Dietary Supplementation with Lysozyme–Cinnamaldehyde Conjugates Enhances Feed Conversion Efficiency by Improving Intestinal Health and Modulating the Gut Microbiota in Weaned Piglets Infected with Enterotoxigenic Escherichia coli

SIMPLE SUMMARY: Intestinal health is an important indicator of the healthy growth of piglets. As the agricultural industry eliminates the use of antibiotics in animal feed, alternatives to antibiotics will be needed. This study aims to evaluate the efficacy of lysozyme–cinnamaldehyde conjugates (LC) as a potential alternative to antibiotics in treating piglets infected with enterotoxigenic Escherichia coli (ETEC). The result shows that the LC-supplemented diet effectively mitigated the adverse effects of E. coli K88, including intestinal barrier damage and inflammation. Furthermore, it improved the structure of the intestinal flora, ultimately contributing to better growth performance in piglets. LC could be a useful, safe, and natural anti-inflammatory feed additive to prevent the decline in piglets’ intestinal health. ABSTRACT: This study aims to evaluate the efficacy of lysozyme–cinnamaldehyde conjugates (LC) as a potential alternative to antibiotics in treating piglets infected with enterotoxigenic Escherichia coli (ETEC). The results demonstrated that piglets fed with the LC diet exhibited lower rectal temperature and fecal scores at 9 h, 24 h, and 48 h post-ETEC challenge. Furthermore, LC supplementation led to significant improvements in the mechanical and immune barriers of the jejunum and ileum, as indicated by an increased villi-height-to-crypt-depth ratio (VCR) and the expression of tight junction proteins, mucin, and β-defensins. Furthermore, the LC diet lowered the levels of pro-inflammatory cytokines TNF-α and IL-1β in the plasma. Further analyses showed that the LC diet downregulated genes (specifically TLR4 and MyD88) linked to the TLRs/MyD88/NF-κB signaling pathway in the small intestine. Additionally, 16SrDNA sequencing data revealed that LC supplementation increased the α diversity of intestinal microorganisms and the relative abundance of Lactobacillus. In summary, the LC-supplemented diet effectively mitigated the adverse effects of E. coli K88, including intestinal barrier damage and inflammation. Furthermore, it improved the structure of the intestinal flora, ultimately contributing to better growth performance in piglets.