Department of Respiratory and Critical Care Medicine, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun, China.
Pediatr Allergy Immunol. 2020 Nov;31(8):962-973. doi: 10.1111/pai.13315. Epub 2020 Jul 28.
Asthma is a serious global health problem, severely affecting the lives of sufferers and their families. An exceptionally hygienic home and reduced microbial exposure can aggravate the incidence of childhood asthma.
Specific-pathogen-free BALB/c mice were pre-treated with bacterial lysate (BL; 1 mg/kg) as a high microbial load maternal mouse model, and then, the offspring mice were established as an allergic airway disease (AAD) model. The expression levels of TLR2, TLR4, and HDAC9 in the mother's intestine and the offspring's lungs were detected. Relevant indicators of regulatory T cells (Tregs) were identified in the mother and offspring mice. The changes in the expression of Th1-, Th2-, Th9-, and Th17-related cytokines in the offspring mice were evaluated among different pre-treated groups.
After augmenting the mothers' intestinal microbiota through oral BL gavage, the expression of TLR2 and TLR4 in the colon mucosa and colon lymphoid tissues was enhanced and that of HDAC9 in the colon mucosa was decreased, and the proportion of spleen Tregs was increased. The offspring showed similar changes in the AAD model compared with the offspring of the control-group mothers: TLR2 and TLR4 expression in the lungs and the proportion of spleen Tregs increased, HDAC9 expression in the lungs decreased, and AAD-induced airway pathologic characteristics were reversed; additionally, Th1/Th2 and Th9 imbalances were rectified.
This study presents a new framework for the prevention of childhood asthma, elucidating the mechanism of regulating the mother's intestinal microbiome to protect the offspring's early asthma via animal experiments.
哮喘是一个严重的全球性健康问题，严重影响着患者及其家庭的生活。异常卫生的家庭和减少微生物暴露会加重儿童哮喘的发病率。
采用细菌裂解物（BL；1mg/kg）预处理特应性无病原体 BALB/c 小鼠作为高微生物负荷的母鼠模型，然后建立子代小鼠过敏性气道疾病（AAD）模型。检测母鼠肠道和子代鼠肺部 TLR2、TLR4 和 HDAC9 的表达水平。鉴定母鼠和子代鼠中调节性 T 细胞（Tregs）的相关指标。评估不同预处理组子代鼠中 Th1、Th2、Th9 和 Th17 相关细胞因子表达的变化。
通过口服 BL 灌胃增强母鼠肠道微生物群后，结肠黏膜和结肠淋巴组织中 TLR2 和 TLR4 的表达增强，结肠黏膜中 HDAC9 的表达降低，脾 Tregs 的比例增加。与对照组母亲的子代相比，AAD 模型中的子代表现出类似的变化：肺中 TLR2 和 TLR4 的表达增加，脾 Tregs 的比例增加，肺中 HDAC9 的表达降低，AAD 诱导的气道病理特征得到逆转；此外，Th1/Th2 和 Th9 失衡得到纠正。
本研究通过动物实验提出了一种预防儿童哮喘的新框架，阐明了调节母鼠肠道微生物群以保护子代早期哮喘的机制。
