Jiang Zipeng, Su Weifa, Yang Mingzhi, Fu Jie, Gong Tao, Li Wentao, Wen Chaoyue, Wang Xinxia, Wang Fengqin, Jin Mingliang, Wang Yizhen, Lu Zeqing
Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, 866 Yuhang Tang Road, Hangzhou, Zhejiang 310058, China; Key Laboratory of Animal Nutrition and Feed, Ministry of Agricultural and Rural Affairs, Zhejiang University, 866 Yuhang Tang Road, Hangzhou, Zhejiang 310058, China; National Engineering Research Center of Green Feeds and Healthy Livestock Industry, Zhejiang University, 866 Yuhang Tang Road, Hangzhou, Zhejiang 310058, China; Zhejiang Key Laboratory of Nutrition and Breeding for High-quality Animal Products, Zhejiang University, 866 Yuhang Tang Road, Hangzhou, Zhejiang 310058, China; College of Animal Science, Institute of Feed Science, Zhejiang University, 866 Yuhang Tang Road, Hangzhou, Zhejiang 310058, China.
Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Zhejiang University, 866 Yuhang Tang Road, Hangzhou, Zhejiang 310058, China; Key Laboratory of Animal Nutrition and Feed, Ministry of Agricultural and Rural Affairs, Zhejiang University, 866 Yuhang Tang Road, Hangzhou, Zhejiang 310058, China; National Engineering Research Center of Green Feeds and Healthy Livestock Industry, Zhejiang University, 866 Yuhang Tang Road, Hangzhou, Zhejiang 310058, China; Zhejiang Key Laboratory of Nutrition and Breeding for High-quality Animal Products, Zhejiang University, 866 Yuhang Tang Road, Hangzhou, Zhejiang 310058, China; College of Animal Science, Institute of Feed Science, Zhejiang University, 866 Yuhang Tang Road, Hangzhou, Zhejiang 310058, China.
J Adv Res. 2025 Jan 22. doi: 10.1016/j.jare.2025.01.033.
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.
产气荚膜梭菌可通过损害肠道屏障功能，导致仔猪坏死性肠炎并使其死亡率升高。解淀粉芽孢杆菌40（BA40）已显示出降低产气荚膜梭菌感染的潜在能力，但其有效性的作用机制仍不清楚。
本研究旨在评估BA40对产气荚膜梭菌诱导的炎症的影响，并解释其治疗作用的潜在机制。我们旨在展示BA40如何通过加强肠道屏障和调节免疫反应来增强仔猪健康。
我们使用仔猪和细胞模型，结合微生物组学、代谢组学和转录组学分析，来研究BA40对产气荚膜梭菌诱导的炎症的影响。利用仔猪和细胞构建产气荚膜梭菌感染模型，以研究BA40对其表型的影响。随后，采用微生物组学、代谢组学和转录组学分析来研究BA40对仔猪肠道屏障的保护和免疫反应机制。
我们的研究表明，给予BA40后仔猪健康状况有显著改善。值得注意的是，BA40加强了肠道黏膜屏障，减轻了产气荚膜梭菌引发的炎症反应。BA40减少了有害细菌并增加了有益细菌。代谢物谱得到改善，有害物质减少。转录组学分析表明BA40在TNF/NF-κB信号通路中发挥作用，暗示其具有调节免疫反应和减轻肠道炎症的能力。细胞试验进一步证实了BA40减少炎性细胞因子释放和促进抗炎巨噬细胞分化的能力。
本研究数据集表明，BA40可调节肠道微生物和代谢物，抑制炎症相关信号通路，并维持肠道屏障功能。我们的研究结果不仅加深了我们对BA40治疗能力的理解，也为开发旨在改善仔猪肠道健康的益生菌和替代疗法提供了理论基础。
