@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.<br><br>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.<br><br>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&#x2009;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.<br><br>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 &amp; 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.<br><br>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.<br><br>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 &#x2265;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).<br><br>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.<br><br>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&#xa0;ml total bacterial count) or the low-dose group (400&#xa0;ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48&#xa0;weeks, including mortality and quality of life.<br><br>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&#xa0;weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications.<br><br>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 &amp; 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.<br><br>AIM: To assess the accuracy of MES in UC and PSC-UC patients, we performed histological scoring using Nancy histological index (NHI).<br><br>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.<br><br>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.<br><br>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 &amp; dosage ; *Probiotics/administration &amp; dosage ; *Synbiotics/administration &amp; 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.<br><br>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.<br><br>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.<br><br>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, &#xd3;R 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 Tecnolog&#xed;as/ ; IN21222//Universidad Nacional Aut&#xf3;noma de M&#xe9;xico/ ; }, 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 &amp; 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 &amp; breathing = Schlaf &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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, &#x3b1;-diversity analysis, &#x3b2;-diversity analysis, species difference analysis, and predictive functional analysis.<br><br>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.<br><br>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 &amp; 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.<br><br>METHODS: We evaluated the association between Fn abundance in pre-surgical stool samples and onset of cachexia at 6&#x2009;months post-surgery in n&#x2009;=&#x2009;87 patients with stages I-III CRC in the ColoCare Study.<br><br>RESULTS: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4-fold increased risk of cachexia onset at 6&#x2009;months post-surgery (OR&#x2009;=&#x2009;4.82, 95% CI&#x2009;=&#x2009;1.15, 20.10, p&#x2009;=&#x2009;0.03).<br><br>CONCLUSION: Our findings suggest that high fecal Fn abundance was associated with an increased risk of cachexia at 6&#x2009;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.<br><br>PURPOSE: Our study aimed to investigate relationship between GSZD and NETs in RA treatment and revealed underlying mechanism.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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&#xae; E, and polyvinyl acetate) and external (Eudragit&#xae; S, Acryl-EZE&#xae;, 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.<br><br>RESULTS: Combining suitable internal (ethylcellulose 1.0&#x202f;%) and external (Eudragit&#xae; S 20.0&#x202f;%) 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&#x202f;min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480&#x202f;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.<br><br>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.<br><br>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.<br><br>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).<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>AREAS COVERED: Strategies used to manage irAEs include corticosteroids, anti-tumor necrosis factor alpha (TNF-&#x3b1;) 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.<br><br>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).<br><br>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 &#x2265;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.<br><br>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.<br><br>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 &amp; derivatives ; *Mannans/chemistry/pharmacology/isolation &amp; purification ; Mice ; *Anti-Obesity Agents/pharmacology/chemistry/isolation &amp; 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).<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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/&#x3b2;-catenin pathway were assessed using qRT-PCR and western blot. The ratio of the fecal microorganisms and metabolomics alteration after FMT were also assessed.<br><br>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/&#x3b2;-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.<br><br>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.<br><br>METHODS: A total of 34 septic patients and 24&#xa0;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.<br><br>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.<br><br>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, &#xc1; 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 &amp; pharmacotherapy = Biomedecine &amp; 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 S&#xf8;r-&#xd8;st RHF/ ; 2017122//Helse S&#xf8;r-&#xd8;st 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 &amp; 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.<br><br>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 (>&#x2009;90%) male populations. Main outcome measures were recurrence, complications, operative time, and bowel function.<br><br>RESULTS: Eight studies (452 patients; median age 45.6&#xa0;years) were included; 80.5% of patients underwent abdominal procedures whereas 19.5% underwent perineal procedures. The prevalence&#xa0;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&#xa0;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&#xa0;after resection rectopexy (83.3-100%) and in fecal incontinence (FI) was noted&#xa0;after posterior mesh rectopexy (86.4-90%). Abdominal procedures had lower rates of recurrence (6% vs. 19.3%, RR 0.50, 95%&#xa0;CI 0.21-1.18, p&#x2009;=&#x2009;0.113), similar complication rates (14.3% vs. 13.6%, RR 0.41, 95%&#xa0;CI 0.06-2.9, p&#x2009;=&#x2009;0.374), and longer operative times (116&#x2009;&#xb1;&#x2009;47.2 vs. 74.2&#x2009;&#xb1;&#x2009;23.6&#xa0;min, p&#x2009;<&#x2009;0.001).<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; dosage/therapeutic use ; Middle Aged ; Female ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation/methods ; Adult ; Treatment Outcome ; Adrenal Cortex Hormones/administration &amp; 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 &amp; 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.<br><br>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.<br><br>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 &amp; dosage/therapeutic use ; Fecal Microbiota Transplantation/methods ; Prebiotics/administration &amp; 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.<br><br>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.<br><br>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&#xa0;male. Average treatment satisfaction score (scale of 0-10) was&#xa0;6.4 and quality of life score was 5.8. A majority (64.9%)&#xa0;expressed interest in fecal microbiota transplant.<br><br>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.<br><br>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.<br><br>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.<br><br>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-&#x3b2;), 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.<br><br>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).<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>RESULTS: Safety data was collected for a total of 587 patients (193 exposed to SDN products, 114&#xa0;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&#x2009;=&#x2009;0.206 and P&#x2009;=&#x2009;0.420, respectively]). Results indicated similar risk of safety events for MDN compared to SDN (RR: 0.83, P&#x2009;=&#x2009;0.159). Positive benefit-risk ratios were demonstrated for MDN and SDN versus placebo (RRs: 1.70 and 1.16, respectively [P&#x2009;=&#x2009;0.003 and P&#x2009;=&#x2009;0.173, respectively]). MDN had a greater benefit-risk ratio compared to SDN (RR: 1.46, P&#x2009;=&#x2009;0.072).<br><br>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.<br><br>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&#x2009;=&#x2009;total bilirubin (TB)&#x2009;<&#x2009;2&#x2009;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&#x2009;=&#x2009;8) comparing AHM versus FO.<br><br>RESULTS: At baseline, 211 infants received AHM and 215 received FO. 53.9% of AHM and 50.5% of FO achieved COJ (p&#x2009;=&#x2009;NS). SNL was insignificantly increased in AHM (odds ratio&#x2009;=&#x2009;1.47, 95% confidence interval: 1.00-2.12, p&#x2009;=&#x2009;0.053). TB decreased in AHM from 4 weeks to 3 months post-KP [4.8-4.0&#x2009;mg/dL (p&#x2009;=&#x2009;0.01)] unlike the FO group (4.9-4.9&#x2009;mg/dL, p&#x2009;=&#x2009;0.4). At 3 months post-KP, AHM infants had greater weight gain (1.88&#x2009;&#xb1;&#x2009;0.66 vs. 1.57&#x2009;&#xb1;&#x2009;0.73&#x2009;kg, p&#x2009;<&#x2009;0.001) and mid-upper arm circumference (12.9&#x2009;&#xb1;&#x2009;1.4 vs. 12.2&#x2009;&#xb1;&#x2009;1.7&#x2009;cm, p&#x2009;<&#x2009;0.001). Other secondary outcomes were not different. Microbiome differences were seen between AHM and FO.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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).<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P30-AR070253//U.S. Department of Health &amp; Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/ ; P40-OD010995//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; P30-DK034987//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; 997397//Crohn's and Colitis Foundation (Crohn's &amp; 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.<br><br>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.<br><br>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.<br><br>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-1&#x3b2;, IFN-&#x3b3;, 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.<br><br>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 Cient&#xed;fico y Tecnol&#xf3;gico (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.<br><br>METHODS: na&#xef;ve 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.<br><br>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.<br><br>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 &amp; inhibitors ; Biomarkers, Tumor/metabolism ; Proto-Oncogene Proteins c-kit/genetics/metabolism/antagonists &amp; 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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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-1&#x3b2; (IL-1&#x3b2;), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-&#x3b1;, 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%).<br><br>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 &amp; 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 &amp; purification/drug effects ; Protective Agents/pharmacology/administration &amp; 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 &amp; dosage ; *Prebiotics/administration &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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&#x2009;<&#x2009;0.0001), CARS scores decreased from 36.22 to 33.33 (p&#x2009;<&#x2009;0.0001), SRS scores decreased from 151.17 to 137.5 (p&#x2009;=&#x2009;0.0002), and the ABC scores decreased 76.39 to 53.17 (p&#x2009;<&#x2009;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&#x2009;=&#x2009;0.034). The FMT group also showed a significant reduction in urinary 5-hydroxyindoleacetic acid (5-HIAA) levels from 8.6 to 7.32&#x2009;mg/L (p&#x2009;=&#x2009;0.022), while other metabolites showed no significant changes.<br><br>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.<br><br>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.<br><br>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&#x202f;<&#x202f;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&#x202f;<&#x202f;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.<br><br>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.<br><br>METHODS: In this randomised, quality improvement trial with a pragmatic design, patients from the Central Denmark Region aged 70&#xa0;years or older with a positive PCR test for C&#xa0;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.<br><br>FINDINGS: Between Sept 1, 2022, and May 3, 2023, we randomly assigned 217&#xa0;patients to CGA (n=109) or standard care (n=108). The median patient age was 78&#xa0;years (IQR 74-84). 116 (53%) of 217&#xa0;patients were female and 101 (47%) were male. 16 (15%; 95% CI 9-23) of 109&#xa0;patients in the CGA group and 22 (20%; 14-29) of 108&#xa0;patients in the standard-care group died within 90&#xa0;days (odds ratio 0&#xb7;66, 95% CI 0&#xb7;32-1&#xb7;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&#xa0;difficile infection were lower in the CGA group (seven [44%] of 16&#xa0;deaths vs 18 [82%] of 22&#xa0;deaths in the standard-care group; p=0&#xb7;020).<br><br>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&#xa0;difficile infection.<br><br>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.<br><br>METHODS: A Bayesian network meta-analysis (NMA) of randomized control trials up to March 2024 was performed to investigate the efficacy of rCDI interventions.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; dosage ; *Brain-Gut Axis/physiology ; *Diet, High-Fat/adverse effects ; *Vagus Nerve ; *Weight Gain/drug effects ; Dysbiosis/microbiology ; Rats, Sprague-Dawley ; Bacteria/classification/isolation &amp; 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 &amp; 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).<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>AIM: To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC).<br><br>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-1&#x3b2;, IL-6, IL-8, IL-10, IL-22, TNF-&#x3b1;, and TGF-&#x3b2;, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-&#x3ba;B, Occludin, MUC-2, Claudin-1, and I&#x3ba;B-&#x3b1; in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing.<br><br>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-&#x3b2;, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-&#x3ba;B, IL-1&#x3b2;, IL-6, TNF-&#x3b1;, IL-22, IL-8, and I&#x3ba;B-&#x3b1; 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.<br><br>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.<br><br>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).<br><br>FINDINGS: The ICI benefit group was enriched for propionate (P&#xa0;=&#xa0;0.01) and butyrate/isobutyrate (P&#xa0;=&#xa0;0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P&#xa0;<&#xa0;0.001, butyrate/isobutyrate P&#xa0;=&#xa0;0.002). The acetyl-CoA pathway (P&#xa0;=&#xa0;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&#xa0;=&#xa0;0.07), which was validated in the Routy cohort (P&#xa0;=&#xa0;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&#xa0;=&#xa0;0.03), propionic acid (P&#xa0;=&#xa0;0.09), and butyric acid (P&#xa0;=&#xa0;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&#xa0;<&#xa0;0.05).<br><br>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).<br><br>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&amp;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.<br><br>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.<br><br>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&#xa0;weeks and once weekly thereafter. EVs were administered in three doses each separated by 72&#xa0;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&#xa0;weeks. Steroids were weaned to low-dose or withdrawn in every patient within 4&#xa0;weeks of ECP/EV treatment. C-reactive protein decreased from an average of 14.75 to 1.6&#xa0;mg/dL post-treatment and fecal calprotectin decreased from average 800&#xa0;mg/g to 31&#xa0;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.<br><br>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).<br><br>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&#x2009;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.<br><br>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-&#x3b1;, 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &#x2265; 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 &#x2265; 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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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 &amp; 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 &amp; purification/metabolism/genetics ; Alanine/analogs &amp; 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.<br><br>METHODS: The gut microbiota of 88 CKD patients (non-dialysis, hemodialysis, and transplant patients) and 26 healthy controls were profiled using 16&#xa0;S-amplicon sequencing. H2S and lanthionine concentrations were measured in serum and fecal samples using the methylene blue method and LC-MS/MS, respectively.<br><br>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.<br><br>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.<br><br>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).<br><br>RESULTS: PS volume decreased by&#xa0;-4702&#xa0;mL/week (-52&#xa0;%; p&#xa0;<&#xa0;0.001) at week 52. Seven patients (78&#xa0;%) achieved &#x2265;1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253&#xa0;g/day (p&#xa0;=&#xa0;0.013). At 48 weeks, increases in wet weight absorption by 316&#xa0;g/day (p&#xa0;=&#xa0;0.039), energy absorption by 1134&#xa0;kJ/day (p&#xa0;=&#xa0;0.041) and carbohydrate absorption by 56.1&#xa0;g/day (p&#xa0;=&#xa0;0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7&#xa0;cm (p&#xa0;=&#xa0;0.012), duodenal wall thickness increased by 0.8&#xa0;mm (p&#xa0;=&#xa0;0.02) and motility in the proximal colon was reduced (p&#xa0;=&#xa0;0.031). A total of 127 adverse events was reported, which were mostly mild to moderate.<br><br>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.<br><br>CLINICALTRIALS: gov, Number NCT04964986.}, }
@article {pmid39460926, year = {2024}, author = {Magnusson, C and Ölfvingsson, E and Hjortswang, H and Östholm, &#xc5; 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).<br><br>OBJECTIVES: To evaluate how treatment with FMT is affecting the health-related quality of life (HRQoL) in patients with rCDI.<br><br>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.<br><br>RESULTS: Patients with rCDI had poor HRQoL, which improved following FMT.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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 &amp; dosage ; *Alopecia/therapy/microbiology ; Synbiotics/administration &amp; 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.<br><br>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.<br><br>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 Fisiopatolog&#xed;a de la Obesidad y Nutrici&#xf3;n (CIBEROBN) and Fondo de Investigaci&#xf3;n 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.<br><br>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&#xa0;S rRNA sequencing and bioinformatics tools. Metabolomics were detected in sera of rats by LC-MS and annotated by using KEGG database.<br><br>RESULTS: Significant increment in occludin-1 and claudin-1 protein expression alleviated the diarrheal severity in IBS-D rats (P&#x2009;<&#x2009;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.<br><br>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 &amp; 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.<br><br>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.<br><br>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&#xb1;64.2, which was higher than IBS-C group (192.9&#xb1;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.<br><br>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 Ci&#xea;ncia e Tecnologia de Ci&#xea;ncia 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.<br><br>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.<br><br>RESULTS: This study demonstrates that patient-derived intestinal microbiota caused midbrain tyrosine hydroxylase positive (TH&#x2009;+) 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&#x2009;+&#x2009;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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>RESULTS: Out of 3755 citations identified, 56 met the inclusion criteria, of which 29 fulfilled quality standards. Higher microbial &#x3b1;-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.<br><br>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.<br><br>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.<br><br>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.<br><br>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-1&#x3b2;, IL-6, and TNF-&#x3b1;), 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-&#x3ba;B pathway-related proteins and increasing Nrf2/HO-1 pathway-related protein expression.<br><br>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 &amp; 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.<br><br>METHODS: This double-masked, placebo-controlled pilot study assessed the proteomic impacts of weekly FMT versus placebo treatment over 8&#xa0;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.<br><br>RESULTS: FMT significantly reduced the plasma levels of 45 inflammatory proteins, including established mortality predictors such as IL6 and TNF-&#x3b1;. We found notable reductions persisting up to 16&#xa0;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.<br><br>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.<br><br>PURPOSE: To investigate the mechanism of XHGZ granules against &#x3b2; cell dedifferentiation in T2DM based on gut microbiota.<br><br>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, &#x3b2; 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.<br><br>RESULTS: XHGZ granules significantly ameliorated hyperglycaemia, improved islet function and pathology, and reduced &#x3b2; 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-&#x3b2; cell dedifferentiation, and anti-inflammation along with the reduction of LPS and the increase of SCFAs in pseudo-germ-free T2DM rats.<br><br>CONCLUSION: Our results show that XHGZ granules alleviate &#x3b2; 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 &#x3b2; 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 &amp; 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.<br><br>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&amp;E, PAS, immunohistochemistry, and other experimental methods.<br><br>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 TNF&#x3b1; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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).<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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, &#x3b3;-aminobutyric acid, glutamate, tryptophan, xanthine, and &#x3b2;-hydroxypyruvate. Network pharmacology analysis, along with in vivo experimental verification, implicated the cAMP/PKA/NF-&#x3ba;B pathway in the action of these metabolites in treating UC, which may be the mechanism responsible for scutellarin's curative effects on UC.<br><br>CONCLUSION: This study demonstrates the potential of scutellarin in alleviating UC by activating the cAMP/PKA/NF-&#x3ba;B 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.<br><br>PURPOSE: This study aimed to investigate the efficacy of FN against UC and its potential regulatory mechanism.<br><br>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.<br><br>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.<br><br>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.<br><br>OBJECTIVES: We describe a detailed protocol, the Glyprotect protocol, for producing glycerol-based capsules to increase FMT accessibility.<br><br>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.<br><br>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.<br><br>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&#x2009;&#xb5;L microbe-glycerol mass, estimated to contain an average of 2.5&#x2009;&#xd7;&#x2009;10[8] non-specified bacteria.<br><br>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.<br><br>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&apos;s and Colitis Foundation (Crohn&apos;s &amp; 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 &amp; 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.<br><br>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.<br><br>RESULTS: (1) At the taxonomic levels of genus and species, there were significant differences in the &#x3b1;-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.<br><br>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 &amp; 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 &amp; 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.<br><br>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).<br><br>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&#xa0;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&#xa0;g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui-Jie-Ling (3.0&#xa0;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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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-&#x3ba;B 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-1&#x3b2;, MPO, TNF-&#x3b1;, and IL-6, reverse the activation of signaling pathway named TLR4/Myd88/ NF-&#x3ba;B 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.<br><br>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-&#x3ba;B 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.<br><br>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.<br><br>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 TNF&#x3b1;, IL-6, IL-1&#x3b2;and 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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-&#x3b2;/Smad pathway, potentially ameliorating endothelial-mesenchymal transitions in atherosclerotic mice.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>AIM: Our aim was to describe the clinical results of FMT performed for the treatment of recurrent CDI.<br><br>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.<br><br>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.<br><br>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.<br><br>AIM OF THE STUDY: This study aimed to elucidate the therapeutic efficacy of CPPS on UC mice and its mechanism of action.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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 &#x2265;&#x2009;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&#x2009;weeks.<br><br>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, &#xd8;B and Botteri, E and Hoff, G and Bretthauer, M and Gulichsen, E and Frigstad, SO and Holme, &#xd8; 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 &amp; numerical data/methods ; Middle Aged ; *Early Detection of Cancer/methods ; Aged ; Norway/epidemiology ; Cross-Sectional Studies ; Risk Factors ; Sigmoidoscopy/adverse effects/methods/statistics &amp; 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.<br><br>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.<br><br>RESULTS: Of the 10&#x2009;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%.<br><br>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.<br><br>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, &#xd8;}, title = {Performance of Faecal Immunochemical Testing for Colorectal Cancer Screening at Varying Positivity Thresholds.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1111/apt.18314}, pmid = {39373173}, issn = {1365-2036}, support = {2015038//Helse S&#xf8;r-&#xd8;st RHF/ ; //Norwegian Parliament/ ; }, abstract = {BACKGROUND: The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries.<br><br>AIMS: To explore the trade-off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial.<br><br>METHODS: We included first participation in biennial FIT screening for 47,265 individuals aged 50-74&#x2009;years. Individuals with FIT&#x2009;>&#x2009;15&#x2009;&#x3bc;g&#x2009;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&#x2009;&#x3bc;g/g.<br><br>RESULTS: At the 15&#x2009;&#x3bc;g/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47&#x2009;&#x3bc;g/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&#x2009;&#x3bc;g/g threshold. At 150&#x2009;&#x3bc;g/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&#x2009;&#x3bc;g/g and 0.11% at 150&#x2009;&#x3bc;g/g. Post-colonoscopy bleeding rates were 0.8% and 1.7%, respectively.<br><br>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.<br><br>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.<br><br>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.<br><br>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).<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 (&#x223c; 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.<br><br>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.<br><br>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).<br><br>DESIGN: &amp; 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.<br><br>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 &#x3b1;-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.<br><br>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.<br><br>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.<br><br>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.<br><br>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%.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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 &#x3b2;-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.<br><br>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 &amp; 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.<br><br>STUDY DESIGN AND METHODS: We created a database of all FMT treatments (n&#x2009;=&#x2009;180) provided by our institution. Quality of all FMT was evaluated by treatment success rates. We compared our caFMT to the imported caFMT.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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 &#x3b1;-diversity but lower fungal &#x3b1;-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.<br><br>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.<br><br>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 &amp; 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 &amp; 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.<br><br>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 &#x3b1;-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&#xa0;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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>PURPOSE: This study aimed to evaluate the efficiency of BAI in ARDS mice and its underlying mechanisms.<br><br>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.<br><br>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.<br><br>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, &#x13d; 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 &amp; purification/genetics/physiology ; Bacteria/classification/virology/genetics/isolation &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>METHODS: Twenty adult male cynomolgus monkeys were divided into the sham (n&#x202f;=&#x202f;4), middle cerebral artery occlusion (MCAO, n&#x202f;=&#x202f;5), MCAO + FMT (n&#x202f;=&#x202f;3), and donor (n&#x202f;=&#x202f;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.<br><br>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&#x202f;&#xb1;&#x202f;3.2&#x202f;% vs 91.3&#x202f;&#xb1;&#x202f;2.5&#x202f;%, 79.0&#x202f;&#xb1;&#x202f;3.75&#x202f;% vs 90.8&#x202f;&#xb1;&#x202f;3.2&#x202f;%, and 69.5&#x202f;&#xb1;&#x202f;4.8&#x202f;% vs 90.5&#x202f;&#xb1;&#x202f;2.7&#x202f;%; all P&#x202f;<&#x202f;0.05), lower relative abundance of Lactobacillus (all P&#x202f;<&#x202f;0.05), and reduced GABA concentrations in the CSF (317.3&#x202f;&#xb1;&#x202f;30.6&#x202f;nmol/L vs 437.7&#x202f;&#xb1;&#x202f;25.6&#x202f;nmol/L, 303.1&#x202f;&#xb1;&#x202f;48.9&#x202f;nmol/L vs 4 40.9&#x202f;&#xb1;&#x202f;37.8&#x202f;nmol/L, and 337.9&#x202f;&#xb1;&#x202f;49.4&#x202f;nmol/L vs 457.4&#x202f;&#xb1;&#x202f;39.2&#x202f;nmol/L; all P&#x202f;<&#x202f;0.05) compared with the sham group. Sleep efficiency at post-FMT weeks 4 and 8 (84.7&#x202f;&#xb1;&#x202f;1.1&#x202f;% vs 79.0&#x202f;&#xb1;&#x202f;3.75&#x202f;%, and 84.1&#x202f;&#xb1;&#x202f;2.0&#x202f;% vs 69.5&#x202f;&#xb1;&#x202f;4.8&#x202f;%; both P&#x202f;<&#x202f;0.05) and GABA concentration in the CSF at post-FMT week 4 (403.1&#x202f;&#xb1;&#x202f;25.4&#x202f;nmol/L vs 303.1&#x202f;&#xb1;&#x202f;48.9&#x202f;nmol/L, P&#x202f;<&#x202f;0.05) was higher in the MCAO+FMT group than in the MCAO group.<br><br>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 &amp; pharmacotherapy = Biomedecine &amp; 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.<br><br>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.<br><br>METHODS: We performed SG or Sham surgery in male, Zucker rats (n&#xa0;=&#xa0;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&#xa0;wk (n&#xa0;=&#xa0;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.<br><br>RESULTS: Ten&#xa0;weeks of SG-FMT treatment significantly lowered systolic blood pressures in surgery-na&#xef;ve, recipient rats compared to vehicle treatment alone (126.8&#xa0;&#xb1;&#xa0;13.3&#xa0;mmHg versus 151.8&#xa0;&#xb1;&#xa0;12.2&#xa0;mmHg, P&#xa0;=&#xa0;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&#xa0;=&#xa0;0.01.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; purification/immunology ; *Poliovirus Vaccine, Oral/genetics/adverse effects ; *Recombination, Genetic ; *Mutation ; *Poliomyelitis/virology/prevention &amp; 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.<br><br>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&#x2009;&#xb1;&#x2009;7&#xa0;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.<br><br>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&#x2009;<&#x2009;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%).<br><br>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 &amp; 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.<br><br>METHODS: &#x2003;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.<br><br>RESULTS: &#x2003;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.<br><br>CONCLUSION: &#x2003;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 &amp; 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.<br><br>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&#xa0;% confidence intervals (CIs), and conducting univariate linear model meta-regressions.<br><br>RESULTS: Data from 21 trial comparisons across 19 studies (n&#xa0;=&#xa0;911) revealed that, compared to placebo/control, microbiome-modulating therapies were associated with statistically significant changes in fasting plasma glucose (MD: 4.03&#xa0;mg/dL [95%CI: 6.93; -1.13]; p effect&#xa0;=&#xa0;0.006, I[2]&#xa0;=&#xa0;89.8&#xa0;%), and fasting insulin (MD: 2.56 &#x3bc;U/mL [95%CI: 4.28; -0.84]; p effect&#xa0;=&#xa0;0.004, I[2]&#xa0;=&#xa0;87.9&#xa0;%), 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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>PURPOSE: To investigate the underlying mechanism of JWP against miscarriage through the gut-uterus axis.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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).<br><br>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).<br><br>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).<br><br>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]&#x2009;=&#x2009;1.44, 95% confidence interval [CI] 0.88-2.33) and changes in IBS Severity Scoring System (IBS-SSS) scores (standardised mean difference [SMD]&#x2009;=&#x2009;&#x2009;-&#x2009;0.31, 95% CI &#x2009;-&#x2009;0.72 to 0.09) and IBS Quality of Life (IBS-QOL) scores (SMD&#x2009;=&#x2009;0.30, 95% CI &#x2009;-&#x2009;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.<br><br>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.<br><br>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 &amp; 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.<br><br>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&#xff06;E staining was used to detect changes in intestinal tissue, the serum levels of LPS and GLP-1 were detected by ELISA.<br><br>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.<br><br>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 &amp; dosage/pharmacology ; *Encephalomyelitis, Autoimmune, Experimental/immunology/drug therapy/microbiology ; *Th17 Cells/immunology ; Mice ; *Prebiotics/administration &amp; 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 &amp; 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 &amp; 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.<br><br>METHODS AND RESULTS: Orally gavaged Esf increased DA-like behaviors, tumor necrosis factor (TNF)-&#x3b1;, and toll-like receptor-4 (TLR4) expression, and NF-&#x3ba;B[+]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-&#x3b1; levels, colonic TNF-&#x3b1; expression and NF-&#x3ba;B-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.<br><br>CONCLUSIONS: esEVs may be translocated into the brain via the vagus nerve and bloodstream, subsequently inducing TNF-&#x3b1; expression and suppressing serotonin, its receptor, and BDNF expression through the activation of TLR4-mediated NF-&#x3ba;B 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.<br><br>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-&#x3ba;B/TNF-&#x3b1; 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.<br><br>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-&#x3ba;B pathway and increase in TNF-&#x3b1; within the renal tissue, whereas toralactone treatment was observed to inhibit the LPS/TLR4/NF-&#x3ba;B/TNF-&#x3b1; pathway.<br><br>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-&#x3ba;B/TNF-&#x3b1; 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 &amp; 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, M&#xc1; and Sánchez Cabello, A and López Ruz, M&#xc1;}, 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.<br><br>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 &#x2265;2). The primary endpoint was clinical recurrence by day 56, defined as >3 unformed stools daily for &#x2265;2 days with or without laboratory confirmation of C. difficile, or death within 56 days.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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-&#x3b1;, IL-1&#x3b2; and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1.<br><br>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&#xa0;POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-&#x3b1; and IL-1&#x3b2; in the serum, increased levels of TNF-&#x3b1; 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-&#x3b1; 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&#xa0;control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-&#x3b1;, IL-1&#x3b2; and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus.<br><br>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.<br><br>HYPOTHESIS/OBJECTIVES: Fecal microbiota transplantation (FMT) in foals with diarrhea influences the intestinal microbiota and improves clinical and clinicopathological outcomes.<br><br>ANIMALS: Twenty-five foals <6&#x2009;months of age with diarrhea and systemic inflammatory response syndrome at 3 veterinary hospitals.<br><br>METHODS: A prospective randomized placebo-controlled cohort study. Foals in the FMT group (n&#x2009;=&#x2009;19) or control group (n&#x2009;=&#x2009;9) received FMT or electrolyte solution once daily for 3&#x2009;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.<br><br>RESULTS: Treatment had no effect on survival (FMT 79%; control 100%, P&#x2009;=&#x2009;.3) or resolution of diarrhea (FMT 68%; control 55%, P&#x2009;=&#x2009;.4). On D3, the white blood cell count of the FMT group was lower than the control group (D3 FMT group median 6.4&#x2009;g/L [5-8.3&#x2009;g/L]; D3 control group median 14.3&#x2009;g/L [6.7-18.9&#x2009;g/L] P&#x2009;=&#x2009;.04). Heart rate reduced over time in the FMT group (D0 median 80&#x2009;bpm [60-150&#x2009;bpm]; D2 median 70&#x2009;bpm [52-110&#x2009;bpm] [P&#x2009;=&#x2009;.005]; and D3 median 64, [54-102&#x2009;bpm] [P&#x2009;<&#x2009;.001]). Phylum Verrucomicrobiota, genus Akkermansia, and family Prevotellaceae were enriched in the FMT group on D1 (linear discriminate analysis&#x2009;>&#x2009;4).<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>METHODS: This was a prospective, multicenter study. Patients with UC &#x2265; 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.<br><br>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).<br><br>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.<br><br>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.<br><br>RESULTS: All 5 patients were successfully treated and followed up for a median of 70.0&#xa0;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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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-1&#x3b2; (IL-1&#x3b2;), tumor necrosis factor-&#x3b1; (TNF-&#x3b1;), 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>OBJECTIVES: We aimed to investigate the effect of PS-MS exposure on high-fat diet (HFD)-induced obesity and underlying mechanisms.<br><br>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.<br><br>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 &#x3b1;-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-&#x3b1; (TNF-&#x3b1;), interleukin-6 (IL-6), IL-1&#x3b2;, 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.<br><br>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 &amp; 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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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/&#xb5;l to 0.000207 pg/&#xb5;l. 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.<br><br>RESULTS: At a temperature of 66 &#xb0;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/&#xb5;l, 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).<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 &amp; 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.<br><br>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.<br><br>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. &#xa9; 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 &amp; 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.<br><br>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.<br><br>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.<br><br>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 &amp; Human Services | National Institutes of Health (NIH)/ ; }, mesh = {*Gastrointestinal Microbiome/genetics ; Humans ; *Feces/microbiology ; *Health Status ; Metagenome ; Bacteria/classification/genetics/isolation &amp; 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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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&#x2009;week, and 1&#x2009;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).<br><br>RESULTS: The mean log number of all bacteria was significantly higher in healthy individuals than kidney transplant recipients (p&#x2009;<&#x2009;0.001) except for Lactobacillus where the mean levels were almost identical in the two groups (p&#x2009;=&#x2009;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&#x2009;=&#x2009;0.12), Bacteroid fragilis (p&#x2009;=&#x2009;0.75), Bifidobacterium (p&#x2009;=&#x2009;0.99), Escherichia coli (p&#x2009;=&#x2009;0.5), Faecalibacterium (p&#x2009;=&#x2009;0.98), and Lactobacilli (p&#x2009;=&#x2009;0.93) between patients with and without delayed graft function (DGF).<br><br>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.<br><br>AIM: To evaluate the complex interplay among MAT, creeping fat, inflammation, and gut microbiota in CD.<br><br>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.<br><br>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.<br><br>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 &amp; 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 &amp; development/physiology/pathogenicity ; *Clostridium Infections/microbiology/prevention &amp; control ; *Gastrointestinal Microbiome/drug effects ; *Germ-Free Life ; *Clostridiales/genetics/growth &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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&#x202f;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.<br><br>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.<br><br>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.<br><br>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.<br><br>RESULTS: The human study revealed that bariatric surgery led to significant weight loss (p&#x2009;>&#x2009;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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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 PPAR&#x3b1; 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.<br><br>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.<br><br>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.<br><br>RESULTS: The group treated with hypertonic sugar saline enema exhibited significantly higher BBPS scores (6.78 &#xb1; 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 &#xb1; 4.86 minutes) compared with the control group (P < 0.05).<br><br>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&amp; AIMS: The protection provided by rotavirus (RV) vaccines is highly heterogeneous amongst individuals. We hypothesized that microbiota composition might influence RV vaccine efficacy.<br><br>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.<br><br>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.<br><br>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 &amp; 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 &amp; control/therapy ; Animals ; *Feces/virology/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; Swine ; Humans ; Bacteria/classification/isolation &amp; purification/genetics ; Animals, Newborn ; Disease Models, Animal ; Virome ; Clostridium perfringens ; Bacteriophages/genetics/physiology ; Diarrhea/therapy/virology/prevention &amp; 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&amp;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.<br><br>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.<br><br>METHODS: Literature related to the relationship between psoriasis and gut microbiota was searched in PubMed and CNKI.<br><br>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-&#x3b3;) along with the NF-kB pathway, thereby suppressing the release of pro-inflammatory cytokines and ameliorating systemic inflammatory conditions.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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.<br><br>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&amp;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.<br><br>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.<br><br>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 &amp; pharmacotherapy = Biomedecine &amp; 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 &amp; 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.<br><br>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.<br><br>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.<br><br>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.<br><br>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&#xa0;=&#xa0;28) vs. conventional treatment (5-aminosalicylic acid, 5-ASA, n&#xa0;=&#xa0;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.<br><br>RESULTS: Serum VD levels collected in the clinic practice indicated that patients with UC had significantly lower VD levels than HC (P&#xa0;<&#xa0;0.001). In the non-RCT, serum 25(OH)D level and VDR expression significantly increased (P&#xa0;=&#xa0;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.<br><br>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 &amp; purification ; Adult ; *Entamoeba histolytica/genetics/isolation &amp; purification ; Female ; Male ; Middle Aged ; Cryptosporidium/genetics/isolation &amp; purification ; Child ; Young Adult ; Child, Preschool ; Intestinal Diseases, Parasitic/diagnosis/parasitology ; Adolescent ; Bench