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Gut microbial metabolites alter IgA immunity in type 1 diabetes
Juan Huang, … , Zhiguang Zhou, Li Wen
Juan Huang, … , Zhiguang Zhou, Li Wen
Published April 16, 2020
Citation Information: JCI Insight. 2020;5(10):e135718. https://doi.org/10.1172/jci.insight.135718.
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Research Article

Gut microbial metabolites alter IgA immunity in type 1 diabetes

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Abstract

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.

Authors

Juan Huang, James A. Pearson, Jian Peng, Youjia Hu, Sha Sha, Yanpeng Xing, Gan Huang, Xia Li, Fang Hu, Zhiguo Xie, Yang Xiao, Shuoming Luo, Chen Chao, F. Susan Wong, Zhiguang Zhou, Li Wen

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Figure 2

IgA-bound bacteria and the correlations with different SCFAs in individuals with T1D and control subjects.

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IgA-bound bacteria and the correlations with different SCFAs in individu...
(A) Representative flow cytometric profiles of IgA-bound bacteria. (B) Summary of IgA-bound bacteria percentage from donors with T1D and healthy controls (n = 19/group). (C–E) Correlations between stool acetate (C), butyrate (D), or propionate (E) concentration and the level of IgA-bound bacteria. (The overall elevation or intercepts between the 2 groups was compared. The black circles show that there were more patients in the upper left areas, i.e., with a higher percentage of IgA-bound bacteria but lower stool SCFAs, n = 14–16.) (F–H) Correlations between stool acetate concentration and the relative abundances of Eubacterium (F) and Hathewayi (Firmicutes) (G), and between stool butyrate concentration and Enterococcaceae (Firmicutes) abundance (H) (n = 17/group). Data are presented as mean ± SEM and were assessed for statistical significance using a 2-tailed Student’s t test (B). Data in (F–H) were analyzed using a 2-tailed Pearson correlation coefficient test and/or linear regression. SCFAs, short-chain fatty acids; T1D, type 1 diabetes.

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