Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Department of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark.
Gut Microbes. 2023 Dec;15(2):2271151. doi: 10.1080/19490976.2023.2271151. Epub 2023 Oct 27.
Delivery by cesarean section (CS) is associated with an altered gut microbiota (GM) colonization and a higher risk of later chronic inflammatory diseases. Studies investigating the association between CS and atopic dermatitis (AD) are contradictive and often biased by confounding factors. The aim of this study was therefore to provide experimental evidence for the association between CS and AD in a mouse model and clarify the role of the GM changes associated with CS. It was hypothesized that CS-delivered mice, and human CS-GM transplanted mice develop severe dermatitis due to early dysbiosis. BALB/c mice delivered by CS or vaginally (VD) as well as BALB/c mice transplanted with GM from CS or VD human donors were challenged with oxazolone on the ear. The severity of dermatitis was evaluated by ear thickness and clinical and histopathological assessment which were similar between all groups. The immune response was assessed by serum IgE concentration, local cytokine response, and presence of immune cells in the draining lymph node. Both CS-delivered mice and mice inoculated with human CS-GM had a higher IgE concentration. A higher proportion of Th2 cells were also found in the CS-GM inoculated mice, but no differences were seen in the cytokine levels in the affected ears. In support of the experimental findings, a human cohort analysis from where the GM samples were obtained found that delivery mode did not affect the children's risk of developing AD. In conclusion, CS-GM enhanced a Th2 biased immune response, but had no effect on oxazolone-induced dermatitis in mice.
剖宫产(CS)与肠道微生物群(GM)定植的改变和日后发生慢性炎症性疾病的风险增加有关。研究 CS 与特应性皮炎(AD)之间关系的研究结果相互矛盾,并且经常受到混杂因素的影响。因此,本研究的目的是在小鼠模型中提供 CS 与 AD 之间关联的实验证据,并阐明与 CS 相关的 GM 变化的作用。假设 CS 分娩的小鼠和接受 CS 人 GM 移植的小鼠由于早期的生态失调而发生严重的皮炎。通过 CS 或阴道(VD)分娩的 BALB/c 小鼠以及接受来自 CS 或 VD 人供体 GM 移植的 BALB/c 小鼠均在耳部用恶唑酮进行了挑战。通过耳厚度和临床及组织病理学评估来评估皮炎的严重程度,所有组之间的评估结果均相似。通过血清 IgE 浓度、局部细胞因子反应和引流淋巴结中免疫细胞的存在来评估免疫反应。CS 分娩的小鼠和接种人 CS-GM 的小鼠的 IgE 浓度均较高。CS-GM 接种的小鼠中也发现 Th2 细胞的比例较高,但受影响耳朵中的细胞因子水平没有差异。支持实验发现,从获得 GM 样本的人类队列分析中发现,分娩方式不会影响儿童患 AD 的风险。总之,CS-GM 增强了 Th2 偏向的免疫反应,但对小鼠的恶唑酮诱导性皮炎没有影响。