Excretory/secretory products from Hymenolepis nana adult worms alleviate ulcerative colitis in mice via tuft/IL-13 signaling pathway.

BACKGROUND: Hymenolepis nana (H. nana) is a zoonotic parasitic worm that parasitizes the small intestines of humans and rodents. Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease. Current symptom-based clinical treatments do not alter the natural course of UC, and mucosal healing has become a primary therapeutic goal for UC. However, the regulatory role of excretory/secretory products (ESPs) from H. nana adult worms in repairing the damaged intestinal mucosal barrier remains unclear. METHODS: This study investigated the protective effects of ESPs on intestinal mucosal integrity by using a dextran sulfate sodium (DSS)-induced colitis mouse model and a mouse small intestine organoid inflammation model. Histopathological alterations of mouse intestinal tissues were determined by pathological staining; the alterations in mucins, tight junction proteins, cytokines, and the number of various intestinal cells were detected by Western blotting (WB), immunohistochemistry (IHC), immunofluorescence (IF) and real-time quantitative polymerase chain reaction (RT-qPCR), etc. RESULTS: ESPs significantly improved DSS-induced intestinal damage in mice. Meanwhile, ESPs increased mucins and tight junction proteins expression and promoted intestinal stem cell proliferation and differentiation, thereby maintaining intestinal mucosal barrier integrity and alleviating UC in mice. In the DSS-induced inflamed small intestinal organoid model, ESPs reduced organoid damage and promoted the proliferation and differentiation of intestinal stem cells. The protective mechanism of ESPs might be related to the activation of the tuft/IL-13 signaling pathway, regulating intestinal barrier function and promoting the regeneration of intestinal stem cells. CONCLUSIONS: In conclusion, H. nana-derived ESPs intervention facilitates healing of intestinal mucosa to alleviate UC in mice, enriching the feasibility and selectivity of "helminthic therapy."