呕吐毒素是我国饲料与饲料原料中污染严重的霉菌毒素，对养猪生产危害极大。围绕呕吐毒素致仔猪肠道损伤的机制及营养调控展开了系列研究，通过构建断奶仔猪和猪肠上皮细胞的呕吐毒素应激模型，揭示了呕吐毒素导致仔猪肠道防御肽表达紊乱的分子机制，建立了肠道微生物与呕吐毒素致断奶仔猪厌食之间的潜在关系。基于上述研究基础探索性发现，丁酸能够缓解呕吐毒素造成的断奶仔猪生长抑制和肠道屏障功能损伤。

1、揭示了呕吐毒素致仔猪肠道防御肽表达紊乱的分子机制

肠道防御肽是机体天然免疫系统的重要组成部分，对维持黏膜稳态和抵御病原微生物感染发挥着至关重要的作用。断奶仔猪饲养试验发现，接近国家饲料卫生标准限量的呕吐毒素（1.28mg/kg）就能显著抑制仔猪不同位点肠段的防御肽表达，从基因和蛋白水平鉴定了 NOD2/caspase-12通路在呕吐毒素干扰仔猪肠道防御肽表达中的作用。

       肠道防御肽表达紊乱会造成肠道微生物菌群失衡，导致慢性肠道疾病。申请人进一步研究了呕吐毒素暴露对断奶仔猪肠道微生物菌群的影响，筛选得到了介导呕吐毒素致断奶仔猪厌食的关键微生物（Lachnospiraceae 和 Ruminococcaceae_UCG-014 等），建立了肠道微生物与呕吐毒素致断奶仔猪厌食之间的潜在关系。上述研究加深了呕吐毒素致断奶仔猪肠道损伤的认识，从调节肠道防御肽表达的角度为缓解呕吐毒素致断奶仔猪肠道毒性奠定了科学依据和理论基础。

2、阐明了丁酸缓解呕吐毒素致断奶仔猪肠道损伤的可行性

丁酸是由结肠微生物发酵膳食纤维而生成的一种短链脂肪酸，在调节生长、炎症、肠道屏障功能和氧化应激中发挥重要作用，并且能够促进宿主防御肽表达。基于前期研究基础探索性发现，日粮中添加 0.2%丁酸钠能够有效缓解呕吐毒素造成的仔猪生长抑制和肠道损伤。进一步发现能够通过调节 NOD2/caspase-12 通路干预呕吐毒素对仔猪肠道防御肽的表达，并维持肠道微生物菌群平衡。本研究首次发现了丁酸钠在缓解呕吐毒素致断奶仔猪肠道损伤中的作用，对指导防控呕吐毒素造成断奶仔猪的毒害具有重要的理论意义和实际价值。

1. Deoxynivalenol triggers porcine intestinal tight junction disorder through hijacking SLC5A1 and PGC1α-mediated mitochondrial function. Xue DF, Yang P, Yang YY, Wang YN, Wu KT, Qi DS, Wang S. Food and Chemical Toxicology, 2022, 163, 112921.

2. Mechanism of deoxynivalenol mediated gastrointestinal toxicity: Insights from mitochondrial dysfunction. Wang S, Wu KT, Xue DF, Zhang C, Rajput SA, Qi DS. Food and Chemical Toxicology, 2021, 153, 112214.

3. Sodium butyrate protects the intestinal barrier by modulating intestinal host defense peptide expression and gut microbiota after a challenge with deoxynivalenol in weaned piglets. Wang S, Zhang C, Yang JC, Wang X, Wu KT, Zhang BY, Zhang JC, Yang A, Rajput SA, Qi DS. Journal of Agricultural and Food Chemistry, 2020, 68, 4515-4527.

4. Deoxynivalenol inhibits porcine intestinal trefoil factors expression in weanling piglets and IPEC-J2 cells. Wang S, Zhang C, Wang X, Yang JC, Wu KT, Zhang JC, Zhang BY, Yang A, Qi DS. Toxins, 2019, 11, 670.

5. Enhancement of macrophages function by the antimicrobial peptide sublancin protects mice from methicillin-resistant Staphylococcus aureus. Wang S, Ye QH, Wang K, Zeng XF, Huang S, Yu HT, Ge Q, Qi DS, Qiao SY. Journal of Immunology Research, 2019, DOI: 10.1155/2019/3979352.

6. Potential link between gut microbiota and deoxynivalenol-induced feed refusal in weaned piglets. Wang S, Yang JC, Zhang BY, Zhang L, Wu KT, Yang A, Li C, Wang YN, Zhang JC, Qi DS. Journal of Agricultural and Food Chemistry, 2019, 67, 4976-4986.

7. Deoxynivalenol impairs porcine intestinal host defense peptide expression in weaned piglets and IPEC-J2 cells. Wang S, Yang JC, Zhang BY, Wu KT, Yang A, Li C, Zhang JC, Zhang C, Rajput SA, Zhang NY, Sun LY, Qi DS. Toxins, 2018, 10, e541.

8. Use of antimicrobial peptide sublancin with combined antibacterial and immunomodulatory activities to protect against methicillin-resistant Staphylococcus aureus infection in mice. Wang S, Wang QW, Zeng XF, Ye QH, Huang S, Yu HT, Yang TR, Qiao SY. Journal of Agricultural and Food Chemistry, 2017, 65, 8595-8605.

9. Prevention of Escherichia coli infection in broiler chickens with Lactobacillus plantarum B1. Wang S, Peng Q, Jia HM, Zeng XF, Zhu JL, Hou CL, Liu XT, Yang FJ, Qiao SY. Poultry Science, 2017, 96, 2576-2586.

10. The antimicrobial peptide sublancin ameliorates necrotic enteritis induced by Clostridium perfringens in broilers. Wang S, Zeng XF, Wang QW, Zhu JL, Peng Q, Hou CL, Thacker P, Qiao SY. Journal of Animal Science, 2015, 93, 4750-4760.