Target intelligence / Profile preview

Bile salt hydrolase (BSH)

Target
BSH
Molecular classification
Enzyme, N-terminal nucleophilic hydrolase family
01

Overview

Bile salt hydrolases (BSHs) are microbial enzymes found predominantly in the gastrointestinal tract that catalyze the hydrolysis (“deconjugation”) of conjugated primary bile acids—removing glycine or taurine moieties to yield unconjugated forms. This reaction is a critical gateway step in the transformation of host-derived primary bile acids into secondary forms by other members of the gut microbiota. The resulting changes influence enterohepatic circulation, reduce serum cholesterol levels by increasing fecal loss, modulate lipid absorption, affect host metabolic signaling pathways including those involved in weight gain and circadian rhythm regulation, and shape both immune function and microbial ecology within the intestine. BSH enzymes belong to the N-terminal nucleophilic hydrolase family. They are widely distributed among commensal bacteria such as Lactobacillus, Bifidobacterium, Enterococcus, Clostridium, and others. There is significant diversity among BSHs regarding substrate specificity—different bacterial species express distinct phylotypes with varying efficiency against different conjugated bile salts. Therapeutically, modulation of intestinal BSH activity—primarily through probiotic supplementation—is being explored as a strategy to lower cholesterol levels and manage obesity/metabolic syndrome risk factors. However, increased deconjugation can also lead to higher production of potentially harmful secondary bile acids if not properly balanced within the ecosystem. Note: The query "Cholesterol metabolism via bile salt hydrolase activity" refers not to a single molecule/receptor but rather describes a pathway/process mediated by multiple related enzymes across various microbes. The canonical molecular target here is "Bile salt hydrolase" (not “cholesterol metabolism via…”), so this entry should be flagged as partially incorrect for structured database purposes—it describes an enzymatic process rather than one discrete molecular entity.

Other names
BSHCholoylglycine hydrolase (CGH)Microbial bile salt hydrolase
02

Mechanism of action

BSH is an enzyme, not a receptor or classical drug target. Probiotic strains expressing high BSH activity lower cholesterol by deconjugating bile acids, which reduces reabsorption and increases excretion.

03

Biological functions

Bile acid metabolism (deconjugation of primary bile acids)Regulation of cholesterol metabolism and homeostasisDetoxification of bile salts for bacterial survival in the gutModulation of host lipid absorption and signaling pathways
04

Disease associations

Obesity and metabolic syndrome (potential intervention target)Hypercholesterolemia/cardiovascular disease riskInfection (modulates gut microbiota, impacts pathogen resistance)Other metabolic disorders
05

Safety considerations

Potential generation of toxic secondary bile acids from deconjugated primary bile acidsAltered gut microbiome composition with unknown long-term effects
06

Interacting drugs

Probiotics with high BSH activity
07

Biomarkers

No established clinical biomarkers specific to BSH activity for patient selection or monitoringGene expression levels (in research)Enzymatic assays (in research)

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