Category: signaling
Bile acids are a two-way signaling currency between host + gut microbiota. Primary bile acids (cholic acid, chenodeoxycholic acid) synthesized in the liver from cholesterol → conjugated with taurine/glycine → secreted into bile → small intestine. Gut bacteria modify them in two steps: (1) deconjugation — bile salt hydrolases (BSH; Bacteroides, Bifidobacterium, Lactobacillus, Clostridium have broad BSH expression) cleave taurine/glycine. (2) 7α-dehydroxylation — performed only by a small Clostridium cluster (XIVa, including C. scindens, C. hylemonae) converting primary → secondary bile acids (CDCA → litho-CA; CA → deoxycholic-CA). Secondary BA differ profoundly in receptor activity (FXR / TGR5, cross-link [[fxr_tgr5_bile_acid_receptor]]) — LCA + DCA are potent TGR5 agonists; tauro-β-muricholic acid (rodents) is a natural FXR antagonist. Enterohepatic recirculation: ~95% reabsorption in terminal ileum via ASBT → portal blood → liver → re-secretion. Disease relevance: dysbiosis (antibiotic-disrupted, IBD, MASH) → altered primary:secondary BA ratio + signaling. C. difficile susceptibility — antibiotic loss of 7α-dehydroxylating bacteria allows C. diff germination (deoxycholic acid normally suppresses germination). FXR-FGF15/19: secondary BA → ileal release of FGF15 (mouse) / FGF19 (human) → hepatic FGFR4 → ↓CYP7A1 → BA synthesis feedback. Therapeutics: UDCA (cytoprotective hydrophilic BA — PBC); colesevelam + cholestyramine (BA sequestrants → ↑synthesis + glycemic + lipid effects); rifaximin (non-absorbed gut antibiotic — IBS-D + HE); FXR agonists (obeticholic acid PBC). Cross-links: [[bile_acid_synthesis]] (upstream), [[fxr_tgr5_bile_acid_receptor]] (host receptors), [[microbiome_scfa_butyrate]] (parallel microbial signaling).