Spermidine improve high copper diet-induced intestinal oxidative stress and microbiota community composition

High copper diet intake detriment animal health and livestock profitability. As a key polyamine, spermidine modulates critical physiological processes, include regulating autophagy and oxidative stress. However, the effect of spermidine in mitigating intestinal oxidative stress triggered by high copper diet has yet to be fully elucidated. In this study, eight-week male C57BL/6J mice were fed either a normal diet or a high-copper diet, supplemented with spermidine through water alone or in combination. The intestinal morphology was analyzed using HE staining, intestinal index, antioxidant capacity, SIgA, the content of copper ion, serum IgA, IgG and D-LA were detection. 16S rRNA was used to assess intestinal microbiota composition. The results showed that high copper diet intake disrupted intestinal morphology, elevated jejunum copper levels by 97% (p < 0.05), increased MDA by 31% and T-AOC by 54% in the duodenum (p < 0.05). Similarly, jejunum MDA increase by 49% and SOD rose by18% (p < 0.05). However, compared to CuSO₄ group, spermidine co-treatment improved duodenum villus-crypt ratio by 37% and enhanced serum IgG and IgA concentrations by 16% and 33% (p < 0.05). Microbial analysis via 16S rRNA sequencing revealed that spermidine reduced Staphylococcus abundance while promoting norank_f_Muribaculaceae. In conclusion, these findings suggest that spermidine supplementation restores intestinal architecture, boosts beneficial microbiota (e.g. Firmicutes, unclassified_f_Lachnospiraceae), and enhances antioxidant markers (SOD, T-AOC) and immune function (IgA).