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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 8

Gene expression of gprs and solute carrier family 16 on B cells.

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Gene expression of gprs and solute carrier family 16 on B cells.
Ex vivo...
Ex vivo splenic B cells were purified from specific pathogen–free NOD mice gavaged with 200 μL of water or equivalent volume of 100 Mm acetate for 10 to 12 weeks, and were stimulated in vitro with 20 μg/mL anti-CD40 mAb and 10 μg/mL LPS in the presence of 10 Mm acetate for 5 days. Gene expression of acetate-stimulated B cells was assessed by qPCR: Gpr41 (A), Gpr43 (B), Slc16a7 (C), Slc16a1 (D), and Slc16a3 (E). All expression data were determined using the 2−ΔΔCt method by normalization with the housekeeping gene GAPDH. Data combined from 2 independent experiments are presented as mean ± SEM and were assessed for statistical significance using a 2-tailed Student’s t test (n = 7–8).

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