Mode of Delivery Shapes Gut Colonization Pattern and Modulates Regulatory Immunity in Mice
Mode of Delivery Shapes Gut Colonization Pattern and Modulates Regulatory Immunity in Mice
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DOI：
10.4049/jimmunol.1400085
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发表时间：
2014-08-01
影响因子：
4.4
通讯作者：
Hansen, Axel K.
中科院分区：
文献类型：
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作者：
Hansen, Camilla H. F.;Andersen, Line S. F.;Hansen, Axel K.
递送模式与肠道微生物群组成的长期变化有关，最近还与免疫系统的变化有关。这进一步表明，剖腹产（剖腹产）与免疫介导的疾病（如1型糖尿病）的风险增加有关。在这项研究中，我们证明了剖腹产和与遗传上不同的菌株交叉培养都会影响小鼠的肠道微生物群组成和免疫关键标志物。通过变性梯度凝胶电泳和基于454/FLX的16 S rRNA基因扩增子测序进行的肠道微生物群分析显示，剖腹产小鼠在断奶时具有独特的细菌谱，其特征在于拟杆菌和毛螺菌科的丰度较高，而Rikenellaceae和Ruminococcus较少。根据交付方法确定的变性梯度凝胶电泳图谱的主成分分析没有聚类是明显的成年小鼠。然而，成年剖腹产小鼠的Foxp 3（+）调节性T细胞，致耐受性CD 103（+）树突状细胞的比例较低，肠系膜淋巴结和脾脏中的IL 10基因表达较少。这证明了对调节性免疫系统的长期全身作用，这在NOD小鼠中也很明显，NOD小鼠是一种通过剖腹产出生的1型糖尿病模型。然而，分娩方式对糖尿病发病率或胰岛炎的发展没有影响。总之，第一次接触微生物似乎对小鼠早期肠道微生物群和调节性免疫系统的启动至关重要，并且递送方式强烈影响这一点。
Delivery mode has been associated with long-term changes in gut microbiota composition and more recently also with changes in the immune system. This has further been suggested to link Cesarean section (C-section) with an increased risk for development of immune-mediated diseases such as type 1 diabetes. In this study, we demonstrate that both C-section and cross-fostering with a genetically distinct strain influence the gut microbiota composition and immune key markers in mice. Gut microbiota profiling by denaturing gradient gel electrophoresis and 454/FLX-based 16S rRNA gene amplicon sequencing revealed that mice born by C-section had a distinct bacterial profile at weaning characterized by higher abundance of Bacteroides and Lachnospiraceae, and less Rikenellaceae and Ruminococcus. No clustering according to delivery method as determined by principal component analysis of denaturing gradient gel electrophoresis profiles was evident in adult mice. However, the adult C-section-born mice had lower proportions of Foxp3(+) regulatory T cells, tolerogenic CD103(+) dendritic cells, and less Il10 gene expression in mesenteric lymph nodes and spleens. This demonstrates long-term systemic effect on the regulatory immune system that was also evident in NOD mice, a model of type 1 diabetes, born by C-section. However, no effect of delivery mode was seen on diabetes incidence or insulitis development. In conclusion, the first exposure to microorganisms seems to be crucial for the early life gut microbiota and priming of regulatory immune system in mice, and mode of delivery strongly influences this.