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21 Cards in this Set
- Front
- Back
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Main functions of gut microflora |
1.Colonization resistance 2. Production of vitamins 3. Metabolism of xenobiotics 4. Digestion of plant polysaccharides (dietary fibers) and host-derived mucopolysaccharides 5. development of intestinal immune system |
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Colonization resistance |
1. Spatial inhibition to counter pathogen colonization -compete for receptor that fimbriae bind to -compete for nutrients, co-factors -produce inhibitory factors 2. Large spectrum antibiotics disrupt colonization resistance, favoir colonization by pathogens (C. difficile and proteobacteria) |
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Effect of antibiotic Streptomycin |
1. induced dysbiosis at day 1, homeostasis recovered by day 5 2. Proliferation of proteobacteria and deferribacteres. |
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Nitrate production |
1. Nitrate (NO3-) is a by-product of host inflammatory response to dysbiosis. 2. derived from reactive nitrogen/oxygen species such as NO(nitric oxide) produced by iNOS and O2-. 3. Anaerobic nitrate respiration leads to proliferation of Proteobacteria (Enterobacteria like E. coli mostly) because Firmicutes and bacteroidetes can't used nitrate as electron acceptor. |
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Production of vitamins by microbiota |
1. Bifidobacteria (phylum Actinobacteria) can synthesize vitamins de novo 2. synthesized vitamins by gut commensals(4): folate, riboflavin(B2), cobalamin(B12), vitamin K |
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Metabolism of Xenobiotis |
xenobiotics include drugs, antibiotics and diet derived bioactive compounds. 1. Actinobacterium Eggerthella lenta can inactivate cardiac drug digoxin(used to treat fibrillation and heart failure.(add two H) 2. Proteobacterium Klebsiella terrigena can produced cyanuric acid from melamine.
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Digestion of plant polysaccharides |
1. indigestible unless microflora metabolizes(4): pectin, cellulose, xilan and starches 2. bacterial metabolism of plant carbohydrates generate short chain fatty acids (acetate, butyrate, propionate) accounting for 10% of daily absorbed calories 3. Bacteroidetes are well equipped for degradation (contain many glycoside hydrolases) |
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Bacteroides thetaiotaomicron |
1. 6.3Mbp 2. glycophile, 163 OMPs that bind carbohydrates, over 250 glycoside hydrolases 3. simple sugars absorbed through intestinal villi |
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Breakdown of starch by B. thetaiotaomicron |
1. SusC and SusD essential for binding of starch to bacterial surface 2. SusG performs limited hydrolysis on OM. SusA performs more extensive hydrolysis in periplasm 3. Uptake of oligosaccharides by ABC-transporters(from periplasm to cytosol) |
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Effects of SCFAs |
1. can reach up to 100 mM in distal colon 2. Although all SCFAs influence colonic health, Butyrate appears to have important specific functions 3. Butyrate acts as energy source for enterocytes |
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List of effects of SCFAs |
1. Competitive exclusion(high fiber expands commensal, deplete pathogen) 2. promotion of mucus 3. secretion of IgA 4. promotion of tissue repair and wound healing 5. promotion of Treg cell development 6. (particularly acetate) enhancement of epithelial integrity by inflammasome activation and IL-18 activation 7. anti-inflammatory effect --> inhibition of NFkB |
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SCFAs reduce Intestinal inflammation |
1. SCFAs ligands for GPR41 and GPR43 expressed by Treg. 2. Stimulate Treg expansion and immune-suppressive properties such as IL-10 production. |
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Butyrate-producing Bacteria |
1. Butyrate produced by Clostridial clusters IV and XIVa -IV: Faecalibacterium prausnitzii -XIVa: Eubacterium rectale, Roseburia intestinalis 2. Clostridium species are very heterogenous. grouped into 19 clusters based on 16s rDNA sequencing. Some were Eubacterium |
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Effects of butyrate |
1. inhibition of HDAC(histone deacetylase) leading to increased expression of Foxp3 gene --> facilitates differentiation of naive CD4+ T cells into Treg 2. Induces TGF-beta secretion by epithelial 3. Butyrate bind to Gpr109a(niacin receptor) on epithelial cell --> cytokine IL-18 production 4. Stimulates IL-10 and retinoic acid production by DC and macrophages. |
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Bacteroides fragilis PSA |
1. B. fragilis produces 8 capsular polysaccharides (CPS) 2. PSA signals through TLR-2 on CD4+ T cells to induce Treg differentiation
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PSA-mediated protection from inflammation |
1.Mice colonized with Helicobacter hepaticus and B. fragilis expressing PSA do not develop colitis.(without PSA, express colitis) 2. release of IL-10 by Treg decrease level of inflammatory cytokines (IL-1beta, IL-23, TNF-alpha) |
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Segmented filamentous bacteria(SFB) |
1.gram-positive bacteria that colonize mice small intestine at time of starvation. A pathobiont 2. association of SFB with intestinal cells modulates enterocytes gene expression 3. Serum amyloid A induced by SFB, stimulate intestinal DCs to produce IL-6/23 that promote Th17 differentiation 4. promote experimental autoimmune diseases like EAE and autoimmune arthritis |
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Immunomodulation by gut microbiota |
1. B. fragilis --> PSA --> TGFbeta(DC) --> Treg 2. Clostridium spp --> TGFbeta --> Treg 3. SCFAs --> GPR43, HDAC inhibitor --> Treg 4. ATP --> Th17 5. SFB --> SAA --> Th17 |
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Probiotics |
Live microorganism that are ingested to improve balance of GI tract microbiota. 1. Lactobacillus rhamnosus GG, L. plantarum 299v and L. acidophilus (G+) 2. Bifidobacterium longum and B. bifidum (Actino, G+) 3. E. coli Nissle 1917 (G-) 4. Saccharomyces boulardii (yeast) |
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Prebiotics |
Dietary supplements that stimulate the growth or activity or certain beneficial gut microbes - inulin, plant polysaccharide |
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E. coli cancer-inducing activity |
1. 34% of commensal E. coli produce genotoxin colibactin - including strains NC101, Nissle 1917, ExPEC isolates 2. toxin induce breaks in DNA of eukaryotic cells 3. Colibactin-producing bacteria found in 20% health ppl, 40% ppl with Inflammatory bowel disease and 66% of colorectal cancer |
