Effects of Ellagic Acid on Gut Microbiota and Tryptophan Metabolism in Paraquat-Challenged Piglets Subjected to Ampicillin-Induced Microbiota Perturbation

Oxidative stress (OS) is closely associated with intestinal dysfunction, gut microbial dysbiosis, and metabolic disturbances in weaned piglets. Ellagic acid (EA) is a dietary polyphenol with antioxidant properties. This study investigated the effects of EA supplementation and ampicillin (AMP)-induced microbial perturbation on OS, gut microbiota, and tryptophan (Trp) metabolism in paraquat (PQ)-challenged piglets. Twenty-four weaned piglets were assigned to four treatments in a 2 × 2 factorial design (±EA, ±AMP), followed by a PQ challenge. Neither EA nor AMP affected growth performance or most serum biochemical parameters. EA significantly decreased malondialdehyde (MDA) in AMP-treated piglets. AMP altered ileal morphology and reshaped the microbial community in both the ileum and colon. Moreover, EA and AMP differentially affected Trp metabolism in serum and intestinal segments; AMP altered kynurenine-pathway and microbiota-associated indole metabolites, with significant EA × AMP interactions for some metabolites. Spearman analysis further revealed distinct associations between gut microbiota and Trp metabolites along the intestinal tract. Collectively, AMP-induced microbial perturbation was accompanied by substantial Trp-metabolism alterations and distinct microbiota–Trp associations, whereas EA modulated MDA levels and selected microbial and metabolic responses under AMP treatment. These observations suggest that EA effects under OS may be associated with gut microbiota-Trp metabolism axis modulation, although causality remains to be established.