Reduction of Intestinal Redox Potential by Coated Ferulic Acid Accelerates Microbial Restoration and Restricts Enterotoxigenic Escherichia coli Colonization in Weaned Piglets

ABSTRACT Weaning stress induces redox perturbation and microbial dysbiosis in piglets, resulting in intestinal disorders and disease susceptibility. This study investigated the effects of coated ferulic acid (FA) on intestinal redox homeostasis, microbial restoration, and host responses during enterotoxigenic Escherichia coli (ETEC) infection. Results showed that coated FA supplementation accelerated the structural and functional recovery of the gut microbiota following weaning stress. Specifically, coated FA accelerated the restoration of ecological complexity and selectively enriched beneficial taxa. Following the ETEC challenge, a reduced redox potential facilitated the recolonization of advantageous taxa—including the genera Lactobacillus , Ligilactobacillus , Lachnospira , Roseburia , Lachnoclostridium , and Blautia— while suppressing E. coli ( p < 0.05). Metagenomic and transcriptomic analyses under coated FA treatment indicated the induction of short‐chain fatty acids synthesis and the downregulation of inflammatory genes ( p < 0.05). Furthermore, genes involved in mitochondrial oxidative phosphorylation ( COX5B , COX6A1 , and COX7A2 ), antioxidant defense ( GPX4 , GPX7 , and GPX8 ), cytokines ( IL‐22 , IL‐17 ), as well as mucins ( MUC1 , MUC2 , and MUC13 ) showed strong association with these beneficial genera. These findings suggest that coated FA helps restore intestinal redox balance, supports the colonization of beneficial bacteria, and enhances host resistance, offering a promising nutritional strategy for swine production.