Indiana University School of Medicine-Northwest, Gary, IN 46408; and.
Department of Mathematics, Indiana University-Northwest, Gary, IN 46408.
J Immunol. 2019 Dec 15;203(12):3113-3125. doi: 10.4049/jimmunol.1900711. Epub 2019 Nov 8.
Changes in intestinal or respiratory microbiomes in infants correlate with increased incidence of asthma, but the causative role of microbiome in the susceptibility to asthma and the host genes that regulate these changes in microbiome are mostly unknown. In this study, we show that decreased responsiveness to allergic asthma in mice (lacking bactericidal peptidoglycan recognition protein 1) could be transferred to germ-free wild-type mice by colonization of mothers and newborns with microbiota from mice. These colonized mice had decreased airway resistance and fewer inflammatory cells, less severe histopathology, and lower levels of IgE and proallergic cytokines and chemokines in the lungs. This microbiome-dependent decreased responsiveness to asthma was most pronounced in colonized germ-free BALB/c mice (genetically predisposed to asthma), only partially evident in outbred germ-free Swiss Webster mice, and marginal in conventional BALB/c mice following depletion of microbiome with antibiotics. Mice with a low asthmatic response colonized with microbiota from mice had increased abundance of and decreased abundance of , , , and in the feces and increased abundance of in the oropharynx. These changes in bacterial abundance in the feces and oropharynx correlated with lower asthmatic responses in the lungs. Thus, our results show that enhances allergic asthmatic responses primarily through its effect on the host intestinal microbiome and identify several bacteria that may increase or decrease sensitivity to asthma. This effect of microbiome is strong in asthma-prone BALB/c mice and weak in asthma-resistant outbred mice and requires germ-free conditions before colonization with microbiota from mice.
肠道或呼吸道微生物组的变化与哮喘发病率的增加有关,但微生物组在哮喘易感性中的因果作用以及调节这些微生物组变化的宿主基因在很大程度上尚不清楚。在这项研究中,我们表明,缺乏杀菌肽聚糖识别蛋白 1 的小鼠对过敏性哮喘的反应性降低,可以通过用来自 小鼠的微生物群定植母亲和新生儿来转移到无菌野生型小鼠中。这些定植的小鼠气道阻力降低,炎症细胞减少,组织病理学严重程度降低,肺部 IgE 和促过敏细胞因子和趋化因子水平降低。这种依赖微生物组的哮喘反应性降低在定植无菌 BALB/c 小鼠(易患哮喘)中最为明显,在杂交无菌瑞士 Webster 小鼠中部分明显,在常规 BALB/c 小鼠中用抗生素耗尽微生物组后则不明显。用来自 小鼠的微生物群定植的低哮喘反应性小鼠的粪便中 和 的丰度增加, 和 的丰度降低,口腔咽部的 的丰度增加。粪便和口腔咽部细菌丰度的这些变化与肺部哮喘反应降低相关。因此,我们的结果表明, 主要通过其对宿主肠道微生物组的影响增强过敏性哮喘反应,并确定了几种可能增加或降低哮喘敏感性的细菌。这种微生物组的作用在易患哮喘的 BALB/c 小鼠中很强,在抗哮喘的杂交小鼠中很弱,并且在定植来自 小鼠的微生物群之前需要无菌条件。