Catalytic mechanisms and physiological consequences of microbial bile acid conjugation

Douglas V. Guzior^1,2

1. Department of Microbiology, Genetics, and Immunology, Michigan State University, East Lansing, MI, USA
2. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA

Abstract

Bile acids (BAs) are an integral component of the human digestion and gastrointestinal health. They function as detergents for nutrient absorption, antimicrobial compounds, and signaling molecules. It has long been known that humans produce both glycine and taurine conjugated primary BAs in the liver from cholesterol, storing them in the gallbladder prior to a meal. Production of these conjugated BAs was thought to be performed exclusively by the host for decades until the gut bacterium Enterocloster bolteae was shown to produce phenylalanine, tyrosine, and leucine conjugated cholate, the first described microbially conjugated bile acids (MCBAs). However, little was known about how MCBAs are made, which microbes produce them, and least of all, their impacts on human health. In this seminar, I will describe the discovery that acyl transfer activity from the enzyme bile salt hydrolase (BSH), one of the most ubiquitous enzymes produced across gut microbiome, is responsible for the production of MCBAs. Diverse BSH enzymes from diverse gut microbes can produce a plethora of MCBAs, greatly expanding the chemistry of the human bile acid pool. Leveraging murine models, I will describe how MCBAs impact the host microbiome and can enter circulation throughout the body. Finally, I show how MCBA concentrations change within both the dysbiotic gut, through a sleeve gastrectomy patient cohort, and within the developing gut, through an infant cohort. Taken together, this work teases apart the “who” and “how” of microbial bile acid conjugation, while also contributing to our understanding of the grand question of “why”.

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