title: Targeting of microbe-derived metabolites to improve human health: The next frontier for drug discovery.
abstract: Recent advances in metabolomic and genome mining approaches have uncovered a poorly understood metabolome that originates solely or in part from bacterial enzyme sources. Whether living on exposed surfaces or within our intestinal tract, our microbial inhabitants produce a remarkably diverse set of natural products and small molecule metabolites that can impact human health and disease. Highlighted here, the gut microbe-derived metabolite trimethylamineN-oxide has been causally linked to the development of cardiovascular diseases. Recent studies reveal drugging this pathway can inhibit atherosclerosis development in mice. Building on this example, we discuss challenges and untapped potential of targeting bacterial enzymology for improvements in human health.
authors.affiliation: From the Departments of Cellular and Molecular Medicine and brownm5@ccf.org.|Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio 44195.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Brown
authors.affiliation: From the Departments of Cellular and Molecular Medicine and hazens@ccf.org.|Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio 44195.|Cardiovascular Medicine and.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology; D055808:Drug Discovery; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008744:Methylamines / Q000378:metabolism / Q000633:toxicity; D051379:Mice
chemical_list: D008744:Methylamines; C005855:trimethyloxamine
keywords: atherosclerosis; cardiovascular disease; drug discovery; metabolomics; microbiome