Hymenolepis nana antigens alleviate ulcerative colitis by promoting intestinal stem cell proliferation and differentiation via AhR/IL-22 signaling pathway

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with an unknown etiology and is difficult to treat. Studies have shown that some helminths and their associated products have therapeutic potential in controlling or preventing inflammatory diseases. This study is to investigate the mitigation effects of Hymenolepis nana antigens (HnAg) on the UC model. HnAg significantly improved the disease activity index, colon length, and colonic pathological damage in mice with dextran sulfate sodium (DSS)-induced colitis. HnAg intervention could protect the number of goblet cells and enhance the expression of tight junction proteins and mucins, thereby improving intestinal barrier integrity. HnAg attenuated small intestinal organoid damage and stimulated intestinal stem cells proliferation in a DSS-induced mouse organoid inflammation model. The protective mechanism of HnAg might be related to the activation of the aryl hydrocarbon receptor (AhR)/IL-22 signaling pathway, which regulates intestinal barrier function and promotes the proliferation and differentiation of intestinal stem cells. In conclusion, HnAg has a therapeutic effect on UC mice. Our study provides a new approach for alleviating UC by Hymenolepis nana and its associated products.