Bile salt hydrolase (BSH) (BSH)

Bile salt hydrolase (BSH) is a microbial enzyme primarily produced by gut bacteria that catalyzes the deconjugation of bile acids, representing a critical "gateway" step in intestinal bile acid transformation. By hydrolyzing the amide bond of glycine- or taurine-conjugated bile salts, BSH releases free bile acids and amino acids into the intestinal lumen. This transformation significantly alters the physicochemical properties of bile acids, reducing their efficiency in dietary lipid emulsification and affecting their reabsorption and signaling through host receptors such as the Farnesoid X Receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). Modulating BSH activity has emerged as a promising strategy for treating metabolic diseases, including obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). Inhibition of BSH increases the levels of conjugated bile acids, which can improve glucose metabolism and prevent weight gain by acting as potent FXR antagonists or TGR5 agonists. Conversely, BSH-expressing probiotics are used to lower serum cholesterol by increasing the fecal excretion of deconjugated bile acids. Beyond metabolism, BSH activity is also implicated in gut inflammation and is being explored as a biomarker and therapeutic target for inflammatory bowel disease (IBD).

Other names

Cholylglycine hydrolaseConjugated bile salt hydrolase (CBSH)Glycocholate hydrolaseBile salt deconjugase

Modulation of bile acid deconjugation to alter the composition of the bile acid pool, thereby shifting signaling through host receptors like FXR and TGR5 to regulate metabolic, inflammatory, and immune pathways.