Host-microbe symbiosis: germ-free / gnotobiotic biology; gut microbiota composition + enterotypes; colonization resistance; dysbiosis; SCFA + bile-acid metabolic axis; mucus and Paneth-cell barriers; secretory IgA; clostridia-induced…
Host-Microbiome
Germ-free animal hypothesis
Pasteur 1885 hypothesised animals require microbes to live; Reyniers et al 1949 produced first viable germ-free mice; refuted Pasteur,…
Gnotobiology
Reyniers; axenic = wholly germ-free vs gnotobiotic = defined-flora; controlled colonisation as causal-inference tool for microbiota studies.
Gut microbiome composition
Adult gut harbours ~10^11 bacteria/g; >1000 species; Firmicutes and Bacteroidetes dominant; community composition individual-stable but…
Arumugam enterotypes
Arumugam et al 2011 Nature; three discrete gut-microbiome enterotypes (Bacteroides, Prevotella, Ruminococcus dominated); diet-correlated;…
Germ-free immune deficit
Germ-free mice show small Peyer's patches, low IgA, reduced gut intra-epithelial lymphocytes; commensal microbes required for normal…
Colonization resistance
van der Waaij 1971; commensal microbiota competitively exclude exogenous pathogens via niche, nutrient and metabolite competition;…
Dysbiosis
Pathological shift in microbial composition or function associated with IBD, obesity, diabetes, atopy; correlative-vs-causal status varies…
Fecal microbiota transplant (FMT)
Eiseman et al 1958 first FMT for pseudomembranous colitis; modernised by Borody and extended to recurrent C. difficile; transplanted donor…
Short-chain fatty acids (SCFA)
Microbial fermentation of dietary fibre yields acetate, propionate, butyrate; butyrate is colonocyte energy source and HDAC inhibitor with…
Bile-acid microbiome axis
Microbial 7-alpha-dehydroxylation converts primary to secondary bile acids; secondary bile acids signal through FXR/TGR5 and regulate host…
Intestinal mucus layer
Johansson-Hansson et al; colon mucus has dense inner layer (sterile) and loose outer layer (microbiota-permissive); MUC2 polymerised…
Paneth-cell defensins
Paneth cells in small-intestine crypts secrete alpha-defensins (cryptdins in mouse, HD5/HD6 in human); shape commensal microbiota and limit…
Secretory IgA and microbiome
Polymeric IgA dimerises, transports across epithelium via pIgR, coats commensal and pathogenic bacteria; T-cell-independent and dependent…
Clostridia-induced Tregs
Atarashi et al 2011 Science; 17-strain Clostridia clusters IV/XIVa cocktail induces colonic regulatory T cells via SCFA and unidentified…
Microbiota-gut-brain axis
Vagal afferents, neuroactive metabolites (SCFA, GABA, tryptophan), immune mediators link gut microbiota to host brain function; Cryan-Dinan…
Germ-free behavioural changes
Sudo et al 2004 J Physiol; germ-free mice have exaggerated HPA-axis stress response and altered anxiety behaviour; reversed by colonisation…
FMT for recurrent C. difficile (RCT)
van Nood et al 2013 NEJM; randomised trial of FMT vs vancomycin for recurrent C. difficile colitis; 81% vs 31% cure; trial halted early for…
Host genetics and microbiome
Twin and GWAS studies show modest heritability of specific microbial taxa; lactase-persistence allele alters Bifidobacterium abundance;…