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Poster Session 2025

Gut Bacterial Conversion of Endogenous Corticoids into GALFs

Presented By: Jasmine Walsh

Gut bacteria convert endogenous steroids found in the gut into new classes of steroids, thereby changing their biological functions in the host. Our lab previously discovered a conversion performed by gut bacteria known as 21-dehydroxylation, which transforms glucocorticoids into progestins. Here, we report our progress towards elucidating a novel bacterial enzymatic pathway that converts tetrahydrocorticosterone, an abundant glucocorticoid secreted in bile, into a glycyrrhetinic acid-like factor (GALF) found in human feces. GALFs increase blood pressure by blocking the mammalian enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSDH), an enzyme that converts cortisol into its inactive form, cortisone. Increased levels of cortisol result in offtarget activation of the mineralocorticoid receptor, leading to increased salt and water retention and ultimately increased blood pressure. By discovering gut bacteria that produce a GALF as well as genes responsible for this transformation, our research may lay the groundwork for new microbiome-targeted therapies to treat diseases characterized by increased cortisol levels, including hypertension.