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Takayasu arteritis (TAK) is a rare disease that shares features of immune\u2010related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n\u00a0=\u00a097) and an independent validation cohort (n\u00a0=\u00a075) including TAK patients, healthy controls, and controls with Beh\u00e7et's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A combined model of bacterial species, including unclassified <jats:italic>Escherichia<\/jats:italic>, <jats:italic>Veillonella parvula<\/jats:italic>, <jats:italic>Streptococcus parasanguinis<\/jats:italic>, <jats:italic>Dorea formicigenerans<\/jats:italic>, <jats:italic>Bifidobacterium adolescentis<\/jats:italic>, <jats:italic>Lachnospiraceae bacterium 7 1 58FAA<\/jats:italic>, <jats:italic>Escherichia coli<\/jats:italic>, <jats:italic>Streptococcus salivarius<\/jats:italic>, <jats:italic>Klebsiella pneumoniae<\/jats:italic>, <jats:italic>Bifidobacterium longum,<\/jats:italic> and <jats:italic>Lachnospiraceae Bacterium 5 1 63FAA<\/jats:italic>, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n\u00a0=\u00a0184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome\u2013metagenome interface in TAK subtype prediction and pathogenesis are suggested.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42331","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T12:09:42Z","timestamp":1661256582000},"page":"266-278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Alterations of Gut Microbiome, Metabolome, and Lipidome in Takayasu Arteritis"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2691-0443","authenticated-orcid":false,"given":"Luyun","family":"Fan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 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