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The aim of this study is to determine relationships among systemic gut microbial metabolite levels and incident cardiovascular disease risks to identify gut microbial pathways as possible targets for personalized therapeutic interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Stable isotope dilution mass spectrometry methods to quantitatively measure aromatic amino acids and their metabolites were used to examine sequential subjects undergoing elective diagnostic cardiac evaluation in two independent cohorts with longitudinal outcome data [US (n = 4000) and EU (n = 833) cohorts]. It was also used in plasma from humans and mice before vs. after a cocktail of poorly absorbed antibiotics to suppress gut microbiota. Multiple aromatic amino acid-derived metabolites that originate, at least in part, from gut bacteria are associated with incident (3-year) major adverse cardiovascular event (MACE) risks (myocardial infarction, stroke, or death) and all-cause mortality independent of traditional risk factors. Key gut microbiota-derived metabolites associated with incident MACE and poorer survival risks include: (i) phenylacetyl glutamine and phenylacetyl glycine (from phenylalanine); (ii) p-cresol (from tyrosine) yielding p-cresol sulfate and p-cresol glucuronide; (iii) 4-OH-phenyllactic acid (from tyrosine) yielding 4-OH-benzoic acid and 4-OH-hippuric acid; (iv) indole (from tryptophan) yielding indole glucuronide and indoxyl sulfate; (v) indole-3-pyruvic acid (from tryptophan) yielding indole-3-lactic acid and indole-3-acetyl-glutamine, and (vi) 5-OH-indole-3-acetic acid (from tryptophan).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Key gut microbiota-generated metabolites derived from aromatic amino acids independently associated with incident adverse cardiovascular outcomes are identified, and thus will help focus future studies on gut-microbial metabolic outputs relevant to host cardiovascular health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehad333","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T17:55:35Z","timestamp":1684950935000},"page":"3085-3096","source":"Crossref","is-referenced-by-count":137,"title":["Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality"],"prefix":"10.1093","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0657-7121","authenticated-orcid":false,"given":"Ina","family":"Nemet","sequence":"first","affiliation":[{"name":"Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute , 9500 Euclid Avenue, Cleveland, Ohio 44195 , USA"},{"name":"Center for Microbiome & Human Health, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195 , 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Human Health, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilja","family":"Demuth","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Charit\u00e9-Universit\u00e4tsmedizin Berlin , Berlin 13353 , Germany"},{"name":"Center for Regenerative Therapies, Berlin Institute of Health (BIH) , Berlin 13353 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Charit\u00e9-Universit\u00e4tsmedizin Berlin , Berlin 13353 , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Steinhagen-Thiessen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Charit\u00e9-Universit\u00e4tsmedizin Berlin , Berlin 13353 , 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