Fan Luyun, Chen Junru, Pan Lili, Xin Xiaohong, Geng Bin, Yang Lirui, Wang Qian, Ma Wenjun, Lou Ying, Bian Jin, Cui Xiao, Li Jing, Wang Lu, Chen Zhenzhen, Wang Wenjie, Cui Changting, Li Shuangyue, Gao Qiannan, Song Qirui, Deng Yue, Fan Jiali, Yu Jiachen, Zhang Huimin, Li Yafeng, Cai Jun
State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China, and Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China.
Arthritis Rheumatol. 2023 Feb;75(2):266-278. doi: 10.1002/art.42331. Epub 2022 Dec 14.
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.
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.
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.
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.
越来越多的证据表明，微生物组和代谢组与全身自身免疫性疾病和心血管疾病（CVD）有关。大动脉炎（TAK）是一种罕见疾病，兼具免疫相关炎症性疾病和CVD的特征，关于该病的信息相对有限。本研究旨在描述TAK患者肠道微生物群失调情况及其与疾病表型的相互作用。
为了确定具有鉴别意义的特征，我们对一个发现队列（n = 97）和一个独立验证队列（n = 75）的粪便宏基因组进行了鸟枪法测序，这两个队列包括TAK患者、健康对照以及白塞病（BD）对照。我们还对血浆和粪便样本进行非靶向代谢组学和脂质组学分析，以完善介导微生物与TAK表型之间关联的特征。
一个由多种细菌组成的联合模型，包括未分类的大肠杆菌、小韦荣球菌、副血链球菌、甲酸多雷氏菌、青春双歧杆菌、毛螺菌科细菌7_1_58FAA、大肠杆菌、唾液链球菌、肺炎克雷伯菌、长双歧杆菌和毛螺菌科细菌5_1_63FAA，可将TAK患者与对照组区分开来，在包括健康或BD对照的训练集、测试集和验证集中，曲线下面积（AUC）分别为87.8%、85.9%、81.1%和71.1%。诊断性细菌种类与TAK的血管受累、炎症、停药及预后等表型直接或间接（通过代谢物或脂质）相关。针对高血压、心房颤动和健康对照的公开宏基因组研究（n = 184）进行外部验证，证实了该模型对TAK的诊断准确性。
本研究首次确定了TAK中具有鉴别意义的肠道微生物。失调的微生物还通过代谢和脂质模块直接或间接与TAK表型相关。建议进一步探索微生物组-宏基因组界面在TAK亚型预测和发病机制中的作用。
