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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 10 Dec 2023 at 01:45 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: ( "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2023-12-07

Qian J, Lu J, Cheng S, et al (2023)

Periodontitis salivary microbiota exacerbates colitis-induced anxiety-like behavior via gut microbiota.

NPJ biofilms and microbiomes, 9(1):93.

The gut-brain axis is a bidirectional communication system between the gut and central nervous system. Many host-related factors can affect gut microbiota, including oral bacteria, making the brain a vulnerable target via the gut-brain axis. Saliva contains a large number of oral bacteria, and periodontitis, a common oral disease, can change the composition of salivary microbiota. However, the role and mechanism of periodontitis salivary microbiota (PSM) on the gut-brain axis remain unclear. Herein, we investigated the nature and mechanisms of this relationship using the mice with dextran sulfate sodium salt (DSS)-induced anxiety-like behavior. Compared with healthy salivary microbiota, PSM worsened anxiety-like behavior; it significantly reduced the number of normal neurons and activated microglia in DSS mice. Antibiotic treatment eliminated the effect of PSM on anxiety-like behavior, and transplantation of fecal microbiota from PSM-gavaged mice exacerbated anxiety-like behavior. These observations indicated that the anxiety-exacerbating effect of PSM was dependent on the gut microbiota. Moreover, the PSM effect on anxiety-like behavior was not present in non-DSS mice, indicating that DSS treatment was a prerequisite for PSM to exacerbate anxiety. Mechanistically, PSM altered the histidine metabolism in both gut and brain metabolomics. Supplementation of histidine-related metabolites had a similar anxiety-exacerbating effect as that of PSM, suggesting that histidine metabolism may be a critical pathway in this process. Our results demonstrate that PSM can exacerbate colitis-induced anxiety-like behavior by directly affecting the host gut microbiota, emphasizing the importance of oral diseases in the gut-brain axis.

RevDate: 2023-12-07

Yu Z, Xiaojia L, Wei Z, et al (2023)

Baicalin circumvents anti-PD-1 resistance by regulating the gut microbiota metabolite short-chain fatty acids.

Pharmacological research pii:S1043-6618(23)00389-4 [Epub ahead of print].

Baicalin is a small molecule medication used to treat hepatitis. Our research group discovered that administering baicalin orally to mice following fecal microbiota transplantation from patients resistant to ICIs supported anti-PD-1 activity. However, the precise mechanisms behind this effect are presently unknown. In this present study, ATB-treated C57BL/6J mice received FMT from patients with advanced NSCLC amenable to αPD-1. Additionally, subcutaneous LLC cells were injected into the mice. Baicalin oral gavage and αPD-1 injection were administered to the mice on days 3 and 9 after tumour inoculation. 16S rRNA, metabolomics, and flow cytometry were utilized to clarify the mechanisms of baicalin's relief of immunosuppression. The results indicated that oral administration of baicalin enriched bacteria such as Akkermansia and Clostridia_UCG-014, resulted in an increase in SCFAs, which improved the ratio of PD-1[+] (CD8[+] T cell/Treg) and promoted the levels of IFN-γ[+] CD8[+] T cells and TNF-α[+] CD8[+] T cells within the tumour microenvironment. In conclusion, baicalin regulates the metabolites of the gut microbiota to improve the PD-1[+] (CD8[+] T cell/Treg) balance and circumvent anti-PD-1 resistance. This is achieved through the regulation of short-chain fatty acids.

RevDate: 2023-12-07

Cheng Y, Tan G, Zhu Q, et al (2023)

Efficacy of fecal microbiota transplantation in patients with Parkinson's disease: clinical trial results from a randomized, placebo-controlled design.

Gut microbes, 15(2):2284247.

The occurrence and development of Parkinson's disease (PD) have been demonstrated to be related to gut dysbiosis, however, the impact of fecal microbiota transplantation (FMT) on microbiota engraftment in PD patients is uncertain. We performed a randomized, placebo-controlled trial at the Department of Neurology, Army Medical University Southwest Hospital in China (ChiCTR1900021405) from February 2019 to December 2019. Fifty-six participants with mild to moderate PD (Hoehn-Yahr stage 1-3) were randomly assigned to the FMT and placebo group, 27 patients in the FMT group and 27 in the placebo group completed the whole trial. During the follow-up, no severe adverse effect was observed, and patients with FMT treatment showed significant improvement in PD-related autonomic symptoms compared with the placebo group at the end of this trial (MDS-UPDRS total score, group×time effect, B = -6.56 [-12.98, -0.13], P < 0.05). Additionally, FMT improved gastrointestinal disorders and a marked increase in the complexity of the microecological system in patients. This study demonstrated that FMT through oral administration is clinically feasible and has the potential to improve the effectiveness of current medications in the clinical symptoms of PD patients.

RevDate: 2023-12-08

Yang C, Hu T, Xue X, et al (2023)

Multi-omics analysis of fecal microbiota transplantation's impact on functional constipation and comorbid depression and anxiety.

BMC microbiology, 23(1):389.

BACKGROUND: Depression and anxiety are common comorbid diseases of constipation. Fecal microbiota transplantation (FMT) significantly relieves gastrointestinal-related symptoms, but its impact on psychiatric symptoms remains uncharted.

METHODS: We collected fecal and serum samples before and after FMT from 4 functional constipation patients with psychiatric symptoms and corresponding donor stool samples. We categorized the samples into two groups: before FMT (Fb) and after FMT (Fa). Parameters associated with constipation, depression, and anxiety symptoms were evaluated. Metagenomics and targeted neurotransmitter metabolomics were performed to investigate the gut microbiota and metabolites. 5-hydroxytryptamine (5-HT) biosynthesis was detected in patients' fecal supernatants exposed to the QGP-1 cell model in vitro.

RESULTS: Our study demonstrated that patient's constipation, depression, and anxiety were improved after FMT intervention. At the genus level, relative abundance of g_Bacteroides and g_Klebsiella decreased in the Fa group, while g_Lactobacillus, and g_Selenomonas content increased in the same group. These observations suggest a potential involvement of these genera in the pathogenesis of constipation with psychiatric symptoms. Metabolomics analysis showed that FMT intervention decreased serum 5-HT levels. Additionally, we found that species, including s_Klebsiella sp. 1_1_55, s_Odoribacter splanchnicus, and s_Ruminococcus gnavus CAG:126, were positively correlated with 5-HT levels. In contrast, s_Acetobacterium bakii, s_Enterococcus hermanniensis, s_Prevotella falsenii, s_Propionispira arboris, s_Schwartzia succinivorans, s_Selenomonas artemidis, and s_Selenomonas sp. FC4001 were negatively correlated with 5-HT levels. Furthermore, we observed that patients' fecal supernatants increased 5-HT biosynthesis in QGP-1 cells.

CONCLUSION: FMT can relieve patients' constipation, depression, and anxiety symptoms by reshaping gut microbiota. The 5-HT level was associated with an altered abundance of specific bacteria or metabolites. This study provides specific evidence for FMT intervention in constipation patients with psychiatric symptoms.

RevDate: 2023-12-08

Yan M, Man S, Sun B, et al (2023)

Gut liver brain axis in diseases: the implications for therapeutic interventions.

Signal transduction and targeted therapy, 8(1):443.

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, β-amyloid (Aβ) metabolism, and epigenetic regulation in the gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet and nanotechnology application regulate the gut liver brain axis. Besides, some special treatments targeting gut-liver axis include farnesoid X receptor (FXR) agonists, takeda G protein-coupled receptor 5 (TGR5) agonists, glucagon-like peptide-1 (GLP-1) receptor antagonists and fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain axis embraces cognitive behavioral therapy (CBT), antidepressants and tryptophan metabolism-related therapies. Targeting liver-brain axis contains epigenetic regulation and Aβ metabolism-related therapies. In the future, a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

RevDate: 2023-12-06

Wang N, Gao X, Huo Y, et al (2023)

Lead exposure aggravates glucose metabolism disorders through gut microbiota dysbiosis and intestinal barrier damage in high-fat diet-fed mice.

Journal of the science of food and agriculture [Epub ahead of print].

BACKGROUND: Lead (Pb) is an ancient toxic metal and is still a major public health issue. Our previous study found that Pb exposure promotes metabolic disorders in obese mice, but the molecular mechanisms remain unclear. The present study explored the effects of Pb exposure on glucose homeostasis in mice fed a normal diet (ND) and high-fat diet (HFD) from the perspective of gut microbiota.

RESULTS: Pb exposure had little effect on glucose metabolism in ND mice, but exacerbated hyperglycemia, insulin resistance, and impaired glucose tolerance in HFD mice. Pb exposure impaired intestinal tight junctions and mucin expression in HFD mice, increasing intestinal permeability and inflammation. Moreover, Pb exposure altered the composition and structure of the gut microbiota and decreased short-chain fatty acids (SCFAs) levels in HFD mice. Correlation analysis revealed that the gut microbiota and SCFAs were significantly correlated with the gut barrier and glucose homeostasis. Further, the fecal microbiota transplantation from Pb-exposed HFD mice resulted in glucose homeostasis imbalance, intestinal mucosal structural damage, and inflammation in recipient mice. However, Pb did not exacerbate the metabolic toxicity in HFD mice under depleted gut microbiota.

CONCLUSION: The findings suggest that Pb induces impairment of glucose metabolism in HFD mice by perturbing the gut microbiota. Our study offered new perspectives on the mechanisms of metabolic toxicity of heavy metals and demonstrate that the gut microbiota may be a target of action for heavy metal exposure. This article is protected by copyright. All rights reserved.

RevDate: 2023-12-06

Sehgal K, Yadav D, Saha S, et al (2023)

Sex-Discordant Fecal Microbiota Transplantation for C. difficile may increase risk of post-infection irritable bowel syndrome.

Gastroenterology pii:S0016-5085(23)05570-1 [Epub ahead of print].

RevDate: 2023-12-06

Liu YF, Xie WJ, Xi P, et al (2023)

Astaxanthin alleviates chronic prostatitis/chronic pelvic pain syndrome by increasing colonization of Akkermansia muciniphila in the intestine.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 123:155249 pii:S0944-7113(23)00608-6 [Epub ahead of print].

BACKGROUND: Astaxanthin (AST) is a natural compound with anti-inflammatory/immunomodulatory properties that has been found to have probiotic properties. However, the role and mechanism of AST in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still not fully understood.

PURPOSE: The aim of this study was to evaluate the effect of AST on CP/CPPS and elucidate the mediating role of the gut microbiota.

MATERIALS AND METHODS: An experimental autoimmune prostatitis (EAP) mouse model was utilized to test the potential role of AST on CP/CPPS. Antibiotic cocktail (ABX) treatment and fecal microbiota transplantation (FMT) were used to elucidate the gut microbiota-mediated effects on AST. In addition, 16S rRNA gene sequencing and qRT-PCR analyses were used to analyze changes in the gut microbiota of EAP mice and CP/CPPS patients. Finally, the mechanism by which AST exerts a protective effect on CP/CPPS was explored by untargeted metabolomics and gut barrier function assays.

RESULTS: Oral administration of AST reduced prostate inflammation scores, alleviated tactile sensitization of the pelvic region in EAP mice, reduced CD4+ T cell and CD68+ macrophage infiltration in the prostatic interstitium, and inhibited the up-regulation of systemic and localized pain/pro-inflammatory mediators in the prostate. After ABX, the protective effect of AST against CP/CPPS was attenuated, whereas colonization with fecal bacteria from AST-treated EAP mice alleviated CP/CPPS. 16S rRNA gene sequencing and qRT-PCR analyses showed that Akkermansia muciniphila in the feces of EAP mice and CP/CPPS patients showed a trend toward a decrease, which was associated with poor progression of CP/CPPS. In contrast, oral administration of AST increased the relative abundance of A. muciniphila, and oral supplementation with A. muciniphila also alleviated inflammation and pain in EAP mice. Finally, we demonstrated that both AST and A. muciniphila interventions increased serum levels of SCFAs acetate, up-regulated expression of colonic tight junction markers, and decreased serum lipopolysaccharide levels in EAP mice.

CONCLUSION: Our results showed that AST improved CP/CPPS by up-regulating A. muciniphila, which provides new potentially effective strategies and ideas for CP/CPPS management.

RevDate: 2023-12-07
CmpDate: 2023-12-07

Gonzales-Luna AJ, Carlson TJ, KW Garey (2023)

Review Article: Safety of Live Biotherapeutic Products Used for the Prevention of Clostridioides difficile Infection Recurrence.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 77(Supplement_6):S487-S496.

Live biotherapeutic products (LBPs) represent a new class of therapeutics indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in adults. However, microbiota-based therapies have been used in CDI management before the Food and Drug Administration (FDA) designated this new drug class. The regulation of these microbiome-based therapies has varied, and several safety concerns have arisen over time. Requirements established by the FDA regarding the development of LBPs minimizes many of these prior concerns, and phase III trials have proven the safety and efficacy of 2 stool donor-derived LBPs: fecal microbiota, live-jslm (Rebyota™; formerly RBX2660) and fecal microbiota spores, live-brpk (Vowst™; formerly SER-109). Mild gastrointestinal side effects are common, but no severe drug-related adverse events have been reported with their use to date. A third LBP entering phase III clinical trials, VE303, follows a novel approach by sourcing bacterial strains from clonal cell banks and has demonstrated a similarly favorable safety profile.

RevDate: 2023-12-06

He K, Gao Q, Su J, et al (2023)

Gut Microbiome and Metabolomics Study of Selenium-Enriched Kiwifruit Regulating Hyperlipidemia in Mice Induced by a High-Fat Diet.

Journal of agricultural and food chemistry [Epub ahead of print].

Our previous study showed that as a substitute for statins, selenium-enriched kiwifruit (Se-Kiwi) might reduce blood lipids and protect the liver in Kunming mice, but the underlying mechanism remains unclear. Metabolic regulation of mammalian intestinal microflora plays an important role in obesity and related diseases induced by a high-fat diet (HFD). Here, samples of serum, liver, colon, and fresh feces from the Se-Kiwi-treated hyperlipidemia C57BL/6J mouse model were collected. Based on metabolome (UHPLC-Q-TOF MS) and gut microbiome (16S rDNA) analyses as well as the integrative analysis of physiological and biochemical indices and pathological data of mice, we aimed to systematically illustrate the gut microbiome and metabolomics mechanism of Se-Kiwi in HFD-induced hyperlipidemic mice. As a result, Se-Kiwi can significantly increase the abundance of potentially beneficial gut bacteria such as Parabacteroides, Bacteroides, and Allobaculum in the colon and improve hyperlipidemia by regulating the digestion and absorption of vitamins, pyrimidine metabolism, purine metabolism, and other metabolic pathways, which have been confirmed by the following fecal microbiota transplantation experiment. This process was significantly regulated by the Ada, Gda, Pank1, Ppara, Pparg, and Cd36 genes. These findings may provide a theoretical basis for the research and development of selenium-enriched functional foods in the treatment of hyperlipidemia.

RevDate: 2023-12-06

Qi L, Peng J, Huang X, et al (2023)

Longitudinal dynamics of gut microbiota in the pathogenesis of acute graft-versus-host disease.

Cancer medicine [Epub ahead of print].

AIM: The gut microbiota has been reported to be associated with acute graft-versus-host disease (aGvHD) in hematopoietic stem cell transplantation (HSCT). Dynamic surveillance of the microbiota is required to understand the detailed pathogenesis involved in the process of aGvHD.

METHODS: Fecal samples were collected prospectively at four timepoints, including pre-HSCT (T1), graft infusion (T2), neutrophil engraftment (T3), and 30 days after transplantation (T4). Fecal samples were profiled by 16S ribosomal RNA gene sequencing to assess the microbiota composition.

RESULTS: From the T1 to T4 timepoint, the diversity of the gut microbiota decreased, and the dominant species also changed, with a decrease in the obligate anaerobic bacteria and a shift toward a "pathogenic community". Compared with non-aGvHD patients, aGvHD patients had a lower abundance of Roseburia at T1 and a higher abundance of Acinetobacter johnsonii at T2. Furthermore, Acinetobacter johnsonii was negatively correlated with the secretion of IL-4 and TNF-α. At T3, Rothia mucilaginos was demonstrated to be linked with a decreased risk of aGvHD, which was accompanied by decreased secretion of IL-8. At T4, higher abundances of Lactobacillus paracasei and Acinetobacter johnsonii were identified to be related with aGvHD. Lactobacillus paracasei was associated with the downregulation of IL-10, and Acinetobacter johnsonii was associated with the downregulation of IL-2 and TNF-α.

CONCLUSIONS: Dynamic changes in gut microbiota composition and related cytokines were found to be related to aGvHD, including pathogenic or protective changes. These findings suggested that manipulation of gut microbiota at different timepoints might be a promising avenue for preventing or treating this common complication.

RevDate: 2023-12-06

Yu Z, Han J, Li L, et al (2023)

Chronic triclosan exposure induce impaired glucose tolerance by altering the gut microbiota.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 183:114305 pii:S0278-6915(23)00707-X [Epub ahead of print].

Triclosan (TCS) is an antimicrobial compound incorporated into more than 2000 consumer products. This compound is frequently detected in the human body and causes ubiquitous contamination in the environment, thereby raising concerns about its impact on human health and environmental pollution. Here, we demonstrated that 20 weeks' exposure of TCS drove the development of glucose intolerance by inducing compositional and functional alterations in intestinal microbiota in rats. Fecal-transplantation experiments corroborated the involvement of gut microbiota in TCS-induced glucose-tolerance impairment. 16S rRNA gene-sequencing analysis of cecal contents showed that TCS disrupted the gut microbiota composition in rats and increased the ratio of Firmicutes to Bacteroidetes. Cecal metabolomic analyses detected that TCS altered host metabolic pathways that are linked to host glucose and amino acid metabolism, particularly branched-chain amino acid (BCAA) biosynthesis. BCAA measurement confirmed the increase in serum BCAAs in rats exposed to TCS. Western blot and immunostaining results further confirmed that elevated BCAAs stimulated mTOR, a nutrient-sensing complex, and following IRS-1 serine phosphorylation, resulted in insulin resistance and glucose intolerance. These results suggested that TCS may induce glucose metabolism imbalance by regulating BCAA concentration by remodeling the gut microbiota.

RevDate: 2023-12-05

Cerdó T, Ruiz-Rodríguez A, Acuña I, et al (2023)

Infant gut microbiota contributes to cognitive performance in mice.

Cell host & microbe pii:S1931-3128(23)00454-7 [Epub ahead of print].

Gut microbiota has been linked to infant neurodevelopment. Here, an association between infant composite cognition and gut microbiota composition is established as soon as 6 months. Higher diversity and evenness characterize microbial communities of infants with composite cognition above (Inf-aboveCC) versus below (Inf-belowCC) median values. Metaproteomic and metabolomic analyses establish an association between microbial histidine ammonia lyase and infant histidine metabolome with cognition. Fecal transplantation from Inf-aboveCC versus Inf-belowCC donors into germ-free mice shows that memory, assessed by a novel object recognition test, is a transmissible trait. Furthermore, Inf-aboveCC mice are enriched in species belonging to Phocaeicola, as well as Bacteroides and Bifidobacterium, previously linked to cognition. Finally, Inf-aboveCC mice show lower fecal histidine and urocanate:histidine and urocanate:glutamate ratios in the perirhinal cortex compared to Inf-belowCC mice. Overall, these findings reveal a causative role of gut microbiota on infant cognition, pointing at the modulation of histidine metabolite levels as a potential underlying mechanism.

RevDate: 2023-12-05

Kelly CR, JR Allegretti (2023)

Review Article: Gastroenterology and Clostridium difficile Infection: Past, Present, and Future.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 77(Supplement_6):S463-S470.

Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms.

RevDate: 2023-12-05

Lavoie T, Appaneal HJ, KL LaPlante (2023)

Advancements in Novel Live Biotherapeutic Products for Clostridioides difficile Infection Prevention.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 77(Supplement_6):S447-S454.

The profound impact of the human microbiome on health and disease has captivated the interest of clinical and scientific communities. The human body hosts a vast array of microorganisms collectively forming the human microbiome, which significantly influences various physiological processes and profoundly shapes overall well-being. Notably, the gut stands out as an exceptional reservoir, harboring the most significant concentration of microorganisms, akin to an organ in itself. The gut microbiome's composition and function are influenced by genetics, environment, age, underlying conditions, and antibiotic usage, leading to dysbiosis and pathogenesis, such as Clostridioides difficile infection (CDI). Conventional CDI treatment, involving antibiotics like oral vancomycin and fidaxomicin, fails to address dysbiosis and may further disrupt gut microbial communities. Consequently, emerging therapeutic strategies are focused on targeting dysbiosis and restoring gut microbiota to advance CDI therapeutics. Fecal microbiota transplantation (FMT) has demonstrated remarkable efficacy in treating recurrent CDI by transferring processed stool from a healthy donor to a recipient, restoring gut dysbiosis and enhancing bacterial diversity. Moreover, 2 newer Food and Drug Administration (FDA)-approved live biotherapeutic products (LBP), namely, Fecal Microbiota Live-JSLM and Fecal Microbiota Spores Live-BRPK, have shown promise in preventing CDI recurrence. This review explores the role of the gut microbiota in preventing and treating CDI, with an emphasis on gut-based interventions like FMT and fecal microbiota-based products that hold potential for gut restoration and prevention of CDI recurrence. Understanding the microbiome's impact on CDI prevention and treatment offers valuable insights for advancing future CDI therapeutics.

RevDate: 2023-12-04

Liu X, Li J, Shi M, et al (2023)

Melatonin improves cholestatic liver disease via the gut-liver axis.

Journal of pineal research [Epub ahead of print].

Cholestatic liver disease is characterized by disturbances in the intestinal microbiota and excessive accumulation of toxic bile acids (BA) in the liver. Melatonin (MT) can improve liver diseases. However, the underlying mechanism remains unclear. This study aimed to explore the mechanism of MT on hepatic BA synthesis, liver injury, and fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-fed and Mdr2[-/-] mice. MT significantly improved hepatic injury and fibrosis with a significant decrease in hepatic BA accumulation in DDC-fed and Mdr2[-/-] mice. MT reprogramed gut microbiota and augmented fecal bile salt hydrolase activity, which was related to increasing intestinal BA deconjugation and fecal BA excretion in both DDC-fed and Mdr2[-/-] mice. MT significantly activated the intestinal farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF-15) axis and subsequently inhibited hepatic BA synthesis in DDC-fed and Mdr2[-/-] mice. MT failed to improve DDC-induced liver fibrosis and BA synthesis in antibiotic-treated mice. Furthermore, MT provided protection against DDC-induced liver injury and fibrosis in fecal microbiota transplantation mice. MT did not decrease liver injury and fibrosis in DDC-fed intestinal epithelial cell-specific FXR knockout mice, suggesting that the intestinal FXR mediated the anti-fibrosis effect of MT. In conclusion, MT ameliorates cholestatic liver diseases by remodeling gut microbiota and activating intestinal FXR/FGF-15 axis-mediated inhibition of hepatic BA synthesis and promotion of BA excretion in mice.

RevDate: 2023-12-05

Fremin BJ, Bhatt AS, NC Kyrpides (2023)

Identification of over ten thousand candidate structured RNAs in viruses and phages.

Computational and structural biotechnology journal, 21:5630-5639.

Structured RNAs play crucial roles in viruses, exerting influence over both viral and host gene expression. However, the extensive diversity of structured RNAs and their ability to act in cis or trans positions pose challenges for predicting and assigning their functions. While comparative genomics approaches have successfully predicted candidate structured RNAs in microbes on a large scale, similar efforts for viruses have been lacking. In this study, we screened over 5 million DNA and RNA viral sequences, resulting in the prediction of 10,006 novel candidate structured RNAs. These predictions are widely distributed across taxonomy and ecosystem. We found transcriptional evidence for 206 of these candidate structured RNAs in the human fecal microbiome. These candidate RNAs exhibited evidence of nucleotide covariation, indicative of selective pressure maintaining the predicted secondary structures. Our analysis revealed a diverse repertoire of candidate structured RNAs, encompassing a substantial number of putative tRNAs or tRNA-like structures, Rho-independent transcription terminators, and potentially cis-regulatory structures consistently positioned upstream of genes. In summary, our findings shed light on the extensive diversity of structured RNAs in viruses, offering a valuable resource for further investigations into their functional roles and implications in viral gene expression and pave the way for a deeper understanding of the intricate interplay between viruses and their hosts at the molecular level.

RevDate: 2023-12-05

Roggiani S, Mengoli M, Conti G, et al (2023)

Gut microbiota resilience and recovery after anticancer chemotherapy.

Microbiome research reports, 2(3):16.

Although research on the role of the gut microbiota (GM) in human health has sharply increased in recent years, what a "healthy" gut microbiota is and how it responds to major stressors is still difficult to establish. In particular, anticancer chemotherapy is known to have a drastic impact on the microbiota structure, potentially hampering its recovery with serious long-term consequences for patients' health. However, the distinguishing features of gut microbiota recovery and non-recovery processes are not yet known. In this narrative review, we first investigated how gut microbiota layouts are affected by anticancer chemotherapy and identified potential gut microbial recovery signatures. Then, we discussed microbiome-based intervention strategies aimed at promoting resilience, i.e., the rapid and complete recovery of a healthy gut microbial network associated with a better prognosis after such high-impact pharmacological treatments.

RevDate: 2023-12-05
CmpDate: 2023-12-05

Meade S, Liu Chen Kiow J, Massaro C, et al (2023)

Gut microbiome-associated predictors as biomarkers of response to advanced therapies in inflammatory bowel disease: a systematic review.

Gut microbes, 15(2):2287073.

Loss of response to therapy in inflammatory bowel disease (IBD) has led to a surge in research focusing on precision medicine. Three systematic reviews have been published investigating the associations between gut microbiota and disease activity or IBD therapy. We performed a systematic review to investigate the microbiome predictors of response to advanced therapy in IBD. Unlike previous studies, our review focused on predictors of response to therapy; so the included studies assessed microbiome predictors before the proposed time of response or remission. We also provide an update of the available data on mycobiomes and viromes. We highlight key themes in the literature that may serve as future biomarkers of treatment response: the abundance of fecal SCFA-producing bacteria and opportunistic bacteria, metabolic pathways related to butyrate synthesis, and non-butyrate metabolomic predictors, including bile acids (BAs), amino acids, and lipids, as well as mycobiome predictors of response.

RevDate: 2023-12-05

Park JC, SH Im (2022)

The gut-immune-brain axis in neurodevelopment and neurological disorders.

Microbiome research reports, 1(4):23.

The gut-brain axis is gaining momentum as an interdisciplinary field addressing how intestinal microbes influence the central nervous system (CNS). Studies using powerful tools, including germ-free, antibiotic-fed, and fecal microbiota transplanted mice, demonstrate how gut microbiota perturbations alter the fate of neurodevelopment. Probiotics are also becoming more recognized as potentially effective therapeutic agents in alleviating symptoms of neurological disorders. While gut microbes may directly communicate with the CNS through their effector molecules, including metabolites, their influence on neuroimmune populations, including newly discovered brain-resident T cells, underscore the host immunity as a potent mediator of the gut-brain axis. In this review, we examine the unique immune populations within the brain, the effects of the gut microbiota on the CNS, and the efficacy of specific probiotic strains to propose the novel concept of the gut-immune-brain axis.

RevDate: 2023-12-05

Aguanno D, Metwaly A, Coleman OI, et al (2022)

Modeling microbiota-associated human diseases: from minimal models to complex systems.

Microbiome research reports, 1(3):17.

Alterations in the intestinal microbiota are associated with various human diseases of the digestive system, including obesity and its associated metabolic diseases, inflammatory bowel diseases (IBD), and colorectal cancer (CRC). All three diseases are characterized by modifications of the richness, composition, and metabolic functions of the human intestinal microbiota. Despite being multi-factorial diseases, studies in germ-free animal models have unarguably identified the intestinal microbiota as a causal driver of disease pathogenesis. However, for an increased mechanistic understanding of microbial signatures in human diseases, models require detailed refinement to closely mimic the human microbiota and reflect the complexity and range of dysbiosis observed in patients. The transplantation of human fecal microbiota into animal models represents a powerful tool for studying the causal and functional role of the dysbiotic human microbiome in a pathological context. While human microbiota-associated models were initially employed to study obesity, an increasing number of studies have applied this approach in the context of IBD and CRC over the past decade. In this review, we discuss different approaches that allow the functional validation of the bacterial contribution to human diseases, with emphasis on obesity and its associated metabolic diseases, IBD, and CRC. We discuss the utility of simple models, such as in vitro fermentation systems of the human microbiota and ex vivo intestinal organoids, as well as more complex whole organism models. Our focus here lies on human microbiota-associated mouse models in the context of all three diseases, as well as highlighting the advantages and limitations of this approach.

RevDate: 2023-12-04

Gómez-Gallego C, H El-Nezami (2023)

Editorial: Novel developments for promoting health through microbiota modulation.

Frontiers in nutrition, 10:1331665.

RevDate: 2023-12-04

Brüssow H (2023)

The human microbiome project at ten years - some critical comments and reflections on "our third genome", the human virome.

Microbiome research reports, 2(1):7.

The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in Clostridioides difficile infection, practical application of microbiome intervention has only achieved modest clinical effects. It is argued here that we need criteria for the link between microbiome and disease modelled on the links between pathogens and infectious disease in Koch's postulates. The most important question is whether the microbiome change is a cause of the given disease or a consequence of a pathology leading to disease where the microbiome change is only a parallel event without a causal connection to the disease - in philosophical parlance, an epiphenomenon. Also discussed here is whether human virome research is a necessary complement to the microbiome project with a high potential for practical applications.

RevDate: 2023-12-04

Chen JH, Zhao CL, Li YS, et al (2023)

Moutai Distiller's grains Polyphenol extracts and rutin alleviate DSS-induced colitis in mice: Modulation of gut microbiota and intestinal barrier function (R2).

Heliyon, 9(11):e22186.

Distiller's grains, byproducts of the brewing process, represent a valuable resource for extracting natural phenolic compounds due to their significant global production. This study presents the first evidence of the protective effects of Moutai distiller's grain polyphenol extract (MDGP) on dextran sulfate sodium (DSS)-induced colitis in mice. These protective effects manifest predominantly through the amelioration of general colitis indices and histopathological improvements. Utilizing liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), the main components of MDGP were identified as rutin, quercetin, naringenin, and dihydroquercetin. Moreover, a novel mechanism was elucidated by which rutin, the primary active component of MDGP, alleviates DSS-induced colitis. Assessment of intestinal barrier function, microbial sequencing, fecal transplantation, and antibiotic depletion experiments revealed that rutin suppresses the abundance of pathogenic bacteria (Helicobacter, Klebsiella, and Veillonella) while promoting the proliferation of beneficial bacteria (Ruminococcus_torques_group, Lachnoclostridium, and norank_f__Muribaculaceae). This modulation culminates in elevated butyric acid concentrations within short-chain fatty acids (SCFAs), amplified integrity of tight (ZO-1, occludin) and adherent (E-cadherin, β-catenin) junctional complexes, fortified intestinal barrier function, and diminished intestinal inflammation.This investigation accentuates the innovative therapeutic potential of MDGP and its main active component, rutin, in assuaging DSS-induced intestinal inflammation and fortifying the intestinal barrier through a mechanism predominantly mediated by the intestinal microbiota. Such insights potentially elevate the prominence of distiller's grains in the realm of functional food development.

RevDate: 2023-12-04
CmpDate: 2023-12-04

Swarte JC, Knobbe TJ, Björk JR, et al (2023)

Health-related quality of life is linked to the gut microbiome in kidney transplant recipients.

Nature communications, 14(1):7968.

Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly related in the general population. Here, we investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR. Multiple bacterial species are associated with lower HRQoL, many of which have previously been associated with adverse health conditions. Gut microbiome distance to the general population is highest among KTR with an impaired physical HRQoL (R = -0.20, P = 2.3 × 10[-65]) and mental HRQoL (R = -0.14, P = 1.3 × 10[-3]). Physical and mental HRQoL explain a significant part of variance in the gut microbiome (R[2] = 0.58%, FDR = 5.43 × 10[-4] and R[2] = 0.37%, FDR = 1.38 × 10[-3], respectively). Additionally, multiple metabolic and neuroactive pathways (gut brain modules) are associated with lower HRQoL. While the observational design of our study does not allow us to analyze causality, we provide a comprehensive overview of the associations between the gut microbiome and HRQoL while controlling for confounders.

RevDate: 2023-12-04
CmpDate: 2023-12-04

Deng ZL, Pieper DH, Stallmach A, et al (2023)

Engraftment of essential functions through multiple fecal microbiota transplants in chronic antibiotic-resistant pouchitis-a case study using metatranscriptomics.

Microbiome, 11(1):269.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the standard of care after total proctocolectomy for ulcerative colitis (UC). Around 50% of patients will experience pouchitis, an idiopathic inflammatory condition. Antibiotics are the backbone of treatment of pouchitis; however, antibiotic-resistant pouchitis develops in 5-10% of those patients. It has been shown that fecal microbiota transplantation (FMT) is an effective treatment for UC, but results for FMT antibiotic-resistant pouchitis are inconsistent.

METHODS: To uncover which metabolic activities were transferred to the recipients during FMT and helped the remission, we performed a longitudinal case study of the gut metatranscriptomes from three patients and their donors. The patients were treated by two to three FMTs, and stool samples were analyzed for up to 140 days.

RESULTS: Reduced expression in pouchitis patients compared to healthy donors was observed for genes involved in biosynthesis of amino acids, cofactors, and B vitamins. An independent metatranscriptome dataset of UC patients showed a similar result. Other functions including biosynthesis of butyrate, metabolism of bile acids, and tryptophan were also much lower expressed in pouchitis. After FMT, these activities transiently increased, and the overall metatranscriptome profiles closely mirrored those of the respective donors with notable fluctuations during the subsequent weeks. The levels of the clinical marker fecal calprotectin were concordant with the metatranscriptome data. Faecalibacterium prausnitzii represented the most active species contributing to butyrate synthesis via the acetyl-CoA pathway. Remission occurred after the last FMT in all patients and was characterized by a microbiota activity profile distinct from donors in two of the patients.

CONCLUSIONS: Our study demonstrates the clear but short-lived activity engraftment of donor microbiota, particularly the butyrate biosynthesis after each FMT. The data suggest that FMT triggers shifts in the activity of patient microbiota towards health which need to be repeated to reach critical thresholds. As a case study, these insights warrant cautious interpretation, and validation in larger cohorts is necessary for generalized applications. In the long run, probiotics with high taxonomic diversity consisting of well characterized strains could replace FMT to avoid the costly screening of donors and the risk of transferring unwanted genetic material. Video Abstract.

RevDate: 2023-12-02

Cai X, Li Z, Yao Y, et al (2023)

Glycolithocholic acid increases the frequency of circulating Tregs through constitutive androstane receptor to alleviate postmenopausal osteoporosis.

Biochemical pharmacology, 219:115951 pii:S0006-2952(23)00544-0 [Epub ahead of print].

BACKGROUND AND PURPOSE: Gut microbiota and their metabolic activity are important regulators of host immunity. However, the role of gut microbiota and their metabolic activity-mediated osteoimmunity in postmenopausal osteoporosis (PMO) remains unknown. This study aimed to explore the role of gut microbiota and their metabolic activity in PMO.

EXPERIMENTAL APPROACH: 16S rDNA sequencing was used for analyzing the gut microbiota diversity of patients with PMO and rat models, and a targeted metabolism study was performed for analyzing metabolite levels. Flow cytometry was used for analyzing the frequency of immune cells. Micro-CT was used for analyzing bone damage in rat models. Fecal microbiota transplantation was performed for exploring the therapeutic effect of the gut microbiota on PMO. CD4[+] T cells were co-cultured with bone marrow mesenchymal stem cells for evaluating their molecular mechanisms.

KEY RESULTS: Patients with PMO exhibited reduced gut microbiota diversity, and fecal glycolithocholic acid (GLCA) levels correlated with the degree of osteoporosis. GLCA levels in the gut were positively correlated with the frequency of circulating Tregs in ovariectomized rats. Restoration of the gut microbiota alleviated osteoporosis in ovariectomized rats. Circulating GLCA augmented CD4[+] T cell differentiation into Tregs via constitutive androstane receptors. The increased frequency of Tregs further promoted the osteogenic differentiation of bone marrow mesenchymal stem cells to alleviate osteoporosis.

CONCLUSION AND IMPLICATIONS: GLCA alleviated PMO by increasing the frequency of circulating Tregs, acting via the constitutive androstane receptor. This study reveals a new strategy for the treatment of PMO, with GLCA as a potential drug candidate.

RevDate: 2023-12-04
CmpDate: 2023-12-04

Van Dingenen L, Segers C, Wouters S, et al (2023)

Dissecting the role of the gut microbiome and fecal microbiota transplantation in radio- and immunotherapy treatment of colorectal cancer.

Frontiers in cellular and infection microbiology, 13:1298264.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and poses a major burden on the human health worldwide. At the moment, treatment of CRC consists of surgery in combination with (neo)adjuvant chemotherapy and/or radiotherapy. More recently, immune checkpoint blockers (ICBs) have also been approved for CRC treatment. In addition, recent studies have shown that radiotherapy and ICBs act synergistically, with radiotherapy stimulating the immune system that is activated by ICBs. However, both treatments are also associated with severe toxicity and efficacy issues, which can lead to temporary or permanent discontinuation of these treatment programs. There's growing evidence pointing to the gut microbiome playing a role in these issues. Some microorganisms seem to contribute to radiotherapy-associated toxicity and hinder ICB efficacy, while others seem to reduce radiotherapy-associated toxicity or enhance ICB efficacy. Consequently, fecal microbiota transplantation (FMT) has been applied to reduce radio- and immunotherapy-related toxicity and enhance their efficacies. Here, we have reviewed the currently available preclinical and clinical data in CRC treatment, with a focus on how the gut microbiome influences radio- and immunotherapy toxicity and efficacy and if these treatments could benefit from FMT.

RevDate: 2023-12-04
CmpDate: 2023-12-04

Mbaye B, Magdy Wasfy R, Borentain P, et al (2023)

Increased fecal ethanol and enriched ethanol-producing gut bacteria Limosilactobacillus fermentum, Enterocloster bolteae, Mediterraneibacter gnavus and Streptococcus mutans in nonalcoholic steatohepatitis.

Frontiers in cellular and infection microbiology, 13:1279354.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) has become a major public health issue as one of the leading causes of liver disease and transplantation worldwide. The instrumental role of the gut microbiota is emerging but still under investigation. Endogenous ethanol (EtOH) production by gut bacteria and yeasts is an emerging putative mechanism. Microbial metagenomics and culture studies targeting enterobacteria or yeasts have been reported, but no culturomics studies have been conducted so far.

AIM: To assess fecal EtOH and other biochemical parameters, characterize NASH-associated dysbiosis and identify EtOH-producing gut microbes associated with the disease, fecal samples from 41 NASH patients and 24 controls were analyzed. High-performance liquid chromatography (HPLC) was used for EtOH, glucose, total proteins, triglyceride and total cholesterol. Viable bacteria were assessed with microbial culturomics. Microbial genetic material was assessed using 16S metagenomics targeting the hypervariable V3V4 region.

RESULTS: Fecal EtOH and glucose was elevated in the stools of NASH patients (p < 0.05) but not triglyceride, total cholesterol or proteins. In culturomics, EtOH-producing Enterocloster bolteae and Limosilactobacillus fermentum were enriched in NASH. V3V4 16S rRNA amplicon sequencing confirmed the enrichment in EtOH-producing bacteria including L. fermentum, Mediterraneibacter gnavus and Streptococcus mutans, species previously associated with NASH and other dysbiosis-associated diseases. Strikingly, E. bolteae was identified only by culturomics. The well-known Lacticaseibacillus casei was identified in controls but never isolated in patients with NASH (p < 0.05).

CONCLUSION: Elevated fecal EtOH and glucose is a feature of NASH. Several different EtOH-producing gut bacteria may play an instrumental role in the disease. Culturomics and metagenomics, two complementary methods, will be critical to identify EtOH-producing bacteria for future diagnostic markers and therapeutic targets for NASH. Suppression of EtOH-producing gut microbes and L. casei administration are options to be tested in NASH treatment.

RevDate: 2023-12-04
CmpDate: 2023-12-04

Allegretti JR, Khanna S, P Feuerstadt (2023)

Practical Use of Fecal Microbiota Spores, Live BRPK for the Prevention of Recurrent Clostridioides difficile Infection.

The American journal of gastroenterology, 118(12):2106-2108.

RevDate: 2023-12-04

Marasco G, Cremon C, Barbaro MR, et al (2022)

Gut microbiota signatures and modulation in irritable bowel syndrome.

Microbiome research reports, 1(2):11.

Irritable bowel syndrome (IBS) affects approximately one tenth of the general population and is characterized by abdominal pain associated with abnormalities in bowel habits. Visceral hypersensitivity, abnormal intestinal motor function, mucosal immune activation, and increased intestinal permeability concur to its pathophysiology. Psychological factors can influence symptom perception at the central nervous system level. In addition, recent evidence suggests that dysbiosis may be a key pathophysiological factor in patients with IBS. Increasing understanding of the pathophysiological mechanisms translates into new and more effective therapeutic approaches. Indeed, in line with this evidence, IBS therapies nowadays include agents able to modulate gut microbiota function and composition, such as diet, prebiotics, probiotics, and antibiotics. In addition, in the last decade, an increasing interest in fecal microbiota transplantation has been paid. An in-depth understanding of the intestinal microenvironment through accurate faucal microbiota and metabolite analysis may provide valuable insights into the pathophysiology of IBS, finally shaping new tailored IBS therapies.

RevDate: 2023-12-02

Yuan QF, Wu HY, Chen XY, et al (2023)

Colonic Endoscopic Tubing Is Safe and Effective Approach for Washed Microbiota Transplantation in Autistic Children.

Gastroenterology research and practice, 2023:7838601.

BACKGROUND: Washed microbiota transplantation (WMT) as the improved methods of fecal microbiota transplantation has been employed as a therapeutic approach for ameliorating symptoms associated with autism spectrum disorder (ASD). In this context, colonic transendoscopic enteral tubing (TET) has been utilized as a novel procedure for administering WMT.

METHODS: Data of children with ASD who received WMT by TET were retrospectively reviewed, including bowel preparation methods, TET operation time, success rate, tube retention time, the comfort of children, adverse events, and parent satisfaction.

RESULTS: A total of 38 participants underwent 124 colonic TET catheterization procedures. The average time of TET operation was 15 minutes, and the success rate was 100% (124/124). There was no significant difference in TET operation time between high-seniority physicians and low-seniority physicians. In 123 procedures (99%), the TET tube allowed the completion of WMT treatment for 6 consecutive days. In 118 procedures (95.2%), the tube was detached spontaneously after the end of the treatment course, and the average TET tube retention time was 8 days. There was no incidence of tube blockage during the treatment course. No severe adverse events occurred during follow-up. Parents of all participants reported a high level of satisfaction with TET.

CONCLUSION: Colonic TET is a safe and feasible method for WMT in children with ASD.

RevDate: 2023-11-30

Bai M, Guo H, XY Zheng (2023)

Inflammatory bowel disease and Clostridium difficile infection: clinical presentation, diagnosis, and management.

Therapeutic advances in gastroenterology, 16:17562848231207280.

As a frequent complication of inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) was confirmed to not only aggravate the symptoms of IBD but also result in unexpected outcomes, including death. With the increasing prevalence rate of IBD and the updating of CDI diagnosis, the incidence of CDI in IBD patients is also seen rising. Although a detection method consisting of glutamate dehydrogenase immunoassay or nucleic acid amplification test and then toxin A/B enzyme immunoassay was recommended and widely adopted, the diagnosis of CDI in IBD is still a challenge because of the overlap between the symptoms of CDI in IBD and CDI itself. Vancomycin and fidaxomicin are the first-line therapy for CDI in IBD; however, the treatment has different effects due to the complexity of IBD patients' conditions and the choice of different treatment schemes. Although the use of fecal microbial transplantation is now in the ascendant for IBD management, the prospects are still uncertain and the prevention and treatment of the recurrence of CDI in IBD remain a clinical challenge. In this paper, the epidemiology, pathophysiology, clinical manifestation, prevention, and therapy of CDI in IBD were summarized and presented.

RevDate: 2023-11-30

Chang TE, Lee KC, Lee PC, et al (2023)

Assuring safety of fecal microbiota transplantation in the COVID-19 era: A single-center experience.

JGH open : an open access journal of gastroenterology and hepatology, 7(11):765-771 pii:JGH312979.

BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) is used to treat recurrent or refractory Clostridioides difficile infection (CDI). In the past, screening of fecal donors required surveillance of personal behavior, medical history, and diseases that could be transmitted by the blood or fecal-oral route. In addition, the exclusion of multidrug-resistant organisms (MDROs) has been recommended since 2018. This task has become more complicated in the era of the coronavirus disease-2019 (COVID-19) pandemic. To prevent fecal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is crucial to commence screening for SARS-CoV-2, alongside other traditional tests. Our aim was to investigate whether hidden carriers of SARS-CoV-2 were enrolled for stool donation, and the status of the presence or incidence of MDRO during fecal donation in Taiwan.

METHODS: Fecal products collected from March 2019 to December 2022 were tested for MDRO and nucleic acid amplification tests for SARS-CoV-2 using the pooling method. The period of fecal product collection crossed the time before and during the COVID pandemic in Taiwan.

RESULTS: A total of 151 fecal samples were collected. The fecal products were tested using polymerase chain reaction (PCR) to detect SARS-CoV-2. The results were negative for all stocks. This was similar to the results of MDRO testing. The safety of FMT products has been guaranteed during the pandemic.

CONCLUSION: Our FMT center produced MDRO-free and COVID-19-free products before and during the COVID-19 outbreak in Taiwan. Our protocol was effective for ensuring the safety of FMT products.

RevDate: 2023-11-30

Zhu Q, Wu K, Yang Q, et al (2023)

Advances in psoriasis and gut microorganisms with co-metabolites.

Frontiers in microbiology, 14:1192543.

This review summarizes the potential role of gut microbes and their metabolites as novel mediators of psoriasis, including their composition and function in disease pathogenesis, progression, and management. Gut microbiota network analysis, colony construction, and in vivo large-scale interaction experiments showed that different degrees of damage and repair in psoriasis, both in animals and humans, involve cross-border homeostasis of the microbial community. Which gut microbiota interactions are present in psoriasis and how they collaborate with immune cells and influence psoriasis development via the gut-skin axis remain incompletely elucidated. In this article, we review the latest information on the unique patterns of gut microbiota and co-metabolites involved in the pathogenesis of psoriasis and attempt to explore microbial-based therapeutic targets derived from mono-and polymicrobial probiotics, fecal microbiota transplantation, pharmacomicrobiomics, and dietary interventions as diagnostic or therapeutic approaches promising to provide new options and long-term management for psoriasis.

RevDate: 2023-11-30

Xiang W, Xiang H, Wang J, et al (2023)

Fecal microbiota transplantation: a novel strategy for treating Alzheimer's disease.

Frontiers in microbiology, 14:1281233.

Alzheimer's disease is a common neurological disorder, which has become one of the major factors affecting human health due to its serious impact on individuals, families and society. It has been confirmed that gut microbiota can affect the occurrence and development of Alzheimer's disease. Especially, fecal microbiota transplantation plays a positive role in the treatment of Alzheimer's disease. The mechanisms for improving Alzheimer's disease might include anti-inflammation and regulation of amyloid β-protein, synaptic plasticity, short-chain fatty acids, and histone acetylation. In this mini-review, the relationship between fecal microbiota transplantation and Alzheimer's disease was summarized. It is hoped that fecal microbiota transplantation would play a positive role in the prevention and treatment of Alzheimer's disease in the future.

RevDate: 2023-11-30

Crossland NA, Beck S, Tan WY, et al (2023)

Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice.

Gut microbes, 15(2):2288187.

Aging is a strong risk factor for colorectal cancer (CRC). It is well established that gut microbial dysbiosis can play a role in the etiology of CRC. Although the composition of the gut microbial community changes with age and is reported to become more pro-inflammatory, it is unclear whether such changes are also pro-tumorigenic for the colon. To address this gap, we conducted fecal microbiota transplants (FMT) from young (DY, ~6 wk) and old (DO, ~72 wk) donor mice into young (8 wk) recipient mice that were pre-treated with antibiotics. After initiating tumorigenesis with azoxymethane, recipients were maintained for 19 wk during which time they received monthly FMT boosters. Compared to recipients of young donors (RY), recipients of old donors (RO) had an approximately 3-fold higher prevalence of histologically confirmed colon tumors (15.8 vs 50%, Chi2 P = .03), approximately 2-fold higher proliferating colonocytes as well as significantly elevated colonic IL-6, IL-1β and Tnf-α. Transcriptomics analysis of the colonic mucosa revealed a striking upregulation of mitochondria-related genes in the RO mice, a finding corroborated by increased mitochondrial abundance. Amongst the differences in fecal microbiome observed between DY and DO mice, the genera Ruminoclostridium, Lachnoclostridium and Marvinbryantia were more abundant in DY mice while the genera Bacteroides and Akkermansia were more abundant in DO mice. Amongst recipients, Ruminoclostridium and Lachnoclostridium were higher in RY mice while Bacteroides was higher in RO mice. Differences in fecal microbiota were observed between young and old mice, some of which persisted upon transplant into recipient mice. Recipients of old donors displayed significantly higher colonic proliferation, inflammation and tumor abundance compared to recipients of young donors. These findings support an etiological role for altered gut microbial communities in the increased risk for CRC with increasing age and establishes that such risk can be transmitted between individuals.

RevDate: 2023-11-29

Liu H, Li J, Yuan J, et al (2023)

Fecal microbiota transplantation as a therapy for treating ulcerative colitis: an overview of systematic reviews.

BMC microbiology, 23(1):371.

AIM: The current overview on published systematic reviews (SRs) and meta-analysis (MAs) aimed to systematically gather, evaluate, and synthesize solid evidence for using fecal microbiota transplantation (FMT) to treat ulcerative colitis (UC).

METHODS: Relevant articles published before January 2023 were collected from Web of Science, Embase, PubMed, and Cochrane Library. Two authors used Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, PRISMA checklists, and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system were applied by two authors to independently evaluate the methodological quality, reporting quality, and evidence quality, respectively. Re-meta-analysis on the primary RCTs was conducted after excluding overlapping randomized controlled trials (RCTs).

RESULTS: Six SRs/MAs involving 12 primary RCTs and 544 participants were included. According to the AMSTAR-2 tool and PRISMA checklist, methodological quality and reporting quality of the included studies was overall satisfactory. The evidence quality of a great majority of outcomes was rated as moderate to high according to the GRADE system. Compared to placebo, the re-meta-analysis found a great advantage of use FMT in inducing combined clinical and endoscopic remission (OR 3.83 [2.31, 6.34]), clinical remission (3.31 [2.09, 5.25]), endoscopic remission (OR 3.75 [2.20, 6.39]), clinical response (OR 2.56 [1.64, 4.00]), and endoscopic response (OR 2.18 [1.12, 4.26]). Pooled data showed no significant difference in serious adverse events between patients receiving FMT and those receiving placebo (OR 1.53 [0.74, 3.19]). Evidence quality of the outcomes derived from re-meta-analysis was significantly higher after overcoming the limitations of previous SRs/MAs.

CONCLUSION: In conclusion, moderate- to high-quality evidence supported a promising use of FMT to safely induce remission in UC. However, further trials with larger sample size are still required to comprehensively analyze the delivery route, total dosage, frequency, and donor selection in FMT.

RevDate: 2023-11-29

Catalán V, J Gómez-Ambrosi (2023)

Will the manipulation of the gut microbiota be effective for the treatment of metabolic diseases?.

European journal of internal medicine pii:S0953-6205(23)00422-3 [Epub ahead of print].

RevDate: 2023-11-29

Gong X, Ma Y, Deng X, et al (2023)

Intestinal dysbiosis exacerbates susceptibility to the anti-NMDA receptor encephalitis-like phenotype by changing blood brain barrier permeability and immune homeostasis.

Brain, behavior, and immunity pii:S0889-1591(23)00364-1 [Epub ahead of print].

Changes in the intestinal microbiota have been observed in patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE). However, whether and how the intestinal microbiota is involved in the pathogenesis of NMDARE susceptibility needs to be demonstrated. Here, we first showed that germ-free (GF) mice that underwent fecal microbiota transplantation (FMT) from NMDARE patients, whose fecal microbiota exhibited low short-chain fatty acid content, decreased abundance of Lachnospiraceae, and increased abundance of Verrucomicrobiota, Akkermansia, Parabacteroides, Oscillospirales, showed significant behavioral deficits. Then, these FMT mice were actively immunized with an amino terminal domain peptide from the GluN1 subunit (GluN1356-385) to mimic the pathogenic process of NMDARE. We found that FMT mice showed an increased susceptibility to an encephalitis-like phenotype characterized by more clinical symptoms, greater pentazole (PTZ)-induced susceptibility to seizures, and higher levels of T2 weighted image (T2WI) hyperintensities following immunization. Furthermore, mice with dysbiotic microbiota had impaired blood-brain barrier integrity and a proinflammatory condition. In NMDARE-microbiota recipient mice, the levels of Evan's blue (EB) dye extravasation increased, ZO-1 and claudin-5 expression decreased, and the levels of proinflammatory cytokines (IL-1, IL-6, IL-17, TNF-α and LPS) increased. Finally, significant brain inflammation, mainly in hippocampal and cortical regions, with modest neuroinflammation, immune cell infiltration, and reduced expression of NMDA receptors were observed in NMDARE microbiota recipient mice following immunization. Overall, our findings demonstrated that intestinal dysbiosis increased NMDARE susceptibility, suggesting a new target for limiting the occurrence of the severe phenotype of NMDARE.

RevDate: 2023-11-30

Xie Z, Zhou J, Zhang X, et al (2023)

Clinical potential of microbiota in thyroid cancer therapy.

Biochimica et biophysica acta. Molecular basis of disease, 1870(2):166971 pii:S0925-4439(23)00337-X [Epub ahead of print].

Thyroid cancer is one of the most common tumors of the endocrine system because of its rapid and steady increase in incidence and prevalence. In recent years, a growing number of studies have identified a key role for the gut, thyroid tissue and oral microbiota in the regulation of metabolism and the immune system. A growing body of evidence has conclusively demonstrated that the microbiota influences tumor formation, prevention, diagnosis, and treatment. We provide extensive information in which oral, gut, and thyroid microbiota have an effect on thyroid cancer development in this review. In addition, we thoroughly discuss the various microbiota species, their potential functions, and the underlying mechanisms for thyroid cancer. The microbiome offers a unique opportunity to improve the effectiveness of immunotherapy and radioiodine therapy thyroid cancer by maintaining the right type of microbiota, and holds great promise for improving clinical outcomes and quality of life for thyroid cancer patients.

RevDate: 2023-11-29

Zhang X, Luo X, Tian L, et al (2023)

The gut microbiome dysbiosis and regulation by fecal microbiota transplantation: umbrella review.

Frontiers in microbiology, 14:1286429.

BACKGROUND: Gut microbiome dysbiosis has been implicated in various gastrointestinal and extra-gastrointestinal diseases, but evidence on the efficacy and safety of fecal microbiota transplantation (FMT) for therapeutic indications remains unclear.

METHODS: The gutMDisorder database was used to summarize the associations between gut microbiome dysbiosis and diseases. We performed an umbrella review of published meta-analyses to determine the evidence synthesis on the efficacy and safety of FMT in treating various diseases. Our study was registered in PROSPERO (CRD42022301226).

RESULTS: Gut microbiome dysbiosis was associated with 117 gastrointestinal and extra-gastrointestinal. Colorectal cancer was associated with 92 dysbiosis. Dysbiosis involving Firmicutes (phylum) was associated with 34 diseases. We identified 62 published meta-analyses of FMT. FMT was found to be effective for 13 diseases, with a 95.56% cure rate (95% CI: 93.88-97.05%) for recurrent Chloridoids difficile infection (rCDI). Evidence was high quality for rCDI and moderate to high quality for ulcerative colitis and Crohn's disease but low to very low quality for other diseases.

CONCLUSION: Gut microbiome dysbiosis may be implicated in numerous diseases. Substantial evidence suggests FMT improves clinical outcomes for certain indications, but evidence quality varies greatly depending on the specific indication, route of administration, frequency of instillation, fecal preparation, and donor type. This variability should inform clinical, policy, and implementation decisions regarding FMT.

RevDate: 2023-11-29

Sun H, Su X, Liu Y, et al (2023)

Roseburia intestinalis relieves intrahepatic cholestasis of pregnancy through bile acid/FXR-FGF15 in rats.

iScience, 26(12):108392 pii:S2589-0042(23)02469-0.

Previous research has demonstrated significant differences in intestinal flora between pregnant women with intrahepatic cholestasis of pregnancy (ICP) and healthy pregnant women. The objective of our study is to identify the key bacteria involved in ICP rats and explore the underlying mechanism. We established an ICP rat model and collected rat feces for metagenomic sequencing and found that Roseburia intestinalis (R.I) is the key bacteria in ICP. Transplantation of R.I improved phenotypes associated with ICP through the bile acid/farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) signaling pathway. We used the FXR antagonist Z-Guggulsterone (Z-Gu) to verify the key role of FXR in ICP and found that Z-Gu reversed the benefits of R.I on ICP rats. Our research highlights the important role of intestinal flora in the pathogenesis of ICP and provides a novel approach for its treatment.

RevDate: 2023-11-29

Mao Z, Hui H, Zhao X, et al (2023)

Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling.

Journal of pharmaceutical analysis, 13(10):1153-1167.

It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease (PD). Dioscin, a bioactive steroidal saponin, shows various activities. However, its effects and mechanisms against PD are limited. In this study, dioscin dramatically alleviated neuroinflammation and oxidative stress, and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus, Streptococcus, Bacteroides and Lactobacillus genera, which further inhibited bile salt hydrolase (BSH) activity and blocked bile acid (BA) deconjugation. Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent. In addition, non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis. Moreover, targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid and β-muricholic acid in feces and serum. In addition, ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice. Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5 (TGR5), glucagon-like peptide-1 receptor (GLP-1R), GLP-1, superoxide dismutase (SOD), and down-regulated NADPH oxidases 2 (NOX2) and nuclear factor-kappaB (NF-κB) levels. Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice, suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.

RevDate: 2023-11-29

Zhao W, Lei J, Ke S, et al (2023)

Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215).

EClinicalMedicine, 66:102315 pii:S2589-5370(23)00492-3.

BACKGROUND: Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence supported a close relationship between gut microbiome and anti-PD-1 efficacy. This study aimed to explore the efficacy and safety of the combination of fecal microbiota transplantation (FMT) and tislelizumab and fruquintinib in refractory MSS mCRC.

METHODS: In the phase II trial, MSS mCRC patients were administered FMT plus tislelizumab and fruquintinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), clinical benefit rate (CBR), safety and quality of life. Feces and peripheral blood were collected for exploratory biomarker analysis. This study is registered with Chictr.org.cn, identifier ChiCTR2100046768.

FINDINGS: From May 10, 2021 to January 17, 2022, 20 patients were enrolled. Median follow-up was 13.7 months. Median PFS was 9.6 months (95% CI 4.1-15.1). Median OS was 13.7 months (95% CI 9.3-17.7). Median DoR was 8.1 months (95% CI 1.7-10.6). ORR was 20% (95% CI 5.7-43.7). DCR was 95% (95% CI 75.1-99.9). CBR was 60% (95% CI 36.1-80.9). Nineteen patients (95%) experienced at least one treatment-related adverse event (TRAE). Six patients (30%) had grade 3-4 TRAEs, with the most common being albuminuria (10%), urine occult blood (10%), fecal occult blood (10%), hypertension (5%), hyperglycemia (5%), liver dysfunction (5%), hand-foot skin reaction (5%), and hypothyroidism (5%). No treatment-related deaths occurred. Responders had a high-abundance of Proteobacteria and Lachnospiraceae family and a low-abundance of Actinobacteriota and Bifidobacterium. The treatment did not change the structure of peripheral blood TCR repertoire. However, the expanded TCRs exhibited the characteristics of antigen-driven responses in responders.

INTERPRETATION: FMT plus tislelizumab and fruquintinib as third-line or above treatment showed improved survival and manageable safety in refractory MSS mCRC, suggesting a valuable new treatment option for this patient population.

FUNDING: This study was supported by the National Natural Science Foundation of China (82102954 to Wensi Zhao) and the Special Project of Central Government for Local Science and Technology Development of Hubei Province (ZYYD2020000169 to Yongshun Chen).

RevDate: 2023-11-29

Sharifa M, Ghosh T, Daher OA, et al (2023)

Unraveling the Gut-Brain Axis in Multiple Sclerosis: Exploring Dysbiosis, Oxidative Stress, and Therapeutic Insights.

Cureus, 15(10):e47058.

This comprehensive review delves into the intricate relationship between the gut microbiota and multiple sclerosis (MS), shedding light on the potential therapeutic avenues for this complex autoimmune disease. It emphasizes the multifactorial nature of MS, including genetic, environmental, and gender-related factors. Furthermore, the article highlights the emerging role of gut microbiota in MS pathophysiology, particularly in terms of gut dysbiosis, oxidative stress, and inflammasome activation within the gut-brain axis. This interplay raises intriguing questions about how the gut microbiota influences the onset and progression of MS. Environmental factors, such as diet and pollutants, add further layers of complexity to the connection between gut health and MS risk. This review also discusses promising therapeutic interventions, such as fecal microbiota transplantation, probiotics, dietary adjustments, and gut-derived metabolites that offer potential avenues for managing MS. It underscores the need for ongoing research to fully unravel the complexities of the role of the gut-brain axis in MS. Ultimately, this article provides a comprehensive exploration of the topic, offering hope for novel preventive and therapeutic strategies that could significantly improve the lives of individuals affected by this challenging autoimmune condition.

RevDate: 2023-11-29

Sehgal K, P Feuerstadt (2023)

The real efficacy of microbiota restoration following standard of care antimicrobial in patients with recurrent Clostridiodes difficile.

Translational gastroenterology and hepatology, 8:31 pii:tgh-08-23-46.

RevDate: 2023-11-29

Hu S, Zhao R, Xu Y, et al (2023)

Orally-administered nanomedicine systems targeting colon inflammation for the treatment of inflammatory bowel disease: latest advances.

Journal of materials chemistry. B [Epub ahead of print].

Inflammatory bowel disease (IBD) is a chronic and idiopathic condition that results in inflammation of the gastrointestinal tract, leading to conditions such as ulcerative colitis and Crohn's disease. Commonly used treatments for IBD include anti-inflammatory drugs, immunosuppressants, and antibiotics. Fecal microbiota transplantation is also being explored as a potential treatment method; however, these drugs may lead to systemic side effects. Oral administration is preferred for IBD treatment, but accurately locating the inflamed area in the colon is challenging due to multiple physiological barriers. Nanoparticle drug delivery systems possess unique physicochemical properties that enable precise delivery to the target site for IBD treatment, exploiting the increased permeability and retention effect of inflamed intestines. The first part of this review comprehensively introduces the pathophysiological environment of IBD, covering the gastrointestinal pH, various enzymes in the pathway, transport time, intestinal mucus, intestinal epithelium, intestinal immune cells, and intestinal microbiota. The second part focuses on the latest advances in the mechanism and strategies of targeted delivery using oral nanoparticle drug delivery systems for colitis-related fields. Finally, we present challenges and potential directions for future IBD treatment with the assistance of nanotechnology.

RevDate: 2023-11-29

Xiao Y, Feng J, Jia J, et al (2023)

Vitamin K1 ameliorates lipopolysaccharide-triggered skeletal muscle damage revealed by faecal bacteria transplantation.

Journal of cachexia, sarcopenia and muscle [Epub ahead of print].

BACKGROUND: Sepsis-associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis-induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis-associated muscle weakness.

METHODS: In a lipopolysaccharide (LPS)-induced inflammation mouse model, mice with different sensitivities to LPS-induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS-triggered muscle damage was investigated, and the underlying mechanism was explored.

RESULTS: Recipients exhibited varying LPS-triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF-1 (0.825 ± 0.063 vs. 0.304 ± 0.293, P = 0.0141) and MAFbx (1.055 ± 0.079 vs. 0.456 ± 0.3, P = 0.0092). Colonic tight junction proteins ZO-1 (0.550 ± 0.087 vs. 0.842 ± 0.094, P = 0.0492) and occludin (0.284 ± 0.057 vs. 0.664 ± 0.191, P = 0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P = 0.0195) and serum of the Res group (P = 0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy-related protein expression downregulated (P < 0.05). Meanwhile SIRT1 protein expression were upregulated (0.320 ± 0.035 vs. 0.685 ± 0.081, P = 0.0281) and pNF-κB protein expression were downregulated (0.815 ± 0.295 vs. 0.258 ± 0.130, P = 0.0308). PI3K (0.365 ± 0.142 vs. 0.763 ± 0.013, P = 0.0475), pAKT (0.493 ± 0.159 vs. 1.183 ± 0.344, P = 0.0254) and pmTOR (0.509 ± 0.088 vs. 1.110 ± 0.190, P = 0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels.

CONCLUSIONS: Vitamin K1 might ameliorate LPS-triggered skeletal muscle damage by antagonizing NF-κB-mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.

RevDate: 2023-11-28

Lin J, Xiong J, Jin Y, et al (2023)

Fecal microbiota transplantation through transendoscopic enteral tubing for inflammatory bowel disease: High acceptance and high satisfaction.

Journal of gastroenterology and hepatology [Epub ahead of print].

BACKGROUND AND AIM: Fecal microbiota transplantation (FMT) has been shown to positively affect the treatment of inflammatory bowel disease (IBD). However, the safety and efficacy of FMT may depend on the route of microbiota delivery. This study investigates the acceptance, satisfaction, and selection preference of a new delivery route, transendoscopic enteral tubing (TET), for treating IBD.

METHODS: A survey was conducted among patients with IBD from five medical centers across China. The objective was to assess their acceptance, subjective feelings, and major concerns regarding two types of TET: colonic TET and mid-gut TET. In addition, the survey also analyzed the factors affecting the selection of TET and TET types among these patients.

RESULTS: The final analysis included 351 questionnaires. Up to 76.6% of patients were willing to accept TET and preferred to choose colonic TET when they first learned about TET. Patients with longer disease duration, history of enema therapy, or enteral nutrition were more open to considering TET among IBD patients. After treatment, 95.6% of patients were satisfied with TET, including colonic TET (95.9%) and mid-gut TET (95.1%). Patients with a history of enema therapy and ulcerative colitis preferred colonic TET. In contrast, those with a history of enteral nutrition and Crohn's disease were willing to choose mid-gut TET. However, some patients hesitated to accept TET due to concerns about efficacy, safety, and cost.

CONCLUSIONS: TET was highly accepted and satisfied patients with IBD. Disease type and combination therapy influenced the choice of colonic or mid-gut TET.

RevDate: 2023-11-28

Li S, Chen T, Zhou Y, et al (2023)

Palmitic acid and trans-4-hydroxy-3-methoxycinnamate, the active ingredients of Yaobishu formula, reduce inflammation and pain by regulating gut microbiota and metabolic changes after lumbar disc herniation to activate autophagy and the Wnt/β-catenin pathway.

Biochimica et biophysica acta. Molecular basis of disease pii:S0925-4439(23)00338-1 [Epub ahead of print].

The imbalance in gut microbiota triggers an inflammatory response that spreads from the gut to the discs and is associated with lumbar disc herniation (LDH). In this study, we investigated the mechanism of palmitic acid (PA) and trans-4-hydroxy-3-methoxycinnamic acid (THMC) on microbiota, metabolic homeostasis, and autophagy after LDH. The LDH rat model was established by puncturing the exposed intervertebral disc. 16S rDNA was used to assess the gut microbiome composition. The microbial metabolites were analyzed by UPLC-MS. The mechanism of PA and THMC in LDH was explored by fecal microbiota transplantation (FMT). We found that Yaobishu, PA, THMC, and the positive control drug Celebrex attenuated intervertebral disc damage in LDH rats and downregulated TRPV1, IL-1β, and IL-18 expression. In addition, Yaobishu reduced Oscillospirales and Ruminococcaceae abundances after LDH. PA increased Bacilli's abundance while decreasing Negativicutes and Ruminococcaceae abundances. Metabolomics showed that Yaobishu increased 2-hexanone, methyl isobutyl ketone, 2-methylpentan-3-one, and nonadecanoic acid levels but decreased pantetheine and urocanate levels. PA and THMC reduced uridine and urocanate levels. Yaobishu, PA, and THMC activated autophagy and the Wnt/β-catenin pathway in LDH rats. Moreover, antibiotics abrogated these effects. FMT-PA and FMT-THMC activated autophagy and decreased IL-1β, IL-18, Wnt1, β-catenin, and TRPV1 expression. FMT-PA and FMT-THMC partially reversed the effects of 3-MA. Taken together, our data suggest that Yaobishu, PA, and THMC relieve inflammation and pain by remodeling the gut microbiota and restoring metabolic homeostasis after LDH to activate autophagy and the Wnt/β-catenin pathway, which provide a new therapeutic target for LDH in the clinic.

RevDate: 2023-11-28

Wu Y, Zhang Y, Xie B, et al (2023)

Esketamine mitigates cognitive impairment following exposure to LPS by modulating the intestinal flora/subdiaphragmatic vagus nerve/spleen axis.

International immunopharmacology, 126:111284 pii:S1567-5769(23)01611-9 [Epub ahead of print].

INTRODUCTION: Susceptibility to secondary infection often increases after primary infection. Secondary infections can lead to more severe inflammatory injuries; however, the underlying mechanisms are not yet fully elucidated.

OBJECTIVE: To investigate whether esketamine treatment immediately after primary lipopolysaccharide (LPS) exposure could alleviate cognitive impairment caused by secondary infection.

METHODS: Mice were injected intraperitoneally (IP) with LPS (5 mg/kg) 10 days apart. Esketamine (10, 15, or 30 mg/kg) was administered IP immediately after the primary LPS injection. Splenectomy or subdiaphragmatic vagotomy (SDV) was performed 7 days before secondary LPS exposure or broad-spectrum antibiotic administration.

RESULTS: Splenomegaly was observed after the primary LPS injection on Days 3 and 10. Splenomegaly was attenuated by treatment with 30 mg/kg esketamine. Esketamine treatment prevented increased plasma proinflammatory cytokines levels and cognitive dysfunction induced by secondary LPS exposure. Mice that underwent splenectomy or SDV had lower proinflammatory cytokines levels, higher hippocampal brain-derived neurotrophic factor (BDNF) levels, and improved cognitive function 1 day after secondary infection, which was not further improved by esketamine. Fecal microbiota transplantation (FMT) from endotoxic mice treated with esketamine attenuated hippocampal BDNF downregulation and cognitive dysfunction only in pseudo germ-free (PGF) mice without splenectomy. FMT with fecal suspensions from esketamine-treated endotoxic mice abrogated splenomegaly only in PGF mice without SDV. Blocking BDNF signaling blocked esketamine's ameliorating effects on secondary LPS exposure-induced cognitive dysfunction.

CONCLUSION: The intestinal flora/subdiaphragmatic vagus nerve/spleen axis-mediated hippocampal BDNF downregulation significantly affected secondary LPS-induced systemic inflammation and cognitive dysfunction. Esketamine preserves cognitive function via this mechanism.

RevDate: 2023-11-28

Gurczynski SJ, Lipinski JH, Strauss JY, et al (2023)

Horizontal transmission of gut microbiota attenuates mortality in lung fibrosis.

JCI insight pii:164572 [Epub ahead of print].

Pulmonary fibrosis is a chronic and often fatal disease. The pathogenesis is characterized by aberrant repair of lung parenchyma resulting in loss of physiological homeostasis, respiratory failure and death. The immune response in pulmonary fibrosis is dysregulated. The gut microbiome is a key regulator of immunity. The role of the gut microbiome in regulating the pulmonary immunity in lung fibrosis is poorly understood. Here, we determine the impact of gut microbiota on pulmonary fibrosis in C57BL/6 mice derived from different vendors (C57BL/6J and C57BL/6NCrl). We use germ free models, fecal microbiota transplantation and cohousing to transmit gut microbiota. Metagenomic studies of feces establish keystone species between sub-strains. Pulmonary fibrosis is microbiota dependent in C57BL/6 mice. Gut microbiota are distinct by β diversity (PERMANOVA P<0.001) and α diversity (P<0.0001). Mortality and lung fibrosis are attenuated in C57BL/6NCrl mice. Elevated CD4+ IL-10+ T cells and lower IL-6 occur in C57BL/6NCrl mice. Horizontal transmission of microbiota by cohousing attenuates mortality in C57BL/6J mice and promotes a transcriptionally altered pulmonary immunity. Temporal changes in lung and gut microbiota demonstrates that gut microbiota contribute largely to immunological phenotype. Key regulatory gut microbiota contribute to lung fibrosis generating rationale for human studies.

RevDate: 2023-11-28

Sun L, Li Z, Hu C, et al (2023)

Age-dependent changes in the gut microbiota and serum metabolome correlate with renal function and human aging.

Aging cell [Epub ahead of print].

Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging.

RevDate: 2023-11-28

Frith ME, Kashyap PC, Linden DR, et al (2023)

Microbiota-dependent early life programming of gastrointestinal motility.

bioRxiv : the preprint server for biology pii:2023.11.08.566304.

Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later - or not at all - showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility.

RevDate: 2023-11-28

Kim N, Ju IG, Jeon SH, et al (2023)

Inhibition of microfold cells ameliorates early pathological phenotypes by modulating microglial functions in Alzheimer's disease mouse model.

Journal of neuroinflammation, 20(1):282.

BACKGROUND: The gut microbiota has recently attracted attention as a pathogenic factor in Alzheimer's disease (AD). Microfold (M) cells, which play a crucial role in the gut immune response against external antigens, are also exploited for the entry of pathogenic bacteria and proteins into the body. However, whether changes in M cells can affect the gut environments and consequently change brain pathologies in AD remains unknown.

METHODS: Five familial AD (5xFAD) and 5xFAD-derived fecal microbiota transplanted (5xFAD-FMT) naïve mice were used to investigate the changes of M cells in the AD environment. Next, to establish the effect of M cell depletion on AD environments, 5xFAD mice and Spib knockout mice were bred, and behavioral and histological analyses were performed when M cell-depleted 5xFAD mice were six or nine months of age.

RESULTS: In this study, we found that M cell numbers were increased in the colons of 5xFAD and 5xFAD-FMT mice compared to those of wild-type (WT) and WT-FMT mice. Moreover, the level of total bacteria infiltrating the colons increased in the AD-mimicked mice. The levels of M cell-related genes and that of infiltrating bacteria showed a significant correlation. The genetic inhibition of M cells (Spib knockout) in 5xFAD mice changed the composition of the gut microbiota, along with decreasing proinflammatory cytokine levels in the colons. M cell depletion ameliorated AD symptoms including amyloid-β accumulation, microglial dysfunction, neuroinflammation, and memory impairment. Similarly, 5xFAD-FMT did not induce AD-like pathologies, such as memory impairment and excessive neuroinflammation in Spib[-/-] mice.

CONCLUSION: Therefore, our findings provide evidence that the inhibiting M cells can prevent AD progression, with therapeutic implications.

RevDate: 2023-11-27

Hart NH, Wallen MP, Farley MJ, et al (2023)

Exercise and the gut microbiome: implications for supportive care in cancer.

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 31(12):724.

PURPOSE: Growing recognition of the gut microbiome as an influential modulator of cancer treatment efficacy and toxicity has led to the emergence of clinical interventions targeting the microbiome to enhance cancer and health outcomes. The highly modifiable nature of microbiota to endogenous, exogenous, and environmental inputs enables interventions to promote resilience of the gut microbiome that have rapid effects on host health, or response to cancer treatment. While diet, probiotics, and faecal microbiota transplant are primary avenues of therapy focused on restoring or protecting gut function in people undergoing cancer treatment, the role of physical activity and exercise has scarcely been examined in this population.

METHODS: A narrative review was conducted to explore the nexus between cancer care and the gut microbiome in the context of physical activity and exercise as a widely available and clinically effective supportive care strategy used by cancer survivors.

RESULTS: Exercise can facilitate a more diverse gut microbiome and functional metabolome in humans; however, most physical activity and exercise studies have been conducted in healthy or athletic populations, primarily using aerobic exercise modalities. A scarcity of exercise and microbiome studies in cancer exists.

CONCLUSIONS: Exercise remains an attractive avenue to promote microbiome health in cancer survivors. Future research should elucidate the various influences of exercise modalities, intensities, frequencies, durations, and volumes to explore dose-response relationships between exercise and the gut microbiome among cancer survivors, as well as multifaceted approaches (such as diet and probiotics), and examine the influences of exercise on the gut microbiome and associated symptom burden prior to, during, and following cancer treatment.

RevDate: 2023-11-27

Choueiry F, Gold A, Xu R, et al (2023)

Secondary-Electrospray Ionization Mass Spectrometry-Based Online Analyses of Mouse Volatilome Uncover Gut Microbiome-Dictated Metabolic Changes in the Host.

Journal of the American Society for Mass Spectrometry [Epub ahead of print].

The symbiotic relationship between the gut microbial population is capable of regulating numerous aspects of host physiology, including metabolism. Bacteria can modulate the metabolic processes of the host by feeding on nutritional components within the lumen and releasing bioactive components into circulation. Endogenous volatile organic compound (VOC) synthesis is dependent on the availability of precursors found in mammalian metabolism. Herein, we report that microbial-mediated metabolic influences can alter the host volatilome and the prominent volatile changes can be uncovered by a novel volatile analysis technique named secondary electrospray ionization mass spectrometry. Mice were subjected to an antibiotic cocktail to deplete the microbiome and then inoculated with either single strain bacteria or fecal matter transplantation (FMT) to replete the microbial population in the gut. VOC sampling was achieved by using an advanced secondary electrospray ionization (SESI) source that directly mounted onto a Thermo Q-Exactive high-resolution mass spectrometer (HRMS). A principal component analysis summarizing the volatile profiles of the mice revealed independent clustering of each strain of the FMT-inoculated groups, suggesting unique volatile profiles. The Mummichog algorithm uncovered phenylalanine metabolism as a significantly altered metabolic profile in the volatilome of the microbiome-repleted mice. Our results indicated that the systemic metabolic changes incurred by the host are translated to unique volatile profiles correlated to the diversity of the microbial population colonized within the host. It is thus possible to take advantage of SESI-HRMS-based platforms for noninvasive screening of VOCs to determine the contribution of various microbial colonization within human gut that may impact host health.

RevDate: 2023-11-27

Liang D, Liu H, Jin R, et al (2023)

Escherichia coli triggers α-synuclein pathology in the LRRK2 transgenic mouse model of PD.

Gut microbes, 15(2):2276296.

Alpha-synuclein (α-syn) pathology is the hallmark of Parkinson's disease (PD). The leucine-rich repeat kinase 2 (LRRK2) gene is a major-effect risk gene for sporadic PD (sPD). However, what environmental factors may trigger the formation of α-syn pathology in carriers of LRRK2 risk variants are still unknown. Here, we report that a markedly increased abundance of Escherichia coli (E. coli) in the intestinal microbiota was detected in LRRK2 risk variant(R1628P or G2385R) carriers with sPD compared with carriers without sPD. Animal experiments showed that E. coli administration triggered pathological α-syn accumulation in the colon and spread to the brain via the gut-brain axis in Lrrk2 R1628P mice, due to the co-occurrence of Lrrk2 variant-induced inhibition of α-syn autophagic degradation and increased phosphorylation of α-syn caused by curli in E. coli-derived extracellular vesicles. Fecal microbiota transplantation (FMT) effectively ameliorated motor deficits and α-syn pathology in Lrrk2 R1628P mice. Our findings elaborate on the mechanism that E. coli triggers α-syn pathology in Lrrk2 R1628P mice, and highlight a novel gene-environment interaction pattern in LRRK2 risk variants. Even more importantly, the findings reveal the interplay between the specific risk gene and the matched environmental factors triggers the initiation of α-syn pathology in sPD.

RevDate: 2023-11-27

Garrett S, Asada MC, J Sun (2023)

Axin1's mystique in manipulating microbiome amidst colitis.

Gut microbes, 15(2):2286674.

Classically, Axin1 is considered a regulator of Wnt/β-catenin signaling. However, Axin1's roles in host-microbial interactions have been unknown. Our recent study has demonstrated that deletion of intestinal epithelial Axin1 in epithelial cells and Paneth cells protects the host against colitis by enhancing Akkermansia muciniphila. Loss of intestinal epithelial or Paneth cell Axin1 results in increased Wnt/β-catenin signaling, proliferation, and cell migration. This is associated with morphologically altered goblet and Paneth cells, including increased Muc2 and decreased lysozyme. Axin1 deletion specifically enriched Akkermansia muciniphila. Akkermansia muciniphila in Axin1 knockout mice is the driver of protection against DSS-induced inflammation. Here, we feature several significant conceptual changes, such as differences between Axin1 and Axin2, Axin1 in innate immunity and microbial homeostasis, and Axin1 reduction of Akkermansia muciniphila. We discuss an important trend in the field related to Paneth cells and tissue-specific Axin1 manipulation of microbiome in health and inflammation.

RevDate: 2023-11-27

Ahmad R, Kumar B, Thapa I, et al (2023)

Loss of claudin-3 expression increases colitis risk by promoting Gut Dysbiosis.

Gut microbes, 15(2):2282789.

Dysregulation of both the gut barrier and microbiota (dysbiosis) promotes susceptibility to and severity of Inflammatory Bowel Diseases (IBD). Leaky gut and dysbiosis often coexist; however, potential interdependence and molecular regulation are not well understood. Robust expression of claudin-3 (CLDN3) characterizes the gut epithelium, and studies have demonstrated a positive association between CLDN3 expression and gut barrier maturity and integrity, including in response to probiotics. However, the exact status and causal role of CLDN3 in IBD and regulation of gut dysbiosis remain unknown. Analysis of mouse and human IBD cohorts helped examine CLDN3 expression in IBD. The causal role was determined by modeling CLDN3 loss of expression during experimental colitis. 16S sequencing and in silico analysis helped examine gut microbiota diversity between Cldn3KO and WT mice and potential host metabolic responses. Fecal microbiota transplant (FMT) studies were performed to assess the role of gut dysbiosis in the increased susceptibility of Cldn3KO mice to colitis. A significant decrease in CLDN3 expression characterized IBD and CLDN3 loss of expression promoted colitis. 16S sequencing analysis suggested gut microbiota changes in Cldn3KO mice that were capable of modulating fatty acid metabolism and oxidative stress response. FMT from naïve Cldn3KO mice promoted colitis susceptibility in recipient germ-free mice (GFM) compared with GFM-receiving microbiota from WT mice. Our data demonstrate a critical role of CLDN3 in maintaining normal gut microbiota and inflammatory responses, which can be harnessed to develop novel therapeutic opportunities for patients with IBD.

RevDate: 2023-11-27

Ye H, Ghosh TS, Hueston CM, et al (2023)

Engraftment of aging-related human gut microbiota and the effect of a seven-species consortium in a pre-clinical model.

Gut microbes, 15(2):2282796.

Human aging is characterized by gut microbiome alteration and differential loss of gut commensal species associated with the onset of frailty. The administration of cultured commensal strains to replenish lost taxa could potentially promote healthy aging. To investigate the interaction of whole microbiomes and administered strains, we transplanted gut microbiota from a frail or healthy elderly subject into germ-free mice. We supplemented the frail-donor recipient group with a defined consortium of taxa (the "S7") that we identified by analyzing healthy aging subjects in our previous studies and whose abundance correlated with health-promoting dietary intervention. Inoculation with a frail or a healthy donor microbiome resulted in differential microbiota compositions in murine recipients 5 weeks post-transplantation. Fecal acetate levels were significantly higher in healthy donor recipient mice than in frail donor recipient mice after 4 weeks. However, the frailty-related phenotype was not replicated in recipient mice with single-dose microbiota transplantation from a healthy and a frail donor. Five S7 species colonized successfully in germ-free mice, with a relatively high abundance of Barnesiella intestinihominis and Eubacterium rectale. The engraftment of five S7 species in germ-free mice increased fecal acetate levels and reduced colon permeability and plasma TNF-ɑ concentration. Supplementation with the S7 in frail-microbiota recipient mice did not increase alpha-diversity but significantly increased the abundance of Barnesiella intestinihominis. S7 supplementation showed the potential for improving spatial reference memory in frail-microbiota recipient mice. Collectively, these data highlight the challenge of elderly microbiota engraftment in the germ-free mouse model but show promise for modulating the gut microbiome of frail elderly subjects by administering an artificial gut microbe consortium associated with healthy aging.

RevDate: 2023-11-27

Xiong Y, He Y, Chen Z, et al (2023)

Lactobacillus induced by irbesartan on spontaneously hypertensive rat contribute to its antihypertensive effect.

Journal of hypertension pii:00004872-990000000-00360 [Epub ahead of print].

OBJECTIVE: Hypertension is linked to gut dysbiosis. Here, the impact of the angiotensin receptor antagonist irbesartan on the gut microbiota of spontaneously hypertensive rats (SHR) were investigated. In addition, we assessed their contribution to its antihypertensive effect.

METHODS: Eight-week-old Wistar-Kyoto (WKY) rats and SHR were administered irbesartan for 8 weeks. Fecal microbiota transplantation (FMT) was performed from SHR treated with irbesartan or untreated SHR to recipient untreated SHR. The preventive effect of Lactobacillus on hypertension in SHR was evaluated. Blood pressure (BP) was calculated using a tail-sleeve sphygmomanometer. To better assess the composition of the gut microbiota, the V3-V4 region of the 16S rRNA gene was amplified while short-chain fatty acids (SCFAs) in feces were tested by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).

RESULTS: Irbesartan restored gut dysbiosis, increased the abundance of Lactobacillus, and improved anti-inflammatory ability, antioxidative ability, intestinal integrity, and intestinal inflammation in SHR. The microbiota in SHR-treated irbesartan could reduce BP and improve antioxidative ability and gut integrity in SHR. Lactobacillus johnsonii (L. johnsonii) and Lactobacillus reuteri (L. reuteri) reduced BP, restored gut dysbiosis and improved anti-inflammatory ability, antioxidative ability, intestinal integrity in SHR. Most notably, irbesartan, L. johnsonii, and L. reuteri can significantly increase SCFA content in SHR feces.

CONCLUSION: The current study demonstrated that irbesartan treatment ameliorated gut dysbiosis in SHR. Irbesartan induced alterations in gut microbiota, with increased prevalence of Lactobacillus.

RevDate: 2023-11-27

Hu S, Zhou J, Hao J, et al (2023)

Emodin ameliorates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis through the remodeling of gut microbiota composition.

American journal of physiology. Cell physiology [Epub ahead of print].

The relationship between gut microbiota and doxorubicin-induced cardiotoxicity (DIC) is becoming increasingly clear. Emodin (EMO), a naturally occurring anthraquinone, exerts cardioprotective effects and plays a protective role by regulating gut microbiota composition. Therefore, the protective effect of EMO against DIC injury and its underlying mechanisms are worth investigating. In this study, we analyzed the differences in the gut microbiota in recipient mice transplanted with different flora using 16S-rDNA sequencing, analyzed the differences in serum metabolites among groups of mice using a non-targeted gas chromatography-mass spectrometry coupling system, and assessed cardiac function based on cardiac morphological staining, cardiac injury markers, and ferroptosis indicator assays. We found EMO ameliorated DIC and ferroptosis, as evidenced by decreased myocardial fibrosis, cardiomyocyte hypertrophy, and myocardial disorganization; improved ferroptosis indicators; and the maintenance of normal mitochondrial morphology. The protective effect of EMO was eliminated by the scavenging effect of antibiotics on the gut microbiota. Through fecal microbiota transplantation (FMT), we found that EMO restored the gut microbiota disrupted by doxorubicin (DOX) to near-normal levels. This was evidenced by an increased proportion of Bacteroidota and a decreased proportion of Verrucomicrobiota. FMT resulted in changes in the composition of serum metabolites. Mice transplanted with EMO-improved gut microbiota showed better cardiac function and ferroptosis indices; however, these beneficial effects were not observed in Nrf2[-/-] mice. Overall, EMO exerted a protective effect against DIC by attenuating ferroptosis, and the above effects occurred by remodeling the composition of gut microbiota perturbed by DOX and required Nrf2 mediation.

RevDate: 2023-11-27
CmpDate: 2023-11-27

Ma J, Zhou M, Song Z, et al (2023)

Clec7a drives gut fungus-mediated host lipid deposition.

Microbiome, 11(1):264.

BACKGROUND: Compared to that of bacteria, the role of gut fungi in obesity development remains unknown.

RESULTS: Here, alterations in gut fungal biodiversity and composition were confirmed in obese pig models and high-fat diet (HFD)-fed mice. Antifungal drugs improved diet-induced obesity, while fungal reconstruction by cohousing or fecal microbiota transplantation maintained the obese phenotype in HFD-fed mice. Fungal profiling identified 5 fungal species associated with obesity. Specifically, Ascomycota_sp. and Microascaceae_sp. were reduced in obese mice and negatively correlated with fat content. Oral supplementation with fungi was sufficient to prevent and treat diet-induced obesity. Clec7a, which is involved in fungal recognition, was highly expressed in HFD-fed mice. The Clec7a agonist accelerated diet-induced obesity, while Clec7a deficieny in mice resulted in resistance to diet-induced obesity and blocked the anti-obese effect of antifungal drugs and fungi.

CONCLUSIONS: Taken together, these results indicate that gut fungi/Clec7a signaling is involved in diet-induced obesity and may have therapeutic implications as a biomarker for metabolic dysregulation in humans. Video Abstract.

RevDate: 2023-11-27

Parigi TL, Vieujean S, Paridaens K, et al (2023)

Efficacy, Safety, and Concerns on Microbiota Modulation, Antibiotics, Probiotics, and Fecal Microbial Transplant for Inflammatory Bowel Disease and Other Gastrointestinal Conditions: Results from an International Survey.

Microorganisms, 11(11):.

The gut microbiota play a pivotal role in human health. Dysbiosis, alterations in microbiota composition and function, is associated with gastrointestinal disorders, including inflammatory bowel disease (IBD). This international survey aimed to assess physicians' experiences, perceptions, and practices related to microbiome modulation for gastrointestinal conditions, with a focus on IBD. Results from 142 healthcare professionals, predominantly gastroenterologists, confirmed a consensus on the relevance of the gut microbiota in IBD pathogenesis. However, the utilization of microbial composition analysis and probiotics in clinical practice was limited, primarily due to the lack of standardized guidelines and supporting evidence. Physicians held conflicting views on antibiotics, recognizing their potential for inducing remission but also causing flares in IBD. Respondents also had varying opinions on the efficacy of fecal microbiota transplantation (FMT) for different gastrointestinal conditions, with higher confidence in FMT effectiveness for irritable bowel syndrome with diarrhea, pouchitis, and ulcerative colitis. Concerns on FMT included uncertainty about effect duration, administration intervals, and conflicting evidence. Donor selection was believed to be a crucial factor in FMT outcomes. This survey highlights the need for further research and evidence-based guidelines to optimize the use of microbiome-based therapies in clinical practice. As our understanding of the gut microbiome continues to evolve, these insights will contribute to more informed and personalized approaches to managing gastrointestinal disorders.

RevDate: 2023-11-27

Salandre A, Delannoy J, Goudiaby MTB, et al (2023)

A Simple In Vitro Test to Select Stools for Fecal Microbiota Transplantation to Limit Intestinal Carriage of Extensively Drug-Resistant Bacteria.

Microorganisms, 11(11):.

Treatment options for multidrug-resistant bacterial infections are limited and often ineffective. Fecal microbiota transplantation (FMT) has emerged as a promising therapy for intestinal multidrug-resistant bacterial decolonization. However, clinical results are discrepant. The aim of our pilot study was to evaluate the screening performance of a simple diagnostic tool to select fecal samples that will be effective in decolonizing the intestine. Fecal samples from 10 healthy subjects were selected. We developed an agar spot test to evaluate their antagonistic activity toward the growth of VanA Enterococcus faecium and OXA-48-producing Klebsiella pneumoniae, two of the most serious and urgent threats of antibiotic resistance. Most fecal samples were able to limit the growth of both bacteria in vitro but with large inter-individual variation. The samples with the highest and lowest antagonistic activity were used for FMT in a mouse model of intestinal colonization. FMT was not successful in reducing intestinal colonization with VanA Enterococcus faecium, whereas FMT performed with the fecal sample showing the highest activity on the agar spot test was able to significantly reduce the intestinal colonization of mice with Klebsiella pneumoniae OXA-48. The agar spot test could thus serve as a reliable screening tool to select stool samples with the best potential to eradicate/reduce multidrug-resistant bacteria carriage after FMT.

RevDate: 2023-11-27

Yan P, Luo S, Guo L, et al (2023)

Unraveling Intestinal Microbial Shifts in ESRD and Kidney Transplantation: Implications for Disease-Related Dysbiosis.

Microorganisms, 11(11):.

The composition of the gut microbiome is profoundly influenced by the accumulation of toxins in end-stage renal disease (ESRD) and specific medical treatments during kidney transplantation (KT). However, variations in results may arise due to factors such as genetics, dietary habits, and the strategy of anti-rejection therapy. Therefore, we conducted a 16S rRNA sequencing study to characterize intestinal microbiomes by using 75 fecal specimens obtained from 25 paired Chinese living donors (LDs) of kidneys and recipients before and after KT. Surprisingly, similar enterotypes were observed between healthy LDs and ESRD recipients. Nonetheless, following KT, the fecal communities of recipients exhibited distinct clustering, which was primarily characterized by Escherichia-Shigella and Streptococcus at the genus level, along with a reduction in the diversity of microbiota. To further explore the characteristics of gut microorganisms in early rejection episodes, two recipients with biopsy-proven borderline changes during follow-up were enrolled in a preliminary sub-cohort study. Our findings reveal a comparable construction of gut microbiota between ESRD patients and their healthy relatives while also highlighting the significant impact of KT on gut microbial composition.

RevDate: 2023-11-27
CmpDate: 2023-11-27

Zhou J, V Ho (2023)

Role of Baseline Gut Microbiota on Response to Fiber Intervention in Individuals with Irritable Bowel Syndrome.

Nutrients, 15(22):.

Irritable bowel syndrome (IBS) is one of the most prevalent functional gut disorders in the world. Partially hydrolyzed guar gum, a low-viscosity soluble fiber, has shown promise in the management of IBS-related symptoms. In this study, we aimed to determine if an individual's baseline gut microbiota impacted their response to a partially hydrolyzed guar gum intervention. Patients diagnosed with IBS undertook a 90-day intervention and follow-up. IBS symptom severity, tolerability, quality-of-life, and fecal microbiome composition were recorded during this study. Patients with normal microbiota diversity (Shannon index ≥ 3) showed significant improvements to IBS symptom scores, quality-of-life, and better tolerated the intervention compared to patients with low microbiota diversity (Shannon index < 3). Our findings suggest that an individual's baseline microbiome composition exerts a substantial influence on their response to fiber intervention. Future investigations should explore a symbiotic approach to the treatment of IBS.

RevDate: 2023-11-27
CmpDate: 2023-11-27

He S, Lin F, Hu X, et al (2023)

Gut Microbiome-Based Therapeutics in Critically Ill Adult Patients-A Narrative Review.

Nutrients, 15(22):.

The gut microbiota plays a crucial role in the human microenvironment. Dysbiosis of the gut microbiota is a common pathophysiological phenomenon in critically ill patients. Therefore, utilizing intestinal microbiota to prevent complications and improve the prognosis of critically ill patients is a possible therapeutic direction. The gut microbiome-based therapeutics approach focuses on improving intestinal microbiota homeostasis by modulating its diversity, or treating critical illness by altering the metabolites of intestinal microbiota. There is growing evidence that fecal microbiota transplantation (FMT), selective digestive decontamination (SDD), and microbiota-derived therapies are all effective treatments for critical illness. However, different treatments are appropriate for different conditions, and more evidence is needed to support the selection of optimal gut microbiota-related treatments for different diseases. This narrative review summarizes the curative effects and limitations of microbiome-based therapeutics in different critically ill adult patients, aiming to provide possible directions for gut microbiome-based therapeutics for critically ill patients such as ventilator-associated pneumonia, sepsis, acute respiratory distress syndrome, and COVID-19, etc.

RevDate: 2023-11-25

Xiao N, Ruan S, Mo Q, et al (2023)

The Effect of Sodium Benzoate on Host Health: Insight into Physiological Indexes and Gut Microbiota.

Foods (Basel, Switzerland), 12(22): pii:foods12224081.

Sodium benzoate (SB) is a common food preservative widely used in the food industry. However, the effects of SB intake on host health at different stages were still unclear. Hence, we investigated the impact of SB with three concentrations (150 mg/kg, 500 mg/kg and 1000 mg/kg) and at three stages (intake for 5-weeks, intake for 10-weeks and removal for 5 weeks) on host health in normal mice. The results showed that SB intake for 5 weeks slightly changed gut microbiota composition, but it significantly increased TG (only 150 mg/kg and 1000 mg/kg) and blood glucose levels (only 500 mg/kg) and promoted the secretion of interleukin (IL)-1β and IL-6 (p < 0.01). However, SB intake for 10 weeks mostly maintained normal glucolipid metabolism; although, IL-1β (p < 0.01) and IL-6 (p < 0.05) levels were also significantly increased and positively regulated the gut microbiota by significantly increasing the relative abundance of Lactobacillus and significantly decreasing the relative abundance of Ileibacterium. Meanwhile, the safety of SB for host metabolism and gut microbiota was also confirmed via a fecal microbiota transplantation experiment. In addition, we found that SB removal after 10 weeks of intake significantly increased the levels of blood glucose, insulin and HOMA-IR index, which might be attributed to gut microbiota dysbiosis. Mechanistically, these positive effects and negative effects had no close relationship with the concentration of short-chain fatty acids in the gut, which might be associated with metabolites of SB or special bacterial strains. In short, this work provided positive evidence for the safety of SB consumption within the recommended range.

RevDate: 2023-11-25

Boicean A, Birlutiu V, Ichim C, et al (2023)

Fecal Microbiota Transplantation in Liver Cirrhosis.

Biomedicines, 11(11): pii:biomedicines11112930.

The human gastrointestinal tract houses a diverse array of probiotic and pathogenic bacteria and any alterations in this microbial composition can exert a significant influence on an individual's well-being. It is well-established that imbalances in the gut microbiota play a pivotal role in the development of liver diseases. In light of this, a new adjuvant therapy for liver diseases could be regulating the intestinal microbiota. Through fecal microbiota transplantation, patients whose microbiomes are compromised are treated with stool from healthy donors in an attempt to restore a normal microbiome and alleviate their symptoms. A review of cross-sectional studies and case reports suggests that fecal microbiota transplants may offer effective treatment for chronic liver diseases. Adding to the potential of this emerging therapy, recent research has indicated that fecal microbiota transplantation holds promise as a therapeutic approach specifically for liver cirrhosis. By introducing a diverse range of beneficial microorganisms into the gut, this innovative treatment aims to address the microbial imbalances often observed in cirrhotic patients. While further validation is still required, these preliminary findings highlight the potential impact of fecal microbiota transplantation as a novel and targeted method for managing liver cirrhosis. We aimed to summarize the current state of understanding regarding this procedure, as a new therapeutic method for liver cirrhosis, as well as to explain its clinical application and future potential.

RevDate: 2023-11-24

Xu H, Fang F, Wu K, et al (2023)

Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia.

Microbiome, 11(1):262.

BACKGROUND: Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipidemic donors (FMT-dd) to study the causal role of gut microbiota in diet-induced dyslipidemia.

RESULTS: We demonstrated that FMT-dd reshaped the gut microbiota of mice by increasing Faecalibaculum and Ruminococcaceae UCG-010, which then elevated serum cholicacid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA), reduced bile acid synthesis and increased cholesterol accumulation via the hepatic farnesoid X receptor-small heterodimer partner (FXR-SHP) axis. Nevertheless, high-fat diet led to decreased Muribaculum in the humanized dyslipidemia mice induced by FMT-dd, which resulted in reduced intestinal hyodeoxycholic acid (HDCA), raised bile acid synthesis and increased lipid absorption via the intestinal farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis.

CONCLUSIONS: Our studies implicated that intestinal FXR is responsible for the regulation of lipid metabolism in diet-induced dyslipidemia mediated by gut microbiota-bile acid crosstalk. Video Abstract.

RevDate: 2023-11-24

Yang Y, Yan J, Li S, et al (2023)

Efficacy of fecal microbiota transplantation in type 2 diabetes mellitus: a systematic review and meta-analysis.

Endocrine [Epub ahead of print].

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is one of the common metabolic diseases worldwide, and studies have found significant differences in the composition and ratio of intestinal flora between patients with T2DM and normal glucose tolerance, and fecal microbiota transplantation (FMT) may modulate the composition of the intestinal microbiota thereby alleviating the hyperglycemic state. We conducted a meta-analysis and systematic review of existing randomized controlled trials (RCTs) to assess the efficacy of FMT in T2DM.

METHODS: We conducted a computer search of PubMed, Embase, The Cochrane Library, and Web of Science to screen randomized controlled trials studies on FMT treatment for T2DM and extracted data from studies that met inclusion criteria. RevMan 5.4 software and Stata 11 software was used for meta-analysis. The indexes of Hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial blood glucose (PBG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), body mass index (BMI), Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) were mainly evaluated after FMT treatment of T2DM patients, and the changes of intestinal flora were evaluated.

RESULTS: Four RCTs met the inclusion criteria and were included in the meta-analysis. Results of the meta-analysis showed that compared with the non-FMT group, FMT combined treatment could significantly reduce the PBG level in patients with type 2 diabetes (MD = -0.51, 95% CI: -1.42-0.40, P = 0.27). Compared with single FMT treatment, FMT combined treatment could reduce TG levels in patients with type 2 diabetes (MD = -0.60, 95% CI: -1.12~-0.07, P = 0.03). The levels of TG (MD = -0.26, 95% CI: -0.51~-0.02, P = 0.03), HOMA-IR (MD = -2.73, 95% CI: -4.71~0.75, P = 0.007) and HDL (MD = -0.06,95% CI: -0.10~-0.02, P = 0.003) were significantly decreased after treatment in the single FMT group. The level of TC (MD = -0.65, 95% CI: -1.00~-0.31, P = 0.0002) was significantly decreased after FMT combined treatment. Compared with before treatment, ALT (MD = -2.52, 95% CI: -3.86~-1.17, P = 0.0002) and DBP (MD = -2, 95% CI: -3.32~0.68, P = 0.003) levels decreased after treatment in the single FMT group and the FMT combined group. FPG (MD = -0.94, 95% CI: -1.86~-0.02, P = 0.04), TG (MD = -0.73, 95% CI: -1.42~-0.04, P = 0.04) and TC (MD = -0.94, 95% CI: -1.45~-0.43, P = 0.0003) were significantly decreased after combined drug and diet therapy. Secondly, FMT can promote the colonization and growth of donor-related flora in patients with type 2 diabetes.

CONCLUSION: In patients with type 2 diabetes mellitus, FMT treatment can reduce the levels of PBG, TG, HOMA-IR, TC, ALT, and DBP, especially in the combined treatment regimen. In addition, FMT can reshape the intestinal flora and establish the balance of dominant flora.

RevDate: 2023-11-24

de-Mendoza C, Pérez L, Rando A, et al (2023)

HTLV-1-associated myelopathy in Spain.

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 169:105619 pii:S1386-6532(23)00242-1 [Epub ahead of print].

BACKGROUND: HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1 carriers develop HTLV-1-associated myelopathy (HAM), a progressive subacute neurological disabling disease.

METHODS: We report the main features of patients diagnosed with HAM up to date in Spain, a non-endemic country with a relatively high migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic.

RESULTS: A total of 451 cases of HTLV-1 had been recorded in Spain until the end of year 2022. HAM had been diagnosed in 58 (12.9%). The current incidence is of 2-3 new cases per year. Women represent 76%. Mean age at diagnosis is 49 years-old. Nearly 60% are Latin Americans. Although sexual transmission is the most likely route of HTLV-1 acquisition, up to 6 individuals had been infected following solid organ transplantation. Rapid onset myelopathy developed in all but one of these transplant recipients from three HTLV-1-positive donors. HTLV-1 subtype 1a transcontinental was the only variant recognized in HAM patients. HTLV-1 proviral load was significantly greater in HAM patients than in asymptomatic HTLV-1 carriers (677 vs 104 HTLV-1 DNA copies/10[4] PBMC; p = 0.012). Symptom relief medications and physiotherapy have been the only treatment providing some benefit to HAM patients. Neither significant clinical nor virological efficacy was noticed using antiretrovirals in at least 9 HAM patients. Two thirds of HAM patients ended up in a wheelchair and with urinary/fecal sphincter incontinence.

CONCLUSION: HAM is the most frequent clinical manifestation of HTLV-1 infection in Spain, a non-endemic country. Middle aged women migrants from Latin America are the most frequently affected. Two thirds end up in a wheelchair despite using antiretroviral therapy.

RevDate: 2023-11-24

Duttagupta S, Hakozaki T, Routy B, et al (2023)

The Gut Microbiome from a Biomarker to a Novel Therapeutic Strategy for Immunotherapy Response in Patients with Lung Cancer.

Current oncology (Toronto, Ont.), 30(11):9406-9427.

The gastrointestinal microbiome has been shown to play a key role in determining the responses to cancer immunotherapy, including immune checkpoint inhibitor (ICI) therapy and CAR-T. In patients with non-small cell lung cancer (NSCLC), increasing evidence suggests that a microbiome composition signature is associated with clinical response to ICIs as well as with the development of immune-related adverse events. In support of this, antibiotic (ATB)-related dysbiosis has been consistently linked with the deleterious impact of ICI response, shortening the overall survival (OS) among patients on ATBs prior to ICI initiation. In parallel, several preclinical experiments have unravelled various strategies using probiotics, prebiotics, diet, and fecal microbiota transplantation as new therapeutic tools to beneficially shift the microbiome and enhance ICI efficacy. These approaches are currently being evaluated in clinical trials and have achieved encouraging preliminary results. In this article, we reviewed the recent studies on the gut microbiome as a potential biomarker and an adjuvant therapy to ICIs in NSCLC patients.

RevDate: 2023-11-24

DuPont HL, MMH Salge (2023)

The Importance of a Healthy Microbiome in Pregnancy and Infancy and Microbiota Treatment to Reverse Dysbiosis for Improved Health.

Antibiotics (Basel, Switzerland), 12(11):.

BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.

METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).

RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during pregnancy, cesarean delivery, prematurity, and formula feeding contribute to dysbiosis in the newborn. Microbiota therapy is an important approach to repair dysbiosis in pregnant women and their infants. Currently available probiotics can have favorable metabolic effects on mothers and infants, but these effects are variable. In research settings, reversal of infant dysbiosis can be achieved via vaginal seeding or FMT. Next generation probiotics in development should replace current probiotics and FMT.

CONCLUSIONS: The most critical phase of human microbiome development is in the first 2-3 years of life. Preventing and treating dysbiosis during pregnancy and early life can have a profound effect on an infant's later health.

RevDate: 2023-11-23

Chen YF, Li SC, EY Huang (2023)

Role of microbiota in radiation-induced small-bowel damage.

Journal of radiation research pii:7441102 [Epub ahead of print].

Radiation-induced gastrointestinal damage is a common acute radiation syndrome. Previous studies have highlighted that Galectin-1 and Interleukin-6 (IL-6) are associated with flaking of small intestinal villi and intestinal radioresistance. Therefore, our goal is to study whether gut bacteria regulated by galectin-1 or IL-6 can mitigate radiation-induced small intestine damage. In this study, differences between galectin-1, sgp130-regulated and wild-type (WT) mice were analyzed by microbiome array. The effects of the Firmicutes/Bacteroidetes (F/B) ratio and the proportion of bacterial distribution at the phylum level were observed after 18 Gy whole abdomen radiation. Fecal microbiota transplantation was used to implant radioresistant gut flora into WT mice, and the number of viable small intestinal crypt foci was observed by immunohistochemistry. Fecal transplantation from galectin-1 knockout and sgp130 transgenic mice, with higher radiation resistance, into WT mice significantly increased the number of surviving small intestinal crypts. This radiation resistance, generated through gene regulation, was not affected by the F/B ratio. We initially found that the small intestinal villi of WT mice receiving radioresistant mouse fecal bacteria demonstrated better repair outcomes after radiation exposure. These results indicate the need for a focus on the identification and application of superior radioresistant bacterial strains. In our laboratory, we will further investigate specific radioresistant bacterial strains to alleviate acute side effects of radiation therapy to improve the patients' immune ability and postoperative quality of life.

RevDate: 2023-11-23

Distante M, Rotulo S, Ranalli M, et al (2023)

Clusters of Disease Activity and Early Risk Factors of Clinical Course of Pediatric Crohn's Disease.

Inflammatory bowel diseases pii:7444933 [Epub ahead of print].

BACKGROUND: This study aimed to define clusters of disease activity and prognostic factors of disease course in a well-characterized cohort of children with Crohn's disease (CD).

METHODS: All patients from the SIGENP IBD (Italian Society of Pediatric Gastroenterology Hepatology and Nutrition Inflammatory Bowel Disease) registry with a 5-year follow-up and 6-monthly evaluation were included. Active disease was defined for each semester as follows: clinical activity (weighted Pediatric Crohn's Disease Activity Index ≥12.5 or Mucosal Inflammation Noninvasive Index ≥8) and active disease on endoscopy (Simple Endoscopic Score for Crohn's Disease >3 or fecal calprotectin >250 µg/g) or imaging. Formula-based clusters were generated based on previously published patterns in adults.

RESULTS: Data from 332 patients were analyzed. A total of 105 (32%) experienced a quiescent disease course; 49 (15%) and 31 (9%) a moderate-to-severe chronically active and chronic intermittent disease, respectively; 104 (31%) and 43 (13%) had active disease in the first 2 years after diagnosis and remission thereafter and vice versa, respectively. Surgery at diagnosis was significantly associated with a quiescent course (odds ratio [OR], 10.05; 95% confidence interval [CI], 3.05-25.22; P=.0005), while growth impairment at the diagnosis and active disease requiring corticosteroids at 6 months were inversely related to the quiescent group (OR, 0.48; 95% CI, 0.27-0.81; P= .007; and OR, 0.35; 95% CI, 0.16-0.71; P= .005, respectively). Perianal involvement at diagnosis and moderate-severe activity at 6 months correlated with disease progression (OR, 3.85; 95% CI, 1.20-12.85; P=.02).

CONCLUSIONS: During the first 5 years of follow-up, one-third of children with CD experience a quiescent course. However, another one-third have a moderate-to-severe disease course. Surgery at the diagnosis is related to a quiescent course, while growth impairment and lack of response to induction therapy correlate with more severe disease activity during follow-up.

RevDate: 2023-11-24
CmpDate: 2023-11-24

Li Z, Zhang X, Wu H, et al (2023)

Hydrangea paniculata coumarins attenuate experimental membranous nephritis by bidirectional interactions with the gut microbiota.

Communications biology, 6(1):1189.

Coumarins isolated from Hydrangea paniculata (HP) had a renal protective effect in experimental membranous nephritis (MN), but the mechanisms are not clear. Currently, we investigate whether the modulation of gut dysbiosis by HP contributes to its renal protection. Experimental MN rats were treated with HP for six weeks. Fecal 16S rDNA sequencing and metabolomics were performed. Fecal microbiota transplantation (FMT) was used for the evaluation study. The results demonstrate that deteriorated renal function and gut dysbiosis are found in MN rats, as manifested by a higher Firmicutes/Bacteroidetes ratio and reduced diversity and richness, but both changes were reversed by HP treatment. Reduced gut dysbiosis is correlated with improved colonic integrity and lower endotoxemia in HP-treated rats. HP normalized the abnormal level of fecal metabolites by increasing short-chain fatty acid production and hindering the production of uremic toxin precursors. FMT of HP-treated feces to MN animals moderately reduced endotoxemia and albuminuria. Moreover, major coumarins in HP were only biotransformed into more bioactive 7-hydroxycoumarin by gut microbiota, which strengthened the effect of HP in vivo. Depletion of the gut microbiota partially abolished its renal protective effect. In conclusion, the bidirectional interaction between HP and the gut microbiota contributes to its beneficial effect.

RevDate: 2023-11-22

Zhang C, Yu L, Ma C, et al (2023)

A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation.

Cell host & microbe pii:S1931-3128(23)00415-8 [Epub ahead of print].

Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria, can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B. longum, but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA-dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA-cluster-carrying B. longum, but not an abfA-deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA-cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies.

RevDate: 2023-11-24
CmpDate: 2023-11-24

Qian X, Hai W, Chen S, et al (2023)

Multi-omics data reveals aberrant gut microbiota-host glycerophospholipid metabolism in association with neuroinflammation in APP/PS1 mice.

Gut microbes, 15(2):2282790.

Numerous studies have described the notable impact of gut microbiota on the brain in Alzheimer's disease (AD) via the gut - brain axis. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of AD are limited. This study aimed to explore the potential mechanisms of gut microbiota in AD by integrating multi-omics data. In this study, APP/PS1 and WT mice at nine months of age were used as study mouse model. Cognitive function was assessed using the Morris water maze test. The levels of Aβ plaque and neuroinflammation in the brain were detected using immunofluorescence and PET/CT. In addition, we not only used 16S rRNA gene sequencing and metabolomics to explore the variation characteristics of gut microbiota and serum metabolism abundance, but also combined spatial metabolomics and transcriptomics to explore the change in the brain and identify their potential correlation. APP/PS1 mice showed significant cognitive impairment and amyloid-β deposits in the brain. The abundance of gut microbiota was significantly changed in APP/PS1 mice, including decreased Desulfoviobrio, Enterococcus, Turicibacter, and Ruminococcus and increased Pseudomonas. The integration of serum untargeted metabolomics and brain spatial metabolomics showed that glycerophospholipid metabolism was a common alteration pathway in APP/PS1 mice. Significant proliferation and activation of astrocyte and microglia were observed in APP/PS1 mice, accompanied by alterations in immune pathways. Integration analysis and fecal microbiota transplantation (FMT) intervention revealed potential association of gut microbiota, host glycerophospholipid metabolism, and neuroinflammation levels in APP/PS1 mice.

RevDate: 2023-11-22

Zhang M, Yang T, Li R, et al (2023)

Gut microbiota of Suncus murinus, a naturally obesity-resistant animal, improves the ecological diversity of the gut microbiota in high-fat-diet-induced obese mice.

PloS one, 18(11):e0293213.

BACKGROUND: The global population of obese individuals is increasing, affecting human health. High-fat diets are a leading cause of this epidemic, and animal models, such as mice, are often used in related research. Obese individuals have a different gut microbiota composition from non-obese ones, characterized by a sizeable population of certain bacteria associated with fat storage. The gut microbiome plays a significant role in regulating human physiological and metabolic functions. Links between obesity, high-fat diets and gut microbiota have become hot topics of discussion. Recently, research on the modulation of the gut microbiota has focused on fecal microbiota transplantation (FMT), which has been recognized as an effective method of studying the function of gut microbiota.

OBJECTIVES: The purpose of this study was to investigate how the gut microbiota of Suncus murinus, a naturally obesity-resistant animal, through FMT, affected the ecology of the gut microbiota of high-fat diet induced obese mice.

METHODS: In this study, Suncus murinus was used as a donor for FMT. High-fat diet induced C57BL/6NCrSIc mice were used as recipients, the body weight changes were measured and changes in their gut flora were analyzed using a 16S rRNA gene analysis.

RESULTS: The study found that, after the FMT procedure, the FMT group tended to have a lower body weight than the control group. At the phylum level, the most predominant phyla in all groups were Firmicutes and Proteobacteria, while Deferribacteres was not detected in the FMT or antibiotic administration groups, and Bacteroidetes was not present in the antibiotic administration group. At the genus level, the FMT group had significantly lower OTU richness than the control group but greater diversity than the control group.

CONCLUSIONS: These results indicate that FMT from Suncus murinus can help reorganize and improve the gut microbiota of mice in a balanced and diverse ecosystem.

RevDate: 2023-11-22

Boatman S, Kaiser T, Nalluri-Butz H, et al (2023)

Diet-induced shifts in the gut microbiota influence anastomotic healing in a murine model of colonic surgery.

Gut microbes, 15(2):2283147.

Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.

RevDate: 2023-11-22

Zhang S, Huang Y, Lu G, et al (2023)

Comparison between washed microbiota transplantation and infliximab: Medical cost during long-term management in patients with inflammatory bowel disease.

Journal of the Chinese Medical Association : JCMA pii:02118582-990000000-00303 [Epub ahead of print].

BACKGROUND: Both infliximab (IFX) and fecal microbiota transplantation (FMT) have shown the efficacy for inflammatory bowel disease (IBD). However, there has no head-to-head study on the cost-value of the such treatments on IBD. This study aimed to compare the medical costs using IFX and the new method of FMT (washed microbiota transplantation, WMT) in the long-term management for IBD under the current health economic condition in China.

METHODS: Patients with IBD who underwent initial WMT via upper gastrointestinal endoscopy, mid-gut tube, or colonic transendoscopic enteral tubing at a university hospital between April 2013 and August 2021 and achieved the long-term sustainment with WMT or WMT combined with mesalazine until August 2022 were recruited in the real-world. The costs and hospitalizations were analyzed among two therapies mentioned above and IFX standard therapy. The charge of WMT was stable in the long term at our center, and the charge of IFX came from virtual statistics publicized by China Healthcare Security.

RESULTS: 60 eligible patients with IBD were included in the study. The long-term costs of patients using WMT monotherapy annually or per hospitalization were lower than those on WMT combined with mesalazine respectively (p < 0.001, respectively). The cumulative costs of IFX at the time of 0.52 and 0.85 years exceeded that of the above WMT respectively (p < 0.001, respectively). Besides, patients on WMT monotherapy paid 51.1k CNY annually in the non-sustain phase but cut down the costs by 7.2k CNY and duration of hospitalization by 5.1 days per hospitalization when reaching the goal of sustainment.

CONCLUSION: This study demonstrated that WMT could dramatically reduce the cost and duration of hospitalizations in the long-term sustainment in the current Chinese IBD cohort. Compared with IFX, WMT could be a good way for the patients with IBD achieving long-term sustainment and saving medical costs.

RevDate: 2023-11-21

Berryhill BA, Burke KB, Fontaine J, et al (2023)

Enteric Populations of Escherichia coli are Likely to be Resistant to Phages Due to O Antigen Production.

bioRxiv : the preprint server for biology pii:2023.11.08.566299.

UNLABELLED: Bioinformatic and experimental data show that bacteriophages are ubiquitous in human enteric microbiomes. However, there are gaps in understanding the contribution of these viruses in shaping the bacterial strain and species composition of the gut microbiome and how these phages are maintained over time. To address these questions, we adapted and analyzed the properties of a mathematical model of the population and evolutionary dynamics of bacteria and phage and performed experiments with Escherichia coli and phages isolated from four fecal microbiota transplantation (FMT) doses as representative samples of non-dysbiotic enteric microbiota. Our models predict and experiments confirm that due to production of the O antigen, E. coli in the enteric microbiome are likely to be resistant to infection with co-occurring phages. However, phages can be maintained in these populations in high densities due to high rates of transition between resistant and sensitive states, which we call leaky resistance. Based on these models and observations, we postulate that the phages found in the human gut are likely to play little role in shaping the composition of E. coli in the enteric microbiome in healthy individuals. How general this is for other species of bacteria in enteric microbiota is not yet clear, although O antigen production is broadly conserved across many taxa.

SIGNIFICANCE STATEMENT: Little is known about the role that bacteriophages play in shaping the bacterial species and strain composition in the human gut microbiome or how they are maintained over time in this dynamic environment. Here we show that Escherichia coli isolated from fecal samples are likely to be resistant to their co-existing phages due to production of the O antigen. However, phages can be maintained in populations of mostly resistant bacteria if there is a rapid transition between resistant and sensitive states, a state called leaky resistance. Based on these results, we postulate that bacteriophages are likely playing little role of shaping the abundance and diversity of bacteria in the human gut microbiome in healthy individuals.

RevDate: 2023-11-20

Oliva-Hemker M, Kahn SA, Steinbach WJ, et al (2023)

Fecal Microbiota Transplantation: Information for the Pediatrician.

Pediatrics pii:195486 [Epub ahead of print].

Fecal microbiota transplantation (FMT) involves the delivery of an entire microbial community from a healthy donor to a recipient with the intention of ameliorating or curing a specific disease. Current evidence strongly supports a role for FMT in the treatment of Clostridiodes difficile infection, with cure rates of approximately 80% to 90%. This success has led to increasing attention for FMT as a potential therapeutic intervention for other conditions associated with disturbances of the intestinal microbiome, including inflammatory bowel diseases, autism spectrum disorder, and obesity. This clinical report endorses the joint society statement by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and the European Society for Pediatric Gastroenterology, Hepatology and Nutrition and is meant to provide the general pediatrician with a broad overview to enable appropriate guidance to families seeking FMT as treatment of a child's condition.

RevDate: 2023-11-20

Arora U, Kedia S, V Ahuja (2023)

The practice of fecal microbiota transplantation in inflammatory bowel disease.

Intestinal research pii:ir.2023.00085 [Epub ahead of print].

Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn's disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.

RevDate: 2023-11-22

Zheng M, Ye H, Yang X, et al (2023)

Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis.

Brain, behavior, and immunity, 115:565-587 pii:S0889-1591(23)00349-5 [Epub ahead of print].

Obesity is a risk factor for cognitive dysfunction and neurodegenerative disease, including Alzheimer's disease (AD). The gut microbiota-brain axis is altered in obesity and linked to cognitive impairment and neurodegenerative disorders. Here, we targeted obesity-induced cognitive impairment by testing the impact of the probiotic Clostridium butyricum, which has previously shown beneficial effects on gut homeostasis and brain function. Firstly, we characterized and analyzed the gut microbial profiles of participants with obesity and the correlation between gut microbiota and cognitive scores. Then, using an obese mouse model induced by a Western-style diet (high-fat and fiber-deficient diet), the effects of Clostridium butyricum on the microbiota-gut-brain axis and hippocampal cognitive function were evaluated. Finally, fecal microbiota transplantation was performed to assess the functional link between Clostridium butyricum remodeling gut microbiota and hippocampal synaptic protein and cognitive behaviors. Our results showed that participants with obesity had gut microbiota dysbiosis characterized by an increase in phylum Proteobacteria and a decrease in Clostridium butyricum, which were closely associated with cognitive decline. In diet-induced obese mice, oral Clostridium butyricum supplementation significantly alleviated cognitive impairment, attenuated the deficit of hippocampal neurite outgrowth and synaptic ultrastructure, improved hippocampal transcriptome related to synapses and dendrites; a comparison of the effects of Clostridium butyricum in mice against human AD datasets revealed that many of the genes changes in AD were reversed by Clostridium butyricum; concurrently, Clostridium butyricum also prevented gut microbiota dysbiosis, colonic barrier impairment and inflammation, and attenuated endotoxemia. Importantly, fecal microbiota transplantation from donor-obese mice with Clostridium butyricum supplementation facilitated cognitive variables and colonic integrity compared with from donor obese mice, highlighting that Clostridium butyricum's impact on cognitive function is largely due to its ability to remodel gut microbiota. Our findings provide the first insights into the neuroprotective effects of Clostridium butyricum on obesity-associated cognitive impairments and neurodegeneration via the gut microbiota-gut-brain axis.

RevDate: 2023-11-19

Liang Y, Liu D, Li Y, et al (2023)

Maternal polysorbate 80 intake promotes offspring metabolic syndrome through vertical microbial transmission in mice.

The Science of the total environment, 909:168624 pii:S0048-9697(23)07252-2 [Epub ahead of print].

Polysorbate 80 (P80) is an emulsifier extensively produced, consumed and discharged into the environment, consequently making human exposure inevitable. Despite evidence suggesting that P80 intake causes metabolic syndrome (MS) in mammals via microbial perturbation, limited data exist on its transgenerational impacts on offspring. In this study, we found that maternal P80 treatment impaired intestinal barrier integrity, leading to metabolic endotoxemia, low-grade inflammation and MS-related symptoms in C57BL/6J female offspring. Further analysis of the gut microbiome revealed MS-related changes in the offspring of P80-treated dams. Fecal microbiota transplantation experiment confirmed the crucial role of the altered microbiome in offspring in the transgenerational impacts of P80. Furthermore, we found that the P80-induced microbial alterations were directly transmitted from P80-treated mothers to their offspring and that interrupting vertical microbial transmission through cesarean section and foster nursing blocked the transgenerational impacts of P80 on the offspring microbiome and metabolic health. Moreover, maternal pectin supplementation also effectively mitigated P80-induced microbial alterations and MS-associated phenotypes in offspring. Together, our results indicated that maternal P80 intake could impair offspring metabolic health through the mother-to-offspring transmission of the microbiome, and maternal pectin supplementation might be a promising strategy for reducing the adverse effects of P80.

RevDate: 2023-11-18

Xi D, Liu P, Feng Y, et al (2023)

Fecal microbiota transplantation regulates the microbiota-gut-spinal cord axis to promote recovery after spinal cord injury.

International immunopharmacology, 126:111212 pii:S1567-5769(23)01539-4 [Epub ahead of print].

Spinal cord injury (SCI) is devastating for patients, and currently lacks effective treatments. Dysbiosis commonly occurs after SCI and has significant immunomodulatory effects, but its impact on recovery remains unclear. The current study investigated the effects and mechanisms of fecal microbiota transplantation (FMT) in SCI. FMT was administered in a rat model of SCI and spinal pathology, inflammatory cytokines, and gut microbiome composition were assessed. Flow cytometry identified a source of interleukin (IL)-17 in spinal cord tissues, and carboxyfluorescein succimidyl ester labeling tracked γδ T cell migration. In vitro coculture was used to analyze the regulatory mechanisms of γδ T cells. Seahorse analysis was used to profile dendritic cell (DC) metabolism. Here we show that FMT improved spinal pathology and dampened post-injury inflammation. It also corrected post-SCI dysbiosis, increasing levels of the beneficial bacterium Akkermansia. The therapeutic effects of FMT were mediated by IL-17 produced by γδ T cells. FMT regulated γδ T cells via DC-T regulatory cell interaction, and induced metabolic reprogramming in DCs. These findings suggest that FMT represents a promising therapeutic approach for SCI, with potential to target IL-17[+] γδ T cells. Elucidating the interconnected pathways between microbiota, immunity, and the spinal cord may facilitate novel treatment strategies.

RevDate: 2023-11-18

Kujawa D, Laczmanski L, Budrewicz S, et al (2023)

Targeting gut microbiota: new therapeutic opportunities in multiple sclerosis.

Gut microbes, 15(2):2274126.

Multiple sclerosis (MS) causes long-lasting, multifocal damage to the central nervous system. The complex background of MS is associated with autoimmune inflammation and neurodegeneration processes, and is potentially affected by many contributing factors, including altered composition and function of the gut microbiota. In this review, current experimental and clinical evidence is presented for the characteristics of gut dysbiosis found in MS, as well as for its relevant links with the course of the disease and the dysregulated immune response and metabolic pathways involved in MS pathology. Furthermore, therapeutic implications of these investigations are discussed, with a range of pharmacological, dietary and other interventions targeted at the gut microbiome and thus intended to have beneficial effects on the course of MS.

RevDate: 2023-11-17

Wang Y, Wang Z, Q Lu (2023)

Microbiome dynamics in rheumatic diseases.

Current opinion in rheumatology pii:00002281-990000000-00095 [Epub ahead of print].

PURPOSE OF REVIEW: Rheumatic disease are characterized by their autoimmune nature, frequently affecting joints, bones, muscles, blood vessels, and connective tissues. The onset of these conditions typically unfolds gradually and subtly. It is noteworthy that individuals with rheumatic diseases often experience shifts in their microbiome, specifically on mucosal surfaces. The purpose of this review is to delve into the intricate interplay between the microbiome, encompassing bacteria, viruses and fungi, and its role in the development and aggravation of various rheumatic diseases. Additionally, it aims to offer insights into microbiome-centered therapeutic approaches for patients in the field of rheumatology.

RECENT FINDINGS: The advent of next-generation sequencing has significantly improved our understanding of microbiome changes. Numerous studies have consistently revealed a strong link between rheumatism and the microbiome, especially in the oral and gut microbiota.

SUMMARY: A deeper comprehension of the microbiome's connection to rheumatism holds potential for enhancing disease diagnosis and treatment. Targeted therapeutic approaches, including probiotics, fecal microbiota transplantation, and combination therapies with medications, offer promising avenues for disease management.

RevDate: 2023-11-18

Guo J, Zhou B, Niu Y, et al (2023)

Engineered probiotics introduced to improve intestinal microecology for the treatment of chronic diseases: present state and perspectives.

Journal of diabetes and metabolic disorders, 22(2):1029-1038.

PURPOSE: Correcting intestinal microecological imbalance has become one of the core strategies to treat chronic diseases. Some traditional microecology-based therapies targeting intestine, such as prebiotic therapy, probiotic therapy and fecal microbiota transplantation therapy, have been used in the prevention and treatment of clinical chronic diseases, which still facing low safety and poor controllability problems. The development of synthetic biology technology has promoted the development of intestinal microecology-based therapeutics for chronic diseases, which exhibiting higher robustness and controllability, and become an important part of the next generation of microecological therapy. The purpose of this review is to summarize the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases.

METHODS: The available literatures were searched to find out experimental studies and relevant review articles on the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases from year 1990 to 2023.

RESULTS: Evidence proposed that synthetic biology has been applied in the intestinal microecology-based therapeutics for chronic diseases, covering metabolic diseases (e.g. diabetes, obesity, nonalcoholic fatty liver disease and phenylketonuria), digestive diseases (e.g. inflammatory bowel disease and colorectal cancer), and neurodegenerative diseases (e.g. Alzheimer's disease and Parkinson's disease).

CONCLUSION: This review summarizes the application of synthetic biology in intestinal microecology-based therapeutics for major chronic diseases and discusses the opportunities and challenges in the above process, providing clinical possibilities of synthetic biology technology applied in microecological therapies.

RevDate: 2023-11-19

Khan FA, Pandupuspitasari NS, Huang C, et al (2023)

Unlocking gut microbiota potential of dairy cows in varied environmental conditions using shotgun metagenomic approach.

BMC microbiology, 23(1):344.

Food security and environmental pollution are major concerns for the expanding world population, where farm animals are the largest source of dietary proteins and are responsible for producing anthropogenic gases, including methane, especially by cows. We sampled the fecal microbiomes of cows from varying environmental regions of Pakistan to determine the better-performing microbiomes for higher yields and lower methane emissions by applying the shotgun metagenomic approach. We selected managed dairy farms in the Chakwal, Salt Range, and Patoki regions of Pakistan, and also incorporated animals from local farmers. Milk yield and milk fat, and protein contents were measured and correlated with microbiome diversity and function. The average milk protein content from the Salt Range farms was 2.68%, with an average peak milk yield of 45 litters/head/day, compared to 3.68% in Patoki farms with an average peak milk yield of 18 litters/head/day. Salt-range dairy cows prefer S-adenosyl-L-methionine (SAMe) to S-adenosyl-L-homocysteine (SAH) conversion reactions and are responsible for low milk protein content. It is linked to Bacteroides fragilles which account for 10% of the total Bacteroides, compared to 3% in the Patoki region. The solid Non-Fat in the salt range was 8.29%, whereas that in patoki was 6.34%. Moreover, Lactobacillus plantarum high abundance in Salt Range provided propionate as alternate sink to [H], and overcoming a Methanobrevibacter ruminantium high methane emissions in the Salt Range. Furthermore, our results identified ruminant fecal microbiomes that can be used as fecal microbiota transplants (FMT) to high-methane emitters and low-performing herds to increase farm output and reduce the environmental damage caused by anthropogenic gases emitted by dairy cows.

RevDate: 2023-11-17

Drefs M, Schardey J, von Ehrlich-Treuenstätt V, et al (2022)

Endoscopic Treatment Options for Gastrointestinal Leaks.

Visceral medicine, 38(5):311-321.

BACKGROUND: Spontaneous or postoperative gastrointestinal defects are still life-threatening complications with elevated morbidity and mortality. Recently, endoscopic treatment options - up and foremost endoscopic vacuum therapy (EVT) - have become increasingly popular and have shown promising results in these patients.

METHODS: We performed an electronic systematic search of the MEDLINE databases (PubMed, EMBASE, and Cochrane) and searched for studies evaluating endoscopic options for the treatment of esophageal and colorectal leakages and/or perforations until March 2022.

RESULTS: The closure rate of both esophageal and colorectal defects by EVT is high and even exceeds the results of surgical revision in parts. Out of all endoscopic treatment options, EVT shows most evidence and appears to have the highest therapeutic success rates. Furthermore, EVT for both indications had a low rate of serious complications without relevant in-hospital mortality. In selected patients, EVT can be applied without fecal diversion and transferred to an outpatient setting.

CONCLUSION: Despite multiple endoscopic treatment options, EVT is increasingly becoming the new gold standard in endoscopic treatment of extraperitoneal defects of the upper and lower GI tract with localized peritonitis or mediastinitis and without close proximity to major blood vessels. However, further prospective, comparative studies are needed to strengthen the current evidence.

RevDate: 2023-11-17

Zeng X, Liao Y, Qiao X, et al (2023)

Novel NIR-II fluorescent probes for biliary atresia imaging.

Acta pharmaceutica Sinica. B, 13(11):4578-4590.

Biliary atresia is a rare infant disease that predisposes patients to liver transplantation and death if not treated in time. However, early diagnosis is challenging because the clinical manifestations and laboratory tests of biliary atresia overlap with other cholestatic diseases. Therefore, it is very important to develop a simple, safe and reliable method for the early diagnosis of biliary atresia. Herein, a novel NIR-II fluorescence probe, HZL2, with high quantum yield, excellent biocompatibility, low cytotoxicity and rapid excretion through the liver and gallbladder was developed based on the oil/water partition coefficient and permeability. A simple fecal sample after injection of HZL2 can be used to efficiently identify the success of the mouse model of biliary atresia for the first time, allowing for an early diagnosis of the disease. This study not only developed a simple and safe method for the early diagnosis of biliary atresia with great potential in clinical translation but also provides a research tool for the development of pathogenesis and therapeutic medicines for biliary atresia.

RevDate: 2023-11-15

Naito Y (2023)

Gut Frailty: Its Concept and Pathogenesis.

Digestion pii:000534733 [Epub ahead of print].

BACKGROUND: There is still a considerable gap between average life expectancy and healthy life expectancy in Japan. Recent research has revealed that gut frailty may be a worsening factor for various diseases, a cause of chronic inflammation, and a precursor to frailty.

SUMMARY: Among self-reported symptoms, constipation is particularly significant as one of the key symptoms of gut frailty. Studies have demonstrated that individuals with constipation have significantly lower survival rates and are also at a higher risk of developing various diseases such as chronic kidney disease, cardiovascular diseases, and neurodegenerative disorders like Parkinson's disease. Various molecular mechanisms could contribute to gut frailty, and the decrease in mucus secretion is an extremely early-stage pathology. Dysbiosis of gut microbiota has a major impact on many conditions associated with gut frailty. Prebiotics, probiotics, post-biotics, and fecal microbiota transplantation are under investigation as a treatment option for gut frailty.

KEY MESSAGE: Although the concept of gut frailty has not yet gained widespread recognition, we hope to propose more practical screening methods, diagnostic approaches, and specific interventions in the future.

RevDate: 2023-11-15

An S, Zhen Z, Wang S, et al (2023)

Intestinal Microbiota Is a Key Target for Load Swimming to Improve Anxiety Behavior and Muscle Strength in Shank 3[-/-] Rats.

Molecular neurobiology [Epub ahead of print].

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social disorder and stereotypical behavior, and its incidence rate is increasing yearly. It is considered that acritical period for the prognosis of young children with ASD exists, thus early treatment is crucial. Swimming, due to its comforting effect, is often used to induce enthusiasm in young children for completing activities and has a good effect in the treatment of ASD, but the effective path of swimming has yet to be reported. The intestinal microbiota of ASD patients and animal models has been reported to be different from that of healthy controls, and these changes may affect the brain environment. Therefore, whether the intestinal microbiota is involved in the treatment of ASD by early swimming is our concern. In this study, we used 8-day old Shank3 gene knockout rats with 8 weeks of early load swimming training and conducted behavioral, small intestine morphology, and intestinal content sequencing after training. The results showed that early load swimming significantly reduced the stereotyped and anxious behaviors of Shank3[-/-] rats, increased their muscle strength, increased the length of intestinal villi and the width of the muscular layer after Shank3 knockout, and affected the abundance of intestinal microorganisms. The abundances with statistical significance were Lactobacillus, Lachnospiraceae, and Alloprevotella. To further confirm the role of intestinal microorganisms in it, we designed a 14-day intestinal stool transplantation experiment. Fecal microbiota transplantation demonstrated that load swimming can significantly reduce the anxiety behavior of Shank3 rats, increase their muscle strength, change the structure of the small intestine, and affect the abundance of intestinal contents. The abundance of Epsilonbateraeota, Prevotella, and Bacteroides significantly changed after transplantation. Our findings confirm the possibility of early load swimming therapy for individuals with ASD and explain that the intestinal microbiota is a key pathway for early exercise therapy for patients with ASD.

RevDate: 2023-11-16

Piazzesi A, Pane S, Russo A, et al (2023)

Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency.

Frontiers in cellular and infection microbiology, 13:1281440.

Cryptosporidium parvum is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While infection is usually self-limiting, it can become chronic and even lethal in these vulnerable populations, in whom Cryptosporidium treatments are generally ineffective, due to their acting in concert with a functioning immune system. Here, we describe a case of chronic cryptosporidiosis in a European child with severe CD40L immunodeficiency infected with Cryptosporidium parvum of the IIa20G1 subgenotype, a lineage which has thus far only ever been described in the Middle East. After years of on-off treatment with conventional and non-conventional anti-parasitic drugs failed to clear parasitosis, we performed targeted metagenomics to observe the bacterial composition of the patient's gut microbiota (GM), and to evaluate fecal microbiota transplantation (FMT) as a potential treatment option. We found that C. parvum infection led to significant shifts in GM bacterial composition in our patient, with consequent shifts in predicted intestinal functional signatures consistent with a state of persistent inflammation. This, combined with the patient's poor prognosis and increasing parasitic burden despite many rounds of anti-parasitic drug treatments, made the patient a potential candidate for an experimental FMT procedure. Unfortunately, given the many comorbidities that were precipitated by the patient's immunodeficiency and chronic C. parvum infection, FMT was postponed in favor of more urgently necessary liver and bone marrow transplants. Tragically, after the first liver transplant failed, the patient lost his life before undergoing FMT and a second liver transplant. With this case report, we present the first description of how cryptosporidiosis can shape the gut microbiota of a pediatric patient with severe immunodeficiency. Finally, we discuss how both our results and the current scientific literature suggest that GM modulations, either by probiotics or FMT, can become novel treatment options for chronic Cryptosporidium infection and its consequent complications, especially in those patients who do not respond to the currently available anti-parasitic therapies.

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In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

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In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

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