Bile salt hydrolase enzyme (BSH)

Bile salt hydrolase enzyme (BSH) is a microbial enzyme predominantly found in various genera within the human gut microbiota, including Lactobacillus, Enterococcus, Bacteroides, and others. It catalyzes the hydrolysis (“deconjugation”) of glycine-conjugated or taurine-conjugated primary bile acids into free (unconjugated) forms. This reaction represents a critical gateway step in enterohepatic circulation and further modification by other microbes into secondary bile acids. BSH enzymes belong to the N-terminal nucleophilic hydrolase family; they typically function as homotetramers but can also form dimers or heterotrimers depending on species. The catalytic mechanism involves an N-terminal cysteine residue essential for amide bond cleavage. Functionally, these enzymes play key roles not only in shaping host lipid absorption and cholesterol metabolism but also influence immunity by modulating signaling pathways through altered pools of bioactive secondary metabolites. In probiotics development, strains with high BSH activity are often selected due to their ability to detoxify harmful conjugated bile salts—improving both bacterial survival under intestinal stress conditions and potentially benefiting host health. However, excessive deconjugation can lead to accumulation of toxic secondary metabolites with adverse effects on both bacteria and host tissues. Thus, while considered a promising therapeutic target—especially for metabolic disorders like hypercholesterolemia—the safety profile requires careful evaluation.

Other names

BSHMicrobial bile salt hydrolaseGut bacterial bile salt hydrolase

Drugs or compounds targeting this enzyme would act by inhibiting its deconjugation activity, thereby altering the composition and function of the gut microbiome and host metabolism. This is an area under investigation for metabolic diseases and infection control.