revealed that dietary konjac flour (KF) could remodel gut microbiota and improve reproductive performance of sows, but its underlying mechanisms remain unclear. This experiment aimed to investigate how dietary KF improves reproductive performance of obese sows. Here, 60 sows were assigned into three groups according to their backfat thickness: normal backfat sows fed with control diet (CON-N), high backfat sows fed with control diet (CON-H) and high backfat sows fed with KF inclusion diet (KF-H). The characteristics of sows and piglets were recorded. Next, fecal microbiota transplantation (FMT) was performed on female mice, followed by recording the characteristics of female mice. The results showed that compared with CON-H group, KF-H group showed downtrend in stillbirth rate (P = 0.07), an increase in placental efficiency (P < 0.01) and average piglet weight (P < 0.01); coupled with a decrease in the values of homeostasis model assessment-insulin resistance (P < 0.01); as well as an increase in placental vascular density and protein expression of angiogenesis markers (P < 0.01). As expected, sows fed KF diets had improved abundance and diversity of gut microbiota. More importantly, compared with CON-H(FMT) group, KF-H(FMT) group showed improvement in reproductive performance and insulin sensitivity (P < 0.05), as well as an increase in placental labyrinth zone and protein expression of angiogenesis markers (P < 0.05). Furthermore, we found a content increase (P < 0.05) of SCFAs in both KF-H group sow and KF-H (FMT) group mice. Overall, KF supplementation could alleviate insulin resistance, promote placental angiogenesis, and ultimately improve the reproductive performance of sows via gut microbiota remodeling.}, } @article {pmid38087070, year = {2023}, author = {Corriero, A and Giglio, M and Inchingolo, F and Moschetta, A and Varrassi, G and Puntillo, F}, title = {Gut Microbiota Modulation and Its Implications on Neuropathic Pain: A Comprehensive Literature Review.}, journal = {Pain and therapy}, volume = {}, number = {}, pages = {}, pmid = {38087070}, issn = {2193-8237}, abstract = {Neuropathic pain (NP) is a chronic pain disorder arising from somatosensory nervous system impairment. Extensive evidence supports the notion that the gut microbiota (GM) is crucial in maintaining human health by performing vital tasks. At the same time, its disruption has been linked to the emergence and advancement of an expanding range of disorders, including NP, in which GM could play a role in its pathophysiology. The crosstalk between the nervous system and GM happens through immune mediators, metabolites, and nervous structures and involves both central and peripheral nervous systems. This literature review aims to thoroughly investigate the function of modulating GM in the treatment of NP. It will achieve this by integrating existing knowledge, identifying underlying mechanisms, and evaluating the possible clinical consequences of exploiting the gut-brain axis. We will cover the main therapeutic applications of the described GM-modulators, such as probiotics, faecal microbiota transplantation, dietary supplements and emotional support, to the main kinds of NP in which any evidence, even if only pre-clinical, has been unravelled in recent years. The explored NP areas include chemotherapy-induced peripheral neuropathy, diabetic neuropathy, trauma-induced neuropathic pain, trigeminal neuralgia, postherpetic neuralgia and low back pain.}, } @article {pmid38084725, year = {2023}, author = {El-Salhy, M and Gilja, OH and Hatlebakk, JG}, title = {Increasing the transplant dose and repeating faecal microbiota transplantation results in the responses of male patients with IBS reaching those of females.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/00365521.2023.2292479}, pmid = {38084725}, issn = {1502-7708}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) performed with a proper protocol is a safe treatment for IBS that has high efficacy and durable effects. Females have been reported to respond better than males to FMT. The present study aimed at determining whether increasing the transplant dose or repeating FMT improve the responses of males to FMT.

METHODS: This study included 186 IBS patients (131 females and 55 males) who were randomized at a 1:1:1 ratio to receive 90 g of donor faeces once into the large intestine, once into the small intestine or twice into the small intestine. Patients completed five questionnaires that assessed their symptoms and quality of life, and provided faecal samples at baseline and at 3, 6 and 12 months after FMT. The faecal bacterial profile and dysbiosis index were determined using 16S rRNA gene PCR DNA amplification covering variable genes V3-V9.

RESULTS: The response rates to FMT at all observation times did not differ significantly between females and males regardless of the transplant administration route or whether it was repeated. Faecal Alistipes levels were higher in females than in males at baseline and increased in both females and males after FMT. In the repeated group, the Alistipes levels did not differ between females and males after FMT.

CONCLUSIONS: Increasing the transplant dose and repeating FMT results in the responses of male IBS patients to FMT reaching those of females regardless of the administration route. Alistipes spp. levels appear to play a role in this improvement.www.clinicaltrials.gov (NCT04236843).}, } @article {pmid38079533, year = {2023}, author = {He, X and Gao, X and Hong, Y and Zhong, J and Li, Y and Zhu, W and Ma, J and Huang, W and Li, Y and Li, Y and Wang, H and Liu, Z and Bao, Y and Pan, L and Zheng, N and Sheng, L and Li, H}, title = {High Fat Diet and High Sucrose Intake Divergently Induce Dysregulation of Glucose Homeostasis through Distinct Gut Microbiota-Derived Bile Acid Metabolism in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c02909}, pmid = {38079533}, issn = {1520-5118}, abstract = {A high calorie diet such as excessive fat and sucrose intake is always accompanied by impaired glucose homeostasis such as T2DM (type 2 diabetes mellitus). However, it remains unclear how fat and sucrose individually affect host glucose metabolism. In this study, mice were fed with high fat diet (HFD) or 30% sucrose in drinking water (HSD) for 24 weeks, and glucose metabolism, gut microbiota composition, as well as bile acid (BA) profile were investigated. In addition, the functional changes of HFD or HSD-induced gut microbiota were further verified by fecal microbiota transplantation (FMT) and ex vivo culture of gut bacteria with BAs. Our results showed that both HFD and HSD caused dysregulated lipid metabolism, while HFD feeding had a more severe effect on impaired glucose homeostasis, accompanied by reduced hyocholic acid (HCA) levels in all studied tissues. Meanwhile, HFD had a more dramatic influence on composition and function of gut microbiota based on α diversity indices, β diversity analysis, as well as the abundance of secondary BA producers than HSD. In addition, the phenotypes of impaired glucose homeostasis and less formation of HCA caused by HFD can be transferred to recipient mice by FMT. Ex vivo culture with gut bacteria and BAs revealed HFD-altered gut bacteria produced less HCA than HSD, which might closely associate with reduced relative abundance of C7 epimerase-coding bacteria g_norank/unclassified_f_Eggerthellaceae and bile salt hydrolase-producing bacteria Lactobacillus and Bifidobacterium in HFD group. Our findings revealed that the divergent effects of different high-calorie diets on glucose metabolism may be due to the gut microbiota-mediated generation and metabolism of BAs, highlighting the importance of dietary management in T2DM.}, } @article {pmid38076985, year = {2023}, author = {Jain, R and Hadjigeorgiou, A and Harkos, C and Mishra, A and Morad, G and Johnson, S and Ajami, N and Wargo, J and Munn, L and Stylianopoulos, T}, title = {Dissecting the Impact of the Gut Microbiome on Cancer Immunotherapy.}, journal = {Research square}, volume = {}, number = {}, pages = {}, doi = {10.21203/rs.3.rs-3647386/v1}, pmid = {38076985}, abstract = {The gut microbiome has emerged as a key regulator of response to cancer immunotherapy. However, there is a gap in our understanding of the underlying mechanisms by which the microbiome influences immunotherapy. To this end, we developed a mathematical model based on i) gut microbiome data derived from preclinical studies on melanomas after fecal microbiota transplant, ii) mechanistic modeling of antitumor immune response, and iii) robust association analysis of murine and human microbiome profiles with model-predicted immune profiles. Using our model, we could distill the complexity of these murine and human studies on microbiome modulation in terms of just two model parameters: the activation and killing rate constants of immune cells. We further investigated associations between specific bacterial taxonomies and antitumor immunity and immunotherapy efficacy. This model can guide the design of studies to refine and validate mechanistic links between the microbiome and immune system.}, } @article {pmid38075901, year = {2023}, author = {Li, Y and Zhang, Y and Luo, X and Meng, Y and Zhong, Z and Zheng, H and Yang, Y}, title = {The fecal microbiota from children with autism impact gut metabolism and learning and memory abilities of honeybees.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1278162}, pmid = {38075901}, issn = {1664-302X}, abstract = {Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders, with an increasing incidence. Gastrointestinal symptoms are common comorbidities of ASD. The gut microbiota composition of children with autism is distinct from that of typical developmental (TD) children, suggesting that the gut microbiota probably influences on hosts via the microbiota-gut-brain axis. However, the relationship between intestinal dysbiosis and host brain function remains unclear. In this study, we creatively developed a honeybee model and investigated the potential effects of fecal microbiota on hosts. Fecal microbiota from children with autism and TD children were transplanted into microbiota-free honeybees (Apis mellifera), resulting in induced ASD-fecal microbiota transplantation (FMT) honeybees (A-BEE group) and TD-FMT honeybees (T-BEE group), respectively. We found that cognitive abilities of honeybees in the A-BEE group were significantly impaired in olfactory proboscis extension response conditioning. Metagenomics was used to evaluate fecal microbiota colonization, revealing several differential species responsible for altered tryptophan metabolism and taurine metabolism within the bee gut, including Bacteroides dorei, Bacteroides fragilis, Lactobacillus gasseri, and Lactobacillus paragasseri. Furthermore, fecal microbiota from children with autism downregulated brain genes involved in neural signaling and synaptic transmission within honeybees. Notably, differentially spliced genes observed within brains of honeybees from the A-BEE group largely overlapped with those identified in human diagnosed with autism via SFARI and SPARK gene sets. These differentially spliced genes were also enriched within pathways related to neural synaptic transmission. Our findings provide novel insights into the pivotal role of the human gut microbiota, which may contribute to neurological processes in honeybees. Additionally, we present a few research sources on gut-brain connections in ASD.}, } @article {pmid38075897, year = {2023}, author = {Bonnet, M and Eckert, C and Tournebize, R}, title = {Decolonization of asymptomatic carriage of multi-drug resistant bacteria by bacteriophages?.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1266416}, pmid = {38075897}, issn = {1664-302X}, abstract = {Antimicrobial resistance is a major threat to human and animal health and accounted for up to 4.5 million deaths worldwide in 2019. Asymptomatic colonization of the digestive tract by multidrug resistant (multi-resistant) bacteria such as extended-spectrum beta-lactamase-, or carbapenemase- producing Enterobacterales is (i) a risk factor for infection by these multi-resistant bacteria, (ii) a risk factor of dissemination of these multi-resistant bacteria among patients and in the community, and (iii) allows the exchange of resistance genes between bacteria. Hence, decolonization or reduction of the gastrointestinal tract colonization of these multi-resistant bacteria needs to be urgently explored. Developing new non-antibiotic strategies to limit or eradicate multi-resistant bacteria carriage without globally disrupting the microbiota is considered a priority to fight against antibiotic resistance. Probiotics or Fecal Microbiota Transplantation are alternative strategies to antibiotics that have been considered to decolonize intestinal tract from MDR bacteria but there is currently no evidence demonstrating their efficacy. Lytic bacteriophages are viruses that kill bacteria and therefore could be considered as a promising strategy to combat antibiotic resistance. Successful decolonization by bacteriophages has already been observed clinically. Here, we discuss the current alternative strategies considered to decolonize the digestive tract of multidrug resistant bacteria, briefly describing probiotics and fecal microbiota transplantation approaches, and then detail the in vivo and in vitro studies using bacteriophages, while discussing their limits regarding the animal models used, the characteristics of phages used and their activity in regards of the gut anatomy.}, } @article {pmid38075879, year = {2023}, author = {Zhang, RX and Xu, JT and Zhong, HJ and Cai, YL and Zhuang, YP and Xie, YT and He, XX}, title = {Gut microbiota from essential tremor patients aggravates tremors in mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1252795}, pmid = {38075879}, issn = {1664-302X}, abstract = {BACKGROUND AND OBJECTIVE: Essential tremor (ET) lacks effective treatments because its underlying mechanism is largely unknown, but may involve gut microbiota via the microbiome-gut-brain axis. We explored the effects of gut microbiota on ET in mice.

METHODS: Specific pathogen-free C57BL/6J mice were gavaged with stools from ET patients or matched healthy individuals. After 3 weeks of gavaging, behavioral tests were performed on all mice. Next, each mouse was injected with harmaline to induce tremors. The tremor duration was recorded; the tremor score was estimated every 30 min. Behavioral tests were repeated after modeling. Intestinal tissues and fecal samples of the mice were examined using histology and 16Sr DNA sequencing, respectively.

RESULTS: Compared with mice receiving microbiota from healthy controls, mice receiving fecal suspensions from ET patients showed worse performance in the pre-modeling behavioral tests. After modeling, ET-group mice showed significantly greater tremor scores, longer tremor duration, and worse motor performance. They also had significantly lower body weight and lower fecal pellet count. Pathological scoring revealed more severe intestinal lesions in ET-group mice. The 16S rDNA sequencing data revealed significant differences in microbiota indices, and a correlation between these indices and tremors in mice. Functional predictions indicated that the abundance of GABA-related enzymes was altered in ET-group mice.

CONCLUSION: Mice transplanted with gut microbiota from ET patients showed worse performance in behavioral tests. After modeling, ET-group mice presented longer tremor duration, higher tremor score, and worse motor performance. This study provides evidence for gut microbiota dysbiosis that may affect the pathogenesis of ET.}, } @article {pmid38074650, year = {2023}, author = {Zhang, H and Xu, Z}, title = {Gut-lung axis: role of the gut microbiota in non-small cell lung cancer immunotherapy.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1257515}, pmid = {38074650}, issn = {2234-943X}, abstract = {Immunotherapy for non-small cell lung cancer (NSCLC) has advanced considerably over the past two decades. In particular, immune checkpoint inhibitors are widely used for treating NSCLC. However, the overall cure and survival rates of patients with NSCLC remain low. Therefore, continuous investigation into complementary treatments is necessary to expand the clinical advantages of immunotherapy to a larger cohort of patients with NSCLC. Recently, the distinctive role of the gut microbiota (GM) in the initiation, progression, and dissemination of cancer has attracted increasing attention. Emerging evidence indicates a close relationship between the gut and lungs, known as the gut-lung axis (GLA). In this review, we aim to provide a comprehensive summary of the current knowledge regarding the connection between the GM and the outcomes of immunotherapy in NSCLC, with particular focus on the recent understanding of GLA. Overall, promising GM-based therapeutic strategies have been observed to improve the effectiveness or reduce the toxicity of immunotherapy in patients with NSCLC, thus advancing the utilization of microbiota precision medicine.}, } @article {pmid38073530, year = {2023}, author = {Taylor, VH and Kumar, V}, title = {Can we manage gut microbiome imbalances in patients with bipolar disorder with pharmacotherapy?.}, journal = {Expert opinion on pharmacotherapy}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/14656566.2023.2288287}, pmid = {38073530}, issn = {1744-7666}, abstract = {INTRODUCTION: A novel new area of exploration in the treatment of bipolar disorder is the gut brain axis. Studies have shown significant differences between the gut microbiome in those with bipolar disorder and those without the illness, as well as documented microbiome changes associated with the effects of bipolar pharmacotherapy and targeted microbial interventions. Although we have evidence suggesting the bi-directional relationship between the gut microbiome and psychiatric disorders, we are still unable to utilize this understanding clinically.

AREAS COVERED: We need to better understand the factors that impact the microbiome in this illness and vice versa.

EXPERT OPINION: Additionally, changes in gut microbiome in bipolar disorder might be used for biomarker identification with a potential to help in diagnosis and monitoring of the condition. It is an important area for further research and may provide improved therapeutic outcomes.}, } @article {pmid38072872, year = {2023}, author = {Yao, S and Yagi, S and Sugimoto, T and Asahara, T and Uemoto, S and Hatano, E}, title = {Occult bacteremia in living donor liver transplantation: a prospective observational study of recipients and donors.}, journal = {Surgery today}, volume = {}, number = {}, pages = {}, pmid = {38072872}, issn = {1436-2813}, support = {18K08567//Japan Society for the Promotion of Science/ ; }, abstract = {PURPOSE: To investigate the incidence and clinical impact of occult bacteremia in liver transplantation (LT).

METHODS: This prospective observational study involved a fixed-point observation for up to 2 weeks after living donor LT in 20 recipients, with 20 donors as comparison subjects. Bacteria in the blood samples were detected using the ribosomal RNA-targeted reverse-transcription quantitative polymerase chain reaction method. To identify the causality with the gut microbiota (GM), fecal samples were collected and analyzed simultaneously.

RESULTS: Occult bacteremia was identified in four recipients (20%) and three donors (15%) before the operation, and in seven recipients (35%) and five donors (25%) after the operation. Clostridium leptum subgroup, Prevotella, Colinesella, Enterobacteriaceae, and Streptococcus were the main pathogens responsible. Although it did not negatively affect the donor post-hepatectomy outcomes, the recipients with occult bacteremia had a higher rate of infectious complications post-LT. The GM analyses showed fewer post-LT predominant obligate anaerobes in both the recipients and donors with occult bacteremia.

CONCLUSIONS: Occult bacteremia is a common condition that occurs in both donors and recipients. While occult bacteremia generally remains subclinical in the healthy population, there is potential risk of the development of an apparent post-LT infection in recipients who are highly immunosuppressed.}, } @article {pmid38072552, year = {2023}, author = {Li, T and Chen, H and Xu, B and Yu, M and Li, J and Shi, Y and Xia, S and Wu, S}, title = {Deciphering the interplay between LPS/TLR4 pathways, neurotransmitter, and deltamethrin-induced depressive-like behavior: Perspectives from the gut-brain axis.}, journal = {Pesticide biochemistry and physiology}, volume = {197}, number = {}, pages = {105697}, doi = {10.1016/j.pestbp.2023.105697}, pmid = {38072552}, issn = {1095-9939}, abstract = {The improper use of deltamethrin (DM) can result in its accumulation in soil, water, food, and even the human body, which is associated with an elevated risk of neurotoxicity and behavioral abnormalities; however, the underlying mechanisms remain insufficiently investigated. Emerging evidence underscores the significance of the gut-brain axis in central nervous system (CNS) dysfunctions. Accordingly, this study investigates the role of the gut-brain axis in DM-induced behavioral anomalies in mice. The results showed that DM exposure induced depressive-like behavior, and the hippocampus, the region that is responsible for the modulation of emotional behavior, showed structural integrity disrupted (neuronal nuclear shrinkage and decreased tight junction protein expression). In addition, DM exposure led to compromised gut barrier integrity (disruptions on crypt surfaces and decreased tight junction protein expression), which might contribute to the gut bacterial-derived lipopolysaccharide (LPS) leakage into the bloodstream and reaching the brain, triggering LPS/toll-like receptor (TLR) 4 -mediated increases in brain pro-inflammatory cytokines. Subsequently, we observed a disturbance in neurotransmitter metabolic pathways following DM exposure, which inhibited the production of 5-hydroxytryptamine (5-HT). Additionally, DM exposure resulted in gut microbiota dysbiosis. Characteristic bacteria, such as Alistipes, Bifidobacterium, Gram-negative bacterium cTPY-13, and Odoribacter exhibited significant correlations with behavior, tight junction proteins, inflammatory response, and neurotransmitters. Further fecal microbiota transplantation (FMT) experiments suggested that DM-induced gut microbiota dysbiosis might contribute to depressive-like behavior. These results provide a new perspective on the toxicity mechanism of DM, indicating that its neurotoxicity may be partially regulated by the microbiota-gut-brain axis.}, } @article {pmid38071422, year = {2023}, author = {Sun, K and Fournier, M and Sundberg, AK and Song, IH}, title = {Maribavir: Mechanism of action, clinical, and translational science.}, journal = {Clinical and translational science}, volume = {}, number = {}, pages = {}, doi = {10.1111/cts.13696}, pmid = {38071422}, issn = {1752-8062}, abstract = {Maribavir is an oral benzimidazole riboside for treatment of post-transplant cytomegalovirus (CMV) infection/disease that is refractory to prior antiviral treatment (with or without resistance). Through competitive inhibition of adenosine triphosphate, maribavir prevents the phosphorylation actions of UL97 to inhibit CMV DNA replication, encapsidation, and nuclear egress. Maribavir is active against CMV strains with viral DNA polymerase mutations that confer resistance to other CMV antivirals. After oral administration, maribavir is rapidly and highly absorbed (fraction absorbed >90%). The approved dose of 400 mg twice daily (BID) achieves a steady-state area under the curve (AUC) per dosing interval of 128 h*μg/mL and trough concentration of 4.90 μg/mL (13.0 μM). Maribavir is highly bound to human plasma proteins (98%) with a small apparent volume of distribution at 27.3 L. Maribavir is primarily cleared by hepatic CYP3A4 metabolism; its major metabolite, VP44669 (pharmacologically inactive), is excreted in the urine and feces. There is no clinically relevant impact on maribavir pharmacokinetics by age, sex, race/ethnicity, body weight, transplant type, or hepatic/renal impairment status. In Phase 2 dose-ranging studies, maribavir showed similar rates of CMV viral clearance across 400, 800, or 1200 mg BID groups, ranging 62.5-70% in Study 202 (NCT01611974) and 74-83% in Study 203 (EudraCT 2010-024247-32). In the Phase 3 SOLSTICE trial (NCT02931539), maribavir 400 mg BID demonstrated superior CMV viremia clearance at week 8 versus investigator-assigned treatments with lower treatment discontinuation rates. Dysgeusia, nausea, vomiting and diarrhea were commonly experienced adverse events among patients treated with maribavir in clinical trials.}, } @article {pmid38068763, year = {2023}, author = {Komorniak, N and Kaczmarczyk, M and Łoniewski, I and Martynova-Van Kley, A and Nalian, A and Wroński, M and Kaseja, K and Kowalewski, B and Folwarski, M and Stachowska, E}, title = {Analysis of the Efficacy of Diet and Short-Term Probiotic Intervention on Depressive Symptoms in Patients after Bariatric Surgery: A Randomized Double-Blind Placebo Controlled Pilot Study.}, journal = {Nutrients}, volume = {15}, number = {23}, pages = {}, pmid = {38068763}, issn = {2072-6643}, abstract = {(1) Background: studies have shown that some patients experience mental deterioration after bariatric surgery. (2) Methods: We examined whether the use of probiotics and improved eating habits can improve the mental health of people who suffered from mood disorders after bariatric surgery. We also analyzed patients' mental states, eating habits and microbiota. (3) Results: Depressive symptoms were observed in 45% of 200 bariatric patients. After 5 weeks, we noted an improvement in patients' mental functioning (reduction in BDI and HRSD), but it was not related to the probiotic used. The consumption of vegetables and whole grain cereals increased (DQI-I adequacy), the consumption of simple sugars and SFA decreased (moderation DQI-I), and the consumption of monounsaturated fatty acids increased it. In the feces of patients after RYGB, there was a significantly higher abundance of two members of the Muribaculaceae family, namely Veillonella and Roseburia, while those after SG had more Christensenellaceae R-7 group, Subdoligranulum, Oscillibacter, and UCG-005. (4) Conclusions: the noted differences in the composition of the gut microbiota (RYGB vs. SG) may be one of the determinants of the proper functioning of the gut-brain microbiota axis, although there is currently a need for further research into this topic using a larger group of patients and different probiotic doses.}, } @article {pmid38065352, year = {2023}, author = {Jingyi, L and Lin, W and Yuan, C and Lingling, Z and Qianqian, J and Anlong, X and Yansong, G}, title = {Intravenous transplantation of bone marrow-derived mesenchymal stem cells improved behavioral deficits and altered fecal microbiota composition of BTBR mice.}, journal = {Life sciences}, volume = {}, number = {}, pages = {122330}, doi = {10.1016/j.lfs.2023.122330}, pmid = {38065352}, issn = {1879-0631}, abstract = {AIMS: It is recognized that autism spectrum disorder (ASD) is a highly complex neurodevelopmental disorder with communication deficits as well as multiple social barriers. The core symptoms of ASD are not treatable with current therapeutics. Therefore, finding new treatment strategies for ASD is urgently needed. Mesenchymal stem cells (MSC) have been shown to be a promising therapeutic approach in previous studies. However, the underlying mechanisms of MSC treatment for ASD through gut microbiota remain unclear and require further investigation.

MAIN METHODS: BTBR mice were used as ASD model and then randomly assigned to the human bone marrow-derived mesenchymal stem cell (hBMMSC) intravenous treatment group or vehicle treatment group. C57BL/6J (C57) mice served as control. Multiple social behavioral tests were performed during the 6-week period and fecal samples were collected at different time points for 16 s rRNA sequencing analysis.

KEY FINDINGS: The administration of hBMMSC improved social deficits of BTBR mice in the open field test (OFT), light-dark box test (LBT), novel object recognition (NOR), and free social test (FST), while also significantly reducing stereotypic behaviors. Additionally, hBMMSC administration notably reversed the alterations of microbiota abundance in BTBR mice, particularly the Firmicutes/Bacteroidetes ratio. Several specific differential taxa were further selected and showed a correlation with the prognosis and behavioral scores of ASD.

SIGNIFICANCE: Overall, intravenous treatment with hBMMSC had a beneficial impact on ASD by ameliorating social deficits and modifying microbiota compositions. This outcome indicates that hBMMSC intravenous transplantation could be a promising therapeutic strategy for enhancing ASD symptoms improvements.}, } @article {pmid38065343, year = {2023}, author = {}, title = {Faecal microbiota transplantation to reverse host-related determinants of resistance to anti-cancer immunotherapy.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2023.12.001}, pmid = {38065343}, issn = {1528-0012}, } @article {pmid38064388, year = {2023}, author = {Khurram, S and Asad, A and Fatima, SZ}, title = {Fecal microbiota transplantation: the need for effective treatment of Clostridioides difficile infection in Pakistan.}, journal = {Journal of infection in developing countries}, volume = {17}, number = {11}, pages = {1626-1627}, doi = {10.3855/jidc.17498}, pmid = {38064388}, issn = {1972-2680}, } @article {pmid38062990, year = {2023}, author = {Dunbar, A and Drigo, B and Djordjevic, SP and Donner, E and Hoye, BJ}, title = {Impacts of coprophagic foraging behaviour on the avian gut microbiome.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.13036}, pmid = {38062990}, issn = {1469-185X}, support = {//University of South Australia's Science, Technology, Engineering, and Mathematics/ ; DE200100884//Australian Research Council/ ; }, abstract = {Avian gut microbial communities are complex and play a fundamental role in regulating biological functions within an individual. Although it is well established that diet can influence the structure and composition of the gut microbiota, foraging behaviour may also play a critical, yet unexplored role in shaping the composition, dynamics, and adaptive potential of avian gut microbiota. In this review, we examine the potential influence of coprophagic foraging behaviour on the establishment and adaptability of wild avian gut microbiomes. Coprophagy involves the ingestion of faeces, sourced from either self (autocoprophagy), conspecific animals (allocoprophagy), or heterospecific animals. Much like faecal transplant therapy, coprophagy may (i) support the establishment of the gut microbiota of young precocial species, (ii) directly and indirectly provide nutritional and energetic requirements, and (iii) represent a mechanism by which birds can rapidly adapt the microbiota to changing environments and diets. However, in certain contexts, coprophagy may also pose risks to wild birds, and their microbiomes, through increased exposure to chemical pollutants, pathogenic microbes, and antibiotic-resistant microbes, with deleterious effects on host health and performance. Given the potentially far-reaching consequences of coprophagy for avian microbiomes, and the dearth of literature directly investigating these links, we have developed a predictive framework for directing future research to understand better when and why wild birds engage in distinct types of coprophagy, and the consequences of this foraging behaviour. There is a need for comprehensive investigation into the influence of coprophagy on avian gut microbiotas and its effects on host health and performance throughout ontogeny and across a range of environmental perturbations. Future behavioural studies combined with metagenomic approaches are needed to provide insights into the function of this poorly understood behaviour.}, } @article {pmid38062089, year = {2023}, author = {Qian, J and Lu, J and Cheng, S and Zou, X and Tao, Q and Wang, M and Wang, N and Zheng, L and Liao, W and Li, Y and Yan, F}, title = {Periodontitis salivary microbiota exacerbates colitis-induced anxiety-like behavior via gut microbiota.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {93}, pmid = {38062089}, issn = {2055-5008}, abstract = {The gut-brain axis is a bidirectional communication system between the gut and central nervous system. Many host-related factors can affect gut microbiota, including oral bacteria, making the brain a vulnerable target via the gut-brain axis. Saliva contains a large number of oral bacteria, and periodontitis, a common oral disease, can change the composition of salivary microbiota. However, the role and mechanism of periodontitis salivary microbiota (PSM) on the gut-brain axis remain unclear. Herein, we investigated the nature and mechanisms of this relationship using the mice with dextran sulfate sodium salt (DSS)-induced anxiety-like behavior. Compared with healthy salivary microbiota, PSM worsened anxiety-like behavior; it significantly reduced the number of normal neurons and activated microglia in DSS mice. Antibiotic treatment eliminated the effect of PSM on anxiety-like behavior, and transplantation of fecal microbiota from PSM-gavaged mice exacerbated anxiety-like behavior. These observations indicated that the anxiety-exacerbating effect of PSM was dependent on the gut microbiota. Moreover, the PSM effect on anxiety-like behavior was not present in non-DSS mice, indicating that DSS treatment was a prerequisite for PSM to exacerbate anxiety. Mechanistically, PSM altered the histidine metabolism in both gut and brain metabolomics. Supplementation of histidine-related metabolites had a similar anxiety-exacerbating effect as that of PSM, suggesting that histidine metabolism may be a critical pathway in this process. Our results demonstrate that PSM can exacerbate colitis-induced anxiety-like behavior by directly affecting the host gut microbiota, emphasizing the importance of oral diseases in the gut-brain axis.}, } @article {pmid38061593, year = {2023}, author = {Yu, Z and Xiaojia, L and Wei, Z and Jian, Z and Aiting, W and Jing, W and Lin, Y and Bangwei, C and Dan, Y}, title = {Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107033}, doi = {10.1016/j.phrs.2023.107033}, pmid = {38061593}, issn = {1096-1186}, abstract = {Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown. In this present study, ATB-treated C57BL/6J mice received FMT from patients with advanced NSCLC amenable to αPD-1. Additionally, subcutaneous LLC cells were injected into the mice. Baicalin oral gavage and αPD-1 injection were administered to the mice on days 3 and 9 after tumour inoculation. 16S rRNA, metabolomics, and flow cytometry were utilized to clarify the mechanisms of baicalin's relief of immunosuppression. The results indicated that oral administration of baicalin enriched bacteria such as Akkermansia and Clostridia_UCG-014, resulted in an increase in SCFAs, which improved the ratio of PD-1[+] (CD8[+] T cell/Treg) and promoted the levels of IFN-γ[+] CD8[+] T cells and TNF-α[+] CD8[+] T cells within the tumour microenvironment. In conclusion, baicalin regulates the metabolites of the gut microbiota to improve the PD-1[+] (CD8[+] T cell/Treg) balance and circumvent anti-PD-1 resistance. This is achieved through the regulation of short-chain fatty acids.}, } @article {pmid38057970, year = {2023}, author = {Cheng, Y and Tan, G and Zhu, Q and Wang, C and Ruan, G and Ying, S and Qie, J and Hu, X and Xiao, Z and Xu, F and Chen, L and Chen, M and Pei, Y and Zhang, H and Tian, Y and Chen, D and Liu, X and Huang, H and Wei, Y}, title = {Efficacy of fecal microbiota transplantation in patients with Parkinson's disease: clinical trial results from a randomized, placebo-controlled design.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2284247}, doi = {10.1080/19490976.2023.2284247}, pmid = {38057970}, issn = {1949-0984}, abstract = {The occurrence and development of Parkinson's disease (PD) have been demonstrated to be related to gut dysbiosis, however, the impact of fecal microbiota transplantation (FMT) on microbiota engraftment in PD patients is uncertain. We performed a randomized, placebo-controlled trial at the Department of Neurology, Army Medical University Southwest Hospital in China (ChiCTR1900021405) from February 2019 to December 2019. Fifty-six participants with mild to moderate PD (Hoehn-Yahr stage 1-3) were randomly assigned to the FMT and placebo group, 27 patients in the FMT group and 27 in the placebo group completed the whole trial. During the follow-up, no severe adverse effect was observed, and patients with FMT treatment showed significant improvement in PD-related autonomic symptoms compared with the placebo group at the end of this trial (MDS-UPDRS total score, group×time effect, B = -6.56 [-12.98, -0.13], P < 0.05). Additionally, FMT improved gastrointestinal disorders and a marked increase in the complexity of the microecological system in patients. This study demonstrated that FMT through oral administration is clinically feasible and has the potential to improve the effectiveness of current medications in the clinical symptoms of PD patients.}, } @article {pmid38057705, year = {2023}, author = {Yang, C and Hu, T and Xue, X and Su, X and Zhang, X and Fan, Y and Shen, X and Dong, X}, title = {Multi-omics analysis of fecal microbiota transplantation's impact on functional constipation and comorbid depression and anxiety.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {389}, pmid = {38057705}, issn = {1471-2180}, support = {202102130501015//Key R&D Program of Shanxi Province/ ; }, abstract = {BACKGROUND: Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted.

METHODS: We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients' fecal supernatants exposed to the QGP-1 cell model in vitro.

RESULTS: Our study demonstrated that patient's constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients' fecal supernatants increased 5-HT biosynthesis in QGP-1 cells.

CONCLUSION: FMT can relieve patients' constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.}, } @article {pmid38057297, year = {2023}, author = {Yan, M and Man, S and Sun, B and Ma, L and Guo, L and Huang, L and Gao, W}, title = {Gut liver brain axis in diseases: the implications for therapeutic interventions.}, journal = {Signal transduction and targeted therapy}, volume = {8}, number = {1}, pages = {443}, pmid = {38057297}, issn = {2059-3635}, support = {82074069//National Natural Science Foundation of China (National Science Foundation of China)/ ; 20YFZCSY00560//Natural Science Foundation of Tianjin Municipal Science and Technology Commission (Natural Science Foundation of Tianjin Municipal Science & Technology Commission)/ ; }, abstract = {Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, β-amyloid (Aβ) metabolism, and epigenetic regulation in the gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet and nanotechnology application regulate the gut liver brain axis. Besides, some special treatments targeting gut-liver axis include farnesoid X receptor (FXR) agonists, takeda G protein-coupled receptor 5 (TGR5) agonists, glucagon-like peptide-1 (GLP-1) receptor antagonists and fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain axis embraces cognitive behavioral therapy (CBT), antidepressants and tryptophan metabolism-related therapies. Targeting liver-brain axis contains epigenetic regulation and Aβ metabolism-related therapies. In the future, a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.}, } @article {pmid38057285, year = {2023}, author = {Wang, N and Gao, X and Huo, Y and Li, Y and Cheng, F and Zhang, Z}, title = {Lead exposure aggravates glucose metabolism disorders through gut microbiota dysbiosis and intestinal barrier damage in high-fat diet-fed mice.}, journal = {Journal of the science of food and agriculture}, volume = {}, number = {}, pages = {}, doi = {10.1002/jsfa.13197}, pmid = {38057285}, issn = {1097-0010}, abstract = {BACKGROUND: Lead (Pb) is an ancient toxic metal and is still a major public health issue. Our previous study found that Pb exposure promotes metabolic disorders in obese mice, but the molecular mechanisms remain unclear. The present study explored the effects of Pb exposure on glucose homeostasis in mice fed a normal diet (ND) and high-fat diet (HFD) from the perspective of gut microbiota.

RESULTS: Pb exposure had little effect on glucose metabolism in ND mice, but exacerbated hyperglycemia, insulin resistance, and impaired glucose tolerance in HFD mice. Pb exposure impaired intestinal tight junctions and mucin expression in HFD mice, increasing intestinal permeability and inflammation. Moreover, Pb exposure altered the composition and structure of the gut microbiota and decreased short-chain fatty acids (SCFAs) levels in HFD mice. Correlation analysis revealed that the gut microbiota and SCFAs were significantly correlated with the gut barrier and glucose homeostasis. Further, the fecal microbiota transplantation from Pb-exposed HFD mice resulted in glucose homeostasis imbalance, intestinal mucosal structural damage, and inflammation in recipient mice. However, Pb did not exacerbate the metabolic toxicity in HFD mice under depleted gut microbiota.

CONCLUSION: The findings suggest that Pb induces impairment of glucose metabolism in HFD mice by perturbing the gut microbiota. Our study offered new perspectives on the mechanisms of metabolic toxicity of heavy metals and demonstrate that the gut microbiota may be a target of action for heavy metal exposure. This article is protected by copyright. All rights reserved.}, } @article {pmid38056511, year = {2023}, author = {Sehgal, K and Yadav, D and Saha, S and Mara, K and Grover, M and Khanna, S}, title = {Sex-Discordant Fecal Microbiota Transplantation for C. difficile may increase risk of post-infection irritable bowel syndrome.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2023.11.295}, pmid = {38056511}, issn = {1528-0012}, } @article {pmid38056144, year = {2023}, author = {Liu, YF and Xie, WJ and Xi, P and Zhang, ZC and Chen, R and Fu, SQ and Lei, KY and Liu, J and Cheng, XF and Nie, YC and Yang, XR and Ma, M and Sun, T and Gong, BB}, title = {Astaxanthin alleviates chronic prostatitis/chronic pelvic pain syndrome by increasing colonization of Akkermansia muciniphila in the intestine.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {123}, number = {}, pages = {155249}, doi = {10.1016/j.phymed.2023.155249}, pmid = {38056144}, issn = {1618-095X}, abstract = {BACKGROUND: Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and mechanism of AST in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not fully understood.

PURPOSE: The aim of this study was to evaluate the effect of AST on CP/CPPS and elucidate the mediating role of the gut microbiota.

MATERIALS AND METHODS: An experimental autoimmune prostatitis (EAP) mouse model was utilized to test the potential role of AST on CP/CPPS. Antibiotic cocktail (ABX) treatment and fecal microbiota transplantation (FMT) were used to elucidate the gut microbiota-mediated effects on AST. In addition, 16S rRNA gene sequencing and qRT-PCR analyses were used to analyze changes in the gut microbiota of EAP mice and CP/CPPS patients. Finally, the mechanism by which AST exerts a protective effect on CP/CPPS was explored by untargeted metabolomics and gut barrier function assays.

RESULTS: Oral administration of AST reduced prostate inflammation scores, alleviated tactile sensitization of the pelvic region in EAP mice, reduced CD4+ T cell and CD68+ macrophage infiltration in the prostatic interstitium, and inhibited the up-regulation of systemic and localized pain/pro-inflammatory mediators in the prostate. After ABX, the protective effect of AST against CP/CPPS was attenuated, whereas colonization with fecal bacteria from AST-treated EAP mice alleviated CP/CPPS. 16S rRNA gene sequencing and qRT-PCR analyses showed that Akkermansia muciniphila in the feces of EAP mice and CP/CPPS patients showed a trend toward a decrease, which was associated with poor progression of CP/CPPS. In contrast, oral administration of AST increased the relative abundance of A. muciniphila, and oral supplementation with A. muciniphila also alleviated inflammation and pain in EAP mice. Finally, we demonstrated that both AST and A. muciniphila interventions increased serum levels of SCFAs acetate, up-regulated expression of colonic tight junction markers, and decreased serum lipopolysaccharide levels in EAP mice.

CONCLUSION: Our results showed that AST improved CP/CPPS by up-regulating A. muciniphila, which provides new potentially effective strategies and ideas for CP/CPPS management.}, } @article {pmid38051970, year = {2023}, author = {Gonzales-Luna, AJ and Carlson, TJ and Garey, KW}, title = {Review Article: Safety of Live Biotherapeutic Products Used for the Prevention of Clostridioides difficile Infection Recurrence.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {Supplement_6}, pages = {S487-S496}, doi = {10.1093/cid/ciad642}, pmid = {38051970}, issn = {1537-6591}, mesh = {Adult ; Humans ; *Clostridioides difficile ; Fecal Microbiota Transplantation/adverse effects ; *Clostridium Infections/microbiology ; Gastrointestinal Tract ; Feces/microbiology ; Recurrence ; }, abstract = {Live biotherapeutic products (LBPs) represent a new class of therapeutics indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in adults. However, microbiota-based therapies have been used in CDI management before the Food and Drug Administration (FDA) designated this new drug class. The regulation of these microbiome-based therapies has varied, and several safety concerns have arisen over time. Requirements established by the FDA regarding the development of LBPs minimizes many of these prior concerns, and phase III trials have proven the safety and efficacy of 2 stool donor-derived LBPs: fecal microbiota, live-jslm (Rebyota™; formerly RBX2660) and fecal microbiota spores, live-brpk (Vowst™; formerly SER-109). Mild gastrointestinal side effects are common, but no severe drug-related adverse events have been reported with their use to date. A third LBP entering phase III clinical trials, VE303, follows a novel approach by sourcing bacterial strains from clonal cell banks and has demonstrated a similarly favorable safety profile.}, } @article {pmid38055355, year = {2023}, author = {He, K and Gao, Q and Su, J and Shang, H and Meng, X and Jiang, S and Liu, D and Huang, B}, title = {Gut Microbiome and Metabolomics Study of Selenium-Enriched Kiwifruit Regulating Hyperlipidemia in Mice Induced by a High-Fat Diet.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c00108}, pmid = {38055355}, issn = {1520-5118}, abstract = {Our previous study showed that as a substitute for statins, selenium-enriched kiwifruit (Se-Kiwi) might reduce blood lipids and protect the liver in Kunming mice, but the underlying mechanism remains unclear. Metabolic regulation of mammalian intestinal microflora plays an important role in obesity and related diseases induced by a high-fat diet (HFD). Here, samples of serum, liver, colon, and fresh feces from the Se-Kiwi-treated hyperlipidemia C57BL/6J mouse model were collected. Based on metabolome (UHPLC-Q-TOF MS) and gut microbiome (16S rDNA) analyses as well as the integrative analysis of physiological and biochemical indices and pathological data of mice, we aimed to systematically illustrate the gut microbiome and metabolomics mechanism of Se-Kiwi in HFD-induced hyperlipidemic mice. As a result, Se-Kiwi can significantly increase the abundance of potentially beneficial gut bacteria such as Parabacteroides, Bacteroides, and Allobaculum in the colon and improve hyperlipidemia by regulating the digestion and absorption of vitamins, pyrimidine metabolism, purine metabolism, and other metabolic pathways, which have been confirmed by the following fecal microbiota transplantation experiment. This process was significantly regulated by the Ada, Gda, Pank1, Ppara, Pparg, and Cd36 genes. These findings may provide a theoretical basis for the research and development of selenium-enriched functional foods in the treatment of hyperlipidemia.}, } @article {pmid38053512, year = {2023}, author = {Qi, L and Peng, J and Huang, X and Zhou, T and Tan, G and Li, F}, title = {Longitudinal dynamics of gut microbiota in the pathogenesis of acute graft-versus-host disease.}, journal = {Cancer medicine}, volume = {}, number = {}, pages = {}, doi = {10.1002/cam4.6557}, pmid = {38053512}, issn = {2045-7634}, support = {20212BCG74001//Science and Technology Innovation Base Construction Project of Jiangxi Province/ ; 20211ZDG02006//Science and Technology Innovation Base Construction Project of Jiangxi Province/ ; }, abstract = {AIM: The gut microbiota has been reported to be associated with acute graft-versus-host disease (aGvHD) in hematopoietic stem cell transplantation (HSCT). Dynamic surveillance of the microbiota is required to understand the detailed pathogenesis involved in the process of aGvHD.

METHODS: Fecal samples were collected prospectively at four timepoints, including pre-HSCT (T1), graft infusion (T2), neutrophil engraftment (T3), and 30 days after transplantation (T4). Fecal samples were profiled by 16S ribosomal RNA gene sequencing to assess the microbiota composition.

RESULTS: From the T1 to T4 timepoint, the diversity of the gut microbiota decreased, and the dominant species also changed, with a decrease in the obligate anaerobic bacteria and a shift toward a "pathogenic community". Compared with non-aGvHD patients, aGvHD patients had a lower abundance of Roseburia at T1 and a higher abundance of Acinetobacter johnsonii at T2. Furthermore, Acinetobacter johnsonii was negatively correlated with the secretion of IL-4 and TNF-α. At T3, Rothia mucilaginos was demonstrated to be linked with a decreased risk of aGvHD, which was accompanied by decreased secretion of IL-8. At T4, higher abundances of Lactobacillus paracasei and Acinetobacter johnsonii were identified to be related with aGvHD. Lactobacillus paracasei was associated with the downregulation of IL-10, and Acinetobacter johnsonii was associated with the downregulation of IL-2 and TNF-α.

CONCLUSIONS: Dynamic changes in gut microbiota composition and related cytokines were found to be related to aGvHD, including pathogenic or protective changes. These findings suggested that manipulation of gut microbiota at different timepoints might be a promising avenue for preventing or treating this common complication.}, } @article {pmid38052405, year = {2023}, author = {Yu, Z and Han, J and Li, L and Zhang, Q and Chen, A and Chen, J and Wang, K and Jin, J and Li, H and Chen, G}, title = {Chronic triclosan exposure induce impaired glucose tolerance by altering the gut microbiota.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {183}, number = {}, pages = {114305}, doi = {10.1016/j.fct.2023.114305}, pmid = {38052405}, issn = {1873-6351}, abstract = {Triclosan (TCS) is an antimicrobial compound incorporated into more than 2000 consumer products. This compound is frequently detected in the human body and causes ubiquitous contamination in the environment, thereby raising concerns about its impact on human health and environmental pollution. Here, we demonstrated that 20 weeks' exposure of TCS drove the development of glucose intolerance by inducing compositional and functional alterations in intestinal microbiota in rats. Fecal-transplantation experiments corroborated the involvement of gut microbiota in TCS-induced glucose-tolerance impairment. 16S rRNA gene-sequencing analysis of cecal contents showed that TCS disrupted the gut microbiota composition in rats and increased the ratio of Firmicutes to Bacteroidetes. Cecal metabolomic analyses detected that TCS altered host metabolic pathways that are linked to host glucose and amino acid metabolism, particularly branched-chain amino acid (BCAA) biosynthesis. BCAA measurement confirmed the increase in serum BCAAs in rats exposed to TCS. Western blot and immunostaining results further confirmed that elevated BCAAs stimulated mTOR, a nutrient-sensing complex, and following IRS-1 serine phosphorylation, resulted in insulin resistance and glucose intolerance. These results suggested that TCS may induce glucose metabolism imbalance by regulating BCAA concentration by remodeling the gut microbiota.}, } @article {pmid38052208, year = {2023}, author = {Cerdó, T and Ruiz-Rodríguez, A and Acuña, I and Torres-Espínola, FJ and Menchén-Márquez, S and Gámiz, F and Gallo, M and Jehmlich, N and Haange, SB and von Bergen, M and Campoy, C and Suárez, A}, title = {Infant gut microbiota contributes to cognitive performance in mice.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2023.11.004}, pmid = {38052208}, issn = {1934-6069}, abstract = {Gut microbiota has been linked to infant neurodevelopment. Here, an association between infant composite cognition and gut microbiota composition is established as soon as 6 months. Higher diversity and evenness characterize microbial communities of infants with composite cognition above (Inf-aboveCC) versus below (Inf-belowCC) median values. Metaproteomic and metabolomic analyses establish an association between microbial histidine ammonia lyase and infant histidine metabolome with cognition. Fecal transplantation from Inf-aboveCC versus Inf-belowCC donors into germ-free mice shows that memory, assessed by a novel object recognition test, is a transmissible trait. Furthermore, Inf-aboveCC mice are enriched in species belonging to Phocaeicola, as well as Bacteroides and Bifidobacterium, previously linked to cognition. Finally, Inf-aboveCC mice show lower fecal histidine and urocanate:histidine and urocanate:glutamate ratios in the perirhinal cortex compared to Inf-belowCC mice. Overall, these findings reveal a causative role of gut microbiota on infant cognition, pointing at the modulation of histidine metabolite levels as a potential underlying mechanism.}, } @article {pmid38051967, year = {2023}, author = {Kelly, CR and Allegretti, JR}, title = {Review Article: Gastroenterology and Clostridium difficile Infection: Past, Present, and Future.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {Supplement_6}, pages = {S463-S470}, doi = {10.1093/cid/ciad644}, pmid = {38051967}, issn = {1537-6591}, abstract = {Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms.}, } @article {pmid38051964, year = {2023}, author = {Lavoie, T and Appaneal, HJ and LaPlante, KL}, title = {Advancements in Novel Live Biotherapeutic Products for Clostridioides difficile Infection Prevention.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {Supplement_6}, pages = {S447-S454}, doi = {10.1093/cid/ciad639}, pmid = {38051964}, issn = {1537-6591}, support = {//Seres and Ferring/ ; }, abstract = {The profound impact of the human microbiome on health and disease has captivated the interest of clinical and scientific communities. The human body hosts a vast array of microorganisms collectively forming the human microbiome, which significantly influences various physiological processes and profoundly shapes overall well-being. Notably, the gut stands out as an exceptional reservoir, harboring the most significant concentration of microorganisms, akin to an organ in itself. The gut microbiome's composition and function are influenced by genetics, environment, age, underlying conditions, and antibiotic usage, leading to dysbiosis and pathogenesis, such as Clostridioides difficile infection (CDI). Conventional CDI treatment, involving antibiotics like oral vancomycin and fidaxomicin, fails to address dysbiosis and may further disrupt gut microbial communities. Consequently, emerging therapeutic strategies are focused on targeting dysbiosis and restoring gut microbiota to advance CDI therapeutics. Fecal microbiota transplantation (FMT) has demonstrated remarkable efficacy in treating recurrent CDI by transferring processed stool from a healthy donor to a recipient, restoring gut dysbiosis and enhancing bacterial diversity. Moreover, 2 newer Food and Drug Administration (FDA)-approved live biotherapeutic products (LBP), namely, Fecal Microbiota Live-JSLM and Fecal Microbiota Spores Live-BRPK, have shown promise in preventing CDI recurrence. This review explores the role of the gut microbiota in preventing and treating CDI, with an emphasis on gut-based interventions like FMT and fecal microbiota-based products that hold potential for gut restoration and prevention of CDI recurrence. Understanding the microbiome's impact on CDI prevention and treatment offers valuable insights for advancing future CDI therapeutics.}, } @article {pmid38047407, year = {2023}, author = {Liu, X and Li, J and Shi, M and Fu, J and Wang, Y and Kang, W and Liu, J and Zhu, F and Huang, K and Chen, X and Liu, Y}, title = {Melatonin improves cholestatic liver disease via the gut-liver axis.}, journal = {Journal of pineal research}, volume = {}, number = {}, pages = {e12929}, doi = {10.1111/jpi.12929}, pmid = {38047407}, issn = {1600-079X}, support = {32102741//National Natural Science Foundation of China/ ; BK20210399//Natural Science Foundation of Jiangsu Province/ ; }, abstract = {Cholestatic liver disease is characterized by disturbances in the intestinal microbiota and excessive accumulation of toxic bile acids (BA) in the liver. Melatonin (MT) can improve liver diseases. However, the underlying mechanism remains unclear. This study aimed to explore the mechanism of MT on hepatic BA synthesis, liver injury, and fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed and Mdr2[-/-] mice. MT significantly improved hepatic injury and fibrosis with a significant decrease in hepatic BA accumulation in DDC-fed and Mdr2[-/-] mice. MT reprogramed gut microbiota and augmented fecal bile salt hydrolase activity, which was related to increasing intestinal BA deconjugation and fecal BA excretion in both DDC-fed and Mdr2[-/-] mice. MT significantly activated the intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) axis and subsequently inhibited hepatic BA synthesis in DDC-fed and Mdr2[-/-] mice. MT failed to improve DDC-induced liver fibrosis and BA synthesis in antibiotic-treated mice. Furthermore, MT provided protection against DDC-induced liver injury and fibrosis in fecal microbiota transplantation mice. MT did not decrease liver injury and fibrosis in DDC-fed intestinal epithelial cell-specific FXR knockout mice, suggesting that the intestinal FXR mediated the anti-fibrosis effect of MT. In conclusion, MT ameliorates cholestatic liver diseases by remodeling gut microbiota and activating intestinal FXR/FGF-15 axis-mediated inhibition of hepatic BA synthesis and promotion of BA excretion in mice.}, } @article {pmid38047235, year = {2023}, author = {Fremin, BJ and Bhatt, AS and Kyrpides, NC}, title = {Identification of over ten thousand candidate structured RNAs in viruses and phages.}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {5630-5639}, pmid = {38047235}, issn = {2001-0370}, abstract = {Structured RNAs play crucial roles in viruses, exerting influence over both viral and host gene expression. However, the extensive diversity of structured RNAs and their ability to act in cis or trans positions pose challenges for predicting and assigning their functions. While comparative genomics approaches have successfully predicted candidate structured RNAs in microbes on a large scale, similar efforts for viruses have been lacking. In this study, we screened over 5 million DNA and RNA viral sequences, resulting in the prediction of 10,006 novel candidate structured RNAs. These predictions are widely distributed across taxonomy and ecosystem. We found transcriptional evidence for 206 of these candidate structured RNAs in the human fecal microbiome. These candidate RNAs exhibited evidence of nucleotide covariation, indicative of selective pressure maintaining the predicted secondary structures. Our analysis revealed a diverse repertoire of candidate structured RNAs, encompassing a substantial number of putative tRNAs or tRNA-like structures, Rho-independent transcription terminators, and potentially cis-regulatory structures consistently positioned upstream of genes. In summary, our findings shed light on the extensive diversity of structured RNAs in viruses, offering a valuable resource for further investigations into their functional roles and implications in viral gene expression and pave the way for a deeper understanding of the intricate interplay between viruses and their hosts at the molecular level.}, } @article {pmid38046820, year = {2023}, author = {Roggiani, S and Mengoli, M and Conti, G and Fabbrini, M and Brigidi, P and Barone, M and D'Amico, F and Turroni, S}, title = {Gut microbiota resilience and recovery after anticancer chemotherapy.}, journal = {Microbiome research reports}, volume = {2}, number = {3}, pages = {16}, pmid = {38046820}, issn = {2771-5965}, abstract = {Although research on the role of the gut microbiota (GM) in human health has sharply increased in recent years, what a "healthy" gut microbiota is and how it responds to major stressors is still difficult to establish. In particular, anticancer chemotherapy is known to have a drastic impact on the microbiota structure, potentially hampering its recovery with serious long-term consequences for patients' health. However, the distinguishing features of gut microbiota recovery and non-recovery processes are not yet known. In this narrative review, we first investigated how gut microbiota layouts are affected by anticancer chemotherapy and identified potential gut microbial recovery signatures. Then, we discussed microbiome-based intervention strategies aimed at promoting resilience, i.e., the rapid and complete recovery of a healthy gut microbial network associated with a better prognosis after such high-impact pharmacological treatments.}, } @article {pmid38044504, year = {2023}, author = {Meade, S and Liu Chen Kiow, J and Massaro, C and Kaur, G and Squirell, E and Bressler, B and Lunken, G}, title = {Gut microbiome-associated predictors as biomarkers of response to advanced therapies in inflammatory bowel disease: a systematic review.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2287073}, doi = {10.1080/19490976.2023.2287073}, pmid = {38044504}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/microbiology ; Feces/microbiology ; Fecal Microbiota Transplantation ; Biomarkers/analysis ; }, abstract = {Loss of response to therapy in inflammatory bowel disease (IBD) has led to a surge in research focusing on precision medicine. Three systematic reviews have been published investigating the associations between gut microbiota and disease activity or IBD therapy. We performed a systematic review to investigate the microbiome predictors of response to advanced therapy in IBD. Unlike previous studies, our review focused on predictors of response to therapy; so the included studies assessed microbiome predictors before the proposed time of response or remission. We also provide an update of the available data on mycobiomes and viromes. We highlight key themes in the literature that may serve as future biomarkers of treatment response: the abundance of fecal SCFA-producing bacteria and opportunistic bacteria, metabolic pathways related to butyrate synthesis, and non-butyrate metabolomic predictors, including bile acids (BAs), amino acids, and lipids, as well as mycobiome predictors of response.}, } @article {pmid38046904, year = {2022}, author = {Park, JC and Im, SH}, title = {The gut-immune-brain axis in neurodevelopment and neurological disorders.}, journal = {Microbiome research reports}, volume = {1}, number = {4}, pages = {23}, pmid = {38046904}, issn = {2771-5965}, abstract = {The gut-brain axis is gaining momentum as an interdisciplinary field addressing how intestinal microbes influence the central nervous system (CNS). Studies using powerful tools, including germ-free, antibiotic-fed, and fecal microbiota transplanted mice, demonstrate how gut microbiota perturbations alter the fate of neurodevelopment. Probiotics are also becoming more recognized as potentially effective therapeutic agents in alleviating symptoms of neurological disorders. While gut microbes may directly communicate with the CNS through their effector molecules, including metabolites, their influence on neuroimmune populations, including newly discovered brain-resident T cells, underscore the host immunity as a potent mediator of the gut-brain axis. In this review, we examine the unique immune populations within the brain, the effects of the gut microbiota on the CNS, and the efficacy of specific probiotic strains to propose the novel concept of the gut-immune-brain axis.}, } @article {pmid38046357, year = {2022}, author = {Aguanno, D and Metwaly, A and Coleman, OI and Haller, D}, title = {Modeling microbiota-associated human diseases: from minimal models to complex systems.}, journal = {Microbiome research reports}, volume = {1}, number = {3}, pages = {17}, pmid = {38046357}, issn = {2771-5965}, abstract = {Alterations in the intestinal microbiota are associated with various human diseases of the digestive system, including obesity and its associated metabolic diseases, inflammatory bowel diseases (IBD), and colorectal cancer (CRC). All three diseases are characterized by modifications of the richness, composition, and metabolic functions of the human intestinal microbiota. Despite being multi-factorial diseases, studies in germ-free animal models have unarguably identified the intestinal microbiota as a causal driver of disease pathogenesis. However, for an increased mechanistic understanding of microbial signatures in human diseases, models require detailed refinement to closely mimic the human microbiota and reflect the complexity and range of dysbiosis observed in patients. The transplantation of human fecal microbiota into animal models represents a powerful tool for studying the causal and functional role of the dysbiotic human microbiome in a pathological context. While human microbiota-associated models were initially employed to study obesity, an increasing number of studies have applied this approach in the context of IBD and CRC over the past decade. In this review, we discuss different approaches that allow the functional validation of the bacterial contribution to human diseases, with emphasis on obesity and its associated metabolic diseases, IBD, and CRC. We discuss the utility of simple models, such as in vitro fermentation systems of the human microbiota and ex vivo intestinal organoids, as well as more complex whole organism models. Our focus here lies on human microbiota-associated mouse models in the context of all three diseases, as well as highlighting the advantages and limitations of this approach.}, } @article {pmid38045814, year = {2023}, author = {Gómez-Gallego, C and El-Nezami, H}, title = {Editorial: Novel developments for promoting health through microbiota modulation.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1331665}, pmid = {38045814}, issn = {2296-861X}, } @article {pmid38045612, year = {2023}, author = {Brüssow, H}, title = {The human microbiome project at ten years - some critical comments and reflections on "our third genome", the human virome.}, journal = {Microbiome research reports}, volume = {2}, number = {1}, pages = {7}, pmid = {38045612}, issn = {2771-5965}, abstract = {The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in Clostridioides difficile infection, practical application of microbiome intervention has only achieved modest clinical effects. It is argued here that we need criteria for the link between microbiome and disease modelled on the links between pathogens and infectious disease in Koch's postulates. The most important question is whether the microbiome change is a cause of the given disease or a consequence of a pathology leading to disease where the microbiome change is only a parallel event without a causal connection to the disease - in philosophical parlance, an epiphenomenon. Also discussed here is whether human virome research is a necessary complement to the microbiome project with a high potential for practical applications.}, } @article {pmid38045189, year = {2023}, author = {Chen, JH and Zhao, CL and Li, YS and Yang, YB and Luo, JG and Zhang, C and Wang, L}, title = {Moutai Distiller's grains Polyphenol extracts and rutin alleviate DSS-induced colitis in mice: Modulation of gut microbiota and intestinal barrier function （R2）.}, journal = {Heliyon}, volume = {9}, number = {11}, pages = {e22186}, pmid = {38045189}, issn = {2405-8440}, abstract = {Distiller's grains, byproducts of the brewing process, represent a valuable resource for extracting natural phenolic compounds due to their significant global production. This study presents the first evidence of the protective effects of Moutai distiller's grain polyphenol extract (MDGP) on dextran sulfate sodium (DSS)-induced colitis in mice. These protective effects manifest predominantly through the amelioration of general colitis indices and histopathological improvements. Utilizing liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), the main components of MDGP were identified as rutin, quercetin, naringenin, and dihydroquercetin. Moreover, a novel mechanism was elucidated by which rutin, the primary active component of MDGP, alleviates DSS-induced colitis. Assessment of intestinal barrier function, microbial sequencing, fecal transplantation, and antibiotic depletion experiments revealed that rutin suppresses the abundance of pathogenic bacteria (Helicobacter, Klebsiella, and Veillonella) while promoting the proliferation of beneficial bacteria (Ruminococcus_torques_group, Lachnoclostridium, and norank_f__Muribaculaceae). This modulation culminates in elevated butyric acid concentrations within short-chain fatty acids (SCFAs), amplified integrity of tight (ZO-1, occludin) and adherent (E-cadherin, β-catenin) junctional complexes, fortified intestinal barrier function, and diminished intestinal inflammation.This investigation accentuates the innovative therapeutic potential of MDGP and its main active component, rutin, in assuaging DSS-induced intestinal inflammation and fortifying the intestinal barrier through a mechanism predominantly mediated by the intestinal microbiota. Such insights potentially elevate the prominence of distiller's grains in the realm of functional food development.}, } @article {pmid38042820, year = {2023}, author = {Swarte, JC and Knobbe, TJ and Björk, JR and Gacesa, R and Nieuwenhuis, LM and Zhang, S and Vila, AV and Kremer, D and Douwes, RM and Post, A and Quint, EE and Pol, RA and Jansen, BH and , and de Borst, MH and de Meijer, VE and Blokzijl, H and Berger, SP and Festen, EAM and Zhernakova, A and Fu, J and Harmsen, HJM and Bakker, SJL and Weersma, RK}, title = {Health-related quality of life is linked to the gut microbiome in kidney transplant recipients.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {7968}, pmid = {38042820}, issn = {2041-1723}, mesh = {Humans ; Quality of Life ; *Gastrointestinal Microbiome/genetics ; *Kidney Transplantation/adverse effects ; Feces/microbiology ; Dysbiosis/microbiology ; }, abstract = {Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly related in the general population. Here, we investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR. Multiple bacterial species are associated with lower HRQoL, many of which have previously been associated with adverse health conditions. Gut microbiome distance to the general population is highest among KTR with an impaired physical HRQoL (R = -0.20, P = 2.3 × 10[-65]) and mental HRQoL (R = -0.14, P = 1.3 × 10[-3]). Physical and mental HRQoL explain a significant part of variance in the gut microbiome (R[2] = 0.58%, FDR = 5.43 × 10[-4] and R[2] = 0.37%, FDR = 1.38 × 10[-3], respectively). Additionally, multiple metabolic and neuroactive pathways (gut brain modules) are associated with lower HRQoL. While the observational design of our study does not allow us to analyze causality, we provide a comprehensive overview of the associations between the gut microbiome and HRQoL while controlling for confounders.}, } @article {pmid38037086, year = {2023}, author = {Deng, ZL and Pieper, DH and Stallmach, A and Steube, A and Vital, M and Reck, M and Wagner-Döbler, I}, title = {Engraftment of essential functions through multiple fecal microbiota transplants in chronic antibiotic-resistant pouchitis-a case study using metatranscriptomics.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {269}, pmid = {38037086}, issn = {2049-2618}, support = {FP7/2007-2013//Innovative Medicines Initiative Joint Undertaking/ ; FP7/2007-2013//Innovative Medicines Initiative Joint Undertaking/ ; FP7/2007-2013//Innovative Medicines Initiative Joint Undertaking/ ; TRR 51//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Pouchitis/therapy/diagnosis/microbiology ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; Feces/microbiology ; *Microbiota ; *Colitis, Ulcerative/surgery ; Butyrates/analysis ; }, abstract = {BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the standard of care after total proctocolectomy for ulcerative colitis (UC). Around 50% of patients will experience pouchitis, an idiopathic inflammatory condition. Antibiotics are the backbone of treatment of pouchitis; however, antibiotic-resistant pouchitis develops in 5-10% of those patients. It has been shown that fecal microbiota transplantation (FMT) is an effective treatment for UC, but results for FMT antibiotic-resistant pouchitis are inconsistent.

METHODS: To uncover which metabolic activities were transferred to the recipients during FMT and helped the remission, we performed a longitudinal case study of the gut metatranscriptomes from three patients and their donors. The patients were treated by two to three FMTs, and stool samples were analyzed for up to 140 days.

RESULTS: Reduced expression in pouchitis patients compared to healthy donors was observed for genes involved in biosynthesis of amino acids, cofactors, and B vitamins. An independent metatranscriptome dataset of UC patients showed a similar result. Other functions including biosynthesis of butyrate, metabolism of bile acids, and tryptophan were also much lower expressed in pouchitis. After FMT, these activities transiently increased, and the overall metatranscriptome profiles closely mirrored those of the respective donors with notable fluctuations during the subsequent weeks. The levels of the clinical marker fecal calprotectin were concordant with the metatranscriptome data. Faecalibacterium prausnitzii represented the most active species contributing to butyrate synthesis via the acetyl-CoA pathway. Remission occurred after the last FMT in all patients and was characterized by a microbiota activity profile distinct from donors in two of the patients.

CONCLUSIONS: Our study demonstrates the clear but short-lived activity engraftment of donor microbiota, particularly the butyrate biosynthesis after each FMT. The data suggest that FMT triggers shifts in the activity of patient microbiota towards health which need to be repeated to reach critical thresholds. As a case study, these insights warrant cautious interpretation, and validation in larger cohorts is necessary for generalized applications. In the long run, probiotics with high taxonomic diversity consisting of well characterized strains could replace FMT to avoid the costly screening of donors and the risk of transferring unwanted genetic material. Video Abstract.}, } @article {pmid38036190, year = {2023}, author = {Cai, X and Li, Z and Yao, Y and Zheng, Y and Zhang, M and Ye, Y}, title = {Glycolithocholic acid increases the frequency of circulating Tregs through constitutive androstane receptor to alleviate postmenopausal osteoporosis.}, journal = {Biochemical pharmacology}, volume = {219}, number = {}, pages = {115951}, doi = {10.1016/j.bcp.2023.115951}, pmid = {38036190}, issn = {1873-2968}, abstract = {BACKGROUND AND PURPOSE: Gut microbiota and their metabolic activity are important regulators of host immunity. However, the role of gut microbiota and their metabolic activity-mediated osteoimmunity in postmenopausal osteoporosis (PMO) remains unknown. This study aimed to explore the role of gut microbiota and their metabolic activity in PMO.

EXPERIMENTAL APPROACH: 16S rDNA sequencing was used for analyzing the gut microbiota diversity of patients with PMO and rat models, and a targeted metabolism study was performed for analyzing metabolite levels. Flow cytometry was used for analyzing the frequency of immune cells. Micro-CT was used for analyzing bone damage in rat models. Fecal microbiota transplantation was performed for exploring the therapeutic effect of the gut microbiota on PMO. CD4[+] T cells were co-cultured with bone marrow mesenchymal stem cells for evaluating their molecular mechanisms.

KEY RESULTS: Patients with PMO exhibited reduced gut microbiota diversity, and fecal glycolithocholic acid (GLCA) levels correlated with the degree of osteoporosis. GLCA levels in the gut were positively correlated with the frequency of circulating Tregs in ovariectomized rats. Restoration of the gut microbiota alleviated osteoporosis in ovariectomized rats. Circulating GLCA augmented CD4[+] T cell differentiation into Tregs via constitutive androstane receptors. The increased frequency of Tregs further promoted the osteogenic differentiation of bone marrow mesenchymal stem cells to alleviate osteoporosis.

CONCLUSION AND IMPLICATIONS: GLCA alleviated PMO by increasing the frequency of circulating Tregs, acting via the constitutive androstane receptor. This study reveals a new strategy for the treatment of PMO, with GLCA as a potential drug candidate.}, } @article {pmid38035338, year = {2023}, author = {Van Dingenen, L and Segers, C and Wouters, S and Mysara, M and Leys, N and Kumar-Singh, S and Malhotra-Kumar, S and Van Houdt, R}, title = {Dissecting the role of the gut microbiome and fecal microbiota transplantation in radio- and immunotherapy treatment of colorectal cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1298264}, pmid = {38035338}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Immunotherapy ; *Colorectal Neoplasms/therapy ; }, abstract = {Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and poses a major burden on the human health worldwide. At the moment, treatment of CRC consists of surgery in combination with (neo)adjuvant chemotherapy and/or radiotherapy. More recently, immune checkpoint blockers (ICBs) have also been approved for CRC treatment. In addition, recent studies have shown that radiotherapy and ICBs act synergistically, with radiotherapy stimulating the immune system that is activated by ICBs. However, both treatments are also associated with severe toxicity and efficacy issues, which can lead to temporary or permanent discontinuation of these treatment programs. There's growing evidence pointing to the gut microbiome playing a role in these issues. Some microorganisms seem to contribute to radiotherapy-associated toxicity and hinder ICB efficacy, while others seem to reduce radiotherapy-associated toxicity or enhance ICB efficacy. Consequently, fecal microbiota transplantation (FMT) has been applied to reduce radio- and immunotherapy-related toxicity and enhance their efficacies. Here, we have reviewed the currently available preclinical and clinical data in CRC treatment, with a focus on how the gut microbiome influences radio- and immunotherapy toxicity and efficacy and if these treatments could benefit from FMT.}, } @article {pmid38035329, year = {2023}, author = {Mbaye, B and Magdy Wasfy, R and Borentain, P and Tidjani Alou, M and Mottola, G and Bossi, V and Caputo, A and Gerolami, R and Million, M}, title = {Increased fecal ethanol and enriched ethanol-producing gut bacteria Limosilactobacillus fermentum, Enterocloster bolteae, Mediterraneibacter gnavus and Streptococcus mutans in nonalcoholic steatohepatitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1279354}, pmid = {38035329}, issn = {2235-2988}, mesh = {Humans ; *Non-alcoholic Fatty Liver Disease/etiology ; Ethanol ; Streptococcus mutans/genetics ; *Limosilactobacillus fermentum ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Glucose ; Cholesterol ; }, abstract = {BACKGROUND: Non-alcoholic steatohepatitis (NASH) has become a major public health issue as one of the leading causes of liver disease and transplantation worldwide. The instrumental role of the gut microbiota is emerging but still under investigation. Endogenous ethanol (EtOH) production by gut bacteria and yeasts is an emerging putative mechanism. Microbial metagenomics and culture studies targeting enterobacteria or yeasts have been reported, but no culturomics studies have been conducted so far.

AIM: To assess fecal EtOH and other biochemical parameters, characterize NASH-associated dysbiosis and identify EtOH-producing gut microbes associated with the disease, fecal samples from 41 NASH patients and 24 controls were analyzed. High-performance liquid chromatography (HPLC) was used for EtOH, glucose, total proteins, triglyceride and total cholesterol. Viable bacteria were assessed with microbial culturomics. Microbial genetic material was assessed using 16S metagenomics targeting the hypervariable V3V4 region.

RESULTS: Fecal EtOH and glucose was elevated in the stools of NASH patients (p < 0.05) but not triglyceride, total cholesterol or proteins. In culturomics, EtOH-producing Enterocloster bolteae and Limosilactobacillus fermentum were enriched in NASH. V3V4 16S rRNA amplicon sequencing confirmed the enrichment in EtOH-producing bacteria including L. fermentum, Mediterraneibacter gnavus and Streptococcus mutans, species previously associated with NASH and other dysbiosis-associated diseases. Strikingly, E. bolteae was identified only by culturomics. The well-known Lacticaseibacillus casei was identified in controls but never isolated in patients with NASH (p < 0.05).

CONCLUSION: Elevated fecal EtOH and glucose is a feature of NASH. Several different EtOH-producing gut bacteria may play an instrumental role in the disease. Culturomics and metagenomics, two complementary methods, will be critical to identify EtOH-producing bacteria for future diagnostic markers and therapeutic targets for NASH. Suppression of EtOH-producing gut microbes and L. casei administration are options to be tested in NASH treatment.}, } @article {pmid37566894, year = {2023}, author = {Allegretti, JR and Khanna, S and Feuerstadt, P}, title = {Practical Use of Fecal Microbiota Spores, Live BRPK for the Prevention of Recurrent Clostridioides difficile Infection.}, journal = {The American journal of gastroenterology}, volume = {118}, number = {12}, pages = {2106-2108}, doi = {10.14309/ajg.0000000000002463}, pmid = {37566894}, issn = {1572-0241}, mesh = {Humans ; Spores, Bacterial ; *Clostridium Infections/prevention & control ; Feces ; *Microbiota ; Fecal Microbiota Transplantation ; Recurrence ; Treatment Outcome ; }, } @article {pmid38045643, year = {2022}, author = {Marasco, G and Cremon, C and Barbaro, MR and Stanghellini, V and Barbara, G}, title = {Gut microbiota signatures and modulation in irritable bowel syndrome.}, journal = {Microbiome research reports}, volume = {1}, number = {2}, pages = {11}, pmid = {38045643}, issn = {2771-5965}, abstract = {Irritable bowel syndrome (IBS) affects approximately one tenth of the general population and is characterized by abdominal pain associated with abnormalities in bowel habits. Visceral hypersensitivity, abnormal intestinal motor function, mucosal immune activation, and increased intestinal permeability concur to its pathophysiology. Psychological factors can influence symptom perception at the central nervous system level. In addition, recent evidence suggests that dysbiosis may be a key pathophysiological factor in patients with IBS. Increasing understanding of the pathophysiological mechanisms translates into new and more effective therapeutic approaches. Indeed, in line with this evidence, IBS therapies nowadays include agents able to modulate gut microbiota function and composition, such as diet, prebiotics, probiotics, and antibiotics. In addition, in the last decade, an increasing interest in fecal microbiota transplantation has been paid. An in-depth understanding of the intestinal microenvironment through accurate faucal microbiota and metabolite analysis may provide valuable insights into the pathophysiology of IBS, finally shaping new tailored IBS therapies.}, } @article {pmid38035162, year = {2023}, author = {Yuan, QF and Wu, HY and Chen, XY and Zheng, YM and Fu, SL and Wang, XH and Zhu, JW and Guo, JD and He, XX and Wu, LH}, title = {Colonic Endoscopic Tubing Is Safe and Effective Approach for Washed Microbiota Transplantation in Autistic Children.}, journal = {Gastroenterology research and practice}, volume = {2023}, number = {}, pages = {7838601}, pmid = {38035162}, issn = {1687-6121}, abstract = {BACKGROUND: Washed microbiota transplantation (WMT) as the improved methods of fecal microbiota transplantation has been employed as a therapeutic approach for ameliorating symptoms associated with autism spectrum disorder (ASD). In this context, colonic transendoscopic enteral tubing (TET) has been utilized as a novel procedure for administering WMT.

METHODS: Data of children with ASD who received WMT by TET were retrospectively reviewed, including bowel preparation methods, TET operation time, success rate, tube retention time, the comfort of children, adverse events, and parent satisfaction.

RESULTS: A total of 38 participants underwent 124 colonic TET catheterization procedures. The average time of TET operation was 15 minutes, and the success rate was 100% (124/124). There was no significant difference in TET operation time between high-seniority physicians and low-seniority physicians. In 123 procedures (99%), the TET tube allowed the completion of WMT treatment for 6 consecutive days. In 118 procedures (95.2%), the tube was detached spontaneously after the end of the treatment course, and the average TET tube retention time was 8 days. There was no incidence of tube blockage during the treatment course. No severe adverse events occurred during follow-up. Parents of all participants reported a high level of satisfaction with TET.

CONCLUSION: Colonic TET is a safe and feasible method for WMT in children with ASD.}, } @article {pmid38034098, year = {2023}, author = {Bai, M and Guo, H and Zheng, XY}, title = {Inflammatory bowel disease and Clostridium difficile infection: clinical presentation, diagnosis, and management.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848231207280}, pmid = {38034098}, issn = {1756-283X}, abstract = {As a frequent complication of inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) was confirmed to not only aggravate the symptoms of IBD but also result in unexpected outcomes, including death. With the increasing prevalence rate of IBD and the updating of CDI diagnosis, the incidence of CDI in IBD patients is also seen rising. Although a detection method consisting of glutamate dehydrogenase immunoassay or nucleic acid amplification test and then toxin A/B enzyme immunoassay was recommended and widely adopted, the diagnosis of CDI in IBD is still a challenge because of the overlap between the symptoms of CDI in IBD and CDI itself. Vancomycin and fidaxomicin are the first-line therapy for CDI in IBD; however, the treatment has different effects due to the complexity of IBD patients' conditions and the choice of different treatment schemes. Although the use of fecal microbial transplantation is now in the ascendant for IBD management, the prospects are still uncertain and the prevention and treatment of the recurrence of CDI in IBD remain a clinical challenge. In this paper, the epidemiology, pathophysiology, clinical manifestation, prevention, and therapy of CDI in IBD were summarized and presented.}, } @article {pmid38034050, year = {2023}, author = {Chang, TE and Lee, KC and Lee, PC and Wang, YP and Lin, YT and Huang, HC and Luo, JC and Ho, HL and Huang, YH and Hou, MC and , }, title = {Assuring safety of fecal microbiota transplantation in the COVID-19 era: A single-center experience.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {11}, pages = {765-771}, doi = {10.1002/jgh3.12979}, pmid = {38034050}, issn = {2397-9070}, abstract = {BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) is used to treat recurrent or refractory Clostridioides difficile infection (CDI). In the past, screening of fecal donors required surveillance of personal behavior, medical history, and diseases that could be transmitted by the blood or fecal-oral route. In addition, the exclusion of multidrug-resistant organisms (MDROs) has been recommended since 2018. This task has become more complicated in the era of the coronavirus disease-2019 (COVID-19) pandemic. To prevent fecal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is crucial to commence screening for SARS-CoV-2, alongside other traditional tests. Our aim was to investigate whether hidden carriers of SARS-CoV-2 were enrolled for stool donation, and the status of the presence or incidence of MDRO during fecal donation in Taiwan.

METHODS: Fecal products collected from March 2019 to December 2022 were tested for MDRO and nucleic acid amplification tests for SARS-CoV-2 using the pooling method. The period of fecal product collection crossed the time before and during the COVID pandemic in Taiwan.

RESULTS: A total of 151 fecal samples were collected. The fecal products were tested using polymerase chain reaction (PCR) to detect SARS-CoV-2. The results were negative for all stocks. This was similar to the results of MDRO testing. The safety of FMT products has been guaranteed during the pandemic.

CONCLUSION: Our FMT center produced MDRO-free and COVID-19-free products before and during the COVID-19 outbreak in Taiwan. Our protocol was effective for ensuring the safety of FMT products.}, } @article {pmid38033573, year = {2023}, author = {Zhu, Q and Wu, K and Yang, Q and Meng, B and Niu, Y and Zhao, F}, title = {Advances in psoriasis and gut microorganisms with co-metabolites.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1192543}, doi = {10.3389/fmicb.2023.1192543}, pmid = {38033573}, issn = {1664-302X}, abstract = {This review summarizes the potential role of gut microbes and their metabolites as novel mediators of psoriasis, including their composition and function in disease pathogenesis, progression, and management. Gut microbiota network analysis, colony construction, and in vivo large-scale interaction experiments showed that different degrees of damage and repair in psoriasis, both in animals and humans, involve cross-border homeostasis of the microbial community. Which gut microbiota interactions are present in psoriasis and how they collaborate with immune cells and influence psoriasis development via the gut-skin axis remain incompletely elucidated. In this article, we review the latest information on the unique patterns of gut microbiota and co-metabolites involved in the pathogenesis of psoriasis and attempt to explore microbial-based therapeutic targets derived from mono-and polymicrobial probiotics, fecal microbiota transplantation, pharmacomicrobiomics, and dietary interventions as diagnostic or therapeutic approaches promising to provide new options and long-term management for psoriasis.}, } @article {pmid38033557, year = {2023}, author = {Xiang, W and Xiang, H and Wang, J and Jiang, Y and Pan, C and Ji, B and Zhang, A}, title = {Fecal microbiota transplantation: a novel strategy for treating Alzheimer's disease.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1281233}, doi = {10.3389/fmicb.2023.1281233}, pmid = {38033557}, issn = {1664-302X}, abstract = {Alzheimer's disease is a common neurological disorder, which has become one of the major factors affecting human health due to its serious impact on individuals, families and society. It has been confirmed that gut microbiota can affect the occurrence and development of Alzheimer's disease. Especially, fecal microbiota transplantation plays a positive role in the treatment of Alzheimer's disease. The mechanisms for improving Alzheimer's disease might include anti-inflammation and regulation of amyloid β-protein, synaptic plasticity, short-chain fatty acids, and histone acetylation. In this mini-review, the relationship between fecal microbiota transplantation and Alzheimer's disease was summarized. It is hoped that fecal microbiota transplantation would play a positive role in the prevention and treatment of Alzheimer's disease in the future.}, } @article {pmid38031252, year = {2023}, author = {Crossland, NA and Beck, S and Tan, WY and Lo, M and Mason, JB and Zhang, C and Guo, W and Crott, JW}, title = {Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2288187}, doi = {10.1080/19490976.2023.2288187}, pmid = {38031252}, issn = {1949-0984}, abstract = {Aging is a strong risk factor for colorectal cancer (CRC). It is well established that gut microbial dysbiosis can play a role in the etiology of CRC. Although the composition of the gut microbial community changes with age and is reported to become more pro-inflammatory, it is unclear whether such changes are also pro-tumorigenic for the colon. To address this gap, we conducted fecal microbiota transplants (FMT) from young (DY, ~6 wk) and old (DO, ~72 wk) donor mice into young (8 wk) recipient mice that were pre-treated with antibiotics. After initiating tumorigenesis with azoxymethane, recipients were maintained for 19 wk during which time they received monthly FMT boosters. Compared to recipients of young donors (RY), recipients of old donors (RO) had an approximately 3-fold higher prevalence of histologically confirmed colon tumors (15.8 vs 50%, Chi2 P = .03), approximately 2-fold higher proliferating colonocytes as well as significantly elevated colonic IL-6, IL-1β and Tnf-α. Transcriptomics analysis of the colonic mucosa revealed a striking upregulation of mitochondria-related genes in the RO mice, a finding corroborated by increased mitochondrial abundance. Amongst the differences in fecal microbiome observed between DY and DO mice, the genera Ruminoclostridium, Lachnoclostridium and Marvinbryantia were more abundant in DY mice while the genera Bacteroides and Akkermansia were more abundant in DO mice. Amongst recipients, Ruminoclostridium and Lachnoclostridium were higher in RY mice while Bacteroides was higher in RO mice. Differences in fecal microbiota were observed between young and old mice, some of which persisted upon transplant into recipient mice. Recipients of old donors displayed significantly higher colonic proliferation, inflammation and tumor abundance compared to recipients of young donors. These findings support an etiological role for altered gut microbial communities in the increased risk for CRC with increasing age and establishes that such risk can be transmitted between individuals.}, } @article {pmid38030980, year = {2023}, author = {Liu, H and Li, J and Yuan, J and Huang, J and Xu, Y}, title = {Fecal microbiota transplantation as a therapy for treating ulcerative colitis: an overview of systematic reviews.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {371}, pmid = {38030980}, issn = {1471-2180}, abstract = {AIM: The current overview on published systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically gather, evaluate, and synthesize solid evidence for using fecal microbiota transplantation (FMT) to treat ulcerative colitis (UC).

METHODS: Relevant articles published before January 2023 were collected from Web of Science, Embase, PubMed, and Cochrane Library. Two authors used Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, PRISMA checklists, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system were applied by two authors to independently evaluate the methodological quality, reporting quality, and evidence quality, respectively. Re-meta-analysis on the primary RCTs was conducted after excluding overlapping randomized controlled trials (RCTs).

RESULTS: Six SRs/MAs involving 12 primary RCTs and 544 participants were included. According to the AMSTAR-2 tool and PRISMA checklist, methodological quality and reporting quality of the included studies was overall satisfactory. The evidence quality of a great majority of outcomes was rated as moderate to high according to the GRADE system. Compared to placebo, the re-meta-analysis found a great advantage of use FMT in inducing combined clinical and endoscopic remission (OR 3.83 [2.31, 6.34]), clinical remission (3.31 [2.09, 5.25]), endoscopic remission (OR 3.75 [2.20, 6.39]), clinical response (OR 2.56 [1.64, 4.00]), and endoscopic response (OR 2.18 [1.12, 4.26]). Pooled data showed no significant difference in serious adverse events between patients receiving FMT and those receiving placebo (OR 1.53 [0.74, 3.19]). Evidence quality of the outcomes derived from re-meta-analysis was significantly higher after overcoming the limitations of previous SRs/MAs.

CONCLUSION: In conclusion, moderate- to high-quality evidence supported a promising use of FMT to safely induce remission in UC. However, further trials with larger sample size are still required to comprehensively analyze the delivery route, total dosage, frequency, and donor selection in FMT.}, } @article {pmid38030463, year = {2023}, author = {Catalán, V and Gómez-Ambrosi, J}, title = {Will the manipulation of the gut microbiota be effective for the treatment of metabolic diseases?.}, journal = {European journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ejim.2023.11.025}, pmid = {38030463}, issn = {1879-0828}, } @article {pmid38030048, year = {2023}, author = {Gong, X and Ma, Y and Deng, X and Li, A and Li, X and Kong, X and Liu, Y and Liu, X and Guo, K and Yang, Y and Li, Z and Wei, H and Zhou, D and Hong, Z}, title = {Intestinal dysbiosis exacerbates susceptibility to the anti-NMDA receptor encephalitis-like phenotype by changing blood brain barrier permeability and immune homeostasis.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2023.11.030}, pmid = {38030048}, issn = {1090-2139}, abstract = {Changes in the intestinal microbiota have been observed in patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE). However, whether and how the intestinal microbiota is involved in the pathogenesis of NMDARE susceptibility needs to be demonstrated. Here, we first showed that germ-free (GF) mice that underwent fecal microbiota transplantation (FMT) from NMDARE patients, whose fecal microbiota exhibited low short-chain fatty acid content, decreased abundance of Lachnospiraceae, and increased abundance of Verrucomicrobiota, Akkermansia, Parabacteroides, Oscillospirales, showed significant behavioral deficits. Then, these FMT mice were actively immunized with an amino terminal domain peptide from the GluN1 subunit (GluN1356-385) to mimic the pathogenic process of NMDARE. We found that FMT mice showed an increased susceptibility to an encephalitis-like phenotype characterized by more clinical symptoms, greater pentazole (PTZ)-induced susceptibility to seizures, and higher levels of T2 weighted image (T2WI) hyperintensities following immunization. Furthermore, mice with dysbiotic microbiota had impaired blood-brain barrier integrity and a proinflammatory condition. In NMDARE-microbiota recipient mice, the levels of Evan's blue (EB) dye extravasation increased, ZO-1 and claudin-5 expression decreased, and the levels of proinflammatory cytokines (IL-1, IL-6, IL-17, TNF-α and LPS) increased. Finally, significant brain inflammation, mainly in hippocampal and cortical regions, with modest neuroinflammation, immune cell infiltration, and reduced expression of NMDA receptors were observed in NMDARE microbiota recipient mice following immunization. Overall, our findings demonstrated that intestinal dysbiosis increased NMDARE susceptibility, suggesting a new target for limiting the occurrence of the severe phenotype of NMDARE.}, } @article {pmid38029942, year = {2023}, author = {Xie, Z and Zhou, J and Zhang, X and Li, Z}, title = {Clinical potential of microbiota in thyroid cancer therapy.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1870}, number = {2}, pages = {166971}, doi = {10.1016/j.bbadis.2023.166971}, pmid = {38029942}, issn = {1879-260X}, abstract = {Thyroid cancer is one of the most common tumors of the endocrine system because of its rapid and steady increase in incidence and prevalence. In recent years, a growing number of studies have identified a key role for the gut, thyroid tissue and oral microbiota in the regulation of metabolism and the immune system. A growing body of evidence has conclusively demonstrated that the microbiota influences tumor formation, prevention, diagnosis, and treatment. We provide extensive information in which oral, gut, and thyroid microbiota have an effect on thyroid cancer development in this review. In addition, we thoroughly discuss the various microbiota species, their potential functions, and the underlying mechanisms for thyroid cancer. The microbiome offers a unique opportunity to improve the effectiveness of immunotherapy and radioiodine therapy thyroid cancer by maintaining the right type of microbiota, and holds great promise for improving clinical outcomes and quality of life for thyroid cancer patients.}, } @article {pmid38029189, year = {2023}, author = {Zhang, X and Luo, X and Tian, L and Yue, P and Li, M and Liu, K and Zhu, D and Huang, C and Shi, Q and Yang, L and Xia, Z and Zhao, J and Ma, Z and Li, J and Leung, JW and Lin, Y and Yuan, J and Meng, W and Li, X and Chen, Y}, title = {The gut microbiome dysbiosis and regulation by fecal microbiota transplantation: umbrella review.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1286429}, pmid = {38029189}, issn = {1664-302X}, abstract = {BACKGROUND: Gut microbiome dysbiosis has been implicated in various gastrointestinal and extra-gastrointestinal diseases, but evidence on the efficacy and safety of fecal microbiota transplantation (FMT) for therapeutic indications remains unclear.

METHODS: The gutMDisorder database was used to summarize the associations between gut microbiome dysbiosis and diseases. We performed an umbrella review of published meta-analyses to determine the evidence synthesis on the efficacy and safety of FMT in treating various diseases. Our study was registered in PROSPERO (CRD42022301226).

RESULTS: Gut microbiome dysbiosis was associated with 117 gastrointestinal and extra-gastrointestinal. Colorectal cancer was associated with 92 dysbiosis. Dysbiosis involving Firmicutes (phylum) was associated with 34 diseases. We identified 62 published meta-analyses of FMT. FMT was found to be effective for 13 diseases, with a 95.56% cure rate (95% CI: 93.88-97.05%) for recurrent Chloridoids difficile infection (rCDI). Evidence was high quality for rCDI and moderate to high quality for ulcerative colitis and Crohn's disease but low to very low quality for other diseases.

CONCLUSION: Gut microbiome dysbiosis may be implicated in numerous diseases. Substantial evidence suggests FMT improves clinical outcomes for certain indications, but evidence quality varies greatly depending on the specific indication, route of administration, frequency of instillation, fecal preparation, and donor type. This variability should inform clinical, policy, and implementation decisions regarding FMT.}, } @article {pmid38025767, year = {2023}, author = {Sun, H and Su, X and Liu, Y and Li, G and Du, Q}, title = {Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats.}, journal = {iScience}, volume = {26}, number = {12}, pages = {108392}, doi = {10.1016/j.isci.2023.108392}, pmid = {38025767}, issn = {2589-0042}, abstract = {Previous research has demonstrated significant differences in intestinal flora between pregnant women with intrahepatic cholestasis of pregnancy (ICP) and healthy pregnant women. The objective of our study is to identify the key bacteria involved in ICP rats and explore the underlying mechanism. We established an ICP rat model and collected rat feces for metagenomic sequencing and found that Roseburia intestinalis (R.I) is the key bacteria in ICP. Transplantation of R.I improved phenotypes associated with ICP through the bile acid/farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling pathway. We used the FXR antagonist Z-Guggulsterone (Z-Gu) to verify the key role of FXR in ICP and found that Z-Gu reversed the benefits of R.I on ICP rats. Our research highlights the important role of intestinal flora in the pathogenesis of ICP and provides a novel approach for its treatment.}, } @article {pmid38024855, year = {2023}, author = {Mao, Z and Hui, H and Zhao, X and Xu, L and Qi, Y and Yin, L and Qu, L and Han, L and Peng, J}, title = {Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling.}, journal = {Journal of pharmaceutical analysis}, volume = {13}, number = {10}, pages = {1153-1167}, doi = {10.1016/j.jpha.2023.06.007}, pmid = {38024855}, issn = {2214-0883}, abstract = {It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease (PD). Dioscin, a bioactive steroidal saponin, shows various activities. However, its effects and mechanisms against PD are limited. In this study, dioscin dramatically alleviated neuroinflammation and oxidative stress, and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus, Streptococcus, Bacteroides and Lactobacillus genera, which further inhibited bile salt hydrolase (BSH) activity and blocked bile acid (BA) deconjugation. Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent. In addition, non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis. Moreover, targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid and β-muricholic acid in feces and serum. In addition, ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice. Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5 (TGR5), glucagon-like peptide-1 receptor (GLP-1R), GLP-1, superoxide dismutase (SOD), and down-regulated NADPH oxidases 2 (NOX2) and nuclear factor-kappaB (NF-κB) levels. Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice, suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.}, } @article {pmid38024475, year = {2023}, author = {Zhao, W and Lei, J and Ke, S and Chen, Y and Xiao, J and Tang, Z and Wang, L and Ren, Y and Alnaggar, M and Qiu, H and Shi, W and Yin, L and Chen, Y}, title = {Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215).}, journal = {EClinicalMedicine}, volume = {66}, number = {}, pages = {102315}, doi = {10.1016/j.eclinm.2023.102315}, pmid = {38024475}, issn = {2589-5370}, abstract = {BACKGROUND: Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence supported a close relationship between gut microbiome and anti-PD-1 efficacy. This study aimed to explore the efficacy and safety of the combination of fecal microbiota transplantation (FMT) and tislelizumab and fruquintinib in refractory MSS mCRC.

METHODS: In the phase II trial, MSS mCRC patients were administered FMT plus tislelizumab and fruquintinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), clinical benefit rate (CBR), safety and quality of life. Feces and peripheral blood were collected for exploratory biomarker analysis. This study is registered with Chictr.org.cn, identifier ChiCTR2100046768.

FINDINGS: From May 10, 2021 to January 17, 2022, 20 patients were enrolled. Median follow-up was 13.7 months. Median PFS was 9.6 months (95% CI 4.1-15.1). Median OS was 13.7 months (95% CI 9.3-17.7). Median DoR was 8.1 months (95% CI 1.7-10.6). ORR was 20% (95% CI 5.7-43.7). DCR was 95% (95% CI 75.1-99.9). CBR was 60% (95% CI 36.1-80.9). Nineteen patients (95%) experienced at least one treatment-related adverse event (TRAE). Six patients (30%) had grade 3-4 TRAEs, with the most common being albuminuria (10%), urine occult blood (10%), fecal occult blood (10%), hypertension (5%), hyperglycemia (5%), liver dysfunction (5%), hand-foot skin reaction (5%), and hypothyroidism (5%). No treatment-related deaths occurred. Responders had a high-abundance of Proteobacteria and Lachnospiraceae family and a low-abundance of Actinobacteriota and Bifidobacterium. The treatment did not change the structure of peripheral blood TCR repertoire. However, the expanded TCRs exhibited the characteristics of antigen-driven responses in responders.

INTERPRETATION: FMT plus tislelizumab and fruquintinib as third-line or above treatment showed improved survival and manageable safety in refractory MSS mCRC, suggesting a valuable new treatment option for this patient population.

FUNDING: This study was supported by the National Natural Science Foundation of China (82102954 to Wensi Zhao) and the Special Project of Central Government for Local Science and Technology Development of Hubei Province (ZYYD2020000169 to Yongshun Chen).}, } @article {pmid38022314, year = {2023}, author = {Sharifa, M and Ghosh, T and Daher, OA and Bhusal, P and Alaameri, YA and Naz, J and Ekhator, C and Bellegarde, SB and Bisharat, P and Vaghani, V and Hussain, A}, title = {Unraveling the Gut-Brain Axis in Multiple Sclerosis: Exploring Dysbiosis, Oxidative Stress, and Therapeutic Insights.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e47058}, doi = {10.7759/cureus.47058}, pmid = {38022314}, issn = {2168-8184}, abstract = {This comprehensive review delves into the intricate relationship between the gut microbiota and multiple sclerosis (MS), shedding light on the potential therapeutic avenues for this complex autoimmune disease. It emphasizes the multifactorial nature of MS, including genetic, environmental, and gender-related factors. Furthermore, the article highlights the emerging role of gut microbiota in MS pathophysiology, particularly in terms of gut dysbiosis, oxidative stress, and inflammasome activation within the gut-brain axis. This interplay raises intriguing questions about how the gut microbiota influences the onset and progression of MS. Environmental factors, such as diet and pollutants, add further layers of complexity to the connection between gut health and MS risk. This review also discusses promising therapeutic interventions, such as fecal microbiota transplantation, probiotics, dietary adjustments, and gut-derived metabolites that offer potential avenues for managing MS. It underscores the need for ongoing research to fully unravel the complexities of the role of the gut-brain axis in MS. Ultimately, this article provides a comprehensive exploration of the topic, offering hope for novel preventive and therapeutic strategies that could significantly improve the lives of individuals affected by this challenging autoimmune condition.}, } @article {pmid38021361, year = {2023}, author = {Sehgal, K and Feuerstadt, P}, title = {The real efficacy of microbiota restoration following standard of care antimicrobial in patients with recurrent Clostridiodes difficile.}, journal = {Translational gastroenterology and hepatology}, volume = {8}, number = {}, pages = {31}, doi = {10.21037/tgh-23-46}, pmid = {38021361}, issn = {2415-1289}, } @article {pmid38018424, year = {2023}, author = {Hu, S and Zhao, R and Xu, Y and Gu, Z and Zhu, B and Hu, J}, title = {Orally-administered nanomedicine systems targeting colon inflammation for the treatment of inflammatory bowel disease: latest advances.}, journal = {Journal of materials chemistry. B}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3tb02302h}, pmid = {38018424}, issn = {2050-7518}, abstract = {Inflammatory bowel disease (IBD) is a chronic and idiopathic condition that results in inflammation of the gastrointestinal tract, leading to conditions such as ulcerative colitis and Crohn's disease. Commonly used treatments for IBD include anti-inflammatory drugs, immunosuppressants, and antibiotics. Fecal microbiota transplantation is also being explored as a potential treatment method; however, these drugs may lead to systemic side effects. Oral administration is preferred for IBD treatment, but accurately locating the inflamed area in the colon is challenging due to multiple physiological barriers. Nanoparticle drug delivery systems possess unique physicochemical properties that enable precise delivery to the target site for IBD treatment, exploiting the increased permeability and retention effect of inflamed intestines. The first part of this review comprehensively introduces the pathophysiological environment of IBD, covering the gastrointestinal pH, various enzymes in the pathway, transport time, intestinal mucus, intestinal epithelium, intestinal immune cells, and intestinal microbiota. The second part focuses on the latest advances in the mechanism and strategies of targeted delivery using oral nanoparticle drug delivery systems for colitis-related fields. Finally, we present challenges and potential directions for future IBD treatment with the assistance of nanotechnology.}, } @article {pmid38018317, year = {2023}, author = {Xiao, Y and Feng, J and Jia, J and Li, J and Zhou, Y and Song, Z and Guan, F and Li, X and Liu, L}, title = {Vitamin K1 ameliorates lipopolysaccharide-triggered skeletal muscle damage revealed by faecal bacteria transplantation.}, journal = {Journal of cachexia, sarcopenia and muscle}, volume = {}, number = {}, pages = {}, doi = {10.1002/jcsm.13379}, pmid = {38018317}, issn = {2190-6009}, support = {2022YFS0632//Sichuan Provincial Science and Technology Plan Joint Innovation Projects/ ; }, abstract = {BACKGROUND: Sepsis-associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis-induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis-associated muscle weakness.

METHODS: In a lipopolysaccharide (LPS)-induced inflammation mouse model, mice with different sensitivities to LPS-induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS-triggered muscle damage was investigated, and the underlying mechanism was explored.

RESULTS: Recipients exhibited varying LPS-triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF-1 (0.825 ± 0.063 vs. 0.304 ± 0.293, P = 0.0141) and MAFbx (1.055 ± 0.079 vs. 0.456 ± 0.3, P = 0.0092). Colonic tight junction proteins ZO-1 (0.550 ± 0.087 vs. 0.842 ± 0.094, P = 0.0492) and occludin (0.284 ± 0.057 vs. 0.664 ± 0.191, P = 0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P = 0.0195) and serum of the Res group (P = 0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy-related protein expression downregulated (P < 0.05). Meanwhile SIRT1 protein expression were upregulated (0.320 ± 0.035 vs. 0.685 ± 0.081, P = 0.0281) and pNF-κB protein expression were downregulated (0.815 ± 0.295 vs. 0.258 ± 0.130, P = 0.0308). PI3K (0.365 ± 0.142 vs. 0.763 ± 0.013, P = 0.0475), pAKT (0.493 ± 0.159 vs. 1.183 ± 0.344, P = 0.0254) and pmTOR (0.509 ± 0.088 vs. 1.110 ± 0.190, P = 0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels.

CONCLUSIONS: Vitamin K1 might ameliorate LPS-triggered skeletal muscle damage by antagonizing NF-κB-mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.}, } @article {pmid38016701, year = {2023}, author = {Lin, J and Xiong, J and Jin, Y and Wang, H and Wu, L and Chen, L and Zhang, F and Ji, G and Cui, B}, title = {Fecal microbiota transplantation through transendoscopic enteral tubing for inflammatory bowel disease: High acceptance and high satisfaction.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16435}, pmid = {38016701}, issn = {1440-1746}, support = {BK20211384//Nature Science Foundation of Jiangsu Province/ ; }, abstract = {BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) has been shown to positively affect the treatment of inflammatory bowel disease (IBD). However, the safety and efficacy of FMT may depend on the route of microbiota delivery. This study investigates the acceptance, satisfaction, and selection preference of a new delivery route, transendoscopic enteral tubing (TET), for treating IBD.

METHODS: A survey was conducted among patients with IBD from five medical centers across China. The objective was to assess their acceptance, subjective feelings, and major concerns regarding two types of TET: colonic TET and mid-gut TET. In addition, the survey also analyzed the factors affecting the selection of TET and TET types among these patients.

RESULTS: The final analysis included 351 questionnaires. Up to 76.6% of patients were willing to accept TET and preferred to choose colonic TET when they first learned about TET. Patients with longer disease duration, history of enema therapy, or enteral nutrition were more open to considering TET among IBD patients. After treatment, 95.6% of patients were satisfied with TET, including colonic TET (95.9%) and mid-gut TET (95.1%). Patients with a history of enema therapy and ulcerative colitis preferred colonic TET. In contrast, those with a history of enteral nutrition and Crohn's disease were willing to choose mid-gut TET. However, some patients hesitated to accept TET due to concerns about efficacy, safety, and cost.

CONCLUSIONS: TET was highly accepted and satisfied patients with IBD. Disease type and combination therapy influenced the choice of colonic or mid-gut TET.}, } @article {pmid38016505, year = {2023}, author = {Li, S and Chen, T and Zhou, Y and Li, X}, title = {Palmitic acid and trans-4-hydroxy-3-methoxycinnamate, the active ingredients of Yaobishu formula, reduce inflammation and pain by regulating gut microbiota and metabolic changes after lumbar disc herniation to activate autophagy and the Wnt/β-catenin pathway.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {}, number = {}, pages = {166972}, doi = {10.1016/j.bbadis.2023.166972}, pmid = {38016505}, issn = {1879-260X}, abstract = {The imbalance in gut microbiota triggers an inflammatory response that spreads from the gut to the discs and is associated with lumbar disc herniation (LDH). In this study, we investigated the mechanism of palmitic acid (PA) and trans-4-hydroxy-3-methoxycinnamic acid (THMC) on microbiota, metabolic homeostasis, and autophagy after LDH. The LDH rat model was established by puncturing the exposed intervertebral disc. 16S rDNA was used to assess the gut microbiome composition. The microbial metabolites were analyzed by UPLC-MS. The mechanism of PA and THMC in LDH was explored by fecal microbiota transplantation (FMT). We found that Yaobishu, PA, THMC, and the positive control drug Celebrex attenuated intervertebral disc damage in LDH rats and downregulated TRPV1, IL-1β, and IL-18 expression. In addition, Yaobishu reduced Oscillospirales and Ruminococcaceae abundances after LDH. PA increased Bacilli's abundance while decreasing Negativicutes and Ruminococcaceae abundances. Metabolomics showed that Yaobishu increased 2-hexanone, methyl isobutyl ketone, 2-methylpentan-3-one, and nonadecanoic acid levels but decreased pantetheine and urocanate levels. PA and THMC reduced uridine and urocanate levels. Yaobishu, PA, and THMC activated autophagy and the Wnt/β-catenin pathway in LDH rats. Moreover, antibiotics abrogated these effects. FMT-PA and FMT-THMC activated autophagy and decreased IL-1β, IL-18, Wnt1, β-catenin, and TRPV1 expression. FMT-PA and FMT-THMC partially reversed the effects of 3-MA. Taken together, our data suggest that Yaobishu, PA, and THMC relieve inflammation and pain by remodeling the gut microbiota and restoring metabolic homeostasis after LDH to activate autophagy and the Wnt/β-catenin pathway, which provide a new therapeutic target for LDH in the clinic.}, } @article {pmid38016344, year = {2023}, author = {Wu, Y and Zhang, Y and Xie, B and Zhang, X and Wang, G and Yuan, S}, title = {Esketamine mitigates cognitive impairment following exposure to LPS by modulating the intestinal flora/subdiaphragmatic vagus nerve/spleen axis.}, journal = {International immunopharmacology}, volume = {126}, number = {}, pages = {111284}, doi = {10.1016/j.intimp.2023.111284}, pmid = {38016344}, issn = {1878-1705}, abstract = {INTRODUCTION: Susceptibility to secondary infection often increases after primary infection. Secondary infections can lead to more severe inflammatory injuries; however, the underlying mechanisms are not yet fully elucidated.

OBJECTIVE: To investigate whether esketamine treatment immediately after primary lipopolysaccharide (LPS) exposure could alleviate cognitive impairment caused by secondary infection.

METHODS: Mice were injected intraperitoneally (IP) with LPS (5 mg/kg) 10 days apart. Esketamine (10, 15, or 30 mg/kg) was administered IP immediately after the primary LPS injection. Splenectomy or subdiaphragmatic vagotomy (SDV) was performed 7 days before secondary LPS exposure or broad-spectrum antibiotic administration.

RESULTS: Splenomegaly was observed after the primary LPS injection on Days 3 and 10. Splenomegaly was attenuated by treatment with 30 mg/kg esketamine. Esketamine treatment prevented increased plasma proinflammatory cytokines levels and cognitive dysfunction induced by secondary LPS exposure. Mice that underwent splenectomy or SDV had lower proinflammatory cytokines levels, higher hippocampal brain-derived neurotrophic factor (BDNF) levels, and improved cognitive function 1 day after secondary infection, which was not further improved by esketamine. Fecal microbiota transplantation (FMT) from endotoxic mice treated with esketamine attenuated hippocampal BDNF downregulation and cognitive dysfunction only in pseudo germ-free (PGF) mice without splenectomy. FMT with fecal suspensions from esketamine-treated endotoxic mice abrogated splenomegaly only in PGF mice without SDV. Blocking BDNF signaling blocked esketamine's ameliorating effects on secondary LPS exposure-induced cognitive dysfunction.

CONCLUSION: The intestinal flora/subdiaphragmatic vagus nerve/spleen axis-mediated hippocampal BDNF downregulation significantly affected secondary LPS-induced systemic inflammation and cognitive dysfunction. Esketamine preserves cognitive function via this mechanism.}, } @article {pmid38015634, year = {2023}, author = {Gurczynski, SJ and Lipinski, JH and Strauss, JY and Alam, S and Huffnagle, GB and Ranjan, P and Kennedy, LH and Moore, BB and O'Dwyer, DN}, title = {Horizontal transmission of gut microbiota attenuates mortality in lung fibrosis.}, journal = {JCI insight}, volume = {}, number = {}, pages = {}, doi = {10.1172/jci.insight.164572}, pmid = {38015634}, issn = {2379-3708}, abstract = {Pulmonary fibrosis is a chronic and often fatal disease. The pathogenesis is characterized by aberrant repair of lung parenchyma resulting in loss of physiological homeostasis, respiratory failure and death. The immune response in pulmonary fibrosis is dysregulated. The gut microbiome is a key regulator of immunity. The role of the gut microbiome in regulating the pulmonary immunity in lung fibrosis is poorly understood. Here, we determine the impact of gut microbiota on pulmonary fibrosis in C57BL/6 mice derived from different vendors (C57BL/6J and C57BL/6NCrl). We use germ free models, fecal microbiota transplantation and cohousing to transmit gut microbiota. Metagenomic studies of feces establish keystone species between sub-strains. Pulmonary fibrosis is microbiota dependent in C57BL/6 mice. Gut microbiota are distinct by β diversity (PERMANOVA P<0.001) and α diversity (P<0.0001). Mortality and lung fibrosis are attenuated in C57BL/6NCrl mice. Elevated CD4+ IL-10+ T cells and lower IL-6 occur in C57BL/6NCrl mice. Horizontal transmission of microbiota by cohousing attenuates mortality in C57BL/6J mice and promotes a transcriptionally altered pulmonary immunity. Temporal changes in lung and gut microbiota demonstrates that gut microbiota contribute largely to immunological phenotype. Key regulatory gut microbiota contribute to lung fibrosis generating rationale for human studies.}, } @article {pmid38015106, year = {2023}, author = {Sun, L and Li, Z and Hu, C and Ding, J and Zhou, Q and Pang, G and Wu, Z and Yang, R and Li, S and Li, J and Cai, J and Sun, Y and Li, R and Zhen, H and Sun, S and Zhang, J and Fang, M and Chen, Z and Lv, Y and Cao, Q and Sun, Y and Gong, R and Huang, Z and Duan, Y and Liu, H and Dong, J and Li, J and Ruan, J and Lu, H and He, B and Li, N and Li, T and Xue, W and Li, Y and Shen, J and Yang, F and Zhao, C and Liang, Q and Zhang, M and Chen, C and Gong, H and Hou, Y and Wang, J and Zhang, Y and Yang, H and Zhu, S and Xiao, L and Jin, Z and Guo, H and Zhao, P and Brix, S and Xu, X and Jia, H and Kristiansen, K and Yang, Z and Nie, C}, title = {Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e14028}, doi = {10.1111/acel.14028}, pmid = {38015106}, issn = {1474-9726}, support = {U23A20470//National Scientific Foundation of P. R. China/ ; 82260289//National Scientific Foundation of P. R. China/ ; 91849132//National Scientific Foundation of P. R. China/ ; 81571385//National Scientific Foundation of P. R. China/ ; BJ-2018-139//Beijing Hospital Nova Project/ ; 2021-I2M-1-050//CAMS Innovation Fund for Medical Sciences/ ; 2021YFE0111800//National Key Research and Development Program of China/ ; 2023YFC3603300//National Key Research and Development Program of China/ ; 2018YFC2000400//National Key Research and Development Program of China/ ; 202001AY070001-011//The Priority Union Foundation of Yunnan Provincial Science and Technology Department/ ; BJ-2023-168//National High Level Hospital Clinical Research Funding/ ; BJ-2023-075//National High Level Hospital Clinical Research Funding/ ; 2022ZD0211600//Science and Technology lnnovation 2030 Major Projects/ ; }, abstract = {Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.}, } @article {pmid38014241, year = {2023}, author = {Frith, ME and Kashyap, PC and Linden, DR and Theriault, B and Chang, EB}, title = {Microbiota-dependent early life programming of gastrointestinal motility.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.11.08.566304}, pmid = {38014241}, abstract = {Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later - or not at all - showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility.}, } @article {pmid38012646, year = {2023}, author = {Kim, N and Ju, IG and Jeon, SH and Lee, Y and Jung, MJ and Gee, MS and Cho, JS and Inn, KS and Garrett-Sinha, LA and Oh, MS and Lee, JK}, title = {Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer's disease mouse model.}, journal = {Journal of neuroinflammation}, volume = {20}, number = {1}, pages = {282}, pmid = {38012646}, issn = {1742-2094}, support = {NRF-2022R1A6A3A01087341//National Research Foundation of Korea/ ; NRF-2017R1A5A2014768//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer's disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown.

METHODS: Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age.

RESULTS: In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib[-/-] mice.

CONCLUSION: Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications.}, } @article {pmid38012463, year = {2023}, author = {Hart, NH and Wallen, MP and Farley, MJ and Haywood, D and Boytar, AN and Secombe, K and Joseph, R and Chan, RJ and Kenkhuis, MF and Buffart, LM and Skinner, TL and Wardill, HR}, title = {Exercise and the gut microbiome: implications for supportive care in cancer.}, journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer}, volume = {31}, number = {12}, pages = {724}, pmid = {38012463}, issn = {1433-7339}, abstract = {PURPOSE: Growing recognition of the gut microbiome as an influential modulator of cancer treatment efficacy and toxicity has led to the emergence of clinical interventions targeting the microbiome to enhance cancer and health outcomes. The highly modifiable nature of microbiota to endogenous, exogenous, and environmental inputs enables interventions to promote resilience of the gut microbiome that have rapid effects on host health, or response to cancer treatment. While diet, probiotics, and faecal microbiota transplant are primary avenues of therapy focused on restoring or protecting gut function in people undergoing cancer treatment, the role of physical activity and exercise has scarcely been examined in this population.

METHODS: A narrative review was conducted to explore the nexus between cancer care and the gut microbiome in the context of physical activity and exercise as a widely available and clinically effective supportive care strategy used by cancer survivors.

RESULTS: Exercise can facilitate a more diverse gut microbiome and functional metabolome in humans; however, most physical activity and exercise studies have been conducted in healthy or athletic populations, primarily using aerobic exercise modalities. A scarcity of exercise and microbiome studies in cancer exists.

CONCLUSIONS: Exercise remains an attractive avenue to promote microbiome health in cancer survivors. Future research should elucidate the various influences of exercise modalities, intensities, frequencies, durations, and volumes to explore dose-response relationships between exercise and the gut microbiome among cancer survivors, as well as multifaceted approaches (such as diet and probiotics), and examine the influences of exercise on the gut microbiome and associated symptom burden prior to, during, and following cancer treatment.}, } @article {pmid38011635, year = {2023}, author = {Choueiry, F and Gold, A and Xu, R and Zhang, S and Zhu, J}, title = {Secondary-Electrospray Ionization Mass Spectrometry-Based Online Analyses of Mouse Volatilome Uncover Gut Microbiome-Dictated Metabolic Changes in the Host.}, journal = {Journal of the American Society for Mass Spectrometry}, volume = {}, number = {}, pages = {}, doi = {10.1021/jasms.3c00304}, pmid = {38011635}, issn = {1879-1123}, abstract = {The symbiotic relationship between the gut microbial population is capable of regulating numerous aspects of host physiology, including metabolism. Bacteria can modulate the metabolic processes of the host by feeding on nutritional components within the lumen and releasing bioactive components into circulation. Endogenous volatile organic compound (VOC) synthesis is dependent on the availability of precursors found in mammalian metabolism. Herein, we report that microbial-mediated metabolic influences can alter the host volatilome and the prominent volatile changes can be uncovered by a novel volatile analysis technique named secondary electrospray ionization mass spectrometry. Mice were subjected to an antibiotic cocktail to deplete the microbiome and then inoculated with either single strain bacteria or fecal matter transplantation (FMT) to replete the microbial population in the gut. VOC sampling was achieved by using an advanced secondary electrospray ionization (SESI) source that directly mounted onto a Thermo Q-Exactive high-resolution mass spectrometer (HRMS). A principal component analysis summarizing the volatile profiles of the mice revealed independent clustering of each strain of the FMT-inoculated groups, suggesting unique volatile profiles. The Mummichog algorithm uncovered phenylalanine metabolism as a significantly altered metabolic profile in the volatilome of the microbiome-repleted mice. Our results indicated that the systemic metabolic changes incurred by the host are translated to unique volatile profiles correlated to the diversity of the microbial population colonized within the host. It is thus possible to take advantage of SESI-HRMS-based platforms for noninvasive screening of VOCs to determine the contribution of various microbial colonization within human gut that may impact host health.}, } @article {pmid38010914, year = {2023}, author = {Liang, D and Liu, H and Jin, R and Feng, R and Wang, J and Qin, C and Zhang, R and Chen, Y and Zhang, J and Teng, J and Tang, B and Ding, X and Wang, X}, title = {Escherichia coli triggers α-synuclein pathology in the LRRK2 transgenic mouse model of PD.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2276296}, doi = {10.1080/19490976.2023.2276296}, pmid = {38010914}, issn = {1949-0984}, abstract = {Alpha-synuclein (α-syn) pathology is the hallmark of Parkinson's disease (PD). The leucine-rich repeat kinase 2 (LRRK2) gene is a major-effect risk gene for sporadic PD (sPD). However, what environmental factors may trigger the formation of α-syn pathology in carriers of LRRK2 risk variants are still unknown. Here, we report that a markedly increased abundance of Escherichia coli (E. coli) in the intestinal microbiota was detected in LRRK2 risk variant(R1628P or G2385R) carriers with sPD compared with carriers without sPD. Animal experiments showed that E. coli administration triggered pathological α-syn accumulation in the colon and spread to the brain via the gut-brain axis in Lrrk2 R1628P mice, due to the co-occurrence of Lrrk2 variant-induced inhibition of α-syn autophagic degradation and increased phosphorylation of α-syn caused by curli in E. coli-derived extracellular vesicles. Fecal microbiota transplantation (FMT) effectively ameliorated motor deficits and α-syn pathology in Lrrk2 R1628P mice. Our findings elaborate on the mechanism that E. coli triggers α-syn pathology in Lrrk2 R1628P mice, and highlight a novel gene-environment interaction pattern in LRRK2 risk variants. Even more importantly, the findings reveal the interplay between the specific risk gene and the matched environmental factors triggers the initiation of α-syn pathology in sPD.}, } @article {pmid38010886, year = {2023}, author = {Garrett, S and Asada, MC and Sun, J}, title = {Axin1's mystique in manipulating microbiome amidst colitis.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2286674}, doi = {10.1080/19490976.2023.2286674}, pmid = {38010886}, issn = {1949-0984}, abstract = {Classically, Axin1 is considered a regulator of Wnt/β-catenin signaling. However, Axin1's roles in host-microbial interactions have been unknown. Our recent study has demonstrated that deletion of intestinal epithelial Axin1 in epithelial cells and Paneth cells protects the host against colitis by enhancing Akkermansia muciniphila. Loss of intestinal epithelial or Paneth cell Axin1 results in increased Wnt/β-catenin signaling, proliferation, and cell migration. This is associated with morphologically altered goblet and Paneth cells, including increased Muc2 and decreased lysozyme. Axin1 deletion specifically enriched Akkermansia muciniphila. Akkermansia muciniphila in Axin1 knockout mice is the driver of protection against DSS-induced inflammation. Here, we feature several significant conceptual changes, such as differences between Axin1 and Axin2, Axin1 in innate immunity and microbial homeostasis, and Axin1 reduction of Akkermansia muciniphila. We discuss an important trend in the field related to Paneth cells and tissue-specific Axin1 manipulation of microbiome in health and inflammation.}, } @article {pmid38010872, year = {2023}, author = {Ahmad, R and Kumar, B and Thapa, I and Talmon, GA and Salomon, J and Ramer-Tait, AE and Bastola, DK and Dhawan, P and Singh, AB}, title = {Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2282789}, doi = {10.1080/19490976.2023.2282789}, pmid = {38010872}, issn = {1949-0984}, abstract = {Dysregulation of both the gut barrier and microbiota (dysbiosis) promotes susceptibility to and severity of Inflammatory Bowel Diseases (IBD). Leaky gut and dysbiosis often coexist; however, potential interdependence and molecular regulation are not well understood. Robust expression of claudin-3 (CLDN3) characterizes the gut epithelium, and studies have demonstrated a positive association between CLDN3 expression and gut barrier maturity and integrity, including in response to probiotics. However, the exact status and causal role of CLDN3 in IBD and regulation of gut dysbiosis remain unknown. Analysis of mouse and human IBD cohorts helped examine CLDN3 expression in IBD. The causal role was determined by modeling CLDN3 loss of expression during experimental colitis. 16S sequencing and in silico analysis helped examine gut microbiota diversity between Cldn3KO and WT mice and potential host metabolic responses. Fecal microbiota transplant (FMT) studies were performed to assess the role of gut dysbiosis in the increased susceptibility of Cldn3KO mice to colitis. A significant decrease in CLDN3 expression characterized IBD and CLDN3 loss of expression promoted colitis. 16S sequencing analysis suggested gut microbiota changes in Cldn3KO mice that were capable of modulating fatty acid metabolism and oxidative stress response. FMT from naïve Cldn3KO mice promoted colitis susceptibility in recipient germ-free mice (GFM) compared with GFM-receiving microbiota from WT mice. Our data demonstrate a critical role of CLDN3 in maintaining normal gut microbiota and inflammatory responses, which can be harnessed to develop novel therapeutic opportunities for patients with IBD.}, } @article {pmid38010168, year = {2023}, author = {Ye, H and Ghosh, TS and Hueston, CM and Vlckova, K and Golubeva, AV and Hyland, NP and O'Toole, PW}, title = {Engraftment of aging-related human gut microbiota and the effect of a seven-species consortium in a pre-clinical model.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2282796}, doi = {10.1080/19490976.2023.2282796}, pmid = {38010168}, issn = {1949-0984}, abstract = {Human aging is characterized by gut microbiome alteration and differential loss of gut commensal species associated with the onset of frailty. The administration of cultured commensal strains to replenish lost taxa could potentially promote healthy aging. To investigate the interaction of whole microbiomes and administered strains, we transplanted gut microbiota from a frail or healthy elderly subject into germ-free mice. We supplemented the frail-donor recipient group with a defined consortium of taxa (the "S7") that we identified by analyzing healthy aging subjects in our previous studies and whose abundance correlated with health-promoting dietary intervention. Inoculation with a frail or a healthy donor microbiome resulted in differential microbiota compositions in murine recipients 5 weeks post-transplantation. Fecal acetate levels were significantly higher in healthy donor recipient mice than in frail donor recipient mice after 4 weeks. However, the frailty-related phenotype was not replicated in recipient mice with single-dose microbiota transplantation from a healthy and a frail donor. Five S7 species colonized successfully in germ-free mice, with a relatively high abundance of Barnesiella intestinihominis and Eubacterium rectale. The engraftment of five S7 species in germ-free mice increased fecal acetate levels and reduced colon permeability and plasma TNF-ɑ concentration. Supplementation with the S7 in frail-microbiota recipient mice did not increase alpha-diversity but significantly increased the abundance of Barnesiella intestinihominis. S7 supplementation showed the potential for improving spatial reference memory in frail-microbiota recipient mice. Collectively, these data highlight the challenge of elderly microbiota engraftment in the germ-free mouse model but show promise for modulating the gut microbiome of frail elderly subjects by administering an artificial gut microbe consortium associated with healthy aging.}, } @article {pmid38009301, year = {2023}, author = {Xiong, Y and He, Y and Chen, Z and Wu, T and Xiong, Y and Peng, Y and Yang, X and Liu, Y and Zhou, J and Zhou, H and Zhang, W and Shu, Y and Li, X and Li, Q}, title = {Lactobacillus induced by irbesartan on spontaneously hypertensive rat contribute to its antihypertensive effect.}, journal = {Journal of hypertension}, volume = {}, number = {}, pages = {}, doi = {10.1097/HJH.0000000000003613}, pmid = {38009301}, issn = {1473-5598}, abstract = {OBJECTIVE: Hypertension is linked to gut dysbiosis. Here, the impact of the angiotensin receptor antagonist irbesartan on the gut microbiota of spontaneously hypertensive rats (SHR) were investigated. In addition, we assessed their contribution to its antihypertensive effect.

METHODS: Eight-week-old Wistar-Kyoto (WKY) rats and SHR were administered irbesartan for 8 weeks. Fecal microbiota transplantation (FMT) was performed from SHR treated with irbesartan or untreated SHR to recipient untreated SHR. The preventive effect of Lactobacillus on hypertension in SHR was evaluated. Blood pressure (BP) was calculated using a tail-sleeve sphygmomanometer. To better assess the composition of the gut microbiota, the V3-V4 region of the 16S rRNA gene was amplified while short-chain fatty acids (SCFAs) in feces were tested by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).

RESULTS: Irbesartan restored gut dysbiosis, increased the abundance of Lactobacillus, and improved anti-inflammatory ability, antioxidative ability, intestinal integrity, and intestinal inflammation in SHR. The microbiota in SHR-treated irbesartan could reduce BP and improve antioxidative ability and gut integrity in SHR. Lactobacillus johnsonii (L. johnsonii) and Lactobacillus reuteri (L. reuteri) reduced BP, restored gut dysbiosis and improved anti-inflammatory ability, antioxidative ability, intestinal integrity in SHR. Most notably, irbesartan, L. johnsonii, and L. reuteri can significantly increase SCFA content in SHR feces.

CONCLUSION: The current study demonstrated that irbesartan treatment ameliorated gut dysbiosis in SHR. Irbesartan induced alterations in gut microbiota, with increased prevalence of Lactobacillus.}, } @article {pmid38009195, year = {2023}, author = {Hu, S and Zhou, J and Hao, J and Zhong, Z and Wu, H and Zhang, P and Yang, J and Guo, H and Chi, J}, title = {Emodin ameliorates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis through the remodeling of gut microbiota composition.}, journal = {American journal of physiology. Cell physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpcell.00477.2023}, pmid = {38009195}, issn = {1522-1563}, support = {No. 82174204//MOST | National Natural Science Foundation of China (NSFC)/ ; No. 81873120//MOST | National Natural Science Foundation of China (NSFC)/ ; }, abstract = {The relationship between gut microbiota and doxorubicin-induced cardiotoxicity (DIC) is becoming increasingly clear. Emodin (EMO), a naturally occurring anthraquinone, exerts cardioprotective effects and plays a protective role by regulating gut microbiota composition. Therefore, the protective effect of EMO against DIC injury and its underlying mechanisms are worth investigating. In this study, we analyzed the differences in the gut microbiota in recipient mice transplanted with different flora using 16S-rDNA sequencing, analyzed the differences in serum metabolites among groups of mice using a non-targeted gas chromatography-mass spectrometry coupling system, and assessed cardiac function based on cardiac morphological staining, cardiac injury markers, and ferroptosis indicator assays. We found EMO ameliorated DIC and ferroptosis, as evidenced by decreased myocardial fibrosis, cardiomyocyte hypertrophy, and myocardial disorganization; improved ferroptosis indicators; and the maintenance of normal mitochondrial morphology. The protective effect of EMO was eliminated by the scavenging effect of antibiotics on the gut microbiota. Through fecal microbiota transplantation (FMT), we found that EMO restored the gut microbiota disrupted by doxorubicin (DOX) to near-normal levels. This was evidenced by an increased proportion of Bacteroidota and a decreased proportion of Verrucomicrobiota. FMT resulted in changes in the composition of serum metabolites. Mice transplanted with EMO-improved gut microbiota showed better cardiac function and ferroptosis indices; however, these beneficial effects were not observed in Nrf2[-/-] mice. Overall, EMO exerted a protective effect against DIC by attenuating ferroptosis, and the above effects occurred by remodeling the composition of gut microbiota perturbed by DOX and required Nrf2 mediation.}, } @article {pmid38007451, year = {2023}, author = {Ma, J and Zhou, M and Song, Z and Deng, Y and Xia, S and Li, Y and Huang, X and Xiao, D and Yin, Y and Yin, J}, title = {Clec7a drives gut fungus-mediated host lipid deposition.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {264}, pmid = {38007451}, issn = {2049-2618}, support = {2022YFD1301500//National Key Research and Development Program of China/ ; 32172761//National Natural Science Foundation of China/ ; CARS-37//Earmarked Fund for China Agriculture Research System/ ; }, mesh = {Humans ; Animals ; Mice ; Swine ; *Antifungal Agents ; *Obesity/metabolism ; Diet, High-Fat/adverse effects ; Lipids ; Fungi ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Compared to that of bacteria, the role of gut fungi in obesity development remains unknown.

RESULTS: Here, alterations in gut fungal biodiversity and composition were confirmed in obese pig models and high-fat diet (HFD)-fed mice. Antifungal drugs improved diet-induced obesity, while fungal reconstruction by cohousing or fecal microbiota transplantation maintained the obese phenotype in HFD-fed mice. Fungal profiling identified 5 fungal species associated with obesity. Specifically, Ascomycota_sp. and Microascaceae_sp. were reduced in obese mice and negatively correlated with fat content. Oral supplementation with fungi was sufficient to prevent and treat diet-induced obesity. Clec7a, which is involved in fungal recognition, was highly expressed in HFD-fed mice. The Clec7a agonist accelerated diet-induced obesity, while Clec7a deficieny in mice resulted in resistance to diet-induced obesity and blocked the anti-obese effect of antifungal drugs and fungi.

CONCLUSIONS: Taken together, these results indicate that gut fungi/Clec7a signaling is involved in diet-induced obesity and may have therapeutic implications as a biomarker for metabolic dysregulation in humans. Video Abstract.}, } @article {pmid38004817, year = {2023}, author = {Parigi, TL and Vieujean, S and Paridaens, K and Dalgaard, K and Peyrin-Biroulet, L and Danese, S}, title = {Efficacy, Safety, and Concerns on Microbiota Modulation, Antibiotics, Probiotics, and Fecal Microbial Transplant for Inflammatory Bowel Disease and Other Gastrointestinal Conditions: Results from an International Survey.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004817}, issn = {2076-2607}, abstract = {The gut microbiota play a pivotal role in human health. Dysbiosis, alterations in microbiota composition and function, is associated with gastrointestinal disorders, including inflammatory bowel disease (IBD). This international survey aimed to assess physicians' experiences, perceptions, and practices related to microbiome modulation for gastrointestinal conditions, with a focus on IBD. Results from 142 healthcare professionals, predominantly gastroenterologists, confirmed a consensus on the relevance of the gut microbiota in IBD pathogenesis. However, the utilization of microbial composition analysis and probiotics in clinical practice was limited, primarily due to the lack of standardized guidelines and supporting evidence. Physicians held conflicting views on antibiotics, recognizing their potential for inducing remission but also causing flares in IBD. Respondents also had varying opinions on the efficacy of fecal microbiota transplantation (FMT) for different gastrointestinal conditions, with higher confidence in FMT effectiveness for irritable bowel syndrome with diarrhea, pouchitis, and ulcerative colitis. Concerns on FMT included uncertainty about effect duration, administration intervals, and conflicting evidence. Donor selection was believed to be a crucial factor in FMT outcomes. This survey highlights the need for further research and evidence-based guidelines to optimize the use of microbiome-based therapies in clinical practice. As our understanding of the gut microbiome continues to evolve, these insights will contribute to more informed and personalized approaches to managing gastrointestinal disorders.}, } @article {pmid38004765, year = {2023}, author = {Salandre, A and Delannoy, J and Goudiaby, MTB and Barbut, F and Thomas, M and Waligora-Dupriet, AJ and Kapel, N}, title = {A Simple In Vitro Test to Select Stools for Fecal Microbiota Transplantation to Limit Intestinal Carriage of Extensively Drug-Resistant Bacteria.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004765}, issn = {2076-2607}, abstract = {Treatment options for multidrug-resistant bacterial infections are limited and often ineffective. Fecal microbiota transplantation (FMT) has emerged as a promising therapy for intestinal multidrug-resistant bacterial decolonization. However, clinical results are discrepant. The aim of our pilot study was to evaluate the screening performance of a simple diagnostic tool to select fecal samples that will be effective in decolonizing the intestine. Fecal samples from 10 healthy subjects were selected. We developed an agar spot test to evaluate their antagonistic activity toward the growth of VanA Enterococcus faecium and OXA-48-producing Klebsiella pneumoniae, two of the most serious and urgent threats of antibiotic resistance. Most fecal samples were able to limit the growth of both bacteria in vitro but with large inter-individual variation. The samples with the highest and lowest antagonistic activity were used for FMT in a mouse model of intestinal colonization. FMT was not successful in reducing intestinal colonization with VanA Enterococcus faecium, whereas FMT performed with the fecal sample showing the highest activity on the agar spot test was able to significantly reduce the intestinal colonization of mice with Klebsiella pneumoniae OXA-48. The agar spot test could thus serve as a reliable screening tool to select stool samples with the best potential to eradicate/reduce multidrug-resistant bacteria carriage after FMT.}, } @article {pmid38004758, year = {2023}, author = {Yan, P and Luo, S and Guo, L and Wang, X and Ren, X and Lv, J and Chen, Y and Lin, X and Chen, J and Wang, R}, title = {Unraveling Intestinal Microbial Shifts in ESRD and Kidney Transplantation: Implications for Disease-Related Dysbiosis.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004758}, issn = {2076-2607}, support = {82070766//National Natural Science Foundation of China/ ; 2022RC147//Medical Health Science and Technology Project of Zhejiang Provincial Health Commission/ ; LQ23H050003//Zhejiang Provincial Natural Science Foundation of China/ ; }, abstract = {The composition of the gut microbiome is profoundly influenced by the accumulation of toxins in end-stage renal disease (ESRD) and specific medical treatments during kidney transplantation (KT). However, variations in results may arise due to factors such as genetics, dietary habits, and the strategy of anti-rejection therapy. Therefore, we conducted a 16S rRNA sequencing study to characterize intestinal microbiomes by using 75 fecal specimens obtained from 25 paired Chinese living donors (LDs) of kidneys and recipients before and after KT. Surprisingly, similar enterotypes were observed between healthy LDs and ESRD recipients. Nonetheless, following KT, the fecal communities of recipients exhibited distinct clustering, which was primarily characterized by Escherichia-Shigella and Streptococcus at the genus level, along with a reduction in the diversity of microbiota. To further explore the characteristics of gut microorganisms in early rejection episodes, two recipients with biopsy-proven borderline changes during follow-up were enrolled in a preliminary sub-cohort study. Our findings reveal a comparable construction of gut microbiota between ESRD patients and their healthy relatives while also highlighting the significant impact of KT on gut microbial composition.}, } @article {pmid38004180, year = {2023}, author = {Zhou, J and Ho, V}, title = {Role of Baseline Gut Microbiota on Response to Fiber Intervention in Individuals with Irritable Bowel Syndrome.}, journal = {Nutrients}, volume = {15}, number = {22}, pages = {}, pmid = {38004180}, issn = {2072-6643}, support = {Investigator Initiated Funding Scheme//Nestlé Foundation/ ; }, mesh = {Humans ; *Irritable Bowel Syndrome/therapy ; *Gastrointestinal Microbiome/physiology ; Feces ; *Microbiota ; Fecal Microbiota Transplantation ; }, abstract = {Irritable bowel syndrome (IBS) is one of the most prevalent functional gut disorders in the world. Partially hydrolyzed guar gum, a low-viscosity soluble fiber, has shown promise in the management of IBS-related symptoms. In this study, we aimed to determine if an individual's baseline gut microbiota impacted their response to a partially hydrolyzed guar gum intervention. Patients diagnosed with IBS undertook a 90-day intervention and follow-up. IBS symptom severity, tolerability, quality-of-life, and fecal microbiome composition were recorded during this study. Patients with normal microbiota diversity (Shannon index ≥ 3) showed significant improvements to IBS symptom scores, quality-of-life, and better tolerated the intervention compared to patients with low microbiota diversity (Shannon index < 3). Our findings suggest that an individual's baseline microbiome composition exerts a substantial influence on their response to fiber intervention. Future investigations should explore a symbiotic approach to the treatment of IBS.}, } @article {pmid38004128, year = {2023}, author = {He, S and Lin, F and Hu, X and Pan, P}, title = {Gut Microbiome-Based Therapeutics in Critically Ill Adult Patients-A Narrative Review.}, journal = {Nutrients}, volume = {15}, number = {22}, pages = {}, pmid = {38004128}, issn = {2072-6643}, support = {z047-02//The national key clinical specialist construction programs of China/ ; }, mesh = {Humans ; Adult ; *Gastrointestinal Microbiome/physiology ; Critical Illness/therapy ; *Microbiota/physiology ; Fecal Microbiota Transplantation/adverse effects ; Prognosis ; Dysbiosis/therapy/etiology ; }, abstract = {The gut microbiota plays a crucial role in the human microenvironment. Dysbiosis of the gut microbiota is a common pathophysiological phenomenon in critically ill patients. Therefore, utilizing intestinal microbiota to prevent complications and improve the prognosis of critically ill patients is a possible therapeutic direction. The gut microbiome-based therapeutics approach focuses on improving intestinal microbiota homeostasis by modulating its diversity, or treating critical illness by altering the metabolites of intestinal microbiota. There is growing evidence that fecal microbiota transplantation (FMT), selective digestive decontamination (SDD), and microbiota-derived therapies are all effective treatments for critical illness. However, different treatments are appropriate for different conditions, and more evidence is needed to support the selection of optimal gut microbiota-related treatments for different diseases. This narrative review summarizes the curative effects and limitations of microbiome-based therapeutics in different critically ill adult patients, aiming to provide possible directions for gut microbiome-based therapeutics for critically ill patients such as ventilator-associated pneumonia, sepsis, acute respiratory distress syndrome, and COVID-19, etc.}, } @article {pmid38002138, year = {2023}, author = {Xiao, N and Ruan, S and Mo, Q and Zhao, M and Feng, F}, title = {The Effect of Sodium Benzoate on Host Health: Insight into Physiological Indexes and Gut Microbiota.}, journal = {Foods (Basel, Switzerland)}, volume = {12}, number = {22}, pages = {}, doi = {10.3390/foods12224081}, pmid = {38002138}, issn = {2304-8158}, support = {32072224,32001693 and 32172214//National Natural Science Foundation of China/ ; LD19C200001and LQ21C200007//Zhejiang Provincial Natural Science Foundation/ ; }, abstract = {Sodium benzoate (SB) is a common food preservative widely used in the food industry. However, the effects of SB intake on host health at different stages were still unclear. Hence, we investigated the impact of SB with three concentrations (150 mg/kg, 500 mg/kg and 1000 mg/kg) and at three stages (intake for 5-weeks, intake for 10-weeks and removal for 5 weeks) on host health in normal mice. The results showed that SB intake for 5 weeks slightly changed gut microbiota composition, but it significantly increased TG (only 150 mg/kg and 1000 mg/kg) and blood glucose levels (only 500 mg/kg) and promoted the secretion of interleukin (IL)-1β and IL-6 (p < 0.01). However, SB intake for 10 weeks mostly maintained normal glucolipid metabolism; although, IL-1β (p < 0.01) and IL-6 (p < 0.05) levels were also significantly increased and positively regulated the gut microbiota by significantly increasing the relative abundance of Lactobacillus and significantly decreasing the relative abundance of Ileibacterium. Meanwhile, the safety of SB for host metabolism and gut microbiota was also confirmed via a fecal microbiota transplantation experiment. In addition, we found that SB removal after 10 weeks of intake significantly increased the levels of blood glucose, insulin and HOMA-IR index, which might be attributed to gut microbiota dysbiosis. Mechanistically, these positive effects and negative effects had no close relationship with the concentration of short-chain fatty acids in the gut, which might be associated with metabolites of SB or special bacterial strains. In short, this work provided positive evidence for the safety of SB consumption within the recommended range.}, } @article {pmid38001930, year = {2023}, author = {Boicean, A and Birlutiu, V and Ichim, C and Brusnic, O and Onișor, DM}, title = {Fecal Microbiota Transplantation in Liver Cirrhosis.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, doi = {10.3390/biomedicines11112930}, pmid = {38001930}, issn = {2227-9059}, abstract = {The human gastrointestinal tract houses a diverse array of probiotic and pathogenic bacteria and any alterations in this microbial composition can exert a significant influence on an individual's well-being. It is well-established that imbalances in the gut microbiota play a pivotal role in the development of liver diseases. In light of this, a new adjuvant therapy for liver diseases could be regulating the intestinal microbiota. Through fecal microbiota transplantation, patients whose microbiomes are compromised are treated with stool from healthy donors in an attempt to restore a normal microbiome and alleviate their symptoms. A review of cross-sectional studies and case reports suggests that fecal microbiota transplants may offer effective treatment for chronic liver diseases. Adding to the potential of this emerging therapy, recent research has indicated that fecal microbiota transplantation holds promise as a therapeutic approach specifically for liver cirrhosis. By introducing a diverse range of beneficial microorganisms into the gut, this innovative treatment aims to address the microbial imbalances often observed in cirrhotic patients. While further validation is still required, these preliminary findings highlight the potential impact of fecal microbiota transplantation as a novel and targeted method for managing liver cirrhosis. We aimed to summarize the current state of understanding regarding this procedure, as a new therapeutic method for liver cirrhosis, as well as to explain its clinical application and future potential.}, } @article {pmid38001551, year = {2023}, author = {Xu, H and Fang, F and Wu, K and Song, J and Li, Y and Lu, X and Liu, J and Zhou, L and Yu, W and Yu, F and Gao, J}, title = {Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {262}, pmid = {38001551}, issn = {2049-2618}, support = {32001696//National Natural Science Foundation of China/ ; 2021AC19445//Specific Research Project of Guangxi for Research Bases and Talents/ ; }, abstract = {BACKGROUND: Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipidemic donors (FMT-dd) to study the causal role of gut microbiota in diet-induced dyslipidemia.

RESULTS: We demonstrated that FMT-dd reshaped the gut microbiota of mice by increasing Faecalibaculum and Ruminococcaceae UCG-010, which then elevated serum cholicacid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA), reduced bile acid synthesis and increased cholesterol accumulation via the hepatic farnesoid X receptor-small heterodimer partner (FXR-SHP) axis. Nevertheless, high-fat diet led to decreased Muribaculum in the humanized dyslipidemia mice induced by FMT-dd, which resulted in reduced intestinal hyodeoxycholic acid (HDCA), raised bile acid synthesis and increased lipid absorption via the intestinal farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis.

CONCLUSIONS: Our studies implicated that intestinal FXR is responsible for the regulation of lipid metabolism in diet-induced dyslipidemia mediated by gut microbiota-bile acid crosstalk. Video Abstract.}, } @article {pmid38001323, year = {2023}, author = {Yang, Y and Yan, J and Li, S and Liu, M and Han, R and Wang, Y and Wang, Z and Wang, D}, title = {Efficacy of fecal microbiota transplantation in type 2 diabetes mellitus: a systematic review and meta-analysis.}, journal = {Endocrine}, volume = {}, number = {}, pages = {}, pmid = {38001323}, issn = {1559-0100}, support = {(No.[2020] No.23)//Project Fund of Clinical Medicine Excellent Talents funded by Hebei Provincial Department of Finance (No.: [2020] No.23);/ ; (No.[2020] No.23)//Project Fund of Clinical Medicine Excellent Talents funded by Hebei Provincial Department of Finance (No.: [2020] No.23);/ ; }, abstract = {OBJECTIVE: Type 2 diabetes mellitus (T2DM) is one of the common metabolic diseases worldwide, and studies have found significant differences in the composition and ratio of intestinal flora between patients with T2DM and normal glucose tolerance, and fecal microbiota transplantation (FMT) may modulate the composition of the intestinal microbiota thereby alleviating the hyperglycemic state. We conducted a meta-analysis and systematic review of existing randomized controlled trials (RCTs) to assess the efficacy of FMT in T2DM.

METHODS: We conducted a computer search of PubMed, Embase, The Cochrane Library, and Web of Science to screen randomized controlled trials studies on FMT treatment for T2DM and extracted data from studies that met inclusion criteria. RevMan 5.4 software and Stata 11 software was used for meta-analysis. The indexes of Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), body mass index (BMI), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) were mainly evaluated after FMT treatment of T2DM patients, and the changes of intestinal flora were evaluated.

RESULTS: Four RCTs met the inclusion criteria and were included in the meta-analysis. Results of the meta-analysis showed that compared with the non-FMT group, FMT combined treatment could significantly reduce the PBG level in patients with type 2 diabetes (MD = -0.51, 95% CI: -1.42-0.40, P = 0.27). Compared with single FMT treatment, FMT combined treatment could reduce TG levels in patients with type 2 diabetes (MD = -0.60, 95% CI: -1.12~-0.07, P = 0.03). The levels of TG (MD = -0.26, 95% CI: -0.51~-0.02, P = 0.03), HOMA-IR (MD = -2.73, 95% CI: -4.71~0.75, P = 0.007) and HDL (MD = -0.06,95% CI: -0.10~-0.02, P = 0.003) were significantly decreased after treatment in the single FMT group. The level of TC (MD = -0.65, 95% CI: -1.00~-0.31, P = 0.0002) was significantly decreased after FMT combined treatment. Compared with before treatment, ALT (MD = -2.52, 95% CI: -3.86~-1.17, P = 0.0002) and DBP (MD = -2, 95% CI: -3.32~0.68, P = 0.003) levels decreased after treatment in the single FMT group and the FMT combined group. FPG (MD = -0.94, 95% CI: -1.86~-0.02, P = 0.04), TG (MD = -0.73, 95% CI: -1.42~-0.04, P = 0.04) and TC (MD = -0.94, 95% CI: -1.45~-0.43, P = 0.0003) were significantly decreased after combined drug and diet therapy. Secondly, FMT can promote the colonization and growth of donor-related flora in patients with type 2 diabetes.

CONCLUSION: In patients with type 2 diabetes mellitus, FMT treatment can reduce the levels of PBG, TG, HOMA-IR, TC, ALT, and DBP, especially in the combined treatment regimen. In addition, FMT can reshape the intestinal flora and establish the balance of dominant flora.}, } @article {pmid38000189, year = {2023}, author = {de-Mendoza, C and Pérez, L and Rando, A and Reina, G and Aguilera, A and Benito, R and Eirós, JM and Rodríguez-Avial, I and Ortega, D and Pozuelo, MJ and Pena, MJ and Soriano, V and , }, title = {HTLV-1-associated myelopathy in Spain.}, journal = {Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology}, volume = {169}, number = {}, pages = {105619}, doi = {10.1016/j.jcv.2023.105619}, pmid = {38000189}, issn = {1873-5967}, abstract = {BACKGROUND: HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1 carriers develop HTLV-1-associated myelopathy (HAM), a progressive subacute neurological disabling disease.

METHODS: We report the main features of patients diagnosed with HAM up to date in Spain, a non-endemic country with a relatively high migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic.

RESULTS: A total of 451 cases of HTLV-1 had been recorded in Spain until the end of year 2022. HAM had been diagnosed in 58 (12.9%). The current incidence is of 2-3 new cases per year. Women represent 76%. Mean age at diagnosis is 49 years-old. Nearly 60% are Latin Americans. Although sexual transmission is the most likely route of HTLV-1 acquisition, up to 6 individuals had been infected following solid organ transplantation. Rapid onset myelopathy developed in all but one of these transplant recipients from three HTLV-1-positive donors. HTLV-1 subtype 1a transcontinental was the only variant recognized in HAM patients. HTLV-1 proviral load was significantly greater in HAM patients than in asymptomatic HTLV-1 carriers (677 vs 104 HTLV-1 DNA copies/10[4] PBMC; p = 0.012). Symptom relief medications and physiotherapy have been the only treatment providing some benefit to HAM patients. Neither significant clinical nor virological efficacy was noticed using antiretrovirals in at least 9 HAM patients. Two thirds of HAM patients ended up in a wheelchair and with urinary/fecal sphincter incontinence.

CONCLUSION: HAM is the most frequent clinical manifestation of HTLV-1 infection in Spain, a non-endemic country. Middle aged women migrants from Latin America are the most frequently affected. Two thirds end up in a wheelchair despite using antiretroviral therapy.}, } @article {pmid37999101, year = {2023}, author = {Duttagupta, S and Hakozaki, T and Routy, B and Messaoudene, M}, title = {The Gut Microbiome from a Biomarker to a Novel Therapeutic Strategy for Immunotherapy Response in Patients with Lung Cancer.}, journal = {Current oncology (Toronto, Ont.)}, volume = {30}, number = {11}, pages = {9406-9427}, pmid = {37999101}, issn = {1718-7729}, abstract = {The gastrointestinal microbiome has been shown to play a key role in determining the responses to cancer immunotherapy, including immune checkpoint inhibitor (ICI) therapy and CAR-T. In patients with non-small cell lung cancer (NSCLC), increasing evidence suggests that a microbiome composition signature is associated with clinical response to ICIs as well as with the development of immune-related adverse events. In support of this, antibiotic (ATB)-related dysbiosis has been consistently linked with the deleterious impact of ICI response, shortening the overall survival (OS) among patients on ATBs prior to ICI initiation. In parallel, several preclinical experiments have unravelled various strategies using probiotics, prebiotics, diet, and fecal microbiota transplantation as new therapeutic tools to beneficially shift the microbiome and enhance ICI efficacy. These approaches are currently being evaluated in clinical trials and have achieved encouraging preliminary results. In this article, we reviewed the recent studies on the gut microbiome as a potential biomarker and an adjuvant therapy to ICIs in NSCLC patients.}, } @article {pmid37998819, year = {2023}, author = {DuPont, HL and Salge, MMH}, title = {The Importance of a Healthy Microbiome in Pregnancy and Infancy and Microbiota Treatment to Reverse Dysbiosis for Improved Health.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {37998819}, issn = {2079-6382}, abstract = {BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.

METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).

RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during pregnancy, cesarean delivery, prematurity, and formula feeding contribute to dysbiosis in the newborn. Microbiota therapy is an important approach to repair dysbiosis in pregnant women and their infants. Currently available probiotics can have favorable metabolic effects on mothers and infants, but these effects are variable. In research settings, reversal of infant dysbiosis can be achieved via vaginal seeding or FMT. Next generation probiotics in development should replace current probiotics and FMT.

CONCLUSIONS: The most critical phase of human microbiome development is in the first 2-3 years of life. Preventing and treating dysbiosis during pregnancy and early life can have a profound effect on an infant's later health.}, } @article {pmid37996087, year = {2023}, author = {Chen, YF and Li, SC and Huang, EY}, title = {Role of microbiota in radiation-induced small-bowel damage.}, journal = {Journal of radiation research}, volume = {}, number = {}, pages = {}, doi = {10.1093/jrr/rrad084}, pmid = {37996087}, issn = {1349-9157}, support = {CORPG8K0161//Kaohsiung Chang Gung Medical Research Project/ ; }, abstract = {Radiation-induced gastrointestinal damage is a common acute radiation syndrome. Previous studies have highlighted that Galectin-1 and Interleukin-6 (IL-6) are associated with flaking of small intestinal villi and intestinal radioresistance. Therefore, our goal is to study whether gut bacteria regulated by galectin-1 or IL-6 can mitigate radiation-induced small intestine damage. In this study, differences between galectin-1, sgp130-regulated and wild-type (WT) mice were analyzed by microbiome array. The effects of the Firmicutes/Bacteroidetes (F/B) ratio and the proportion of bacterial distribution at the phylum level were observed after 18 Gy whole abdomen radiation. Fecal microbiota transplantation was used to implant radioresistant gut flora into WT mice, and the number of viable small intestinal crypt foci was observed by immunohistochemistry. Fecal transplantation from galectin-1 knockout and sgp130 transgenic mice, with higher radiation resistance, into WT mice significantly increased the number of surviving small intestinal crypts. This radiation resistance, generated through gene regulation, was not affected by the F/B ratio. We initially found that the small intestinal villi of WT mice receiving radioresistant mouse fecal bacteria demonstrated better repair outcomes after radiation exposure. These results indicate the need for a focus on the identification and application of superior radioresistant bacterial strains. In our laboratory, we will further investigate specific radioresistant bacterial strains to alleviate acute side effects of radiation therapy to improve the patients' immune ability and postoperative quality of life.}, } @article {pmid37995723, year = {2023}, author = {Distante, M and Rotulo, S and Ranalli, M and Pedace, E and Lionetti, P and Arrigo, S and Alvisi, P and Miele, E and Martinelli, M and Zuin, G and Bramuzzo, M and Cananzi, M and Aloi, M and , }, title = {Clusters of Disease Activity and Early Risk Factors of Clinical Course of Pediatric Crohn's Disease.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izad275}, pmid = {37995723}, issn = {1536-4844}, abstract = {BACKGROUND: This study aimed to define clusters of disease activity and prognostic factors of disease course in a well-characterized cohort of children with Crohn's disease (CD).

METHODS: All patients from the SIGENP IBD (Italian Society of Pediatric Gastroenterology Hepatology and Nutrition Inflammatory Bowel Disease) registry with a 5-year follow-up and 6-monthly evaluation were included. Active disease was defined for each semester as follows: clinical activity (weighted Pediatric Crohn's Disease Activity Index ≥12.5 or Mucosal Inflammation Noninvasive Index ≥8) and active disease on endoscopy (Simple Endoscopic Score for Crohn's Disease >3 or fecal calprotectin >250 µg/g) or imaging. Formula-based clusters were generated based on previously published patterns in adults.

RESULTS: Data from 332 patients were analyzed. A total of 105 (32%) experienced a quiescent disease course; 49 (15%) and 31 (9%) a moderate-to-severe chronically active and chronic intermittent disease, respectively; 104 (31%) and 43 (13%) had active disease in the first 2 years after diagnosis and remission thereafter and vice versa, respectively. Surgery at diagnosis was significantly associated with a quiescent course (odds ratio [OR], 10.05; 95% confidence interval [CI], 3.05-25.22; P=.0005), while growth impairment at the diagnosis and active disease requiring corticosteroids at 6 months were inversely related to the quiescent group (OR, 0.48; 95% CI, 0.27-0.81; P= .007; and OR, 0.35; 95% CI, 0.16-0.71; P= .005, respectively). Perianal involvement at diagnosis and moderate-severe activity at 6 months correlated with disease progression (OR, 3.85; 95% CI, 1.20-12.85; P=.02).

CONCLUSIONS: During the first 5 years of follow-up, one-third of children with CD experience a quiescent course. However, another one-third have a moderate-to-severe disease course. Surgery at the diagnosis is related to a quiescent course, while growth impairment and lack of response to induction therapy correlate with more severe disease activity during follow-up.}, } @article {pmid37993541, year = {2023}, author = {Li, Z and Zhang, X and Wu, H and Ma, Z and Liu, X and Ma, J and Zhang, D and Sheng, L and Chen, X and Zhang, S}, title = {Hydrangea paniculata coumarins attenuate experimental membranous nephritis by bidirectional interactions with the gut microbiota.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {1189}, pmid = {37993541}, issn = {2399-3642}, mesh = {Rats ; Animals ; *Gastrointestinal Microbiome ; Coumarins/pharmacology ; *Hydrangea ; Dysbiosis ; *Endotoxemia ; *Nephritis ; }, abstract = {Coumarins isolated from Hydrangea paniculata (HP) had a renal protective effect in experimental membranous nephritis (MN), but the mechanisms are not clear. Currently, we investigate whether the modulation of gut dysbiosis by HP contributes to its renal protection. Experimental MN rats were treated with HP for six weeks. Fecal 16S rDNA sequencing and metabolomics were performed. Fecal microbiota transplantation (FMT) was used for the evaluation study. The results demonstrate that deteriorated renal function and gut dysbiosis are found in MN rats, as manifested by a higher Firmicutes/Bacteroidetes ratio and reduced diversity and richness, but both changes were reversed by HP treatment. Reduced gut dysbiosis is correlated with improved colonic integrity and lower endotoxemia in HP-treated rats. HP normalized the abnormal level of fecal metabolites by increasing short-chain fatty acid production and hindering the production of uremic toxin precursors. FMT of HP-treated feces to MN animals moderately reduced endotoxemia and albuminuria. Moreover, major coumarins in HP were only biotransformed into more bioactive 7-hydroxycoumarin by gut microbiota, which strengthened the effect of HP in vivo. Depletion of the gut microbiota partially abolished its renal protective effect. In conclusion, the bidirectional interaction between HP and the gut microbiota contributes to its beneficial effect.}, } @article {pmid37992712, year = {2023}, author = {Zhang, C and Yu, L and Ma, C and Jiang, S and Zhang, Y and Wang, S and Tian, F and Xue, Y and Zhao, J and Zhang, H and Liu, L and Chen, W and Huang, S and Zhang, J and Zhai, Q}, title = {A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2023.10.011}, pmid = {37992712}, issn = {1934-6069}, abstract = {Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria, can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B. longum, but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA-dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA-cluster-carrying B. longum, but not an abfA-deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA-cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies.}, } @article {pmid37992400, year = {2023}, author = {Qian, X and Hai, W and Chen, S and Zhang, M and Jiang, X and Tang, H}, title = {Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2282790}, doi = {10.1080/19490976.2023.2282790}, pmid = {37992400}, issn = {1949-0984}, mesh = {Mice ; Animals ; Amyloid beta-Protein Precursor/genetics/metabolism ; Mice, Transgenic ; Neuroinflammatory Diseases ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Multiomics ; Positron Emission Tomography Computed Tomography ; *Alzheimer Disease/complications ; Glycerophospholipids ; Disease Models, Animal ; }, abstract = {Numerous studies have described the notable impact of gut microbiota on the brain in Alzheimer's disease (AD) via the gut - brain axis. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of AD are limited. This study aimed to explore the potential mechanisms of gut microbiota in AD by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months of age were used as study mouse model. Cognitive function was assessed using the Morris water maze test. The levels of Aβ plaque and neuroinflammation in the brain were detected using immunofluorescence and PET/CT. In addition, we not only used 16S rRNA gene sequencing and metabolomics to explore the variation characteristics of gut microbiota and serum metabolism abundance, but also combined spatial metabolomics and transcriptomics to explore the change in the brain and identify their potential correlation. APP/PS1 mice showed significant cognitive impairment and amyloid-β deposits in the brain. The abundance of gut microbiota was significantly changed in APP/PS1 mice, including decreased Desulfoviobrio, Enterococcus, Turicibacter, and Ruminococcus and increased Pseudomonas. The integration of serum untargeted metabolomics and brain spatial metabolomics showed that glycerophospholipid metabolism was a common alteration pathway in APP/PS1 mice. Significant proliferation and activation of astrocyte and microglia were observed in APP/PS1 mice, accompanied by alterations in immune pathways. Integration analysis and fecal microbiota transplantation (FMT) intervention revealed potential association of gut microbiota, host glycerophospholipid metabolism, and neuroinflammation levels in APP/PS1 mice.}, } @article {pmid37992054, year = {2023}, author = {Zhang, M and Yang, T and Li, R and Ren, K and Li, J and He, M and Chen, J and Yi, SQ}, title = {Gut microbiota of Suncus murinus, a naturally obesity-resistant animal, improves the ecological diversity of the gut microbiota in high-fat-diet-induced obese mice.}, journal = {PloS one}, volume = {18}, number = {11}, pages = {e0293213}, pmid = {37992054}, issn = {1932-6203}, abstract = {BACKGROUND: The global population of obese individuals is increasing, affecting human health. High-fat diets are a leading cause of this epidemic, and animal models, such as mice, are often used in related research. Obese individuals have a different gut microbiota composition from non-obese ones, characterized by a sizeable population of certain bacteria associated with fat storage. The gut microbiome plays a significant role in regulating human physiological and metabolic functions. Links between obesity, high-fat diets and gut microbiota have become hot topics of discussion. Recently, research on the modulation of the gut microbiota has focused on fecal microbiota transplantation (FMT), which has been recognized as an effective method of studying the function of gut microbiota.

OBJECTIVES: The purpose of this study was to investigate how the gut microbiota of Suncus murinus, a naturally obesity-resistant animal, through FMT, affected the ecology of the gut microbiota of high-fat diet induced obese mice.

METHODS: In this study, Suncus murinus was used as a donor for FMT. High-fat diet induced C57BL/6NCrSIc mice were used as recipients, the body weight changes were measured and changes in their gut flora were analyzed using a 16S rRNA gene analysis.

RESULTS: The study found that, after the FMT procedure, the FMT group tended to have a lower body weight than the control group. At the phylum level, the most predominant phyla in all groups were Firmicutes and Proteobacteria, while Deferribacteres was not detected in the FMT or antibiotic administration groups, and Bacteroidetes was not present in the antibiotic administration group. At the genus level, the FMT group had significantly lower OTU richness than the control group but greater diversity than the control group.

CONCLUSIONS: These results indicate that FMT from Suncus murinus can help reorganize and improve the gut microbiota of mice in a balanced and diverse ecosystem.}, } @article {pmid37990909, year = {2023}, author = {Boatman, S and Kaiser, T and Nalluri-Butz, H and Khan, MH and Dietz, M and Kohn, J and Johnson, AJ and Gaertner, WB and Staley, C and Jahansouz, C}, title = {Diet-induced shifts in the gut microbiota influence anastomotic healing in a murine model of colonic surgery.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2283147}, doi = {10.1080/19490976.2023.2283147}, pmid = {37990909}, issn = {1949-0984}, abstract = {Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.}, } @article {pmid37988085, year = {2023}, author = {Zhang, S and Huang, Y and Lu, G and Zhang, Z and Wang, Y and Liu, Y and Wang, W and Li, Q and Li, P and Wen, Q and Cui, B and Zhang, F}, title = {Comparison between washed microbiota transplantation and infliximab: Medical cost during long-term management in patients with inflammatory bowel disease.}, journal = {Journal of the Chinese Medical Association : JCMA}, volume = {}, number = {}, pages = {}, doi = {10.1097/JCMA.0000000000001025}, pmid = {37988085}, issn = {1728-7731}, abstract = {BACKGROUND: Both infliximab (IFX) and fecal microbiota transplantation (FMT) have shown the efficacy for inflammatory bowel disease (IBD). However, there has no head-to-head study on the cost-value of the such treatments on IBD. This study aimed to compare the medical costs using IFX and the new method of FMT (washed microbiota transplantation, WMT) in the long-term management for IBD under the current health economic condition in China.

METHODS: Patients with IBD who underwent initial WMT via upper gastrointestinal endoscopy, mid-gut tube, or colonic transendoscopic enteral tubing at a university hospital between April 2013 and August 2021 and achieved the long-term sustainment with WMT or WMT combined with mesalazine until August 2022 were recruited in the real-world. The costs and hospitalizations were analyzed among two therapies mentioned above and IFX standard therapy. The charge of WMT was stable in the long term at our center, and the charge of IFX came from virtual statistics publicized by China Healthcare Security.

RESULTS: 60 eligible patients with IBD were included in the study. The long-term costs of patients using WMT monotherapy annually or per hospitalization were lower than those on WMT combined with mesalazine respectively (p < 0.001, respectively). The cumulative costs of IFX at the time of 0.52 and 0.85 years exceeded that of the above WMT respectively (p < 0.001, respectively). Besides, patients on WMT monotherapy paid 51.1k CNY annually in the non-sustain phase but cut down the costs by 7.2k CNY and duration of hospitalization by 5.1 days per hospitalization when reaching the goal of sustainment.

CONCLUSION: This study demonstrated that WMT could dramatically reduce the cost and duration of hospitalizations in the long-term sustainment in the current Chinese IBD cohort. Compared with IFX, WMT could be a good way for the patients with IBD achieving long-term sustainment and saving medical costs.}, } @article {pmid37986824, year = {2023}, author = {Berryhill, BA and Burke, KB and Fontaine, J and Brink, CE and Harvill, MG and Goldberg, DA and Konstantinidis, KT and Levin, BR and Woodworth, MH}, title = {Enteric Populations of Escherichia coli are Likely to be Resistant to Phages Due to O Antigen Production.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.11.08.566299}, pmid = {37986824}, abstract = {UNLABELLED: Bioinformatic and experimental data show that bacteriophages are ubiquitous in human enteric microbiomes. However, there are gaps in understanding the contribution of these viruses in shaping the bacterial strain and species composition of the gut microbiome and how these phages are maintained over time. To address these questions, we adapted and analyzed the properties of a mathematical model of the population and evolutionary dynamics of bacteria and phage and performed experiments with Escherichia coli and phages isolated from four fecal microbiota transplantation (FMT) doses as representative samples of non-dysbiotic enteric microbiota. Our models predict and experiments confirm that due to production of the O antigen, E. coli in the enteric microbiome are likely to be resistant to infection with co-occurring phages. However, phages can be maintained in these populations in high densities due to high rates of transition between resistant and sensitive states, which we call leaky resistance. Based on these models and observations, we postulate that the phages found in the human gut are likely to play little role in shaping the composition of E. coli in the enteric microbiome in healthy individuals. How general this is for other species of bacteria in enteric microbiota is not yet clear, although O antigen production is broadly conserved across many taxa.

SIGNIFICANCE STATEMENT: Little is known about the role that bacteriophages play in shaping the bacterial species and strain composition in the human gut microbiome or how they are maintained over time in this dynamic environment. Here we show that Escherichia coli isolated from fecal samples are likely to be resistant to their co-existing phages due to production of the O antigen. However, phages can be maintained in populations of mostly resistant bacteria if there is a rapid transition between resistant and sensitive states, a state called leaky resistance. Based on these results, we postulate that bacteriophages are likely playing little role of shaping the abundance and diversity of bacteria in the human gut microbiome in healthy individuals.}, } @article {pmid37981872, year = {2023}, author = {Oliva-Hemker, M and Kahn, SA and Steinbach, WJ and , and , }, title = {Fecal Microbiota Transplantation: Information for the Pediatrician.}, journal = {Pediatrics}, volume = {}, number = {}, pages = {}, doi = {10.1542/peds.2023-062922}, pmid = {37981872}, issn = {1098-4275}, abstract = {Fecal microbiota transplantation (FMT) involves the delivery of an entire microbial community from a healthy donor to a recipient with the intention of ameliorating or curing a specific disease. Current evidence strongly supports a role for FMT in the treatment of Clostridiodes difficile infection, with cure rates of approximately 80% to 90%. This success has led to increasing attention for FMT as a potential therapeutic intervention for other conditions associated with disturbances of the intestinal microbiome, including inflammatory bowel diseases, autism spectrum disorder, and obesity. This clinical report endorses the joint society statement by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition and is meant to provide the general pediatrician with a broad overview to enable appropriate guidance to families seeking FMT as treatment of a child's condition.}, } @article {pmid37981746, year = {2023}, author = {Arora, U and Kedia, S and Ahuja, V}, title = {The practice of fecal microbiota transplantation in inflammatory bowel disease.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2023.00085}, pmid = {37981746}, issn = {1598-9100}, abstract = {Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.}, } @article {pmid37981012, year = {2023}, author = {Zheng, M and Ye, H and Yang, X and Shen, L and Dang, X and Liu, X and Gong, Y and Wu, Q and Wang, L and Ge, X and Fang, X and Hou, B and Zhang, P and Tang, R and Zheng, K and Huang, XF and Yu, Y}, title = {Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis.}, journal = {Brain, behavior, and immunity}, volume = {115}, number = {}, pages = {565-587}, doi = {10.1016/j.bbi.2023.11.016}, pmid = {37981012}, issn = {1090-2139}, abstract = {Obesity is a risk factor for cognitive dysfunction and neurodegenerative disease, including Alzheimer's disease (AD). The gut microbiota-brain axis is altered in obesity and linked to cognitive impairment and neurodegenerative disorders. Here, we targeted obesity-induced cognitive impairment by testing the impact of the probiotic Clostridium butyricum, which has previously shown beneficial effects on gut homeostasis and brain function. Firstly, we characterized and analyzed the gut microbial profiles of participants with obesity and the correlation between gut microbiota and cognitive scores. Then, using an obese mouse model induced by a Western-style diet (high-fat and fiber-deficient diet), the effects of Clostridium butyricum on the microbiota-gut-brain axis and hippocampal cognitive function were evaluated. Finally, fecal microbiota transplantation was performed to assess the functional link between Clostridium butyricum remodeling gut microbiota and hippocampal synaptic protein and cognitive behaviors. Our results showed that participants with obesity had gut microbiota dysbiosis characterized by an increase in phylum Proteobacteria and a decrease in Clostridium butyricum, which were closely associated with cognitive decline. In diet-induced obese mice, oral Clostridium butyricum supplementation significantly alleviated cognitive impairment, attenuated the deficit of hippocampal neurite outgrowth and synaptic ultrastructure, improved hippocampal transcriptome related to synapses and dendrites; a comparison of the effects of Clostridium butyricum in mice against human AD datasets revealed that many of the genes changes in AD were reversed by Clostridium butyricum; concurrently, Clostridium butyricum also prevented gut microbiota dysbiosis, colonic barrier impairment and inflammation, and attenuated endotoxemia. Importantly, fecal microbiota transplantation from donor-obese mice with Clostridium butyricum supplementation facilitated cognitive variables and colonic integrity compared with from donor obese mice, highlighting that Clostridium butyricum's impact on cognitive function is largely due to its ability to remodel gut microbiota. Our findings provide the first insights into the neuroprotective effects of Clostridium butyricum on obesity-associated cognitive impairments and neurodegeneration via the gut microbiota-gut-brain axis.}, } @article {pmid37979881, year = {2023}, author = {Liang, Y and Liu, D and Li, Y and Hou, H and Li, P and Ma, X and Li, P and Zhan, J and Wang, P}, title = {Maternal polysorbate 80 intake promotes offspring metabolic syndrome through vertical microbial transmission in mice.}, journal = {The Science of the total environment}, volume = {909}, number = {}, pages = {168624}, doi = {10.1016/j.scitotenv.2023.168624}, pmid = {37979881}, issn = {1879-1026}, abstract = {Polysorbate 80 (P80) is an emulsifier extensively produced, consumed and discharged into the environment, consequently making human exposure inevitable. Despite evidence suggesting that P80 intake causes metabolic syndrome (MS) in mammals via microbial perturbation, limited data exist on its transgenerational impacts on offspring. In this study, we found that maternal P80 treatment impaired intestinal barrier integrity, leading to metabolic endotoxemia, low-grade inflammation and MS-related symptoms in C57BL/6J female offspring. Further analysis of the gut microbiome revealed MS-related changes in the offspring of P80-treated dams. Fecal microbiota transplantation experiment confirmed the crucial role of the altered microbiome in offspring in the transgenerational impacts of P80. Furthermore, we found that the P80-induced microbial alterations were directly transmitted from P80-treated mothers to their offspring and that interrupting vertical microbial transmission through cesarean section and foster nursing blocked the transgenerational impacts of P80 on the offspring microbiome and metabolic health. Moreover, maternal pectin supplementation also effectively mitigated P80-induced microbial alterations and MS-associated phenotypes in offspring. Together, our results indicated that maternal P80 intake could impair offspring metabolic health through the mother-to-offspring transmission of the microbiome, and maternal pectin supplementation might be a promising strategy for reducing the adverse effects of P80.}, } @article {pmid37979452, year = {2023}, author = {Xi, D and Liu, P and Feng, Y and Teng, Y and Liang, Y and Zhou, J and Deng, H and Zeng, G and Zong, S}, title = {Fecal microbiota transplantation regulates the microbiota-gut-spinal cord axis to promote recovery after spinal cord injury.}, journal = {International immunopharmacology}, volume = {126}, number = {}, pages = {111212}, doi = {10.1016/j.intimp.2023.111212}, pmid = {37979452}, issn = {1878-1705}, abstract = {Spinal cord injury (SCI) is devastating for patients, and currently lacks effective treatments. Dysbiosis commonly occurs after SCI and has significant immunomodulatory effects, but its impact on recovery remains unclear. The current study investigated the effects and mechanisms of fecal microbiota transplantation (FMT) in SCI. FMT was administered in a rat model of SCI and spinal pathology, inflammatory cytokines, and gut microbiome composition were assessed. Flow cytometry identified a source of interleukin (IL)-17 in spinal cord tissues, and carboxyfluorescein succimidyl ester labeling tracked γδ T cell migration. In vitro coculture was used to analyze the regulatory mechanisms of γδ T cells. Seahorse analysis was used to profile dendritic cell (DC) metabolism. Here we show that FMT improved spinal pathology and dampened post-injury inflammation. It also corrected post-SCI dysbiosis, increasing levels of the beneficial bacterium Akkermansia. The therapeutic effects of FMT were mediated by IL-17 produced by γδ T cells. FMT regulated γδ T cells via DC-T regulatory cell interaction, and induced metabolic reprogramming in DCs. These findings suggest that FMT represents a promising therapeutic approach for SCI, with potential to target IL-17[+] γδ T cells. Elucidating the interconnected pathways between microbiota, immunity, and the spinal cord may facilitate novel treatment strategies.}, } @article {pmid37979154, year = {2023}, author = {Kujawa, D and Laczmanski, L and Budrewicz, S and Pokryszko-Dragan, A and Podbielska, M}, title = {Targeting gut microbiota: new therapeutic opportunities in multiple sclerosis.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2274126}, doi = {10.1080/19490976.2023.2274126}, pmid = {37979154}, issn = {1949-0984}, abstract = {Multiple sclerosis (MS) causes long-lasting, multifocal damage to the central nervous system. The complex background of MS is associated with autoimmune inflammation and neurodegeneration processes, and is potentially affected by many contributing factors, including altered composition and function of the gut microbiota. In this review, current experimental and clinical evidence is presented for the characteristics of gut dysbiosis found in MS, as well as for its relevant links with the course of the disease and the dysregulated immune response and metabolic pathways involved in MS pathology. Furthermore, therapeutic implications of these investigations are discussed, with a range of pharmacological, dietary and other interventions targeted at the gut microbiome and thus intended to have beneficial effects on the course of MS.}, } @article {pmid37976078, year = {2023}, author = {Wang, Y and Wang, Z and Lu, Q}, title = {Microbiome dynamics in rheumatic diseases.}, journal = {Current opinion in rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/BOR.0000000000000993}, pmid = {37976078}, issn = {1531-6963}, abstract = {PURPOSE OF REVIEW: Rheumatic disease are characterized by their autoimmune nature, frequently affecting joints, bones, muscles, blood vessels, and connective tissues. The onset of these conditions typically unfolds gradually and subtly. It is noteworthy that individuals with rheumatic diseases often experience shifts in their microbiome, specifically on mucosal surfaces. The purpose of this review is to delve into the intricate interplay between the microbiome, encompassing bacteria, viruses and fungi, and its role in the development and aggravation of various rheumatic diseases. Additionally, it aims to offer insights into microbiome-centered therapeutic approaches for patients in the field of rheumatology.

RECENT FINDINGS: The advent of next-generation sequencing has significantly improved our understanding of microbiome changes. Numerous studies have consistently revealed a strong link between rheumatism and the microbiome, especially in the oral and gut microbiota.

SUMMARY: A deeper comprehension of the microbiome's connection to rheumatism holds potential for enhancing disease diagnosis and treatment. Targeted therapeutic approaches, including probiotics, fecal microbiota transplantation, and combination therapies with medications, offer promising avenues for disease management.}, } @article {pmid37975092, year = {2023}, author = {Guo, J and Zhou, B and Niu, Y and Liu, L and Yang, L}, title = {Engineered probiotics introduced to improve intestinal microecology for the treatment of chronic diseases: present state and perspectives.}, journal = {Journal of diabetes and metabolic disorders}, volume = {22}, number = {2}, pages = {1029-1038}, pmid = {37975092}, issn = {2251-6581}, abstract = {PURPOSE: Correcting intestinal microecological imbalance has become one of the core strategies to treat chronic diseases. Some traditional microecology-based therapies targeting intestine, such as prebiotic therapy, probiotic therapy and fecal microbiota transplantation therapy, have been used in the prevention and treatment of clinical chronic diseases, which still facing low safety and poor controllability problems. The development of synthetic biology technology has promoted the development of intestinal microecology-based therapeutics for chronic diseases, which exhibiting higher robustness and controllability, and become an important part of the next generation of microecological therapy. The purpose of this review is to summarize the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases.

METHODS: The available literatures were searched to find out experimental studies and relevant review articles on the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases from year 1990 to 2023.

RESULTS: Evidence proposed that synthetic biology has been applied in the intestinal microecology-based therapeutics for chronic diseases, covering metabolic diseases (e.g. diabetes, obesity, nonalcoholic fatty liver disease and phenylketonuria), digestive diseases (e.g. inflammatory bowel disease and colorectal cancer), and neurodegenerative diseases (e.g. Alzheimer's disease and Parkinson's disease).

CONCLUSION: This review summarizes the application of synthetic biology in intestinal microecology-based therapeutics for major chronic diseases and discusses the opportunities and challenges in the above process, providing clinical possibilities of synthetic biology technology applied in microecological therapies.}, } @article {pmid37974103, year = {2023}, author = {Khan, FA and Pandupuspitasari, NS and Huang, C and Negara, W and Ahmed, B and Putri, EM and Lestari, P and Priyatno, TP and Prima, A and Restitrisnani, V and Surachman, M and Akhadiarto, S and Darmawan, IWA and Wahyuni, DS and Herdis, H}, title = {Unlocking gut microbiota potential of dairy cows in varied environmental conditions using shotgun metagenomic approach.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {344}, pmid = {37974103}, issn = {1471-2180}, abstract = {Food security and environmental pollution are major concerns for the expanding world population, where farm animals are the largest source of dietary proteins and are responsible for producing anthropogenic gases, including methane, especially by cows. We sampled the fecal microbiomes of cows from varying environmental regions of Pakistan to determine the better-performing microbiomes for higher yields and lower methane emissions by applying the shotgun metagenomic approach. We selected managed dairy farms in the Chakwal, Salt Range, and Patoki regions of Pakistan, and also incorporated animals from local farmers. Milk yield and milk fat, and protein contents were measured and correlated with microbiome diversity and function. The average milk protein content from the Salt Range farms was 2.68%, with an average peak milk yield of 45 litters/head/day, compared to 3.68% in Patoki farms with an average peak milk yield of 18 litters/head/day. Salt-range dairy cows prefer S-adenosyl-L-methionine (SAMe) to S-adenosyl-L-homocysteine (SAH) conversion reactions and are responsible for low milk protein content. It is linked to Bacteroides fragilles which account for 10% of the total Bacteroides, compared to 3% in the Patoki region. The solid Non-Fat in the salt range was 8.29%, whereas that in patoki was 6.34%. Moreover, Lactobacillus plantarum high abundance in Salt Range provided propionate as alternate sink to [H], and overcoming a Methanobrevibacter ruminantium high methane emissions in the Salt Range. Furthermore, our results identified ruminant fecal microbiomes that can be used as fecal microbiota transplants (FMT) to high-methane emitters and low-performing herds to increase farm output and reduce the environmental damage caused by anthropogenic gases emitted by dairy cows.}, } @article {pmid37970585, year = {2022}, author = {Drefs, M and Schardey, J and von Ehrlich-Treuenstätt, V and Wirth, U and Burian, M and Zimmermann, P and Werner, J and Kühn, F}, title = {Endoscopic Treatment Options for Gastrointestinal Leaks.}, journal = {Visceral medicine}, volume = {38}, number = {5}, pages = {311-321}, pmid = {37970585}, issn = {2297-4725}, abstract = {BACKGROUND: Spontaneous or postoperative gastrointestinal defects are still life-threatening complications with elevated morbidity and mortality. Recently, endoscopic treatment options - up and foremost endoscopic vacuum therapy (EVT) - have become increasingly popular and have shown promising results in these patients.

METHODS: We performed an electronic systematic search of the MEDLINE databases (PubMed, EMBASE, and Cochrane) and searched for studies evaluating endoscopic options for the treatment of esophageal and colorectal leakages and/or perforations until March 2022.

RESULTS: The closure rate of both esophageal and colorectal defects by EVT is high and even exceeds the results of surgical revision in parts. Out of all endoscopic treatment options, EVT shows most evidence and appears to have the highest therapeutic success rates. Furthermore, EVT for both indications had a low rate of serious complications without relevant in-hospital mortality. In selected patients, EVT can be applied without fecal diversion and transferred to an outpatient setting.

CONCLUSION: Despite multiple endoscopic treatment options, EVT is increasingly becoming the new gold standard in endoscopic treatment of extraperitoneal defects of the upper and lower GI tract with localized peritonitis or mediastinitis and without close proximity to major blood vessels. However, further prospective, comparative studies are needed to strengthen the current evidence.}, } @article {pmid37969732, year = {2023}, author = {Zeng, X and Liao, Y and Qiao, X and Liang, K and Luo, Q and Deng, M and Liu, Y and Zhang, W and Hong, X and Xiao, Y}, title = {Novel NIR-II fluorescent probes for biliary atresia imaging.}, journal = {Acta pharmaceutica Sinica. B}, volume = {13}, number = {11}, pages = {4578-4590}, pmid = {37969732}, issn = {2211-3835}, abstract = {Biliary atresia is a rare infant disease that predisposes patients to liver transplantation and death if not treated in time. However, early diagnosis is challenging because the clinical manifestations and laboratory tests of biliary atresia overlap with other cholestatic diseases. Therefore, it is very important to develop a simple, safe and reliable method for the early diagnosis of biliary atresia. Herein, a novel NIR-II fluorescence probe, HZL2, with high quantum yield, excellent biocompatibility, low cytotoxicity and rapid excretion through the liver and gallbladder was developed based on the oil/water partition coefficient and permeability. A simple fecal sample after injection of HZL2 can be used to efficiently identify the success of the mouse model of biliary atresia for the first time, allowing for an early diagnosis of the disease. This study not only developed a simple and safe method for the early diagnosis of biliary atresia with great potential in clinical translation but also provides a research tool for the development of pathogenesis and therapeutic medicines for biliary atresia.}, } @article {pmid37967548, year = {2023}, author = {Naito, Y}, title = {Gut Frailty: Its Concept and Pathogenesis.}, journal = {Digestion}, volume = {}, number = {}, pages = {1-9}, doi = {10.1159/000534733}, pmid = {37967548}, issn = {1421-9867}, abstract = {BACKGROUND: There is still a considerable gap between average life expectancy and healthy life expectancy in Japan. Recent research has revealed that gut frailty may be a worsening factor for various diseases, a cause of chronic inflammation, and a precursor to frailty.

SUMMARY: Among self-reported symptoms, constipation is particularly significant as one of the key symptoms of gut frailty. Studies have demonstrated that individuals with constipation have significantly lower survival rates and are also at a higher risk of developing various diseases such as chronic kidney disease, cardiovascular diseases, and neurodegenerative disorders like Parkinson's disease. Various molecular mechanisms could contribute to gut frailty, and the decrease in mucus secretion is an extremely early-stage pathology. Dysbiosis of gut microbiota has a major impact on many conditions associated with gut frailty. Prebiotics, probiotics, post-biotics, and fecal microbiota transplantation are under investigation as a treatment option for gut frailty.

KEY MESSAGE: Although the concept of gut frailty has not yet gained widespread recognition, we hope to propose more practical screening methods, diagnostic approaches, and specific interventions in the future.}, } @article {pmid37966684, year = {2023}, author = {An, S and Zhen, Z and Wang, S and Sang, M and Zhang, S}, title = {Intestinal Microbiota Is a Key Target for Load Swimming to Improve Anxiety Behavior and Muscle Strength in Shank 3[-/-] Rats.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {37966684}, issn = {1559-1182}, support = {7232239//Beijing Municipal Natural Science Foundation/ ; 21BTY023//National Social Science Fund of China/ ; 19YTA007//Key project of Beijing Social Science Foundation/ ; BNUXKJC2110//BNU Interdisciplinary Research Foundation for the First-Year Doctoral Candidates/ ; 20YJA890036//Research and planning fund for Humanities and social sciences of the Ministry of Education/ ; AEEA2020017//Priority topics of Beijing's 13th five year plan for Educational Science/ ; }, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social disorder and stereotypical behavior, and its incidence rate is increasing yearly. It is considered that acritical period for the prognosis of young children with ASD exists, thus early treatment is crucial. Swimming, due to its comforting effect, is often used to induce enthusiasm in young children for completing activities and has a good effect in the treatment of ASD, but the effective path of swimming has yet to be reported. The intestinal microbiota of ASD patients and animal models has been reported to be different from that of healthy controls, and these changes may affect the brain environment. Therefore, whether the intestinal microbiota is involved in the treatment of ASD by early swimming is our concern. In this study, we used 8-day old Shank3 gene knockout rats with 8 weeks of early load swimming training and conducted behavioral, small intestine morphology, and intestinal content sequencing after training. The results showed that early load swimming significantly reduced the stereotyped and anxious behaviors of Shank3[-/-] rats, increased their muscle strength, increased the length of intestinal villi and the width of the muscular layer after Shank3 knockout, and affected the abundance of intestinal microorganisms. The abundances with statistical significance were Lactobacillus, Lachnospiraceae, and Alloprevotella. To further confirm the role of intestinal microorganisms in it, we designed a 14-day intestinal stool transplantation experiment. Fecal microbiota transplantation demonstrated that load swimming can significantly reduce the anxiety behavior of Shank3 rats, increase their muscle strength, change the structure of the small intestine, and affect the abundance of intestinal contents. The abundance of Epsilonbateraeota, Prevotella, and Bacteroides significantly changed after transplantation. Our findings confirm the possibility of early load swimming therapy for individuals with ASD and explain that the intestinal microbiota is a key pathway for early exercise therapy for patients with ASD.}, } @article {pmid37965266, year = {2023}, author = {Piazzesi, A and Pane, S and Russo, A and Del Chierico, F and Francalanci, P and Cotugno, N and Rossi, P and Locatelli, F and Palma, P and Putignani, L}, title = {Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1281440}, pmid = {37965266}, issn = {2235-2988}, abstract = {Cryptosporidium parvum is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While infection is usually self-limiting, it can become chronic and even lethal in these vulnerable populations, in whom Cryptosporidium treatments are generally ineffective, due to their acting in concert with a functioning immune system. Here, we describe a case of chronic cryptosporidiosis in a European child with severe CD40L immunodeficiency infected with Cryptosporidium parvum of the IIa20G1 subgenotype, a lineage which has thus far only ever been described in the Middle East. After years of on-off treatment with conventional and non-conventional anti-parasitic drugs failed to clear parasitosis, we performed targeted metagenomics to observe the bacterial composition of the patient's gut microbiota (GM), and to evaluate fecal microbiota transplantation (FMT) as a potential treatment option. We found that C. parvum infection led to significant shifts in GM bacterial composition in our patient, with consequent shifts in predicted intestinal functional signatures consistent with a state of persistent inflammation. This, combined with the patient's poor prognosis and increasing parasitic burden despite many rounds of anti-parasitic drug treatments, made the patient a potential candidate for an experimental FMT procedure. Unfortunately, given the many comorbidities that were precipitated by the patient's immunodeficiency and chronic C. parvum infection, FMT was postponed in favor of more urgently necessary liver and bone marrow transplants. Tragically, after the first liver transplant failed, the patient lost his life before undergoing FMT and a second liver transplant. With this case report, we present the first description of how cryptosporidiosis can shape the gut microbiota of a pediatric patient with severe immunodeficiency. Finally, we discuss how both our results and the current scientific literature suggest that GM modulations, either by probiotics or FMT, can become novel treatment options for chronic Cryptosporidium infection and its consequent complications, especially in those patients who do not respond to the currently available anti-parasitic therapies.}, } @article {pmid37962812, year = {2023}, author = {Lachmansingh, DA and Lavelle, A and Cryan, JF and Clarke, G}, title = {Microbiota-Gut-Brain Axis and Antidepressant Treatment.}, journal = {Current topics in behavioral neurosciences}, volume = {}, number = {}, pages = {}, pmid = {37962812}, issn = {1866-3370}, abstract = {In the treatment of depressive disorders, conventional antidepressant therapy has been the mainstay of clinical management, along with well-established nonpharmacological interventions such as various kinds of psychotherapy. Over the last 2 decades, there has been considerable interest in the role of the gastrointestinal system and its microbiota on brain function, behavior, and mental health. Components of what is referred to as the microbiota-gut-brain axis have been uncovered, and further research has elicited functional capabilities such as "gut-brain modules." Some studies have found associations with compositional alterations of gut microbiota in patients with depressive disorders and individuals experiencing symptoms of depression. Regarding the pathogenesis and neurobiology of depression itself, there appears to be a multifactorial contribution, in addition to the theories involving deficits in catecholaminergic and monoamine neurotransmission. Interestingly, there is evidence to suggest that antidepressants may play a role in modulating the gut microbiota, thereby possibly having an impact on the microbiota-gut-brain axis in this manner. The development of prebiotics, probiotics, and synbiotics has led to studies investigating not only their impact on the microbiota but also their therapeutic value in mental health. These psychobiotics have the potential to be used as therapeutic adjuncts in the treatment of depression. Regarding future directions, and in an attempt to further understand the role of the microbiota-gut-brain axis in depression, more studies such as those involving fecal microbiota transplantation will be required. In addition to recent findings, it is also suggested that more research will have to be undertaken to elicit whether specific strains of gut organisms are linked to depression. In terms of further investigation of the therapeutic potential of prebiotics, probiotics, and synbiotics as adjuncts to antidepressant treatment, we also expect there to be more research targeting specific microorganisms, as well as a strong focus on the effects of specific prebiotic fibers from an individualized (personalized) point of view.}, } @article {pmid37962207, year = {2023}, author = {Yang, T and Xie, S and Cao, L and Li, M and Ding, L and Wang, L and Pang, S and Wang, Z and Geng, L}, title = {Astragaloside IV modulates gut macrophages M1/M2 polarization by reshaping gut microbiota and SCFA in sepsis.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000002262}, pmid = {37962207}, issn = {1540-0514}, abstract = {M1 macrophage-mediated inflammation is critical in sepsis. We previously found protective role of Astragaloside IV (AS-IV) in sepsis-associated gut impairment, whose specific mechanism remains unknown. Gut microbiota modulates gut homeostatic balance to avoid excessive inflammation. Here, we aimed to investigate effects of AS-IV on gut macrophages polarization and potential roles of gut microbiota and short chain fatty acids (SCFA) in septic gut damage. Mice were pre-treated by AS-IV gavage for 7 days before cecal ligation and puncture (CLP). M1 polarization of gut lamina propria macrophages (LpMs) was promoted by CLP, accompanied by abnormal cytokines release and intestinal barrier dysfunction. NLRP3 inflammasome was activated in M1 LpMs. 16S rRNA sequencing demonstrated gut microbiota imbalance. The levels of acetate, propionate and butyrate in fecal samples decreased. Notably, AS-IV reversed LpMs M1/M2 polarization, lightened gut inflammation and barrier injury, reduced NLRP3 inflammasome expression in LpMs, restored the diversity of gut microbiome and increased butyrate levels. Similarly, these benefits were mimicked by fecal microbiota transplantation (FMT) or exogenous butyrate supplementation. In Caco-2 and THP-1 co-cultured model, lipopolysaccharide (LPS) and interferon-γ (IFN-γ) caused THP-1 M1 polarization, Caco-2 barrier impairment, abnormal cytokines release and high NLRP3 inflammasome expression in THP-1 cells, all of which were mitigated by butyrate administration. However, these protective effects of butyrate were abrogated by NLRP3 gene overexpression in THP-1. In conclusion, AS-IV can ameliorate sepsis-induced gut inflammation and barrier dysfunction by modulating M1/M2 polarization of gut macrophages, whose underlying mechanism may be restoring gut microbiome and SCFA to restrain NLRP3 inflammasome activation.}, } @article {pmid37961950, year = {2023}, author = {Guo, S and Shi, Y and Xu, A and Wang, Y and Xu, P}, title = {Liubao tea extract ameliorates ovalbumin-induced allergic asthma by regulating gut microbiota in mice.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo03470d}, pmid = {37961950}, issn = {2042-650X}, abstract = {Asthma, a chronic airway inflammatory disease, has a complicated pathogenesis and limited therapeutic treatment. Evidence shows that the intestinal microbiota exhibits crucial functional interaction with asthma syndrome. Liubao tea (LBT), a type of postfermented tea in China, positively modulates gut microbiota. However, the potential benefits of LBT extract (LBTE) for allergic asthma are still not understood. Herein, the anti-inflammatory effects of LBTE and its modulation of the gut microbiota of asthmatic mice induced by ovalbumin were explored. The results demonstrate that LBTE significantly inhibited airway hyper-responsiveness and restrained the proliferation of proinflammatory cytokines and inflammatory cells associated with allergic asthma. Additionally, LBTE suppressed inflammatory infiltration, mucus secretion, and excessive goblet cell production by downregulating the gene expression of inflammatory indicators. Interestingly, fecal microbiota transplantation results further implied that the modulation of LBTE on gut microbiota played an essential role in alleviating airway inflammatory symptoms of allergic asthma.}, } @article {pmid37961091, year = {2023}, author = {Dubey, H and Roychoudhury, R and Alex, A and Best, C and Liu, S and White, A and Carlson, A and Azcarate-Peril, MA and Mansfield, LS and Knickmeyer, R}, title = {Effect of Human Infant Gut Microbiota on Mouse Behavior, Dendritic Complexity, and Myelination.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.24.563309}, pmid = {37961091}, abstract = {UNLABELLED: The mammalian gut microbiome influences numerous developmental processes. In human infants it has been linked with cognition, social skills, hormonal responses to stress, and brain connectivity. Yet, these associations are not necessarily causal. The present study tested whether two microbial stool communities, common in human infants, affected behavior, myelination, dendritic morphology, and spine density when used to colonize mouse models. Humanized animals were more like specific-pathogen free mice than germ-free mice for most phenotypes, although in males, both humanized groups were less social. Both humanized groups had thinner myelin sheaths in the hippocampus, than did germ-free animals. Humanized animals were similar to each other except for dendritic morphology and spine density where one group had greater dendritic length in the prefrontal cortex, greater dendritic volume in the nucleus accumbens, and greater spine density in both regions, compared to the other. Results add to a body of literature suggesting the gut microbiome impacts brain development.

TEASER: Fecal transplants from human infants with highly abundant Bifidobacterium , an important inhabitant of the intestinal tract of breastfed newborns, may promote brain connectivity in mice.}, } @article {pmid37960284, year = {2023}, author = {Zheng, Y and Bonfili, L and Wei, T and Eleuteri, AM}, title = {Understanding the Gut-Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders.}, journal = {Nutrients}, volume = {15}, number = {21}, pages = {}, doi = {10.3390/nu15214631}, pmid = {37960284}, issn = {2072-6643}, support = {Fondi Studenti PhD//University of Camerino/ ; }, mesh = {Humans ; Brain-Gut Axis ; *Neurodegenerative Diseases/therapy ; *Gastrointestinal Microbiome ; *Alzheimer Disease/therapy ; *Parkinson Disease/therapy ; Brain ; Dysbiosis/therapy ; }, abstract = {The gut-brain axis (GBA) is a complex bidirectional communication network connecting the gut and brain. It involves neural, immune, and endocrine communication pathways between the gastrointestinal (GI) tract and the central nervous system (CNS). Perturbations of the GBA have been reported in many neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others, suggesting a possible role in disease pathogenesis. The gut microbiota is a pivotal component of the GBA, and alterations in its composition, known as gut dysbiosis, have been associated with GBA dysfunction and neurodegeneration. The gut microbiota might influence the homeostasis of the CNS by modulating the immune system and, more directly, regulating the production of molecules and metabolites that influence the nervous and endocrine systems, making it a potential therapeutic target. Preclinical trials manipulating microbial composition through dietary intervention, probiotic and prebiotic supplementation, and fecal microbial transplantation (FMT) have provided promising outcomes. However, its clear mechanism is not well understood, and the results are not always consistent. Here, we provide an overview of the major components and communication pathways of the GBA, as well as therapeutic approaches targeting the GBA to ameliorate NDDs.}, } @article {pmid37958637, year = {2023}, author = {Han, Z and Min, Y and Pang, K and Wu, D}, title = {Therapeutic Approach Targeting Gut Microbiome in Gastrointestinal Infectious Diseases.}, journal = {International journal of molecular sciences}, volume = {24}, number = {21}, pages = {}, doi = {10.3390/ijms242115654}, pmid = {37958637}, issn = {1422-0067}, support = {2022-I2M-1-003//CAMS Innovation Fund for Medical Sciences/ ; }, abstract = {While emerging evidence highlights the significance of gut microbiome in gastrointestinal infectious diseases, treatments like Fecal Microbiota Transplantation (FMT) and probiotics are gaining popularity, especially for diarrhea patients. However, the specific role of the gut microbiome in different gastrointestinal infectious diseases remains uncertain. There is no consensus on whether gut modulation therapy is universally effective for all such infections. In this comprehensive review, we examine recent developments of the gut microbiome's involvement in several gastrointestinal infectious diseases, including infection of Helicobacter pylori, Clostridium difficile, Vibrio cholerae, enteric viruses, Salmonella enterica serovar Typhimurium, Pseudomonas aeruginosa Staphylococcus aureus, Candida albicans, and Giardia duodenalis. We have also incorporated information about fungi and engineered bacteria in gastrointestinal infectious diseases, aiming for a more comprehensive overview of the role of the gut microbiome. This review will provide insights into the pathogenic mechanisms of the gut microbiome while exploring the microbiome's potential in the prevention, diagnosis, prediction, and treatment of gastrointestinal infections.}, } @article {pmid37957893, year = {2023}, author = {Garner, W and Hamza, A and Haidar, G}, title = {Investigational non-antibiotic therapeutics for infections in hematopoietic cell transplant recipients and patients with hematologic malignancies receiving cellular therapies.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e14193}, doi = {10.1111/tid.14193}, pmid = {37957893}, issn = {1399-3062}, abstract = {In the age of progressive antimicrobial resistance and increased difficulty combating infections in immunocompromised hosts, there has been renewed interest in the use of nontraditional therapeutics for infections. Herein, we review the use of investigational non-pharmaceutical anti-infective agents targeting fungal, bacterial, and viral infections in patients with hematologic malignancies, focusing on those receiving hematopoietic cell transplantation or cellular therapies. We discuss immune checkpoint inhibitors, granulocyte transfusions, bone marrow colony-stimulating factors, bacteriophages, fecal microbiota transplantation, and virus specific T-cell therapy. Although there is promising early experience with many of these treatments, further studies will be required to define their optimal role in the therapeutic armamentarium against infections in immunocompromised hosts.}, } @article {pmid37956701, year = {2023}, author = {Bornbusch, SL and Power, ML and Schulkin, J and Drea, CM and Maslanka, MT and Muletz-Wolz, CR}, title = {Integrating microbiome science and evolutionary medicine into animal health and conservation.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.13030}, pmid = {37956701}, issn = {1469-185X}, support = {BCS 1749465//National Science Foundation/ ; IOS 2131060//National Science Foundation/ ; U4DMC39438//Pregnancy-Related Care Research Network (HRSA; HHS)/ ; //Smithsonian George E. Burch Fellowship in Theoretical Medicine and Affiliated Theoretical Science/ ; }, abstract = {Microbiome science has provided groundbreaking insights into human and animal health. Similarly, evolutionary medicine - the incorporation of eco-evolutionary concepts into primarily human medical theory and practice - is increasingly recognised for its novel perspectives on modern diseases. Studies of host-microbe relationships have been expanded beyond humans to include a wide range of animal taxa, adding new facets to our understanding of animal ecology, evolution, behaviour, and health. In this review, we propose that a broader application of evolutionary medicine, combined with microbiome science, can provide valuable and innovative perspectives on animal care and conservation. First, we draw on classic ecological principles, such as alternative stable states, to propose an eco-evolutionary framework for understanding variation in animal microbiomes and their role in animal health and wellbeing. With a focus on mammalian gut microbiomes, we apply this framework to populations of animals under human care, with particular relevance to the many animal species that suffer diseases linked to gut microbial dysfunction (e.g. gut distress and infection, autoimmune disorders, obesity). We discuss diet and microbial landscapes (i.e. the microbes in the animal's external environment), as two factors that are (i) proposed to represent evolutionary mismatches for captive animals, (ii) linked to gut microbiome structure and function, and (iii) potentially best understood from an evolutionary medicine perspective. Keeping within our evolutionary framework, we highlight the potential benefits - and pitfalls - of modern microbial therapies, such as pre- and probiotics, faecal microbiota transplants, and microbial rewilding. We discuss the limited, yet growing, empirical evidence for the use of microbial therapies to modulate animal gut microbiomes beneficially. Interspersed throughout, we propose 12 actionable steps, grounded in evolutionary medicine, that can be applied to practical animal care and management. We encourage that these actionable steps be paired with integration of eco-evolutionary perspectives into our definitions of appropriate animal care standards. The evolutionary perspectives proposed herein may be best appreciated when applied to the broad diversity of species under human care, rather than when solely focused on humans. We urge animal care professionals, veterinarians, nutritionists, scientists, and others to collaborate on these efforts, allowing for simultaneous care of animal patients and the generation of valuable empirical data.}, } @article {pmid37955340, year = {2023}, author = {Bibbò, S and Porcari, S and Del Vecchio, LE and Severino, A and Mullish, BH and Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Gut microbiota and immunotherapy of renal cell carcinoma.}, journal = {Human vaccines & immunotherapeutics}, volume = {19}, number = {3}, pages = {2268982}, doi = {10.1080/21645515.2023.2268982}, pmid = {37955340}, issn = {2164-554X}, mesh = {Humans ; *Carcinoma, Renal Cell/therapy ; *Gastrointestinal Microbiome ; Immunotherapy ; *Kidney Neoplasms/therapy ; Immune Checkpoint Inhibitors/therapeutic use ; *Neoplasms ; }, abstract = {The gut microbiome has recently been proposed as a key player in cancer development and progression. Several studies have reported that the composition of the gut microbiome plays a role in the response to immune checkpoint inhibitors (ICIs). The gut microbiome modulation has been investigated as a potential therapeutic strategy for cancer, mainly in patients undergoing therapy with ICIs. In particular, modulation through probiotics, FMT or other microbiome-related approaches have proven effective to improve the response to ICIs. In this review, we examine the role of the gut microbiome in enhancing clinical responses to ICIs in the treatment of renal cancer.}, } @article {pmid37954280, year = {2023}, author = {Vasudevan, D and Ramakrishnan, A and Velmurugan, G}, title = {Exploring the diversity of blood microbiome during liver diseases: Unveiling Novel diagnostic and therapeutic Avenues.}, journal = {Heliyon}, volume = {9}, number = {11}, pages = {e21662}, pmid = {37954280}, issn = {2405-8440}, abstract = {Liver diseases are a group of major metabolic and immune or inflammation related diseases caused due to various reasons including infection, abnormalities in immune system, genetic defects, and lifestyle habits. However, the cause-effect relationship is not completely understood in liver disease. The role of microbiome, particularly, the role of gut and oral microbiome in liver diseases has been extensively studied in recent years. More interestingly, the presence of blood microbiome and tissue microbiome has been identified in many liver diseases. The translocation of microbes from the gut into the portal circulation has been attributed to be the major reason for the presence of blood microbial components and its clinical implications in liver disorders. Besides microbial translocation, Pathogen associated Molecular Patterns (PAMPs) derived from gut microbiota might also translocate. The presence of blood microbiome in liver disease has been reviewed earlier. However, the role of blood microbiome as a biomarker and therapeutic target in liver diseases has not been analysed earlier. In this review, we confabulate the origin and physiology of blood microbiome and blood microbial components in relation to the progression and pathogenesis of liver disease. In conclusion, we discuss the translational perspectives targeting the blood microbial components in the diagnosis and therapy of liver disease.}, } @article {pmid37953693, year = {2023}, author = {Lee, RB and Gasparetto, M}, title = {Novel pharmacological developments in the management of paediatric inflammatory bowel disease: Time for guideline update - A narrative review.}, journal = {Journal of paediatrics and child health}, volume = {}, number = {}, pages = {}, doi = {10.1111/jpc.16519}, pmid = {37953693}, issn = {1440-1754}, abstract = {AIM: The incidence of paediatric inflammatory bowel disease (IBD) continues to increase in both adults and children across the globe, with more than one third of the patients not responding to anti-tumour necrosis factor biologics and immune modulators. This narrative review provides an overview of novel pharmacological developments in the management of paediatric IBD, including new biological therapies.

METHODS: A PubMed Medline search was performed to include randomised controlled trials, retrospective and prospective observational studies, and relevant case reports of children with IBD published between 2018 and January 2023. Guidelines and protocols from relevant paediatric and adult gastroenterology societies, such as the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation, were also included. Non-pharmacological treatments including therapeutic diets and faecal microbiota transplantation were outside the scope of this work.

RESULTS: Early real-world evidence suggests that newer biologics and small molecules, such as anti-integrins, interleukin-12 and/or interleukin-23 inhibitors, Janus kinase and signal transducer and activator of transcription proteins inhibitors, are safe and effective in adult patients with IBD, with promising growing evidence for paediatric IBD.

CONCLUSION: While many developments have been achieved with novel pharmacological treatments to manage IBD, ongoing research is required to confirm their effectiveness and safety in the paediatric age. Extending the licence of novel treatments to children will be crucial to tackle the increasing loss of response to conventional treatments. International guidelines will require timely updating to incorporate novel treatments within the existing protocols.}, } @article {pmid37951913, year = {2023}, author = {Mousavinasab, F and Karimi, R and Taheri, S and Ahmadvand, F and Sanaaee, S and Najafi, S and Halvaii, MS and Haghgoo, A and Zamany, M and Majidpoor, J and Khosravifar, M and Baniasadi, M and Talebi, M and Movafagh, A and Aghaei-Zarch, SM and Khorram, N and Farnia, P and Kalhor, K}, title = {Microbiome modulation in inflammatory diseases: Progress to microbiome genetic engineering.}, journal = {Cancer cell international}, volume = {23}, number = {1}, pages = {271}, pmid = {37951913}, issn = {1475-2867}, abstract = {Recent developments in sequencing technology and analytical approaches have allowed researchers to show that the healthy gut microbiome is very varied and capable of performing a wide range of tasks. The importance of gut microbiota in controlling immunological, neurological, and endocrine function is becoming well-recognized. Thereby, numerous inflammatory diseases, including those that impact the gastrointestinal system, as well as less obvious ones, including Rheumatoid arthritis (RA), cancer, gestational diabetes (GD), type 1 diabetes (T1D), and type 2 diabetes (T2D), have been linked to dysbiotic gut microbiota. Microbiome engineering is a rapidly evolving frontier for solutions to improve human health. Microbiome engineering seeks to improve the function of an ecosystem by manipulating the composition of microbes. Thereby, generating potential therapies against metabolic, inflammatory, and immunological diseases will be possible through microbiome engineering. This essay first provides an overview of the traditional technological instruments that might be used for microbiome engineering, such as Fecal Microbiota Transplantation (FMT), prebiotics, and probiotics. Moreover, we will also discuss experimental genetic methods such as Metagenomic Alteration of Gut microbiome by In situ Conjugation (MAGIC), Bacteriophage, and Conjugative plasmids in manipulating intestinal microbiota.}, } @article {pmid37950332, year = {2023}, author = {Promsuwan, O and Malathum, K and Ingsathit, A}, title = {Epidemiology of extended-spectrum β-lactamase-producing Enterobacterales infection in kidney transplant recipients.}, journal = {Antimicrobial resistance and infection control}, volume = {12}, number = {1}, pages = {123}, pmid = {37950332}, issn = {2047-2994}, support = {ID 863//Faculty of Medicine Ramathibodi Hospital, Mahidol University/ ; }, mesh = {Humans ; Escherichia coli ; Prospective Studies ; *Kidney Transplantation/adverse effects ; beta-Lactamases ; *Bacteremia/epidemiology ; }, abstract = {BACKGROUND: Extended-spectrum b-lactamase (ESBL)-producing gram-negative bacilli (ESBL-GNB) are the most important pathogenic bacteria infecting kidney transplant patients. Kidney transplantation has been shown to be a risk factor for nosocomial ESBL-GNB bacteremia. The aims of this study were to describe the epidemiology of ESBL-GNB acquisition and to identify factors associated with ESBL-GNB infection in kidney transplant recipients, including pretransplant ESBL-GNB fecal carriage.

METHODS: A prospective study of patients undergoing kidney transplantation at Ramathibodi Hospital from March 1, 2019-November 30, 2020 was conducted. During this period, 66 patients who underwent kidney transplantation. Perianal swab cultures and urine cultures for ESBL-GNB were obtained from all subjects upon admission for transplantation and on Days 3, 7, 14 and 21 after surgery to determine the prevalence, incidence, and duration of admission before acquisition of the organisms.

RESULTS: Of the 66 patients undergoing kidney transplantation, 18 preoperative perianal swabs were detected to be positive for ESBL-GNB upon admission, representing 27.3% of the cases. The in-hospital perianal swab tests showed a significant increase to 96.8% positive ESBL-GNB cultures at the end of week 3. Approximately one-fourth (27.8%) of patients who acquired ESBL-GNB developed a postoperative symptomatic infection. The infection occurred in 13% of such patients who were not ESBL positive at first. These infections included urinary tract infections (20 cases, [30%], of which 55% were due to ESBL-GNB) and bloodstream infections (13 cases; of which 9 [69.2%] were due to ESBL-GNB). E. coli was the most common pathogen. Previous exposure to antibiotics, including surgical prophylaxis, underlying disease, duration of indwelling urinary catheters and ureteric stents, as well as other operative factors were not found to be significantly associated with the acquisition of ESBL-producing organisms in this dataset.

CONCLUSIONS: ESBL carriage may be a risk factor for the development of bacteremia and other serious infections among kidney transplant recipients, although a statistically significant difference could not be demonstrated owing to the small size of the sample. The high rate of ESBL acquisition suggests that more stringent infection prevention and control efforts are needed.}, } @article {pmid37948152, year = {2023}, author = {Song, W and Wang, Y and Li, G and Xue, S and Zhang, G and Dang, Y and Wang, H}, title = {Modulating the gut microbiota is involved in the effect of low-molecular-weight Glycyrrhiza polysaccharide on immune function.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2276814}, doi = {10.1080/19490976.2023.2276814}, pmid = {37948152}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Molecular Weight ; Polysaccharides/pharmacology ; *Glycyrrhiza ; Immunity ; }, abstract = {Low molecular weight (6.5 kDa) Glycyrrhiza polysaccharide (GP) exhibits good immunomodulatory activity, however, the mechanism underlying GP-mediated regulation of immunity and gut microbiota remains unclear. In this study, we aimed to reveal the mechanisms underlying GP-mediated regulation of immunity and gut microbiota using cyclophosphamide (CTX)-induced immunosuppressed and intestinal mucosal injury models. GP reversed CTX-induced intestinal structural damage and increased the number of goblet cells, CD4[+], CD8[+] T lymphocytes, and mucin content, particularly by maintaining the balance of helper T lymphocyte 1/helper T lymphocyte 2 (Th1/Th2). Moreover, GP alleviated immunosuppression by down-regulating extracellular regulated protein kinases/p38/nuclear factor kappa-Bp50 pathways and increasing short-chain fatty acids level and secretion of cytokines, including interferon-γ, interleukin (IL)-4, IL-2, IL-10, IL-22, and transforming growth factor-β3 and immunoglobulin (Ig) M, IgG and secretory immunoglobulin A. GP treatment increased the total species and diversity of the gut microbiota. Microbiota analysis showed that GP promoted the proliferation of beneficial bacteria, including Muribaculaceae_unclassified, Alistipes, Lachnospiraceae_NK4A136_group, Ligilactobacillus, and Clostridia_vadinBB60_group, and reduced the abundance of Proteobacteria and CTX-derived bacteria (Clostridiales_unclassified, Candidatus_Arthromitus, Firmicutes_unclassified, and Clostridium). The studies of fecal microbiota transplantation and the pseudo-aseptic model conformed that the gut microbiota is crucial in GP-mediated immunity regulation. GP shows great potential as an immune enhancer and a natural medicine for treating intestinal inflammatory diseases.}, } @article {pmid37947218, year = {2023}, author = {Gudi, RR and Johnson, BM and Gaudreau, MC and Sun, W and Ball, L and Vasu, C}, title = {Intestinal permeability and inflammatory features of juvenile age correlate with the eventual systemic autoimmunity in lupus-prone female SWR × NZB F1 (SNF1) mice.}, journal = {Immunology}, volume = {}, number = {}, pages = {}, doi = {10.1111/imm.13713}, pmid = {37947218}, issn = {1365-2567}, support = {R21AI136339/NH/NIH HHS/United States ; R01AI138511/NH/NIH HHS/United States ; R01DK136094/NH/NIH HHS/United States ; }, abstract = {The incidence of systemic lupus erythematosus (SLE) is about nine times higher in women than in men, and the underlying mechanisms that contribute to this gender bias are not fully understood. Previously, using lupus-prone (SWR × NZB)F1 (SNF1) mice, we have shown that the intestinal immune system could play a role in the initiation and progression of disease in SLE, and depletion of gut microbiota produces more pronounced disease protection in females than in males. Here, we show that the gut permeability features of lupus-prone female SNF1 mice at juvenile ages directly correlate with the expression levels of pro-inflammatory factors, faecal IgA abundance and nAg reactivity and the eventual systemic autoantibody levels and proteinuria onset. Furthermore, we observed that the disease protection achieved in female SNF1 mice upon depletion of gut microbiota correlates with the diminished gut inflammatory protein levels, intestinal permeability and circulating microbial DNA levels. However, faecal microbiota transplant from juvenile male and females did not result in modulation of gut inflammatory features or permeability. Overall, these observations suggest that the early onset of intestinal inflammation, systemic autoantibody production and clinical stage disease in lupus-prone females is linked to higher gut permeability in them starting at as early as juvenile age. While the higher gut permeability in juvenile lupus-prone females is dependent on the presence of gut microbes, it appears to be independent of the composition of gut microbiota.}, } @article {pmid37944820, year = {2023}, author = {Zeng, K and Brewster, R and Kang, JB and Tkachenko, E and Brooks, E and Bhatt, AS and Fodor, AA and Andermann, TM}, title = {Acute steroid-refractory GI GVHD is not associated with significant differences in gut taxonomic composition compared to steroid-sensitive GI GVHD immediately prior to onset of disease: GI GVHD is not characterized by gut microbial differences preceding symptom onset.}, journal = {Transplantation and cellular therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtct.2023.11.006}, pmid = {37944820}, issn = {2666-6367}, abstract = {BACKGROUND: Taxonomic composition of the gut microbiota at the time of neutrophil engraftment is associated with the development of acute gastrointestinal graft-versus-host disease (GI GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation. However, less is known about the relationship between the gut microbiota and development of steroid-refractory GI GVHD immediately prior to the onset of disease.

OBJECTIVES: Markers of steroid-refractory GI GVHD are needed in order to identify patients who may benefit from the early initiation of non-corticosteroid-based GVHD treatment. Our aim was to identify differences in taxonomic composition in stool samples from patients without GVHD, with steroid-responsive GVHD and with steroid-refractory GI GVHD in order to identify predictive microbiome biomarkers of steroid-refractory GI GVHD.

STUDY DESIGN: We conducted a retrospective case-control, single institution study, performing shotgun metagenomic sequencing on stool samples from patients with (n=36) and without GVHD (n=34) matched for time since transplant. We compared the taxonomic composition of the gut microbiome in those with steroid-sensitive GI GVHD (n=17) and steroid-refractory GI GVHD (n=19) to each other and to those without GVHD. We also performed associations between steroid-refractory GI GVHD, gut taxonomic composition, and fecal calprotectin, a marker of GI GVHD to develop composite fecal markers of steroid-refractory GVHD prior to the onset of GI disease.

RESULTS: We found that fecal samples within 30 days of GVHD onset from patients with and without GVHD or with and without steroid-refractory GI GVHD did not differ significantly in Shannon diversity (alpha-diversity) or in overall taxonomic composition (beta-diversity). While those patients without GVHD had higher relative abundance of Clostridium spp., those with and without steroid-refractory GI GVHD did not significantly differ in taxonomic composition between one another. In our study, fecal calprotectin prior to disease onset was significantly higher in patients with GVHD compared to those without GVHD and higher in patients with steroid-refractory GI GVHD compared to steroid-sensitive GI GVHD. No taxa were significantly associated with higher levels of calprotectin.}, } @article {pmid37944641, year = {2023}, author = {D, T and Venkatesh, MP}, title = {Fecal Microbiota Transplantation: History, Procedure and Regulatory Considerations.}, journal = {Presse medicale (Paris, France : 1983)}, volume = {}, number = {}, pages = {104204}, doi = {10.1016/j.lpm.2023.104204}, pmid = {37944641}, issn = {2213-0276}, abstract = {Fecal microbiota transplantation (FMT) is a medical treatment which involves the transfer of feces from a healthy donor to a recipient to restore the balance of gut microbiota and improve clinical outcomes. FMT has gained recognition in recent years due to its effectiveness in treating recurrent Clostridioides difficile infections (rCDI) and other gastrointestinal disorders. Additionally, it has been studied as an intervention for some other conditions, like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This review covers regulatory considerations related to FMT, including the current state of FMT regulation and the need for further research to fully understand the safety and efficacy of this treatment. For transplantation of fecal microbiota, the Food and Drug Administration (FDA) classifies the treatment as an investigational new drug (IND), which typically requires physicians and scientists to submit an IND application. Ethical issues surrounding FMT, including the necessity of informed consent from donors and recipients and the potential transmission of infectious agents, are also discussed. Overall, FMT has the potential to offer significant therapeutic benefits, but it also raises regulatory and ethical considerations that require careful consideration. Further research is necessary to fully comprehend risks and benefits of FMT and to develop guidelines for its use in clinical practice.}, } @article {pmid37942659, year = {2023}, author = {Normington, C and Chilton, CH and Buckley, AM}, title = {Clostridioides difficile infections; new treatments and future perspectives.}, journal = {Current opinion in gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MOG.0000000000000989}, pmid = {37942659}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: As a significant cause of global morbidity and mortality, Clostridioides difficile infections (CDIs) are listed by the Centres for Disease Control and prevention as one of the top 5 urgent threats in the USA. CDI occurs from gut microbiome dysbiosis, typically through antibiotic-mediated disruption; however, antibiotics are the treatment of choice, which can result in recurrent infections. Here, we highlight new treatments available and provide a perspective on different classes of future treatments.

RECENT FINDINGS: Due to the reduced risk of disease recurrence, the microbiome-sparing antibiotic Fidaxomicin has been recommended as the first-line treatment for C. difficile infection. Based on the success of faecal microbiota transplantations (FMT) in treating CDI recurrence, defined microbiome biotherapeutics offer a safer and more tightly controlled alterative as an adjunct to antibiotic therapy. Given the association between antibiotic-mediated dysbiosis of the intestinal microbiota and the recurrence of CDI, future prospective therapies aim to reduce the dependence on antibiotics for the treatment of CDI.

SUMMARY: With current first-in-line antibiotic therapy options associated with high levels of recurrent CDI, the availability of new generation targeted therapeutics can really impact treatment success. There are still unknowns about the long-term implications of these new CDI therapeutics, but efforts to expand the CDI treatment toolbox can offer multiple solutions for clinicians to treat this multifaceted infectious disease to reduce patient suffering.}, } @article {pmid37942583, year = {2023}, author = {Wang, Q and Lin, H and Shen, C and Zhang, M and Wang, X and Yuan, M and Yuan, M and Jia, S and Cao, Z and Wu, C and Chen, B and Gao, A and Bi, Y and Ning, G and Wang, W and Wang, J and Liu, R}, title = {Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2274124}, doi = {10.1080/19490976.2023.2274124}, pmid = {37942583}, issn = {1949-0984}, mesh = {Mice ; Animals ; *Glucagon-Like Peptide 1/metabolism ; *Gastrointestinal Microbiome ; Signal Transduction ; Receptors, G-Protein-Coupled/genetics/metabolism ; Bile Acids and Salts ; Ileum ; }, abstract = {The gut microbiota interacts with intestinal epithelial cells through microbial metabolites to regulate the release of gut hormones. We investigated whether the gut microbiota affects the postprandial glucagon-like peptide-1 (GLP-1) response using antibiotic-treated mice and germ-free mice. Gut microbiome depletion completely abolished postprandial GLP-1 response in the circulation and ileum in a lipid tolerance test. Microbiome depletion did not influence the GLP-1 secretory function of primary ileal cells in response to stimulators in vitro, but dramatically changed the postprandial dynamics of endogenous bile acids, particularly ω-muricholic acid (ωMCA) and hyocholic acid (HCA). The bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) but not farnesoid X receptor (FXR), participated in the regulation of postprandial GLP-1 response in the circulation and ileum, and ωMCA or HCA stimulated GLP-1 secretion via TGR5. Finally, fecal microbiota transplantation or ωMCA and HCA supplementation restored postprandial GLP-1 response. In conclusion, gut microbiota is indispensable for maintaining the postprandial GLP-1 response specifically in the ileum, and bile acid (ωMCA and HCA)-TGR5 signaling is involved in this process. This study helps to understand the essential interplay between the gut microbiota and host in regulating postprandial GLP-1 response and opens the foundation for new therapeutic targets.}, } @article {pmid37939900, year = {2023}, author = {Bu, X and Pan, W and Liu, L and Wang, J and Yin, Z and Gao, Y and Ping, B}, title = {Human amniotic membrane-derived mesenchymal stem cells prevent acute graft-versus-host disease in an intestinal microbiome-dependent manner.}, journal = {Transplantation and cellular therapy}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtct.2023.11.005}, pmid = {37939900}, issn = {2666-6367}, abstract = {Acute graft-versus-host disease (aGVHD) represents a fatal severe complication following allogeneic hematopoietic stem cell transplantation. As a promising cell therapeutic strategy of aGVHD, the mechanism of mesenchymal stem cells (MSC) to ameliorate aGVHD has not been fully clarified, especially in the field of intestinal homeostasis including the intestinal microbiome involved in the pathogenesis of aGVHD. The present study aimed to explore the effect of MSC on intestinal homeostasis including the intestinal barrier and intestinal microbiome and its metabolites as well as the role of intestinal microbiome in the preventive process of hAMSCs ameliorating aGVHD. The preventive effects of human amniotic membrane-derived MSC (hAMSCs) was assessed in humanized aGVHD models. Immunohistochemistry and RT-qPCR were used to evaluate intestinal barrier function. 16S rRNA sequencing and targeted metabolomics assay were performed to observe the alternation of intestinal microbiome and the amounts of medium-chain fatty acids (MCFAs) and short-chain fatty acids (SCFAs), respectively. Flow cytometer was performed to analyze the frequencies of T immune cells. Through animal experiments, we found that hAMSCs had the potential to prevent aGVHD. hAMSCs could repair the damage of intestinal barrier structure and function as well as improve the dysbiosis of intestinal microbiome induced by aGVHD, and meanwhile, upregulate the concentration of metabolites SCFAs, so as to reshape intestinal homeostasis. Gut microbiota depletion and fecal microbial transplantation confirmed the involvement of intestinal microbiome in the preventive process of hAMSCs on aGVHD. Our findings showed that hAMSCs prevented aGVHD in an intestinal microbiome-dependent manner, which might shed light on a new mechanism of hAMSCs inhibiting aGVHD and promote the development of new prophylaxis regimes for aGVHD prevention.}, } @article {pmid37938097, year = {2023}, author = {León-Janampa, N and Caballero-Posadas, I and Barc, C and Darrouzain, F and Moreau, A and Guinoiseau, T and Gatault, P and Fleurot, I and Riou, M and Pinard, A and Pezant, J and Rossignol, C and Gaudy-Graffin, C and Brand, D and Marlet, J}, title = {A pig model of chronic hepatitis E displaying persistent viremia and a downregulation of innate immune responses in the liver.}, journal = {Hepatology communications}, volume = {7}, number = {11}, pages = {}, doi = {10.1097/HC9.0000000000000274}, pmid = {37938097}, issn = {2471-254X}, mesh = {Humans ; Swine ; Animals ; *Hepatitis E ; Down-Regulation ; Viremia ; Tacrolimus ; Immunity, Innate/genetics ; }, abstract = {BACKGROUND: Hepatitis E virus (HEV) is a zoonotic virus transmitted by pig meat and responsible for chronic hepatitis E in immunocompromised patients. It has proved challenging to reproduce this disease in its natural reservoir. We therefore aimed to develop a pig model of chronic hepatitis E to improve the characterization of this disease.

METHODS: Ten pigs were treated with a tacrolimus-based regimen and intravenously inoculated with HEV. Tacrolimus trough concentration, HEV viremia, viral diversity, innate immune responses, liver histology, clinical disease and biochemical markers were monitored for 11 weeks post-infection (p.i.).

RESULTS: HEV viremia persisted for 11 weeks p.i. HEV RNA was detected in the liver, small intestine, and colon at necropsy. Histological analysis revealed liver inflammation and fibrosis. Several mutations selected in the HEV genome were associated with compartmentalization in the feces and intestinal tissues, consistent with the hypothesis of extrahepatic replication in the digestive tract. Antiviral responses were characterized by a downregulation of IFN pathways in the liver, despite an upregulation of RIG-I and ISGs in the blood and liver.

CONCLUSIONS: We developed a pig model of chronic hepatitis E that reproduced the major hallmarks of this disease. This model revealed a compartmentalization of HEV genomes in the digestive tract and a downregulation of innate immune responses in the liver. These original features highlight the relevance of our model for studies of the pathogenesis of chronic hepatitis E and for validating future treatments.}, } @article {pmid37937304, year = {2023}, author = {Chen, Z and Guan, D and Wang, Z and Li, X and Dong, S and Huang, J and Zhou, W}, title = {Microbiota in cancer: molecular mechanisms and therapeutic interventions.}, journal = {MedComm}, volume = {4}, number = {6}, pages = {e417}, pmid = {37937304}, issn = {2688-2663}, abstract = {The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, and metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant cell signaling pathways, influencing tumor cell metabolism, promoting revascularization, and remodeling the tumor immune microenvironment. These microbiota-mediated effects significantly impact overall survival and the recurrence of tumors after surgery by affecting the efficacy of chemoradiotherapy. Moreover, leveraging the microbiota for the development of biovectors, probiotics, prebiotics, and synbiotics, in addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, and fecal microbiota transplantation, offers promising alternatives for cancer treatment. Nonetheless, due to the extensive and diverse nature of the microbiota, along with tumor heterogeneity, the molecular mechanisms underlying the role of microbiota in cancer remain a subject of intense debate. In this context, we refocus on various cancers, delving into the molecular signaling pathways associated with the microbiota and its derivatives, the reshaping of the tumor microenvironmental matrix, and the impact on tolerance to tumor treatments such as chemotherapy and radiotherapy. This exploration aims to shed light on novel perspectives and potential applications in the field.}, } @article {pmid37937006, year = {2023}, author = {Secondo, D and Massaro, D and Verrienti, G and Perri, F and Biscaglia, G}, title = {Clostridioides difficile Infection in the Neurorehabilitation Setting: Importance of a Multidisciplinary Approach and Impact of the Fecal Microbiota Transplantation.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e46574}, pmid = {37937006}, issn = {2168-8184}, abstract = {Clostridioides difficile infection (CDI) is considered to be one of the most frequent causes of bacterial infectious diarrhea in nosocomial settings. The prolonged hospitalization in bed-ridden conditions and the frequent administration of antibiotic therapy are usually encountered among the risk factors for CDI. Therefore, it is not surprising that CDI rates among rehabilitation hospitals are higher in neurologic facilities. In the neurorehabilitation setting, CDIs, especially if they present with refractory or recurrent aspects, may interrupt the normal course of rehabilitation, influencing, subsequently, the neurological outcomes. CDI treatment depends on the severity of the disease and includes both conservative and surgical approaches, with the latter reserved for severe complicated CDI. Another emerging, highly effective therapeutic option is represented by fecal microbiota transplantation (FMT), which consists of the transfer of screened healthy donor stool to a recipient's gastrointestinal tract. In this paper, we report two cases of refractory CDI, affecting patients in the neurorehabilitation pathway; both cases were resolved through FMT. On the one hand, our cases provide more evidence of FMT efficacy in refractory CDIs; on the other hand, they emphasize the need for a multidisciplinary approach to grant the best care to CDI patients.}, } @article {pmid37936686, year = {2023}, author = {Reynolds, HM and Bettini, ML}, title = {Early-life microbiota-immune homeostasis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1266876}, pmid = {37936686}, issn = {1664-3224}, support = {T32 AI138945/AI/NIAID NIH HHS/United States ; R01 AI173406/AI/NIAID NIH HHS/United States ; R01 AI136963/AI/NIAID NIH HHS/United States ; }, mesh = {Infant, Newborn ; Humans ; *Probiotics/therapeutic use ; Dysbiosis ; *Microbiota ; *Gastrointestinal Microbiome ; Homeostasis ; }, abstract = {As the prevalence of allergy and autoimmune disease in industrialized societies continues to rise, improving our understanding of the mechanistic roles behind microbiota-immune homeostasis has become critical for informing therapeutic interventions in cases of dysbiosis. Of particular importance, are alterations to intestinal microbiota occurring within the critical neonatal window, during which the immune system is highly vulnerable to environmental exposures. This review will highlight recent literature concerning mechanisms of early-life microbiota-immune homeostasis as well as discuss the potential for therapeutics in restoring dysbiosis in early life.}, } @article {pmid37936242, year = {2023}, author = {Pan, C and Zhang, H and Zhang, L and Chen, L and Xu, L and Xu, N and Liu, X and Meng, Q and Wang, X and Zhang, ZY}, title = {Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {248}, pmid = {37936242}, issn = {2049-2618}, support = {82201325//National Natural Science Foundation of China/ ; 82204382//National Natural Science Foundation of China/ ; 82071209//National Natural Science Foundation of China/ ; 21KJB310009//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; 22KJB310005//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; }, abstract = {BACKGROUND: Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Gut microbial dysbiosis is associated with neurological diseases; however, the mechanisms by which the microbiota regulates postoperative gastrointestinal and cognitive function are incompletely understood.

METHODS: Behavioral testing, MiSeq 16S rRNA gene sequencing, non-target metabolism, intestinal permeability detection, protein assays, and immunofluorescence staining were employed to discern the impacts of surgery on microbial profiles, intestinal barriers, serum metabolism, and the brain. Interventions in mice included fecal microbiota transplantation, the anti-inflammatory agent dexamethasone, Lactobacillus supplementation, indole propionic acid supplementation, and palmitic amide administration.

RESULTS: Surgery-induced cognitive impairment occurs predominantly in aged mice, and surgery-induced alterations in the microbiota composition profile exacerbate intestinal barrier disruption in aged mice. These adverse effects can be mitigated by transferring microbiota from young donors or by bolstering the intestinal barrier function using dexamethasone, Lactobacillus, or indole propionic acid. Moreover, microbiota composition profiles can be restored by transplanting feces from young mice to aged surgical mice, improving neuropathology and cognitive function, and these effects coincide with increased intestinal permeability. Metabolomic screening identified alterations in metabolites in mouse serum after surgery, especially the increase in palmitic amide. Palmitic amide levels in serum and brain can be decreased by transplanting feces from young mice to aged surgical mice. Oral palmitic amide exacerbates cognitive impairment and neuropathological changes in mice.

CONCLUSIONS: Gut microbial dysbiosis in mice after surgery is a key mechanism leading to cognition dysfunction, which disrupts the intestinal barrier and metabolic abnormalities, resulting in neuroinflammation and dendritic spine loss. Intestinal barrier damage and high level of palmitic amide in old mice may be the cause of high incidence of PND in the elderly. Preoperative microbiota regulation and intestinal barrier restoration may be of therapeutic benefit in preventing PND. Video Abstract.}, } @article {pmid37935653, year = {2023}, author = {Pandey, H and Jain, D and Tang, DWT and Wong, SH and Lal, D}, title = {Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2023.00080}, pmid = {37935653}, issn = {1598-9100}, abstract = {Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.}, } @article {pmid37935276, year = {2023}, author = {Ye, X and Sun, P and Lao, S and Wen, M and Zheng, R and Lin, Y and Gan, L and Fan, X and Wang, P and Li, Z and Yan, X and Zhao, L}, title = {Fgf21-Dubosiella axis mediates the protective effects of exercise against NAFLD development.}, journal = {Life sciences}, volume = {}, number = {}, pages = {122231}, doi = {10.1016/j.lfs.2023.122231}, pmid = {37935276}, issn = {1879-0631}, abstract = {AIM: To explore the mechanism of gut microbiota mediates protective effects of exercise against non-alcoholic fatty liver disease (NAFLD) development.

MAIN METHODS: The male C57BL/6 mice were fed with high fat food (HFD) or normal diet (CON) respectively, and the obese mice were randomly divided into sedentariness (HFD) and exercise groups (HFD + Exe). The total intervention period was 18 weeks. Antibiotic treatment and fecal microbiota transplantation were applied to evaluate gut microbiota mediates the protective effects of exercise against NAFLD development. 16S rDNA profiling of gut microbiota and extracorporeal rehydration of Dubosiella newyorkensis were performed to identify the crucial role of Dubosiella in NAFLD improvement during exercise training. FGF21 knock-out mice were used to reveal the potential mechanism of exercise increased the abundance of Dubosiella. RT-PCR, Western blot, Histopathological examinations and Biochemical testing were performed to evaluate the lipid deposition and function in the liver.

KEY FINDINGS: Treadmill exercise significantly ameliorated hepatic function and mitigated lipid accumulation in NAFLD mice, and these hepatoprotective benefits were mostly mediated by the Dubosiella. In addition, the increased abundance of Dubosiella during exercise training was modulated by FGF21 specifically.

SIGNIFICANCE: In short, Dubosiella, chiefly regulated by FGF21 signaling during exercise training, has been discovered to govern the protective impacts of exercising counter to the development of NAFLD and exhibits a promising treatment target for NAFLD.}, } @article {pmid37934614, year = {2023}, author = {Zhang, T and Gao, G and Kwok, LY and Sun, Z}, title = {Gut microbiome-targeted therapies for Alzheimer's disease.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2271613}, pmid = {37934614}, issn = {1949-0984}, abstract = {The advent of high-throughput 'omics' technologies has improved our knowledge of gut microbiome in human health and disease, including Alzheimer's disease (AD), a neurodegenerative disorder. Frequent bidirectional communications and mutual regulation exist between the gastrointestinal tract and the central nervous system through the gut-brain axis. A large body of research has reported a close association between the gut microbiota and AD development, and restoring a healthy gut microbiota may curb or even improve AD symptoms and progression. Thus, modulation of the gut microbiota has become a novel paradigm for clinical management of AD, and emerging effort has focused on developing potential novel strategies for preventing and/or treating the disease. In this review, we provide an overview of the connection and causal relationship between gut dysbiosis and AD, the mechanisms of gut microbiota in driving AD progression, and the successes and challenges of implementing available gut microbiome-targeted therapies (including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation) in preventive and/or therapeutic preclinical and clinical intervention studies of AD. Finally, we discuss the future directions in this field.}, } @article {pmid37934064, year = {2023}, author = {Cao, Y and Zhang, L and Xiong, F and Guo, X and Kan, X and Song, S and Liang, B and Liang, B and Yu, L and Zheng, C}, title = {Effect of probiotics and fecal microbiota transplantation in dirty rats with established primary liver cancer.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {}, doi = {10.2217/fmb-2022-0234}, pmid = {37934064}, issn = {1746-0921}, abstract = {Background: The modulating effects of probiotics and fecal microbiota transplantation (FMT) on gut flora and their direct antitumor effects remain unclear in dirty rats with established primary liver cancer. Materials & methods: Probiotics (VSL#3), FMT or tap water were administrated to three groups. Fresh fecal samples were collected from all groups for 16S rRNA analysis. Liver cancer tissues were collected to evaluate the tumor response. Results: Significant modulation of β-diversity (p = 0.023) was observed after FMT. VSL#3 and FMT had no inhibitory effect on tumors, but the density of Treg cells decreased (p = 0.031) in the FMT group. Conclusion: FMT is a more attractive alternative to probiotics in dirty rats with liver cancer.}, } @article {pmid37933950, year = {2023}, author = {Zhang, M and Mo, R and Wang, H and Liu, T and Zhang, G and Wu, Y}, title = {Grape seed proanthocyanidin improves intestinal inflammation in canine through regulating gut microbiota and bile acid compositions.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {37}, number = {12}, pages = {e23285}, doi = {10.1096/fj.202300819RR}, pmid = {37933950}, issn = {1530-6860}, mesh = {Dogs ; Animals ; *Gastrointestinal Microbiome ; Bile Acids and Salts ; *Inflammatory Bowel Diseases/microbiology ; Inflammation ; Polyphenols/pharmacology ; }, abstract = {Although certain progress has been made in treating canine inflammatory bowel disease (IBD), a large proportion of dogs have a poor prognosis and may develop resistance and side effects. Therefore, it is of great significance to prevent or alleviate canine IBD through nutritional intervention. Plant polyphenol can interact with intestinal bacteria and has important prospects in the intestinal health improvement. This study evaluated the effect of grape seed proanthocyanidin (GSP), a plant-derived natural polyphenol, on Labrador Retrievers with mild IBD. In Experiment 1 of this study, GSP alleviated persistent intestinal inflammation in canines by improving inflammatory indexes and reducing intestinal permeability. Moreover, GSP treatment increased the abundance of bacteria with potential anti-inflammatory properties and engaging bile acid metabolism, including Ruminococcaceae, Faecalibacterium, Ruminococcus_torques_group, and Lachnospiraceae_NK4A136_group. Notably, targeted metabolomic analysis identified elevated productions of fecal chenodeoxycholic acid and its microbial transformation product lithocholic acid, which might contribute to relieving canine intestinal inflammation. Further, in Experiment 2, fecal microbiota transplantation was used to determine whether gut microbiota is a potential mechanism for GSP efficacy. Dogs with mild IBD received the fecal microbiota from the group administered GSP and mirrored the improvement effects of GSP, which results verified that gut microbial alteration could be an underlying mechanism for GSP efficiency on canine IBD. Our findings highlight that the mechanism of the GSP function on canine IBD is mediated by altering gut microbial composition and improving bile acid metabolism. This study proposes a natural polyphenol-based dietary strategy for improving canine intestinal health.}, } @article {pmid37932511, year = {2023}, author = {Blake, SJ and Wolf, Y and Boursi, B and Lynn, DJ}, title = {Role of the microbiota in response to and recovery from cancer therapy.}, journal = {Nature reviews. Immunology}, volume = {}, number = {}, pages = {}, pmid = {37932511}, issn = {1474-1741}, abstract = {Our understanding of how the microbiota affects the balance between response to and failure of cancer treatment by modulating the tumour microenvironment and systemic immune system has advanced rapidly in recent years. Microbiota-targeting interventions in patients with cancer are an area of intensive investigation. Promisingly, phase I-II clinical trials have shown that interventions such as faecal microbiota transplantation can overcome resistance to immune checkpoint blockade in patients with melanoma, improve therapeutic outcomes in treatment-naive patients and reduce therapy-induced immunotoxicities. Here, we synthesize the evidence showing that the microbiota is an important determinant of both cancer treatment efficacy and treatment-induced acute and long-term toxicity, and we discuss the complex and inter-related mechanisms involved. We also assess the potential of microbiota-targeting interventions, including bacterial engineering and phage therapy, to optimize the response to and recovery from cancer therapy.}, } @article {pmid37928687, year = {2023}, author = {Okamura, T and Hasegawa, Y and Hamaguchi, M and Sasano, R and Fukui, M}, title = {The role of chicken eggs in modulating sarcopenic obesity and gut microbiota in db/db mice.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1281217}, pmid = {37928687}, issn = {1664-302X}, abstract = {BACKGROUND: Sarcopenia obesity, in which loss of muscle mass and fat accumulation occur simultaneously, is the pathological basis of type 2 diabetes mellitus. The usefulness of chicken eggs in sarcopenia prevention has been reported in several previous studies. The purpose of this study was to determine the beneficial effects of chicken eggs in the prevention of sarcopenic obesity in db/db mice.

METHODS: We raised 8-week-old db/db male mice, a model of sarcopenia obesity, for 8 weeks and fed them a diet mixed with dried whole eggs. The fecal microbiota transplant (FMT) group was treated with antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age.

RESULTS: Eggs administered to db/db mice showed increased grip strength (p = 0.022) and muscle mass (p = 0.013), decreased visceral fat mass (p = 0.005), and significantly increased physical activity (p < 0.001). The FMT group of egg-fed mice showed a significant improvement in glucose intolerance and sarcopenic obesity. Sequencing of gene expression in the small intestine showed that the gene expression of amino acid transporters such as Slc6a18, Slc6a19, and Slc38a6 was increased in egg-fed mice. 16S rRNA sequencing of the gut microbiota showed an increase in the genus Vampirovibrio in both the egg-fed and FMT groups compared to that in egg-fed mice.

CONCLUSION: The results of this study indicate that egg consumption not only increases the intake of amino acids and other nutrients but also alters the intestinal microbiota and increases amino acid absorption from the intestinal tract, suggesting that eggs might contribute to the ameliorative mechanism of sarcopenic obesity.}, } @article {pmid37927130, year = {2023}, author = {Lee, J and Kim, EJ and Park, GS and Kim, J and Kim, TE and Lee, YJ and Park, J and Kang, J and Koo, JW and Choi, TY}, title = {Lactobacillus reuteri ATG-F4 Alleviates Chronic Stress-induced Anhedonia by Modulating the Prefrontal Serotonergic System.}, journal = {Experimental neurobiology}, volume = {32}, number = {5}, pages = {313-327}, doi = {10.5607/en23028}, pmid = {37927130}, issn = {1226-2560}, abstract = {Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD). Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.}, } @article {pmid37922956, year = {2023}, author = {Pilonis, N}, title = {Positive fecal immunochemical test but negative colonoscopy: what's next?.}, journal = {Endoscopy}, volume = {}, number = {}, pages = {}, doi = {10.1055/a-2182-6316}, pmid = {37922956}, issn = {1438-8812}, } @article {pmid37923839, year = {2023}, author = {Routy, B and Lenehan, JG and Miller, WH and Jamal, R and Messaoudene, M and Daisley, BA and Hes, C and Al, KF and Martinez-Gili, L and Punčochář, M and Ernst, S and Logan, D and Belanger, K and Esfahani, K and Richard, C and Ninkov, M and Piccinno, G and Armanini, F and Pinto, F and Krishnamoorthy, M and Figueredo, R and Thebault, P and Takis, P and Magrill, J and Ramsay, L and Derosa, L and Marchesi, JR and Parvathy, SN and Elkrief, A and Watson, IR and Lapointe, R and Segata, N and Haeryfar, SMM and Mullish, BH and Silverman, MS and Burton, JP and Maleki Vareki, S}, title = {Author Correction: Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41591-023-02650-8}, pmid = {37923839}, issn = {1546-170X}, } @article {pmid37921501, year = {2023}, author = {Wang, H and Bi, H and Yang, M and Wang, X and Song, C and Yang, W and Wang, Y and Xie, D and Li, H and Zhou, Z}, title = {Intestinal flora altered and correlated with interleukin-2/4 in patients with primary immune thrombocytopenia.}, journal = {Hematology (Amsterdam, Netherlands)}, volume = {28}, number = {1}, pages = {2277501}, doi = {10.1080/16078454.2023.2277501}, pmid = {37921501}, issn = {1607-8454}, mesh = {Humans ; *Purpura, Thrombocytopenic, Idiopathic ; Interleukin-2 ; *Gastrointestinal Microbiome ; Interleukin-4 ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Little is known about the changes and mechanisms of intestinal flora in primary immune thrombocytopenia (ITP) patients.

AIM: To explore the structural and functional differences of intestinal flora between ITP patients and healthy controls, and clarify the correlation between intestinal flora and Th1/Th2 imbalance.

METHODS: Feces from ITP patients and healthy controls were studied by 16S rRNA and metagenomic techniques at phylum, genus, species or functional levels. Blood samples were collected for the detection of interleukin -2 (IL-2) and IL-4 concentrations.

RESULTS: The following changes in ITP patients were found: a decrease of Bacteroidetes phylum, an increase of Proteobacteria phylum and alterations of ten genera and 1045 species. IL-2 and IL-4 were significantly correlated with six and five genera, respectively. Species of C. freundii, C. rodentium, and C. youngae were negatively correlated with bleeding scores, and S. infantis was positively related to platelet counts. Functionally, the intestinal flora of ITP patients changed mainly in terms of motility, chemotaxis, membrane transport, and metabolism.

CONCLUSION: The mechanism underlying functional and structural changes of intestinal flora in ITP patients may be related to inflammation and immunity, providing possibilities of probiotics or fecal transplants for ITP.}, } @article {pmid37918500, year = {2023}, author = {Feng, W and Zhang, Y and Zhang, Y and Dong, Y and Wu, J and Chen, Q and Liu, M and Wang, D and Wu, Y and Wang, T}, title = {Anemoside B4 ameliorates dextran sulfate sodium (DSS)-induced colitis through inhibiting NLRP3 inflammasome and modulating gut microbiota.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {176164}, doi = {10.1016/j.ejphar.2023.176164}, pmid = {37918500}, issn = {1879-0712}, abstract = {Ulcerative colitis (UC) has been recognized as a chronic and relapsing inflammatory disease of the gastrointestinal tract. Clinically, aminosalicylates, immunosuppressants and biological agents are commonly used to treat UC at different stages of the disease. However, these drugs often have side effects. Here, we investigated the anti-UC activity of Anemoside B4 (AB4) in mice with dextran sulfate sodium (DSS) induced colitis. Colon tissues, serum, and colonic contents were collected for assessment of intestinal barrier function, inflammatory cytokines production and microenvironment of intestinal microbiota. Results showed that AB4 alleviated colon shortening, weight lossing and histopathological damage in DSS-induced mice. In addition, we demonstrated both in vivo and in vitro that AB4 remarkably ameliorated colonic inflammation through suppressing NLRP3 pathway. Moreover, AB4 strengthened the intestinal epithelial barrier by regulating myosin light chain kinase (MLCK)-phosphorylated myosin light chain 2 (pMLC2) signaling pathway. Furthermore, we performed 16 S rRNA gene sequencing and fecal microbiome transplantation (FMT) experiments to demonstrate that AB4 alleviated colitis through regulating dysbiosis of intestinal microbiota. These results revealed that AB4 effectively ameliorate experimental UC mainly through regulating MLCK/pMLC2 pathway, NLRP3 pathway and dysbiosis of microbiota, provided new insights into the development of novel anti-UC drugs.}, } @article {pmid37918459, year = {2023}, author = {Ross, FC and Mayer, DE and Gupta, A and Richard Gill, CI and Del Rio, D and Cryan, JF and Lavelle, A and Ross, RP and Stanton, C and Mayer, EA}, title = {Existing and future strategies to manipulate the gut microbiota with diet as a potential adjuvant treatment for psychiatric disorders.}, journal = {Biological psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.biopsych.2023.10.018}, pmid = {37918459}, issn = {1873-2402}, abstract = {Nutrition and diet quality play key roles in preventing and slowing cognitive decline and have been linked to multiple brain disorders. This review compiles available evidence from preclinical studies and clinical trials on the impact of nutrition and interventions regarding major psychiatric conditions and some neurological disorders. We emphasize the potential role of diet-related microbiome alterations in these effects and highlight commonalities between various brain disorders related to the microbiome. Despite numerous studies shedding light on these findings, there are still gaps in our understanding due to the limited availability of definitive human trial data firmly establishing a causal link between a specific diet and microbially mediated brain functions and symptoms. The positive impact of certain diets on the microbiome and cognitive function is frequently ascribed with the anti-inflammatory effects of certain microbial metabolites or a reduction of proinflammatory microbial products. We also critically review recent research on pro- and prebiotics and non-dietary interventions, particularly fecal microbial transplants. The recent focus on diet in relation to brain disorders could lead to improved treatment outcomes with combined dietary, pharmacological, and behavioral interventions.}, } @article {pmid37918425, year = {2023}, author = {Scharl, M and Rogler, G}, title = {[Microbiome: from pathophysiology to clinical application?].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {148}, number = {22}, pages = {1419-1424}, doi = {10.1055/a-1951-0063}, pmid = {37918425}, issn = {1439-4413}, mesh = {Humans ; *Clostridium Infections/therapy ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Microbiota ; *Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {The "microbiome" or the intestinal microbiota is currently in the focus of scientific interest. The number of publications on the topic of the microbiome is increasing every year. In particular, the role of the microbiome in the pathophysiology of various diseases has been studied. Currently it is impossible to have an overview on all new developments with over 25.000 publication in the field per year. However, some key news stand out from this large number of publications. The first microbiota compounds for the therapy of Clostridioides difficile colitis were approved by the FDA last year or are about to be approved. This means that, for the first time, standardized microbiome products are available in addition to fecal microbiota transplantation (FMT) and are finding their way into everyday clinical practice.}, } @article {pmid37916626, year = {2023}, author = {Zhang, L and Ma, XG}, title = {A Comprehensive Review on Biotransformation, Interaction, and Health of Gut Microbiota and Bioactive Components.}, journal = {Combinatorial chemistry & high throughput screening}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113862073257733231011072004}, pmid = {37916626}, issn = {1875-5402}, abstract = {BACKGROUND: The relationship between gut microbiota and bioactive components has become the research focus in the world. We attempted to clarify the relationship between biotransformation and metabolites of gut microbiota and bioactive components, and explore the metabolic pathway and mechanism of bioactive ingredients in vivo, which will provide an important theoretical basis for the clinical research of bioactive ingredients and rationality of drugs, and also provide an important reference for the development of new drugs with high bioavailability.

METHODS: The related references of this review on microbiota and bioactive components were collected from both online and offline databases, such as ScienceDirect, PubMed, Elsevier, Willy, SciFinder, Google Scholar, Web of Science, Baidu Scholar, SciHub, Scopus, and CNKI.

RESULTS: This review summarized the biotransformation of bioactive components under the action of gut microbiota, including flavonoids, terpenoids, phenylpropanoids, alkaloids, steroids, and other compounds. The interaction of bioactive components and gut microbiota is a key link for drug efficacy. Relevant research is crucial to clarify bioactive components and their mechanisms, which involve the complex interaction among bioactive components, gut microbiota, and intestinal epithelial cells. This review also summarized the individualized, precise, and targeted intervention of gut microbiota in the field of intestinal microorganisms from the aspects of dietary fiber, microecological agents, fecal microbiota transplantation, and postbiotics. It will provide an important reference for intestinal microecology in the field of nutrition and health for people.

CONCLUSION: To sum up, the importance of human gut microbiota in the research of bioactive components metabolism and transformation has attracted the attention of scholars all over the world. It is believed that with the deepening of research, human gut microbiota will be more widely used in the pharmacodynamic basis, drug toxicity relationship, new drug discovery, drug absorption mechanism, and drug transport mechanism in the future.}, } @article {pmid37915416, year = {2023}, author = {Zhang, D and Tang, Y and Bai, X and Li, D and Zhou, M and Yu, C and Wu, H}, title = {Efficacy and safety of fecal microbiota transplantation for the treatment of irritable bowel syndrome: an overview of overlapping systematic reviews.}, journal = {Frontiers in pharmacology}, volume = {14}, number = {}, pages = {1264779}, pmid = {37915416}, issn = {1663-9812}, abstract = {Aim: Evidence from overlapping systematic reviews (SRs) and meta-analyses (MAs) has yielded conflicting results on the treatment of irritable bowel syndrome (IBS) with fecal microbiota transplantation (FMT). To thoroughly gather, assess, and synthesize evidence on FMT for IBS, we carried out the present study. Methods: A comprehensive search was conducted in Cochrane Library, Web of Science, PubMed, and Embase from inception to May 2023. Tools for assessing the methodological quality, reporting quality, and confidence in outcomes, including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2), Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Seven eligible SRs/MAs were finally included in this overview. By AMSTAR-2, the methodological quality of SRs/MAs included five that were very low quality, one that was low quality, and one that was high quality. According to PRISMA, limitations were associated with items 5 (Method: Protocol and Registration), 8 (Method: Search), and 27 (Funding). In GRADE, a total of 19 outcomes were included in the seven reviews, of which 12 outcomes were low quality and seven outcomes were moderate quality. Imprecision due to small sample size was the primary factor leading to evidence downgrading. Conclusion: We conclude that there is insufficient evidence to determine whether FMT has a more beneficial effect on patient with IBS than placebo treatment. Well-designed, larger trails are needed to provide evidence in this field. In addition, selection of donor, route of administration, dosage, and frequency still need to be determined.}, } @article {pmid37915336, year = {2023}, author = {Carrington, AE and Maloh, J and Nong, Y and Agbai, ON and Bodemer, AA and Sivamani, RK}, title = {The Gut and Skin Microbiome in Alopecia: Associations and Interventions.}, journal = {The Journal of clinical and aesthetic dermatology}, volume = {16}, number = {10}, pages = {59-64}, pmid = {37915336}, issn = {1941-2789}, abstract = {OBJECTIVE: This review examines the current literature on the gut-skin connection in alopecia and summarizes interventions that impact hair growth by modulation of the gut or skin microbiome.

METHODS: PubMed searches were done to assess studies of the gut and skin microbiome and forms of alopecia including, alopecia areata (AA), androgenic alopecia (AGA), alopecia universalis (AU), central centrifugal cicatricial alopecia (CCCA) and lichen planopilaris (LPP). Filters were applied for human and animal studies. Articles not translated to English and studies assessing supplemental therapies on alopecia were excluded.

RESULTS: There is evidence that scalp, hair follicle, and gut microbiome alterations are associated with various types of alopecia. There is potential in the use of interventions targeting microbiome dysbiosis, including fecal transplants and probiotics.

LIMITATIONS: This field of study still requires more high-quality research and studies with larger participant populations.

CONCLUSION: Dysbiosis on the scalp, within the hair follicle and the gut seem to have a role in the pathophysiology of various forms of alopecia. There is evidence that interventions targeting dysbiosis may have potential in the treatment and management of hair loss. Further studies are needed to establish a direct connection and to clarify specific effects of these interventions.}, } @article {pmid37914662, year = {2023}, author = {Yu, Y and Wang, W and Zhang, F}, title = {The Next Generation Fecal Microbiota Transplantation: To Transplant Bacteria or Virome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2301097}, doi = {10.1002/advs.202301097}, pmid = {37914662}, issn = {2198-3844}, support = {2021YFA0717004//National Key Research and Development Program of China/ ; //Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine/ ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for dysbiosis-related diseases. However, the clinical practice of crude fecal transplants presents limitations in terms of acceptability and reproductivity. Consequently, two alternative solutions to FMT are developed: transplanting bacteria communities or virome. Advanced methods for transplanting bacteria mainly include washed microbiota transplantation and bacteria spores treatment. Transplanting the virome is also explored, with the development of fecal virome transplantation, which involves filtering the virome from feces. These approaches provide more palatable options for patients and healthcare providers while minimizing research heterogeneity. In general, the evolution of the next generation of FMT in global trends is fecal microbiota components transplantation which mainly focuses on transplanting bacteria or virome.}, } @article {pmid37914097, year = {2023}, author = {He, H and He, H and Mo, L and You, Z and Zhang, J}, title = {Priming of microglia with dysfunctional gut microbiota impairs hippocampal neurogenesis and fosters stress vulnerability of mice.}, journal = {Brain, behavior, and immunity}, volume = {115}, number = {}, pages = {280-294}, doi = {10.1016/j.bbi.2023.10.031}, pmid = {37914097}, issn = {1090-2139}, abstract = {BACKGROUND: Mental disorders may be involved in neuroinflammatory processes that are triggered by gut microbiota. How gut microbiota influence microglia-mediated sensitivity to stress remains unclear. Here we explored in an animal model of depression whether disruption of the gut microbiome primes hippocampal microglia, thereby impairing neurogenesis and sensitizing to stress.

METHODS: Male C57BL/6J mice were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, and effects on gut microbiota were assessed using 16S rRNA sequencing. Fecal microbiota was transplanted from control or CUMS mice into naïve animals. The depression-like behaviors of recipients were evaluated in a forced swimming test and sucrose preference test. The morphology and phenotype of microglia in the hippocampus of recipients were examined using immunohistochemistry, quantitative PCR, and enzyme-linked immunosorbent assays. The recipients were treated with lipopolysaccharide or chronic stress exposure, and effects were evaluated on behavior, microglial responses and hippocampal neurogenesis. Finally, we explored the ability of minocycline to reverse the effects of CUMS on hippocampal neurogenesis and stress sensitivity in recipients.

RESULTS: CUMS altered the gut microbiome, leading to higher relative abundance of some bacteria (Helicobacter, Bacteroides, and Desulfovibrio) and lower relative abundance of some bacteria (Lactobacillus, Bifidobacterium, and Akkermansia). Fecal microbiota transplantation from CUMS mice to naïve animals induced microglial priming in the dentate gyrus of recipients. This microglia showed hyper-ramified morphology, and became more sensitive to LPS challenge or chronic stress, which characterized by more significant morphological changes and inflammatory responses, as well as impaired hippocampal neurogenesis and increased depressive-like behaviors. Giving minocycline to recipients reversed these effects of fecal transplantation.

CONCLUSIONS: These findings suggest that gut microbiota from stressed animals can induce microglial priming in the dentate gyrus, which is associated with a hyper-immune response to stress and impaired hippocampal neurogenesis. Remodeling the gut microbiome or inhibiting microglial priming may be strategies to reduce sensitivity to stress.}, } @article {pmid37910603, year = {2023}, author = {Woodworth, MH and Conrad, RE and Haldopoulos, M and Pouch, SM and Babiker, A and Mehta, AK and Sitchenko, KL and Wang, CH and Strudwick, A and Ingersoll, JM and Philippe, C and Lohsen, S and Kocaman, K and Lindner, BG and Hatt, JK and Jones, RM and Miller, C and Neish, AS and Friedman-Moraco, R and Karadkhele, G and Liu, KH and Jones, DP and Mehta, CC and Ziegler, TR and Weiss, DS and Larsen, CP and Konstantinidis, KT and Kraft, CS}, title = {Fecal microbiota transplantation promotes reduction of antimicrobial resistance by strain replacement.}, journal = {Science translational medicine}, volume = {15}, number = {720}, pages = {eabo2750}, doi = {10.1126/scitranslmed.abo2750}, pmid = {37910603}, issn = {1946-6242}, abstract = {Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (Akkermansia muciniphila, Alistipes putredinis, Phocaeicola dorei, Phascolarctobacterium faecium, Alistipes species, Mesosutterella massiliensis, Barnesiella intestinihominis, and Faecalibacterium prausnitzii) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum β-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.}, } @article {pmid37909786, year = {2023}, author = {Richie, TG and Heeren, L and Kamke, A and Monk, K and Pogranichniy, S and Summers, T and Wiechman, H and Ran, Q and Sarkar, S and Plattner, BL and Lee, STM}, title = {Limitation of amino acid availability by bacterial populations during enhanced colitis in IBD mouse model.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0070323}, doi = {10.1128/msystems.00703-23}, pmid = {37909786}, issn = {2379-5077}, abstract = {Members of the Enterobacteriaceae and Enterococcus are associated with persistent gut inflammation due to rapid colonization combined with pathogenic tendencies. Here, we investigated the functions of gut microbial populations resulting in persistent gut inflammation. In this study, we utilized the IL-10 knockout mouse model and induced colitis using dextran sulfate sodium (2%) after development. Dams during gestation were provided cefoperazone to induce vertically transmitted dysbiosis in the pups that were monitored in this study. We characterized the dysbiotic gut microbial community and potential crosstalk of these microbes, and host gene expression changes to identify bacterial populations and potential functions that were involved in gut inflammation. We isolated Enterobacteriaceae populations from mice to validate the utilization of sulfur-containing amino acids. Members of Enterobacteriaceae and Enterococcus were highly detected in inflamed mice. Enterobacteriaceae populations containing L-cysteine dioxygenase were strongly correlated with the upregulation of host gene CSAD, responsible for cysteine breakdown. We observed that bacterial isolates from dysbiotic mice displayed increased growth rates when supplemented with L-cysteine, highlighting the use of sulfur metabolism. Our results show that microbial populations use alternate metabolisms and sequester host nutrients for growth, associated with inflammation in the gut.IMPORTANCEInflammatory bowel disease is associated with an increase in Enterobacteriaceae and Enterococcus species; however, the specific mechanisms are unclear. Previous research has reported the associations between microbiota and inflammation, here we investigate potential pathways that specific bacteria populations use to drive gut inflammation. Richie et al. show that these bacterial populations utilize an alternate sulfur metabolism and are tolerant of host-derived immune-response products. These metabolic pathways drive host gut inflammation and fuel over colonization of these pathobionts in the dysbiotic colon. Cultured isolates from dysbiotic mice indicated faster growth supplemented with L-cysteine, showing these microbes can utilize essential host nutrients.}, } @article {pmid37906091, year = {2023}, author = {Zhou, H and Yu, B and Sun, J and Chen, H and Liu, Z and Ge, L and Chen, D}, title = {Gut microbiota absence and transplantation affect diarrhea: an investigation in the germ-free piglet model.}, journal = {Animal biotechnology}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/10495398.2023.2248200}, pmid = {37906091}, issn = {1532-2378}, abstract = {This experiment was conducted to explore the effects of gut microbiota on neonatal diarrhea in a germ-free (GF) pig model. Twelve hysterectomy-derived GF piglets were housed in six sterile isolators. Among them, six piglets were treated as the GF group, and the other six piglets were orally introduced with healthy sow fecal suspension and regarded as the fecal microbiota transplantation (FMT) group. Another six piglets from natural birth were considered as the conventional (CV) group. The GF and FMT piglets were hand-fed with sterile milk powder for 21 days, and the CV piglets were suckled for the same days. Then, all piglets were fed with sterile feed for another 21 days. Results exhibited that the GF group's fecal score and moisture level were higher than those in the CV and FMT groups (p < 0.05). Meanwhile, the abundances of colonic AQP1 and AQP8 in the GF group were the greatest among these treatments (p < 0.05). However, FMT piglets had a lower fecal score in d 22-28 and d 29-35 than that in the CV piglets (p < 0.05). Collectively, the absence of gut microbiota may cause diarrhea in the piglet model, and transplantation of maternal fecal microbiota may reverse it.}, } @article {pmid37475479, year = {2023}, author = {Lawenius, L and Cowardin, C and Grahnemo, L and Scheffler, JM and Horkeby, K and Engdahl, C and Wu, J and Vandenput, L and Koskela, A and Tuukkanen, J and Coward, E and Hveem, K and Langhammer, A and Abrahamsson, S and Gordon, JI and Sjögren, K and Ohlsson, C}, title = {Transplantation of gut microbiota from old mice into young healthy mice reduces lean mass but not bone mass.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2236755}, pmid = {37475479}, issn = {1949-0984}, mesh = {Young Adult ; Humans ; Mice ; Animals ; Aged ; Infant ; *Gastrointestinal Microbiome ; *Microbiota ; Fecal Microbiota Transplantation ; Aging ; Cecum ; }, abstract = {Aging is associated with low bone and lean mass as well as alterations in the gut microbiota (GM). In this study, we determined whether the reduced bone mass and relative lean mass observed in old mice could be transferred to healthy young mice by GM transplantation (GMT). GM from old (21-month-old) and young adult (5-month-old) donors was used to colonize germ-free (GF) mice in three separate studies involving still growing 5- or 11-week-old recipients and 17-week-old recipients with minimal bone growth. The GM of the recipient mice was similar to that of the donors, demonstrating successful GMT. GM from old mice did not have statistically significant effects on bone mass or bone strength, but significantly reduced the lean mass percentage of still growing recipient mice when compared with recipients of GM from young adult mice. The levels of propionate in the cecum of mice receiving old donor GM were significantly lower than those in mice receiving young adult donor GM. Bacteroides ovatus was enriched in the microbiota of recipient mice harboring GM from young adult donors. The presence of B. ovatus was not only significantly associated with high lean mass percentage in mice, but also with lean mass adjusted for fat mass in the large human HUNT cohort. In conclusion, GM from old mice reduces lean mass percentage but not bone mass in young, healthy, still growing recipient mice. Future studies are warranted to determine whether GM from young mice improves the musculoskeletal phenotype of frail elderly recipient mice.}, } @article {pmid37905694, year = {2023}, author = {Tian, X and Wang, G and Teng, F and Xue, X and Pan, J and Mao, Q and Guo, D and Song, X and Ma, K}, title = {Zhi Zi Chi decoction (Gardeniae fructus and semen Sojae Praeparatum) attenuates anxious depression via modulating microbiota-gut-brain axis in corticosterone combined with chronic restraint stress-induced mice.}, journal = {CNS neuroscience & therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/cns.14519}, pmid = {37905694}, issn = {1755-5949}, support = {//National Natural Science Foundation of China/ ; //Natural Science Foundation of Shandong Province/ ; //Shandong Province Universities' Development Plan for Youth Innovation Teams/ ; }, abstract = {BACKGROUND: The microbiota-gut-brain axis plays a critical role in neuropsychiatric disorders, particularly anxious depression, and attracts more attention gradually. Zhi Zi Chi decoction (ZZCD) consisting of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr, is a classic formula in clinic and widely applied in anxiety and depression treatment. However, the underlying mechanisms of regulating microbiota-gut-brain axis in the treatment of anxious depression by oral administration of ZZCD remain elusive.

MATERIALS AND METHODS: In this project, we clarified the origin and preparation methods of the Gardenia jasminoides J. Ellis and Glycine max (L.) Merr and examined the chemical ingredients of ZZCD by liquid chromatograph mass spectrometer. Then, corticosterone combined with chronic restraint stress was applied to establish an anxious depression model. After treated with ZZCD standard decoction, based on enzyme-linked immunosorbent assay (ELISA), 16S rRNA technology, high-throughput sequencing, quantitative RT-PCR and fecal microbiota transplantation (FMT), the multiple associations between nucleus accumbens and intestinal flora in anxious depression mice were determined to clarify the mechanism of ZZCD in the treatment of anxiety and depression disorder.

RESULTS: We found various substances with antidepressant and antianxiety properties in ZZCD such as rosiridin and oleanolic acid. ZZCD could alleviate depressive and anxiety behaviors in anxious depression mice via regulating the disturbance of gut microbiota. Meanwhile, the bioactive compounds of ZZCD might directly active on neurodevelopment and neuroimmune-related genes. Furthermore, the secretion of prolactin and estrogen, and interfering with mitogen-activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling pathways were mainly involved in the multi-target therapeutic effects of ZZCD against anxiety and depression.

CONCLUSIONS: These findings suggested that ZZCD exerts antidepressant effects pleiotropically through modulating the microbiota-gut-brain.}, } @article {pmid37902074, year = {2023}, author = {Balzano, T and Llansola, M and Arenas, YM and Izquierdo-Altarejos, P and Felipo, V}, title = {Hepatic encephalopathy: investigational drugs in preclinical and early phase development.}, journal = {Expert opinion on investigational drugs}, volume = {}, number = {}, pages = {}, doi = {10.1080/13543784.2023.2277386}, pmid = {37902074}, issn = {1744-7658}, abstract = {INTRODUCTION: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, in patients with liver disease, which affects life quality and span. Current treatments are lactulose or rifaximin, acting on gut microbiota. Treatments aiming ammonia levels reduction have been tested with little success.

AREAS COVERED: Pre-clinical research shows that the process inducing HE involves sequentially: liver failure, altered microbiome, hyperammonemia, peripheral inflammation, changes in immunophenotype and extracellular vesicles and neuroinflammation which alters neurotransmission impairing cognitive and motor function. HE may be reversed using drugs acting at any step: modulating microbiota with probiotics or fecal transplantation; reducing peripheral inflammation with anti-TNFα, autotaxin inhibitors or silymarin; reducing neuroinflammation with sulforaphane, p38 MAP kinase or phosphodiesteras 5, antagonists of sphingosine-1-phosphate receptor2, enhancing meningeal lymphatic drainage or with extracellular vesicles from mesenchymal stem cells; reducing GABAergic neurotransmission with indomethacin or golexanolone.

EXPERT OPINION: A factor limiting the progress of HE treatment is the lack of translation of research advances into clinical trials. Only drugs acting on microbiota or ammonia reduction have been tested in patients. t is urgent to change the mentality on how to approach HE treatment to develop clinical trials to assess drugs acting on the immune system/peripheral inflammation, neuroinflammation or neurotransmission to improve HE.}, } @article {pmid37896894, year = {2023}, author = {Louge Uriarte, EL and Badaracco, A and Spetter, MJ and Miño, S and Armendano, JI and Zeller, M and Heylen, E and Späth, E and Leunda, MR and Moreira, AR and Matthijnssens, J and Parreño, V and Odeón, AC}, title = {Molecular Epidemiology of Rotavirus A in Calves: Evolutionary Analysis of a Bovine G8P[11] Strain and Spatio-Temporal Dynamics of G6 Lineages in the Americas.}, journal = {Viruses}, volume = {15}, number = {10}, pages = {}, pmid = {37896894}, issn = {1999-4915}, support = {AESA 203971 and PNSA 1115053//Instituto Nacional de Tecnología Agropecuaria (INTA)/ ; PICT N 38308//Ministerio de Ciencia, Tecnología e Innovación (MINCyT)/ ; }, mesh = {Animals ; Cattle ; *Rotavirus/genetics ; Molecular Epidemiology ; Phylogeny ; *Rotavirus Infections/epidemiology/veterinary ; Diarrhea/epidemiology/veterinary ; Genotype ; Feces ; *Cattle Diseases/epidemiology ; }, abstract = {Rotavirus A (RVA) causes diarrhea in calves and frequently possesses the G6 and P[5]/P[11] genotypes, whereas G8 is less common. We aimed to compare RVA infections and G/P genotypes in beef and dairy calves from major livestock regions of Argentina, elucidate the evolutionary origin of a G8 strain and analyze the G8 lineages, infer the phylogenetic relationship of RVA field strains, and investigate the evolution and spatio-temporal dynamics of the main G6 lineages in American countries. Fecal samples (n = 422) from diarrheic (beef, 104; dairy, 137) and non-diarrheic (beef, 78; dairy, 103) calves were analyzed by ELISA and semi-nested multiplex RT-PCR. Sequencing, phylogenetic, phylodynamic, and phylogeographic analyses were performed. RVA infections were more frequent in beef (22.0%) than in dairy (14.2%) calves. Prevalent genotypes and G6 lineages were G6(IV)P[5] in beef (90.9%) and G6(III)P[11] (41.2%) or mixed genotypes (23.5%) in dairy calves. The only G8 strain was phylogenetically related to bovine and artiodactyl bovine-like strains. Re-analyses inside the G8 genotype identified G8(I) to G8(VIII) lineages. Of all G6 strains characterized, the G6(IV)P[5](I) strains from "Cuenca del Salado" (Argentina) and Uruguay clustered together. According to farm location, a clustering pattern for G6(IV)P[5] strains of beef farms was observed. Both G6 lineage strains together revealed an evolutionary rate of 1.24 × 10[-3] substitutions/site/year, and the time to the most recent common ancestor was dated in 1853. The most probable ancestral locations were Argentina in 1981 for G6(III) strains and the USA in 1940 for G6(IV) strains. The highest migration rates for both G6 lineages together were from Argentina to Brazil and Uruguay. Altogether, the epidemiology, genetic diversity, and phylogeny of RVA in calves can differ according to the production system and farm location. We provide novel knowledge about the evolutionary origin of a bovine G8P[11] strain. Finally, bovine G6 strains from American countries would have originated in the USA nearly a century before its first description.}, } @article {pmid37895006, year = {2023}, author = {Kim, S and Noh, JH and Lee, MJ and Park, YJ and Kim, BM and Kim, YS and Hwang, S and Park, C and Kim, K}, title = {Effects of Mitochondrial Transplantation on Transcriptomics in a Polymicrobial Sepsis Model.}, journal = {International journal of molecular sciences}, volume = {24}, number = {20}, pages = {}, pmid = {37895006}, issn = {1422-0067}, support = {NRF- 2020R1A2C3004508//National Research Foundation of Korea/ ; }, mesh = {Rats ; Animals ; *Transcriptome ; Mitochondria/genetics/metabolism ; Gene Expression Profiling ; *Sepsis/genetics/metabolism ; }, abstract = {Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobial sepsis. Total RNA from splenocytes of sham-operated (SHAM, n = 10), sepsis-induced (SEPSIS, n = 7), and sepsis receiving mitochondrial transplantation (SEPSIS + MT, n = 8) samples was extracted and we conducted a comparative transcriptome-wide analysis between three groups. We also confirmed these results with qPCR. In terms of percentage of mitochondrial mapped reads, the SEPSIS + MT group had a significantly higher mapping ratio than the others. RT1-M2 and Cbln2 were identified as highly expressed in SEPSIS + MT compared with SEPSIS. Using SHAM expression levels as another control variable, we further identified six genes (Fxyd4, Apex2l1, Kctd4, 7SK, SNORD94, and SNORA53) that were highly expressed after sepsis induction and observed that their expression levels were attenuated by mitochondrial transplantation. Changes in transcriptomic features were identified after mitochondrial transplantation in sepsis. This might provide a hint for exploring the mechanism of mitochondrial transplantation in sepsis.}, } @article {pmid37894615, year = {2023}, author = {Ni, Z and Li, J and Qian, X and Yong, Y and Wu, M and Wang, Y and Lv, W and Zhang, S and Zhang, Y and Shao, Y and Chen, A}, title = {Phellinus igniarius Polysaccharides Ameliorate Hyperglycemia by Modulating the Composition of the Gut Microbiota and Their Metabolites in Diabetic Mice.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {20}, pages = {}, pmid = {37894615}, issn = {1420-3049}, support = {BY2022773//Jiangsu Province's industry university research cooperation project/ ; BY2022777//Jiangsu Province's industry university research cooperation project/ ; KC22477//Xuzhou Science and Technology Program/ ; }, mesh = {Mice ; Animals ; *Diabetes Mellitus, Type 2/drug therapy ; *Diabetes Mellitus, Experimental ; *Gastrointestinal Microbiome ; Dysbiosis/drug therapy/microbiology ; *Hyperglycemia/drug therapy ; Polysaccharides/pharmacology/therapeutic use ; }, abstract = {Gut microbiota dysbiosis has been reported as a risk factor in the development of type 2 diabetes mellitus (T2DM). Polysaccharides from Phellinus igniarius (P. igniarius) possess various properties that help manage metabolic diseases; however, their underlying mechanism of action remains unclear. Therefore, in this study, we aimed to evaluate the effect of P. igniarius polysaccharides (SH-P) on improving hyperglycemia in mice with T2DM and clarified its association with the modulation of gut microbiota and their metabolites using 16S rDNA sequencing and liquid chromatography-mass spectrometry. Fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. SH-P supplementation alleviated hyperglycemia symptoms in T2DM mice, ameliorated gut dysbiosis, and significantly increased the abundance of Lactobacillus in the gut. Pathway enrichment analysis indicated that SH-P treatment altered metabolic pathways associated with the occurrence and development of diabetes. Spearman's correlation analysis revealed that changes in the dominant bacterial genera were significantly correlated with metabolite levels closely associated with hyperglycemia. Additionally, FMT significantly improved insulin sensitivity and antioxidative capacity and reduced inflammation and tissue injuries, indicating improved glucose homeostasis. These results indicate that the ameliorative effects of SH-P on hyperglycemia are associated with the modulation of gut microbiota composition and its metabolites.}, } @article {pmid37894194, year = {2023}, author = {Lopetuso, LR and Laterza, L and Petito, V and Pecere, S and Quaranta, G and Del Chierico, F and Puca, P and Schiavoni, E and Napolitano, D and Poscia, A and Ianiro, G and Pugliese, D and Putignani, L and Sanguinetti, M and Armuzzi, A and Masucci, L and Gasbarrini, A and Cammarota, G and Scaldaferri, F}, title = {Serial Fecal Microbiota Infusions via Colonoscopy for Active Ulcerative Colitis: A Feasibility, Safety, and Translational Monocentric Italian Study.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894194}, issn = {2076-2607}, abstract = {The effectiveness of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study aimed to investigate the feasibility and effectiveness of serial fecal infusions via colonoscopy in patients with active UC. Subjects with mild-to-moderate UC received three consecutive fecal infusions via colonoscopy. A control population with the same baseline features receiving Infliximab treatment was enrolled. Adverse events and clinical, endoscopic, and microbial outcomes were investigated. Nineteen patients with mildly-to-moderately active UC were enrolled. Clinical response was obtained in six patients at week 2, in eight at week 6, and in nine at week 12. Clinical response was maintained in eight patients at week 24. Endoscopic remission at week 12 was reached in six patients. In the control population, 13/19 patients achieved clinical response at week 6, and 10/19 patients maintained clinical response after 6 months. Microbiota richness was higher in responders compared with the non-responders. Peptostreptococcus, Lactobacillus, and Veillonella were higher in non-responders, while Parabacteroides, Bacteroides, Faecalibacterium, and Akkermansia were higher in responders at all timepoints. Serial FMT infusions appear to be feasible, safe, and effective in UC patients, with a potential role in inducing and maintaining clinical response. Specific bacteria predict the response to FMT.}, } @article {pmid37894186, year = {2023}, author = {Beharry, KD and Latkowska, M and Valencia, AM and Allana, A and Soto, J and Cai, CL and Golombek, S and Hand, I and Aranda, JV}, title = {Factors Influencing Neonatal Gut Microbiome and Health with a Focus on Necrotizing Enterocolitis.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894186}, issn = {2076-2607}, abstract = {Maturational changes in the gut start in utero and rapidly progress after birth, with some functions becoming fully developed several months or years post birth including the acquisition of a full gut microbiome, which is made up of trillions of bacteria of thousands of species. Many factors influence the normal development of the neonatal and infantile microbiome, resulting in dysbiosis, which is associated with various interventions used for neonatal morbidities and survival. Extremely low gestational age neonates (<28 weeks' gestation) frequently experience recurring arterial oxygen desaturations, or apneas, during the first few weeks of life. Apnea, or the cessation of breathing lasting 15-20 s or more, occurs due to immature respiratory control and is commonly associated with intermittent hypoxia (IH). Chronic IH induces oxygen radical diseases of the neonate, including necrotizing enterocolitis (NEC), the most common and devastating gastrointestinal disease in preterm infants. NEC is associated with an immature intestinal structure and function and involves dysbiosis of the gut microbiome, inflammation, and necrosis of the intestinal mucosal layer. This review describes the factors that influence the neonatal gut microbiome and dysbiosis, which predispose preterm infants to NEC. Current and future management and therapies, including the avoidance of dysbiosis, the use of a human milk diet, probiotics, prebiotics, synbiotics, restricted antibiotics, and fecal transplantation, for the prevention of NEC and the promotion of a healthy gut microbiome are also reviewed. Interventions directed at boosting endogenous and/or exogenous antioxidant supplementation may not only help with prevention, but may also lessen the severity or shorten the course of the disease.}, } @article {pmid37885166, year = {2023}, author = {El-Salhy, M and Gilja, OH and Hatlebakk, JG}, title = {Letter: A step forward towards a standard FMT protocol for IBS.}, journal = {Alimentary pharmacology & therapeutics}, volume = {58}, number = {10}, pages = {1115-1116}, doi = {10.1111/apt.17749}, pmid = {37885166}, issn = {1365-2036}, mesh = {Humans ; *Irritable Bowel Syndrome/diagnosis/therapy ; Fecal Microbiota Transplantation/methods ; Feces ; Antineoplastic Combined Chemotherapy Protocols ; Treatment Outcome ; }, } @article {pmid37894065, year = {2023}, author = {Martinelli, S and Nannini, G and Cianchi, F and Staderini, F and Coratti, F and Amedei, A}, title = {Microbiota Transplant and Gynecological Disorders: The Bridge between Present and Future Treatments.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, doi = {10.3390/microorganisms11102407}, pmid = {37894065}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is a procedure that involves transferring fecal bacteria from a healthy donor to a patients' intestines to restore gut-immunity homeostasis. While FMT was primarily supposed to treat gastrointestinal disorders such as inflammatory bowel disease and irritable bowel syndrome-and especially Clostridium difficile infection (currently the only used as clinical treatment)-recent research has suggested that it may also become a potential treatment for gynecological disorders, including endometriosis and polycystic ovary syndrome (PCOS). On the contrary, vaginal microbiota transplantation (VMT) is a newer and less commonly used procedure than the FMT approach, and its potential applications are still being explored. It involves direct grafting of the entire vaginal microbiota of healthy women into the vaginal tract of patients to easily rebuild the local microbiota environment, restoring vaginal eubiosis and relieving symptoms. Like FMT, VMT is thought to have potential in treating different microbiota-related conditions. In fact, many gynecological disorders, such as bacterial vaginosis and vulvovaginal candidiasis, are thought to be caused by an imbalance in the vaginal microbiota. In this review, we will summarize the development, current challenges, and future perspectives of microbiota transplant, with the aim of exploring new strategies for its employment as a promising avenue for treating a broad range of gynecological diseases.}, } @article {pmid37894027, year = {2023}, author = {Napolitano, M and Fasulo, E and Ungaro, F and Massimino, L and Sinagra, E and Danese, S and Mandarino, FV}, title = {Gut Dysbiosis in Irritable Bowel Syndrome: A Narrative Review on Correlation with Disease Subtypes and Novel Therapeutic Implications.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, doi = {10.3390/microorganisms11102369}, pmid = {37894027}, issn = {2076-2607}, abstract = {Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community. Emerging research spotlights the intricate involvement of microbiota dysbiosis in IBS pathogenesis. Studies have demonstrated reduced microbial diversity and stability and specific microbial alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and even diet, offer exciting prospects for managing IBS. However, definitive conclusions are hindered by the heterogeneity of these studies. Further research should focus on elucidating the mechanisms, developing microbiome-based diagnostics, and enabling personalized therapies tailored to an individual's microbiome profile. This review takes a deep dive into the microscopic world inhabiting our guts, and its implications for IBS. Our aim is to elucidate the complex interplay between gut microbiota and each IBS subtype, exploring novel microbiota-targeted treatments and providing a comprehensive overview of the current state of knowledge.}, } @article {pmid37892453, year = {2023}, author = {Wu, S and Wu, Z and Chen, Y}, title = {Effect of Cordyceps militaris Powder Prophylactic Supplementation on Intestinal Mucosal Barrier Impairment and Microbiota-Metabolites Axis in DSS-Injured Mice.}, journal = {Nutrients}, volume = {15}, number = {20}, pages = {}, doi = {10.3390/nu15204378}, pmid = {37892453}, issn = {2072-6643}, support = {82070543//National Natural Science Foundation of China/ ; 82270581//National Natural Science Foundation of China/ ; 2021YFA0717001//National Key R&D Program of China/ ; KCXFZ20211020163558024//Shenzhen Science and Technology Planning Project/ ; ZDSYS20220606100800002//Shenzhen Science and Technology Program/ ; }, abstract = {Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease with an unknown pathogenesis and increasing incidence. The objective of this study is to investigate the impact of prophylactic treatment with Cordyceps militaris on UC. The findings demonstrate that prophylactic supplementation of C. militaris powder effectively mitigates disease symptoms in DSS-injured mice, while also reducing the secretion of pro-inflammatory cytokines. Furthermore, C. militaris powder enhances the integrity of the intestinal mucosal barrier by up-regulating MUC2 protein expression and improving tight junction proteins (ZO-1, occludin, and claudin 1) in DSS-injured mice. Multiomics integration analyses revealed that C. militaris powder not only reshaped gut microbiota composition, with an increase in Lactobacillus, Odoribacter, and Mucispirillum, but also exerted regulatory effects on various metabolic pathways including amino acid, glyoxylates, dicarboxylates, glycerophospholipids, and arachidonic acid. Subsequent analysis further elucidated the intricate interplay of gut microbiota, the intestinal mucosal barrier, and metabolites, suggesting that the microbiota-metabolite axis may involve the effect of C. militaris on intestinal mucosal barrier repair in UC. Moreover, in vitro experiments demonstrated that peptides and polysaccharides, derived from C. militaris, exerted an ability to change the gut microbiota structure of UC patients' feces, particularly by promoting the growth of Lactobacillus. These findings suggest that regulatory properties of C. militaris on gut microbiota may underlie the potential mechanism responsible for the protective effect of C. militaris in UC. Consequently, our study will provide support for the utilization of C. militaris as a whole food-based ingredient against the occurrence and development of UC.}, } @article {pmid37891616, year = {2023}, author = {Moreno, AF and Lavín-Alconero, L and de Ugarriza, PL and Blanco, LS and Hernández, SC and Burgués, JMB and de Miguel, MI and Huerta, AJG and Zarzuela, MP and Boluda, B and Humala, K and Calabuig, ML and Amigo, ML and Casas, MC and Del Mar García-Saiz, M and Verdugo, AF and Domínguez, JF and Bernal, T}, title = {FOVOCIP study: a multicenter randomized trial of fosfomycin versus ciprofloxacin for febrile neutropenia in hematologic patients-efficacy and microbiologic safety.}, journal = {Trials}, volume = {24}, number = {1}, pages = {694}, pmid = {37891616}, issn = {1745-6215}, support = {FIS PI21/01590//Instituto de Salud Carlos III/ ; }, abstract = {BACKGROUND: Multidrug-resistant Gram-negative bacterial (MRGNB) infections represent a major public health threat. Cancer patients and, among them, hematological patients are most vulnerable to these infections. Gut colonization by MRGNB is a common phenomenon occurring during hospitalization and chemotherapy exposure. In the neutropenic phase that occurs after chemotherapy, MRGNB translocation occurs increasing patient's mortality. Fluoroquinolone prophylaxis with ciprofloxacin or levofloxacin efficacy is now being questioned due to the increase of incidence in MRGNB.

METHODS: A phase III randomized, controlled, clinical trial, open-label parallel-group with a 1:1 ratio, aimed to demonstrate the non-inferiority of oral fosfomycin versus oral ciprofloxacin for febrile neutropenia prevention in patients with acute leukemia (AL) or hematopoietic cell transplant (HSC) receptors. Weekly surveillance cultures are planned to detect gut colonization. Changes in fecal microbiome at the beginning and end of prophylaxis will also be analyzed.

DISCUSSION: This trial will provide evidence of the efficacy of an alternative drug to ciprofloxacin for febrile neutropenia prevention in high-risk hematological patients. The battery of planned microbiological studies will allow us to evaluate prospectively the microbiological safety of both pharmacological strategies in terms of the selection of MRGNB occurring in each arm. In addition, valuable information on the way in which each drug changes the fecal microbiome of the patients throughout the treatment will be generated.

TRIAL REGISTRATION: Clinical trials NCT05311254, Registered on 5 April 2022, https://clinicaltrials.gov/ct2/show/NCT05311254?term=FOVOCIP&cntry=ES&draw=2&rank=1 .

PROTOCOL VERSION: 3.0, dated 20 May 2022.}, } @article {pmid37888102, year = {2023}, author = {Kaltsas, A and Zachariou, A and Markou, E and Dimitriadis, F and Sofikitis, N and Pournaras, S}, title = {Microbial Dysbiosis and Male Infertility: Understanding the Impact and Exploring Therapeutic Interventions.}, journal = {Journal of personalized medicine}, volume = {13}, number = {10}, pages = {}, pmid = {37888102}, issn = {2075-4426}, abstract = {The human microbiota in the genital tract is pivotal for maintaining fertility, but its disruption can lead to male infertility. This study examines the relationship between microbial dysbiosis and male infertility, underscoring the promise of precision medicine in this field. Through a comprehensive review, this research indicates microbial signatures associated with male infertility, such as altered bacterial diversity, the dominance of pathogenic species, and imbalances in the genital microbiome. Key mechanisms linking microbial dysbiosis to infertility include inflammation, oxidative stress, and sperm structural deterioration. Emerging strategies like targeted antimicrobial therapies, probiotics, prebiotics, and fecal microbiota transplantation have shown potential in adjusting the genital microbiota to enhance male fertility. Notably, the application of precision medicine, which customizes treatments based on individual microbial profiles and specific causes of infertility, emerges as a promising approach to enhance treatment outcomes. Ultimately, microbial dysbiosis is intricately linked to male infertility, and embracing personalized treatment strategies rooted in precision medicine principles could be the way forward in addressing infertility associated with microbial factors.}, } @article {pmid37887364, year = {2023}, author = {Jess, AT and Eskander, GH and Vu, MH and Michail, S}, title = {Short-Chain Fatty Acid Levels after Fecal Microbiota Transplantation in a Pediatric Cohort with Recurrent Clostridioides difficile Infection.}, journal = {Metabolites}, volume = {13}, number = {10}, pages = {}, pmid = {37887364}, issn = {2218-1989}, abstract = {Though antibiotics are the mainstay treatment for Clostridioides difficile, a large population of individuals infected will experience recurrence. In turn, fecal microbiota transplantation (FMT) has emerged as a promising treatment for recurrent C. difficile infection (rCDI). Mechanistically, by providing a healthy, diverse flora to the infected individual, FMT "resets" the underlying gut microbiome dysbiosis associated with rCDI. A proposed mechanism through which this occurs is via microbiome metabolites such as short-chain fatty acids (SCFAs); however, this has not been previously studied in pediatric patients. Using mass spectroscopy, we quantified pre- and post-transplant levels of acetate, isovalerate, butyrate, formate, and propionate in pediatric patients diagnosed with rCDI (n = 9). We compared pre- and post-transplant levels within the rCDI cohort at 1, 3, 6, and 12 months post-transplant and correlated these levels with healthy controls (n = 19). We witnessed a significant difference in the combined SCFA levels and the individual levels of acetate, butyrate, isovalerate, and propionate in the pre-treatment rCDI cohort compared to the healthy controls. In addition, there was a significant increase in combined SCFA levels at 12 months post-transplant within the rCDI group compared to that of their pre-transplant levels, and, more specifically, acetate, propionate, and isovalerate increased from pre-transplant to 12 months post-transplant. The longitudinal aspect of this study allowed us to identify mechanisms that contribute to the durability of responses to FMT, as well as characterize the unique patterns of short-chain fatty acid level recovery in rCDI pediatric patients.}, } @article {pmid37887204, year = {2023}, author = {Pang, J and Beyi, AF and Looft, T and Zhang, Q and Sahin, O}, title = {Fecal Microbiota Transplantation Reduces Campylobacter jejuni Colonization in Young Broiler Chickens Challenged by Oral Gavage but Not by Seeder Birds.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, doi = {10.3390/antibiotics12101503}, pmid = {37887204}, issn = {2079-6382}, support = {2018-67017-28117//United States Department of Agriculture/ ; }, abstract = {Campylobacter spp., particularly C. jejuni and C. coli, are major food safety concerns, transmitted to humans mainly via contaminated poultry meat. In a previous study, we found that some commercial broiler farms consistently produced Campylobacter-free flocks while others consistently reared Campylobacter-colonized flocks, and significant differences in the gut microbiota compositions between the two types of farm categories were revealed. Therefore, we hypothesized that gut microbiota influences Campylobacter colonization in poultry and that the microbiota from Campylobacter-free flocks may confer colonization resistance to Campylobacter in the chicken intestine. In this study, two fecal microbiota transplantation (FMT) trials were performed to test the hypothesis. Newly hatched chicks were given FMT via oral gavage of the cecal content of Campylobacter-free adult chickens (treatment groups) or PBS (control groups) before the feed consumption. Approximately two weeks after the FMT, the birds were challenged with C. jejuni either by oral gavage (trial 1) or by co-mingling with Campylobacter-colonized seeder birds (trial 2) to evaluate the potential protective effect of the FMT. Cecal contents were collected (3 times, 5 days apart) to determine the Campylobacter colonization levels via culture and microbiota compositions via 16S rRNA gene sequencing. FMT reduced cecal Campylobacter colonization significantly (log10 1.2-2.54 CFU/g) in trial 1 but not in trial 2, although FMT significantly impacted the diversity and compositions of the gut microbiota in both trials. Several genera, such as Butyricimonas, Parabacteroides, Parasutterella, Bilophila, Fournierella, Phascolarctobacterium, and Helicobacter, had increased abundance in the FMT-treated groups in both trials. Furthermore, Campylobacter abundance was found to be negatively correlated with the Escherichia and Ruminococcus_torques_group genera. These findings indicate that even though FMT with adult cecal microbiota can positively affect the subsequent development of the gut microbiota in young broilers, its inhibitory effect on Campylobacter colonization varies and appears to be influenced by the challenge models.}, } @article {pmid37879794, year = {2023}, author = {Liu, Y and Wu, H and Wang, T and Shi, X and He, H and Huang, H and Yang, Y and Dai, M}, title = {Paeonol reduces microbial metabolite α-hydroxyisobutyric acid to alleviate the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in atherosclerosis mice.}, journal = {Chinese journal of natural medicines}, volume = {21}, number = {10}, pages = {759-774}, doi = {10.1016/S1875-5364(23)60506-0}, pmid = {37879794}, issn = {1875-5364}, mesh = {Mice ; Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/genetics ; Reactive Oxygen Species ; Endothelial Cells ; Inflammation/drug therapy ; *Atherosclerosis/drug therapy ; Mice, Inbred C57BL ; Diet, High-Fat ; }, abstract = {Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE[-/-] mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg[-1]) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.}, } @article {pmid37879793, year = {2023}, author = {Zhou, J and Fan, Q and Cai, X and Zhang, Y and Hou, Y and Cao, S and Li, Z and Feng, M and Wang, Q and Zhang, J and Wang, G and Zheng, X and Hao, H}, title = {Ginkgo biloba extract protects against depression-like behavior in mice through regulating gut microbial bile acid metabolism.}, journal = {Chinese journal of natural medicines}, volume = {21}, number = {10}, pages = {745-758}, doi = {10.1016/S1875-5364(23)60496-0}, pmid = {37879793}, issn = {1875-5364}, mesh = {Humans ; Mice ; Animals ; *Depression/drug therapy ; *Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba ; }, abstract = {Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.}, } @article {pmid37873265, year = {2023}, author = {Chang, D and Gupta, VK and Hur, B and Cobo-López, S and Cunningham, KY and Han, NS and Lee, I and Kronzer, VL and Teigen, LM and Karnatovskaia, LV and Longbrake, EE and Davis, JM and Nelson, H and Sung, J}, title = {Gut Microbiome Wellness Index 2 for Enhanced Health Status Prediction from Gut Microbiome Taxonomic Profiles.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.09.30.560294}, pmid = {37873265}, abstract = {Recent advancements in human gut microbiome research have revealed its crucial role in shaping innovative predictive healthcare applications. We introduce Gut Microbiome Wellness Index 2 (GMWI2), an advanced iteration of our original GMWI prototype, designed as a robust, disease-agnostic health status indicator based on gut microbiome taxonomic profiles. Our analysis involved pooling existing 8069 stool shotgun metagenome data across a global demographic landscape to effectively capture biological signals linking gut taxonomies to health. GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence (i.e., outside the "reject option"). The enhanced classification accuracy of GMWI2 outperforms both the original GMWI model and traditional species-level α-diversity indices, suggesting a more reliable tool for differentiating between healthy and non-healthy phenotypes using gut microbiome data. Furthermore, by reevaluating and reinterpreting previously published data, GMWI2 provides fresh insights into the established understanding of how diet, antibiotic exposure, and fecal microbiota transplantation influence gut health. Looking ahead, GMWI2 represents a timely pivotal tool for evaluating health based on an individual's unique gut microbial composition, paving the way for the early screening of adverse gut health shifts. GMWI2 is offered as an open-source command-line tool, ensuring it is both accessible to and adaptable for researchers interested in the translational applications of human gut microbiome science.}, } @article {pmid37872499, year = {2023}, author = {Skjevling, LK and Hanssen, HM and Valle, PC and Goll, R and Juul, FE and Arlov, Ø and Johnsen, PH}, title = {Colonic distribution of FMT by different enema procedures compared to colonoscopy - proof of concept study using contrast fluid.}, journal = {BMC gastroenterology}, volume = {23}, number = {1}, pages = {363}, pmid = {37872499}, issn = {1471-230X}, mesh = {Humans ; Fecal Microbiota Transplantation/methods ; Cross-Over Studies ; Proof of Concept Study ; *Clostridioides difficile ; Colonoscopy ; *Clostridium Infections/therapy ; Treatment Outcome ; Enema ; Colon/diagnostic imaging ; Recurrence ; Feces ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has become an important treatment method in recurrent Clostridioides difficile infections and is under investigation as a treatment for several other diseases. FMT's mechanism of action is assumed to be through alterations of the colon microbiota. FMT can be delivered by several methods, but few studies have directly compared how FMT is distributed in the colon by different methods. Specifically, the proximal distribution of FMT delivered by enema is unknown.

METHODS: In eight participants, we administered contrast fluid (CF) with viscosity similar to an FMT in a crossover study design. First, CF was administered by colonoscopy, followed by an abdominal X-ray to visualize the CF distribution. Next, after four to eight weeks, participants were given CF, but as an enema, followed by a positioning procedure. X-rays were obtained before (enema ÷) and after (enema +) the positioning procedure.

CONCLUSION: Proportion of participants with CF in cecum were 100% after colonoscopy, 50% after enema + and 38% after enema ÷. In the transverse colon, proportions were 100% (colonoscopy), 88% (enema +) and 63% (enema ÷). There were no adverse events.

INTERPRETATION: This study shows proof of concept for the distribution of FMT to proximal colon when delivered by enema. A positioning procedure after the enema slightly improves the proximal distribution. However, colonoscopy is the only method that ensures delivery to the cecum. Studies are needed to see if FMT colon distribution correlates with treatment effectiveness.

TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov (NCT05121285) (16/11/2021).}, } @article {pmid37872356, year = {2023}, author = {Jadhav, G and Dudhabhate, BB and Kokare, DM and Sakharkar, AJ}, title = {Gut Microbiota Regulates Epigenetic Remodelling in the Amygdala: A Role in Repeated Mild Traumatic Brain Injury (rMTBI)-Induced Anxiety.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {37872356}, issn = {1559-1182}, support = {RUSA-CBS-TH 4.5//Rashtriya Uchchatar Shiksha Abhiyan/ ; CRG/2020/004971//Science and Engineering Research Board (IN), SERB/ ; }, abstract = {Gut microbiota serves in the development and maintenance of phenotype. However, the underlying mechanisms are still in its infancy. The current study shows epigenetic remodelling in the brain as a causal mechanism in the gut microbiota-brain axis. Like in trauma patients, gut dysbiosis and anxiety were comorbid in adult male Wistar rats subjected to repeated mild traumatic brain injuries (rMTBI). rMTBI caused epigenetic dysregulation of brain-derived neurotrophic factor (Bdnf) expression in the amygdala, owing to the formation of transcriptional co-repressor complex due to dynamic interaction between histone deacetylase and DNA methylation modification at the Bdnf gene promoter. The probiosis after faecal microbiota transplantation (FMT) from healthy naïve rats or by administration of single strain probiotic (SSP), Lactobacillus rhamnosus GG (LGG), recuperated rMTBI-induced anxiety. Concurrently, LGG infusion or naïve FMT also dislodged rMTBI-induced co-repressor complex resulting in the normalization of Bdnf expression and neuronal plasticity as measured by Golgi-Cox staining. Furthermore, sodium butyrate, a short-chain fatty acid, produced neurobehavioural effects similar to naïve FMT or LGG administration. Interestingly, the gut microbiota from rMTBI-exposed rats per se was able to provoke anxiety in naïve rats in parallel with BDNF deficits. Therefore, gut microbiota seems to be causally linked with the chromatin remodelling necessary for neuroadaptations via neuronal plasticity which drives experience-dependent behavioural manifestations.}, } @article {pmid37871256, year = {2023}, author = {Peled, JU and van den Brink, MRM}, title = {Fecal Transplantation in Hematopoietic Transplantation.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {}, number = {}, pages = {JCO2301169}, doi = {10.1200/JCO.23.01169}, pmid = {37871256}, issn = {1527-7755}, } @article {pmid37870235, year = {2023}, author = {Duan, R and von Ehrlich-Treuenstätt, VH and Kakoschke, SC and Schardey, J and Wirth, U and Albertsmeier, M and Renz, BW and Andrassy, J and Bazhin, AV and Hodin, R and Werner, J and Ilmer, M and Kühn, F}, title = {Effect of Surgery on Postoperative Levels of the Gut Homeostasis-Regulating Enzyme Intestinal Alkaline Phosphatase.}, journal = {Journal of the American College of Surgeons}, volume = {}, number = {}, pages = {}, doi = {10.1097/XCS.0000000000000879}, pmid = {37870235}, issn = {1879-1190}, abstract = {BACKGROUND: Intestinal homeostasis is a crucial factor for complication-free short- and long-term postoperative recovery. The brush border enzyme intestinal alkaline phosphatase (IAP) is an important regulator of gut barrier function, intestinal homeostasis, and prevents endotoxemia by detoxifying lipopolysaccharides (LPS). As IAP is predominantly secreted by enterocytes in the duodenum, we hypothesized that pancreaticoduodenectomy (PD) leads to a significant stronger decrease in IAP than other major abdominal surgery.

STUDY DESIGN: Pre- and postoperative blood, stool, and intestinal samples were collected from patients undergoing PD as well as other major surgical procedures without duodenectomy. Samples were analyzed using enzyme histochemistry, the para-nitrophenyl phosphate (pNPP) method for IAP, and limulus amebocyte lysate (LAL) assay for LPS.

RESULTS: Overall, 88 patients were prospectively enrolled in the study. Fecal IAP activity negatively correlated with serum LPS (r = -0.3603, p = 0.0006). PD led to a significant decline in IAP compared to preoperative baseline levels (p< 0.0001). The decline in IAP correlated with the length of proximal small intestinal resection (r = 0.4271, p=0.0034). Compared to controls, PD was associated with a much more pronounced reduction in IAP - also after adjusting for surgical trauma (operative time, blood loss; r = 0.4598, p = 0.0086). Simultaneously, PD triggered a clearly more prominent increase in serum LPS compared to controls (p=0.0001). Increased postoperative LPS was associated with an elongated hospitalization (r = 0.7534, p=0.0062) and more prominent in pancreatic cancer (p = 0.0009).

CONCLUSION: Based upon the functional roles for IAP, supplementation with exogenous IAP might be a new treatment option to improve short- and long-term outcome after PD.}, } @article {pmid37868345, year = {2023}, author = {Yuan, C and He, Y and Xie, K and Feng, L and Gao, S and Cai, L}, title = {Review of microbiota gut brain axis and innate immunity in inflammatory and infective diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1282431}, pmid = {37868345}, issn = {2235-2988}, abstract = {The microbiota gut brain (MGB) axis has been shown to play a significant role in the regulation of inflammatory and infective diseases. Exploring the structure and communication mode of MGB axis is crucial for understanding its role in diseases, and studying the signaling pathways and regulatory methods of MGB axis regulation in diseases is also of profound significance for future clinical research. This article reviews the composition, communication mechanism of MGB axis and its role in inflammatory and infective diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD), depression, psoriasis, irritable bowel syndrome (IBS), and inflammatory bowel diseases (IBD). In addition, our investigation delved into the regulatory functions of the inflammasome, IFN-I, NF-κB, and PARK7/DJ-1 innate immune signaling pathway in the context of inflammatory and infective diseases. Ultimately, we discussed the efficacy of various interventions, including fecal microbiota transplantation (FMT), antibiotics, probiotics, prebiotics, synbiotics, and postbiotics, in the management of inflammatory and infective diseases. Understanding the role and mechanism of the MGB axis might make positive effects in the treatment of inflammatory and infective diseases.}, } @article {pmid37867202, year = {2023}, author = {Ma, J and Wen, S and Dong, A and Fan, W and Kang, Y}, title = {Gut Microbiome (Bacteria, Fungi, and Viruses) and HIV Infection: Revealing Novel Treatment Strategies.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2300566}, doi = {10.1002/mnfr.202300566}, pmid = {37867202}, issn = {1613-4133}, support = {202103021223240//Natural Science Foundation of Shanxi Province for Youths/ ; SD2009//Science Research Start-up Fund of Shanxi Province for Doctors/ ; XD2014//Science Research Start-up Fund of Shanxi Medical University for Doctor/ ; 2021L217//Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi/ ; }, abstract = {Plenty of research on microbial-viral interactions has revealed that some commensal microorganisms in the gut, including bacteria, fungi, and viruses, can resist or promote viral infection, whereas other microorganisms are involved in pathogenicity. Therefore, the balance between commensal microorganisms and human organisms is a key factor for determining infection and disease progression, and commensal microorganisms have become a hot research area in the medical field. In this review, the compositional characteristics of gut microbiota (bacteria, fungi, and viruses) during HIV infection are reviewed and changes in gut microbiota among different HIV-infected populations are described. Furthermore, the latest progress of potential microbial therapeutic methods, including a) probiotics, prebiotics, and synbiotics, b) fecal microbiota transplantation (FMT), c) phage therapy, and d) antifungal strategy, microbial enzyme inhibition, and dietary therapeutics, is analyzed based on gut bacteria, fungi, and viruses in the field of HIV infection. This study aims to provide a useful reference for developing novel strategies for the prevention and treatment of HIV infection based on commensal microorganisms.}, } @article {pmid37865904, year = {2023}, author = {Clifford, T}, title = {Practice Corner: Fecal Microbiota Transplant.}, journal = {Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jopan.2023.08.011}, pmid = {37865904}, issn = {1532-8473}, } @article {pmid37865177, year = {2023}, author = {Guha, L and Agnihotri, TG and Jain, A and Kumar, H}, title = {Gut microbiota and traumatic central nervous system injuries: Insights into pathophysiology and therapeutic approaches.}, journal = {Life sciences}, volume = {334}, number = {}, pages = {122193}, doi = {10.1016/j.lfs.2023.122193}, pmid = {37865177}, issn = {1879-0631}, abstract = {Traumatic brain injury and spinal cord injury are two distinct but fundamentally similar types of acute insults to the central nervous system (CNS) that often culminate in death or cognitive and motor impairment. Over the past decade, researchers have tapped into research to discover the potential role being played by gut bacteria in CNS. After an acute CNS injury, the altered composition of the gut microbiota disturbs the balance of the bidirectional gut-brain axis, aggravating secondary CNS injury, motor dysfunctions, and cognitive deficits, which worsens the patient's prognosis. Some of the well-known therapeutic interventions which can also be used as adjuvant therapy for alleviating CNS injuries include, the use of pro and prebiotics, fecal microbiota transplantation, and microbial engineering. In this review, we aim to discuss the importance of gut microbes in our nervous system, anatomy, and signaling pathways involved in regulating the gut-brain axis, the alteration of the gut microbiome in CNS injuries, and the therapeutic strategies to target gut microbiomes in traumatic CNS injuries.}, } @article {pmid37863204, year = {2023}, author = {Guan, Y and Liu, T and Xu, F and Xie, S and Gu, W and Bie, Y}, title = {Integration of 16S rRNA gene sequencing and LC/MS-based metabolomic analysis of early biomarkers of acute stroke in Tibetan miniature pigs.}, journal = {Journal of microbiological methods}, volume = {}, number = {}, pages = {106846}, doi = {10.1016/j.mimet.2023.106846}, pmid = {37863204}, issn = {1872-8359}, abstract = {Acute ischaemic stroke (AIS) is a complex, systemic, pathological, and physiological process. Systemic inflammatory responses and disorders of the gut microbiome contribute to increased mortality and disability following AIS. We conducted 16S high-throughput sequencing and ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry-based non-targeted metabolomic analyses of the plasma from a Tibetan miniature pig middle cerebral artery occlusion (MCAO) model. A significant decrease in the abundance of Firmicutes and a significant increase in the abundance of Actinobacteria were observed after the onset of AIS. Among the plasma metabolites, the levels of phospholipids and amino acids were considerably altered. Loading values and differential metabolite-bacterial group association analyses of the metabolome and microbiome indicated a correlation between the microbiome and metabolome of Tibetan miniature pigs after MCAO. Furthermore, significant changes were observed in the ABC transporter pathway and purine metabolism in the gut microbiome-plasma metabolome during the early stage of AIS. Kyoto Encyclopaedia of Genes and Genomes enrichment analysis showed that arginine, proline, and cyanoamino acid metabolism was upregulated while ABC transporter metabolism pathway and carbohydrate digestion and absorption were substantially downregulated. The results of this study suggest that AIS affects the gut microbiota and plasma metabolites in Tibetan miniature pigs and that faecal microbiota transplantation could be a potential therapeutic approach for AIS.}, } @article {pmid37862466, year = {2023}, author = {Diaz, LA and Winder, GS and Leggio, L and Bajaj, JS and Bataller, R and Arab, JP}, title = {New insights into the molecular basis of alcohol abstinence and relapse in alcohol-associated liver disease.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/HEP.0000000000000645}, pmid = {37862466}, issn = {1527-3350}, abstract = {Alcohol use disorder (AUD) remains a significant public health concern, affecting around 5% of adults worldwide. Novel pathways of damage have been described during the last years, providing insight into the mechanism of injury due to alcohol misuse beyond the direct effect of ethanol byproducts on the liver parenchyma and neurobehavioral mechanisms. Thus, the gut-liver-brain axis and immune system involvement could be therapeutic targets for AUD. In particular, a change in gut microbiota composition and function, especially bile acid homeostasis, and these changes can improve after alcohol cessation. Alcohol can also directly disrupt intestinal and blood-brain barriers. Activation of the immune system can be triggered by intestinal barrier dysfunction and translocation of bacteria, pathogen-associated molecular patterns (such as lipopolysaccharide), cytokines, and damage-associated molecular patterns. These factors in turn promote liver and brain inflammation and progression of liver fibrosis. Other involved mechanisms include oxidative stress, apoptosis, autophagy, and the release of extracellular vesicles and miRNA from hepatocytes. Potential therapeutic targets include gut microbiota (probiotics and fecal microbiota transplantation), neuroinflammatory pathways, as well as neuroendocrine pathways, e.g.: the ghrelin system (ghrelin receptor blockade), incretin mimetics (GLP-1 analogs), and the mineralocorticoid receptor system (spironolactone). In addition, support with psychological and behavioral treatments is essential to address the multiple dimensions of AUD. In the future, a personalized approach considering these novel targets can contribute to significantly decreasing the alcohol-related burden of disease.}, } @article {pmid37860535, year = {2023}, author = {Ma, L and Song, J and Chen, X and Dai, D and Chen, J and Zhang, L}, title = {Fecal microbiota transplantation regulates TFH/TFR cell imbalance via TLR/MyD88 pathway in experimental autoimmune hepatitis.}, journal = {Heliyon}, volume = {9}, number = {10}, pages = {e20591}, pmid = {37860535}, issn = {2405-8440}, abstract = {OBJECTIVE: Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. Intestinal flora disturbance in AIH is closely related to TFH/TFR cell imbalances. As a new method of microbial therapy, the role of fecal microbiota transplantation (FMT) in AIH remains elusive. Here, we attempted to verify the functional role and molecular mechanism of FMT in AIH.

METHODS: An experimental autoimmune hepatitis (EAH) mouse model was established to mimic the characteristics of AIH. H&E staining was used to detect histological features in mouse liver tissues. Serological tests were employed to identify several liver function biomarkers. Flow cytometry was utilized to examine the status of TFH/TFR cell subsets. Western blotting was used to evaluate TLR pathway-associated protein abundance. RT‒qPCR was applied to evaluate Treg cell markers and inflammation marker levels in mouse liver tissues.

RESULTS: There was significant liver inflammation and dysregulated TFR/TFH cells with elevated levels of liver inflammation-associated biomarkers in EAH mice. Interestingly, transferring therapeutic FMT into EAH mice dramatically reduced liver injury and improved the imbalance between splenic TFR and TFH cells. FMT treatment also reduced elevated contents of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in EAH mice. Furthermore, therapeutic FMT reversed the increased levels of IL-21 while promoting IL-10 and TGF-β cytokines. Mechanistically, FMT regulated TFH cell response in EAH mice in a TLR4/11/MyD88 pathway-dependent manner.

CONCLUSION: Our findings demonstrated that liver injury and dysregulation between TFR and TFH cells in EAH might be reversed by therapeutic FMT via the TLR4/11-MyD88 signaling pathway.}, } @article {pmid37858797, year = {2023}, author = {Yang, J and Wei, H and Lin, Y and Chu, ES and Zhou, Y and Gou, H and Guo, S and Lau, HC and Cheung, AH and Chen, H and To, KF and Sung, JJ and Wang, Y and Yu, J}, title = {High soluble fiber promotes colorectal tumorigenesis through modulating gut microbiota and metabolites in mice.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2023.10.012}, pmid = {37858797}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Dietary fibers are mainly fermented by the gut microbiota, but their roles in colorectal cancer (CRC) are largely unclear. Here, we investigated the associations of different fibers with colorectal tumorigenesis in mice.

METHODS: Apc[min/+] mice and C57BL/6 mice with azoxymethane (AOM) injection were used as CRC mouse models. Mice were fed with mixed high-fiber diet (20% soluble fiber and 20% insoluble fiber), high-inulin diet, high-guar gum diet, high-cellulose diet, or diets with different inulin dose. Germ-free mice were used for validation. Fecal microbiota and metabolites were profiled by shotgun metagenomic sequencing and liquid chromatography-mass spectrometry, respectively.

RESULTS: Mixed high-fiber diet promoted colorectal tumorigenesis with increased tumor number and tumor load in AOM-treated and Apc[min/+] mice. Antibiotics use abolished the pro-tumorigenic effect of mixed high-fiber diet, while transplanting stools from mice fed with mixed high-fiber diet accelerated tumor growth in AOM-treated germ-free mice. We therefore characterized the contribution of soluble and insoluble fiber in CRC separately. Our results revealed that soluble fiber inulin or guar gum, but not insoluble fiber cellulose, promoted colorectal tumorigenesis in AOM-treated and Apc[min/+] mice. Soluble fiber induced gut dysbiosis with Bacteroides uniformis enrichment and Bifidobacterium pseudolongum depletion, accompanied with increased fecal butyrate and serum bile acids and decreased inosine. We also identified a positive correlation between inulin dosage and colorectal tumorigenesis. Moreover, transplanting stools from mice fed with high-inulin diet increased colonic cell proliferation and oncogene expressions in germ-free mice.

CONCLUSION: High-dose soluble but not insoluble fiber potentiates colorectal tumorigenesis in a dose-dependent manner by dysregulating gut microbiota and metabolites in mice.}, } @article {pmid37858192, year = {2023}, author = {Zhong, HJ and Xie, X and Chen, WJ and Zhuang, YP and Hu, X and Cai, YL and Zeng, HL and Xiao, C and Li, Y and Ding, Y and Xue, L and Chen, M and Zhang, J and Wu, Q and He, XX}, title = {Washed microbiota transplantation improves renal function in patients with renal dysfunction: a retrospective cohort study.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {740}, pmid = {37858192}, issn = {1479-5876}, support = {2022B1111070006//Guangdong Science and Technology Department/ ; 2021M700034//Postdoctoral Research Foundation of China/ ; 2021KCXTD025//Department of Education of Guangdong Province/ ; }, abstract = {BACKGROUND: Changes in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction.

METHODS: A comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed.

RESULTS: Principal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P = 0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P < 0.05) compared with those who did not undergo WMT. The incidence of adverse events associated with WMT treatment was low (2.91%). After WMT, the Shannon index of gut microbiota and the abundance of several probiotic bacteria significantly increased in patients with renal dysfunction, aligning their gut microbiome profiles more closely with those of healthy donors (all P < 0.05). Additionally, the urine of patients after WMT demonstrated relatively higher levels of three toxic metabolites, namely hippuric acid, cinnamoylglycine, and indole (all P < 0.05).

CONCLUSIONS: WMT is a safe and effective method for improving renal function in patients with renal dysfunction by modulating the gut microbiota and promoting toxic metabolite excretion.}, } @article {pmid37857731, year = {2023}, author = {Bahar Halpern, K and Korem Kohanim, Y and Biram, A and Harnik, Y and Egozi, A and Yakubovsky, O and Shulman, Z and Itzkovitz, S}, title = {The cellular states and fates of shed intestinal cells.}, journal = {Nature metabolism}, volume = {}, number = {}, pages = {}, pmid = {37857731}, issn = {2522-5812}, abstract = {The intestinal epithelium is replaced every few days[1]. Enterocytes are shed into the gut lumen predominantly from the tips of villi[2,3] and have been believed to rapidly die upon their dissociation from the tissue[4,5]. However, technical limitations prohibited studying the cellular states and fates of shed intestinal cells. Here we show that shed epithelial cells remain viable and upregulate distinct anti-microbial programmes upon shedding, using bulk and single-cell RNA sequencing of male mouse intestinal faecal washes. We further identify abundant shedding of immune cells, which is elevated in mice with dextran sulfate sodium-induced colitis. We find that faecal host transcriptomics reflect changes in the intestinal tissue following perturbations. Our study suggests potential functions of shed cells in the intestinal lumen and demonstrates that host cell transcriptomes in intestinal washes can be used to probe tissue states.}, } @article {pmid37857710, year = {2023}, author = {Riwes, MM and Golob, JL and Magenau, J and Shan, M and Dick, G and Braun, T and Schmidt, TM and Pawarode, A and Anand, S and Ghosh, M and Maciejewski, J and King, D and Choi, S and Yanik, G and Geer, M and Hillman, E and Lyssiotis, CA and Tewari, M and Reddy, P}, title = {Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {37857710}, issn = {1546-170X}, support = {P01 HL149633/HL/NHLBI NIH HHS/United States ; P01 HL149633/HL/NHLBI NIH HHS/United States ; P01 HL149633/HL/NHLBI NIH HHS/United States ; }, abstract = {Evaluation of the impact of dietary intervention on gastrointestinal microbiota and metabolites after allogeneic hematopoietic stem cell transplantation (HCT) is lacking. We conducted a feasibility study as the first of a two-phase trial. Ten adults received resistant potato starch (RPS) daily from day -7 to day 100. The primary objective was to test the feasibility of RPS and its effect on intestinal microbiome and metabolites, including the short-chain fatty acid butyrate. Feasibility met the preset goal of 60% or more, adhering to 70% or more doses; fecal butyrate levels were significantly higher when participants were on RPS than when they were not (P < 0.0001). An exploratory objective was to evaluate plasma metabolites. We observed longitudinal changes in plasma metabolites compared to baseline, which were independent of RPS (P < 0.0001). However, in recipients of RPS, the dominant plasma metabolites were more stable compared to historical controls with significant difference at engraftment (P < 0.05). These results indicate that RPS in recipients of allogeneic HCT is feasible; in this study, it was associated with significant alterations in intestinal and plasma metabolites. A phase 2 trial examining the effect of RPS on graft-versus-host disease in recipients of allogeneic HCT is underway. ClinicalTrials.gov registration: NCT02763033 .}, } @article {pmid37857552, year = {2023}, author = {Chen, Z and Lv, M and Liang, J and Yang, K and Li, F and Zhou, Z and Qiu, M and Chen, H and Cai, Z and Cui, W and Li, Z}, title = {Neuropeptide Y-Mediated Gut Microbiota Alterations Aggravate Postmenopausal Osteoporosis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2303015}, doi = {10.1002/advs.202303015}, pmid = {37857552}, issn = {2198-3844}, support = {81871090//National Natural Science Foundation of China/ ; 32171340//National Natural Science Foundation of China/ ; 32101104//National Natural Science Foundation of China/ ; 2020YFA0908200//National Key Research and Development Program of China/ ; 202140127//Shanghai Municipal Health Planning Commission/ ; }, abstract = {Postmenopausal osteoporosis (PMO) is often accompanied by neuroendocrine changes in the hypothalamus, which closely associates with the microbial diversity, community composition, and intestinal metabolites of gut microbiota (GM). With the emerging role of GM in bone metabolism, a potential neuroendocrine signal neuropeptide Y (NPY) mediated brain-gut-bone axis has come to light. Herein, it is reported that exogenous overexpression of NPY reduced bone formation, damaged bone microstructure, and up-regulated the expressions of pyroptosis-related proteins in subchondral cancellous bone in ovariectomized (OVX) rats, but Y1 receptor antagonist (Y1Ra) reversed these changes. In addition, it is found that exogenous overexpression of NPY aggravated colonic inflammation, impaired intestinal barrier integrity, enhanced intestinal permeability, and increased serum lipopolysaccharide (LPS) in OVX rats, and Y1Ra also reversed these changes. Most importantly, NPY and Y1Ra modulated the microbial diversity and changed the community composition of GM in OVX rats, and thereby affecting the metabolites of GM (e.g., LPS) entering the blood circulation. Moreover, fecal microbiota transplantation further testified the effect of NPY-mediated GM changes on bone. In vitro, LPS induced pyroptosis, reduced viability, and inhibited differentiation of osteoblasts. The study demonstrated the existence of NPY-mediated brain-gut-bone axis and it might be a novel emerging target to treat PMO.}, } @article {pmid37856155, year = {2023}, author = {Cheng, J and Liu, D and Huang, Y and Chen, L and Li, Y and Yang, Z and Fu, S and Hu, G}, title = {Phlorizin Mitigates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating Gut Microbiota and Inhibiting Ferroptosis.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c01497}, pmid = {37856155}, issn = {1520-5118}, abstract = {Phlorizin (PHZ) is the main active component of apple peel and presents a potential application value. In the past few years, some reports have suggested that PHZ may have antioxidant and anti-inflammatory effects. Herein, we have attempted to assess the protective effects of PHZ on dextran sodium sulfate (DSS)-induced colitis in mice and to determine the underlying molecular mechanisms. Our results suggested that early intervention with PHZ (20, 40, and 80 mg/kg) significantly reduced the severity of DSS-induced colitis in mice, as presented by a longer colon, improved tight junction protein, decreased disease activity index, and attenuated inflammatory factors. Additionally, early intervention with + (20, 40, and 80 mg/kg) significantly inhibited ferroptosis by decreasing the surrogate ferroptosis marker levels (MDA and Iron Content). Additionally, PHZ (80 mg/kg) increased the diversity of intestinal flora in colitic mice by elevating the levels of beneficial bacteria (Lactobacillaceae and Muribaculaceae) and reducing the levels of harmful bacteria (Lachnospiraceae). This indirectly led to an increase in the amount of short-chain fatty acids. A fecal microbial transplantation (FMT) test was conducted to show that PHZ (80 mg/kg) ameliorated ulcerative colitis (UC) by regulating gut dysbiosis. In conclusion, early intervention with PHZ decreased DSS-induced colitis in mice by preserving their intestinal barrier and regulating their intestinal flora.}, } @article {pmid37854336, year = {2023}, author = {Guo, C and Zhang, P and Li, J and Zhou, C and Yang, Z and Zhang, Y and Luo, Y and Zhou, J and Cai, Y and Ming, Y}, title = {The characteristics of intestinal microbiota in patients with chronic schistosomiasis japonica-induced liver fibrosis by 16S rRNA gene sequence.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1276404}, pmid = {37854336}, issn = {1664-302X}, abstract = {BACKGROUND: The intestinal microbiota is known to play a role in the development of liver disease, there is a limited understanding of the intestinal microbiota associated with chronic schistosomiasis japonica. This study sought to explore the characteristics of the intestinal microbiota in patients with chronic schistosomiasis japonica and identify potential biomarkers that could aid diagnosis.

METHODS: A total of 40 residents of Qingshan Island in Yueyang (Hunan, China) were enrolled in this cross-sectional study. These individuals were divided into two groups for analysis of the intestinal microbiota: patients with chronic schistosomiasis japonica-induced liver fibrosis group (CSJ group, n = 10) and a healthy control group (HC group, n = 30). Feces were collected from each participant and analyzed by 16S rRNA gene sequencing, which included species composition analysis at the phylum and family levels, α and β diversity analysis, LEfSe, Kyoto Encyclopedia of Genes and Genome (KEGG) and Clusters of Orthologous Groups of proteins (COG) analysis.

RESULTS: Our results indicated that Schistosoma japonicum infection changed the composition and abundance of intestinal microbiota at the phylum and family levels. Compared with the HC group, the α and β diversity results showed that CSJ group had low diversity of species of the intestinal microbiome. LEfSe and relative abundance analysis found that the Prevotella 7, Alloprevotella, and Holdemanella genera were significantly higher in the CSJ group than in the HC group. Meanwhile, the ROC analysis showed that the area under the curve (AUC) of Prevotella 7, Alloprevotella, and Holdemanella genera was 0.779, 0.769, and 0.840, respectively. KEGG and COG analysis showed that the Replication and Repair, and Defense Mechanism pathways correlated strongly with chronic schistosomiasis japonica infection.

CONCLUSION: The current study was the first to explore differences in the intestinal microbiota of patients with chronic schistosomiasis japonica-induced liver fibrosis and healthy people from Qingshan Island, which indicated that Prevotella 7, Alloprevotella, and Holdemanella genera could have a potential value in non-invasive diagnosis of chronic schistosomiasis japonica-induced fibrosis.}, } @article {pmid37852131, year = {2023}, author = {Fang, G and Wang, S and Chen, Q and Luo, H and Lian, X and Shi, D}, title = {Time-restricted feeding affects the fecal microbiome metabolome and its diurnal oscillations in lung cancer mice.}, journal = {Neoplasia (New York, N.Y.)}, volume = {45}, number = {}, pages = {100943}, doi = {10.1016/j.neo.2023.100943}, pmid = {37852131}, issn = {1476-5586}, abstract = {The homeostasis of the gut microbiota and circadian rhythm is critical to host health, and both are inextricably intertwined with lung cancer. Although time-restricted feeding (TRF) can maintain circadian synchronization and improve metabolic disorders, the effects of TRF on the fecal microbiome, metabolome and their diurnal oscillations in lung cancer have not been discussed. We performed 16S rRNA sequencing and untargeted metabonomic sequencing of the feces prepared from models of tumor-bearing BALB/c nude mice and urethane-induced lung cancer. We demonstrated for the first time that TRF significantly delayed the growth of lung tumors. Moreover, TRF altered the abundances of the fecal microbiome, metabolome and circadian clocks, as well as their rhythmicity, in lung cancer models of tumor-bearing BALB/c nude mice and/or urethane-induced lung cancer C57BL/6J mice. The results of fecal microbiota transplantation proved that the antitumor effects of TRF occur by regulating the fecal microbiota. Notably, Lactobacillus and Bacillus were increased upon TRF and were correlated with most differential metabolites. Pathway enrichment analysis of metabolites revealed that TRF mainly affected immune and inflammatory processes, which might further explain how TRF exerted its anticancer benefits. These findings underscore the possibility that the fecal microbiome/metabolome regulates lung cancer following a TRF paradigm.}, } @article {pmid37851840, year = {2023}, author = {Zhang, Z and Cheng, N and Liang, J and Deng, Y and Xiang, P and Hei, Z and Li, X}, title = {Gut microbiota changes in animal models of spinal cord injury: a preclinical systematic review and meta-analysis.}, journal = {Annals of medicine}, volume = {55}, number = {2}, pages = {2269379}, doi = {10.1080/07853890.2023.2269379}, pmid = {37851840}, issn = {1365-2060}, abstract = {BACKGROUND: An increasing number of studies show that the intestinal flora is closely related to spinal cord injury. Many researchers are exploring the changes in the richness, diversity, and evenness of intestinal flora in spinal cord injury animal models to identify the characteristic bacteria.

METHODS: A comprehensive literature search was conducted using three databases: PubMed, Embase, and Web of Science. A meta-analysis was performed using R 4.3.1 to evaluate the comparison of microbiota diversity, richness, and evenness and the relative abundance of intestinal microbiota in animals with spinal cord injury and blank controls.

RESULTS: Fifteen studies were included in the meta-analysis, of which 12 involved gut microbiota distribution indicators and 11 included intestinal microflora relative abundance indicators. Meta-analysis of high-dimensional indicators describing the distribution of the gut microbiota identified a substantial decline in the evenness and richness of the intestinal flora. In addition, the Actinobacteria phylum and Erysipelotrichales and Clostridiales orders were significantly different between the spinal cord injury and sham groups; therefore, they may be the characteristic bacteria in spinal cord injury models.

CONCLUSION: Our meta-analysis suggested that the gut microbiota in the spinal cord injury animal model group was altered compared with that in the control group, with varying degrees of changes in richness and evenness and potentially pathogenic characteristic flora. More rigorous methodological studies are needed because of the high heterogeneity and limited sample size. Further research is needed to clinically apply intestinal microbiota and potentially guide fecal microbiota transplantation therapy.}, } @article {pmid37851313, year = {2023}, author = {Pan, I and Issac, PK and Rahman, MM and Guru, A and Arockiaraj, J}, title = {Gut-Brain Axis a Key Player to Control Gut Dysbiosis in Neurological Diseases.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {37851313}, issn = {1559-1182}, abstract = {Parkinson's disease is a chronic neuropathy characterised by the formation of Lewy bodies (misfolded alpha-synuclein) in dopaminergic neurons of the substantia nigra and other parts of the brain. Dopaminergic neurons play a vital role in generating both motor and non-motor symptoms. Finding therapeutic targets for Parkinson's disease (PD) is hindered due to an incomplete understanding of the disease's pathophysiology. Existing evidence suggests that the gut microbiota participates in the pathogenesis of PD via immunological, neuroendocrine, and direct neural mechanisms. Gut microbial dysbiosis triggers the loss of dopaminergic neurons via mitochondrial dysfunction. Gut dysbiosis triggers bacterial overgrowth in the small intestine, which increases the permeability barrier and induces systemic inflammation. It results in excessive stimulation of the innate immune system. In addition to that, activation of enteric neurons and enteric glial cells initiates the aggregation of alpha-synuclein. This alpha-synucleinopathy thus affects all levels of the brain-gut axis, including the central, autonomic, and enteric nervous systems. Though the neurobiological signaling cascade between the gut microbiome and the central nervous system is poorly understood, gut microbial metabolites may serve as a promising therapeutic strategy for PD. This article summarises all the known possible ways of bidirectional signal communication, i.e., the "gut-brain axis," where microbes from the middle gut interact with the brain and vice versa, and highlights a unique way to treat neurodegenerative diseases by maintaining homeostasis. The tenth cranial nerve (vagus nerve) plays a significant part in this signal communication. However, the leading regulatory factor for this axis is a diet that helps with microbial colonisation and brain function. Short-chain fatty acids (SCFAs), derived from microbially fermented dietary fibres, link host nutrition to maintain intestinal homeostasis. In addition to that, probiotics modulate cognitive function and the metabolic and behavioural conditions of the body. As technology advances, new techniques will emerge to study the tie-up between gut microbes and neuronal diseases.}, } @article {pmid37849493, year = {2023}, author = {Lan, KY and Le, PH and Chiu, CT and Chen, CC and Yeh, YM and Cheng, HT and Kuo, CJ and Chen, CL and Chen, YC and Yeh, PJ and Chiu, CH and Chang, CJ}, title = {Fecal microbiota transplantation for treatment of refractory or recurrent Clostridioides difficile infection in Taiwan: a cost-effectiveness analysis.}, journal = {Frontiers in medicine}, volume = {10}, number = {}, pages = {1229148}, pmid = {37849493}, issn = {2296-858X}, abstract = {BACKGROUND: Compared to antibiotic treatment, fecal microbiota transplantation (FMT) is a more effective treatment for refractory or recurrent CDI (rCDI). Patients with inflammatory bowel disease (IBD) have a higher incidence of CDI and worse outcomes. There has been no study from Asia to evaluate the cost-effectiveness of FMT for overall rCDI patients and rCDI patients with IBD.

METHODS: We applied a Markov model with deterministic and probabilistic sensitivity analyses to evaluate the cost and effectiveness of different treatments for rCDI patients with a time horizon of 1 year from the payer's perspective. We compared the cost and clinical outcomes of FMT through colonoscopy to two antibiotics (vancomycin and fidaxomicin) using data from Chang Gung Memorial Hospital, Taoyuan, Taiwan.

RESULTS: Compared to vancomycin, FMT was cost-effective in overall rCDI patients as well as IBD patients with rCDI [USD 39356 (NT$1,101,971.98)/quality-adjusted life year (QALY) gained in overall patients; USD65490 (NT$1,833,719.14)/QALY gained in IBD patients]. Compared to fidaxomicin, FMT was only cost-effective in overall rCDI patients [USD20255 (NT$567,133.45)/QALY gained] but slightly increased QALY (0.0018 QALY gained) in IBD patients with rCDI.

CONCLUSION: FMT is cost-effective, compared to vancomycin or fidaxomicin, for the treatment of rCDI in most scenarios from the payers' perspective in Taiwan.}, } @article {pmid37849266, year = {2023}, author = {Cui, JQ and Tian, HL and Wang, XJ and Wang, L and Liu, YK and Ye, C and Ding, LF and Li, N and Chen, QY}, title = {[Analysis of short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {26}, number = {10}, pages = {955-962}, doi = {10.3760/cma.j.cn441530-20230816-00052}, pmid = {37849266}, issn = {1671-0274}, support = {202240177//Shanghai Health Commission's Surface Project/ ; }, abstract = {Objective: To explore the short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction. Methods: The cohort of this prospective cohort study comprised 45 patients (nine men and 36 women) with radiation-induced enteritis complicated by intestinal obstruction admitted to Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2022 to October 2022. The median age was 53 (42-65) years. Thirty-five of the patients had gynecological tumors and 10 colorectal malignancies. The patients were randomly allocated to a fecal microbiota transplantation group of 20 patients who underwent fecal microbiota transplantation starting 2 weeks before surgery for 6 days, in addition to receiving conventional perioperative treatment, and a conventional treatment group of 25 patients who only received nutritional support during the perioperative period. There were no significant differences in baseline characteristics (sex, age, preoperative nutritional indices, and surgical procedure) between the two groups (all P>0.05). Postoperative recovery (time to passing flatus or a bowel movement, length of stay) and complications were compared between the two groups. Postoperative complications within 30 days after surgery classified in accordance with the international Clavien-Dindo classification of surgical complications (I-V) were statistically analyzed. Improvement in gastrointestinal symptoms, namely abdominal pain, distension, diarrhea, and rectal bleeding) and gastrointestinal quality of life scores (which include 36 problems rated 0-144 points related to physical, psychological, social activities and family life; the lower the score, the more severe the symptoms) were compared between the two groups. Nutritional recovery was assessed by body mass, body mass index, total protein, albumin, prealbumin, and hemoglobin. Results: Compared with the conventional treatment group, the postoperative hospital stay was shorter in the fecal microbiota transplantation group (8.0±4.3 days vs. 11.2±5.4 days, t=2.157, P=0.037) and the time to passage of flatus or having a bowel movement was earlier (2.2±3.2 days vs. 3.9±2.3 days, t=2.072, P=0.044). There were 26 postoperative complications in the fecal microbiota transplantation group and 59 in the conventional treatment group. There were 20 and 36 Grade I to II complications and no and three Grade III to V complications in the transplantation and conventional treatment group, respectively. The overall grade of complication did not differ significantly between the two groups (P=0.544). However, the incidence of postoperative intestinal inflammatory obstruction was lower in the fecal microbiota transplantation than the conventional treatment group (10.0% [2/20] vs. 40.0% [10/25], P=0.040). One patient in the conventional treatment group died. This patient had complete intestinal obstruction complicated by severe malnutrition preoperatively, and an intestinal fistula complicated by abdominal infection postoperatively, and died despite active treatment. Nineteen and 23 patients in the transplantation and conventional treatment group, respectively, attended for follow-up 1 month after surgery; 19 and 21, respectively, attended for follow-up 3 months after surgery, and 17 and 20, respectively, attended for follow-up 6 months after surgery. There were no significant differences between the two groups in abdominal pain or rectal bleeding 1, 3, or 6 months after surgery (all P>0.05). One month after surgery, the incidence of abdominal distension and diarrhea was lower in the fecal microbiota transplantation than in the conventional treatment group (3/19 vs. 48.0% [11/23], P=0.048; 3/19 vs. 52.2% [12/23], P=0.023). However, at the 3 and 6 month follow-ups the incidence of abdominal distension and diarrhea had gradually decreased in both groups and the differences between the groups were not statistically significant (P>0.05 for all). Scores for gastrointestinal quality of life improved significantly in both treatment groups compared with preoperative values (F=71.250, P<0.001; F=79.130, P<0.001, respectively). Scores for gastrointestinal quality of life were higher in the fecal microbiota transplantation than the conventional treatment group at all follow-up time points (P<0.05). One-way ANOVA showed that body mass, body mass index, and total protein, albumin and hemoglobin concentrations improved in both groups compared with preoperative values (all P<0.05). Prealbumin concentration improved significantly in the transplantation (F=5.514, P=0.002), but not in the conventional, group (F=1.535, P=0.211). The improvements in body mass, body mass index, total protein, and albumin were better in the fecal microbiota transplantation than conventional treatment group at 3 and 6 months of follow-up (all P<0.05). Conclusion: Perioperative fecal microbiota transplantation combined with nutritional support is effective in improving early postoperative nutritional status and quality of life in patients with radiation-induced enteritis complicated by intestinal obstruction.}, } @article {pmid37849234, year = {2023}, author = {Grabrucker, S and Marizzoni, M and Silajdžić, E and Lopizzo, N and Mombelli, E and Nicolas, S and Dohm-Hansen, S and Scassellati, C and Moretti, DV and Rosa, M and Hoffmann, K and Cryan, JF and O'Leary, OF and English, JA and Lavelle, A and O'Neill, C and Thuret, S and Cattaneo, A and Nolan, YM}, title = {Microbiota from Alzheimer's patients induce deficits in cognition and hippocampal neurogenesis.}, journal = {Brain : a journal of neurology}, volume = {}, number = {}, pages = {}, doi = {10.1093/brain/awad303}, pmid = {37849234}, issn = {1460-2156}, support = {MR/S00484X/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Alzheimer's disease is a complex neurodegenerative disorder leading to a decline in cognitive function and mental health. Recent research has positioned the gut microbiota as an important susceptibility factor in Alzheimer's disease by showing specific alterations in the gut microbiome composition of Alzheimer's patients and in rodent models. However, it is unknown whether gut microbiota alterations are causal in the manifestation of Alzheimer's symptoms. To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera. Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.}, } @article {pmid37846600, year = {2023}, author = {Li, Y and Liu, Q and Zhang, L and Zou, J and He, R and Zhou, Y and Qian, C and Zhu, Y and Chen, R and Zhang, Y and Cai, P and Wang, M and Shao, W and Ji, M and Wu, H and Zhang, F and Liu, Z and Liu, Y}, title = {Washed microbiota transplantation reduces glycemic variability in unstable diabetes.}, journal = {Journal of diabetes}, volume = {}, number = {}, pages = {}, doi = {10.1111/1753-0407.13485}, pmid = {37846600}, issn = {1753-0407}, support = {2022YFA0806103//National Key R&D Program of China/ ; 81770778//National Natural Science Foundation of China/ ; 81800724//National Natural Science Foundation of China/ ; 81800735//National Natural Science Foundation of China/ ; 82070849//National Natural Science Foundation of China/ ; 82270871//National Natural Science Foundation of China/ ; BK20180672//Natural Science Foundation of Jiangsu Province/ ; 18KJB310005//Natural Science Foundation of the Jiangsu Higher Education Institutions/ ; BE2022794//the Jiangsu Provincial Key Research Development Program/ ; }, abstract = {BACKGROUND: Dysbiosis of gut microbiota is causally linked to impaired host glucose metabolism. We aimed to study effects of the new method of fecal microbiota transplantation, washed microbiota transplantation (WMT), on reducing glycemic variability (GV) in unstable diabetes.

METHODS: Fourteen eligible patients received three allogenic WMTs and were followed up at 1 week, 1 month, and 3 months. Primary outcomes were daily insulin dose, glucose excursions during meal tests, and GV indices calculated from continuous monitoring or self-monitoring glucose values. Secondary outcomes were multiomics data, including 16S rRNA gene sequencing, metagenomics, and metabolomics to explore underlying mechanisms.

RESULTS: Daily insulin dose and glucose excursions markedly dropped, whereas GV indices significantly improved up to 1 month. WMT increased gut microbial alpha diversity, beta diversity, and network complexity. Taxonomic changes featured lower abundance of genera Bacteroides and Escherichia-Shigella, and higher abundance of genus Prevotella. Metagenomics functional annotations revealed enrichment of distinct microbial metabolic pathways, including methane biosynthesis, citrate cycle, amino acid degradation, and butyrate production. Derived metabolites correlated significantly with improved GV indices. WMT did not change circulating inflammatory cytokines, enteroendocrine hormones, or C-peptide.

CONCLUSIONS: WMT showed strong ameliorating effect on GV, raising the possibility of targeting gut microbiota as an effective regimen to reduce GV in diabetes.}, } @article {pmid37842639, year = {2023}, author = {Patra, D and Banerjee, D and Ramprasad, P and Roy, S and Pal, D and Dasgupta, S}, title = {Recent insights of obesity-induced gut and adipose tissue dysbiosis in type 2 diabetes.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1224982}, pmid = {37842639}, issn = {2296-889X}, abstract = {An imbalance in microbial homeostasis, referred to as dysbiosis, is critically associated with the progression of obesity-induced metabolic disorders including type 2 diabetes (T2D). Alteration in gut microbial diversity and the abundance of pathogenic bacteria disrupt metabolic homeostasis and potentiate chronic inflammation, due to intestinal leakage or release of a diverse range of microbial metabolites. The obesity-associated shifts in gut microbial diversity worsen the triglyceride and cholesterol level that regulates adipogenesis, lipolysis, and fatty acid oxidation. Moreover, an intricate interaction of the gut-brain axis coupled with the altered microbiome profile and microbiome-derived metabolites disrupt bidirectional communication for instigating insulin resistance. Furthermore, a distinct microbial community within visceral adipose tissue is associated with its dysfunction in obese T2D individuals. The specific bacterial signature was found in the mesenteric adipose tissue of T2D patients. Recently, it has been shown that in Crohn's disease, the gut-derived bacterium Clostridium innocuum translocated to the mesenteric adipose tissue and modulates its function by inducing M2 macrophage polarization, increasing adipogenesis, and promoting microbial surveillance. Considering these facts, modulation of microbiota in the gut and adipose tissue could serve as one of the contemporary approaches to manage T2D by using prebiotics, probiotics, or faecal microbial transplantation. Altogether, this review consolidates the current knowledge on gut and adipose tissue dysbiosis and its role in the development and progression of obesity-induced T2D. It emphasizes the significance of the gut microbiota and its metabolites as well as the alteration of adipose tissue microbiome profile for promoting adipose tissue dysfunction, and identifying novel therapeutic strategies, providing valuable insights and directions for future research and potential clinical interventions.}, } @article {pmid37842346, year = {2023}, author = {Warraich, F and Sohail, SH and Knee, A and Smith, J and Schlecht, H and Skiest, D}, title = {Factors Associated With Fecal Microbiota Transplant Failure in the Treatment of Recurrent Clostridioides difficile Infection: A Single-Center Retrospective Study.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e45118}, pmid = {37842346}, issn = {2168-8184}, abstract = {Background Clostridioides difficile infection (CDI) is a major cause of hospital-acquired diarrhea and is associated with substantial morbidity and mortality. Recurrences following treatment are common. Fecal microbiota transplantation (FMT) is a therapeutic intervention in which stool from a healthy donor is administered to a patient with recurrent CDI. Studies to date of predictors of FMT failure have primarily included inpatients. In this study, we aimed to describe FMT failure rates within one year of FMT and evaluate factors associated with FMT failure. Methodology We conducted an exploratory retrospective study of consecutive patients who underwent outpatient FMT at a single tertiary care center in Western Massachusetts from December 2014 through September 2018. We collected patient data including demographics, CDI-related factors, and FMT-related factors. FMT failure was defined as non-response or recurrence of diarrhea, associated with positive stool C. difficile toxin or polymerase chain reaction. Unadjusted relative risk (RR) and 95% confidence intervals for factors associated with FMT failure were estimated using log-binomial regression. Results A total of 92 patients were included with a mean age of 64 years. CDI severity was mild or moderate in 73% and severe or fulminant in 27%. The most common FMT indication was recurrent CDI in 76% of patients. FMT failure occurred in 25 of 92 (27%) patients, with half occurring within 11 days. Factors associated with FMT failure were active malignancy (RR = 2.56), prior hospitalizations (RR = 2.42), and receipt of non-CDI antibiotics within six months of FMT (RR = 2.80). We did not observe strong associations for risk of FMT failure with age ≥65, sex, use of proton pump inhibitors or H2 receptor agonists, history of colectomy, immunosuppression, history of malignancy, diabetes, appendectomy, CDI severity, or probiotic use. Conclusions Active malignancy, prior CDI hospitalizations, and non-CDI antibiotics within six months before FMT were associated with FMT failure in the outpatient setting. Knowledge of the above factors may help inform shared decision-making with patients at risk for FMT failure.}, } @article {pmid37842104, year = {2023}, author = {Quattrini, C and Bozorgmanesh, R and Egli, P and Magdesian, KG}, title = {Fecal microbiota transplant for treatment of diarrhea in adult hospitalized horses-111 cases (2013-2018).}, journal = {Open veterinary journal}, volume = {13}, number = {9}, pages = {1135-1140}, pmid = {37842104}, issn = {2218-6050}, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) is increasingly administered as part of the treatment of colitis in horses, yet there is little data as to its effectiveness.

AIM: Retrospective evaluation of the effects of FMT on discharge status, fecal consistency, length of hospitalization, and improvement in clinical signs in horses hospitalized for diarrhea.

METHODS: Retrospective case-control study. Medical records of adult horses (>1 year old) that received at least one transfaunation treatment (2013-2018) in two referral hospitals were identified through a medical records database search. Medical records of contemporary adult horses with diarrhea who did not receive FMT at the same study centers were used as controls.

RESULTS: Control horses had statistically significant shorter hospitalization [7 (1-21)] as compared to the transfaunation group [12 (3-31)] (p = 0.0006). There were no significant differences between groups in the number of days to the improvement of feces (p = 0.38), or in days to normalization of fecal consistency (p = 0.43), respiratory rate (p = 0.42), heart rate (p = 0.27), body temperature (p = 0.12), peripheral white blood cell count (p = 0.37), improvement in appetite (p = 0.81), or attitude (p = 0.06). There was also no significant difference in survival to discharge (transfaunation 28/37, 75.7%; control 56/74, 75.7%, p = 1.0).

CONCLUSION: There were no significant advantages of performing FMTs in horses with diarrhea in this retrospective study. This highlights the need for prospective, randomized studies to evaluate the efficacy of FMT, as well as different formulations, in horses with colitis before this can become standard practice.}, } @article {pmid37841750, year = {2023}, author = {Huang, J and Gong, C and Zhou, A}, title = {Modulation of gut microbiota: a novel approach to enhancing the effects of immune checkpoint inhibitors.}, journal = {Therapeutic advances in medical oncology}, volume = {15}, number = {}, pages = {17588359231204854}, pmid = {37841750}, issn = {1758-8340}, abstract = {Although immune checkpoint inhibitors (ICIs) have greatly improved the prognosis of some cancer patients, the majority still fail to respond adequately, and the available biomarkers cannot reliably predict drug efficacy. The gut microbiota has received widespread attention among the various intrinsic and extrinsic factors contributing to drug resistance. As an essential regulator of physiological function, the impact of gut microbiota on host immunity and response to cancer therapy is increasingly recognized. Several studies have demonstrated significant differences in gut microbiota between responders and nonresponders. The gut microbiota associated with better clinical outcomes is called 'favorable gut microbiota'. Significantly, interventions can alter the gut microbiota. By shifting the gut microbiota to the 'favorable' one through various modifications, preclinical and clinical studies have yielded more pronounced responses and better clinical outcomes when combined with ICIs treatment, providing novel approaches to improve the efficacy of cancer immunotherapy. These findings may be attributed to the effects of gut microbiota and its metabolites on the immune microenvironment and the systemic immune system, but the underlying mechanisms remain to be discovered. In this review, we summarize the clinical evidence that the gut microbiota is strongly associated with the outcomes of ICI treatment and describe the gut microbiota characteristics associated with better clinical outcomes. We then expand on the current prevalent modalities of gut microbiota regulation, provide a comprehensive overview of preclinical and clinical research advances in improving the therapeutic efficacy and prognosis of ICIs by modulating gut microbiota, and suggest fundamental questions we need to address and potential directions for future research expansion.}, } @article {pmid37841685, year = {2023}, author = {Fagan, MM and Welch, CB and Scheulin, KM and Sneed, SE and Jeon, JH and Golan, ME and Cheek, SR and Barany, DA and Oeltzschner, G and Callaway, TR and Zhao, Q and Park, HJ and Lourenco, JM and Duberstein, KJ and West, FD}, title = {Fecal microbial transplantation limits neural injury severity and functional deficits in a pediatric piglet traumatic brain injury model.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1249539}, pmid = {37841685}, issn = {1662-4548}, abstract = {Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children. Due to bidirectional communication between the brain and gut microbial population, introduction of key gut bacteria may mitigate critical TBI-induced secondary injury cascades, thus lessening neural damage and improving functional outcomes. The objective of this study was to determine the efficacy of a daily fecal microbial transplant (FMT) to alleviate neural injury severity, prevent gut dysbiosis, and improve functional recovery post TBI in a translational pediatric piglet model. Male piglets at 4-weeks of age were randomly assigned to Sham + saline, TBI + saline, or TBI + FMT treatment groups. A moderate/severe TBI was induced by controlled cortical impact and Sham pigs underwent craniectomy surgery only. FMT or saline were administered by oral gavage daily for 7 days. MRI was performed 1 day (1D) and 7 days (7D) post TBI. Fecal and cecal samples were collected for 16S rRNA gene sequencing. Ipsilateral brain and ileum tissue samples were collected for histological assessment. Gait and behavior testing were conducted at multiple timepoints. MRI showed that FMT treated animals demonstrated decreased lesion volume and hemorrhage volume at 7D post TBI as compared to 1D post TBI. Histological analysis revealed improved neuron and oligodendrocyte survival and restored ileum tissue morphology at 7D post TBI in FMT treated animals. Microbiome analysis indicated decreased dysbiosis in FMT treated animals with an increase in multiple probiotic Lactobacilli species, associated with anti-inflammatory therapeutic effects, in the cecum of the FMT treated animals, while non-treated TBI animals showed an increase in pathogenic bacteria, associated with inflammation and disease such in feces. FMT mediated enhanced cellular and tissue recovery resulted in improved motor function including stride and step length and voluntary motor activity in FMT treated animals. Here we report for the first time in a highly translatable pediatric piglet TBI model, the potential of FMT treatment to significantly limit cellular and tissue damage leading to improved functional outcomes following a TBI.}, } @article {pmid37841431, year = {2023}, author = {Wang, Y and Han, W and Wang, N and Han, M and Ban, M and Dai, J and Dong, Y and Sun, T and Xu, J}, title = {The role of microbiota in the development and treatment of gastric cancer.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1224669}, pmid = {37841431}, issn = {2234-943X}, abstract = {The stomach was once considered a sterile organ until the discovery of Helicobacter pylori (HP). With the application of high-throughput sequencing technology and macrogenomics, researchers have identified fungi and fivemajor bacterial phyla within the stomachs of healthy individuals. These microbial communities exert regulatory influence over various physiological functions, including energy metabolism and immune responses. HP is a well-recognized risk factor for gastric cancer, significantly altering the stomach's native microecology. Currently, numerous studies are centered on the mechanisms by which HP contributes to gastric cancer development, primarily involving the CagA oncoprotein. However, aside from exogenous infections such as HP and EBV, certain endogenous dysbiosis can also lead to gastric cancer through multiple mechanisms. Additionally, gut microbiota and its metabolites significantly impact the development of gastric cancer. The role of microbial therapies, including diet, phages, probiotics and fecal microbiota transplantation, in treating gastric cancer should not be underestimated. This review aims to study the mechanisms involved in the roles of exogenous pathogen infection and endogenous microbiota dysbiosis in the development of gastric cancer. Also, we describe the application of microbiota therapy in the treatment and prognosis of gastric cancer.}, } @article {pmid37841129, year = {2023}, author = {Li, MY and Duan, JQ and Wang, XH and Liu, M and Yang, QY and Li, Y and Cheng, K and Liu, HQ and Wang, F}, title = {Inulin Inhibits the Inflammatory Response through Modulating Enteric Glial Cell Function in Type 2 Diabetic Mellitus Mice by Reshaping Intestinal Flora.}, journal = {ACS omega}, volume = {8}, number = {40}, pages = {36729-36743}, pmid = {37841129}, issn = {2470-1343}, abstract = {Inulin, a commonly used dietary fiber supplement, is capable of modulating the gut microbiome. Chronic inflammation resulting from metabolic abnormalities and gut flora dysfunction plays a significant role in the development of type 2 diabetes mellitus (T2DM). Our research has demonstrated that inulin administration effectively reduced colonic inflammation in T2DM mice by inducing changes in the gut microbiota and increasing the concentration of butyric acid, which in turn modulated the function of enteric glial cells (EGCs). Experiments conducted on T2DM mice revealed that inulin administration led to an increase in the Bacteroidetes/Firmicutes ratio and the concentration of butyric acid in the colon. The anti-inflammatory effects of altered gastrointestinal flora and its metabolites were further confirmed through fecal microbiota transplantation. Butyric acid was found to inhibit the activation of the κB inhibitor kinase β/nuclear factor κB pathway, regulate the expression levels of interleukin-6 and tumor necrosis factor-α, suppress the abnormal activation of EGCs, and prevent the release of inflammatory factors by EGCs. Similar results were observed in vitro experiments with butyric acid. Our findings demonstrate that inulin, by influencing the intestinal flora, modifies the activity of EGCs to effectively reduce colonic inflammation in T2DM mice.}, } @article {pmid37840733, year = {2023}, author = {Hua, F and Cui, E and Lv, L and Wang, B and Li, L and Lu, H and Chen, N and Chen, W}, title = {Fecal microbiota transplantation from HUC-MSC-treated mice alleviates acute lung injury in mice through anti-inflammation and gut microbiota modulation.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1243102}, pmid = {37840733}, issn = {1664-302X}, abstract = {INTRODUCTION: Acute lung injury (ALI) is a severe respiratory tract disorder facilitated by dysregulated inflammation, oxidative stress and intestinal ecosystem. Fecal microbiota transplantation (FMT) is a rapid method for gut microbiota (GM) reconstruction. Furthermore, our previous studies have confirmed that human umbilical cord mesenchymal stromal cells (HUC-MSCs) can alleviate ALI by improving GM composition. Therefore, we aimed to explore the efficacy and mechanism of FMT from HUC-MSCs-treated mice on ALI.

METHODS: In brief, fresh feces from HUC-MSCs-treated mice were collected for FMT, and the mice were randomly assigned into NC, FMT, LPS, ABX-LPS, and ABX-LPS-FMT groups (n = 12/group). Subsequently, the mice were administrated with antibiotic mixtures to deplete GM, and given lipopolysaccharide and FMT to induce ALI and rebuild GM. Next, the therapeutic effect was evaluated by bronchoalveolar lavage fluid (BALF) and histopathology. Immune cells in peripheral blood and apoptosis in lung tissues were measured. Furthermore, oxidative stress- and inflammation-related parameter levels were tested in BALF, serum, lung and ileal tissues. The expressions of apoptosis-associated, TLR4/NF-κB pathway-associated, Nrf2/HO-1 pathway related and tightly linked proteins in the lung and ileal tissues were assessed. Moreover, 16S rRNA was conducted to assess GM composition and distribution.

RESULTS: Our results revealed that FMT obviously improved the pathological damage of lung and ileum, recovered the immune system of peripheral blood, decreased the cell apoptosis of lung, and inhibited inflammation and oxidative stress in BALF, serum, lung and ileum tissues. Moreover, FMT also elevated ZO-1, claudin-1, and occludin protein expressions, activating the Nrf2/HO-1 pathway but hindering the TLR4/NF-κB pathway. Of note, the relative abundances of Bacteroides, Christensenella, Coprococcus, and Roseburia were decreased, while the relative abundances of Xenorhabdus, Sutterella, and Acinetobacter were increased in the ABX-LPS-FMT group.

CONCLUSION: FMT from HUC-MSCs-treated mice may alleviate ALI by inhibiting inflammation and reconstructing GM, additionally, we also found that the TLR4/NF-κB and Nrf2/HO-1 pathways may involve in the improvement of FMT on ALI, which offers novel insights for the functions and mechanisms of FMT from HUC-MSCs-treated mice on ALI.}, } @article {pmid37840104, year = {2023}, author = {Jayachandran, M and Qu, S}, title = {Non-alcoholic fatty liver disease and gut microbial dysbiosis- underlying mechanisms and gut microbiota mediated treatment strategies.}, journal = {Reviews in endocrine & metabolic disorders}, volume = {}, number = {}, pages = {}, pmid = {37840104}, issn = {1573-2606}, support = {2018YFC1314101//The National Key R&D Program of China/ ; 2016YFC1305600//The National Key R&D Program of China/ ; 81970677//National Natural Science Foundation of China/ ; 82170861//National Natural Science Foundation of China/ ; 22120190210//Fundamental Research Funds for the Central Universities of Tongji University/ ; SHDC2020CR1017B//Clinical Research Plan of SHDC/ ; 19DZ1910200//Shanghai Committee of Science and Technology, China/ ; 17DZ1910603//Shanghai Committee of Science and Technology, China/ ; 18411951803//Shanghai Committee of Science and Technology, China/ ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is by far the most prevalent form of liver disease worldwide. It's also the leading cause of liver-related hospitalizations and deaths. Furthermore, there is a link between obesity and NAFLD risk. A projected 25% of the world's population grieves from NAFLD, making it the most common chronic liver disorder. Several factors, such as obesity, oxidative stress, and insulin resistance, typically accompany NAFLD. Weight loss, lipid-lowering agents, thiazolidinediones, and metformin help prominently control NAFLD. Interestingly, pre-clinical studies demonstrate gut microbiota's potential causal role in NAFLD. Increased intestinal permeability and unhindered transport of microbial metabolites into the liver are the major disruptions due to gut microbiome dysbiosis, contributing to the development of NAFLD by dysregulating the gut-liver axis. Hence, altering the pathogenic bacterial population using probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) could benefit patients with NAFLD. Therefore, it is crucial to acknowledge the importance of microbiota-mediated therapeutic approaches for NAFLD and comprehend the underlying mechanisms that establish a connection between NAFLD and gut microbiota. This review provides a comprehensive overview of the affiliation between dysbiosis of gut microbiota and the progress of NAFLD, as well as the potential benefits of prebiotic, probiotic, synbiotic supplementation, and FMT in obese individuals with NAFLD.}, } @article {pmid37839834, year = {2023}, author = {Yang, Y and Lv, L and Shi, S and Cai, G and Yu, L and Xu, S and Zhu, T and Su, X and Mao, N and Zhang, Y and Peng, S and He, J and Liu, Z and Wang, D}, title = {Polysaccharide from walnut green husk alleviates liver inflammation and gluconeogenesis dysfunction by altering gut microbiota in ochratoxin A-induced mice.}, journal = {Carbohydrate polymers}, volume = {322}, number = {}, pages = {121362}, doi = {10.1016/j.carbpol.2023.121362}, pmid = {37839834}, issn = {1879-1344}, abstract = {Walnut green husk polysaccharides (WGP) are isolated from the walnut green husk with a mean molecular weight of 12.77 kDa. The structural characterization revealed by methylation and NMR analysis indicated that WGP might consist of →4-α-D-Galp-(1→, α-D-Galp (1→, and →2)-α-L-Rhap-(1→. Previous studies have been demonstrated that WGP effectively prevented liver injury and modulated gut microbiota in high fructose-treated mice and high fat diet-treated rats. In this study, we found for the first time that WGP presenting outstanding protective effects on liver inflammation and gluconeogenesis dysfunction induced by ochratoxin A (OTA) in mice. Firstly, WGP decreased oxidative stress, down-regulated the expression of inflammatory factors and inhibited the TLR4/p65/IκBα pathway in the liver. Then, WGP reversed OTA-induced lower phosphoenolpyruvate carboxyl kinase (PEPCK), and glucose 6-phosphatase (G6PC) activities in the liver. Furthermore, WGP increased the diversity of gut microbiota and the abundance of beneficial bacteria, especially Lactobacillus and Akkermansia. Importantly, the results of fecal microbiota transplantation (FMT) experiment further confirmed that gut microbiota involved in the protective effects of WGP on liver damage induced by OTA. Our results indicated that the protective effect of WGP on liver inflammation and gluconeogenesis dysfunction caused by OTA may be due to the regulation of gut microbiota.}, } @article {pmid37839771, year = {2023}, author = {Wang, C and Jiang, S and Zheng, H and An, Y and Zheng, W and Zhang, J and Liu, J and Lin, H and Wang, G and Wang, F}, title = {Integration of gut microbiome and serum metabolome revealed the effect of Qing-Wei-Zhi-Tong Micro-pills on gastric ulcer in rats.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {117294}, doi = {10.1016/j.jep.2023.117294}, pmid = {37839771}, issn = {1872-7573}, abstract = {Qing-Wei-Zhi-Tong Micro-pills (QWZT) is herbal compound used in the treatment of GU, whose functions include clearing the stomach and fire, softening the liver and relieving pain. However, its mechanistic profile on host intestinal microbiota and metabolism has not been determined.

AIM OF THE STUDY: The present study aimed to observe the healing effect of QWZT on acetic acid-induced gastric ulcer in a rat model and to preliminarily elucidate its possible therapeutic mechanism from the perspective of host intestinal microbiota and metabolism.

MATERIALS AND METHODS: The Wistar male rats (7 weeks old; weight 180-200 g) were randomly divided into normal control group (NC), acetic acid-induced gastric ulcer group (GU), and QWZT treatment group (High dose: 1250 mg/kg/day, Middle dose: 625 mg/kg/day, Low dose: 312.5 mg/kg/day) of 6 rats each. An acetic acid-induced gastric ulcer rat model was constructed based on anatomical surgery. QWZT (High dose, Middle dose, and Low dose) was used to treat gastric ulcer rats for 7 days by gavage. At the end of treatment, the body weight, macroscopic condition of gastric tissue ulcers, pathological changes (HE staining), inflammatory factors, oxidative stress factors, and endocrine factors were assessed in each group of rats. Fresh feces and serum from each group of rats were collected for microbiome and metabolome analysis on the machine, respectively. Drug-disease common targets and functional pathways were captured based on network pharmacology. The complex network of Herbs-Targets-Pathways-Metabolites-Microbiota interactions was constructed. Ultimately, Fecal Microbiota Transplantation (FMT) evaluated the contribution of gut microbiota in disease.

RESULTS: QWZT increased the abundance of beneficial bacteria (Bacteroides, Alloprevotella, Rikenellaceae_RC9_gut_group, Lactobacillus, Lachnospiraceae_NK4A136_group, Parabacteroides, etc.), reduced the abundance of harmful bacteria (Micromonospora, Geobacter, Nocardioides, and Arenimonas, etc.), reduced the levels of inflammatory mediators (12,13-EpOME, 9,10-Epoxyoctadecenoic acid, SM(d18:1/16:0) and Leukotriene A4, etc.), restored host metabolic disorders (Linoleic acid metabolism, Glycerophospholipid metabolism, and Arachidonic acid metabolism), and regulated the level of cytokines (IL-6, TNF-a, SOD, MDA, PEG-2 and NO), ultimately exerting an anti-ulcer effect. Apart from that, FMT improved acetic acid-induced gastric ulcers in rats.

CONCLUSION: QWZT improved acetic acid-induced gastric ulcers in rats by remodeling intestinal microbiota and regulating host metabolism. This work may promote the process of developing and utilizing clinical applications of QWZT.}, } @article {pmid37839469, year = {2023}, author = {Tao, Y and Zhou, H and Li, Z and Wu, H and Wu, F and Miao, Z and Shi, H and Huang, F and Wu, X}, title = {TGR5 deficiency-induced anxiety and depression-like behaviors: The role of gut microbiota dysbiosis.}, journal = {Journal of affective disorders}, volume = {344}, number = {}, pages = {219-232}, doi = {10.1016/j.jad.2023.10.072}, pmid = {37839469}, issn = {1573-2517}, abstract = {BACKGROUND AND PURPOSE: Anxiety and depression have been associated with imbalances in the gut microbiota and bile acid metabolism. Takeda G protein-coupled receptor 5 (TGR5), a bile acid receptor involved in metabolism, is influenced by the gut microbiota. This study aimed to investigate the relationship between anxiety, depression, and microbiota using TGR5 knockout mice.

METHODS: We employed the following methods: (1) Assessment of behavioral changes, (2) Measurement of 5-HT levels and protein expression, (3) Analysis of stool samples, (4) Utilization of gene sequencing and statistical analysis to identify microbial signatures, (5) Examination of correlations between microbial signatures and 5-HT levels, and (6) Fecal microbiota transplantation experiments of TGR5[-/-] mice.

RESULTS: The deletion of TGR5 was found to result in increased anxiety- and depression-like behaviors in mice. TGR5 knockout mice exhibited significant reductions in 5-hydroxytryptamine (5-HT) levels in both serum and hippocampus, accompanied by a decrease in the expression of 5-HT1A receptor in the hippocampus. Moreover, TGR5 deficiency was associated with a decrease in the species richness of the gut microbiota. Specifically, the gut microbiota compositions of TGR5 knockout mice displayed distinct differences compared to their littermates, characterized by higher abundances of Anaeroplasma, Prevotella, Staphylococcus, Jeotgalicoccus, and Helicobacter, and a lower abundance of Bifidobacterium. Notably, a strong association between Jeotgalicoccus as well as Staphylococcus and serum 5-HT levels was observed in co-occurrence network. Furthermore, mice that received fecal microbiota transplants from TGR5[-/-] mice displayed anxiety and depression -like behaviors, accompanied by alterations in 5-HT levels in the hippocampus and serum.

LIMITATIONS: Study limitations for gut bacteria were analyzed at the genus level only.

CONCLUSION: TGR5 deletion in mice induces anxiety and depression-like behaviors, linked to reduced 5-HT levels in serum and the hippocampus. Gut microbiota changes play a direct role in these behaviors and serotonin alterations. This implicates TGR5 and gut bacteria in mood regulation, with potential therapeutic implications.}, } @article {pmid37834066, year = {2023}, author = {Zhou, Y and Bi, Z and Hamilton, MJ and Zhang, L and Su, R and Sadowsky, MJ and Roy, S and Khoruts, A and Chen, C}, title = {p-Cresol Sulfate Is a Sensitive Urinary Marker of Fecal Microbiota Transplantation and Antibiotics Treatments in Human Patients and Mouse Models.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834066}, issn = {1422-0067}, support = {R21AI091907//National Institute of Health/ ; R01DA043252//National Institute of Health/ ; MIN-18-125//National Institute of Food and Agriculture/ ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) and also a potential therapy for other diseases associated with dysbiotic gut microbiota. Monitoring metabolic changes in biofluids and excreta is a noninvasive approach to identify the biomarkers of microbial recolonization and to understand the metabolic influences of FMT on the host. In this study, the pre-FMT and post FMT urine samples from 11 rCDI patients were compared through metabolomic analyses for FMT-induced metabolic changes. The results showed that p-cresol sulfate in urine, a microbial metabolite of tyrosine, was rapidly elevated by FMT and much more responsive than other microbial metabolites of aromatic amino acids (AAAs). Because patients were treated with vancomycin prior to FMT, the influence of vancomycin on the microbial metabolism of AAAs was examined in a mouse feeding trial, in which the decreases in p-cresol sulfate, phenylacetylglycine, and indoxyl sulfate in urine were accompanied with significant increases in their AAA precursors in feces. The inhibitory effects of antibiotics and the recovering effects of FMT on the microbial metabolism of AAAs were further validated in a mouse model of FMT. Overall, urinary p-cresol sulfate may function as a sensitive and convenient therapeutic indicator on the effectiveness of antibiotics and FMT for the desired manipulation of gut microbiota in human patients.}, } @article {pmid37834010, year = {2023}, author = {Jamshidi, P and Farsi, Y and Nariman, Z and Hatamnejad, MR and Mohammadzadeh, B and Akbarialiabad, H and Nasiri, MJ and Sechi, LA}, title = {Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834010}, issn = {1422-0067}, abstract = {Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients' symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39-2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07-1.32), p = 0.11, and OR = 1.67, 95%CI (0.59-4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20-5.37), p = 0.01, and OR = 2.2, 95%CI (1.20-4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.}, } @article {pmid37833682, year = {2023}, author = {Diwan, B and Yadav, R and Singh, A and Kumar, D and Sharma, R}, title = {Murine sterile fecal filtrate is a potent pharmacological agent that exerts age-independent immunomodulatory effects in RAW264.7 macrophages.}, journal = {BMC complementary medicine and therapies}, volume = {23}, number = {1}, pages = {362}, pmid = {37833682}, issn = {2662-7671}, support = {IFA17-LSPA79//Department of Science and Technology, Ministry of Science and Technology, India/ ; }, abstract = {BACKGROUND: Sterile fecal filtrate (SFF) is being considered a safer alternative to fecal microbiota transplantation (FMT) therapy; however, its bioactive potency is very little understood. The present study thus assessed the age-dependent immunostimulatory and immunomodulatory attributes of murine SFF in vitro.

METHODS: SFF from young (Y-SFF) and old (O-SFF) Swiss albino mice were prepared. Immunostimulatory and immunomodulatory effects of SFF were evaluated in resting and lipopolysaccharide (LPS) stimulated macrophage cells by measuring intracellular reactive oxygen species (ROS), nitric oxide (NO) production, inflammatory cytokines profile, as well as gene expression of oxidative and inflammatory transcription factors. SFF were also evaluated for native antioxidant capacity by measuring DPPH and ABTS free radical scavenging activity. Bioactive components present in SFF were also determined by GC/MS analysis.

RESULTS: Both Y-SFF and O-SFF induced potent immunostimulatory effects characterized by changes in cell morphology, a significant increase in NO production, ROS levels, and an increased ratio of pro-inflammatory (IL-6, TNF-α, IL-1β) to anti-inflammatory (IL-10) secretory proteins although no significant aggravation in the transcription of NF-κB and Nrf-2 could be observed. Application of LPS to cells significantly augmented a pro-oxidative and pro-inflammatory response which was much higher in comparison to Y-SFF or O-SFF application alone and mediated by strong suppression of Nrf-2 gene expression. Pre-treatment of macrophages with both Y-SFF and O-SFF robustly attenuated cellular hyperresponsiveness to LPS characterized by significantly decreased levels of NO, ROS, and inflammatory cytokines while a concomitant increase in anti-inflammatory protein (IL-10) was observed. Further, both Y-SFF and O-SFF strongly resisted LPS-induced downregulation of Nrf-2 expression although O-SFF appeared to protect cells slightly better from the overall LPS threat. Neat SFF samples exhibited moderate antioxidant capacity and GC/MS analysis of SFF revealed diverse volatile organic compounds characterized by alkanes, organosulphur compounds, furans, amides, amino acids, and antimicrobial elements.

CONCLUSION: Our results indicate that SFF is a potent stimulant of macrophages and confers strong anti-inflammatory effects regardless of donor age thereby suggesting its therapeutic efficacy in lieu of FMT therapy.}, } @article {pmid37831533, year = {2023}, author = {Keller, JJ and Terveer, EM}, title = {Editorial: Continuous monitoring to improve outcome of treatment-the next step towards safe and effective faecal microbiota transplantation.}, journal = {Alimentary pharmacology & therapeutics}, volume = {58}, number = {9}, pages = {946-947}, doi = {10.1111/apt.17694}, pmid = {37831533}, issn = {1365-2036}, } @article {pmid37831529, year = {2023}, author = {Lesmana, E and Grover, M}, title = {Editorial: Faecal microbiota transplantation in IBS-Moving closer or away from success?.}, journal = {Alimentary pharmacology & therapeutics}, volume = {58}, number = {9}, pages = {950-951}, doi = {10.1111/apt.17724}, pmid = {37831529}, issn = {1365-2036}, } @article {pmid37831526, year = {2023}, author = {Su, Q and Yau, YK and Ng, SC}, title = {Editorial: Faecal microbiota transplantation in IBS-Moving closer or away from success? Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {58}, number = {9}, pages = {952-953}, doi = {10.1111/apt.17729}, pmid = {37831526}, issn = {1365-2036}, support = {//InnoHK/ ; //Government of Hong Kong, Special Administrative Region of the People's Republic of China/ ; }, } @article {pmid37831525, year = {2023}, author = {Baunwall, SMD and Hansen, MM and Andreasen, SE and Eriksen, MK and Rågård, N and Kelsen, J and Grosen, AK and Mikkelsen, S and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Editorial: Continuous monitoring to improve outcome of treatment-the next step towards safe and effective faecal microbiota transplantation. Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {58}, number = {9}, pages = {948-949}, doi = {10.1111/apt.17721}, pmid = {37831525}, issn = {1365-2036}, support = {8056-00006B//Innovationsfonden/ ; R373-2021-1202//Lundbeck Foundation/ ; NNF22OC0074080//Novo Nordisk Fonden/ ; }, } @article {pmid37830929, year = {2023}, author = {Qian, X and Jiang, H and Wu, Y and Shao, H and He, W and He, Y and Bao, X and He, L and Jia, Y and Xu, Z}, title = {Fecal microbiota transplantation combined with prebiotics ameliorates ulcerative colitis in mice.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {}, doi = {10.2217/fmb-2023-0001}, pmid = {37830929}, issn = {1746-0921}, abstract = {Aim: To investigate the effect of treatment with fecal microbiota transplantation (FMT) and galacto- and fructo-oligosaccharides on ulcerative colitis (UC) in mice. Materials & methods: A total of 90 mice, divided into nine groups, were administered FMT or prebiotics or combined treatment. The disease activity index scores, gut microbiota and inflammation factors were evaluated. Results: The treatment using FMT combined with galacto- and fructo-oligosaccharides in a 9:1 ratio significantly reduced intestinal barrier damage and alleviated symptoms of UC. Lactobacillus and Bifidobacterium and short-chain fatty acids were significantly increased after the combined treatment. Conclusion: The results demonstrate that FMT with prebiotics is a new method for UC treatment.}, } @article {pmid37828613, year = {2023}, author = {Guo, C and Kong, L and Xiao, L and Liu, K and Cui, H and Xin, Q and Gu, X and Jiang, C and Wu, J}, title = {The impact of the gut microbiome on tumor immunotherapy: from mechanism to application strategies.}, journal = {Cell & bioscience}, volume = {13}, number = {1}, pages = {188}, pmid = {37828613}, issn = {2045-3701}, support = {82272819//National Natural Science Foundation of China/ ; 81972888//National Natural Science Foundation of China/ ; JNL202204A//the Research Project of Jinan Microecological Biomedicine Shandong Laboratory/ ; JNL202219B//the Research Project of Jinan Microecological Biomedicine Shandong Laboratory/ ; JNL-2023017D//the Research Project of Jinan Microecological Biomedicine Shandong Laboratory/ ; BE2022840//the Primary Research & Development Plan of Jiangsu Province/ ; SYS202202//Shandong Provincial Laboratory Project/ ; 2020YLXK007//the Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine/ ; }, abstract = {Immunotherapy is one of the fastest developing areas in the field of oncology. Many immunological treatment strategies for refractory tumors have been approved and marketed. Nevertheless, much clinical and preclinical experimental evidence has shown that the efficacy of immunotherapy in tumor treatment varies markedly among individuals. The commensal microbiome mainly colonizes the intestinal lumen in humans, is affected by a variety of factors and exhibits individual variation. Moreover, the gut is considered the largest immune organ of the body due to its influence on the immune system. In the last few decades, with the development of next-generation sequencing (NGS) techniques and in-depth research, the view that the gut microbiota intervenes in antitumor immunotherapy through the immune system has been gradually confirmed. Here, we review important studies published in recent years focusing on the influences of microbiota on immune system and the progression of malignancy. Furthermore, we discuss the mechanism by which microbiota affect tumor immunotherapy, including immune checkpoint blockade (ICB) and adoptive T-cell therapy (ACT), and strategies for modulating the microbial composition to facilitate the antitumor immune response. Finally, opportunity and some challenges are mentioned to enable a more systematic understanding of tumor treatment in the future and promote basic research and clinical application in related fields.}, } @article {pmid37824034, year = {2023}, author = {Zhou, J and Qiu, X and Chen, X and Ma, S and Chen, Z and Wang, R and Tian, Y and Jiang, Y and Fan, L and Wang, J}, title = {Comprehensive Analysis of Gut Microbiota Alteration in the Patients and Animal Models with Polycystic Ovary Syndrome.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {}, number = {}, pages = {}, pmid = {37824034}, issn = {1976-3794}, support = {WJ2023M169//Scientific research Project of Hubei Provincial Health Commission/ ; No. 22Y26//Scientific and Technological Project of Shiyan City of Hubei Province/ ; S202110929010//National Undergraduate Training Program for Innovation and Entrepreneurship/ ; 2016QDJZR17//Cultivating Project for Young Scholar at Hubei University of Medicine/ ; }, abstract = {Polycystic ovary syndrome (PCOS) is a common disease of endocrine-metabolic disorder, and its etiology remains largely unknown. The gut microbiota is possibly involved in PCOS, while the association remains unclear. The comprehensive analysis combining gut microbiota with PCOS typical symptoms was performed to analyze the role of gut microbiota in PCOS in this study. The clinical patients and letrozole-induced animal models were determined on PCOS indexes and gut microbiota, and fecal microbiota transplantation (FMT) was conducted. Results indicated that the animal models displayed typical PCOS symptoms, including disordered estrous cycles, elevated testosterone levels, and ovarian morphological change; meanwhile, the symptoms were improved after FMT. Furthermore, the microbial diversity exhibited disordered, and the abundance of the genus Ruminococcus and Lactobacillus showed a consistent trend in PCOS rats and patients. The microbiota diversity and several key genera were restored subjected to FMT, and correlation analysis also supported relevant conclusions. Moreover, LEfSe analysis showed that Gemmiger, Flexispira, and Eubacterium were overrepresented in PCOS groups. Overall, the results indicate the involvement of gut microbiota in PCOS and its possible alleviation of endocrinal and reproductive dysfunctions through several special bacteria taxa, which can function as the biomarker or potential target for diagnosis and treatment. These results can provide the new insights for treatment and prevention strategies of PCOS.}, } @article {pmid37823985, year = {2023}, author = {Jothimani, D and Paramasivam, R and Manoharan, M and Ramachandran, H and Muthusamy, S and Simon, E and Ravichandran, J and Rela, M}, title = {Fecal calprotectin in patients with liver cirrhosis.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {37823985}, issn = {0975-0711}, abstract = {BACKGROUND AND OBJECTIVES: Sepsis is the most challenging complication in patients with liver cirrhosis. It destabilizes patients leading to worsening of liver dysfunction and increased mortality. Intestinal bacterial dysbiosis, release of endotoxins, increased gut permeability and associated immune dysregulation have been described in cirrhotic patients with septic complications. Calprotectin is a major cytosolic protein secreted by the inflammatory cells and has been widely studied in patients with inflammatory bowel disease. We aimed at evaluating the role of fecal calprotectin (FCAL) in patients with liver cirrhosis.

METHODS: A prospective, observational study on the utility of FCAL test was conducted in patients with liver cirrhosis. Fifteen milligrams of fecal specimen was collected and analyzed within 48 hours of hospitalization from patients with end-stage liver disease (ESLD), acute-on-chronic liver failure (ACLF) and at the time of outpatient visit for stable cirrhotics. Five healthy volunteers underwent FCAL test as control population.

RESULTS: The mean FCAL (µg/g) level in healthy control (n = 5), stable cirrhotics (n = 10), ESLD (n = 10) and ACLF (n = 10) patients was 109.2 (95% CI: - 53.39 to 271.79), 143.3 (95% CI: 50.5-236.45), 176.9 (95% CI: 122.93-230.87) and 543.5 (95% CI: 207.09-879.91) (p = 0.005), respectively. Sepsis was identified in 13 (43.3%) patients. Area under the receiver-operating characteristics curve (AUROC) of FCAL was 0.80 (p = 0.005) and FCAL ≥ 200 µg/g (OR = 10.8, p = 0.006) was associated with sepsis. Nine (25.7%) patients expired. FCAL level was significantly higher in dead patients compared to survivors (mean, 493.67 (95% CI: 142.20-845.14) vs. 199.71 (95% CI: 99.84-299.59) μg/g,p = 0.005.

CONCLUSIONS: FCAL levels are increased in patients with chronic liver disease, with highest level in ACLF. An FCAL level of ≥ 200 µg/g was associated with sepsis and mortality in cirrhotic patients. Larger studies are required to identify the role of FCAL in these patients. Early identification and initiation of anti-microbials may mitigate sepsis and reduce mortality.}, } @article {pmid37823635, year = {2023}, author = {Li, J and Zhang, Q and Li, X and Liu, J and Wang, F and Zhang, W and Liu, X and Li, T and Wang, S and Wang, Y and Zhang, X and Meng, Y and Ma, Y and Wang, H}, title = {QingXiaoWuWei decoction alleviates methicillin-resistant Staphylococcus aureus-induced pneumonia in mice by regulating metabolic remodeling and macrophage gene expression network via the microbiota-short-chain fatty acids axis.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0034423}, doi = {10.1128/spectrum.00344-23}, pmid = {37823635}, issn = {2165-0497}, abstract = {QingXiaoWuWei decoction (QXWWD) exerts a prominent therapeutic effect on the methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia model in mice; however, its pharmacological mechanisms remain unclear. This study aimed to investigate the underlying pharmacological mechanisms of QXWWD in MRSA-induced pneumonia. In the present study, 62 compounds were identified using high-resolution mass spectrometry. Network analysis, leveraging mass spectrometry, pinpointed the infection-linked, immunity-associated, and inflammation-related pathways as predominant targets. QXWWD significantly alleviated MRSA-induced pneumonia in mice and decreased the levels of pro-inflammatory cytokines and chemokines. 16S ribosomal RNA (16S rRNA) sequencing revealed that QXWWD regulated gut microbiota composition in mice with MRSA-induced pneumonia, which correlated with the enrichment of certain short-chain fatty acids (SCFAs)-producing strains. Further analysis with targeted metabolomics confirmed that the acetic, propionic, and butyric acid levels in the mice's serum were elevated significantly after QXWWD treatment. The fecal microbiota transplantation experiment suggested that gut microbiota from QXWWD-treated mice and SCFAs treatment may alleviate MRSA-induced pneumonia. Additionally, the untargeted metabolomic analysis further demonstrated that metabolic remodeling is significantly regulated by the QXWWD, particularly by the enhancement of the citrate cycle. In the case of QXWWD treatment, global transcriptome profiling revealed that genes, such as NLRP12 and CYP1A1, associated with macrophage antibacterial and immune activity, were downregulated. The results revealed that QXWWD regulated metabolic remodeling and macrophage gene expression network via the microbiota-SCFAs axis and thus alleviated MRSA-induced pneumonia in mice.IMPORTANCEMethicillin-resistant Staphylococcus aureus (MRSA) colonizes the upper respiratory airways and is resistant to antibiotics. MRSA is a frequently acquired infection in hospital and community settings, including cases of MRSA-induced pneumonia. Multidrug-resistant Staphylococcus aureus and the limited efficacy of antibiotics necessitate alternative strategies for preventing or treating the infection. QingXiaoWuWei decoction (QXWWD) protects against both gut microbiota dysbiosis and MRSA-induced pneumonia. Furthermore, the QXWWD-regulated metabolic remodeling and macrophage gene expression network contribute to its protective effects through the microbiota-short-chain fatty acid axis. The results of this study suggest that QXWWD and its pharmacodynamic compounds might have the potential to prevent and treat pulmonary infections, especially those caused by multidrug-resistant organisms. Our study provides a theoretical basis for the future treatment of pulmonary infectious diseases by manipulating gut microbiota and their metabolites via traditional Chinese medicine.}, } @article {pmid37823111, year = {2023}, author = {He, G and Chen, T and Huang, L and Zhang, Y and Feng, Y and Liu, Q and Yin, X and Qu, S and Yang, C and Wan, J and Liang, L and Yan, J and Liu, W}, title = {Tibetan tea reduces obesity brought on by a high-fat diet and modulates gut flora in mice.}, journal = {Food science & nutrition}, volume = {11}, number = {10}, pages = {6582-6595}, pmid = {37823111}, issn = {2048-7177}, abstract = {It has been shown that Tibetan tea (TT) inhibits obesity and controls lipid metabolism. The fundamental processes by which TT prevents obesity are yet entirely unknown. Consequently, this research aimed to ascertain if TT may prevent obesity by modifying the gut flora. Our research demonstrated that TT prevented mice from gaining weight and accumulating fat due to the high-fat diet (HFD), decreased levels of blood total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and raised levels of high-density lipoprotein cholesterol (HDL-C). Adipogenesis-related genes such as acetyl-Coenzyme A carboxylase 1 (ACC1, LOC107476), fatty acid synthase (Fas, LOC14104), sterol regulatory element-binding protein-1c (SREBP-1c, LOC20787), CCAAT/enhancer-binding protein α (C/EBPα, LOC12606), stearoyl-CoA desaturase 1 (SCD1, LOC20249), and peroxisome proliferator-activated receptor γ (PPARγ, LOC19016) had their expression downregulated by lowering the Firmicutes/Bacteroidetes (F/B) ratio and controlling the number of certain gut bacteria. TT also alleviated HFD-induced abnormalities of the gut microbiota. The Muribaculaceae, Lachnospiraceae NK4A136_group, Alistipes, and Odoribacter families were identified as the major beneficial gut microorganisms using Spearman's correlation analysis. Fecal microbiota transplantation (FMT) demonstrated that TT's anti-obesity and gut microbiota-modulating benefits might be transmitted to mice on an HFD, demonstrating that one of TT's targets for preventing obesity is the gut microbiota. TT also increased the amount of short-chain fatty acids (SCFAs) in the feces, including acetic, propionic, and butyric acids. These results indicate the possible development of TT as a prebiotic to combat obesity and associated disorders. These results suggest that TT may act as a prebiotic against obesity and its associated diseases.}, } @article {pmid37822750, year = {2023}, author = {Zhu, J and Lyu, J and Zhao, R and Liu, G and Wang, S}, title = {Gut macrobiotic and its metabolic pathways modulate cardiovascular disease.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1272479}, pmid = {37822750}, issn = {1664-302X}, abstract = {Thousands of microorganisms reside in the human gut, and extensive research has demonstrated the crucial role of the gut microbiota in overall health and maintaining homeostasis. The disruption of microbial populations, known as dysbiosis, can impair the host's metabolism and contribute to the development of various diseases, including cardiovascular disease (CVD). Furthermore, a growing body of evidence indicates that metabolites produced by the gut microbiota play a significant role in the pathogenesis of cardiovascular disease. These bioactive metabolites, such as short-chain fatty acids (SCFAs), trimethylamine (TMA), trimethylamine N-oxide (TMAO), bile acids (BAs), and lipopolysaccharides (LPS), are implicated in conditions such as hypertension and atherosclerosis. These metabolites impact cardiovascular function through various pathways, such as altering the composition of the gut microbiota and activating specific signaling pathways. Targeting the gut microbiota and their metabolic pathways represents a promising approach for the prevention and treatment of cardiovascular diseases. Intervention strategies, such as probiotic drug delivery and fecal transplantation, can selectively modify the composition of the gut microbiota and enhance its beneficial metabolic functions, ultimately leading to improved cardiovascular outcomes. These interventions hold the potential to reshape the gut microbial community and restore its balance, thereby promoting cardiovascular health. Harnessing the potential of these microbial metabolites through targeted interventions offers a novel avenue for tackling cardiovascular health issues. This manuscript provides an in-depth review of the recent advances in gut microbiota research and its impact on cardiovascular health and offers a promising avenue for tackling cardiovascular health issues through gut microbiome-targeted therapies.}, } @article {pmid37822139, year = {2023}, author = {Tie, Y and Huang, Y and Chen, R and Li, L and Chen, M and Zhang, S}, title = {Current insights on the roles of gut microbiota in inflammatory bowel disease-associated extra-intestinal manifestations: pathophysiology and therapeutic targets.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2265028}, doi = {10.1080/19490976.2023.2265028}, pmid = {37822139}, issn = {1949-0984}, abstract = {Inflammatory bowel disease (IBD) is a chronic, recurrent inflammatory disease of the gastrointestinal tract. In addition to digestive symptoms, patients with IBD may also develop extra-intestinal manifestations (EIMs), the etiology of which remains undefined. The gut microbiota has been reported to exert a critical role in the pathogenesis of IBD, with a similar pattern of gut dysbiosis observed between patients with IBD and those with EIMs. Therefore, it is hypothesized that the gut microbiota is also involved in the pathogenesis of EIMs. The potential mechanisms are presented in this review, including: 1) impaired gut barrier: dysbiosis induces pore formation in the intestinal epithelium, and activates pattern recognition receptors to promote local inflammation; 2) microbial translocation: intestinal pathogens, antigens, and toxins translocate via the impaired gut barrier into extra-intestinal sites; 3) molecular mimicry: certain microbial antigens share similar epitopes with self-antigens, inducing inflammatory responses targeting extra-intestinal tissues; 4) microbiota-related metabolites: dysbiosis results in the dysregulation of microbiota-related metabolites, which could modulate the differentiation of lymphocytes and cytokine production; 5) immunocytes and cytokines: immunocytes are over-activated and pro-inflammatory cytokines are excessively released. Additionally, we summarize microbiota-related therapies, including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation, to promote better clinical management of IBD-associated EIMs.}, } @article {pmid37821652, year = {2023}, author = {Yost, RT and Fowler, AE and Adler, LS}, title = {Gut Transplants from Bees Fed an Antipathogenic Pollen Diet Do Not Confer Pathogen Resistance to Recipients.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, pmid = {37821652}, issn = {1432-184X}, support = {2128221//National Science Foundation/ ; NE2001//U.S. Department of Agriculture/ ; }, abstract = {Pollinators are threatened by diverse stressors, including microbial pathogens such as Crithidia bombi. Consuming sunflower pollen dramatically reduces C. bombi infection in the bumble bee Bombus impatiens, but the mechanism behind this medicinal effect is unclear. We asked whether diet mediates resistance to C. bombi through changes in the gut microbiome. We hypothesized that sunflower pollen changes the gut microbiome, which in turn reduces Crithidia infection. To test this, we performed a gut transplant experiment. We fed donor bees either a sunflower pollen treatment or buckwheat pollen as a control treatment and then inoculated recipient bees with homogenized guts from either sunflower-fed or buckwheat-fed donor bees. All recipient bees were then fed a wildflower pollen diet. Two days after the transplant, we infected recipients with C. bombi, and 2 days later, we provided another donor gut transplant. To quantify infection, we performed both fecal screens and dissections of the recipient bees. We found no significant differences in C. bombi infection intensity or presence between bees that received sunflower-fed microbiomes versus buckwheat-fed microbiomes. This suggests that sunflower pollen's effects on pathogen resistance are not mediated by gut microbiota.}, } @article {pmid37820424, year = {2023}, author = {Xu, C and Zhao, L and Zhou, W and Li, Y and Hu, H and Wang, Z}, title = {Synergistic effect of berberine hydrochloride and dehydrocostus lactone in the treatment of ulcerative colitis: Take gut microbiota as the target.}, journal = {International immunopharmacology}, volume = {124}, number = {Pt B}, pages = {111009}, doi = {10.1016/j.intimp.2023.111009}, pmid = {37820424}, issn = {1878-1705}, abstract = {Ulcerative colitis (UC) is a difficult-to-cure and recurrent inflammatory bowel disease, and it is difficult to maintain long-term results with a single drug. Inspired by clinical medication in traditional Chinese medicine, we used berberine hydrochloride (BBH) and dehydrocostus lactone (DEH) in combination for the first time and focused on studying their mechanism of treating UC based on gut microbiota. Therefore, we evaluated the therapeutic effects of BBH and DEH on DSS-induced UC mice using ELISA, HE and AB-PAS staining, 16s rDNA amplicon sequencing technology, and fecal transplantation experiments (FMT). In this study, the combination of BBH and DEH significantly relieved symptoms, colonic inflammation, and intestinal barrier damage of DSS-induced UC mice, and they did not show antagonism. In addition, the co-administration of BBH and DEH altered the composition and function of gut microbiota, with BBH increasing the abundance of key beneficial bacterial genus Akkermansia and DEH aiming to enhance species diversity and supplying intestinal proteins to prevent overconsumption. Furthermore, our data showed that BBH and DEH improve the levels of short-chain fatty acids, which also proved the positive regulation of gut microbiota by BBH and DEH. Finally, the FMT confirmed the strong correlation between BBH, DEH, and the gut microbiota. In conclusion, the co-administration of BBH and DEH protected the intestinal barrier and reduced inflammatory damage by regulating gut microbiota, targeting the key beneficial bacterial genus Akkermansia, and maintaining a normal supply of intestinal proteins.}, } @article {pmid37820064, year = {2023}, author = {Liu, Y and Tu, J and Shi, L and Fang, Z and Fan, M and Zhang, J and Ding, L and Chen, Y and Wang, Y and Zhang, E and Xu, S and Sharma, N and Gillece, JD and Reining, LJ and Jin, L and Huang, W}, title = {CYP8B1 downregulation mediates the metabolic effects of vertical sleeve gastrectomy in mice.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/HEP.0000000000000627}, pmid = {37820064}, issn = {1527-3350}, abstract = {BACKGROUND AIMS: Although the benefits of vertical sleeve gastrectomy surgery (VSG) are well known, the molecular mechanisms by which VSG alleviates obesity and its complications remain unclear. We aim to determine a role of CYP8B1 (cytochrome P450, family 8, subfamily B, polypeptide 1) in mediating the metabolic benefits of VSG.

APPROACH RESULTS: We found that expression of CYP8B1, a key enzyme in controlling the 12α-hydroxylated (12α-OH) bile acid (BA) to non-12α-OH BA ratio, was strongly downregulated after VSG. Using genetic mouse models of CYP8B1 overexpression, knockdown, and knockout (KO), we demonstrated that overexpression of CYP8B1 dampened the metabolic improvements associated with VSG. In contrast, shRNA mediated CYP8B1 knockdown improved metabolism similar to those observed after VSG. Cyp8b1 deficiency diminished the metabolic effects of VSG. Further, VSG-induced alterations to the 12α-OH/non-12α-OH BA ratio in the BA pool depended on CYP8B1 expression level. Consequently, intestinal lipid absorption was restricted, and the gut microbiota (GM) profile was altered. Fecal microbiota transplantation (FMT) from wild type (WT)-VSG mice (vs. FMT from WT-sham mice) improved metabolism in recipient mice, while there were no differences between mice that received FMT from KO-sham and KO-VSG mice.

CONCLUSIONS: CYP8B1 is a critical downstream target of VSG. Modulation of BA composition and GM profile by targeting CYP8B1 may provide novel insight into the development of therapies that non-invasively mimic bariatric surgery to treat obesity and its complications.}, } @article {pmid37819130, year = {2023}, author = {Van Den Ham, KM and Little, MR and Bednarski, OJ and Fusco, EM and Mandal, RK and Mitra, R and Li, S and Doumbo, S and Doumtabe, D and Kayentao, K and Ongoiba, A and Traore, B and Crompton, PD and Schmidt, NW}, title = {Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0155423}, doi = {10.1128/spectrum.01554-23}, pmid = {37819130}, issn = {2165-0497}, abstract = {Gut microbiota are increasingly being recognized as a contributing factor in the etiology of numerous diseases and as a potential determinant in the immune response to various treatments. Recent work has suggested that the suboptimal immunogenic response to vaccination in low- and middle-income countries may be associated with differences in the gut microbiome, which are known to be substantially different between Western and non-Western countries. However, insufficient consideration has been given to the characterization of non-Western microbiomes and their relationship with well-being and immunity. Humanized gnotobiotic mouse models have been used to better understand the causal associations between the gut microbiota and health outcomes but have largely been limited to the study of Western microbiota. Thus, we were interested in determining the applicability of gavage strategies used to humanize germ-free mice with Western microbiota to the humanization of germ-free mice with rural African fecal samples. Here, we assessed the impact of the number and frequency of gavages and the effect of a donor-matched diet on the colonization of Malian fecal microbiota in germ-free mice. One gavage was insufficient to provide a stable establishment of the Malian microbiome, whereas four weekly gavages resulted in a more consistent colonization of the human donor taxa. Interestingly, the donor-matched diet did not improve colonization over the fixed-formula, grain-based mouse chow. Subsequent phenotypic studies using African gut microbiota-humanized gnotobiotic mouse models will allow for a better understanding of the interaction between African gut microbiota and well-being and potentially aid in developing improved treatments for microbiota-dependent diseases in non-Western populations. IMPORTANCE There is increasing evidence that microbes residing within the intestines (gut microbiota) play important roles in the well-being of humans. Yet, there are considerable challenges in determining the specific role of gut microbiota in human diseases owing to the complexity of diverse internal and environmental factors that can contribute to diseases. Mice devoid of all microorganisms (germ-free mice) can be colonized with human stool samples to examine the specific contribution of the gut microbiota to a disease. These approaches have been primarily focused on stool samples obtained from individuals in Western countries. Thus, there is limited understanding as to whether the same methods used to colonize germ-free mice with stool from Western individuals would apply to the colonization of germ-free mice with stool from non-Western individuals. Here, we report the results from colonizing germ-free mice with stool samples of Malian children.}, } @article {pmid37818040, year = {2023}, author = {Zhan, X and Zuo, Q and Huang, G and Qi, Z and Wang, Y and Zhu, S and Zhong, Y and Xiong, Y and Chen, T and Tan, B}, title = {Tripterygium glycosides sensitizes cisplatin chemotherapeutic potency by modulating gut microbiota in epithelial ovarian cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1236272}, pmid = {37818040}, issn = {2235-2988}, abstract = {Epithelial ovarian cancer (EOC) is a fatal gynecological malignancy with limited therapeutic options. Previous research has demonstrated that Tripterygium glycosides (GTW) can enhance effectiveness of cisplatin (DDP) chemotherapy against EOC. However, the underlying mechanism of GTW alleviating EOC still remains unclear. In this article, an ID8 cell-derived xenograft mouse model was established to evaluate the anti-tumor efficacy of GTW combined with DDP. Consistent with previous findings, the results suggested that GTW combined with DDP can exhibit a stronger tumor suppressive effect than DDP alone. Additionally, GTW was found can further exert gastrointestinal protection against DDP by reducing pathological damage on colon tissue. Secondly, to verify whether gut microbiota play an instrumental role in GTW's anticancer effect, we treated mice models with antibiotic to eliminate gut microbiota. And our experimental results indicated that all drug groups showed a weaker tumor suppressive effect and more severe gastrointestinal damage post antibiotic supplement. At genus level, the relative abundance of Lactobacillus was dramatically diminished by the antibiotic treatment, while combined treatment of GTW and DDP can significantly restore the level. Moreover, we performed Lactobacillus acidophilus transplantation and healthy mice fecal microbiota transplantation experiments to further investigate the link between the anticancer effect of GTW and gut microbiota. Our results suggested that both cisplatin-sensitizing and intestinal barrier-protecting effects of GTW can be recovered to a different extent. In conclusion, our results indicated that GTW is a promising chemosensitization and intestinal barrier repair drug for EOC, and the potential mechanism may corelate with the restoration of the compromised intestinal microbial balance.}, } @article {pmid37815701, year = {2023}, author = {Emile, SH and Horesh, N and Freund, MR and Garoufalia, Z and Gefen, R and Khan, SM and Silva-Alvarenga, E and Wexner, SD}, title = {A Systematic Review and Meta-analysis of Randomized Clinical Trials on the Prevention and Treatment of Pouchitis after Ileoanal Pouch Anastomosis.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {}, number = {}, pages = {}, pmid = {37815701}, issn = {1873-4626}, abstract = {BACKGROUND: This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA).

METHODS: PubMed, Scopus, and Web of Science were searched for randomized clinical trials that assessed prevention or treatment of pouchitis. The systematic review was reported in line with updated 2020 PRISMA guidelines. Risk of bias in the trials included was assessed using the ROB-2 tool and certainty of evidence was assessed using GRADE. The main outcomes were the incidence of new pouchitis episodes in the preventative studies and resolution or improvement of active pouchitis in the treatment studies.

RESULTS: Fifteen randomized trials were included. A meta-analysis of 7 trials on probiotics revealed significantly lower odds of pouchitis with the use of probiotics (RR: 0.26, 95% CI: 0.16-0.42, I[2] = 20%, p < 0.001) and similar odds of adverse effects to placebo (RR: 2.43, 95% CI: 0.11-55.9, I[2] = 0, p = 0.579). One trial investigated the prophylactic role of allopurinol in preventing pouchitis and found a comparable incidence of pouchitis in the two groups (31% vs 28%; p = 0.73). Seven trials assessed different treatments for active pouchitis. One recorded the resolution of pouchitis in all patients treated with ciprofloxacin versus 67% treated with metronidazole. Both budesonide enema and oral metronidazole were associated with similar significant improvement in pouchitis (58.3% vs 50%, p = 0.67). Rifaximin, adalimumab, fecal microbiota transplantation, and bismuth carbomer foam enema were not effective in treating pouchitis.

CONCLUSIONS: Probiotics are effective in preventing pouchitis after IPAA. Antibiotics, including ciprofloxacin and metronidazole, are likely effective in treating active pouchitis.}, } @article {pmid37814565, year = {2023}, author = {Korpak, K and Defourny, L and Lali, S and Delvallée, M and Demeester, R and Toussaint, E}, title = {Treatment of recurrent Clostridioides difficile infections with faecal microbiota transplantation: peri-procedural methods in a consecutive case series.}, journal = {Acta gastro-enterologica Belgica}, volume = {86}, number = {3}, pages = {486-489}, doi = {10.51821/86.3.11795}, pmid = {37814565}, issn = {1784-3227}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has high efficacy against recurrent Clostridioides difficile infection (CDI). Despite the increasing use of this therapy, the delay between diagnosis and treatment is excessive. Furthermore, donor selection is an important and time-consuming process.

METHODS: We reviewed patients who underwent FMT for recurrent CDI at the CHU Charleroi Hospital between 2015 and 2022. The general context, type of administration, adverse events, and donor selection were reported. FMT was conducted using gastroduodenoscopy, colonoscopy, and enema with either fresh or frozen material.

RESULTS: Ten patients with multiple comorbidities were treated by FMT. Seven patients were cured after one procedure. One patient was successfully cured after a change to an unrelated donor, and preliminary efficacy was established.

CONCLUSIONS: FMT is an effective treatment that should be considered during the earlier phases of treatment. Stool donors should be thoroughly screened for infectious diseases and other criteria related to microbiota composition.}, } @article {pmid37814439, year = {2023}, author = {Zhang, J and Zhang, C and Zhang, T and Zhang, L and Duan, L}, title = {Distinct Effects of Non-absorbed Agents Rifaximin and Berberine on the Microbiota-Gut-Brain Axis in Dysbiosis-induced Visceral Hypersensitivity in Rats.}, journal = {Journal of neurogastroenterology and motility}, volume = {29}, number = {4}, pages = {520-531}, doi = {10.5056/jnm22182}, pmid = {37814439}, issn = {2093-0879}, abstract = {BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is accepted as a disorder of gut-brain interactions. Berberine and rifaximin are non-absorbed antibiotics and have been confirmed effective for IBS treatment, but there is still lack of direct comparison of their effects. This study aims to compare the effect of the 2 drugs on the alteration of gut-brain axis caused by gut microbiota from IBS patients.

METHODS: Germ-free rats received fecal microbiota transplantation from screened IBS patients and healthy controls. After 14 days' colonization, rats were administrated orally with berberine, rifaximin or vehicle respectively for the next 14 days. The visceral sensitivity was evaluated, fecal microbiota profiled and microbial short chain fatty acids were determined. Immunofluorescence staining and morphological analysis were performed to evaluate microglial activation.

RESULTS: Visceral hypersensitivity induced by IBS-fecal microbiota transplantation was relieved by berberine and rifaximin, and berberine increased sucrose preference rate. Microbial α-diversity were reduced by both drugs. Compared with rifaximin, berberine significantly changed microbial structure and enriched Lachnoclostridium. Furthermore, berberine but not rifaximin significantly increased fecal concentrations of acetate and propionate acids. Berberine restored the morphological alterations of microglia induced by dysbiosis, which may be associated with its effect on the expression of microbial gene pathways involved in peptidoglycan biosynthesis. Rifaximin affected neither the numbers of activated microglial cells nor the microglial morphological alterations.

CONCLUSIONS: Berberine enriched Lachnoclostridium, reduced the expression of peptidoglycan biosynthesis genes and increased acetate and propionate. The absence of these actions of rifaximin may explain the different effects of the drugs on microbiota-gut-brain axis.}, } @article {pmid37813835, year = {2023}, author = {Han, D and Wu, Y and Lu, D and Pang, J and Hu, J and Zhang, X and Wang, Z and Zhang, G and Wang, J}, title = {Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation.}, journal = {Cell death & disease}, volume = {14}, number = {10}, pages = {656}, pmid = {37813835}, issn = {2041-4889}, support = {32125036//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32172750//National Natural Science Foundation of China (National Science Foundation of China)/ ; 31902170//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Mice ; Animals ; *Gastrointestinal Microbiome ; Polyphenols/pharmacology/metabolism ; Neutrophils/metabolism ; Ellagic Acid/metabolism/pharmacology ; *Colitis/metabolism ; Inflammation/pathology ; Diet ; Macrophages/metabolism ; Dextran Sulfate/toxicity ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/pathology ; }, abstract = {Dietary phenolic acids alleviate intestinal inflammation through altering gut microbiota composition and regulating macrophage activation. However, it is unclear how individual phenolic acids affect the interactions between intestinal microbiota and macrophages in the context of inflammatory bowel disease (IBD). Here, we aim to elucidate the mechanism by which phenolic acids alleviate gut inflammation. Mice with or without depletion of macrophages were administered with four individual phenolic acids including chlorogenic, ferulic, caffeic, and ellagic acids, following dextran sulfate sodium (DSS) treatment. Gut microbiota depletion and fecal microbiota transplantation were further performed in mice to investigate the role of the gut microbiota in phenolic acid-mediated protective effect. Colitis severity was evaluated using histological, serological, and immunological measurements. Absence of intestinal microbiota and macrophage deteriorate the epithelial injury in DSS colitis. Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation. However, ferulic acid-mediated reduction of colitis was neutrophil-dependent through diminishing the formation of neutrophil extracellular traps. On the other hand, the beneficial effects of caffeic acid and ellagic acid were dependent upon the gut microbiota. In fact, urolithin A (UroA), a metabolite transformed from ellagic acid by the gut microbiota, was found to alleviate colitis and enhance gut barrier function in an IL22-dependent manner. Overall, our findings demonstrated that the mechanisms by which phenolic acid protected against colitis were resulted from the interaction between gut microbiota and macrophage-neutrophil.}, } @article {pmid37809261, year = {2023}, author = {Masood, L and Müller, A and Ali, NZ and Mummadisetty, A and Yahya, A and Burugu, SS and Sajid, R and Lakkimsetti, M and Sagireddy, S and Abdin, ZU and Nazir, Z}, title = {A Narrative Literature Review on Sepsis: A Primary Manifestation of Colorectal Neoplasm.}, journal = {Cureus}, volume = {15}, number = {9}, pages = {e44803}, pmid = {37809261}, issn = {2168-8184}, abstract = {Sepsis and colorectal cancer (CRC) exhibit a complex relationship that warrants further exploration. This review delves into the interplay of factors between sepsis and CRC, uncovering shared pathophysiological traits and potential bacterial associations. Understanding these connections could pave the way for earlier diagnosis, improved management, and enhanced outcomes in CRC patients. The role of immune system dysfunction, hypoalbuminemia, and specific microbial imbalances, such as Streptococcus bovis and Clostridium septicum, are discussed. Recognizing sepsis in CRC patients is crucial for timely intervention, and tailored approaches encompassing antibiotic therapy, source control measures, and cancer treatment are essential for comprehensive care. Monitoring biomarkers and ratios can provide valuable insights into complications and overall health outcomes. A multidisciplinary approach involving various specialists is necessary to address the global burden of CRC and its association with sepsis while exploring novel interventions, such as fecal microbiota transplantation and personalized care. We conducted a thorough search using reputable databases such as PubMed, Scopus, and Google Scholar to investigate the connection between sepsis and CRC. We refined our search terms, utilized sidebar filters, and examined references in selected articles. This meticulous process helped us create a comprehensive literature review and gain valuable insights into this relationship.}, } @article {pmid37807005, year = {2023}, author = {Arjomand Fard, N and Bording-Jorgensen, M and Wine, E}, title = {A Potential Role for Gut Microbes in Mediating Effects of Omega-3 Fatty Acids in Inflammatory Bowel Diseases: A Comprehensive Review.}, journal = {Current microbiology}, volume = {80}, number = {11}, pages = {363}, pmid = {37807005}, issn = {1432-0991}, abstract = {Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with several inflammatory conditions, including inflammatory bowel diseases (IBDs), and found to have an impact on gut microbiota. In fact, some randomized controlled studies suggest benefits to IBD patients, but others do not. Our aim was to review recent evidence on the effects of omega-3 on IBD and establish the contribution of the gut microbiome. Omega-3 mediate anti-inflammatory effects in IBD through various mechanisms, including suppression of NLR family pyrin domain-containing 3 (NLRP3) inflammasome, Toll-like receptor-4 (TLR4), and nucleotide-binding oligomerization domain 2 (NOD2) signaling; this results in the repression of the nuclear factor-kappa B (Nf-kB) pathway and the secretion of pro-inflammatory cytokines. Omega-3 can also affect gut microbiota and revert the bacterial community to patterns associated with healthy status by increasing short-chain fatty acid (SCFA)-producing bacteria and enhancing the mucosal gut barrier, thus promoting homeostasis. The combination of these immunoregulatory effects and anti-inflammation properties with the promotion of a balanced gut microbiome environment could suggest that omega-3 might benefit IBD patients. Considering the microbiota of IBD patients while using omega-3 might predict and improve omega-3 effectiveness. Combining omega-3 with bacteria-altering therapy, such as probiotics and fecal microbiota transplantation, may further enhance its efficacy; however, further studies are required to elucidate mechanisms and potential preventive or treatment roles of omega-3 in IBD.}, } @article {pmid37806386, year = {2023}, author = {Kumbhare, SV and Pedroso, I and Ugalde, JA and Márquez-Miranda, V and Sinha, R and Almonacid, DE}, title = {Drug and gut microbe relationships: Moving beyond antibiotics.}, journal = {Drug discovery today}, volume = {}, number = {}, pages = {103797}, doi = {10.1016/j.drudis.2023.103797}, pmid = {37806386}, issn = {1878-5832}, abstract = {Our understanding of drug-microbe relationships has evolved from viewing microbes as mere drug producers to a dynamic, modifiable system where they can serve as drugs or targets of precision pharmacology. This review highlights recent findings on the gut microbiome, particularly focusing on four aspects of research: (i) drugs for bugs, covering recent strategies for targeting gut pathogens; (ii) bugs as drugs, including probiotics; (iii) drugs from bugs, including postbiotics; and (iv) bugs and drugs, discussing additional types of drug-microbe interactions. This review provides a perspective on future translational research, including efficient companion diagnostics in pharmaceutical interventions. Teaser This review highlights the dynamic relationship between drugs and bugs in the human gut microbiome, providing insights into potential strategies for novel therapies and companion diagnostics for precision pharmacology.}, } @article {pmid37806074, year = {2023}, author = {Pötgens, SA and Lecop, S and Havelange, V and Li, F and Neyrinck, AM and Neveux, N and Maertens, J and Walter, J and Schoemans, H and Delzenne, NM and Bindels, LB}, title = {Gut microbiota alterations induced by intensive chemotherapy in acute myeloid leukaemia patients are associated with gut barrier dysfunction and body weight loss.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {42}, number = {11}, pages = {2214-2228}, doi = {10.1016/j.clnu.2023.09.021}, pmid = {37806074}, issn = {1532-1983}, abstract = {BACKGROUND & AIMS: Acute myeloid leukaemia (AML) chemotherapy has been reported to impact gut microbiota composition. In this study, we investigated using a multi -omics strategy the changes in the gut microbiome induced by AML intense therapy and their association with gut barrier function and cachectic hallmarks.

METHODS: 10 AML patients, allocated to standard induction chemotherapy (SIC), were recruited. Samples and data were collected before any therapeutic intervention (T0), at the end of the SIC (T1) and at discharge (T4). Gut microbiota composition and function, markers of inflammation, metabolism, gut barrier function and cachexia, as well as faecal, blood and urine metabolomes were assessed.

RESULTS: AML patients demonstrated decreased appetite, weight loss and muscle wasting during hospitalization, with an incidence of cachexia of 50%. AML intensive treatment transiently impaired the gut barrier function and led to a long-lasting change of gut microbiota composition characterized by an important loss of diversity. Lactobacillaceae and Campylobacter concisus were increased at T1 while Enterococcus faecium and Staphylococcus were increased at T4. Metabolomics analyses revealed a reduction in urinary hippurate and faecal bacterial amino acid metabolites (bAAm) (2-methylbutyrate, isovalerate, phenylacetate). Integration using DIABLO revealed a deep interconnection between all the datasets. Importantly, we identified bacteria which disappearance was associated with impaired gut barrier function (Odoribacter splanchnicus) and body weight loss (Gemmiger formicilis), suggesting these bacteria as actionable targets.

CONCLUSION: AML intensive therapy transiently impairs the gut barrier function while inducing enduring alterations in the composition and metabolic activity of the gut microbiota that associate with body weight loss.

TRIAL REGISTRATION: NCT03881826, https://clinicaltrials.gov/ct2/show/NCT03881826.}, } @article {pmid37805634, year = {2023}, author = {Peña-Cearra, A and Song, D and Castelo, J and Palacios, A and Lavín, JL and Azkargorta, M and Elortza, F and Fuertes, M and Pascual-Itoiz, MA and Barriales, D and Martín-Ruiz, I and Fullaondo, A and Aransay, AM and Rodríguez, H and Palm, NW and Anguita, J and Abecia, L}, title = {Mitochondrial dysfunction promotes microbial composition that negatively impacts on ulcerative colitis development and progression.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {74}, pmid = {37805634}, issn = {2055-5008}, support = {PID2021-124328OB-100//Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)/ ; }, abstract = {Recent evidence demonstrates potential links between mitochondrial dysfunction and inflammatory bowel diseases (IBD). In addition, bidirectional interactions between the intestinal microbiota and host mitochondria may modulate intestinal inflammation. We observed previously that mice deficient in the mitochondrial protein MCJ (Methylation-controlled J protein) exhibit increased susceptibility to DSS colitis. However, it is unclear whether this phenotype is primarily driven by MCJ[-/-] associated gut microbiota dysbiosis or by direct effects of MCJ-deficiency. Here, we demonstrate that fecal microbiota transplantation (FMT) from MCJ-deficient into germ-free mice was sufficient to confer increased susceptibility to colitis. Therefore, an FMT experiment by cohousing was designed to alter MCJ-deficient microbiota. The phenotype resulting from complex I deficiency was reverted by FMT. In addition, we determined the protein expression pathways impacted by MCJ deficiency, providing insight into the pathophysiology of IBD. Further, we used magnetic activated cell sorting (MACS) and 16S rRNA gene sequencing to characterize taxa-specific coating of the intestinal microbiota with Immunoglobulin A (IgA-SEQ) in MCJ-deficient mice. We show that high IgA coating of fecal bacteria observed in MCJ-deficient mice play a potential role in disease progression. This study allowed us to identify potential microbial signatures in feces associated with complex I deficiency and disease progression. This research highlights the importance of finding microbial biomarkers, which might serve as predictors, permitting the stratification of ulcerative colitis (UC) patients into distinct clinical entities of the UC spectrum.}, } @article {pmid37802720, year = {2023}, author = {Portincasa, P and Khalil, M and Graziani, A and Frühbeck, G and Baffy, G and Garruti, G and Di Ciaula, A and Bonfrate, L}, title = {Gut microbes in metabolic disturbances. Promising role for therapeutic manipulations?.}, journal = {European journal of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ejim.2023.10.002}, pmid = {37802720}, issn = {1879-0828}, abstract = {The prevalence of overweight, obesity, type 2 diabetes, metabolic syndrome and steatotic liver disease is rapidly increasing worldwide with a huge economic burden in terms of morbidity and mortality. Several genetic and environmental factors are involved in the onset and development of metabolic disorders and related complications. A critical role also exists for the gut microbiota, a complex polymicrobial ecology at the interface of the internal and external environment. The gut microbiota contributes to food digestion and transformation, caloric intake, and immune response of the host, keeping the homeostatic control in health. Mechanisms of disease include enhanced energy extraction from the non-digestible dietary carbohydrates, increased gut permeability and translocation of bacterial metabolites which activate a chronic low-grade systemic inflammation and insulin resistance, as precursors of tangible metabolic disorders involving glucose and lipid homeostasis. The ultimate causative role of gut microbiota in this respect remains to be elucidated, as well as the therapeutic value of manipulating the gut microbiota by diet, pre- and pro- synbiotics, or fecal microbial transplantation.}, } @article {pmid37802272, year = {2023}, author = {Jangi, S and Hsia, K and Zhao, N and Kumamoto, CA and Friedman, S and Singh, S and Michaud, DS}, title = {Dynamics of the Gut Mycobiome in Patients with Ulcerative Colitis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2023.09.023}, pmid = {37802272}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC), however it remains unclear if fungal composition is altered during active vs quiescent disease.

METHODS: We analyzed clinical and metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's & Colitis Foundation. We evaluated the fungal composition of fecal samples from 421 patients with UC during clinical activity and remission. Within a longitudinal subcohort (n=52), we assessed for dynamic taxonomic changes across alterations in clinical activity over time. We examined if fungal amplicon sequence variants and fungal-bacterial relationships were altered during activity vs remission. Finally, we classified activity in UC using a supervised machine learning random forest model trained on fungal abundance data.

RESULTS: During clinical activity, the relative abundance of genus Candida was increased 3.5-fold (p-adj < 1 x 10[-4]) compared to during remission. Patients with longitudinal reductions in clinical activity demonstrated parallel reductions in Candida relative abundance (p<0.05). Candida relative abundance correlated with Parabacteroides diastonis, Faecalibacterium prausnitzii and Bacteroides dorei relative abundance (p<0.05) during remission, however these correlations were disrupted during activity. Fungal abundance data successfully classified patients with active or quiescent UC (AUC ∼0.80), with Candida relative abundance critical to the success of the model.

CONCLUSIONS: Clinical activity in UC is associated with an increased relative abundance of Candida, cross-sectionally and dynamically over time. The role of fecal Candida as a target for therapeutics in UC should be evaluated.}, } @article {pmid37800288, year = {2023}, author = {Hosonuma, M and Murayama, M and Yoshimura, K}, title = {[The Gut Microbiota Metabolite A Enhances the Anti-Tumor Effects of Anti-PD-1 Antibody Therapy through Immune Modulation].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {50}, number = {9}, pages = {960-964}, pmid = {37800288}, issn = {0385-0684}, abstract = {The gut microbiota is an important partner in humans, and its dysregulation is associated with the development of inflammatory bowel diseases and cancer. Furthermore, the gut microbiota is involved in the therapeutic effects of immune checkpoint inhibitors, and controlling the gut microbiota may enhance the efficacy of cancer immunotherapy. Currently, the development of therapies to control the gut microbiota includes fecal transplantation, probiotics, prebiotics, and postbiotics. In this article, we introduce SCFA-A, a type of short-chain fatty acid(SCFA)and a metabolite of gut microbiota, which is involved in the activation of T cells and induction of M1 macrophages, thereby enhancing the anti-tumor effects of anti- PD-1 antibody therapy. SCFA-A holds promise as a novel treatment approach in cancer immunotherapy as a postbiotic.}, } @article {pmid37798771, year = {2023}, author = {Zhou, C and Li, J and Guo, C and Zhou, Z and Yang, Z and Zhang, Y and Jiang, J and Cai, Y and Zhou, J and Xia, M and Ming, Y}, title = {Alterations in gut microbiome and metabolite profile of patients with Schistosoma japonicum infection.}, journal = {Parasites & vectors}, volume = {16}, number = {1}, pages = {346}, pmid = {37798771}, issn = {1756-3305}, support = {81771722//National Natural Science Foundation of China/ ; 2021SK2032//Key Research and Development Plan of Hunan Province/ ; }, abstract = {BACKGROUND: Schistosoma infection is a significant public health issue, affecting over 200 million individuals and threatening 700 million people worldwide. The species prevalent in China is Schistosoma japonicum. Recent studies showed that both gut microbiota and metabolome are closely related to schistosomiasis caused by S. japonicum, but clinical study is limited and the underlying mechanism is largely unclear. This study aimed to explore alterations as well as function of gut microbiota and metabolite profile in the patients with S. japonicum infection.

METHODS: This study included 20 patients diagnosed with chronic schistosomiasis caused by S. japonicum, eight patients with advanced schistosomiasis caused by S. japonicum and 13 healthy volunteers. The fresh feces of these participators, clinical examination results and basic information were collected. 16S ribosomal RNA gene sequencing was used to investigate gut microbiota, while ultraperformance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to explore the metabolome of patients in different stages of schistosomiasis.

RESULTS: The study found that gut microbiota and metabolites were altered in patients with different stages of S. japonicum infection. Compared with healthy control group, the gut microbial diversity in patients with chronic S. japonicum infection was decreased significantly. However, the diversity of gut microbiota in patients with chronic schistosomiasis was similar to that in patients with advanced schistosomiasis. Compared with uninfected people, patients with schistosomiasis showed decreased Firmicutes and increased Proteobacteria. As disease progressed, Firmicutes was further reduced in patients with advanced S. japonicum infection, while Proteobacteria was further increased. In addition, the most altered metabolites in patients with S. japonicum infection were lipids and lipid-like molecules as well as organo-heterocyclic compounds, correlated with the clinical manifestations and disease progress of schistosomiasis caused by S. japonicum.

CONCLUSIONS: This study suggested that the gut microbiota and metabolome altered in patients in different stages of schistosomiasis, which was correlated with progression of schistosomiasis caused by S. japonicum. This inter-omics analysis may shed light on a better understanding of the mechanisms of the progression of S. japonicum infection and contribute to identifying new potential targets for the diagnosis and prognosis of S. japonicum infection. However, a large sample size of validation in clinic is needed, and further study is required to investigate the underlying mechanism.}, } @article {pmid37798034, year = {2023}, author = {Vendrik, KE and Chernova, VO and Kuijper, EJ and Terveer, EM and van Hilten, JJ and Contarino, MF and , }, title = {Safety and feasibility of faecal microbiota transplantation for patients with Parkinson's disease: a protocol for a self-controlled interventional donor-FMT pilot study.}, journal = {BMJ open}, volume = {13}, number = {10}, pages = {e071766}, doi = {10.1136/bmjopen-2023-071766}, pmid = {37798034}, issn = {2044-6055}, abstract = {INTRODUCTION: Experimental studies suggest a role of gut microbiota in the pathophysiology of Parkinson's disease (PD) via the gut-brain axis. The gut microbiota can also influence the metabolism of levodopa, which is the mainstay of treatment of PD. Therefore, modifying the gut microbiota by faecal microbiota transplantation (FMT) could be a supportive treatment strategy.

METHODS AND ANALYSIS: We have developed a study protocol for a single-centre, prospective, self-controlled, interventional, safety and feasibility donor-FMT pilot study with randomisation and double-blinded allocation of donor faeces. The primary objectives are feasibility and safety of FMT in patients with PD. Secondary objectives include exploring whether FMT leads to alterations in motor complications (fluctuations and dyskinesias) and PD motor and non-motor symptoms (including constipation), determining alterations in gut microbiota composition, assessing donor-recipient microbiota similarities and their association with PD symptoms and motor complications, evaluating the ease of the study protocol and examining FMT-related adverse events in patients with PD. The study population will consist of 16 patients with idiopathic PD that use levodopa and experience motor complications. They will receive FMT with faeces from one of two selected healthy human donors. FMT will be administered via a gastroscope into the duodenum, after treatment with oral vancomycin, bowel lavage and domperidone. There will be seven follow-up moments during 12 months.

ETHICS AND DISSEMINATION: This study was approved by the Medical Ethical Committee Leiden Den Haag Delft (ref. P20.087). Study results will be disseminated through publication in peer-reviewed journals and international conferences.

TRIAL REGISTRATION NUMBER: International Clinical Trial Registry Platform: NL9438.}, } @article {pmid37797200, year = {2023}, author = {Han, Q and Liu, R and Wang, H and Zhang, R and Liu, H and Li, J and Bao, J}, title = {Gut Microbiota-Derived 5-Hydroxyindoleacetic Acid Alleviates Diarrhea in Piglets via the Aryl Hydrocarbon Receptor Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.3c04658}, pmid = {37797200}, issn = {1520-5118}, abstract = {With the improvement in sow prolificacy, formula feeding has been increasingly used in the pig industry. Diarrhea remains a serious health concern in formula-fed (FF) piglets. Fecal microbiota transplantation (FMT) is an efficacious strategy to reshape gut microbiota and the metabolic profile for treating diarrhea. This study aims to investigate whether FMT from breast-fed piglets could alleviate diarrhea in FF piglets. The piglets were randomly assigned to the control (CON) group, FF group, and FMT group. Our results showed that FF piglets exhibited a higher diarrhea incidence, damaged colonic morphology, and disrupted barrier function. In contrast, FMT treatment normalized the morphology and barrier function. FMT suppressed the JNK/MAPK pathway and production of proinflammatory cytokines. Additionally, FF piglets had a lower abundance of the beneficial bacterial genus Bifidobacterium compared to CON piglets. Following FMT administration, Bifidobacterium was restored. Meanwhile, 5-HIAA, a metabolite of tryptophan, and AHR-responsive CYP1A1 and CYP1B1 were upregulated. Importantly, integrated multiomics analysis revealed a strong positive correlation between Bifidobacterium and 5-HIAA. In vitro, 5-HIAA supplementation reversed the LPS-induced disruption of tight junctions and production of proinflammatory cytokines in IPEC-J2 cells. In conclusion, FMT reduced diarrhea incidence and improved growth performance. The alleviative effect of FMT on diarrhea was associated with Bifidobacterium and 5-HIAA.}, } @article {pmid37796494, year = {2023}, author = {Stewart, AK and Foley, MH and Dougherty, MK and McGill, SK and Gulati, AS and Gentry, EC and Hagey, LR and Dorrestein, PC and Theriot, CM and Dodds, JN and Baker, ES}, title = {Using Multidimensional Separations to Distinguish Isomeric Amino Acid-Bile Acid Conjugates and Assess Their Presence and Perturbations in Model Systems.}, journal = {Analytical chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.analchem.3c03057}, pmid = {37796494}, issn = {1520-6882}, abstract = {Bile acids play key roles in nutrient uptake, inflammation, signaling, and microbiome composition. While previous bile acid analyses have primarily focused on profiling 5 canonical primary and secondary bile acids and their glycine and taurine amino acid-bile acid (AA-BA) conjugates, recent studies suggest that many other microbial conjugated bile acids (or MCBAs) exist. MCBAs are produced by the gut microbiota and serve as biomarkers, providing information about early disease onset and gut health. Here we analyzed 8 core bile acids synthetically conjugated with 22 proteinogenic and nonproteogenic amino acids totaling 176 MCBAs. Since many of the conjugates were isomeric and only 42 different m/z values resulted from the 176 MCBAs, a platform coupling liquid chromatography, ion mobility spectrometry, and mass spectrometry (LC-IMS-MS) was used for their separation. Their molecular characteristics were then used to create an in-house extended bile acid library for a combined total of 182 unique compounds. Additionally, ∼250 rare bile acid extracts were also assessed to provide additional resources for bile acid profiling and identification. This library was then applied to healthy mice dosed with antibiotics and humans having fecal microbiota transplantation (FMT) to assess the MCBA presence and changes in the gut before and after each perturbation.}, } @article {pmid37796016, year = {2023}, author = {Kamer, O and Rinott, E and Tsaban, G and Kaplan, A and Yaskolka Meir, A and Zelicha, H and Knights, D and Tuohy, K and Fava, F and Uwe Scholz, M and Ziv, O and Rubin, E and Blüher, M and Stumvoll, M and Ceglarek, U and Clément, K and Koren, O and Hu, FB and Stampfer, MJ and Wang, DD and Youngster, I and Shai, I}, title = {Successful weight regain attenuation by autologous fecal microbiota transplantation is associated with non-core gut microbiota changes during weight loss; randomized controlled trial.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2264457}, doi = {10.1080/19490976.2023.2264457}, pmid = {37796016}, issn = {1949-0984}, abstract = {We previously reported that autologous-fecal-microbiota-transplantation (aFMT), following 6 m of lifestyle intervention, attenuated subsequent weight regain and insulin rebound for participants consuming a high-polyphenol green-Mediterranean diet. Here, we explored whether specific changes in the core (abundant) vs. non-core (low-abundance) gut microbiome taxa fractions during the weight-loss phase (0-6 m) were differentially associated with weight maintenance following aFMT. Eighty-two abdominally obese/dyslipidemic participants (age = 52 years; 6 m weightloss = -8.3 kg) who provided fecal samples (0 m, 6 m) were included. Frozen 6 m's fecal samples were processed into 1 g, opaque and odorless aFMT capsules. Participants were randomly assigned to receive 100 capsules containing their own fecal microbiota or placebo over 8 m-14 m in ten administrations (adherence rate > 90%). Gut microbiome composition was evaluated using shotgun metagenomic sequencing. Non-core taxa were defined as ≤ 66% prevalence across participants. Overall, 450 species were analyzed. At baseline, 13.3% were classified as core, and Firmicutes presented the highest core proportion by phylum. During 6 m weight-loss phase, abundance of non-core species changed more than core species (P < .0001). Subject-specific changes in core and non-core taxa fractions were strongly correlated (Jaccard Index; r = 0.54; P < .001). Following aFMT treatment, only participants with a low 6 m change in core taxa, and a high change in non-core taxa, avoided 8-14 m weight regain (aFMT = -0.58 ± 2.4 kg, corresponding placebo group = 3.18 ± 3.5 kg; P = .02). In a linear regression model, low core/high non-core 6 m change was the only combination that was significantly associated with attenuated 8-14 m weight regain (P = .038; P = .002 for taxa patterns/treatment intervention interaction). High change in non-core, low-abundance taxa during weight-loss might mediate aFMT treatment success for weight loss maintenance.ClinicalTrials.gov: NCT03020186.}, } @article {pmid37795613, year = {2023}, author = {Wang, C and Liu, XL and Sun, Q and Zhao, FY and Dai, PQ and Li, LX and Hu, DG}, title = {Apple consumption affects cecal health by regulating 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) levels through modifying the microbiota in rats.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d3fo03207h}, pmid = {37795613}, issn = {2042-650X}, abstract = {Apples are rich in many nutrients and functional components. However, the mechanism of the effect of fresh apple consumption on rats remains unclear. In the present study, fresh apples (10 g kg[-1]) were added to the diet of Wistar rats, and changes in the microbiota and metabolite content of the cecum were analyzed after 28 days of feeding, and changes in the 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) content and indicators related to inflammation, oxidative stress, and apoptosis were detected. Subsequently, a fecal microbiota transplantation (FMT) protocol was designed and carried out to verify the relationship between the microbiota and 12(S)-HETE, the cecal structure, and inflammatory factors. The results show that apple consumption significantly reduced the serum levels of alanine aminotransferase (ALT) and immunoglobulin G (IgG), altered the cecal histomorphology, and significantly upregulated the gene expression of claudin-1 and zonula occludens-1 (ZO-1), which encode tight junction proteins. Apple consumption also changed the structure of the cecal microbiota, increasing the abundance of some species (such as Shuttleworthia) and decreasing the abundance of others (such as Alphaproteobacteria). Metabolomic screening identified 64 significantly different metabolites. The FMT results showed that apple consumption reduced 12(S)-HETE metabolite levels in the cecal contents, improved the intestinal structure, and reduced the levels of proinflammatory factor expression by altering the cecal microbiota. In conclusion, this study provides further insight into the effects of apples on animals using rats as experimental animals. It provides basic data for future exploration of the mechanisms of the effect of apple consumption on humans.}, } @article {pmid37795305, year = {2023}, author = {Yang, Y and Cui, B and Lv, Y and Lu, X and Shen, W and Feng, M and Ding, X and Dong, P and Wang, Y}, title = {Plateau pika fecal microbiota transplantation ameliorates inflammatory bowel disease manifestations in a mouse model of colitis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1228778}, pmid = {37795305}, issn = {1664-302X}, abstract = {Inflammatory bowel disease (IBD) is a serious global public health concern. Although the pathogenesis of the disease is currently unknown, it has been reported to be associated with both intestinal microbiota and inflammatory mediators. There is evidence suggesting that the feces of the Plateau pika is useful for treating gastrointestinal injuries and pain. Although fecal microbiota transplantation is highly efficacious intervention for IBD prevention, however, potential the transfer of pathogenic microbes or toxic substances is potentially hazardous. Fortunately, micropore filtering of the donor feces can minimize the risk of bacterial infection allowing retention of the therapeutic effects of the residual bacteriophages. Here, we demonstrated that Plateau pika feces not only alleviated the IBD symptoms but also promoted optimal structure and composition of the intestinal microbiota. Additionally, Plateau pika feces transfer also enhanced phenotypic features, such as, body-weight, disease activity index, and histological scores. In conclusion, Plateau pika feces was found to protect mice against colitis induced by dextran sodium sulfate by reducing inflammation and regulating microbial dysbiosis. These findings suggest the potential of Plateau pika feces as an alternative therapy for IBD.}, } @article {pmid37794047, year = {2023}, author = {Li, G and Liu, L and Lu, T and Sui, Y and Zhang, C and Wang, Y and Zhang, T and Xie, Y and Xiao, P and Zhao, Z and Cheng, C and Hu, J and Chen, H and Xue, D and Chen, H and Wang, G and Kong, R and Tan, H and Bai, X and Li, Z and McAllister, F and Li, L and Sun, B}, title = {Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {6179}, pmid = {37794047}, issn = {2041-1723}, support = {82270665//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82070658//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. Moreover, Bacteroides uniformis or taurine inhibits the activation of NF-κB and IL-17 signaling pathways in neutrophils which harness NETs and alleviate pancreatic injury. Our findings establish roles of endogenous Bacteroides uniformis-derived metabolic and inflammatory products on suppressing NETs release, which provides potential insights of ameliorating HTGP through gut microbiota modulation.}, } @article {pmid37793354, year = {2023}, author = {Shi, X and Li, Z and Lin, W and Shi, W and Hu, R and Chen, G and Li, X and Li, X and Zhang, S}, title = {Altered intestinal microbial flora and metabolism in patients with idiopathic membranous nephropathy.}, journal = {American journal of nephrology}, volume = {}, number = {}, pages = {}, doi = {10.1159/000533537}, pmid = {37793354}, issn = {1421-9670}, abstract = {INTRODUCTION: Dysbiosis of the intestinal microbiome and related metabolites have been observed in chronic kidney disease (CKD), yet their roles in idiopathic membranous nephropathy (IMN) is poorly understood.

METHODS: In this study, we describe the variation of intestinal bacteria and fecal metabolites in patients with IMN in Chinese population. Stool samples are collected from 41 IMN patients at the beginning of diagnosis confirmation and 41 gender and age matched healthy control (HC). Microbial communities are investigated by sequencing of 16S rRNA genes and functional profiles predicted using Tax4Fun, and the correlation between intestinal bacteria and IMN clinical characteristics is also analyzed. Untargeted metabolomic analysis is performed to explore the relationship between colon's microbiota and fecal metabolites.

RESULTS: IMN gastrointestinal microbiota demonstrates lower richness and diversity compared to HC, and exhibits a marked taxonomic and inferred functional dysbiosis when compared to HC. Some genera are closely related to the clinical parameters, such as Citrobacter and Akkermansia. 20 characteristic microbial biomarkers are selected to establish a disease prediction model with a diagnostic accuracy of 93.53%. Fecal metabolomics shows that tryptophan metabolism is reduced in IMN patients but uremic toxin accumulation in feces is not noticeable. Fecal microbiota transplantation demonstrates that gut dysbiosis impairs gut permeability in microbiota-depleted mice and induces NOD-like receptor activation in kidneys.

DISCUSSION/CONCLUSIONS: Clarifying the changes in intestinal microbiota in IMN patients will help further know the pathogenesis of this disease, and microbiota-targeted biomarkers will provide a potentially powerful tool for diagnosing and treating IMN.}, } @article {pmid37793163, year = {2023}, author = {Zhang, S and Zhao, X and Wang, X and Jin, H and Chen, L and Ma, Y and Chi, Y and Zhang, J and Zhang, J and Gao, Y}, title = {Gut microecology may be involved in pathogenesis of Hashimoto's thyroiditis by reducing production of hydrogen sulfide.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1210/clinem/dgad588}, pmid = {37793163}, issn = {1945-7197}, abstract = {CONTEXT: Hashimoto's thyroiditis (HT) is related to intestinal microbiota alteration, but the causal relationship remains unclear. Hydrogen sulfide (H2S) is a microbiota-derived metabolite. We speculated that abnormal intestinal microbiota might limit H2S production capacity, promoting HT pathogenesis.

OBJECTIVE: To illustrate that the intestinal microbiota plays important roles in HT pathogenesis via microbiota-derived H2S levels.

METHODS: We collected feces from HT patients and healthy donors for fecal microbiota transplantation (FMT). Thirty-six female CBA/J mice were randomized into four groups: experimental autoimmune thyroiditis (EAT) group, EAT + Health group, EAT + HT group, and EAT + HT + H2S group. 16S rRNA sequencing was performed to examine gut microbiota alterations and H2S production pathway. Serum TgAb and H2S levels were assayed by ELISA and H2S-selective sensors, respectively. T-cell subpopulations in the spleen were detected by flow cytometry.

RESULTS: The gut microbiota was different after FMT among the EAT, EAT + Health and EAT + HT groups. The thyroiditis score assessed by H&E staining was higher in the EAT + HT group than that in the EAT and EAT + HT + H2S groups. Th1 and Th17 cell differentiation ratios were increased in EAT + HT group compared to the other three groups. Serum H2S levels were decreased and the dissimilatory sulfate reduction (DSR) pathway was attenuated in the EAT + HT group compared to the EAT + Health group.

CONCLUSIONS: H2S alleviated thyroiditis severity and related immune disorders, which was aggravated by the FMT from HT patients. The attenuated DSR pathway in the gut microbiota from HT patients might be involved in thyroiditis pathogenesis.}, } @article {pmid37791342, year = {2023}, author = {Kamiya, S}, title = {Microbial ecology between Clostridioides difficile and gut microbiota.}, journal = {Bioscience of microbiota, food and health}, volume = {42}, number = {4}, pages = {229-235}, pmid = {37791342}, issn = {2186-6953}, abstract = {Clostridioides difficile colonizes a polymicrobial environment in the intestine and is a causative agent for antibiotic-associated diarrhea (AAD) and pseudomembranous colitis (PMC). The most important virulence factors of C. difficile are bacterial toxins, and three toxins (toxin A, toxin B, and binary toxin) are produced by toxigenic strains. Other virulence factors include spores, flagella, capsules, biofilms, hydrolytic enzymes and adhesins. C. difficile infection (CDI) is specifically diagnosed by anaerobic culture and toxin detection by either nucleic acid amplification test (NAAT) or enzyme-linked immunosorbent assay (ELISA). For treatment of CDI, metronidazole, vancomycin and fidaxomicin are used based on the severity of CDI. Mutual interaction between C. difficile and gut microbiota is associated with pathogenesis of CDI, and decreased microbial diversity with altered gut microbiome was detected in CDI patients. Restoration of certain gut microbiota is considered to be potentially effective for the prevention and treatment of CDI, and an ideal goal for CDI patients is restoration of the gut microbiota to a healthy state. Fecal microbiota transplantation (FMT) is a highly successful method of microbiome restoration and has been reported to be effective for the prevention of recurrent CDI. In addition, approaches to restoring the gut microbiota by using probioitcs and live biotherapeutic products (LBPs) are currently being studied to examine the effect on CDI. Further microbial ecological research on C. difficile and gut microbiota could lead to a better understanding of the pathogenesis and treatment of CDI.}, } @article {pmid37789073, year = {2023}, author = {Battipaglia, G and Mooyaart, JE and Meyer, R and Mohty, M and Sadowska-Klasa, A and Goloshchapov, O and Locatelli, F and Styczynski, J and Pavlu, J and Dybko, J and Bronin, G and Salmenniemi, U and Jindra, P and Hoogenboom, JD and Kuball, J and Ruggeri, A and Malard, F}, title = {Current use of fecal microbiota transfer in patients with hematologic diseases: a survey on behalf of the Cellular Therapy and Immunobiology Working Party of the EBMT.}, journal = {Bone marrow transplantation}, volume = {}, number = {}, pages = {}, pmid = {37789073}, issn = {1476-5365}, } @article {pmid37788279, year = {2023}, author = {Wang, J and Liu, X and Sun, R and Mao, H and Liu, M and Jin, X}, title = {Akkermansia muciniphila participates in the host protection against helminth-induced cardiac fibrosis via TLR2.}, journal = {PLoS pathogens}, volume = {19}, number = {10}, pages = {e1011683}, pmid = {37788279}, issn = {1553-7374}, abstract = {Helminth Trichinella spiralis (Ts) is one of the major pathogens of human infective myocarditis that can lead to cardiac fibrosis (CF). The gut microbiota involved in this pathology are of interest. Here, we use mice infected with Ts as a model to examine the interactions between gut microbes and host protection to CF. Infected mice show enhanced CF severity. We find that antibiotics treatment to deplete the microbiota aggravates the disease phenotype. Attempts to restore microbiota using fecal microbiota transplantation ameliorates helminth-induced CF. 16S rRNA gene sequencing and metagenomics sequencing reveal a higher abundance of Akkermansia muciniphila in gut microbiomes of Ts-infected mice. Oral supplementation with alive or pasteurized A. muciniphila improves CF via TLR2. This work represents a substantial advance toward our understanding of causative rather than correlative relationships between the gut microbiota and CF.}, } @article {pmid37787998, year = {2023}, author = {Rashidi, A and Ebadi, M and Rehman, TU and Elhusseini, H and Kazadi, D and Halaweish, H and Khan, MH and Hoeschen, A and Cao, Q and Luo, X and Kabage, AJ and Lopez, S and Holtan, SG and Weisdorf, DJ and Khoruts, A and Staley, C}, title = {Potential of fecal microbiota transplantation to prevent acute graft-versus-host disease: Analysis from a phase 2 trial.}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, volume = {}, number = {}, pages = {}, doi = {10.1158/1078-0432.CCR-23-2369}, pmid = {37787998}, issn = {1557-3265}, abstract = {PURPOSE: Intestinal microbiota disruptions early after allogeneic hematopoietic cell transplantation have been associated with increased risk for acute graft-versus-host disease (aGVHD). In our recent randomized phase 2 trial of oral, encapsulated, third-party fecal microbiota transplantation (FMT) versus placebo, FMT at the time of neutrophil recovery was safe and ameliorated dysbiosis. Here, we evaluated in post hoc analysis whether donor microbiota engraftment after FMT may protect against acute GVHD.

PATIENTS AND METHODS: We analyzed pre- and post-FMT stool samples and estimated donor microbiota engraftment (a pre-planned secondary endpoint) by determining the fraction of post-FMT microbiota formed by unique donor taxa (donor microbiota fraction; dMf).

RESULTS: dMf was higher in patients who later developed grade I or no aGVHD (median 33.9%, range 1.6-74.3%) than those who developed grade II-IV aGVHD (median 25.3%, range 2.2-34.8%) (P = 0.006). The cumulative incidence of grade II-IV aGVHD by day 180 was lower in the group with greater-than-median dMf than the group with less-than-median dMf (14.3% [95%CI, 2.1-37.5%] vs. 76.9% [95% CI, 39.7-92.8%], P = 0.008). The only determinant of dMf in cross-validated LASSO-regularized regression was the patient's pre-FMT microbiota diversity (Pearson's correlation coefficient -0.82, P = 1.6x10-9), indicating more potent microbiota modulation by FMT in patients with more severe dysbiosis. Microbiota network analysis revealed major rewiring including changes in the most central nodes, without emergence of keystone species, as a potential mechanism of FMT effect.

CONCLUSIONS: FMT may have protective effects against aGVHD, especially in patients with more severe microbiota disruptions.}, } @article {pmid37787835, year = {2023}, author = {Li, S and Zhao, L and Xiao, J and Guo, Y and Fu, R and Zhang, Y and Xu, S}, title = {The gut microbiome: an important role in neurodegenerative diseases and their therapeutic advances.}, journal = {Molecular and cellular biochemistry}, volume = {}, number = {}, pages = {}, pmid = {37787835}, issn = {1573-4919}, support = {No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 81973626, No. 81774059//National Natural Science Foundation of China/ ; No. 21JCYBJC01620//Tianjin Municipal Science and Technology Commission of China/ ; No. 21JCYBJC01620//Tianjin Municipal Science and Technology Commission of China/ ; No. 21JCYBJC01620//Tianjin Municipal Science and Technology Commission of China/ ; No. 2021099//Tianjin Health Committee/ ; No. 2021099//Tianjin Health Committee/ ; No. 2021099//Tianjin Health Committee/ ; No. 2021KJ146//Tianjin Education Committee/ ; No. 2021KJ146//Tianjin Education Committee/ ; No. 2021KJ146//Tianjin Education Committee/ ; }, abstract = {There are complex interactions between the gut and the brain. With increasing research on the relationship between gut microbiota and brain function, accumulated clinical and preclinical evidence suggests that gut microbiota is intimately involved in the pathogenesis of neurodegenerative diseases (NDs). Increasingly studies are beginning to focus on the association between gut microbiota and central nervous system (CNS) degenerative pathologies to find potential therapies for these refractory diseases. In this review, we summarize the changes in the gut microbiota in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis and contribute to our understanding of the function of the gut microbiota in NDs and its possible involvement in the pathogenesis. We subsequently discuss therapeutic approaches targeting gut microbial abnormalities in these diseases, including antibiotics, diet, probiotics, and fecal microbiota transplantation (FMT). Furthermore, we summarize some completed and ongoing clinical trials of interventions with gut microbes for NDs, which may provide new ideas for studying NDs.}, } @article {pmid37787395, year = {2023}, author = {Lo Porto, D and Mularoni, A and Castagnola, E and Saffioti, C}, title = {Clostridioides difficile infection in the allogeneic hematopoietic cell transplant recipient.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e14159}, doi = {10.1111/tid.14159}, pmid = {37787395}, issn = {1399-3062}, support = {Ricerca Corrente: RC 2022 Linea 1//Italian Ministry of Health/ ; }, abstract = {Clostridioides difficile (CD) is one of the most important causes of diarrhea in hospitalized patients, in particular those who undergo an allogeneic hematopoietic cell transplant (allo-HCT) and who are more at risk of developing a CD infection (CDI) due to frequent hospitalizations, iatrogenic immunosuppression, and prolonged antibiotic cycles. CDI may represent a severe condition in allo-HCT patients, increasing the length of hospitalization, influencing the intestinal microbiome with a bidirectional association with graft-versus-host disease, and leading to unfavorable outcomes, including death. The diagnosis of CDI requires the exclusion of other probable causes of diarrhea in HCT patients and is based on highly sensitive and highly specific tests to distinguish colonization from infection. In adult patients, fidaxomicin is recommended as first-line, with oral vancomycin as an alternative agent. Bezlotoxumab may be used to reduce the risk of recurrence. In pediatric patients, vancomycin and metronidazole are still suggested as first-line therapy, but fidaxomicin will probably become standard in pediatrics in the near future. Because of insufficient safety data, fecal microbiota transplantation is not routinely recommended in HCT in spite of promising results for the management of recurrences in other populations.}, } @article {pmid37787118, year = {2023}, author = {Shou, D and Luo, Q and Tang, W and Cao, C and Huang, H and Chen, H and Zhou, Y}, title = {Hepatobiliary and pancreatic: Multi-donor fecal microbiota transplantation attenuated high-fat diet-induced hepatic steatosis in mice by remodeling the gut microbiota.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16359}, pmid = {37787118}, issn = {1440-1746}, support = {81970507//Natural Science Foundation of China/ ; 82170585//Natural Science Foundation of China/ ; 2023A0505010007//Science and Technology Planning Project of Guangdong Province/ ; 2021A1515011290//Natural Science Foundation of Guangdong Province/ ; 2023A03J0955//Guangzhou Municipal Science and Technology Project/ ; }, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) can improve the symptoms of nonalcoholic fatty liver disease (NAFLD) by restoring the gut microbiota. This study was aimed to evaluate the therapeutic effects of single-donor (SD) or multi-donor (MD) FMT in a mouse model of hepatic steatosis and explore the underlying mechanisms.

METHODS: Fecal samples were collected from NAFLD patients and healthy controls with similar baseline characteristics, with gut microbiota analyzed. Mice were fed either a normal-chow diet (NCD) or a high-fat diet (HFD) for 3 weeks and then administered fecal microbiota collected from healthy SDs or MDs for 12 weeks.

RESULTS: Fecal samples from NAFLD patients showed significantly lower microbial diversity than those from healthy controls. MD-FMT reduced liver fat accumulation and body weight and significantly improved serum and liver biochemical indices in HFD-fed mice. Compared to untreated HFD-fed mice, MD-FMT significantly decreased the relative expression of IL-1β, IL-6, TNF-α, IFN-γ, and IL-1β mRNAs in the liver. The relative protein level of intestinal barrier components, including claudin-1, occludin, and E-cadherin, as well as serum lipopolysaccharide (LPS) level in mice, were found to be improved following MD-FMT intervention. Furthermore, FMT reversed HFD-induced gut dysbiosis and increased the abundance of beneficial bacteria such as Blautia and Akkermansia.

CONCLUSION: NAFLD patients and healthy controls showed distinct gut microbiota. Likewise, HFD altered gut microbiota in mice compared to NCD-fed controls. MD-FMT restored gut dysbiosis in HFD-fed mice and attenuated liver steatosis, and should be considered as an effective treatment option for NAFLD.}, } @article {pmid37781523, year = {2023}, author = {Shao, X and Liu, L and Zhou, Y and Zhong, K and Gu, J and Hu, T and Yao, Y and Zhou, C and Chen, W}, title = {High-fat diet promotes colitis-associated tumorigenesis by altering gut microbial butyrate metabolism.}, journal = {International journal of biological sciences}, volume = {19}, number = {15}, pages = {5004-5019}, pmid = {37781523}, issn = {1449-2288}, abstract = {Background: Dietary fat intake is associated with an increased risk of colitis associated cancer (CAC). A high-fat diet (HFD) leads to systemic low-grade inflammation. The colon is believed to be the first organ suffering from inflammation caused by the infiltration of pro-inflammatory macrophages, and promotes CAC progression. We explored the role of HFD in driving CAC by altering gut microbial butyrate metabolism. Methods: Changes in the gut microbiota caused by HFD were investigated via HFD treatment or fecal microbiota transplantation (FMT). The underlying mechanisms were further explored by analyzing the role of gut microbiota, microbial butyrate metabolism, and NLRP3 inflammasome in colon tissues in a CAC mouse model. Results: HFD accelerated CAC progression in mice, and it could be reversed by broad-spectrum antibiotics (ABX). 16S-rRNA sequencing revealed that HFD inhibited the abundance of butyrate-producing bacteria in the gut. The level of short-chain fatty acids (SCFAs), especially butyrate, in the gut of mice treated with HFD was significantly reduced. In addition, treatment with exogenous butyrate reversed the M1 polarization of proinflammatory macrophages, aggravation of intestinal inflammation, and accelerated tumor growth induced by HFD; the NLRP3/Caspase-1 pathway activated by HFD in the colon was also significantly inhibited. In vitro, macrophages were treated with lipopolysaccharide combined with butyrate to detect the M1 polarization level and NLRP3/Caspase-1 pathway expression, and the results were consistent with those of the in vivo experiments. Conclusion: HFD drives colitis-associated tumorigenesis by inducing gut microbial dysbiosis and inhibiting butyrate metabolism to skew macrophage polarization. Exogenous butyrate is a feasible new treatment strategy for CAC, and has good prospect for clinical application.}, } @article {pmid37781044, year = {2023}, author = {Zhang, L and Ji, Q and Chen, Q and Wei, Z and Liu, S and Zhang, L and Zhang, Y and Li, Z and Liu, H and Sui, H}, title = {Akkermansia muciniphila inhibits tryptophan metabolism via the AhR/β-catenin signaling pathway to counter the progression of colorectal cancer.}, journal = {International journal of biological sciences}, volume = {19}, number = {14}, pages = {4393-4410}, pmid = {37781044}, issn = {1449-2288}, mesh = {Humans ; Mice ; Animals ; beta Catenin/metabolism ; Tryptophan/adverse effects ; Receptors, Aryl Hydrocarbon/genetics/metabolism ; Base Composition ; Phylogeny ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; *Colorectal Neoplasms/metabolism ; *Colonic Neoplasms ; Wnt Signaling Pathway ; Mice, Inbred C57BL ; }, abstract = {Akkermansia muciniphila (A. muciniphila), a gram-negative anaerobic bacterium, is selectively decreased in the fecal microbiota of patients with colorectal cancer (CRC), but its molecular mechanism in CRC development remains inconclusive. In this study, we first confirmed the inhibitory effect of A. muciniphila on CRC formation and analyzed the metabolic role of intestinal flora in human Polyps, A-CRA (advanced colorectal adenoma) and CRC samples. To better clarify the role of A. muciniphila in CRC development, a pseudo-germ-free (GF) azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model was established, followed by infection with or without A. muciniphila. Metabolomic analysis and RNA-seq analysis showed tryptophan-mediated aryl hydrocarbon receptor (AhR) was significantly down-regulated in A. muciniphila-infected CRC mice. Then, mice with intestinal specific AhR deficiency (AhR[fl/fl] Cre) were generated and were used in 2 murine models: AOM/DSS treatment as a model of carcinogen-induced colon cancer and a genetically induced model using Apc[Min/+] mice. Notably, AhR deficiency inhibited CRC growth in the AOM/DSS and Apc[Min/+] mouse model. Moreover, AhR deficiency inhibited, rather than enhanced, tumor formation and tumor-derived organoids in Apc-deficient cells both in vivo and in vitro by activating Wnt/β-catenin signaling and TCF4/LEF1-dependent transcription. Furthermore, the antitumor effectiveness of A. muciniphila was abolished either in a human colon cancer tumor model induced by subcutaneous transplantation of AhR-silenced CRC cells, or AhR-deficienty spontaneous colorectal cancer model. In conclusion, supplementation with A. muciniphila. protected mice from CRC development by specifically inhibiting tryptophan-mediated AhR/β-catenin signaling.}, } @article {pmid37780282, year = {2023}, author = {Li, W and Zhang, W and Fan, X and Xu, H and Yuan, H and Wang, Y and Yang, R and Tian, H and Wu, Y and Yang, H}, title = {Fructo-oligosaccharide enhanced bioavailability of polyglycosylated anthocyanins from red radish via regulating gut microbiota in mice.}, journal = {Food chemistry: X}, volume = {19}, number = {}, pages = {100765}, pmid = {37780282}, issn = {2590-1575}, abstract = {The anthocyanins from red radish (ARR) rich in polyglycosylated pelargonidin glucosides were used as pigment. However, bioavailability of anthocyanins was considered at low level. This work examined the intensive effects of fructo-oligosaccharide (FOS) on ARR bioavailability. Pelargonidin, cyanidin and pelargonidin-3-glucoside showed higher level in serum of mice fed with FOS together with ARR for 8 weeks than that fed with only ARR. Co-ingestion of FOS and ARR more effectively elevated the hepatic antioxidant activity by increase in total antioxidant capacity and activities of superoxide dismutase and glutathione peroxidase when compared with intake of ARR. FOS also markedly increased pelargonidin level in cecum of mice. 16S RNA sequencing found that Bacteroides genus play an important role in FOS elevating bioavailability of ARR. Fecal bacteria transplantation verified the positive effects of FOS on ARR bioavailability. These results suggested that combined ingestion of FOS and ARR is effective strategy for bioactivity of ARR.}, } @article {pmid37779873, year = {2023}, author = {Machado, AP and Shatila, M and De Toni, EN and Török, HP and Philpott, J and Zhao, D and Zhou, Y and Varatharajalu, K and Shafi, MA and Zhang, HC and Thomas, AS and Wang, Y}, title = {Colon Adenoma After Diagnosis of Immune Checkpoint Inhibitor-mediated Colitis.}, journal = {Journal of Cancer}, volume = {14}, number = {14}, pages = {2686-2693}, pmid = {37779873}, issn = {1837-9664}, abstract = {Purpose: While the occurrence of colitis during immune checkpoint inhibitor (ICI) treatment is recognized as a sign of robust immune activation and correlates with better oncological outcomes, the long-term impact of ICI-mediated colitis on the colonic mucosa has not been studied. We thus aim to describe the colonoscopy and histology findings in patients at a follow-up time of ≥ 6 months post initial colitis event. Methods: This retrospective analysis included adult cancer patients diagnosed with ICI colitis at a tertiary cancer center between October 2013 and June 2020. The study group included patients diagnosed with immune mediated colitis who had also undergone a follow up colonoscopy or flex sigmoidoscopy. The control group was patients exposed to ICI without immune mediated colitis. We reported patients' colitis clinical course, treatment, outcomes, and endoscopic and histologic features at diagnosis and at follow-up time of ≥ 6 months. Results: Total 39 patients met the study criteria, with 82% being male, and 35.8% having melanoma. Most patients received a combination of CTLA-4 and PD-1/L1 inhibitors (82%). On initial endoscopic evaluation, inflammation without ulceration was reported in 76.9% of patients and active inflammation on histologic examination in 79.3% of patients. Most patients (79.4%) received corticosteroids, and 56.4% received add-on selective immunosuppressive therapy. Four patients received fecal microbiota transplantation. On follow-up, new incidence of colonic polyps was reported in 51.2% of patients, including adenomas in 33.3% among the colitis patients with median follow up duration of 12 months. The incidence of adenoma polyps 12 months after the colitis event was significantly higher compared to the control group without colitis based on the time-to-event analysis (p=0.041). Conclusion: At a median follow up of 12 months after their initial colitis diagnosis, 51.2% of the patients had new incidence of colonic polyps, including a third with adenoma, at a significantly higher incidence than the control group without colitis. Studies with larger sample sizes are needed to further define the long-term impact of colitis and its treatments on colon health and to refine recommendations for surveillance of colonic adenomas and colorectal cancer.}, } @article {pmid37778924, year = {2023}, author = {Custer, GF and Bresciani, L and Dini-Andreote, F}, title = {Toward an integrative framework for microbial community coalescence.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2023.09.001}, pmid = {37778924}, issn = {1878-4380}, abstract = {Community coalescence is defined as the mixing of intact ecological communities. From river confluences to fecal microbiota transplantation, community coalescence constitutes a common ecological occurrence affecting natural and engineered microbial systems. In this opinion article, we propose an integrative framework for microbial community coalescence to guide advances in our understanding of this important - yet underexplored - ecological phenomenon. We start by aligning community coalescence with the unified framework of biological invasion and enumerate commonalities and idiosyncrasies between these two analogous processes. Then, we discuss how organismal interactions and cohesive establishment affect coalescence outcomes with direct implications for community functioning. Last, we propose the use of ecological null modeling to study the interplay of ecological processes structuring community reassembly following coalescence.}, } @article {pmid37777765, year = {2023}, author = {Wen, Y and Yang, L and Wang, Z and Liu, X and Gao, M and Zhang, Y and Wang, J and He, P}, title = {Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {218}, pmid = {37777765}, issn = {2049-2618}, support = {2017YFC1600306//National Key Research and Development Program of China/ ; 2017YFC1600306//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: High-copper diets have been widely used to promote growth performance of pigs, but excess copper supplementation can also produce negative effects on ecosystem stability and organism health. High-copper supplementation can damage the intestinal barrier and disturb the gut microbiome community. However, the specific relationship between high-copper-induced intestinal damage and gut microbiota or its metabolites is unclear.

OBJECTIVE: Using fecal microbiota transplantation and metagenomic sequencing, responses of colonic microbiota to a high-copper diet was profiled. In addition, via comparison of specific bacteria and its metabolites rescue, we investigated a network of bacteria-metabolite interactions involving conversion of specific metabolites as a key mechanism linked to copper-induced damage of the colon.

RESULTS: High copper induced colonic damage, Lactobacillus extinction, and reduction of SCFA (acetate and butyrate) concentrations in pigs. LefSe analysis and q-PCR results confirmed the extinction of L. johnsonii. In addition, transplanting copper-rich fecal microbiota to ABX mice reproduced the gut characteristics of the pig donors. Then, L. johnsonii rescue could restore decreased SCFAs (mainly acetate and butyrate) and colonic barrier damage including thinner mucus layer, reduced colon length, and tight junction protein dysfunction. Given that acetate and butyrate concentrations exhibited a positive correlation with L. johnsonii abundance, we investigated how L. johnsonii exerted its effects by supplementing acetate and butyrate. L. johnsonii and butyrate administration but not acetate could correct the damaged colonic barrier. Acetate administration had no effects on butyrate concentration, indicating blocked conversion from acetate to butyrate. Furthermore, L. johnsonii rescue enriched a series of genera with butyrate-producing ability, mainly Lachnospiraceae NK4A136 group.

CONCLUSIONS: For the first time, we reveal the microbiota-mediated mechanism of high-copper-induced colonic damage in piglets. A high-copper diet can induce extinction of L. johnsonii which leads to colonic barrier damage and loss of SCFA production. Re-establishment of L. johnsonii normalizes the SCFA-producing pathway and restores colonic barrier function. Mechanistically, Lachnospiraceae NK4A136 group mediated conversion of acetate produced by L. johnsonii to butyrate is indispensable in the protection of colonic barrier function. Collectively, these findings provide a feasible mitigation strategy for gut damage caused by high-copper diets. Video Abstract.}, } @article {pmid37775582, year = {2023}, author = {Samaey, A and Vázquez-Castellanos, JF and Caenepeel, C and Evenepoel, P and Vermeire, S and Raes, J and Knops, N}, title = {Effects of fecal microbiota transplantation for recurrent Clostridium difficile infection in children on kidney replacement therapy: a pilot study.}, journal = {Pediatric nephrology (Berlin, Germany)}, volume = {}, number = {}, pages = {}, pmid = {37775582}, issn = {1432-198X}, support = {1236321N//FWO Vlaanderen/ ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (rCDI) is a rising problem in children with chronic diseases. Fecal microbiota transplantation (FMT) is a recent alternative for rCDI patients who do not respond to conventional treatment. FMT could have an additional positive effect on the intestinal dysbiosis and accumulation of uremic retention molecules (URM) associated with chronic kidney disease (CKD). Our aim was to investigate the clinical efficacy of FMT for rCDI in children with CKD together with the effect on dysbiosis and URM levels.

METHODS: We analyzed stool and blood samples before and until 3 months after FMT in 3 children between 4 and 8 years old with CKD and rCDI. The microbiome was analyzed by 16 s rRNA sequencing. URM were analyzed with ultra-performance liquid chromatography-tandem mass spectrometry. CRP and fecal calprotectin were analyzed as parameters for systemic and gut inflammation, respectively.

RESULTS: CDI resolved after FMT in all three without adverse events; one patient needed a second FMT. No significant effect on CRP and calprotectin was observed. Stool samples demonstrated a reduced richness and bacterial diversity which did not improve after FMT. We did observe a trend in the decrease of specific URM up to 3 months after FMT.

CONCLUSION: FMT is an effective treatment for rCDI in patients with CKD. Analysis of the microbiome showed an important intestinal dysbiosis that, besides a significant reduction in Clostridium difficile, did not significantly change after FMT. A trend for reduction was seen in some of the measured URM after FMT. A higher resolution version of the Graphical abstract is available as Supplementary information.}, } @article {pmid37774733, year = {2023}, author = {Mandal, S and Simmons, R and Ireland, G and Charlett, A and Desai, M and Coughlan, L and Powell, A and Leeman, D and Williams, C and Neill, C and O'Leary, MC and Sawyer, C and Rowley, F and Harris, C and Houlihan, C and Gordon, C and Rampling, T and Callaby, H and Hoschler, K and Cogdale, J and Renz, E and Sebastianpilli, P and Thompson, C and Talts, T and Celma, C and Davies, EA and Ahmad, S and Machin, N and Gifford, L and Moore, C and Dickson, EM and Divala, TH and Henderson, D and Li, K and Broadbent, P and Ushiro-Lumb, I and Humphreys, C and Grammatikopoulos, T and Hartley, J and Kelgeri, C and Rajwal, S and Okike, I and Kelly, DA and Guiver, M and Borrow, R and Bindra, R and Demirjian, A and Brown, KE and Ladhani, SN and Ramsay, ME and Bradley, DT and Gjini, A and Roy, K and Chand, M and Zambon, M and Watson, CH}, title = {Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.}, journal = {The Lancet. Child & adolescent health}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2352-4642(23)00215-8}, pmid = {37774733}, issn = {2352-4650}, abstract = {BACKGROUND: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes.

METHODS: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups.

FINDINGS: Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37·4 [95% CI 15·5-90·3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (β 0·06 [95% CI 0·02-0·11]). No association was identified for SARS-CoV-2 antibody seropositivity.

INTERPRETATION: We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation.

FUNDING: None.}, } @article {pmid37771706, year = {2023}, author = {Feng, E and Yang, X and Zhao, K and Li, Y and Zhu, H and Wang, Z and Zhang, Z}, title = {Gut microbiota is associated with spatial memory and seed-hoarding behavior of South China field mice (Apodemus draco).}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1236359}, pmid = {37771706}, issn = {1664-302X}, abstract = {BACKGROUND: Scatter-hoarding animals store food in multiple locations within their home range and rely on spatial memory for subsequent localization and retrieval. The relationship between memory and scatter-hoarding behavior has been widely demonstrated, but the association of gut microbiota with spatial memory and seed-hoarding behavior of animals remains unclear.

METHODS: In this study, by using enclosure behavior tests, memory tests including an object location test (OLT) and a novel object recognition test (NORT), and fecal microbiota transplantation (FMT) experiment, we evaluated the role of gut microbiota in affecting the memory and seed-hoarding behavior of rodents. According to their scatter-hoarding intensity, South China field mice (Apodemus draco) were divided into scatter-hoarding group (SG) and non-scatter-hoarding group (NG).

RESULTS: We found that the SG performed better than the NG in the NORT. FMT from SG donor mice altered the NG recipient mice's gut microbiota structure. Further tests demonstrated FMT from SG donor mice increased memory of NG recipient mice in laboratory tests and seed larder hoarding intensity of NG recipient mice in enclosures.

CONCLUSION: Our results suggest gut microbiota could modulate the memory and seed-hoarding behavior of animals.}, } @article {pmid37771694, year = {2023}, author = {Tang, J and Zhang, H and Yin, L and Zhou, Q and Zhang, H}, title = {The gut microbiota from maintenance hemodialysis patients with sarcopenia influences muscle function in mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1225991}, pmid = {37771694}, issn = {2235-2988}, abstract = {BACKGROUND: Sarcopenia is a common complication in patients undergoing maintenance hemodialysis (MHD). Growing evidence suggests a close relationship between the gut microbiota and skeletal muscle. However, research on gut microbiota in patients with sarcopenia undergoing MHD (MS) remains scarce. To bridge this knowledge gap, we aimed to evaluate the pathogenic influence of gut microbiota in the skeletal muscle of patients with MS, to clarify the causal association between gut microbiota and skeletal muscle symptoms in patients with MS and identify the potential mechanisms underlying this causal association.

METHODS: Fecal samples were collected from 10 patients with MS and 10 patients without MS (MNS). Bacteria were extracted from these samples for transplantation. Mice (n=42) were randomly divided into three groups and, after antibiotic treatment, fecal microbiota transplantation (FMT) was performed once a day for 3 weeks. Skeletal muscle and fecal samples from the mice were collected for 16S rRNA gene sequencing and for histological, real-time PCR, and metabolomic analyses.

RESULTS: Mice colonized with gut microbiota from MS patients exhibited notable decreases in muscle function and muscle mass, compared with FMT from patients with MNS. Moreover, 16S rRNA sequencing revealed that the colonization of MS gut microbiota reduced the abundance of Akkermansia in the mouse intestines. Metabolome analysis revealed that seven metabolic pathways were notably disrupted in mice transplanted with MS microbiota.

CONCLUSION: This study established a connection between skeletal muscle and the gut microbiota of patients with MS, implying that disruption of the gut microbiota may be a driving factor in the development of skeletal muscle disorders in patients undergoing MHD. This finding lays the foundation for understanding the pathogenesis and potential treatment methods for sarcopenia in patients undergoing MHD.}, } @article {pmid37771199, year = {2023}, author = {Horvath, A and Zukauskaite, K and Hazia, O and Balazs, I and Stadlbauer, V}, title = {Human gut microbiome: Therapeutic opportunities for metabolic syndrome-Hype or hope?.}, journal = {Endocrinology, diabetes & metabolism}, volume = {}, number = {}, pages = {e436}, doi = {10.1002/edm2.436}, pmid = {37771199}, issn = {2398-9238}, support = {KLI741//Austrian Science Fund/ ; }, abstract = {Shifts in gut microbiome composition and metabolic disorders are associated with one another. Clinical studies and experimental data suggest a causal relationship, making the gut microbiome an attractive therapeutic goal. Diet, intake of probiotics or prebiotics and faecal microbiome transplantation (FMT) are methods to alter a person's microbiome composition. Although FMT may allow establishing a proof of concept to use microbiome modulation to treat metabolic disorders, studies show mixed results regarding the effects on metabolic parameters as well as on the composition of the microbiome. This review summarizes the current knowledge on diet, probiotics, prebiotics and FMT to treat metabolic diseases, focusing on studies that also report alterations in microbiome composition. Furthermore, clinical trial results on the effects of common drugs used to treat metabolic diseases are synopsized to highlight the bidirectional relationship between the microbiome and metabolic diseases. In conclusion, there is clear evidence that microbiome modulation has the potential to influence metabolic diseases; however, it is not possible to distinguish which intervention is the most successful. In addition, a clear commitment from all stakeholders is necessary to move forward in the direction of developing targeted interventions for microbiome modulation.}, } @article {pmid37770953, year = {2023}, author = {Zhang, M and Liu, J and Xia, Q}, title = {Role of gut microbiome in cancer immunotherapy: from predictive biomarker to therapeutic target.}, journal = {Experimental hematology & oncology}, volume = {12}, number = {1}, pages = {84}, pmid = {37770953}, issn = {2162-3619}, support = {2022ZZ01016//Shanghai Organ Transplantation Research Center/ ; 92059205//National Natural Science Foundation of China/ ; }, abstract = {Immunotherapy has emerged as an effective treatment for various types of cancers. Recent studies have highlighted a significant correlation between the gut microbiome and patients' response to immunotherapy. Several characteristics of the gut microbiome, such as community structures, taxonomic compositions, and molecular functions, have been identified as crucial biomarkers for predicting immunotherapy response and immune-related adverse events (irAEs). Unlike other -omics, the gut microbiome can serve as not only biomarkers but also potential targets for enhancing the efficacy of immunotherapy. Approaches for modulating the gut microbiome include probiotics/prebiotics supplementation, dietary interventions, fecal microbiota transplantation (FMT), and antibiotic administration. This review primarily focuses on elucidating the potential role of the gut microbiome in predicting the response to cancer immunotherapy and improving its efficacy. Notably, we explore reasons behind inconsistent findings observed in different studies, and highlight the underlying benefits of antibiotics in liver cancer immunotherapy.}, } @article {pmid37769622, year = {2023}, author = {Rossier, L and Matter, C and Burri, E and Galperine, T and Hrúz, P and Juillerat, P and Schoepfer, A and Vavricka, SR and Zahnd, N and Décosterd, N and Seibold, F}, title = {Swiss expert opinion: current approaches in faecal microbiota transplantation in daily practice.}, journal = {Swiss medical weekly}, volume = {153}, number = {}, pages = {40100}, doi = {10.57187/smw.2023.40100}, pmid = {37769622}, issn = {1424-3997}, abstract = {INTRODUCTION: Faecal microbiota transplantation (FMT) is an established therapy for recurrent C. difficile infection, and recent studies have reported encouraging results of FMT in patients with ulcerative colitis. Few international consensus guidelines exist for this therapy, and thus FMT policies and practices differ among European countries. As of 2019, stool transplants are considered a non-standardised medicinal product in Switzerland, and a standardised production process requires authorisation by the Swiss Agency for Therapeutic Products. This authorisation leads to prolonged administrative procedures and increasing costs, which reduces treatment accessibility. In particular, patients with ulcerative colitis in Switzerland can only benefit from FMT off-label, even though it is a valid therapeutic option. Therefore, this study summarised the available data on FMT and established a framework for the standardised use of FMT.

METHODS: A panel of Swiss gastroenterologists with a special interest in inflammatory bowel disease was established to identify the current key issues of FMT. After a comprehensive review of the literature, statements were formulated about FMT indications, donor screening, stool transplant preparation and administration, and safety aspects. The panel then voted on the statements following the Delphi process; the statements were reformulated and revoted until a consensus was reached. The manuscript was then reviewed by an infectiologist (the head of Lausanne's FMT centre).

RESULTS: The established statements are summarised in the supplementary tables in the appendix to this paper. The working group hopes these will help standardise FMT practice in Switzerland and contribute to making faecal microbiota transplantation a safe and accessible treatment for patients with recurrent C. difficile infections and selected patients with ulcerative colitis, as well as other indications in the future.}, } @article {pmid37764957, year = {2023}, author = {Boicean, A and Bratu, D and Fleaca, SR and Vasile, G and Shelly, L and Birsan, S and Bacila, C and Hasegan, A}, title = {Exploring the Potential of Fecal Microbiota Transplantation as a Therapy in Tuberculosis and Inflammatory Bowel Disease.}, journal = {Pathogens (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {37764957}, issn = {2076-0817}, support = {contract no. 28PFE/30.12.2021//Ministerul Cercetării și Inovării/ ; }, abstract = {This review explores the potential benefits of fecal microbiota transplantation (FMT) as an adjunct treatment in tuberculosis (TB), drawing parallels from its efficacy in inflammatory bowel disease (IBD). FMT has shown promise in restoring the gut microbial balance and modulating immune responses in IBD patients. Considering the similarities in immunomodulation and dysbiosis between IBD and TB, this review hypothesizes that FMT may offer therapeutic benefits as an adjunct therapy in TB. Methods: We conducted a systematic review of the existing literature on FMT in IBD and TB, highlighting the mechanisms and potential implications of FMT in the therapeutic management of both conditions. The findings contribute to understanding FMT's potential role in TB treatment and underscore the necessity for future research in this direction to fully leverage its clinical applications. Conclusion: The integration of FMT into the comprehensive management of TB could potentially enhance treatment outcomes, reduce drug resistance, and mitigate the side effects of conventional therapies. Future research endeavors should focus on well-designed clinical trials to develop guidelines concerning the safety and short- and long-term benefits of FMT in TB patients, as well as to assess potential risks.}, } @article {pmid37764783, year = {2023}, author = {Li, L and Wu, L and Jiang, T and Liang, T and Yang, L and Li, Y and Gao, H and Zhang, J and Xie, X and Wu, Q}, title = {Lactiplantibacillus plantarum 124 Modulates Sleep Deprivation-Associated Markers of Intestinal Barrier Dysfunction in Mice in Conjunction with the Regulation of Gut Microbiota.}, journal = {Nutrients}, volume = {15}, number = {18}, pages = {}, pmid = {37764783}, issn = {2072-6643}, support = {(2022B1111070006)//the Key Research and Development Program of Guangdong Province/ ; 2019QN01N107//the Department of Science and Technology of Guangdong Province/ ; 2020GDASYL-20200102003//GDAS' Project of Science and Technology Development/ ; }, mesh = {Animals ; Mice ; Mice, Inbred C57BL ; *Gastrointestinal Microbiome ; Sleep Deprivation ; *Gastrointestinal Diseases ; *Intestinal Diseases ; Firmicutes ; Cytokines ; }, abstract = {Intestinal diseases caused by sleep deprivation (SD) are severe public health threats worldwide. However, whether or not probiotics attenuate the intestinal damage associated with SD remains unclear. In this study, we used antibiotic pretreatment and fecal microbiota transplantation to investigate the protective role of Lactiplantibacillus plantarum (L. plantarum) 124 against SD-related intestinal barrier damage in C57BL/6 mice. Compared with those of a normal sleeping mouse, we observed that intestinal antioxidant capacity and anti-inflammatory cytokine levels were decreased, while pro-inflammatory cytokines were increased in sleep deprivation mice with an increasing duration of sleep deprivation. This resulted in decreased tight junction protein expression and increased intestinal barrier permeability. In contrast, intragastric administration with L. plantarum 124 reversed SD-associated intestinal oxidative stress, inflammation, colonic barrier damage, and the dysbiosis of the microbiota in the colon. In addition, L. plantarum 124 restored gut microbiota homeostasis via restoring abundance, including that of Dubosiella, Faecalibaculum, Bacillus, Lachnoclostridium, and Bifidobacterium. Further studies showed that gut microbiota mediated SD-associated intestinal damage and the treatment L. plantarum 124 in SD-associated colonic barrier damage. L. plantarum 124 is a potential candidate for alleviating SD-associated intestinal barrier damage. Overall, L. plantarum 124 consumption attenuates intestinal oxidative stress, inflammation, and intestinal barrier damage in SD-associated mice via the modulation of gut microbes.}, } @article {pmid37764082, year = {2023}, author = {Bénard, MV and Arretxe, I and Wortelboer, K and Harmsen, HJM and Davids, M and de Bruijn, CMA and Benninga, MA and Hugenholtz, F and Herrema, H and Ponsioen, CY}, title = {Anaerobic Feces Processing for Fecal Microbiota Transplantation Improves Viability of Obligate Anaerobes.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, doi = {10.3390/microorganisms11092238}, pmid = {37764082}, issn = {2076-2607}, support = {innovation grant 2021 - Amsterdam Gastroenterology Endocrinology Metabolism (AGEM)//University of Amsterdam/ ; }, abstract = {Fecal microbiota transplantation (FMT) is under investigation for several indications, including ulcerative colitis (UC). The clinical success of FMT depends partly on the engraftment of viable bacteria. Because the vast majority of human gut microbiota consists of anaerobes, the currently used aerobic processing protocols of donor stool may diminish the bacterial viability of transplanted material. This study assessed the effect of four processing techniques for donor stool (i.e., anaerobic and aerobic, both direct processing and after temporary cool storage) on bacterial viability. By combining anaerobic culturing on customized media for anaerobes with 16S rRNA sequencing, we could successfully culture and identify the majority of the bacteria present in raw fecal suspensions. We show that direct anaerobic processing of donor stool is superior to aerobic processing conditions for preserving the bacterial viability of obligate anaerobes and butyrate-producing bacteria related to the clinical response to FMT in ulcerative colitis patients, including Faecalibacterium, Eubacterium hallii, and Blautia. The effect of oxygen exposure during stool processing decreased when the samples were stored long-term. Our results confirm the importance of sample conditioning to preserve the bacterial viability of oxygen-sensitive gut bacteria. Anaerobic processing of donor stool may lead to increased clinical success of FMT, which should further be investigated in clinical trials.}, } @article {pmid37764025, year = {2023}, author = {Metafuni, E and Di Marino, L and Giammarco, S and Bellesi, S and Limongiello, MA and Sorà, F and Frioni, F and Maggi, R and Chiusolo, P and Sica, S}, title = {The Role of Fecal Microbiota Transplantation in the Allogeneic Stem Cell Transplant Setting.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, doi = {10.3390/microorganisms11092182}, pmid = {37764025}, issn = {2076-2607}, abstract = {Microbiota changes during allogeneic hematopoietic stem cell transplantation has several known causes: conditioning chemotherapy and radiation, broad-spectrum antibiotic administration, modification in nutrition status and diet, and graft-versus-host disease. This article aims to review the current knowledge about the close link between microbiota and allogeneic stem cell transplantation setting. The PubMed search engine was used to perform this review. We analyzed data on microbiota dysbiosis related to the above-mentioned affecting factors. We also looked at treatments aimed at modifying gut dysbiosis and applications of fecal microbiota transplantation in the allogeneic stem cell transplant field, with particular interest in fecal microbiota transplantation for graft-versus-host disease (GvHD), multidrug-resistant and clostridium difficile infections, and microbiota restoration after chemotherapy and antibiotic therapy.}, } @article {pmid37764005, year = {2023}, author = {Dicks, LMT}, title = {Biofilm Formation of Clostridioides difficile, Toxin Production and Alternatives to Conventional Antibiotics in the Treatment of CDI.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, doi = {10.3390/microorganisms11092161}, pmid = {37764005}, issn = {2076-2607}, abstract = {Clostridioides difficile is considered a nosocomial pathogen that flares up in patients exposed to antibiotic treatment. However, four out of ten patients diagnosed with C. difficile infection (CDI) acquired the infection from non-hospitalized individuals, many of whom have not been treated with antibiotics. Treatment of recurrent CDI (rCDI) with antibiotics, especially vancomycin (VAN) and metronidazole (MNZ), increases the risk of experiencing a relapse by as much as 70%. Fidaxomicin, on the other hand, proved more effective than VAN and MNZ by preventing the initial transcription of RNA toxin genes. Alternative forms of treatment include quorum quenching (QQ) that blocks toxin synthesis, binding of small anion molecules such as tolevamer to toxins, monoclonal antibodies, such as bezlotoxumab and actoxumab, bacteriophage therapy, probiotics, and fecal microbial transplants (FMTs). This review summarizes factors that affect the colonization of C. difficile and the pathogenicity of toxins TcdA and TcdB. The different approaches experimented with in the destruction of C. difficile and treatment of CDI are evaluated.}, } @article {pmid37762509, year = {2023}, author = {Zabolotneva, AA and Gaponov, AM and Roumiantsev, SA and Vasiliev, IY and Grigoryeva, TV and Kit, OI and Zlatnik, EY and Maksimov, AY and Goncharova, AS and Novikova, IA and Appolonova, SA and Markin, PA and Shestopalov, AV}, title = {Alkylresorcinols as New Modulators of the Metabolic Activity of the Gut Microbiota.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, doi = {10.3390/ijms241814206}, pmid = {37762509}, issn = {1422-0067}, abstract = {Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db, and LDLR (-/-) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol's regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (-/-) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (-/-) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.}, } @article {pmid37761817, year = {2023}, author = {Carapeto, S and Cunha, E and Serrano, I and Pascoal, P and Pereira, M and Abreu, R and Neto, S and Antunes, B and Dias, R and Tavares, L and Oliveira, M}, title = {Effect of the Administration of a Lyophilised Faecal Capsules on the Intestinal Microbiome of Dogs: A Pilot Study.}, journal = {Genes}, volume = {14}, number = {9}, pages = {}, doi = {10.3390/genes14091676}, pmid = {37761817}, issn = {2073-4425}, support = {UIDB/00276/2020//Fundação para a Ciência e Tecnologia/ ; LA/P/0059/2020//AL4AnimalS/ ; }, abstract = {Faecal Microbiota Transplantation (FMT) is a promising strategy for modulating the gut microbiome. We aimed to assess the effect of the oral administration of capsules containing lyophilised faeces on dogs with diarrhoea for 2 months as well as evaluate their long-term influence on animals' faecal consistency and intestinal microbiome. This pilot study included five dogs: two used as controls and three with diarrhoea. Animals were evaluated for four months by performing a monthly faecal samples collection and physical examination, which included faecal consistency determination using the Bristol scale. The total number of viable bacteria present in the capsules was quantified and their bacterial composition was determined by 16S rRNA gene sequencing, which was also applied to the faecal samples. During the assay, no side effects were reported. Animals' faecal consistency improved and, after ending capsules administration, Bristol scale values remained stable in two of the three animals. The animals' microbiome gradually changed toward a composition associated with a balanced microbiota. After FMT, a slight shift was observed in its composition, but the capsules' influence remained evident during the 4-month period. Capsules administration seems to have a positive effect on the microbiota modulation; however, studies with more animals should be performed to confirm our observations.}, } @article {pmid37761327, year = {2023}, author = {Stojic, J and Kukla, M and Grgurevic, I}, title = {The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {18}, pages = {}, doi = {10.3390/diagnostics13182960}, pmid = {37761327}, issn = {2075-4418}, abstract = {Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.}, } @article {pmid37760856, year = {2023}, author = {Wu, L and Lin, ZH and Lu, XJ and Hu, X and Zhong, HJ and Lin, DJ and Liu, T and Xu, JT and Lin, WY and Wu, QP and He, XX}, title = {Washed Microbiota Transplantation Improves Patients with Overweight by the Gut Microbiota and Sphingolipid Metabolism.}, journal = {Biomedicines}, volume = {11}, number = {9}, pages = {}, doi = {10.3390/biomedicines11092415}, pmid = {37760856}, issn = {2227-9059}, support = {2022B1111070006//Key-Area Research and Development Program of Guangdong Province/ ; B2022209//Medical Scientific Research Foundation of Guangdong Province/ ; 20221232//Scientific Research Projects of Guangdong Bureau of Traditional Chinese Medicine/ ; 2021KCXTD025//Guangdong Innovation Research Team for Higher Education/ ; }, abstract = {BACKGROUND: Overweight (OW) and obesity have become increasingly serious public health problems worldwide. The clinical impact of washed microbiota transplantation (WMT) from healthy donors in OW patients is unclear. This study aimed to investigate the effect of WMT in OW patients.

METHODS: The changes in body mass index (BMI = weight (kg)/height (m)[2]), blood glucose, blood lipids and other indicators before and after WMT were compared. At the same time, 16S rRNA gene amplicon sequencing was performed on fecal samples of OW patients before and after transplantation. Finally, serum samples were tested for sphingolipids targeted by lipid metabolomics.

RESULTS: A total of 166 patients were included, including 52 in the OW group and 114 in the normal weight (NOW) group. For OW patients, WMT significantly improved the comprehensive efficacy of OW. In the short term (about 1 month) and medium term (about 2 months), a significant reduction in BMI was seen. At the same time, in the short term (about 1 month), liver fat attenuation (LFA), triglyceride (TG) and fasting blood glucose (FBG) were significantly reduced. In the long term (about 5 months), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein (non-HDL-c), etc. were significantly reduced. WMT improved the gut microbiota of OW patients, and also had an improvement effect on OW patients by regulating sphingolipid metabolism.

CONCLUSION: WMT had a significant improvement effect on OW patients. WMT could restore gut microbiota homeostasis and improve OW patients by regulating sphingolipid metabolism.}, } @article {pmid37756370, year = {2023}, author = {Zhou, J and Hao, J and Zhong, Z and Yang, J and Lv, T and Zhao, B and Lin, H and Chi, J and Guo, H}, title = {Fecal microbiota transplantation in mice exerts a protective effect against doxorubicin-induced cardiac toxicity by regulating Nrf2-mediated cardiac mitochondrial fission and fusion.}, journal = {Antioxidants & redox signaling}, volume = {}, number = {}, pages = {}, doi = {10.1089/ars.2023.0355}, pmid = {37756370}, issn = {1557-7716}, abstract = {AIMS: The relationship between gut microbiota and cardiovascular system has been increasingly clarified. Fecal microbiota transplantation (FMT), used to improve gut microbiota, has been applied clinically for disease treatment and has great potential in combatting doxorubicin (DOX)-induced cardiotoxicity. However, the application of FMT in the cardiovascular field and its molecular mechanisms are poorly understood.

RESULTS: During DOX-induced stress, FMT alters the gut microbiota and serum metabolites, leading to a reduction in cardiac injury. Correlation analysis indicated a close association between serum metabolite Indole-3-propionic acid (IPA) and cardiac function. FMT and IPA achieves this by facilitating the translocation of Nfe2l2 (Nrf2) from the cytoplasm to the nucleus, thereby activating the expression of antioxidant molecules, reducing ROS production, and inhibiting excessive mitochondrial fission. Consequently, mitochondrial function is preserved, leading to the mitigation of cardiac injury under DOX-induced stress.

INNOVATION: FMT has the ability to modify the composition of the gut microbiota, providing not only protection to the intestinal mucosa but also influencing the generation of serum metabolites and regulating the Nrf2 gene to modulate the balance of cardiac mitochondrial fission and fusion. This study comprehensively demonstrates the efficacy of FMT in countering DOX-induced myocardial damage and elucidates the pathways linking the microbiota and the heart.

CONCLUSION: FMT alters the gut microbiota and serum metabolites of recipient mice, promoting nuclear translocation of Nrf2 and subsequent activation of downstream antioxidant molecule expression, while inhibiting excessive mitochondrial fission to preserve cardiac integrity. Correlation analysis highlights IPA as a key contributor among differentially regulated metabolites.}, } @article {pmid37756322, year = {2023}, author = {Stefansson, M and Bladh, O and Flink, O and Skolling, O and Ekre, HP and Rombo, L and Engstrand, L and Ursing, J}, title = {Safety and tolerability of frozen, capsulized autologous faecal microbiota transplantation. A randomized double blinded phase I clinical trial.}, journal = {PloS one}, volume = {18}, number = {9}, pages = {e0292132}, pmid = {37756322}, issn = {1932-6203}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is recommended treatment for recurrent Clostridioides difficile infection and is studied as a potential modifier of other gastrointestinal and systemic disorders. Autologous FMT limits the potential risks of donor transplant material and enables prophylactic treatment. Capsulized FMT is convenient and accessible, but safety data are lacking.

AIMS: To describe safety and tolerability of capsules containing autologous FMT, compared to placebo, in healthy volunteers treated with antibiotics.

METHOD: Healthy volunteers without antibiotic exposure during the past three months, that had a negative Clostridioides difficile stool sample, were recruited. Study persons donated faeces for production of capsules containing autologous microbiota. They were then given Clindamycin for seven days to disrupt the intestinal microbiota, which was followed by a two-day washout. Study persons were then randomized (1:1) to unsupervised treatment with autologous faecal matter or placebo, with two capsules twice daily for five days. A standardized questionnaire about side effects and tolerability, daily until day 28, and on days 60 and 180, was completed.

RESULTS: Twenty-four study persons were included, all completed the treatment. One person from the placebo and FMT groups each, were lost to follow up from days 21 and 60, respectively. No study person experienced serious side effects, but severe fatigue was reported during the antibiotic period (n = 2). Reported side effects were mild to moderate and there were no significant differences between the groups. Reported general and intestinal health improved significantly and similarly in both groups after the antibiotic treatment. Time to normalized intestinal habits were 17 and 19 days from study start in the placebo group and the FMT group, respectively (p = 0.8).

CONCLUSION: Capsulized frozen autologous faecal microbiota transplantation was safe and well tolerated but did not affect time to normalized intestinal habits compared to placebo.

TRIAL REGISTRATION: EudraCT 2017-002418-30.}, } @article {pmid37756083, year = {2023}, author = {Rojas, CA and Entrolezo, Z and Jarett, JK and Jospin, G and Kingsbury, DD and Martin, A and Eisen, JA and Ganz, HH}, title = {Microbiome Responses to Fecal Microbiota Transplantation in Cats with Chronic Digestive Issues.}, journal = {Veterinary sciences}, volume = {10}, number = {9}, pages = {}, doi = {10.3390/vetsci10090561}, pmid = {37756083}, issn = {2306-7381}, support = {AB-1001//AnimalBiome/ ; }, abstract = {There is growing interest in the application of fecal microbiota transplants (FMTs) in small animal medicine, but there are few published studies that have tested their effects in the domestic cat (Felis catus). Here we use 16S rRNA gene sequencing to examine fecal microbiome changes in 46 domestic cats with chronic digestive issues that received FMTs using lyophilized stool that was delivered in oral capsules. Fecal samples were collected from FMT recipients before and two weeks after the end of the full course of 50 capsules, as well as from their stool donors (N = 10), and other healthy cats (N = 113). The fecal microbiomes of FMT recipients varied with host clinical signs and dry kibble consumption, and shifts in the relative abundances of Clostridium, Collinsella, Megamonas, Desulfovibrio and Escherichia were observed after FMT. Overall, donors shared 13% of their bacterial amplicon sequence variants (ASVs) with FMT recipients and the most commonly shared ASVs were classified as Prevotella 9, Peptoclostridium, Bacteroides, and Collinsella. Lastly, the fecal microbiomes of cats with diarrhea became more similar to the microbiomes of age-matched and diet-matched healthy cats compared to cats with constipation. Overall, our results suggest that microbiome responses to FMT may be modulated by the FMT recipient's initial presenting clinical signs, diet, and their donor's microbiome.}, } @article {pmid37754772, year = {2023}, author = {Liu, X and Yang, M and Liu, R and Zhou, F and Zhu, H and Wang, X}, title = {The impact of Parkinson's disease-associated gut microbiota on the transcriptome in Drosophila.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0017623}, doi = {10.1128/spectrum.00176-23}, pmid = {37754772}, issn = {2165-0497}, abstract = {Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people, and many studies have confirmed that the disorder of gut microbiota is involved in the pathophysiological process of PD. However, the molecular mechanism of gut microbiota in regulating the pathogenesis of PD is still lacking. In this study, to investigate the impact of PD-associated gut microbiota on host transcriptome, we established various PD models with fecal microbiota transplantation (FMT) in the model organism Drosophila followed by integrative data analysis of microbiome and transcriptome. We first constructed rotenone-induced PD models in Drosophila followed by FMT in different groups. Microbial analysis by 16S rDNA sequencing showed that gut microbiota from PD Drosophila could affect bacterial structure of normal Drosophila, and gut microbiota from normal Drosophila could affect bacterial structure of PD Drosophila. Transcriptome analysis revealed that PD-associated gut microbiota influenced expression patterns of genes enriched in neuroactive ligand-receptor interaction, lysosome, and diverse metabolic pathways. Importantly, to verify our findings, we transplanted Drosophila with fecal samples from clinical PD patients. Compared to the control, Drosophila transplanted with fecal samples from PD patients had reduced microbiota Acetobacter and Lactobacillus, and differentially expressed genes enriched in diverse metabolic pathways. In summary, our results reveal the influence of PD-associated gut microbiota on host gene expression, and this study can help better understand the link between gut microbiota and PD pathogenesis through gut-brain axis. IMPORTANCE Gut microbiota plays important roles in regulating host gene expression and physiology through complex mechanisms. Recently, it has been suggested that disorder of gut microbiota is involved in the pathophysiological process of Parkinson's disease (PD). However, the molecular mechanism of gut microbiota in regulating the pathogenesis of PD is still lacking. In this study, to investigate the impact of PD-associated gut microbiota on host transcriptome, we established various PD models with fecal microbiota transplantation in the model organism Drosophila followed by integrative data analysis of microbiome and transcriptome. We also verified our findings by transplanting Drosophila with fecal samples from clinical PD patients. Our results demonstrated that PD-associated gut microbiota can induce differentially expressed genes enriched in diverse metabolic pathways. This study can help better understand the link between gut microbiota and PD pathogenesis through gut-brain axis.}, } @article {pmid37754239, year = {2023}, author = {Malnick, SDH and Ohayon Michael, S}, title = {The Intestinal Microbiome and the Metabolic Syndrome-How Its Manipulation May Affect Metabolic-Associated Fatty Liver Disease (MAFLD).}, journal = {Current issues in molecular biology}, volume = {45}, number = {9}, pages = {7197-7211}, doi = {10.3390/cimb45090455}, pmid = {37754239}, issn = {1467-3045}, abstract = {Metabolic-associated fatty liver disease (MAFLD) is now the predominant liver disease worldwide consequent to the epidemic of obesity. The intestinal microbiome (IM), consisting of the bacteria, fungi, archaea, and viruses residing in the gastrointestinal tract, plays an important role in human metabolism and preserving the epithelial barrier function. Disturbances in the IM have been shown to influence the development and progression of MAFLD and play a role in the development of metabolic syndrome (MS). The main treatment for MAFLD involves lifestyle changes, which also influence the IM. Manipulation of the IM by fecal microbial transplantation (FMT) has been approved for the treatment of recurrent Closteroides difficile infection. This may be administered by endoscopic administration from the lower or upper GI tract. Other methods of administration include nasogastric tube, enema, and oral capsules of stool from healthy donors. In this narrative review, we elaborate on the role of the IM in developing MS and MAFLD and on the current experience with IM modulation by FMT on MAFLD.}, } @article {pmid37753568, year = {2023}, author = {Liu, Y and Zhang, P and Sheng, H and Xu, D and Li, D and An, L}, title = {16S rRNA gene sequencing and machine learning reveal correlation between drug abuse and human host gut microbiota.}, journal = {Addiction biology}, volume = {28}, number = {10}, pages = {e13311}, doi = {10.1111/adb.13311}, pmid = {37753568}, issn = {1369-1600}, support = {41830321//Key Program National Natural Science Foundation of China/ ; 17ZD2WA017//National Science and Technology Major Project in Gansu/ ; }, abstract = {Over the past few years, there has been increasing evidence highlighting the strong connection between gut microbiota and overall well-being of the host. This has led to a renewed emphasis on studying and addressing substance use disorder from the perspective of brain-gut axis. Previous studies have suggested that alcohol, food, and cigarette addictions are strongly linked to gut microbiota and faecal microbiota transplantation or the use of probiotics achieved significant efficacy. Unfortunately, little is known about the relationship between drug abuse and gut microbiota. This paper aims to reveal the potential correlation between gut microbiota and drug abuse and to develop an accurate identification model for drug-related faeces samples by machine learning. Faecal samples were collected from 476 participants from three regions in China (Shanghai, Yunnan, and Shandong). Their gut microbiota information was obtained using 16S rRNA gene sequencing, and a substance use disorder identification model was developed by machine learning. Analysis revealed a lower diversity and a more homogeneous gut microbiota community structure among participants with substance use disorder. Bacteroides, Prevotella_9, Faecalibacterium, and Blautia were identified as important biomarkers associated with substance use disorder. The function prediction analysis revealed that the citrate and reductive citrate cycles were significantly upregulated in the substance use disorder group, while the shikimate pathway was downregulated. In addition, the machine learning model could distinguish faecal samples between substance users and nonsubstance users with an AUC = 0.9, indicating its potential use in predicting and screening individuals with substance use disorder within the community in the future.}, } @article {pmid37753524, year = {2023}, author = {Ejtahed, HS and Parsa, M and Larijani, B}, title = {Ethical challenges in conducting and the clinical application of human microbiome research.}, journal = {Journal of medical ethics and history of medicine}, volume = {16}, number = {}, pages = {5}, pmid = {37753524}, issn = {2008-0387}, } @article {pmid37753364, year = {2023}, author = {Gulumbe, BH and Abdulrahim, A}, title = {Pushing the frontiers in the fight against antimicrobial resistance: the potential of fecal and maggot therapies.}, journal = {Future science OA}, volume = {9}, number = {10}, pages = {FSO899}, pmid = {37753364}, issn = {2056-5623}, abstract = {The escalating crisis of antimicrobial resistance (AMR) warrants innovative therapeutic strategies. Fecal microbiota transplantation (FMT) and maggot debridement therapy (MDT) represent paradigm-shifting approaches, leveraging biological systems to mitigate AMR. FMT restores a healthy gut microbiome, providing a biotherapeutic counter to pathogenic bacteria, thereby reducing reliance on traditional antibiotics. Conversely, MDT, a form of bio-debridement, utilizes the antimicrobial secretions of maggots to cleanse wounds and eliminate resistant bacteria. Despite the promise these therapies hold, their broader clinical adoption faces multifaceted challenges including the need for rigorous scientific substantiation, standardized protocols, deepened understanding of mechanisms of action, and surmounting regulatory and public acceptance barriers. However, their potential integration with precision medicine could revolutionize disease management, particularly with antibiotic-resistant infections.}, } @article {pmid37752615, year = {2023}, author = {Jin, Z and Yang, Y and Cao, Y and Wen, Q and Xi, Y and Cheng, J and Zhao, Q and Weng, J and Hong, K and Jiang, H and Hang, J and Zhang, Z}, title = {The gut metabolite 3-hydroxyphenylacetic acid rejuvenates spermatogenic dysfunction in aged mice through GPX4-mediated ferroptosis.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {212}, pmid = {37752615}, issn = {2049-2618}, support = {2022YFC2702600//National Key Research and Development Program of China/ ; 20220484160//Beijing Nova Program/ ; 7222208//Natural Science Foundation of Beijing Municipality/ ; }, abstract = {BACKGROUND: Aging-related fertility decline is a prevalent concern globally. Male reproductive system aging is mainly characterized by a decrease in sperm quality and fertility. While it is known that intestinal physiology changes with age and that microbiota is shaped by physiology, the underlying mechanism of how the microbiota affects male reproductive aging is still largely unexplored.

RESULTS: Here, we utilized fecal microbiota transplantation (FMT) to exchange the fecal microbiota between young and old mice. Cecal shotgun metagenomics and metabolomics were used to identify differences in gut microbiota composition and metabolic regulation during aging. Our results demonstrated that FMT from young to old mice alleviated aging-associated spermatogenic dysfunction through an unexpected mechanism mediated by a gut bacteria-derived metabolite, 3-hydroxyphenylacetic acid (3-HPAA). 3-HPAA treatment resulted in an improvement of spermatogenesis in old mice. RNA sequencing analysis, qRT-PCR and Western blot revealed that 3-HPAA induced an upregulation of GPX4, thereby restraining ferroptosis and restoring spermatogenesis. These findings were further confirmed by in vitro induction of ferroptosis and inhibition of GPX4 expression.

CONCLUSIONS: Our results demonstrate that the microbiome-derived metabolite, 3-HPAA, facilitates spermatogenesis of old mice through a ferroptosis-mediated mechanism. Overall, these findings provide a novel mechanism of dysregulated spermatogenesis of old mice, and suggest that 3-HPAA could be a potential therapy for fertility decline of aging males in clinical practice. Video Abstract.}, } @article {pmid37752426, year = {2023}, author = {Lapauw, L and Dupont, J and Amini, N and Vercauteren, L and Verschueren, S and Tournoy, J and Raes, J and Gielen, E}, title = {Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT): protocol of a cross-sequential study to explore the gut-muscle axis in the development and treatment of sarcopenia in community-dwelling older adults.}, journal = {BMC geriatrics}, volume = {23}, number = {1}, pages = {599}, pmid = {37752426}, issn = {1471-2318}, abstract = {BACKGROUND: Gut microbiota (GM) might play a role in muscle metabolism and physiological processes through a hypothesized gut-muscle axis, influencing muscle mass and function and thus, sarcopenia. The Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT) aims to explore the gut-muscle axis in sarcopenia.

METHODS: First, in a cross-sectional case-control phase, 100 community-dwelling adults without sarcopenia will be compared to 100 community-dwelling adults (≥ 65 years) with sarcopenia of similar age-, gender and BMI-ratio, participating in the ongoing 'Exercise and Nutrition for Healthy AgeiNg' (ENHANce; NCT03649698) study. Sarcopenia is diagnosed according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. GM composition and intestinal inflammatory markers (fecal calprotectin, lactoferrin and S100A12) will be determined in fecal samples. Systemic inflammatory markers (hs-CRP, IL-4, IL-6, TNF-α, IL-13, IL-1β and creatine kinase) will be determined in fasted blood samples. Both groups will be compared using appropriate statistical testing, whereas linear regression will be used for cross-sectional associations between gut, inflammatory and sarcopenia parameters. Second, in the longitudinal phase, sarcopenic older adults will be requested to deliver five fecal samples during the 12-week intervention to assess the effects of protein, omega-3 and a physical exercise program on the GM.

DISCUSSION: TEMPUS-FUGIT aims to explore the gut-muscle axis by comparing GM composition between sarcopenic and non-sarcopenic older adults and to determine the association of GM with intestinal and systemic inflammatory markers and sarcopenia-defining parameters (muscle mass, muscle strength and physical performance). Furthermore, effects of single or combined, optimized and individualized anabolic interventions (exercise, protein and omega-3 supplementation), on GM will be explored in persons with sarcopenia. TEMPUS-FUGIT aims to impact clinical practice by clarifying the relationship between the gut-muscle axis and sarcopenia. TEMPUS-FUGIT is expected to contribute to the discovery of clinical and microbial biomarkers for sarcopenia and insights in its pathophysiology, opening possible future perspectives for novel sarcopenia treatment strategies targeting GM.

TRIAL REGISTRATION: ClinicalTrails.gov NCT05008770, registered on August 17, 2021; first participant enrolled on September 21 2021.}, } @article {pmid37752225, year = {2023}, author = {Luo, Y and Liu, C and Luo, Y and Zhang, X and Li, J and Hu, C and Yang, S}, title = {Thiostrepton alleviates experimental colitis by promoting RORγt ubiquitination and modulating dysbiosis.}, journal = {Cellular & molecular immunology}, volume = {}, number = {}, pages = {}, pmid = {37752225}, issn = {2042-0226}, support = {81802460//National Natural Science Foundation of China (National Science Foundation of China)/ ; CSTB2022NSCQ-MSX0184//Natural Science Foundation of Chongqing (Natural Science Foundation of Chongqing Municipality)/ ; }, abstract = {Thiostrepton (TST) is a natural antibiotic with pleiotropic properties. This study aimed to elucidate the therapeutic effect of TST on experimental colitis and identify its targets. The effect of TST on colon inflammation was evaluated in a dextran sulfate sodium (DSS)-induced colitis model and a T-cell transfer colitis model. The therapeutic targets of TST were investigated by cytokine profiling, immunophenotyping and biochemical approaches. The effect of TST on the gut microbiota and its contribution to colitis were evaluated in mice with DSS-induced colitis that were subjected to gut microbiota depletion and fecal microbiota transplantation (FMT). Alterations in the gut microbiota caused by TST were determined by 16S rDNA and metagenomic sequencing. Here, we showed that TST treatment significantly ameliorated colitis in the DSS-induced and T-cell transfer models. Specifically, TST targeted the retinoic acid-related orphan nuclear receptor RORγt to reduce the production of IL-17A by γδ T cells, type 3 innate lymphoid cells (ILC3s) and Th17 cells in mice with DSS-induced colitis. Similarly, TST selectively prevented the development of Th17 cells in the T-cell transfer colitis model and the differentiation of naïve CD4[+] T cells into Th17 cells in vitro. Mechanistically, TST induced the ubiquitination and degradation of RORγt by promoting the binding of Itch to RORγt. Moreover, TST also reversed dysbiosis to control colonic inflammation. Taken together, these results from our study describe the previously unexplored role of TST in alleviating colonic inflammation by reducing IL-17A production and modulating dysbiosis, suggesting that TST is a promising candidate drug for the treatment of IBD.}, } @article {pmid37750481, year = {2023}, author = {Gryschek, RCB and Corral, MA and Sitta, RB and Gottardi, M and Pierrotti, LC and Costa, SF and Abdala, E and Chieffi, PP and de Paula, FM}, title = {Strongyloides infection screening in transplant candidates: What is the best strategy?.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e14153}, doi = {10.1111/tid.14153}, pmid = {37750481}, issn = {1399-3062}, support = {2010/51110-2//Fundação de Amparo à Pesquisa do EStado de São Paulo (FAPESP)/ ; 2013/04236-9//Fundação de Amparo à Pesquisa do EStado de São Paulo (FAPESP)/ ; }, abstract = {BACKGROUND: The potential that Strongyloides stercoralis infection has to cause major morbidity and high mortality when the disseminated form occurs in transplant patients is of particular concern.

METHODS: In this study, the objective was to observe S. stercoralis infection in patients who are candidates for transplantation by using parasitological, serological, and molecular techniques and to propose an algorithm for the detection of that infection in transplant candidates.

RESULTS: By parasitological techniques, 10% of fecal samples were positive. Anti-Strongyloides antibodies immunoglobulin G were detected in 19.3% and 20.7% of patients by immunofluorescence assay and enzyme-linked immunosorbent assay, respectively. S. stercoralis DNA was observed in 17.3% of samples by conventional polymerase chain reaction and 32.7% of samples by quantitative polymerase chain reaction (qPCR).

CONCLUSION: The set of results allows us to reinforce that a positive result by parasitological techniques and/or qPCR indicates that the specific treatment should be applied. However, the improvement of diagnostic techniques may suggest changes in the screening for strongyloidiasis in these patients.}, } @article {pmid37749611, year = {2023}, author = {Liu, A and Liang, X and Wang, W and Wang, C and Song, J and Guo, J and Sun, D and Wang, D and Song, M and Qian, J and Zhang, X}, title = {Human umbilical cord mesenchymal stem cells ameliorate colon inflammation via modulation of gut microbiota-SCFAs-immune axis.}, journal = {Stem cell research & therapy}, volume = {14}, number = {1}, pages = {271}, pmid = {37749611}, issn = {1757-6512}, support = {82270545//National Natural Science Foundation of China/ ; 82070563//National Natural Science Foundation of China/ ; H2020206497//Natural Science Foundation of Hebei Province/ ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays a pivotal pathogenic role. Mesenchymal stem cells (MSCs) therapy has emerged as a prospective novel tool for managing IBD, and which can also regulate the composition of gut microbiota. However, the functional significance of MSCs-induced changes in gut microbiome is poorly understood.

METHODS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of human umbilical cord MSCs (HUMSCs) on DSS-induced colitis. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Spectrum antibiotic cocktail (ABX), fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) were employed to evaluate the protective effect of intestinal flora and its metabolites. Cytokine microarray, Enzyme-linked immunosorbent assay (ELISA), and flow cytometry were conducted to assess the effect on CD4[+]T homeostasis.

RESULTS: Here, we investigated for the first time the role of gut microbiota in mediating the protective effect of MSCs on DSS-induced colitis. By performing gut microbiota depletion and fecal microbiota transplantation (FMT) experiments, we revealed that MSCs derived from human umbilical cord ameliorated colon inflammation and reshaped T-cells immune homeostasis via remodeling the composition and diversity of gut flora, especially up-regulated SCFAs-producing bacterial abundance, such as Akkermansia, Faecalibaculum, and Clostridia_UCG_014. Consistently, targeted metabolomics manifested the increased SCFAs production with MSCs administration, and there was also a significant positive correlation between differential bacteria and SCFAs. Meanwhile, combined with sterile fecal filtrate (SFF) gavage experiments, the underlying protective mechanism was further associated with the improved Treg/Th2/Th17 balance in intestinal mucosa mediated via the increased microbiota-derived SCFAs production.

CONCLUSION: The present study advances understanding of MSCs in the protective effects on colitis, providing evidence for the new role of the microbiome-metabolite-immune axis in the recovery of colitis by MSCs.}, } @article {pmid37746903, year = {2023}, author = {Verhoef, J and Klont, E and van Overveld, FJ and Rijkers, GT}, title = {The long and winding road of fecal microbiota transplants to targeted intervention for improvement of immune checkpoint inhibition therapy.}, journal = {Expert review of anticancer therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14737140.2023.2262765}, pmid = {37746903}, issn = {1744-8328}, abstract = {INTRODUCTION: Immune checkpoint inhibition (ICI) therapy has revolutionized the treatment of cancer. The principle of this treatment is that inhibitory molecules, either on the tumor or on cells of the immune system, are blocked by antibodies. The immune system of the patient subsequently should be able to attack and eradicate the tumor. Not all patients respond to ICI therapy, and response or non-response has been associated with composition of gut microbiota.

AREA COVERED: Fecal microbiota transplantation (FMT) is used as adjunctive therapy in order to improve the outcome of ICI. Clinical Trials.gov, Clinical Trials in the European Union, Australian New Zealand Clinical Trials Registry, and the International Clinical Trials Registry Platform of the World Health Organization were searched (October 2022) for studies dealing with gut microbiota modification and the outcome of ICI.

EXPERT OPINION: There is ample evidence for the beneficial effect of FMT on the outcome of ICI therapy for cancer, especially melanoma. The optimal treatment schedule, as well as donor selection criteria, still must be worked out. Progress is being made in the unraveling of the mechanisms by which microbiota and their metabolites (butyrate and the tryptophan metabolite indole-3-aldehyde) interact with the mucosal immune system of the host. A better understanding of these mechanisms contributes to improving FMT outcomes and developing novel therapeutic approaches. It will allow the identification of key bacterial species which mediate the effect of FMT. Promising species are Faecalibacterium prausnitzii, Eubacterium rectale, and three Bifidobacterium species (B. adolescentis, B.bifidum, and B. longum), because they are important direct and indirect butyrate producers, which could form the basis of targeted microbiota therapy.}, } @article {pmid37743861, year = {2023}, author = {Hu, X and Jin, H and Yuan, S and Ye, T and Chen, Z and Kong, Y and Liu, J and Xu, K and Sun, J}, title = {Fecal microbiota transplantation inhibited neuroinflammation of traumatic brain injury in mice via regulating the gut-brain axis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1254610}, pmid = {37743861}, issn = {2235-2988}, mesh = {Animals ; Mice ; *Brain-Gut Axis ; Neuroinflammatory Diseases ; Fecal Microbiota Transplantation ; *Brain Injuries, Traumatic/therapy ; Cytokines ; Disease Models, Animal ; }, abstract = {INTRODUCTION: Recent studies have highlighted the vital role of gut microbiota in traumatic brain injury (TBI). Fecal microbiota transplantation (FMT) is an effective means of regulating the microbiota-gut-brain axis, while the beneficial effect and potential mechanisms of FMT against TBI remain unclear. Here, we elucidated the anti-neuroinflammatory effect and possible mechanism of FMT against TBI in mice via regulating the microbiota-gut-brain axis.

METHODS: The TBI mouse model was established by heavy object falling impact and then treated with FMT. The neurological deficits, neuropathological change, synaptic damage, microglia activation, and neuroinflammatory cytokine production were assessed, and the intestinal pathological change and gut microbiota composition were also evaluated. Moreover, the population of Treg cells in the spleen was measured.

RESULTS: Our results showed that FMT treatment significantly alleviated neurological deficits and neuropathological changes and improved synaptic damage by increasing the levels of the synaptic plasticity-related protein such as postsynaptic density protein 95 (PSD-95) and synapsin I in the TBI mice model. Moreover, FMT could inhibit the activation of microglia and reduce the production of the inflammatory cytokine TNF-α, alleviating the inflammatory response of TBI mice. Meanwhile, FMT treatment could attenuate intestinal histopathologic changes and gut microbiota dysbiosis and increase the Treg cell population in TBI mice.

CONCLUSION: These findings elucidated that FMT treatment effectively suppressed the TBI-induced neuroinflammation via regulating the gut microbiota-gut-brain axis, and its mechanism was involved in the regulation of peripheral immune cells, which implied a novel strategy against TBI.}, } @article {pmid37742728, year = {2023}, author = {Ciernikova, S and Sevcikova, A and Drgona, L and Mego, M}, title = {Modulating the gut microbiota by probiotics, prebiotics, postbiotics, and fecal microbiota transplantation: An emerging trend in cancer patient care.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {}, number = {}, pages = {188990}, doi = {10.1016/j.bbcan.2023.188990}, pmid = {37742728}, issn = {1879-2561}, abstract = {Treatment resistance, together with acute and late adverse effects, represents critical issues in the management of cancer patients. Promising results from preclinical and clinical research underline the emerging trend of a microbiome-based approach in oncology. Favorable bacterial species and higher gut diversity are associated with increased treatment efficacy, mainly in chemo- and immunotherapy. On the other hand, alterations in the composition and activity of gut microbial communities are linked to intestinal dysbiosis and contribute to high treatment-induced toxicity. In this Review, we provide an overview of studies concerning gut microbiota modulation in patients with solid and hematologic malignancies with a focus on probiotics, prebiotics, postbiotics, and fecal microbiota transplantation. Targeting the gut microbiome might bring clinical benefits and improve patient outcomes. However, a deeper understanding of mechanisms and large clinical trials concerning microbiome and immunological profiling is warranted to identify safe and effective ways to incorporate microbiota-based interventions in routine clinical practice.}, } @article {pmid37741298, year = {2023}, author = {Liu, Z and Sun, M and Jin, C and Sun, X and Feng, F and Niu, X and Wang, B and Zhang, Y and Wang, J}, title = {Naringenin confers protection against experimental autoimmune encephalomyelitis through modulating the gut-brain axis: A multi-omics analysis.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109448}, doi = {10.1016/j.jnutbio.2023.109448}, pmid = {37741298}, issn = {1873-4847}, abstract = {Multiple sclerosis (MS) is a disease of the central nervous system that involves the immune system attacking the protective covering of nerve fibers. This disease can be influenced by both environmental and genetic factors. Evidence has highlighted the critical role of the intestinal microbiota in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). The composition of gut microflora is mainly determined by dietary components, which, in turn, modulate host homeostasis. A diet rich in naringenin at 0.5% can effectively mitigate the severity of EAE in mice. However, there is little direct data on the impact of naringenin at optimal doses on EAE development, as well as its intestinal microbiota and metabolites. Our study revealed that 2.0% naringenin resulted in the lowest clinical score and pathological changes in EAE mice, and altered the gene expression profiles associated with inflammation and immunity in spinal cord tissue. We then used untargeted metabolomics and 16S rRNA gene sequence to identify metabolites and intestinal microbiota, respectively. Naringenin supplementation enriched gut microbiota in EAE mice, including increasing the abundance of Paraprevotellaceae and Comamonadaceae, while decreasing the abundance of Deltaproteobacteria, RF39, and Desulfovibrionaceae. Furthermore, the changes in gut microbiota affected the production of metabolites in the feces and brain, suggesting a role in regulating the gut-brain axis. Finally, we conducted a fecal transplantation experiment to validate that gut microbiota partly mediates the effect of naringenin on EAE alleviation. In conclusion, naringenin has potential immunomodulatory effects that are influenced to some extent by the gut microbiome.}, } @article {pmid37741061, year = {2023}, author = {Yue, C and Luan, W and Gu, H and Qiu, D and Ding, X and Liu, P and Wang, X and Hashimoto, K and Yang, JJ}, title = {The role of the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve in chronic inflammatory pain and comorbid spatial working memory impairment in complete Freund's adjuvant mice.}, journal = {Journal of psychiatric research}, volume = {166}, number = {}, pages = {61-73}, doi = {10.1016/j.jpsychires.2023.09.003}, pmid = {37741061}, issn = {1879-1379}, abstract = {Chronic inflammatory pain (CIP) is a common public medical problem, often accompanied by memory impairment. However, the mechanisms underlying CIP and comorbid memory impairment remain elusive. This study aimed to examine the role of the gut-microbiota-brain axis in CIP and comorbid memory impairment in mice treated with complete Freund's adjuvant (CFA). 16S rRNA analysis showed the altered diversity of gut microbiota from day 1 to day 14 after CFA injection. Interestingly, fecal microbiota transplantation (FMT) from healthy naive mice ameliorated comorbidities, such as mechanical allodynia, thermal hyperalgesia, spatial working memory impairment, neuroinflammation, and abnormal composition of gut microbiota in the CFA mice. Additionally, subdiaphragmatic vagotomy (SDV) blocked the onset of these comorbidities. Interestingly, the relative abundance of the bacterial genus or species was also correlated with these comorbidities after FMT or SDV. Therefore, our results suggest that the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve is crucial for the development of CIP and comorbid spatial working memory impairment in CFA mice.}, } @article {pmid37736702, year = {2023}, author = {Kragsnaes, MS and Miguens Blanco, J and Mullish, BH and Contreras-Serrano, JI and Kjeldsen, J and Horn, HC and Pedersen, JK and Munk, HL and Nilsson, AC and Salam, A and Lewis, MR and Chekmeneva, E and Kristiansen, K and Marchesi, JR and Ellingsen, T}, title = {Small Intestinal Permeability and Metabolomic Profiles in Feces and Plasma Associate With Clinical Response in Patients With Active Psoriatic Arthritis Participating in a Fecal Microbiota Transplantation Trial: Exploratory Findings From the FLORA Trial.}, journal = {ACR open rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.1002/acr2.11604}, pmid = {37736702}, issn = {2578-5745}, support = {//Fabrikant Vilhelm Pedersen's Mindelegat (on recommendation by the Novo Nordisk Foundation)/ ; MC_PC_12025//Medical Research Council and National Institute for Health Research/ ; //Medicin Fund of the Danish Regions (Regionernes Medicin- og behandlingspulje)/ ; CL-2019-21-002//NIHR Academic Clinical Lectureship/ ; //NIHR Imperial Biomedical Research Centre/ ; //Research Fund of Odense University Hospital/ ; 2022-0026//Sygeforsikringen "danmark"/ ; //the Danish Psoriasis Research Foundation/ ; //The Danish Rheumatism Association/ ; //University of Southern Denmark Research Fund/ ; 21228//Versus Arthritis (formerly Arthritis Research UK)/ ; }, abstract = {OBJECTIVE: We investigated intestinal permeability and fecal, plasma, and urine metabolomic profiles in methotrexate-treated active psoriatic arthritis (PsA) and how this related to clinical response following one sham or fecal microbiota transplantation (FMT).

METHODS: This exploratory study is based on the FLORA trial cohort, in which 31 patients with moderate-to-high peripheral PsA disease activity, despite at least 3 months of methotrexate-treatment, were included in a 26-week, double-blind, 1:1 randomized, sham-controlled trial. Participants were randomly allocated to receive either one healthy donor FMT (n = 15) or sham (n = 16) via gastroscopy. The primary trial end point was the proportion of treatment failures through 26 weeks. We performed a lactulose-to-mannitol ratio (LMR) test at baseline (n = 31) and at week 26 (n = 26) to assess small intestinal permeability. Metabolomic profiles in fecal, plasma, and urine samples collected at baseline, weeks 4, 12, and 26 were measured using [1] H Nuclear Magnetic Resonance.

RESULTS: Trial failures (n = 7) had significantly higher LMR compared with responders (n = 19) at week 26 (0.027 [0.017-0.33]) vs. 0.012 [0-0.064], P = 0.013), indicating increased intestinal permeability. Multivariate analysis revealed a significant model for responders (n = 19) versus failures (n = 12) at all time points based on their fecal (P < 0.0001) and plasma (P = 0.005) metabolomic profiles, whereas urine metabolomic profiles did not differ between groups (P = 1). Fecal N-acetyl glycoprotein GlycA correlated with Health Assessment Questionnaire Disability Index (coefficient = 0.50; P = 0.03) and fecal propionate correlated with American College of Rheumatology 20 response at week 26 (coefficient = 27, P = 0.02).

CONCLUSION: Intestinal permeability and fecal and plasma metabolomic profiles of patients with PsA were associated with the primary clinical trial end point, failure versus responder.}, } @article {pmid37734581, year = {2023}, author = {Yau, YK and Lau, LHS and Lui, RNS and Wong, SH and Guo, CL and Mak, JWY and Ching, JYL and Ip, M and Kamm, MA and Rubin, DT and Chan, PKS and Chan, FKL and Ng, SC}, title = {Long-term Safety Outcomes of Fecal Microbiota Transplantation: Real-World Data over Eight Years from the Hong Kong FMT Registry.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2023.09.001}, pmid = {37734581}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Prospective long-term real-world safety data after fecal microbiota transplantation (FMT) remain limited. We reported long-term outcomes of FMT from a population-based FMT registry in Hong Kong.

METHODS: We recruited patients undergoing FMT for recurrent Clostridioides difficile infection (CDI) and non-CDI indications from clinical trials, from June 2013 to April 2022 in Hong Kong. We captured data on demographics, FMT indications and procedures, clinical outcomes and short-to-long-term safety. New medical diagnoses were obtained from electronic medical records and independently adjudicated by clinicians. Long-term safety in patients with recurrent CDI was compared with a control group treated with antibiotics.

RESULTS: Overall, 123 subjects (median age 53 years; range 13-90; 52.0% male) underwent 510 FMTs and were prospectively followed up for a median of 30.3 months (range, 1-57.9). The most common indication for FMT was type 2 diabetes mellitus (DM). The most common short-term adverse events within one month of FMT included diarrhea and abdominal pain. At long-term follow-up beyond 12 months, 16 patients reported 21 new onset medical conditions confirmed by electronic medical records. All were adjudicated to be unlikely to be related to FMT. There was no new case of inflammatory bowel disease, irritable bowel syndrome, allergy, DM or psychiatric disorder. In a subgroup of patients with recurrent CDI, FMT was associated with a significantly higher cumulative survival probability compared with matched controls.

CONCLUSION: This prospective real-world data from Asia's first FMT registry demonstrated that FMT has an excellent long-term safety profile. The risk of developing new medical conditions beyond 12 months after FMT is low.}, } @article {pmid37733476, year = {2023}, author = {Kashyap, Y and Wang, ZJ}, title = {Gut microbiota dysbiosis alters chronic pain behaviors in a humanized transgenic mouse model of sickle cell disease.}, journal = {Pain}, volume = {}, number = {}, pages = {}, doi = {10.1097/j.pain.0000000000003034}, pmid = {37733476}, issn = {1872-6623}, support = {R35 HL140021/HL/NHLBI NIH HHS/United States ; }, abstract = {Pain is the most common symptom experienced by patients with sickle cell disease (SCD) throughout their lives and is the main cause of hospitalization. Despite the progress that has been made towards understanding the disease pathophysiology, major gaps remain in the knowledge of SCD pain, the transition to chronic pain, and effective pain management. Recent evidence has demonstrated a vital role of gut microbiota in pathophysiological features of SCD. However, the role of gut microbiota in SCD pain is yet to be explored. We sought to evaluate the compositional differences in the gut microbiota of transgenic mice with SCD and nonsickle control mice and investigate the role of gut microbiota in SCD pain by using antibiotic-mediated gut microbiota depletion and fecal material transplantation (FMT). The antibiotic-mediated gut microbiota depletion did not affect evoked pain but significantly attenuated ongoing spontaneous pain in mice with SCD. Fecal material transplantation from mice with SCD to wild-type mice resulted in tactile allodynia (0.95 ± 0.17 g vs 0.08 ± 0.02 g, von Frey test, P < 0.001), heat hyperalgesia (15.10 ± 0.79 seconds vs 8.68 ± 1.17 seconds, radiant heat, P < 0.01), cold allodynia (2.75 ± 0.26 seconds vs 1.68 ± 0.08 seconds, dry ice test, P < 0.01), and anxiety-like behaviors (Elevated Plus Maze Test, Open Field Test). On the contrary, reshaping gut microbiota of mice with SCD with FMT from WT mice resulted in reduced tactile allodynia (0.05 ± 0.01 g vs 0.25 ± 0.03 g, P < 0.001), heat hyperalgesia (5.89 ± 0.67 seconds vs 12.25 ± 0.76 seconds, P < 0.001), and anxiety-like behaviors. These findings provide insights into the relationship between gut microbiota dysbiosis and pain in SCD, highlighting the importance of gut microbial communities that may serve as potential targets for novel pain interventions.}, } @article {pmid37731574, year = {2023}, author = {Zyoud, SH and Shakhshir, M and Abushanab, AS and Koni, A and Shahwan, M and Jairoun, AA and Abu Taha, A and Al-Jabi, SW}, title = {Unveiling the hidden world of gut health: Exploring cutting-edge research through visualizing randomized controlled trials on the gut microbiota.}, journal = {World journal of clinical cases}, volume = {11}, number = {26}, pages = {6132-6146}, pmid = {37731574}, issn = {2307-8960}, abstract = {BACKGROUND: The gut microbiota plays a crucial role in gastrointestinal and overall health. Randomized clinical trials (RCTs) play a crucial role in advancing our knowledge and evaluating the efficacy of therapeutic interventions targeting the gut microbiota.

AIM: To conduct a comprehensive bibliometric analysis of the literature on RCTs involving the gut microbiota.

METHODS: Using bibliometric tools, a descriptive cross-sectional investigation was conducted on scholarly publications concentrated on RCTs related to gut microbiota, spanning the years 2003 to 2022. The study used VOSviewer version 1.6.9 to examine collaboration networks between different countries and evaluate the frequently employed terms in the titles and abstracts of the retrieved publications. The primary objective of this analysis was to identify key research areas and focal points associated with RCTs involving the gut microbiota.

RESULTS: A total of 1061 relevant articles were identified from the 24758 research articles published between 2003 and 2022. The number of publications showed a notable increase over time, with a positive correlation (R[2] = 0.978, P < 0.001). China (n = 276, 26.01%), the United States (n = 254, 23.94%), and the United Kingdom (n = 97, 9.14%) were the leading contributing countries. Københavns Universitet (n = 38, 3.58%) and Dankook University (n = 35, 3.30%) were the top active institutions. The co-occurrence analysis shows current gut microbiota research trends and important topics, such as obesity interventions targeting the gut microbiota, the efficacy and safety of fecal microbiota transplantation, and the effects of dietary interventions on humans.

CONCLUSION: The study highlights the rapid growth and importance of research on RCTs that involve the gut microbiota. This study provides valuable insight into research trends, identifies key players, and outlines potential future directions in this field. Additionally, the co-occurrence analysis identified important topics that play a critical role in the advancement of science and provided insights into future research directions in this field.}, } @article {pmid37730588, year = {2023}, author = {Wang, H and Liu, S and Xie, L and Wang, J}, title = {Gut microbiota signature in children with autism spectrum disorder who suffered from chronic gastrointestinal symptoms.}, journal = {BMC pediatrics}, volume = {23}, number = {1}, pages = {476}, pmid = {37730588}, issn = {1471-2431}, mesh = {Female ; Male ; Child ; Humans ; Child, Preschool ; *Gastrointestinal Microbiome ; *Autism Spectrum Disorder ; *Microbiota ; Anxiety ; Constipation ; }, abstract = {BACKGROUND: Children diagnosed with autism spectrum disorder (ASD) frequently suffer from persistent gastrointestinal symptoms, such as constipation and diarrhea. Various studies have highlighted differences in gut microbiota composition between individuals with ASD and healthy controls of similar ages. However, it's essential to recognize that these disparities may be influenced by cultural practices, dietary habits, and environmental factors.

METHODS: In this study, we collected fecal samples from both children diagnosed with ASD (n = 42) and healthy individuals (n = 41) residing in the southeastern coastal region of China. Subsequently, 16 S rRNA gene sequencing and advanced bioinformatics analyses were conducted to investigate the distinctive features of gut microbial communities within each group.

RESULTS: The ASD group consisted of 28 males and 14 females, with a median age of 5.8 years, while the control group included 25 males and 16 females, with a median age of 6.8 years. Among the 83 sequenced fecal samples, a total of 1031 operational taxonomic units (OTUs) were identified. These included 122 unique OTUs specific to the control group and 285 unique OTUs specific to the ASD group. Analyses of α-diversity and β-diversity unveiled significant differences in the abundance and composition of gut microbiota between the two groups. It was found that the dominant bacterial taxa in healthy individuals were UBA1819, Flavonifractor, and Bradyrhizobium. In contrast, the ASD group exhibited a prevalence of Streptococcus, Ruminococcus, and Ruminiclostridium. Further analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) showed significant differences in the metabolic functionalities of the gut microbiota between the two groups. Notably, the metabolic pathway related to alpha-linolenic acid (ALA) in the gut microbiota of the ASD group was notably diminished compared to the control group. Conversely, the ASD group demonstrated significantly elevated levels of metabolic pathways involving uncharacterized conserved proteins, aminoglycoside phosphotransferase, and inorganic pyrophosphatase compared to the control group.

CONCLUSIONS: Overall, these results confirm that there are significant differences in the gut microbiota structure between children with ASD and healthy controls in the southeast coastal region of China. This underscores the critical significance of delving into clinical interventions capable of mitigating the gastrointestinal and psychological symptoms encountered by children with ASD. A particularly encouraging path for such interventions lies in the realm of fecal microbiota transplantation, a prospect that merits deeper inquiry.}, } @article {pmid36946907, year = {2023}, author = {Wood, N and Propst, K and Yao, M and Ferrando, CA}, title = {Fecal Microbiota Transfer for Clostridium difficile Infection and Its Effects on Recurrent Urinary Tract Infection.}, journal = {Urogynecology (Philadelphia, Pa.)}, volume = {29}, number = {10}, pages = {814-826}, pmid = {36946907}, issn = {2771-1897}, mesh = {Humans ; Female ; Fecal Microbiota Transplantation ; Retrospective Studies ; Treatment Outcome ; *Clostridioides difficile ; Recurrence ; *Clostridium Infections/epidemiology ; *Urinary Tract Infections/epidemiology ; }, abstract = {IMPORTANCE: Recurrent urinary tract infection (rUTI) poses a significant management challenge, and fecal microbiota transfer (FMT) has been shown in a limited manner to positively effect rUTI.

OBJECTIVES: The objective of this study was to compare UTI rates after FMT for Clostridium difficile infection (CDI) in patients with previously diagnosed rUTI and patients without a previous diagnosis of rUTI.

STUDY DESIGN: This was a retrospective cohort study of female patients who underwent FMT between 2015 and 2020 and were identified from a database at a tertiary care referral center. The electronic medical record was queried for demographic and UTI characteristics in the 3 years before and 5 years after FMT, which were compared between patients with or without a preexisting history of rUTI.

RESULTS: One hundred thirty-five patients were included, 17 of whom had a preexisting history of rUTI. The median number of culture-proven UTIs was 1 in the rUTI group versus 0 in the non-rUTI group both in the 1 year (P = 0.003) and 3 years (P < 0.001) before FMT. Most UTIs before and after FMT were Escherichia coli UTIs (53.8%) and carried some antibiotic resistance (54.6%). Comparatively, in the year after FMT, there were no differences between groups in UTI frequency or antibiotic administration (0 [0-1] vs 0.5 [0-1], P = 0.28). A trend toward decreased frequency of UTI in the 1 year after FMT was seen in the rUTI group. On survival analysis, there was a nonsignificant decrease in the 3-year UTI-free rate for the rUTI group compared with the non-rUTI group (76.5% vs 90.1%, P = 0.07).

CONCLUSIONS: Patients with recurrent UTI undergoing FMT for recurrent CDI experienced a trend toward a decrease in frequency of UTI after FMT.}, } @article {pmid37727718, year = {2023}, author = {Del Giglio, A and Atui, FC}, title = {Fecal transplantation in patient with metastatic melanoma refractory to immunotherapy: A case report.}, journal = {World journal of clinical cases}, volume = {11}, number = {24}, pages = {5830-5834}, pmid = {37727718}, issn = {2307-8960}, abstract = {BACKGROUND: Immunotherapy has revolutionized the treatment of metastatic melanoma, but a significant proportion of patients still experience treatment resistance. Fecal microbiota transplantation (FMT) has emerged as a potential strategy to overcome immunotherapy resistance by modulating the gut microbiome.

CASE SUMMARY: We present a case report of a 57-year-old male with metastatic melanoma refractory to immunotherapy who received FMT in combination with anti-programmed death-ligand 1 (PD-L1) immunotherapy (pembrolizumab). After failing multiple lines of treatment, the patient underwent a single FMT procedure by colonoscopy using fecal material from a female metastatic melanoma donor who successfully responded to immunotherapy. Following FMT, the patient demonstrated a response with decreased subcutaneous disease and subsequently underwent surgery to remove the residual disease. Despite a subsequent recurrence in the small bowel that was resected, the patient remained on pembrolizumab without evidence of melanoma recurrence at the time of writing.

CONCLUSION: The favorable clinical and long-lasting effect we saw in our patient without significant toxicity suggests that this procedure should be considered in similar patients with immunotherapy refractory melanomas.}, } @article {pmid37727287, year = {2023}, author = {Li, Y and Li, X and Nie, C and Wu, Y and Luo, R and Chen, C and Niu, J and Zhang, W}, title = {Effects of two strains of Lactobacillus isolated from the feces of calves after fecal microbiota transplantation on growth performance, immune capacity, and intestinal barrier function of weaned calves.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1249628}, pmid = {37727287}, issn = {1664-302X}, abstract = {INTRODUCTION: Weaning stress seriously affects the welfare of calves and causes huge economic losses to the cattle breeding industry. Probiotics play an important role in improving animal growth performance, enhancing immune function, and improving gut microbiota. The newly isolated strains of Lactobacillus reuteri L81 and Lactobacillus johnsonii L29 have shown potential as probiotics. Here, we studied the probiotic properties of these two strains on weaned calves.

METHODS: Forty calves were randomly assigned to four groups before weaning, with 10 calves in each group, control group (Ctrl group), L. reuteri L81 supplementation group (2 g per day per calf), L. johnsonii L29 supplementation group (2 g per day per calf), L. reuteri L81 and L. johnsonii L29 composite group (2 g per day per calf), and the effects of Lactobacillus reuteri L81 and Lactobacillus johnsonii L29 supplementation on growth performance, immune status, antioxidant capacity, and intestinal barrier function of weaned calves were evaluated.

RESULTS: The results showed that probiotics supplementation increased the average daily weight gain of calves after weaning, reduced weaning diarrhea index (p < 0.05), and increased serum IgA, IgM, and IgG levels (p < 0.05). L. reuteri L81 supplementation significantly decreased IL-6, increased IL-10 and superoxide dismutase (SOD) levels at 21 d after weaning (p < 0.05). Moreover, probiotics supplementation significantly decreased serum endotoxin (ET), diamine oxidase (DAO), and D-lactic acid (D-LA) levels at different time points (p < 0.05). In addition, supplementation with L. reuteri L81 significantly reduced the crypt depth and increased the ratio of villus height to crypt depth (p < 0.05) in the ileum, increased gene expression of tight junction protein ZO-1, Claudin-1 and Occludin in jejunum and ileum mucosa, reduced the gene expression of INF- γ in ileum mucosa and IL-8 in jejunum mucosa, and increased the abundance of beneficial bacteria, including Bifidobacterium, Lactobacillus, Oscillospira, etc.

DISCUSSION: verall, these results showed that the two strains isolated from cattle feces after low concentration fecal microbiota transplantation improved the growth performance, immune performance, antioxidant capacity, and intestinal barrier function of weaned calves, indicating their potential as supplements to alleviate weaning diarrhea in calves.}, } @article {pmid37725892, year = {2023}, author = {Shang, S and Zhu, J and Liu, X and Wang, W and Dai, T and Wang, L and Li, B}, title = {The Impacts of Fecal Microbiota Transplantation from Same Sex on the Symptoms of Ulcerative Colitis Patients.}, journal = {Polish journal of microbiology}, volume = {72}, number = {3}, pages = {247-268}, pmid = {37725892}, issn = {2544-4646}, mesh = {Adolescent ; Humans ; Female ; Male ; *Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Prospective Studies ; RNA, Ribosomal, 16S ; Abdominal Pain ; Bifidobacterium ; Diarrhea ; *Fabaceae ; Lactobacillus ; }, abstract = {We aimed to compare the clinical efficacy of fecal microbiota transplantation (FMT) from the same sex on ulcerative colitis (UC) patients. A total of 272 UC patients were selected in the prospective clinical study, which incorporated four distinct groups, each comprising male and female patients, who were either receiving FMT or placebo, respectively. FMT was performed by sending the gut microbiota of healthy female or male adolescents to the same gender patients via gastroscope three times (one time/three weeks), and a placebo was used with an equal volume of saline. Abdominal pain, diarrhea, thick bloody stool, intestinal mucosal lesion, and Mayo scores were measured. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated. The changes of intestinal flora were detected by the 16S rRNA sequencing. FMT reduced the scores of diarrhea, abdominal pain, mucosal lesion, and Mayo, SAS, and SDS in UC patients compared to the placebo group (p < 0.05). Clostridiales and Desulfovibrionaceae were dominant in gut microbiota from male patients and were reduced after FMT. Meanwhile, the abundance of Prevotella, Lactobacillus, and Bifidobacterium was increased in the male group. Female patients had a higher abundance of Escherichia-Shigella, Desulfovibrionaceae, and Staphylococcaceae before FMT, and it was reduced after FMT. Meanwhile, the abundance of Porphyromonadaceae, Prevotella, Lactobacillus, and Bifidobacterium was increased in the female group. There were no significant changes for the species in the corresponding placebo groups. FMT improved the UC symptoms of male and female patients, which may be associated with different gut microbiota changes.}, } @article {pmid37721283, year = {2024}, author = {Cui, Y and Liu, J and Lei, X and Liu, S and Chen, H and Wei, Z and Li, H and Yang, Y and Zheng, C and Li, Z}, title = {Dual-directional regulation of spinal cord injury and the gut microbiota.}, journal = {Neural regeneration research}, volume = {19}, number = {3}, pages = {548-556}, doi = {10.4103/1673-5374.380881}, pmid = {37721283}, issn = {1673-5374}, abstract = {There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis. The spinal cord is a vital important part of the central nervous system; however, the underlying association between spinal cord injury and gut interactions remains unknown. Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis. Alterations in the gut microbiota can cause disruption in the int