Bacteroides ⇒ Bacteroides fragilis {10000104} Record Keys Parent:Bacteroides Definition:Bacteroides fragilis Details Initialisation date:2019-05-14 LinksSource Meta Information Rank: Species Domain: Bacteria Zone:[ ] Enzyme:[ ] Function:Mucin-degrading, Cancerogenic, Anti-inflammatory Notes: [ ]Shared Reference Notes [1.1] - The immunomodulatory molecule polysaccharide A derived from the human commensal Bacteroides fragilis mediates the conversion of CD4+ T cells into FOXP3+ Treg cells that produce IL-10 during commensal colonization, stimulating immunological development within mammalian hosts [1.2] - During colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system, correcting systemic T cell deficiencies and TH1/TH2 imbalances and directing lymphoid organogenesis. - PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. [1.3] [#Multiple Sclerosis] - Addition of a single probiotic bacterial species, Bacteroides fragilis Depending on Polysaccharide A Expression, can ameliorate MS disease through immunomodulation . [1.4] [#Cancer] [#Bacteroides fragilis toxin] - Bacteroides fragilis toxin (Bft), can indirectly damage the host DNA by eliciting high levels of reactive oxygen species (ROS) [1.5] [#Colon polyps] [#Lipopolysaccharide] - BF is enriched in patients with polyps > inflammatory cytokines in the mucosa adjacent to polyps. - BF from polyps is enriched for LPS biosynthesis genes, activates TLR4, and induces IL-12 > induce a pro-inflammatory response. - Presence of LPS genes and elevated expression of LPS are found in polyp tissues. [1.6] - The colon has two distinct mucus structures: the outer layer is colonized by mucin-degrading bacteria and is characterized by the presence of Bacteroides acidifaciens, Bacteroides fragilis, Bifidobacteriaceae and Akkermansia muciniphila and the inner layer and crypts are penetrated at low density by a more restricted community that includes Bacteroides fragilis and Acinetobacter spp. [1.7] - #Sulforaphane can normalize the intestinal flora imbalance of #Bladder cancer mice with a significant increase in Bacteroides fragilis and #Clostridium cluster I [1.8] [#Alzheimer’s disease] [#Amyloid-beta] - Presence of #Amyloid deposits was associated with greater abundance of proinflammatory taxa (#Escherichia/#Shigella), which were in turn correlated with proinflammatory cytokines, and with reduced abundance of #Eubacterium rectale and B. fragilis, 2 taxa with anti-inflammatory activity - Bacteroides fragilis metabolite #Polysaccharide A has anti-inflammatory properties, [1.9] [#Alzheimer’s disease] [#Lipopolysaccharide] - Bacteroides fragilis in the human gastrointestinal (GI) tract generates > neurotoxin #BF-LPS > #BF-LPS leaks out of the GI tract, crosses the blood brain barrier via the circulatory system, and accesses brain compartments > inreases inflammation in brain cells and inhibits neuron-specific neurofilament light (NF-L,) a protein that supports cell integrity > deficiency of NF-L > consequent atrophy of the neuronal cytoskeleton and the disruption of synaptic organization. - #Bacteroides thetaiotaomicron, #Akkermansia muciniphila, Ruminoccous gnavus, Bacteroides fragilis, and #Bifidobacterium bifidium are predominant bacteria within the mucus layer that utilize #Glycans as their energy source by glycosidase, sulphatase, and sialidase enzymes [1.11] - Bacteroides fragilis and several #Clostridia species have been reported to cause an anti-inflammatory response [1.12] [#Pancreatic Cancer] [#Bacteroides fragilis toxin] - Enterotoxigenic Bacteroides fragilis (ETBF) produces Bacteroides fragilis toxin (BFT), which is associated with acute diarrheal, inflammatory bowel disease, and #Colorectal cancer (CRC). [1.13] [#Colorectal cancer] - certain bacterial species, such as #Fusobacterium nucleatum, #Streptococcus bovis, and Bacteroides fragilis have been linked to CRC, either by producing virulence factors or by producing pathogenic microbial metabolites. [1.14] [#Prostate cancer] - species such as Bacteroides fragilis, Saimiriine betaherpesvirus, #Staphylococcus saprophyticus, and Vibrio parahaemolyticus had a significantly reduced abundance in the malignant as compared to the benign prostate tissue samples. [1.15] [#Pancreatic Cancer] Pancreatic ductal adenocarcinoma (PDAC) > chemotherapy > microbiota-derived tryptophan metabolite #Indole-3-acetic acid (3-IAA) is enriched in patients who respond to treatment. - Faecal microbiota transplantation, short-term dietary manipulation of tryptophan and oral 3-IAA administration increase the efficacy of chemotherapy in humanized gnotobiotic mouse models of PDAC. - In humans > a significant correlation between the levels of 3-IAA and the efficacy of therapy in two independent PDAC cohorts. - Pancreatic ductal adenocarcinoma (PDAC) > Bacteroides fragilis and #Bacteroides thetaiotaomicron produced 3-IAA in vitro were increased in Responder patients. [1.16] - Bacteroides fragilis, which produces a specific bacterial #Polysaccharide, directly impacts the cellular and physical maturation of the immune system including correcting T cell deficiencies and Th1/Th2 imbalances observed in germ-free mice [1.17] [#Mild Cognitive Impairment] - the ratio of #Ruminococcus sp. CAG:330 to Bacteroides fragilis CAG: 47 is consistently elevated in MCI [1.18] [#Human milk oligosaccharides] [#Adult] - Among the HMOs, 6′SL specifically stimulated #Propionate (linked to Bacteroides fragilis in #Children and #Phocaeicola massiliensis in adults) [1.19] - #Polysaccharide A, a Toll-like receptor (TLR) 2 ligand, of Bacteroides fragilis, induces Treg cells and suppresses pro-inflammatory TH17 cell responses, thus promoting gut immune tolerance and host–microbial symbiosis. [#Bacteroides thetaiotaomicron] - Some members of the #Bacteroides genus, although belonging to the normal gastrointestinal microbiota, can cause opportunistic infections if the integrity of the intestinal mucosal barrier is broken. These infections are usually polymicrobial, but B. fragilis and B. thetaiotaomicron are the most frequent species isolated. [1.21] [#Autism] [#Prevotella copri] - P. copri and Bacteroides fragilis both co-occurred with phages enriched in #Children with ASD or in neurotypical #Children [1.22] [#ICI therapy] - Bacteroides thetalotaomicron and fragilis with increased anti-CTLA-4 efficacy [#Colorectal cancer] - Certain strains of Bacteroides fragilis, a known intestinal symbiont, have been shown to up-regulate Wnt/B-catenin and NF–KB signaling in chronic #Colitis and CRC tissue. - These strains secrete a specific exotoxin, associated with increased pro-inflammatory Th17 T-cell activity, promoting cell survival [1.23] [#Systemic lupus erythematosus] - Bacteroides fragilis treatment restored the Th17/Treg balance and ameliorated the lupus activity of MRL/lpr mice [1.24] [#Crohn’s disease] - B. fragilis metabolites promote barrier integrity, the prevalence of this bacteria has been associated with disease exacerbation in CD patients [1.25] - The enterotoxigenic Bacteroides fragilis, which has the toxic gene encoding #Fragilysin, has been associated with different diseases. [#Polycystic ovary syndrome] [#Escherichia coli] - In patients with PCOS, there were enrichment of #Fusobacterium, #Escherichia, and #Bacteroides at the genus level and #Bacteroides fragilis and #Escherichia coli at the species level. [1.26] - Bacteroides fragilis and #Prevotella copri (#Bacteroidetes), #Bifidobacterium longum and #Collinsella aerofaciens (#Actinobacteria), and #Helicobacter pylori (#Proteobacteria) can produce #Vitamin B6 as they have these biosynthetic mechanisms [#Bifidobacterium infantis, #Bifidobacterium longum, #Clostridioides difficile, #Kingella denitrificans, #Propionibacterium freudenreichii] - #Vitamin B12 producer are > #Pseudomonas denitrificans, #Bacillus megaterium, and Propionibacterium freudenreichi, Bacteroides fragilis, #Prevotella copri, #Clostridium difficile, #Faecalibacterium prausnitzii, #Ruminococcus lactaris, #Bifidobacterium animalis, B.infantis, B.longum, and #Fusobacterium varium [#Clostridioides difficile, #Lactobacillus bulgaricus, #Lactobacillus delbrueckii, #Limosilactobacillus (Lactobacillus) reuteri] - There are several bacteria that can produce #Folate in the gut, which include Bacteroides fragilis, #Prevotella copri, #Clostridium difficile, #Lactobacillus plantarum, L. reuteri, L. delbrueckii ssp. bulgaricus, #Streptococcus thermophilus, #Bifidobacterium spp. (some species), #Fusobacterium varium, and #Salmonella enterica [#Escherichia coli] [#Biotin] - Bacteria that can produce vitamin B7 include Bacteroides fragilis, #Prevotella copri, #Fusobacterium varium, and #Campylobacter coli [#Niacin] - Bacteroides fragilis, #Prevotella copri, and #Ruminococcus lactaris can also produce vitamin B3 in the gut as they possess a vitamin B3 biosynthesis pathway [1.27] [#Keto diet] - #Bacteroides increased significantly after KD intervention, especially #Bacteroides fragilis. [1.28] - Enterotoxigenic Bacteroides fragilis (ETBF) produces toxins that target the tight junctions of intestinal epithelial cells, cleaving #E-cadherin and promoting inflammation and destruction of the intestinal mucosal barrier. [1.29] [#Colorectal cancer] [#Fusobacterium nucleatum, #Prevotella intermedia] - F. nucleatum-positive CRC tissues featured non-random co-colonization with commensals such as B. fragilis or P. intermedia, whereas tissues lacking F. nucleatum featured different bacterial colonization patterns - Bacteroides fragilis, a typical constituent of the gut microbiota, drives the differentiation of #IL-10-secreting Treg cells by signaling via its capsular #Polysaccharide. - Bacteroides fragilis also were found to protect mice from infection with #Helicobacter hepaticus and #Colitis induced by trinitrobenzene sulfonic acid (TNBS) [1.31] - B. fragilis, was able to ameliorate #Autism spectrum disorder (ASD)–like symptoms in a mouse model by consuming a microbially dependent metabolite #4-ethylphenylsulfate (4EPS) [1.32] [#Bacteroides fragilis group] [#Bacteroides fragilis toxin] - BFT expression increased goblet cell number and goblet-cell-associated passage formation. [1.33] - Enterotoxigenic Bacteroides fragilis (ETBF) is present in colonic mucosa of people with #Familial adenomatous polyposis and promotes oncogenic processes in a tumour-prone mice model. - ETBF does not cause a unique mutational signature unlike the SBS88 and ID18 signatures associated with pks+ E. coli. - epithelium exposed to ETBF undergoes inflammation-driven tumorigenesis and caused a unique DNA methylation signature [1.34] [#Autism] - Treatment of #Adult offspring with B. fragilis attenuated the ASD-like behavioral phenotypes. [#Autism] - ASD > increased #Cholesterol biosynthesis genes in the cortices of B. fragilis treated mice. [#Autism] - The increase in #Bacteroides was initially rather surprising considering a previous rodent study demonstrating that a species of #Bacteroides, B. fragilis, may attenuate ASD-associated behavior. - B. fragilis can affect proper brain development. [#Bacteroides fragilis toxin, #E-cadherin] - Specific strains of B. fragilis excrete a toxin known as B. fragilis toxin (BFT), which is a metalloprotease capable of cleaving E-cadherins > increases gut permeability and may lead to leaky gut. [1.35] [#Major depressive disorder] [#Bacteroides thetaiotaomicron] - the increased availability of mucin may weaken the mucous layer of the intestinal wall, and some #Bacteroides can degrade mucin during survival, such as B. thetaiotaomicron, B. fragilis, as a result, harmful molecules in MDD are more likely to cross the gut and enter the circulatory or endocrine system [1.36] - B. fragilis has the ability to induce the phagocytes of the lamina propria to produce the anti-inflammatory cytokine #IL-10, thereby activating Treg and increasing immune regulation [1.37] [#Colorectal cancer] [#Teenager] - well-known CRC-associated taxa, such as #Clostridium symbiosum, #Peptostreptococcus stomatis, #Parvimonas micra and #Hungatella hathewayi were significantly enriched in both old- and young-onset patients. - Similar strain-level patterns of #Fusobacterium nucleatum, Bacteroides fragilis and #Escherichia coli were observed for oCRC and yCRC. - Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. [1.38] [#Inflamatory bowel disease] - the promoter of #Polysaccharide A (PSA) of Bacteroides fragilis, which induces regulatory T cells (Tregs) and ameliorates experimental #Colitis was mostly oriented “OFF” in IBD patients, which correlated with increased B. fragilis-associated bacteriophages. - in mice colonized with a healthy human microbiota and B. fragilis, induction of #Colitis caused a decline of PSA in the “ON” orientation that reversed as inflammation resolved. - Monocolonization of mice with B. fragilis revealed that bacteriophage infection increased the frequency of PSA in the “OFF” orientation, causing reduced PSA expression and decreased Treg cells. [1.39] [#Immune checkpoint inhibitor] - resistance is attributable to the activity of #Vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis, which positively regulates #Cancer immunity. - enterotoxigenic Bacteroides fragilis (ETBF) was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant #Chemotherapy. - ETBF, albeit at low biomass, secreted the toxic protein #BFT-1 to promote #Breast cancer cell stemness and chemoresistance. - #BFT-1 directly bound to NOD1 and stabilized NOD1 protein.References Notes[ ]