Bile Salt Hydrolase Activity‐Based Probes for Monitoring Gut Microbial Bile Acid Metabolism

Apr 2, 2024Chembiochem : a European journal of chemical biology

Tools for Tracking Gut Bacteria's Processing of Bile Acids

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Abstract

Both gut microbiota-associated bile salt hydrolase activity and substrate preference is rhythmic.

The study develops a panel of activity-based probes to assess bile salt hydrolase (BSH) from gut bacteria.
Bile salt hydrolase is crucial for the metabolism of bile acids by gut microbiota.
Rhythmic changes in BSH activity and substrate preference are linked to the feeding patterns of mice.
This approach may help profile BSH activity in different physiological and disease states influenced by circadian rhythms.

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Bile acids are bioactive metabolites that are biotransformed into secondary bile acids by the gut microbiota, a vast consortium of microbes that inhabit the intestines. The first step in intestinal secondary bile acid metabolism is carried out by a critical enzyme, bile salt hydrolase (BSH), that catalyzes the gateway reaction that precedes all subsequent microbial metabolism of these important metabolites. As gut microbial metabolic activity is difficult to probe due to the complex nature of the gut microbiome, approaches are needed to profile gut microbiota-associated enzymes such as BSH. Here, we develop a panel of BSH activity-based probes (ABPs) to determine how changes in diurnal rhythmicity of gut microbiota-associated metabolism affects BSH activity and substrate preference. This panel of covalent probes enables determination of BSH activity and substrate specificity from multiple gut anerobic bacteria derived from the human and mouse gut microbiome. We found that both gut microbiota-associated BSH activity and substrate preference is rhythmic, likely due to feeding patterns of the mice. These results indicate that this ABP-based approach can be used to profile changes in BSH activity in physiological and disease states that are regulated by circadian rhythms.

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Bile Salt Hydrolase Activity‐Based Probes for Monitoring Gut Microbial Bile Acid Metabolism

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