{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang Z"],"funding":["NIDDK NIH HHS","NHLBI NIH HHS","PHS HHS","NIH HHS"],"pagination":["1585-95"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4871610"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["163(7)"],"pubmed_abstract":["Trimethylamine (TMA) N-oxide (TMAO), a gut-microbiota-dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here, we investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial TMA production, on diet-induced atherosclerosis. A structural analog of choline, 3,3-dimethyl-1-butanol (DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production from physiologic polymicrobial cultures (e.g., intestinal contents, human feces) and reduce TMAO levels in mice fed a high-choline or L-carnitine diet. DMB inhibited choline diet-enhanced endogenous macrophage foam cell formation and athero"],"journal":["Cell"],"pubmed_title":["Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis."],"pmcid":["PMC4871610"],"funding_grant_id":["P20 HL113452","P01H28481","R01 HL103866","P01 HL028481","S10 OD016346","R01HL103866","R01106000","R01 DK106000"],"pubmed_authors":["Gu X","Fu X","Org E","Roberts AB","Krajcik D","Hazen SL","DiDonato JA","Hazen JE","Huang Y","Buffa JA","Levison BS","Lusis AJ","Zhu W","DiDonato AJ","Wang Z","Zamanian-Daryoush M","Culley MK"],"additional_accession":[]},"is_claimable":false,"name":"Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis.","description":"Trimethylamine (TMA) N-oxide (TMAO), a gut-microbiota-dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here, we investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial TMA production, on diet-induced atherosclerosis. A structural analog of choline, 3,3-dimethyl-1-butanol (DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production from physiologic polymicrobial cultures (e.g., intestinal contents, human feces) and reduce TMAO levels in mice fed a high-choline or L-carnitine diet. DMB inhibited choline diet-enhanced endogenous macrophage foam cell formation and athero","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Dec","modification":"2026-05-30T11:26:30.458Z","creation":"2019-03-27T02:14:08Z"},"accession":"S-EPMC4871610","cross_references":{"pubmed":["26687352"],"doi":["10.1016/j.cell.2015.11.055"]}}