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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 5

Long-term effect of acetate treatment on IgA response in SPF NOD mice.

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Long-term effect of acetate treatment on IgA response in SPF NOD mice.
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(A) Timeline of SPF NOD mice gavaged with acetate or water. (B) Longitudinal proportion of IgA-bound stool bacteria before and after gavage (n = 8–9). (C) Gut permeability (n = 7–9). (D) IgA concentrations in intestinal flush (n = 6–7). (E) Percentage of IgA-bound bacteria in the intestinal flush (n = 8–9). (F) Intestinal Pigr expression post-acetate treatment (n = 14–16). (G) IgA reactive to gut bacterial products. Stool microbiota from Rag-deficient mice (without any type/form of antibodies) were used to assess IgAs reacting to gut bacterial products. IgAs reacting to the bacterial products in small intestinal flush from the mice with or without acetate treatment were determined by anti-mouse IgA by ELISA (n = 14–16). (H) Proportion of CD4+ or CD8+ T cells and CD19+ B cells in Peyer’s patch (n = 6–7). (I) Proportion of splenic IgA+ B cells (n = 6–7). Data were pooled from 2 or more independent experiments, and analyzed using either a 2-way ANOVA (B) or a 2-tailed Student’s t test (C–I, Data are presented as mean ± SEM). SPF, specific pathogen–free.

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