Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1871 Frederiksberg C, Denmark;
Department of Food Science, Faculty of Science, University of Copenhagen, 1958 Frederiksberg, Denmark.
J Immunol. 2019 Jan 1;202(1):142-150. doi: 10.4049/jimmunol.1800666. Epub 2018 Nov 28.
Epidemiological studies have shown that children born by cesarean section (CS) are at higher risk of developing chronic inflammatory diseases, and it has been suggested that a skewed gut microbial colonization process early in life and altered priming of the immune system are causative. The aim of this study was to clarify whether impaired regulatory immunity in CS-delivered C57BL/6 mice is dependent on gut microbiota (GM) disturbances. The GM of conventionally bred mice born by CS differed clearly from mice born by vaginal delivery. The proportion of regulatory T cells was reduced in mice born by CS, whereas the invariant NKT (iNKT) cell subset was increased compared with vaginal delivery mice. In addition, regulatory markers (, , ) and macrophage markers (, , ) were downregulated, whereas iNKT markers (, were upregulated in ileum of CS-delivered mice. The GM of CS-delivered mice was sufficient to transfer the shifts in immunity associated with delivery mode when inoculated into germ-free mice. Feeding a prebiotic diet reestablished gene expression of intestinal immune markers and iNKT cells in CS mice but was not sufficient to restore the level of regulatory T cells. The results support that CS delivery is associated with microbiota-mediated shifts in regulatory immunity and, therefore, provide a basis for future microbiota-directed therapeutics to infants born by CS.
流行病学研究表明，剖宫产（CS）分娩的儿童患慢性炎症性疾病的风险较高，有人认为，生命早期肠道微生物定植过程的倾斜和免疫系统的初始改变是致病的原因。本研究旨在阐明 CS 分娩的 C57BL/6 小鼠受损的调节性免疫是否依赖于肠道微生物群（GM）的紊乱。CS 分娩的常规饲养小鼠的 GM 与阴道分娩的小鼠明显不同。CS 分娩的小鼠中调节性 T 细胞的比例减少，而与阴道分娩的小鼠相比，不变自然杀伤 T（iNKT）细胞亚群增加。此外，调节性标记物（、、）和巨噬细胞标记物（、、）下调，而 CS 分娩小鼠的 iNKT 标记物（、上调。将 CS 分娩小鼠的 GM 接种到无菌小鼠中，足以转移与分娩方式相关的免疫变化。喂食益生元饮食可恢复 CS 小鼠肠道免疫标志物和 iNKT 细胞的基因表达，但不足以恢复调节性 T 细胞的水平。研究结果表明 CS 分娩与微生物介导的调节性免疫变化有关，因此为未来针对 CS 分娩婴儿的微生物定向治疗提供了依据。
