Department of Immunology, University of Connecticut Health, Farmington, CT, USA.
Department of Pediatrics, University of Connecticut Health, Farmington, CT, USA.
Pediatr Res. 2018 Sep;84(3):426-434. doi: 10.1038/s41390-018-0031-y. Epub 2018 Jul 2.
Early-life exposure to antibiotics (ABX) has been linked to increases in asthma severity and prevalence in both children and laboratory animals. We explored the immunologic mechanisms behind this association using a mouse model of house dust mite (HDM)-induced asthma and early-life ABX exposure.
Mice were exposed to three short courses of ABX following weaning and experimental asthma was thereafter induced. Airway cell counts and differentials; serum immunoglobulin E (IgE); pulmonary function; lung histopathology; pulmonary regulatory T cells (Tregs); and the fecal microbiome were characterized following ABX exposure and induction of experimental asthma.
Asthma severity was increased in mice exposed to ABX, including: airway eosinophilia, airway hyper-reactivity, serum HDM-specific IgE, and lung histopathology. ABX treatment led to sharp reduction in fecal microbiome diversity, including the loss of pro-regulatory organisms such as Lachnospira. Pulmonary Tregs were reduced with ABX treatment, and this reduction was directly proportional to diminished microbiome diversity.
Intermittent exposure to ABX early in life worsened the severity of experimental asthma and reduced pulmonary Tregs; the latter change correlated with decreased microbiome diversity. These data may suggest targets for immunologic or probiotic therapy to counteract the harmful effects of childhood ABX.
儿童时期接触抗生素（ABX）与哮喘严重程度和患病率的增加有关，这在儿童和实验动物中均有体现。我们使用屋尘螨（HDM）诱导的哮喘和儿童早期 ABX 暴露的小鼠模型来探索这种关联背后的免疫机制。
断奶后，小鼠接受了三次短疗程的 ABX 暴露，随后诱导实验性哮喘。在 ABX 暴露和实验性哮喘诱导后，对气道细胞计数和分类；血清免疫球蛋白 E（IgE）；肺功能；肺组织病理学；肺调节性 T 细胞（Tregs）；和粪便微生物组进行了特征描述。
暴露于 ABX 的小鼠哮喘严重程度增加，包括气道嗜酸性粒细胞增多、气道高反应性、血清 HDM 特异性 IgE 和肺组织病理学。ABX 治疗导致粪便微生物组多样性急剧下降，包括对调节性的生物体如 Lachnospira 的丧失。ABX 治疗导致肺部 Tregs 减少，且这种减少与微生物组多样性的减少直接相关。
生命早期间歇性接触 ABX 会加重实验性哮喘的严重程度并减少肺部 Tregs；后者的变化与微生物组多样性的减少相关。这些数据可能提示针对免疫或益生菌治疗的靶点，以抵消儿童 ABX 的有害影响。
