Jason Ridlon, PhD, is helping find treatment strategies to improve human health and animal well-being. He studies gut microbiology, specifically the biochemistry and molecular biology of steroid and bile acid biotransformations by the gut microbiota. He is trying to understand how microbial metabolites promote gastrointestinal tract diseases such as liver and colorectal cancers, as well as essential hypertension.
Bile acids are detergent molecules that allow absorption of dietary fats and fat-soluble vitamins into the bloodstream. Bile acids are synthesized from cholesterol in the liver, secreted into the small intestine where fats are taken up, and transported back to the liver in a recycling process known as the enterohepatic circulation (EHC). The EHC is 95% efficient; however, several hundred milligrams of bile acids enters the large intestine each day where they are converted to toxic and cancer-promoting secondary bile acids by gut bacteria. Secondary bile acids promote diseases of the gastrointestinal tract such as liver and colorectal cancers, and cholesterol gallstone disease. Indeed, a major treatment strategies involves diluting out harmful secondary bile acids by giving patients a bile acid known as ursodeoxycholic acid (UDCA), a minor constituent in humans, but as its name implies makes up the lion's share of bear bile. Problematically, UDCA is converted to a secondary bile acid in the gut, reducing its efficacy. Bacteria capable of metabolizing bile acids are relegated to a small number of species of anaerobic bacteria in the genus Clostridium. A major focus of our research is working out the biochemistry and molecular biology of the pathway that leads to secondary bile acids in Clostridium scindens and related species. In particular, the rate-limiting step in the metabolism of the therapeutic compound UDCA.