Heritable Vaginal Bacteria Relate to Allergic Sensitization. Heritable Vaginal Bacteria Promote Immune Tolerance and Relate to Early-life Markers of Allergic Sensitization

Perturbed infant gut microbiota associates with risk of childhood allergic diseases. Maternal asthma status and exposures during pregnancy further increase childhood asthma risk, which suggests these observations are linked by inter-generational microbial transmission. Using maternal vaginal (n=184) and paired infant stool (n=172) samples, we identified four compositionally and functionally distinct Lactobacillus-dominated vaginal microbiota clusters (VCs), differentially related with maternal exposures and infant allergic sensitization. Variance in inherited vaginal bacteria correlated with VC, maternal allergy and asthma status and with infant serum IgE. Inherited IgE-discriminatory bacterial pathways were identified and fatty acid synthesis, histamine and tryptophan degradation bacterial pathways were associated with lower IgE. Two strains of vertically-transmitted Lactobacillus were isolated from fetal meconium and induced immunosuppressive phenotypes on human antigen presenting cells in vitro. In vivo, supplementation with Lactobacillus jensenii reduced lung eosinophils, neutrophilic expansion and the proportion of IL4+ CD4+ T cells. Thus, bacterial and asthma heritability are intimately linked, and implicate a microbial basis of inter-generational disease transmission.

婴幼儿肠道菌群紊乱与儿童过敏性疾病的发病风险存在显著关联。产妇哮喘患病状态及孕期暴露因素可进一步升高儿童哮喘的发病风险，这提示上述关联可能通过跨代微生物传递机制建立联系。
本研究利用184份产妇阴道样本与172份配对的婴幼儿粪便样本，鉴定出4组以乳酸杆菌（Lactobacillus）为优势菌群、在组成与功能层面均存在显著差异的阴道菌群簇（vaginal microbiota clusters, VCs），这些菌群簇与产妇孕期暴露因素及婴幼儿过敏性致敏反应存在差异化关联。
垂直传递的阴道菌群的变异程度与菌群簇类型、产妇过敏及哮喘患病状态，以及婴幼儿血清免疫球蛋白E（IgE）水平均存在相关性。研究还鉴定出可区分IgE水平的细菌代谢通路，其中脂肪酸合成、组胺及色氨酸降解相关的细菌代谢通路与更低的血清IgE水平相关。
研究人员从胎儿胎粪中分离出两株垂直传递的乳酸杆菌，在体外实验中可诱导人抗原呈递细胞产生免疫抑制表型。在体内实验中，补充詹森乳酸杆菌（Lactobacillus jensenii）可降低肺部嗜酸性粒细胞数量、中性粒细胞扩增程度以及IL4+ CD4+ T细胞的占比。
综上，细菌菌群与哮喘的遗传易感性密切相关，这提示跨代疾病传递存在微生物学基础。