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

Area of Science:

• Microbiology
• Metabolomics
• Enzymology

Background:

• Bile acids are crucial metabolites transformed by gut microbiota into secondary bile acids.
• Bile salt hydrolase (BSH) is a key enzyme initiating microbial metabolism of bile acids.
• Probing gut microbial enzyme activity, like BSH, is challenging due to microbiome complexity.

Purpose of the Study:

• To develop activity-based probes (ABPs) for profiling bile salt hydrolase (BSH) activity.
• To investigate the impact of diurnal rhythmicity on gut microbiota-associated BSH activity and substrate preference.

Main Methods:

• Developed a panel of covalent BSH activity-based probes (ABPs).
• Utilized ABPs to determine BSH activity and substrate specificity in anaerobic bacteria from human and mouse gut microbiomes.

Main Results:

• Demonstrated that gut microbiota-associated BSH activity exhibits diurnal rhythmicity.
• Showed that BSH substrate preference is also rhythmic, potentially influenced by feeding patterns.
• Confirmed the utility of ABPs for assessing BSH activity in complex microbial communities.

Conclusions:

• Gut microbiota-associated BSH activity and substrate preference are rhythmic, correlating with host feeding patterns.
• The developed ABP approach is effective for profiling BSH activity.
• This method can be applied to study BSH in physiological and disease states influenced by circadian rhythms.