Dietary Sanguinarine Enhances Antioxidant Capacity and Intestinal Barrier Function in Yellow-Feathered Broilers via Modulation of Microbiota-Associated Butyrate Signaling

Sanguinarine (SA), a bioactive benzophenanthridine alkaloid, has emerged as a potential alternative to antibiotic growth promoters; however, its effects on intestinal redox homeostasis and epithelial regeneration remain incompletely understood. This study investigated whether dietary SA could improve growth performance and intestinal health in yellow-feathered broilers and explored the potential involvement of gut microbiota-associated metabolite signaling pathways. Broilers were fed diets supplemented with different concentrations of SA (0.5 or 0.7 mg/kg feed), with an antibiotic-supplemented group serving as a comparator. High-dose SA (0.7 mg/kg feed) improved body weight and average daily gain while reducing the feed-to-gain ratio. SA also alleviated intestinal barrier dysfunction, as evidenced by reduced circulating diamine oxidase, D-lactate, and lipopolysaccharide levels, together with increased jejunal expression of tight-junction proteins and MUC2. In parallel, SA enhanced systemic and intestinal antioxidant capacity, as indicated by increased total antioxidant capacity and superoxide dismutase activity and decreased malondialdehyde accumulation. These changes were accompanied by increased immunoglobulin levels, reduced expression of pro-inflammatory mediators, and enhanced expression of anti-inflammatory cytokines. Cecal microbiota analysis demonstrated that SA markedly reshaped the microbial community, with enrichment of Faecalibacterium and depletion of several potentially unfavorable taxa. These microbial alterations, which were associated with improved antioxidant and immune indices, were accompanied by a selective increase in cecal butyrate levels. Consistently, SA enhanced intestinal GPR109A expression and upregulated genes associated with Wnt/β-catenin signaling. In LPS-challenged intestinal organoids, SA restored organoid growth and budding capacity, reduced apoptosis, increased Ki67-positive cell proliferation, and restored the expression of genes associated with Wnt/β-catenin signaling. Collectively, these findings indicate that dietary SA improves growth performance and intestinal homeostasis in broilers by attenuating oxidative stress and inflammation, strengthening epithelial barrier function, and supporting epithelial regeneration. The microbiota-associated butyrate/GPR109A/Wnt/β-catenin signaling pathway may contribute to these protective intestinal effects.