Platycodon grandiflorum polysaccharide (PGP) extracted from Platycodon grandiflorum, which has the advantages of anti-inflammatory, antioxidant, anti-tumor, and no side effects on the organism. This study evaluated whether dietary PGP alleviates weaning-induced intestinal dysfunction in piglets. A total of 18 newly weaned piglets (6.46±0.31 kg) were allocated to 3 treatments (n = 6/group) for a 28-day feeding trial. The control group received a basal diet, while the L-PGP and H-PGP groups were supplemented with 1 g/kg and 2 g/kg PGP, respectively. On day 28, piglets were electrically stunned and euthanized by exsanguination; spleen, liver, and colon samples were collected to assess inflammatory/antioxidant markers, barrierrelated genes, and colonic microbiota. The supplementation of PGP increased the average daily gain (p<0.05), and reduced the feed-to-gain ratio of weaned piglets. In addition, PGP reduced the expression of splenic IL-1β, IL-2, and IL-4 (p<0.05). This effect was associated with upregulated mRNA levels of the key tight junction proteins Occludin, ZO‑1, and Claudin‑1 in the colonic mucosa and tissue (p<0.05). Compared with the control group, the mRNA expression levels of PKC, Nrf2 and KEAP1 in the colonic tissue of weaned piglets were increased in the HPGP (p<0.05). More importantly, H-PGP supplementation increased the relative abundances of Bacteroidota, while decreasing the abundance of Proteobacteria. Moreover, Spearman correlation analysis revealed that short-chain fatty acid-producing commensal genera (Faecalibacterium) were negatively correlated with pro-inflammatory cytokines and signaling genes, but positively correlated with antioxidant genes (p<0.05). Conversely, the relative abundance of Escherichia-Shigella was negatively correlated with the mRNA expression of PKC, Nrf2, and Keap1 (p<0.05). PGP can alleviate the weaning stress in piglets, by modulating the colonic microbiota and enhancing systemic anti-inflammatory capacity and intestinal barrier function.
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