Institute of Molecular Cancer Research, University of Zürich, Zurich, Switzerland.
Human Microbiome Program, New York University Langone Medical Center, New York, NY.
J Allergy Clin Immunol. 2019 Apr;143(4):1496-1512.e11. doi: 10.1016/j.jaci.2018.07.046. Epub 2018 Sep 19.
Transmaternal exposure to tobacco, microbes, nutrients, and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand and is inversely associated with allergies and chronic inflammatory conditions on the other.
Here we investigate the consequences of transmaternal exposure to H pylori in utero and/or during lactation for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and development of immune cell populations in the lungs and lymphoid organs.
We use experimental models of house dust mite- or ovalbumin-induced airway inflammation and influenza A virus or Citrobacter rodentium infection along with metagenomics analyses, multicolor flow cytometry, and bisulfite pyrosequencing, to study the effects of H pylori on allergy severity and immunologic and microbiome correlates thereof.
Perinatal exposure to H pylori extract or its immunomodulator vacuolating cytotoxin confers robust protective effects against allergic airway inflammation not only in first- but also second-generation offspring but does not increase susceptibility to viral or bacterial infection. Immune correlates of allergy protection include skewing of regulatory over effector T cells, expansion of regulatory T-cell subsets expressing CXCR3 or retinoic acid-related orphan receptor γt, and demethylation of the forkhead box P3 (FOXP3) locus. The composition and diversity of the gastrointestinal microbiota is measurably affected by perinatal H pylori exposure.
We conclude that exposure to H pylori has consequences not only for the carrier but also for subsequent generations that can be exploited for interventional purposes.
母体暴露于烟草、微生物、营养物质和其他环境因素会通过表观遗传过程塑造胎儿的免疫系统。幽门螺杆菌是人类微生物群的一个古老组成部分，它一方面会引起胃部疾病，另一方面与过敏和慢性炎症性疾病呈负相关。
本研究旨在探讨母体宫内和/或哺乳期暴露于幽门螺杆菌对病毒和细菌感染易感性、过敏性气道炎症易感性以及肺部和淋巴器官中免疫细胞群体发育的影响。
我们使用屋尘螨或卵清蛋白诱导的气道炎症以及甲型流感病毒或柠檬酸杆菌感染的实验模型，结合宏基因组分析、多色流式细胞术和亚硫酸氢盐焦磷酸测序，研究幽门螺杆菌对过敏严重程度及其免疫和微生物组相关因素的影响。
围产期暴露于幽门螺杆菌提取物或其免疫调节剂空泡细胞毒素可显著增强对过敏性气道炎症的保护作用，不仅在第一代后代中如此，而且在第二代后代中也是如此，但不会增加对病毒或细菌感染的易感性。过敏保护的免疫相关因素包括调节性 T 细胞相对于效应 T 细胞的倾斜、表达 CXCR3 或维甲酸相关孤儿受体γt 的调节性 T 细胞亚群的扩增，以及叉头框 P3（FOXP3）基因座的去甲基化。围产期幽门螺杆菌暴露可显著影响胃肠道微生物群的组成和多样性。
我们得出结论，暴露于幽门螺杆菌不仅对携带者而且对后代都有影响，这可以为干预目的所利用。
