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The research in our laboratory focuses on the role of steroid and bile acid metabolism on human and animal health and disease. Small modifications to host steroids and bile acids can have large physiological consequences for the host. We focus on discovering genes encoding enzymes involved in steroid and bile acid biotransformations. We view host-associated microbiomes as extensions of the host endocrine system, and the mapping out of biochemical pathways is an important step in shifting host steroid and bile acid profiles to promote health. Prof. Ridlon defines the “sterolbiome” as the the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. A mechanistic approach to understanding the role of bacterial sterolbiome genes is to compare the effect of colonization of genetically identical bacterial strains that differ only in the presence or absence of a particular gene or set of genes on physiological, immunological, and gene-expression changes in a germ-free animal. Two focus areas in our laboratory include: (1) Conversion of cortisol to 11-oxy-androgens by gut and urinary tract bacteria. We are utilizing a germ-free piglet and mouse model to understand the effect of 11-oxy-androgen formation on intestinal physiology and the global distribution of 11-oxy-androgens. A clinical study is currently underway to understand the role of urinary 11-oxy-androgen formation in the development of prostate cancer. (2) Oxidation, epimerization, and 7-dehydroxylation of host primary bile acids. The gut microbiome greatly diversifies the composition of bile acid metabolites which alters their signaling properties and toxicity both for the host and the microbiome. We are working out biochemical pathways involved in hydroxyl group modification of bile acids and the role of these metabolites in human and animal physiology and disease. We utilize a combination of approaches including anaerobic microbial culturing & engineering, transcriptomics, metabolomics, enzymology & structural biology, microbiome sequencing, gnotobiotic animal models, and clinical studies to uncover the role of the sterolbiome in host physiology and diseases such as colorectal cancer and prostate cancer.