Creating a lasting blocker for gut bacteria enzymes that process bile salts

A covalent pan-inhibitor of gut bacterial BSHs was developed that can significantly reduce BSH activity in vivo.

• Bile salt hydrolase enzymes are crucial for the conversion of bile acids in the gut.
• The identified lead compound modifies BSH at a specific site, effectively inhibiting its activity.
• In conventional mouse feces, this inhibitor completely abolished BSH activity.
• Mice treated with the inhibitor showed reduced BSH activity and lower levels of deconjugated bile acids in their feces.
• These findings suggest that modulation of bile acid composition could be achieved using this covalent inhibitor.

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