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Gut microbial metabolites alter IgA immunity in type 1 diabetes
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
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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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 3

Role of gut microbiota from patients with T1D and control subjects in modulating host immune responses in GF NOD mice.

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Role of gut microbiota from patients with T1D and control subjects in mo...
(A) Timeline for GF NOD mice gavaged with stool bacteria from patients with T1D or control subjects. (B) Unweighted principal coordinate analysis of stool microbiota from GF NOD mice received bacteria from either T1D donors or healthy control subjects (n = 22–23). (C) Gut microbiota composition at the species level (n = 22–23). (D) Gut permeability (n = 9–15). (E) Expression of Cramp (n = 16/group). (F) IgA+ B cell frequency in the spleen, PLN, MLN, and PP (n = 27–30). (G and H) Representative flow cytometric profiles of IgA-bound bacteria (G), and summary of IgA-bound bacteria percentage (H). Statistical analysis was performed by an analysis of similarities (B), multiple t tests with Bonferroni’s correction (C) or a 2-tailed Student’s t test(D–F and H, data combined from 2 or more independent experiments are presented as mean ± SEM). T1D, type 1 diabetes; GF, germ-free; PLN, pancreatic lymph node; MLN, mesenteric lymph node; PP, Peyer’s patch.

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ISSN 2379-3708

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