To unravel the critical roles bile acids play in human health within the gut, we have developed photoaffinity bile acid probes to use in profiling experiments to target (1) the microbial cells and enzymes associated with their metabolism, and (2) their interactions with host signaling pathways. Bile acids are cholesterol-derived molecules that play a role in nutrient absorption, and have been shown to regulate host energy and lipid metabolism in mammals. Changes in the profile of the bile acid pool have been associated with decreased weight gain and reduction of obesity co-morbidities such as insulin resistance. The gut microbiome can alter the composition of the bile acid pool through chemical modification of primary bile acids to produce secondary bile acids, which have unique biological activity. It will be important to understand the microbial taxa and enzymes involved in conversion of primary bile acids to secondary bile acids. Additionally, understanding how the interactions of bile acids with host nuclear receptors change as a result of perturbation (e.g., diet) will help clarify their role in human health. Our understanding of bile acid metabolism has been greatly hampered by the lack of technologies capable of identifying mechanistic relationships between the specific enzymes and taxa within the microbiome that are directly responsible for bile acid modification, and the host pathways that respond to those metabolites. We demonstrate that our activity-based protein profiling approach is well-suited to answer these important questions.

Activity-based protein profiling of bile acid metabolism and host signaling in the gut microbiome

254th National Meeting (2017)

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