Establishing a high microbial load maternal-offspring asthma model in adult mice

Although it is widely accepted that the “hygiene hypothesis” explains the increased incidence of asthma, the lack of suitable animal models hinders further in-depth studies of the underlying molecular immune mechanisms. Therefore, we aimed to develop a robust mouse asthma model to investigate the role of bacteria in preventing asthma. BALB/c female mice were fed a mixture of eight common bacterial lysates (BL; Broncho-Vaxom®) and a commercial probiotic (Bifidobacterium tetravaccine tablets) at different concentrations before and during pregnancy to simulate different microbial load levels. Faeces from the mother mice were subjected to bacterial 16S rRNA sequencing to quantify the maternal microbial load. TLR2/4 expression and the proportion of regulatory T cells (Tregs) in the intestinal tract of female mice were determined, and the safety of the microbial load was evaluated. An asthma model was established in the offspring mice after weaning, and the extent of pulmonary pathological changes and Treg proportion were evaluated. A BL concentration of 1 mg/kg enriched the intestinal flora, increased the proportion of Tregs, and increased the expression of TLR2/4 in the maternal mice. The proportion of peripheral blood Tregs was increased, whereas the risk of asthma decreased only in the offspring from mothers with a high microbial load relative to control mice. This study established a safe and stable high microbial load maternal-offspring mouse asthma model, laying the foundation for a study on the molecular mechanism underlying the protective effects of a high microbial load against asthma.