Bile acid receptor signaling in metabolic dysfunction-associated steatotic liver disease: Mechanistic insights and emerging therapeutic strategies

Table 3 Microbial enzymes, bile acid transformations, and receptor-mediated effects in metabolic dysfunction-associated steatotic liver disease pathogenesis[53,54]

Microbial enzyme	Bile acid transformation	Key products	Receptor binding	Pathophysiological effects in MASLD
BSH	Deconjugation of taurine/glycine-conjugated BAs	Free primary BAs (e.g., CA, CDCA)	↑FXR (CDCA) ↓TGR5	Facilitates FXR activation in ileum to ↑FGF19 to ↓BA synthesis; however, dysregulation may lead to FXR desensitization
7α-dehydroxylase	Removal of 7α-hydroxyl group from primary BAs	DCA (from CA), LCA (from CDCA)	↑TGR5 ↓FXR (weak agonists)	↑GLP-1, ↑energy expenditure (via TGR5); ↑pro-inflammatory signaling (via TLR4, MAPK); ↓intestinal FXR signaling
HSDH	Epimerization and oxidation of hydroxyl groups	Iso- and oxo-BA forms	Varies (limited data)	May alter BA pool toxicity and gut-liver signaling; epimers often show reduced receptor affinity
Sulfatases	Desulfation of secondary bile acids	Unconjugated secondary BAs	↑TGR5	Increases bioavailability of TGR5 agonists (e.g., LCA) to promotes anti-inflammatory and metabolic signaling
Dehydrogenases and reductases	Oxidation-reduction reactions of hydroxyl/keto groups	Oxo-bile acids, dehydro forms	↓FXR (typically weak)	May lead to accumulation of hepatotoxic bile acid species to ↑oxidative stress and inflammation

BSH: Bile salt hydrolase; HSDH: Hydroxysteroid dehydrogenase; BA: Bile acid; CA: Cholic acid; CDCA: Chenodeoxycholic acid; DCA: Deoxycholic acid; LCA: Lithocholic acid; FXR: Farnesoid X Receptor; TGR5: Takeda G Protein-Coupled Receptor 5; FGF19: Fibroblast growth factor 19; TLR4: Toll-like receptor 4; MAPK: Mitogen-activated protein kinase; MASLD: Metabolic dysfunction-associated steatotic liver disease.