支气管哮喘的发生与遗传背景及环境因素有关。除了外部环境，机体内部微生态环境起到了至关重要的作用。研究表明，生命早期体内微生态系统失衡会导致免疫相关性疾病的产生，但其与哮喘之间的关系及其调控机制仍不清楚。近年来研究发现，微生态失衡引起的某些菌群代谢产物的累积会介导细胞DNA损伤反应。而在DNA损伤与气道炎症的研究中也发现，DNA损伤参与了哮喘发病的病理过程。本课题组的前期研究发现，生命早期万古霉素干预后体内微生态失衡会引起哮喘气道炎症反应的加重。本项目拟进一步深入研究机体的菌群改变诱导细胞DNA损伤，引起炎症反应影响哮喘发病的分子机制，阐明在微生态失衡下DNA损伤修复介导的上皮细胞炎症反应及其调控气道炎症的病理机制，并探索乳杆菌干预对于微生态失衡后气道炎症反应的调节作用。通过上述研究，将为微生态在哮喘发病中的作用及机制提供新的认识，并为支气管哮喘的早期预防及治疗提供新的理论基础。

The occurrence of asthma is thought to be a combination of genetic and environmental factors. In addition to external environment, internal microbiome plays a crucial role in the onset of asthma. Studies have shown that microbiome dysbiosis in early life can lead to immune-related diseases, but the relationship between asthma and microbiome remains unclear. It has been found that the metabolites of certain bacteria can cause DNA damage in cells. In the study of DNA damage and airway inflammation, it is also found that DNA damage is involved in the pathological process of asthma and mediates the occurrence of inflammatory response. Our previous study found that the intervention of Vancomycin in early life changed the composition of microbiome, and exacerbated the airway inflammation in asthma model. This project intends to uncover the roles of microbial dysbiosis induced-DNA damage response in inflammatory response in the pathogenesis of asthma, clarify the mechanism of DNA damage repair response-induced inflammatory response in the state of microbiome dysbiosis, and to explore the role of Lactobacillus in regulating airway inflammation after microecological imbalance. It may provide new insight into the role and mechanism of microbiome in the occurrence and development of asthma, and provide a potential strategy for the early prevention and treatment of asthma.