Evidence for the Role of the Cecal Microbiome in Maintenance of Immune Regulation and Homeostasis
Evidence for the Role of the Cecal Microbiome in Maintenance of Immune Regulation and Homeostasis
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DOI：
10.1097/sla.0000000000002930
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发表时间：
2018-09-01
影响因子：
9
通讯作者：
Brayman, Kenneth L.
中科院分区：
文献类型：
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作者：
Chhabra, Preeti;Spano, Anthony J.;Brayman, Kenneth L.
目的：我们的目的是研究在有或没有 IgM 治疗的 1 型糖尿病 (T1D) 发展过程中盲肠微生物组成的变化，并将这些变化与相应的免疫特征相关联。方法：(1) 用 IgM 或盐水治疗的雌性非肥胖糖尿病 (NOD) 小鼠（n = 20/组）分为 5 周龄非糖尿病组； 9至12周龄高血糖前期1期； >= 13 周龄高血糖前期 2 期；和糖尿病群体。 16S rRNA 文库由细菌 DNA 制备并进行深度测序。 (2)新发糖尿病小鼠接受IgM治疗(第1、3、5天200μg)并监测血糖2个月。结果：随着T1D发展的进展，在盲肠微生物组中观察到显着的菌群失调。微生物组组成的改变的特点是拟杆菌与厚壁菌门比例的增加。相反，IgM 保留了正常的拟杆菌：厚壁菌门比例，并且这种作用是持久的。此外，与对照组相比，使用 IgM 治疗小鼠的盲肠内容物进行口服灌胃显着降低了糖尿病的发病率，这表明 IgM 特异性影响粘膜相关微生物，并且这种影响是因果关系，而不是附带现象。此外，在 IgM 治疗的小鼠中，调节性免疫细胞群（骨髓来源的抑制细胞和调节性 T 细胞）增加，胰岛素自身抗体的产生减少。此外，IgM 疗法逆转了 70% 的新发糖尿病小鼠 (n = 10) 的高血糖，并且在整个治疗后观察期内小鼠的血糖保持正常。结论：盲肠微生物组似乎对维持免疫稳态和正常免疫反应很重要。
Objective (s): Our objective was to investigate alterations in the cecal microbial composition during the development of type 1 diabetes (T1D) with or without IgM therapy, and correlate these alterations with the corresponding immune profile.Methods: (1) Female nonobese diabetic (NOD) mice treated with IgM or saline (n = 20/group) were divided into 5-week-old nondiabetic; 9 to 12-week-old prehyperglycemic stage-1; >= 13-week-old prehyperglycemic stage-2; and diabetic groups. 16S rRNA libraries were prepared from bacterial DNA and deep-sequenced. (2) New-onset diabetic mice were treated with IgM (200 mu g on Days 1, 3, and 5) and their blood glucose monitored for 2 months.Results: Significant dysbiosis was observed in the cecal microbiome with the progression of T1D development. The alteration in microbiome composition was characterized by an increase in the bacteroidetes:firmicutes ratio. In contrast, IgM conserved normal bacteroidetes:firmicutes ratio and this effect was long-lasting. Furthermore, oral gavage using cecal content from IgM-treated mice significantly diminished the incidence of diabetes compared with controls, indicating that IgM specifically affected mucosa-associated microbes, and that the affect was causal and not an epiphenomenon. Also, regulatory immune cell populations (myeloid-derived suppressor cells and regulatory T cells) were expanded and insulin autoantibody production diminished in the IgM-treated mice. In addition, IgM therapy reversed hyperglycemia in 70% of new-onset diabetic mice (n = 10) and the mice remained normoglycemic for the entire post-treatment observation period.Conclusions: The cecal microbiome appears to be important in maintaining immune homeostasis and normal immune responses.