Huang Juan, Pearson James A, Peng Jian, Hu Youjia, Sha Sha, Xing Yanpeng, Huang Gan, Li Xia, Hu Fang, Xie Zhiguo, Xiao Yang, Luo Shuoming, Chao Chen, Wong F Susan, Zhou Zhiguang, Wen Li
Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China.
Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
JCI Insight. 2020 May 21;5(10):135718. doi: 10.1172/jci.insight.135718.
The incidence of type 1 diabetes (T1D) has been increasing among children and adolescents, in which environmental factors, including gut microbiota, play an important role. However, the underlying mechanisms are yet to be determined. Here, we show that patients with newly diagnosed T1D displayed not only a distinct profile of gut microbiota associated with decreased short-chain fatty acids (SCFAs) production, but also an altered IgA-mediated immunity compared with healthy control subjects. Using germ-free NOD mice, we demonstrate that gut microbiota from patients with T1D promoted different IgA-mediated immune responses compared with healthy control gut microbiota. Treatment with the SCFA, acetate, reduced gut bacteria-induced IgA response accompanied by decreased severity of insulitis in NOD mice. We believe our study provides new insights into the functional effects of gut microbiota on inducing IgA immune response in T1D, suggesting that SCFAs might be potential therapeutic agents in T1D prevention and/or treatment.
1型糖尿病（T1D）在儿童和青少年中的发病率一直在上升，其中包括肠道微生物群在内的环境因素起着重要作用。然而，其潜在机制尚待确定。在这里，我们表明，与健康对照受试者相比，新诊断的T1D患者不仅表现出与短链脂肪酸（SCFAs）产生减少相关的独特肠道微生物群特征，而且IgA介导的免疫也发生了改变。使用无菌NOD小鼠，我们证明与健康对照肠道微生物群相比，T1D患者的肠道微生物群促进了不同的IgA介导的免疫反应。用SCFA醋酸盐治疗可降低肠道细菌诱导的IgA反应，并伴有NOD小鼠胰岛炎严重程度的降低。我们相信我们的研究为肠道微生物群在T1D中诱导IgA免疫反应的功能作用提供了新的见解，表明SCFAs可能是T1D预防和/或治疗的潜在治疗剂。
