Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
Mucosal Immunol. 2019 Nov;12(6):1348-1357. doi: 10.1038/s41385-019-0207-8. Epub 2019 Sep 25.
Children born by cesarean section (CS) have an increased risk of developing inflammatory bowel disease (IBD), possibly due to skewed microbial colonization during birth and consequently impaired bacterial stimulation of the developing immune system. The aim of this study was to investigate the association between CS and experimental colitis in a murine model of IBD. It was hypothesized that CS aggravates colonic inflammation due to a change in gut microbiota (GM) composition. C57BL/6 mice, delivered by CS or vaginal delivery (VD), were intra-rectally challenged with oxazolone at 8 weeks of age and monitored for colitis symptoms. The results showed that CS delivered mice experienced an increased body weight loss and colon weight, together with higher colonic concentrations of TNF-α and MPO compared with VD mice. Increased infiltration of inflammatory cells was present in CS delivered mice, as well as a downregulation in expression of the gut integrity genes occludin and tight junction protein 1 indicative of an impaired barrier function. The GM from CS delivered mice without colitis partly contributed to the increase in colitis symptoms when inoculated into germ-free recipient mice. In conclusion, CS increased sensitivity to oxazolone induced colitis in mice.
剖宫产(CS)出生的儿童患炎症性肠病(IBD)的风险增加,这可能是由于出生时微生物定植的偏倚,从而导致发育中的免疫系统受到细菌刺激受损。本研究旨在探讨 CS 与 IBD 小鼠模型中实验性结肠炎之间的关系。假设 CS 会由于肠道微生物群(GM)组成的改变而加重结肠炎症。在 8 周龄时,通过 CS 或阴道分娩(VD)分娩的 C57BL/6 小鼠接受 oxazolone 直肠内挑战,并监测结肠炎症状。结果表明,CS 分娩的小鼠体重减轻和结肠重量增加,与 VD 小鼠相比,结肠 TNF-α和 MPO 浓度更高。CS 分娩的小鼠中炎症细胞浸润增加,同时肠完整性基因紧密连接蛋白 1 和 occludin 的表达下调,表明屏障功能受损。没有结肠炎的 CS 分娩小鼠的 GM 部分导致无特定病原体受体小鼠结肠炎症状增加。总之,CS 增加了小鼠对 oxazolone 诱导的结肠炎的敏感性。