BackgroundSpermine has been shown to promote intestinal maturation and protect intestinal health. However, its potential as a dietary feed additive for improving intestinal health in Wuzhishan piglets remains unclear. In this study, eighteen weaned Wuzhishan piglets were randomly assigned to three groups (n = 6 per group) and provided with either a basal diet (control), a diet supplemented with 0.01% spermine, or a diet supplemented with 0.03% spermine for 28 days.ResultsDietary supplementation with 0.01% spermine significantly improved growth performance (p < 0.05) and increased small intestinal α-amylase and trypsin activities (p < 0.05). It also significantly upregulated anti-inflammatory cytokines and downregulated pro-inflammatory cytokines in small intestine (p < 0.05). Compared with the control group, the relative abundance of the beneficial gut bacterium Prevotella was significantly increased in the 0.01% spermine group, while that of the harmful bacterium Streptococcus was significantly decreased in both the 0.01 and 0.03% spermine groups (p < 0.05). Additionally, DNA synthesis-related metabolic capacity and immune-related metabolite levels were significantly elevated in both the 0.01 and 0.03% spermine groups (p < 0.05).ConclusionThese findings suggest that dietary supplementation with 0.01% spermine can effectively alleviate weaning-induced intestinal dysfunction in Wuzhishan piglets by improving intestinal morphology, digestive enzyme activity, and immune responses, modulating the relative abundance of specific gut bacteria, and enhancing metabolic capacity.