Paragonimus proliferus Metacercaria-derived antigens mitigate DSS-Induced Ulcerative Colitis via immunomodulation and gut microbiota reconfiguration

Ulcerative colitis (UC) is a chronic inflammatory bowel illness with few treatment options, which means that new ways to treat it are needed. This study examined the protective effects and mechanisms of Paragonimus proliferus metacercaria-derived antigens (PmAg) in a dextran sulfate sodium (DSS)-induced mouse ulcerative colitis model. We discovered that intraperitoneal delivery of PmAg substantially mitigated colitis severity, as demonstrated by decreased weight loss, lower disease activity index scores, maintained colon length, and enhanced histopathological findings. Mechanistically, PmAg inhibited pro-inflammatory cytokines (IL-1β, TNF-α), increased the anti-inflammatory cytokine IL-10, and bolstered antioxidant defenses (SOD, GSH). It also restored the integrity of the intestinal barrier by boosting the number of goblet cells and the expression of tight junction proteins (Occludin, Claudin-1), while stopping the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Moreover, 16S rRNA sequencing demonstrated that PmAg reinstated gut microbiota α-diversity, diminished pathogenic genera (e.g., Escherichia-Shigella), and enhanced beneficial taxa (e.g., Lachnospiraceae_NK4A136_group and Alistipes). Integrated fecal metabolomics research revealed that PmAg altered metabolic profiles, specifically as significantly enriched the primary bile acid biosynthesis pathway, alpha-Linolenic acid metabolism pathway and Ubiquinone and other terpenoid-quinone biosynthesis pathways. In conclusion, our results suggested that PmAg could mitigates experimental colitis in mice by anti-inflammatory, improving gut microbiota and modulating fecal metabolomics.