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Science Advances Jan 2023Although gut microbiota has been linked to exercise, whether alterations in the abundance of specific bacteria improve exercise performance remains ambiguous. In a... (Randomized Controlled Trial)
Randomized Controlled Trial
Although gut microbiota has been linked to exercise, whether alterations in the abundance of specific bacteria improve exercise performance remains ambiguous. In a cross-sectional study involving 25 male long-distance runners, we found a correlation between abundance in feces and the 3000-m race time. In addition, we administered flaxseed lignan or α-cyclodextrin as a test tablet to healthy, active males who regularly exercised in a randomized, double-blind, placebo-controlled study to increase in the gut (UMIN000033748). The results indicated that α-cyclodextrin supplementation improved human endurance exercise performance. Moreover, administration in mice increased swimming time to exhaustion, cecal short-chain fatty acid concentrations, and the gene expression of enzymes associated with gluconeogenesis in the liver while decreasing hepatic glycogen content. These findings indicate that enhances endurance exercise performance, which may be mediated by facilitating hepatic endogenous glucose production.
Topics: Humans; Mice; Male; Animals; Cross-Sectional Studies; alpha-Cyclodextrins; Bacteroides; Gastrointestinal Microbiome
PubMed: 36696509
DOI: 10.1126/sciadv.add2120 -
Brain, Behavior, and Immunity May 2022Gut microbiome disturbances have been widely implicated in major depressive disorder (MDD), although the identity of causal microbial species and the underlying...
Gut microbiome disturbances have been widely implicated in major depressive disorder (MDD), although the identity of causal microbial species and the underlying mechanisms are yet to be fully elucidated. Here we show that Bacteroides species enriched in the gut microbiome from MDD patients differentially impact the susceptibility to depressive behaviors. Transplantation of fecal microbiome from MDD patients into antibiotic-treated mice induced anxiety and despair-like behavior and impaired hippocampal neurogenesis. Colonization of Bacteroides fragilis, Bacteroides uniformis, and, to a lesser extent, Bacteroides caccae, but not Bacteroides ovatus, recapitulated the negative effects of MDD microbiome on behavior and neurogenesis. The varying impacts of Bacteroides species were partially explained by differential alternations of tryptophan pathway metabolites and neurotransmitters along the gut-brain axis. Notably, an intensified depletion of cerebral serotonin concurred with the enhanced susceptibility to depression. Together, these findings identify select Bacteroidetes species that contribute to depression susceptibility in mice by metabolic regulation along the gut-brain axis.
Topics: Animals; Bacteroides; Brain; Depression; Depressive Disorder, Major; Gastrointestinal Microbiome; Humans; Mice
PubMed: 35143877
DOI: 10.1016/j.bbi.2022.02.007 -
NPJ Biofilms and Microbiomes Aug 2023Inflammatory bowel disease (IBD) is associated with gut dysbiosis and can lead to colitis-associated malignancies. Bacteroides uniformis (Bu) regulates animal intestinal...
Inflammatory bowel disease (IBD) is associated with gut dysbiosis and can lead to colitis-associated malignancies. Bacteroides uniformis (Bu) regulates animal intestinal homeostasis; however, the mechanism by which it alleviates colitis in mice remains unknown. We investigated the effects of B. uniformis JCM5828 and its metabolites on female C57BL/6J mice with dextran sulfate sodium salt (DSS) induced colitis. Treatment with Bu considerably alleviated colitis progression and restored the mechanical and immune barrier protein expression. Additionally, Bu increased the abundance of the symbiotic bacteria Bifidobacterium and Lactobacillus vaginalis while decreasing that of pathogenic Escherichia-Shigella, and modulated intestinal bile acid metabolism. Bu largely regulated the expression of key regulatory proteins of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways in colonic tissues and the differentiation of TH17 cells. However, Bu could not directly inhibit TH17 cell differentiation in vitro; it modulated the process in the lamina propria by participating in bile acid metabolism and regulating key metabolites (alpha-muricholic, hyodeoxycholic, and isolithocholic acid), thereby modulating the intestinal immune response. Our findings suggest that Bu or bile acid supplements are potential therapies for colitis and other diseases associated with intestinal barrier dysfunction.
Topics: Female; Mice; Animals; Th17 Cells; Bile Acids and Salts; Gastrointestinal Microbiome; Mice, Inbred C57BL; Colitis; Microbiota; Cell Differentiation; Dextran Sulfate
PubMed: 37580334
DOI: 10.1038/s41522-023-00420-5 -
Cell Surface Xyloglucan Recognition and Hydrolysis by the Human Gut Commensal Bacteroides uniformis.Applied and Environmental Microbiology Jan 2022Xyloglucan (XyG) is a ubiquitous plant cell wall hemicellulose that is targeted by a range of syntenic, microheterogeneous xyloglucan utilization loci (XyGUL) in... (Review)
Review
Xyloglucan (XyG) is a ubiquitous plant cell wall hemicellulose that is targeted by a range of syntenic, microheterogeneous xyloglucan utilization loci (XyGUL) in species of the human gut microbiota (HGM), including Bacteroides ovatus and B. uniformis. Comprehensive biochemical and biophysical analyses have identified key differences in the protein complements of each locus that confer differential access to structurally diverse XyG side chain variants. A second, nonsyntenic XyGUL was previously identified in B. uniformis, although its function in XyG utilization compared to its syntenic counterpart was unclear. Here, complementary enzymatic product profiles and bacterial growth curves showcase the notable preference of XyGUL2 surface glycan-binding proteins (SGBPs) to bind full-length XyG, as well as a range of oligosaccharides produced by the glycoside hydrolase family 5 (GH5_4) -xyloglucanase from this locus. We use isothermal titration calorimetry (ITC) to characterize this binding capacity and pinpoint the specific contributions of each protein to nutrient capture. The high-resolution structure of XyGUL2 SGBP-B reveals remarkable putative binding site conservation with the canonical XyG-binding XyGUL SGBP-B, supporting similar roles for these proteins in glycan capture. Together, these data underpin the central role of complementary XyGUL function in B. uniformis and broaden our systems-based and mechanistic understanding of XyG utilization in the HGM. The omnipresence of xyloglucans in the human diet has led to the evolution of heterogeneous gene clusters in several species in the HGM, each specially tuned to respond to the structural variations of these complex plant cell wall polysaccharides. Our research illuminates the complementary roles of syntenic and nonsyntenic XyGUL in B. uniformis in conferring growth on a variety of XyG-derived substrates, providing evidence of glycan-binding protein microadaptation within a single species. These data serve as a comprehensive overview of the binding capacities of the SGBPs from a nonsyntenic B. uniformis XyGUL and will inform future studies on the roles of complementary loci in glycan targeting by key HGM species.
Topics: Bacteroides; Gastrointestinal Tract; Glucans; Humans; Hydrolysis; Xylans
PubMed: 34731054
DOI: 10.1128/AEM.01566-21 -
Gut Microbes 2021Gut microbiota represents a therapeutic target for obesity. We hypothesize that CECT 7771 combined with wheat bran extract (WBE), its preferred carbon source, may exert...
Gut microbiota represents a therapeutic target for obesity. We hypothesize that CECT 7771 combined with wheat bran extract (WBE), its preferred carbon source, may exert superior anti-obesity effects. We performed a 17-week intervention in diet-induced obese mice receiving either , WBE, or their combination to identify interactions and independent actions on metabolism and immunity. combined with WBE was the most effective intervention, curbing weight gain and adiposity, while exerting more modest effects separately. The combination restored insulin-dependent metabolic routes in fat and liver, although the bacterium was the primary driver for improving whole-body glucose disposal. Moreover, -combined with WBE caused the highest increases in butyrate and restored the proportion of induced intraepithelial lymphocytes and type-3 innate lymphoid cells in the intestinal epithelium. Thus, strengthening the first line of immune defense against unhealthy diets and associated dysbiosis in the intestine. This intervention also attenuated the altered IL22 signaling and liver inflammation. Our study shows opportunities for employing , combined with WBE, to aid in the treatment of obesity.
Topics: Adipose Tissue; Animals; Bacteroides; Cecum; Diet, High-Fat; Dietary Fiber; Epididymis; Fatty Acids; Gastrointestinal Microbiome; Inflammation; Insulin; Interleukins; Intestinal Mucosa; Liver; Lymphocytes; Male; Mice; Obesity; Signal Transduction; Thermogenesis; Weight Gain; Interleukin-22
PubMed: 33499721
DOI: 10.1080/19490976.2020.1865706 -
Microbiology Resource Announcements Oct 2022Here, we describe the isolation and genomic annotation of two novel siphovirus species of bacteriophages that infect Bacteroides uniformis: Bacteroides phage EMB1 and...
Here, we describe the isolation and genomic annotation of two novel siphovirus species of bacteriophages that infect Bacteroides uniformis: Bacteroides phage EMB1 and Bacteroides phage EMB2. EMB1 has a 34,204-bp genome with 48 coding sequences, and EMB2 has a 34,008-bp genome with 47 coding sequences.
PubMed: 36121235
DOI: 10.1128/mra.00610-22 -
Scientific Reports Jun 2021This study investigated the immune mechanisms whereby administration of Bacteroides uniformis CECT 7771 reduces metabolic dysfunction in obesity. C57BL/6 adult male mice...
This study investigated the immune mechanisms whereby administration of Bacteroides uniformis CECT 7771 reduces metabolic dysfunction in obesity. C57BL/6 adult male mice were fed a standard diet or a Western diet high in fat and fructose, supplemented or not with B. uniformis CECT 7771 for 14 weeks. B. uniformis CECT 7771 reduced body weight gain, plasma cholesterol, triglyceride, glucose, and leptin levels; and improved oral glucose tolerance in obese mice. Moreover, B. uniformis CECT 7771 modulated the gut microbiota and immune alterations associated with obesity, increasing Tregs and reducing B cells, total macrophages and the M1/M2 ratio in both the gut and epididymal adipose tissue (EAT) of obese mice. B. uniformis CECT 7771 also increased the concentration of the anti-inflammatory cytokine IL-10 in the gut, EAT and peripheral blood, and protective cytokines TSLP and IL-33, involved in Treg induction and type 2 innate lymphoid cells activation, in the EAT. It also restored the obesity-reduced TLR5 expression in the ileum and EAT. The findings indicate that the administration of a human intestinal bacterium with immunoregulatory properties on the intestinal mucosa helps reverse the immuno-metabolic dysfunction caused by a Western diet acting over the gut-adipose tissue axis.
Topics: Adaptive Immunity; Adipose Tissue; Animals; Bacteroides; Bacteroides Infections; Cytokines; Disease Models, Animal; Energy Metabolism; Gastroenteritis; Gastrointestinal Microbiome; Immunity, Innate; Inflammation Mediators; Mice; Mice, Obese; Phenotype; Signal Transduction; Toll-Like Receptor 5
PubMed: 34083551
DOI: 10.1038/s41598-021-90888-y -
Molecular Neurobiology Oct 2021Food addiction (FA) is characterized by behavioral and neurochemical changes linked to loss of food intake control. Gut microbiota may influence appetite and food intake...
Food addiction (FA) is characterized by behavioral and neurochemical changes linked to loss of food intake control. Gut microbiota may influence appetite and food intake via endocrine and neural routes. The gut microbiota is known to impact homeostatic energy mechanisms, but its role in regulating the reward system is less certain. We show that the administration of Bacteroides uniformis CECT 7771 (B. uniformis) in a rat FA model impacts on the brain reward response, ameliorating binge eating and decreasing anxiety-like behavior. These effects are mediated, at least in part, by changes in the levels of dopamine, serotonin, and noradrenaline in the nucleus accumbens and in the expression of dopamine D1 and D2 receptors in the prefrontal cortex and intestine. B. uniformis reverses the fasting-induced microbiota changes and increases the abundance of species linked to healthy metabolotypes. Our data indicate that microbiota-based interventions might help to control compulsive overeating by modulating the reward response.
Topics: Animals; Anxiety; Bacteroides; Binge-Eating Disorder; Brain; Gastrointestinal Microbiome; Humans; Infant, Newborn; Male; Microdialysis; Rats; Rats, Inbred WKY; Reward
PubMed: 34228269
DOI: 10.1007/s12035-021-02462-2 -
Nature Communications Oct 2023Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with...
Hypertriglyceridemic pancreatitis (HTGP) is featured by higher incidence of complications and poor clinical outcomes. Gut microbiota dysbiosis is associated with pancreatic injury in HTGP and the mechanism remains unclear. Here, we observe lower diversity of gut microbiota and absence of beneficial bacteria in HTGP patients. In a fecal microbiota transplantation mouse model, the colonization of gut microbiota from HTGP patients recruits neutrophils and increases neutrophil extracellular traps (NETs) formation that exacerbates pancreatic injury and systemic inflammation. We find that decreased abundance of Bacteroides uniformis in gut microbiota impairs taurine production and increases IL-17 release in colon that triggers NETs formation. Moreover, Bacteroides uniformis or taurine inhibits the activation of NF-κB and IL-17 signaling pathways in neutrophils which harness NETs and alleviate pancreatic injury. Our findings establish roles of endogenous Bacteroides uniformis-derived metabolic and inflammatory products on suppressing NETs release, which provides potential insights of ameliorating HTGP through gut microbiota modulation.
Topics: Mice; Animals; Humans; Extracellular Traps; Interleukin-17; Gastrointestinal Microbiome; Pancreatitis; Taurine
PubMed: 37794047
DOI: 10.1038/s41467-023-41950-y -
Gut Mar 2022Our goals were to evaluate the antitumour efficacy of GG (LGG) in combination with immune checkpoint blockade (ICB) immunotherapies on tumour growth and to investigate...
OBJECTIVE
Our goals were to evaluate the antitumour efficacy of GG (LGG) in combination with immune checkpoint blockade (ICB) immunotherapies on tumour growth and to investigate the underlying mechanisms.
DESIGN
We used murine models of colorectal cancer and melanoma to evaluate whether oral administration of LGG improves the efficacy of ICB therapies. We performed the whole genome shotgun metagenome sequencing of intestinal contents and RNA sequencing of dendritic cells (DCs). In a series of in vitro and in vivo experiments, we further defined the immunological and molecular mechanisms of LGG-mediated antitumour immunity.
RESULTS
We demonstrate that oral administration of live LGG augmented the antitumour activity of anti-programmed cell death 1 (PD-1) immunotherapy by increasing tumour-infiltrating DCs and T cells. Moreover, the combination treatment shifted the gut microbial community towards enrichment in and , that are known to increase DC activation and CD8tumour recruitment. Mechanistically, treatment with live LGG alone or in combination with anti-PD-1 antibody triggered type I interferon (IFN) production in DCs, enhancing the cross-priming of antitumour CD8 T cells. In DCs, cyclic GMP-AMP synthase (cGAS)/stimulator of IFN genes (STING) was required for IFN-β induction in response to LGG, as evidenced by the significant decrease in IFN-β levels in cGAS or STING-deficient DCs. LGG induces IFN-β production via the cGAS/STING/TANK binding kinase 1/interferon regulatory factor 7 axis in DCs.
CONCLUSION
Our findings have offered valuable insight into the molecular mechanisms of live LGG-mediated antitumour immunity and establish an empirical basis for developing oral administration of live LGG as a combination agent with ICB for cancer therapies.
Topics: Administration, Oral; Animals; Colorectal Neoplasms; Disease Models, Animal; Immune Checkpoint Inhibitors; Interferon Type I; Lacticaseibacillus rhamnosus; Melanoma; Mice; Probiotics
PubMed: 33685966
DOI: 10.1136/gutjnl-2020-323426