The First Affiliated Hospital of Chongqing Medical University , Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, China.
Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai, China.
Gut Microbes. 2020 May 3;11(3):539-555. doi: 10.1080/19490976.2019.1700754. Epub 2020 Jan 13.
Vogt-Koyanagi-Harada (VKH) disease is a multisystemic autoimmune disorder characterized by granulomatous panuveitis. Gut microbiome has been considered to play a role in the pathogenesis of this disease but whether the alternation of gut microbiome was involved is unclear. This study was set up to identify abnormalities of gut microbiome composition in VKH disease.
Depleted butyrate-producing bacteria, lactate-producing bacteria and methanogens as well as enriched Gram-negative bacteria were identified in the active VKH patients, as well as in VKH patients of Mix enterotype and enterotype. Changes of gut microbiome in the VKH patients were partially restored after an immunosuppressive treatment. The disease susceptibility genotype HLA-DRA was associated with and . A microbial marker profile including 40 disease-associated species was established to differentiate patients from controls. Another microbial marker profile including 37 species was found to be associated with the response to treatment. An animal experiment showed that transfer of gut microbiome from VKH patients could significantly exacerbate disease activity clinically and pathologically in the recipient mice.
Our results revealed a distinct gut microbiome signature in VKH patients and showed an exacerbating effect of this gut microbiome on experimental autoimmune uveitis (EAU). We also developed two microbial marker profiles in differentiating VKH patients from healthy controls as well as predicting the effectiveness of treatment.
Vogt-小柳-原田(VKH)病是一种多系统自身免疫性疾病,其特征为肉芽肿性全葡萄膜炎。肠道微生物群被认为在这种疾病的发病机制中起作用,但肠道微生物群的改变是否参与其中尚不清楚。本研究旨在确定 VKH 病中肠道微生物组组成的异常。
在活动期 VKH 患者以及混合肠型和肠型 VKH 患者中,发现丁酸产生菌、乳酸产生菌和产甲烷菌减少,革兰氏阴性菌富集。免疫抑制治疗后,VKH 患者的肠道微生物组变化部分得到恢复。疾病易感性基因型 HLA-DRA 与 和 相关。建立了一个包括 40 种疾病相关物种的微生物标志物特征谱,以将患者与对照区分开来。还发现另一个包括 37 个物种的微生物标志物特征谱与治疗反应相关。动物实验表明,从 VKH 患者转移的肠道微生物群可显著在受者小鼠中临床和病理上加重疾病活动。
我们的结果揭示了 VKH 患者中独特的肠道微生物组特征,并显示了这种肠道微生物组对实验性自身免疫性葡萄膜炎(EAU)的加重作用。我们还开发了两种微生物标志物特征谱,用于将 VKH 患者与健康对照区分开来,以及预测治疗效果。