Dietary serine supplementation improves growth performance and intestinal immunity and modulates gut microbiota in chronic oxidative stress-induced weaned piglets.

Serine is crucial for maintaining proper immune system function in both humans and animals. This study aimed to investigate the effects of dietary serine supplementation on microbial interactions and intestinal immunity in weaned piglets. In Exp. 1, a total of 35 weaned piglets (age 21 d, initial body weight [BW] 7.01 ± 0.07 kg, n = 7) were allocated to five dietary treatments for 42 d, a basal diet with no serine and supplemented with 0.25%, 0.50%, 0.75%, or 1.00% serine. The results showed that supplementation with 1.00% serine in the diet increased final BW and significantly elevated serum concentrations of immunoglobulin (Ig) A, IgG, and IgM (P < 0.05), supporting its selection for subsequent experiments. In Exp. 2, a total of 21 weaned piglets (age 21 d, initial BW 7.09 ± 0.09 kg, n = 7) were divided into three groups and fed for 28 d: basal diet (Ctrl), basal diet with D-galactose (D-Gal), and basal diet with 1.00% serine and D-galactose (Ser). D-galactose treatment significantly reduced average daily feed intake and aggravated intestinal morphological damage (P < 0.05), whereas serine supplementation effectively alleviated these effects (P < 0.05). Serine also enhanced systemic humoral immunity by increasing serum IgG and IgM on d 14 (P < 0.001) and serum IgA on d 28 (P = 0.003), and improved intestinal barrier function as evidenced by higher villus height to crypt depth ratios in the jejunum (P = 0.041) and ileum (P = 0.033). Furthermore, serine supplementation significantly downregulated the ileal mRNA expression of autophagy markers (becline, microtubule associated protein 1 light chain 3 beta [Lc3b-1], enhancer of polycomb 2 [Ep2c], and sequestosome 1 [P62]) and reduced phosphorylated- nuclear factor-kappa B (NF-κB) p65 subunit protein levels in the ileum of D-galactose-treated piglets (P < 0.05). It also enhanced microbial diversity and increased Bacteroidetes abundance while lowering Firmicutes abundance and the Firmicutes/Bacteroidetes ratio (P < 0.05). In addition, Spearman correlation analysis showed that ileal secretory immunoglobulin G (SIgG) was positively correlated with Acidobacteria, Chloroflexi, Streptococcus, and Actinobacteria, but negatively correlated with Firmicutes and Lactobacillus (P < 0.05). Collectively, these findings indicated that serine improves growth performance, mitigates chronic oxidative stress, and regulates NF-κB signaling and gut microbiota composition in weaned piglets.