Early-life microbiota exposure and prevention of childhood asthma: immunological mechanisms and intervention perspectives.

Asthma is one of the most prevalent chronic diseases among children, affecting approximately one in ten globally. Preventing asthma in the early life benefits individuals both during childhood and into adulthood. During the critical prenatal period, exposure to diverse maternal microbiota may enhance immune tolerance in fetal and neonatal stages. This exposure can train the immunity of innate immune cells through functional reprogramming of epigenetic mechanisms, potentially altering susceptibility to allergic diseases like asthma. Additionally, microbiota transmission during childbirth, close maternal-child contact, and breastfeeding influence offspring immunity. Furthermore, childhood exposure to a microbiota-rich environment, a diverse gut microbiota, and reduced viral infections are crucial for preventing asthma in children. Early-life exposure to diverse microbiota influences host cells via bacterial metabolites, soluble immune effectors, and other mediators, thereby shaping immune development. These microbial signals activate specific immune pathways and foster tolerance, changes that have been linked to a lower risk of allergic disease. Most evidence to date derives from observational human studies and animal models; consequently, mechanisms remain incompletely defined and standardized intervention strategies are lacking. Longitudinal human cohorts are therefore needed to delineate microbiota-host interaction mechanisms and to enable individualized, precision-based prevention of childhood asthma.