How Bacterial Enzymes Work in the Gut Microbiome

The human intestines are host to trillions of microorganisms, collectively known as the gut microbiome. In human and animal hosts, the gut microbiome produces enzymes that metabolize small molecules through a series of biochemical transformations. Growing evidence suggests that this metabolic activity confers major immunological and physiological benefits to the host organism.

Identifying the bacterial enzymes at work and understanding their function could provide a basis for treatment and prevention of inflammatory bowel disease, cancer, allergies, metabolic syndrome diseases, and other diseases influenced by the gut microbiome. The metabolic processes, however, remain poorly characterized at the enzymatic level; and current genomics-based techniques have had limited success in elucidating the biochemical pathways involved.

Pamela V. Chang, Microbiology and Immunology, is developing chemical probes that identify active bile salt hydrolases (BSHs)—a critical class of enzymes in the gut microbiome. Chang’s chemical approach will define how bacterial enzymes contribute to the metabolism of important small-molecule metabolites that regulate host physiology and pathology. By applying the chemical probes to mouse models and human patient samples, Chang’s lab will compare BSH activity in healthy hosts and in hosts with inflammatory diseases of the intestines. The probes will also facilitate imaging of active BSHs in healthy and diseased tissues, enabling Chang’s lab to locate active bacterial niches.

The project provides a deeper understanding of host-microbiome interactions in the gut and how they influence human health and disease.

NIH Award Number: 1R35GM133501-01

Cornell Researchers

Funding Received

$1.9 Million spanning 5 years