{"doi":"10.17615/vrx4-j764","title":"Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk","abstract":"Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (N>4000) independently predicted incident (3 yr) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced submaximal stimulus-dependent platelet activation from multiple agonists through augmented Ca2+ release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation, collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential, and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk.","journal":"UNC Libraries","year":2020,"id":65158,"datarank":1.8560166006894168,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":1.234546391730687,"self_endowment_contribution":0.62147020895873,"citer_contribution":1.234546391730687,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":61,"citers_with_citation_signal":38,"citers_with_endowment":38,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9484,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":344666,"name":"Elin Org","orcid":"0000-0001-8688-9717","position":1,"is_corresponding":false},{"id":108894,"name":"Joseph A. DiDonato","orcid":"0000-0002-1641-1758","position":2,"is_corresponding":false},{"id":36349,"name":"R. Balfour Sartor","orcid":"0000-0002-7820-632X","position":3,"is_corresponding":false},{"id":30816,"name":"W. H. Wilson Tang","orcid":"0000-0002-8335-735X","position":4,"is_corresponding":false},{"id":109852,"name":"Roy L. Silverstein","orcid":"0000-0001-7859-9154","position":5,"is_corresponding":false},{"id":344667,"name":"Xiaoming Fu","orcid":"0000-0002-8012-4753","position":6,"is_corresponding":false},{"id":108884,"name":"Weifei Zhu","orcid":"0000-0003-4355-134X","position":7,"is_corresponding":false},{"id":108883,"name":"Nilaksh Gupta","orcid":"0000-0002-9449-2610","position":8,"is_corresponding":false},{"id":346395,"name":"Jill C. Gregory","orcid":null,"position":9,"is_corresponding":false},{"id":261938,"name":"J. Mark Brown","orcid":"0000-0003-2708-7487","position":10,"is_corresponding":false},{"id":15457,"name":"Aldons J. Lusis","orcid":"0000-0001-9013-0228","position":11,"is_corresponding":false},{"id":108895,"name":"Stanley L. Hazen","orcid":"0000-0001-7124-6639","position":12,"is_corresponding":false},{"id":236693,"name":"Margarete Mehrabian","orcid":"0000-0002-8569-8852","position":13,"is_corresponding":false},{"id":344668,"name":"Thomas M. McIntyre","orcid":"0000-0001-7802-5900","position":14,"is_corresponding":false},{"id":261936,"name":"Zeneng Wang","orcid":"0000-0002-6455-8228","position":15,"is_corresponding":false},{"id":346396,"name":"Jennifer A. Buffa","orcid":null,"position":16,"is_corresponding":false},{"id":344669,"name":"Yuping Wu","orcid":"0000-0002-0833-1205","position":17,"is_corresponding":false},{"id":344665,"name":"Lin Li","orcid":"0000-0001-9418-9470","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:13:23.327603Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}