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American Journal of Physiology.... May 2024Fecal microbiota transplantation (FMT) is a promising therapy for inflammatory bowel disease (IBD) via rectifying gut microbiota. The aim of this study was to identify a...
Fecal microbiota transplantation (FMT) is a promising therapy for inflammatory bowel disease (IBD) via rectifying gut microbiota. The aim of this study was to identify a mechanism of how specific bacteria-associated immune response contributes to alleviated colitis. Forty donors were divided into high () and low () groups according to the diversity and the abundance of and by 16S rRNA sequencing. FMT was performed on dextran sulfate sodium (DSS)-induced colitis in mice. Mice with colitis showed significant improvement in intestinal injury and immune imbalance after FMT with ( < 0.05). and were identified as targeted strains in donor feces by real-time PCR and droplet digital PCR. Mice with colitis were treated with mono- or dual-bacterial gavage therapy. Dual-bacterial therapy significantly ameliorated intestinal injury compared with mono-bacterial therapy ( < 0.05). Dual-bacterial therapy increased the M2/M1 macrophage polarization and improved the Th17/Treg imbalance and elevated IL-10 production by Tregs compared with the DSS group ( < 0.05). Metabolomics showed increased abundance of lecithin in the glycerophospholipid metabolism pathway. In conclusion, , as the key bacteria in donor feces, alleviate colitis in mice. The mechanism may involve increasing lecithin and regulating IL-10 production of intestinal Tregs. We demonstrate that donors with high abundance of and ameliorate dextran sulfate sodium (DSS)-induced colitis in mice by fecal microbiota transplantation (FMT). The combination therapy of and is superior to mono-bacterial therapy in ameliorating colitis in mice, of which mechanism may involve promoting lecithin and inducing IL-10 production of intestinal Tregs.
Topics: Animals; Fecal Microbiota Transplantation; Colitis; Faecalibacterium prausnitzii; Mice; Gastrointestinal Microbiome; Male; Humans; Bacteroides thetaiotaomicron; Dextran Sulfate; Mice, Inbred C57BL; Interleukin-10; Adult; Female; Feces; Disease Models, Animal; Middle Aged
PubMed: 38502145
DOI: 10.1152/ajpgi.00303.2023 -
Frontiers in Immunology 2021Inhibition of allergic airway diseases (AAD) by immunomodulation of the adaptive immune system through restoration of the enteric dysbiosis is an emerging therapeutic...
Inhibition of allergic airway diseases (AAD) by immunomodulation of the adaptive immune system through restoration of the enteric dysbiosis is an emerging therapeutic strategy. Patients with allergic rhinitis (n = 6) and healthy controls (n = 6) were enrolled, and gut microbiome composition analysis was performed by 16S rDNA sequencing. We also established an ovalbumin (OVA)-induced allergic airway inflammation murine model. Dysbiosis of the gut flora was observed in both AAD patients and the mice, with the decrease of the biodiversity and the quantity of the Bacteroidetes phylum. Oral application of ameliorated the symptoms of OVA-induced airway hyperresponsiveness (AHR) and attenuated the airway inflammation in mice. In addition, nasal lavage fluid (NALF) and bronchoalveolar lavage fluid (BALF) from AAD mice orally administered with showed reduced numbers of immune cells, and diminished secretion of T helper (Th)-2 cytokines (IL-4, IL-5, and IL-13) compared with the corresponding control mice, whereas the levels of Th1 cytokineIFN-γ was not changed in both the groups. When was co-administered with metronidazole in AAD mice, the immunomodulatory effect was weakened and the allergic inflammatory response was aggravated. The ratios of CD4Foxp3 cells, CD4ICOS T cells, CD4ICOS Foxp3 regulatory T cells, and IL-10-expressing CD4Foxp3 cells were increased in lymphocytes of spleen, mesenteric, and cervical lymph nodes of AAD mice administrated with . Therefore, our data indicate that oral administration of effectively inhibited the development of AAD in murine model; inhibition was mediated by the activation of Tregs and inhibition of Th2 response without promoting a Th1 response.
Topics: Allergens; Animals; Bacteroides thetaiotaomicron; Cells, Cultured; Cytokines; Gastrointestinal Microbiome; Humans; Hypersensitivity; Immunomodulation; Inducible T-Cell Co-Stimulator Protein; Inflammation; Mice; Mice, Inbred BALB C; Models, Animal; Ovalbumin; Respiratory Hypersensitivity; Respiratory System; T-Lymphocytes, Regulatory; Th2 Cells
PubMed: 33815374
DOI: 10.3389/fimmu.2021.620943 -
Gut Microbes 2024Gut microbiota plays an essential role in the progression of nonalcoholic fatty liver disease (NAFLD), making the gut-liver axis a potential therapeutic strategy....
Gut microbiota plays an essential role in the progression of nonalcoholic fatty liver disease (NAFLD), making the gut-liver axis a potential therapeutic strategy. Bacteroides genus, the enriched gut symbionts, has shown promise in treating fatty liver. However, further investigation is needed to identify specific beneficial Bacteroides strains for metabolic disorders in NAFLD and elucidate their underlying mechanisms. In this study, we observed a positive correlation between the abundance of () and the alleviation of metabolic syndrome in the early and end stages of NAFLD. Administration of to HFD-fed mice for 12 weeks reduced body weight and fat accumulation, decreased hyperlipidemia and insulin resistance, and prevented hepatic steatohepatitis and liver injury. Notably, did not affect these indicators in low-fat diet (LFD)-fed mice and exhibited good safety. Mechanistically, regulated gut microbial composition, characterized by a decreased Firmicutes/Bacteroidetes ratio in HFD-Fed mice. It also increased gut-liver folate levels and hepatic metabolites, alleviating metabolic dysfunction. Additionally, treatment with increased the proportion of polyunsaturated fatty acid in the mouse liver, offering a widely reported benefit for NAFLD improvement. In conclusion, this study provides evidence that ameliorates NAFLD by regulating gut microbial composition, enhancing gut-liver folate and unsaturated fatty acid metabolism, highlighting the therapeutic role of as a potential probiotic for NAFLD.
Topics: Mice; Animals; Non-alcoholic Fatty Liver Disease; Bacteroides thetaiotaomicron; Gastrointestinal Microbiome; Diet, High-Fat; Liver; Mice, Inbred C57BL
PubMed: 38277137
DOI: 10.1080/19490976.2024.2304159 -
Cell Host & Microbe Jun 2022Microbially-derived gut metabolites are important contributors to host phenotypes, many of which may link microbiome composition to metabolic disease. However,...
Microbially-derived gut metabolites are important contributors to host phenotypes, many of which may link microbiome composition to metabolic disease. However, relatively few metabolites with known bioactivity have been traced from specific microbes to host tissues. Here, we use a labeling strategy to characterize and trace bacterial sphingolipids from the gut symbiont Bacteroides thetaiotaomicron to mouse colons and livers. We find that bacterial sphingolipid synthesis rescues excess lipid accumulation in a mouse model of hepatic steatosis and observe the transit of a previously uncharacterized bacterial sphingolipid to the liver. The addition of this sphingolipid to hepatocytes improves respiration in response to fatty-acid overload, suggesting that sphingolipid transfer to the liver could potentially contribute to microbiota-mediated liver function. This work establishes a role for bacterial sphingolipids in modulating hepatic phenotypes and defines a workflow that permits the characterization of other microbial metabolites with undefined functions in host health.
Topics: Animals; Bacteroides thetaiotaomicron; Gastrointestinal Microbiome; Liver; Mice; Microbiota; Sphingolipids
PubMed: 35623356
DOI: 10.1016/j.chom.2022.05.002 -
Microbiology Spectrum Mar 2023Members of the phylum are abundant in healthy gastrointestinal (GI) tract flora. Bacteroides thetaiotaomicron is a commensal heme auxotroph and representative of this...
Members of the phylum are abundant in healthy gastrointestinal (GI) tract flora. Bacteroides thetaiotaomicron is a commensal heme auxotroph and representative of this group. are sensitive to host dietary iron restriction but proliferate in heme-rich environments that are also associated with colon cancer. We hypothesized that B. thetaiotaomicron may act as a host reservoir for iron and/or heme. In this study, we defined growth-promoting quantities of iron for B. thetaiotaomicron. B. thetaiotaomicron preferentially consumed and hyperaccumulated iron in the form of heme when presented both heme and nonheme iron sources in excess of its growth needs, leading to an estimated 3.6 to 8.4 mg iron in a model GI tract microbiome consisting solely of B. thetaiotaomicron. Protoporphyrin IX was identified as an organic coproduct of heme metabolism, consistent with anaerobic removal of iron from the heme leaving the intact tetrapyrrole as the observed product. Notably, no predicted or discernible pathway for protoporphyrin IX generation exists in B. thetaiotaomicron. Heme metabolism in congeners of B. thetaiotaomicron has previously been associated with the 6-gene operon, based on genetic studies. A bioinformatics survey demonstrated that the intact operon is widespread in but confined to members of the phylum and ubiquitous in healthy human GI tract flora. Anaerobic heme metabolism by commensal via is likely a major contributor to human host metabolism of the heme from dietary red meat and a driver for the selective growth of these species in the GI tract consortium. Research on bacterial iron metabolism has historically focused on the host-pathogen relationship, where the host suppresses pathogen growth by cutting off access to iron. Less is known about how host iron is shared with bacterial species that live commensally in the anaerobic human GI tract, typified by members of phylum . While many facultative pathogens avidly produce and consume heme iron, most GI tract anaerobes are heme auxotrophs whose metabolic preferences we aimed to describe. Understanding iron metabolism by model microbiome species like Bacteroides thetaiotaomicron is essential for modeling the ecology of the GI tract, which serves the long-term biomedical goals of manipulating the microbiome to facilitate host metabolism of iron and remediate dysbiosis and associated pathologies (e.g., inflammation and cancer).
PubMed: 36862015
DOI: 10.1128/spectrum.04815-22 -
Cell Host & Microbe Mar 2020During short-lived perturbations, such as inflammation, the gut microbiota exhibits resilience and reverts to its original configuration. Although microbial access to...
During short-lived perturbations, such as inflammation, the gut microbiota exhibits resilience and reverts to its original configuration. Although microbial access to the micronutrient iron is decreased during colitis, pathogens can scavenge iron by using siderophores. How commensal bacteria acquire iron during gut inflammation is incompletely understood. Curiously, the human commensal Bacteroides thetaiotaomicron does not produce siderophores but grows under iron-limiting conditions using enterobacterial siderophores. Using RNA-seq, we identify B. thetaiotaomicron genes that were upregulated during Salmonella-induced gut inflammation and were predicted to be involved in iron uptake. Mutants in the xusABC locus (BT2063-2065) were defective for xenosiderophore-mediated iron uptake in vitro. In the normal mouse gut, the XusABC system was dispensable, while a xusA mutant colonized poorly during colitis. This work identifies xenosiderophore utilization as a critical mechanism for B. thetaiotaomicron to sustain colonization during inflammation and suggests a mechanism of how interphylum iron metabolism contributes to gut microbiota resilience.
Topics: Animals; Bacteroides thetaiotaomicron; Colitis; Enterobacteriaceae; Female; Gastrointestinal Microbiome; Genes, Bacterial; Iron; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; RNA-Seq; Siderophores; Symbiosis
PubMed: 32075741
DOI: 10.1016/j.chom.2020.01.010 -
Journal of Microbiology (Seoul, Korea) Jan 2022The gut microbiome plays an important role in lipid metabolism. Consumption of a high-fat diet (HFD) alters the bacterial communities in the gut, leading to metabolic...
The gut microbiome plays an important role in lipid metabolism. Consumption of a high-fat diet (HFD) alters the bacterial communities in the gut, leading to metabolic disorders. Several bacterial species have been associated with diet-induced obesity, nonalcoholic fatty liver disease, and metabolic syndrome. However, the mechanisms underlying the control of lipid metabolism by symbiotic bacteria remain elusive. Here, we show that the human symbiont Bacteroides thetaiotaomicron aggravates metabolic disorders by promoting lipid digestion and absorption. Administration of B. thetaiotaomicron to HFD-fed mice promoted weight gain, elevated fasting glucose levels, and impaired glucose tolerance. Furthermore, B. thetaiotaomicron treatment upregulated the gene expression of the fatty acid transporter and increased fatty acid accumulation in the liver. B. thetaiotaomicron inhibits expression of the gene encoding a lipoprotein lipase inhibitor, angiopoietin-like protein 4 (ANGPTL4), thereby increasing lipase activity in the small intestine. In particular, we found that B. thetaiotaomicron induced the expression of hepcidin, the master regulator of iron metabolism and an antimicrobial peptide, in the liver. Hepcidin treatment resulted in a decrease in ANGPTL4 expression in Caco-2 cells, whereas treatment with an iron chelator restored ANGPTL4 expression in hepcidin-treated cells. These results indicate that B. thetaiotaomicron-mediated regulation of iron storage in intestinal epithelial cells may contribute to increased fat deposition and impaired glucose tolerance in HFD-fed mice.
Topics: Angiopoietin-Like Protein 4; Animals; Bacteroides thetaiotaomicron; Diet, High-Fat; Gastrointestinal Microbiome; Hepcidins; Humans; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Obesity
PubMed: 34964947
DOI: 10.1007/s12275-022-1614-1 -
Journal of Immunology (Baltimore, Md. :... Sep 2023The gut microbiome and intestinal immune system are engaged in a dynamic interplay that provides myriad benefits to host health. However, the microbiome can also elicit...
The gut microbiome and intestinal immune system are engaged in a dynamic interplay that provides myriad benefits to host health. However, the microbiome can also elicit damaging inflammatory responses, and thus establishing harmonious immune-microbiome interactions is essential to maintain homeostasis. Gut microbes actively coordinate the induction of anti-inflammatory responses that establish these mutualistic interactions. Despite this, the microbial pathways that govern this dialogue remain poorly understood. We investigated the mechanisms through which the gut symbiont Bacteroides thetaiotaomicron exerts its immunomodulatory functions on murine- and human-derived cells. Our data reveal that B. thetaiotaomicron stimulates production of the cytokine IL-10 via secreted factors that are packaged into outer membrane vesicles, in a TLR2- and MyD88-dependent manner. Using a transposon mutagenesis-based screen, we identified a key role for the B. thetaiotaomicron-encoded NADH:ubiquinone oxidoreductase (NQR) complex, which regenerates NAD+ during respiration, in this process. Finally, we found that disruption of NQR reduces the capacity of B. thetaiotaomicron to induce IL-10 by impairing biogenesis of outer membrane vesicles. These data identify a microbial pathway with a previously unappreciated role in gut microbe-mediated immunomodulation that may be targeted to manipulate the capacity of the microbiome to shape host immunity.
Topics: Mice; Humans; Animals; Bacteroides thetaiotaomicron; Interleukin-10; Mutagenesis; Gastrointestinal Tract; Cytokines
PubMed: 37486212
DOI: 10.4049/jimmunol.2200892 -
Journal of Structural Biology Jan 2019Galactooligosaccharides (GOS) are prebiotic compounds synthesized from lactose using bacterial enzymes and are known to stimulate growth of beneficial bifidobacteria in... (Review)
Review
Structural and functional characterization of a family GH53 β-1,4-galactanase from Bacteroides thetaiotaomicron that facilitates degradation of prebiotic galactooligosaccharides.
Galactooligosaccharides (GOS) are prebiotic compounds synthesized from lactose using bacterial enzymes and are known to stimulate growth of beneficial bifidobacteria in the human colon. Bacteroides thetaiotaomicron is a prominent human colon commensal bacterial species that hydrolyzes GOS using an extracellular Glycosyl Hydrolase (GH) family GH53 endo-galactanase enzyme (BTGH53), releasing galactose-based products for growth. Here we dissect the molecular basis for GOS activity of this B. thetaiotaomicron GH53 endo-galactanase. Elucidation of its X-ray crystal structure revealed that BTGH53 has a relatively open active site cleft which was not observed with the bacterial enzyme from Bacillus licheniformis (BLGAL). BTGH53 acted on GOS with degree of polymerization ≤3 and therefore more closely resembles activity of fungal GH53 enzymes (e.g. Aspergillus aculeatus AAGAL and Meripileus giganteus MGGAL). Probiotic lactobacilli that lack galactan utilization systems constitute a group of bacteria with relevance for a healthy (infant) gut. The strains tested were unable to use GOS ≥ DP3. However, they completely consumed GOS in the presence of BTGH53, resulting in clear stimulation of their extent of growth. The extracellular BTGH53 enzyme thus may play an important role in carbohydrate metabolism in complex microbial environments such as the human colon. It also may find application for the development of synergistic synbiotics.
Topics: Bacteroides thetaiotaomicron; Galactose; Glycoside Hydrolases; Humans; Oligosaccharides; Prebiotics
PubMed: 30553858
DOI: 10.1016/j.jsb.2018.12.002 -
Scientific Reports Jul 2020Alterations to the gut microbiota can cause an amplification of the inflammatory response to intestinal pathogens. We assessed the effect of Bacteroides thetaiotaomicron...
Alterations to the gut microbiota can cause an amplification of the inflammatory response to intestinal pathogens. We assessed the effect of Bacteroides thetaiotaomicron and Lactobacillus johnsonii on the elimination of Candida species and whether restoration of these two anaerobic bacteria could attenuate the development of colitis in mice. In this study, L. johnsonii and B. thetaiotaomicron interacted directly with Candida species and induced a degradation of the fungal cell wall, mediated via chitinase-like and mannosidase-like activities, which promoted the inhibition of Candida species growth. In the DSS-induced colitis model, oral administration of L. johnsonii and B. thetaiotaomicron to mice reduced the overgrowth of Escherichia coli, Enterococcus faecalis and Candida glabrata populations and resulted in a significant reduction in inflammatory parameters. L. johnsonii and B. thetaiotaomicron decreased pro-inflammatory mediators and enhanced the anti-inflammatory cytokine response with high TLR9 expression and chitinase-like protein-1 activation, which promoted the elimination of C. glabrata from the gut. Overall, these findings provide evidence that L. johnsonii and B. thetaiotaomicron decrease the development of colitis mediated by TLR9 and promote the elimination of C. glabrata from the gut via chitinase-like and mannosidase-like activities.
Topics: Animals; Bacteroides thetaiotaomicron; Candida glabrata; Cell Wall; Gastrointestinal Microbiome; Hydrolysis; Inflammation; Inflammation Mediators; Lactobacillus johnsonii; Mice
PubMed: 32661259
DOI: 10.1038/s41598-020-68214-9