BACKGROUND: Asthma is increasingly prevalent worldwide, and novel strategies to prevent or treat this disease are needed. Probiotic intervention has recently been reported to be effective for asthma prevention. Here, we explored the effects of Faecalibacterium prausnitzii on the development of allergic airway inflammation in a murine model of house dust mite (HDM)induced allergic asthma. RESULTS: Supplementation with living and dead F. prausnitzii blocked eosinophil, neutrophil, lymphocyte and macrophage influx and alleviated the pathological changes. Moreover, both living and dead F. prausnitzii administration decreased the levels of interleukin (IL)-4, IL-5, IL-13 and immunoglobulin G1, elevated regulatory T cell (Tregs) ratio, improved microbial dysbiosis and enhanced short-chain fatty acid (SCFA) production. Network correlation analysis revealed that the immune indicators were strongly associated with SCFA production. Based on the linear discriminant analysis effect size, Turicibacter was found to be the core genus related to HDM-induced asthma. Living F. prausnitzii treatment enriched Faecalibaculum, Dubosiella and Streptococcus, while dead F. prausnitzii treatment increased Muribaculaceae and Parabacteroides. Interestingly, both living and dead F. prausnitzii administration enriched Lachnoclostridium and normalized the pathways involving carbohydrate and lipid metabolism, which might be related to SCFA production. CONCLUSION: Faecalibacterium prausnitzii exerts an anti-asthmatic effect partly by gut microbiota modulation and SCFA production, suggesting its potential as a probiotic agent for allergic asthma prevention.