Inhibiting Disease-Associated Anaerobic Choline Metabolism by Human Gut Bacteria

Abstract

The anaerobic gut microbial pathway that converts choline into trimethylamine (TMA) is broadly linked to human disease. Here, we describe the discovery that betaine aldehyde inhibits TMA production from choline by human gut bacterial isolates and a complex gut community. The workflow we establish for identifying and characterizing betaine aldehyde provides a framework for developing additional inhibitors of gut microbial choline metabolism. We also describe further efforts towards discovering small molecule inhibitors of CutC-mediated choline cleavage. Overall, our results show that small molecules can interfere with choline metabolism by anaerobic gut microbes and sets the stage for more extensive efforts to discover novel potent inhibitors of this pathway.