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

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 4

Role of acetate in modulating gut microbiota composition and IgA immune response.

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Role of acetate in modulating gut microbiota composition and IgA immune ...
(A) Spleen cells from specific pathogen–free NOD mice were stimulated with acetate, butyrate, or propionate (all 0.1 Mm) in the presence of anti-CD40 mAb (20 μg/mL) and LPS (10 μg/mL), and secreted IgA in the culture supernatant was measured (n = 8/group). (B) Timeline of GF NOD mice gavaged with stool bacteria from patients with T1D, followed by acetate or water gavage. (C–E) Gut microbiota in fecal samples were analyzed by 16S rRNA sequencing (n = 7–8). Chao richness (C), and relative abundance of Porphyromonadaceae (D) and Staphylococcaceae (E) at family level. (F) Proportion of TCRβ+CD4+ T cells, TCRβ+CD8+ T cells, and TCRβ–CD19+ B cells in PP (n = 7–8). (G) Frequency of CD4+CD25+Foxp3+ Treg cells in Peyer’s patch (n = 7–8). (H) Proportion of IgA+ B cells in PLN (n = 6–8). (I) Proportion of IgA+, IgM+, and IgD+ B cells in bone marrow (n = 7–8). (J) IgA concentration from the content of small intestine, cecum and colon (n = 7–8). Data combined from 2 independent experiments are presented as mean ± SEM and were analyzed with a 1-way ANOVA, followed by a Tukey’s test with Dunn’s correction for subsequent multiple comparisons between 2 groups (A) or a 2-tailed Student’s t test (C–J). GF, germ-free; T1D, type 1 diabetes; SCFAs, short-chain fatty acids; PLN, pancreatic lymph node.