Integrated multi-omics reveals the Bacillus amyloliquefaciens BA40 against Clostridium perfringens infection in weaned piglets

Clostridium perfringens (C. perfringens) can cause necrotic enteritis and higher mortality rates in piglets, by impairing the intestinal barrier function. Bacillus amyloliquefaciens 40 (BA40) has showed potential ability to reduce C. perfringens infections, but the mechanisms responsible for its effectiveness remain unclear. This study aims to evaluate the impact of BA40 on inflammation induced by C. perfringens and to explain the mechanisms underlying its therapeutic effects. We aim to show how BA40 can bolster piglet health by strengthening the intestinal barrier and regulating immune responses. We used piglets and cellular models, alongside microbiomics, metabolomic, and transcriptomic analyses, to investigate BA40's impact on C. perfringens-induced inflammation. A model of C. perfringens infection was constructed using piglets and cells to investigate the effect of BA40 on its phenotype. Microbiomics, metabolomics, and transcriptomics analyses were subsequently used to investigate the mechanisms of protection and immune response to BA40 on the intestinal barrier of piglets. Our study revealed significant improvements in piglet health following BA40 administration. Notably, BA40 strengthened the intestinal mucosal barrier and mitigated the inflammatory response triggered by C. perfringens BA40 decreased harmful bacteria and increased beneficial bacteria. Metabolite profiles improved, showing a reduction in harmful substances. Transscriptomics analysis indicated BA40's role in TNF/NF-κB signaling pathway, hinting at its ability to regulate immune responses and reduce intestinal inflammation. Cellular assays further confirmed BA40's capacity to diminish inflammatory cytokine release and encourage the differentiation of anti-inflammatory macrophages. Datasets from the present study demonstrate that BA40 modulates gut microbes and metabolites, inhibits inflammation-related signaling pathways, and maintains gut barrier function. Our findings not only deepen our understanding of the therapeutic capacity of BA40 but also provide a theoretical foundation for the development of probiotics and alternative therapies aimed at improving piglet gut health.