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Objective Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune‐related 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. Methods To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet'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. Results A combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, 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 = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK. Conclusion 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–metagenome interface in TAK subtype prediction and pathogenesis are suggested.

Background and aim: Takayasu's arteritis (TA) is a chronic inflammation that frequently involves the aorta and its major branches. It has been known that atherosclerosis can occur in some TA patients. Objectives: This study aimed to identify the risk factors associated with the development of atherosclerosis in TA. Methods: This retrospective study enrolled a total of 101 TA patients. All patients were divided into two groups according to the absence or presence of atherosclerosis. Baseline demographic features and clinical characteristics were compared between two groups. A logistic model was applied to determine the risk factors associated with the development of atherosclerosis. Results: Our data suggested that the disease duration of patients in the atherosclerosis group was significantly longer than that of patients in the non-atherosclerosis group [96(18.00, 180.00) versus 48.00(12.00, 111.00) months] ( P = .015). In addition, the average age of patients with atherosclerosis was significantly older compared to patients without atherosclerosis [44.00(38.00, 48.00)versus 28.50(24.00，37.00)years] ( P  < .001). Logistic regression analysis showed that the risk of developing atherosclerosis increased by 9.2% per 1 year increase in the disease duration ( P = .005, OR 1.092, 95%CI: 1.027-1.162). Patients with TG/HDL-C ratio more than 0.8875 were associated with a 5.861fold increase of risk developing atherosclerosis ( P  < .001, OR 5.861, 95%CI: 2.299-14.939). Conclusion: Our study indicated that prolonged disease duration and elevated TG/HDL-C ratio are associated with the development of atherosclerosis in TA patients.