Bile Salt Hydrolase (BSH)

Downstream Consequences#

Deconjugated bile acids undergo further microbial transformation (7α-dehydroxylation) to produce secondary bile acids (deoxycholic acid, lithocholic acid), which.

Activate FXR and TGR5 nuclear receptors → regulate cholesterol metabolism, gluconeogenesis, and energy expenditure. Are directly antimicrobial—secondary bile acids inhibit C. difficile germination (basis of Colonization Resistance). At high concentrations, are pro-carcinogenic—DCA promotes CRC by generating ROS and activating Wnt/β-catenin.^{[1]Rezen et al. 2022 — The Role of Bile Acids in CarcinogenesisRezen T, Rozman D, Kovacs T et al. · 2022Open reference 1 ↓}

WikiBiome Relevance#

BSH activity determines the balance between primary and secondary bile acids—a balance disrupted by Dysbiosis.

Antibiotic-induced loss of BSH-producing bacteria → primary bile acid accumulation → C. difficile spore germination (primary bile acids promote it; secondary bile acids inhibit it).

BSH is a target for probiotic engineering—enhancing BSH activity could improve cholesterol metabolism.