The gut microbiota has been associated with metabolic diseases, such as type 2 diabetes. In my ERC consolidator award we demonstrated that the gut microbiota is altered following bariatric surgery and that the altered microbiota may be directly linked to some of the metabolic improvements observed following surgery. Interestingly, improved metabolism was associated with altered metabolite production capacity from the microbiota and we observed that a metabolite, imidazole propionate, was reduced after surgery. In associated projects we have demonstrated that imidazole propionate is associated with type 2 diabetes in humans and induce insulin resistance in primary hepatocytes and when injected into mice. Imidazole propionate is synthesized by the microbial enzyme UrdA from histidine. This POC will explore the potential of identifying inhibitors of UrdA to reduce production of imidazole propionate and thereby improve insulin sensitivity. If successful we envision a new class of diabetes medication based on the concept of drug the bug.
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