Helminth Excretory/Secretory Proteins Ameliorate Colitis Through Preservation of Intestinal Homeostasis

Inflammatory bowel disease (IBD) manifests as a sustained gastrointestinal condition driven by an ongoing dysregulated immunity, defective mucosal barrier, and microbiota dysbiosis. Parasitic helminths exert immunomodulation chiefly via excretory/secretory proteins (ESP). This study assessed the remedial effects alongside the mechanistic pathways of the ESP derived from Echinococcus multilocularis (Emu-ESP) within a dextran sulfate sodium (DSS)-provoked colitis paradigm in mice. Our results indicated that Emu-ESP treatment significantly mitigated DSS-induced colitis and notably alleviated gut microbiota dysbiosis associated with colitis. Mechanistically, Emu-ESP preserved the gut barrier by enhancing the expression of mucin and epithelial junction genes in vivo and reduced organoid injury ex vivo with decreased apoptosis and NF-κB signaling. Furthermore, Emu-ESP could promote macrophage polarization toward the M2 phenotype during colitis. In conclusion, the therapeutic effectiveness of Emu-ESP is linked to its regulation of pathways that suppress inflammation, maintain intestinal barrier function, and prevent microbiota dysbiosis, suggesting it as a promising treatment for intestinal inflammatory disorders.