IDDF2023-ABS-0270 The role and mechanism of gut microbiota and its metabolites in the healing of IBD intestinal mucosa induced by anti-TNF-α therapy

Background

To study the role and mechanism of anti-tumor necrosis factor (TNF-α) treatment in the induction of intestinal mucosal healing in inflammatory bowel disease (IBD).

Methods

The IFX treatment-altered intestinal flora/supernatant-treated DSS-induced wild-type acute colitis mouse model was constructed, and the disease activity, colon length, and histopathological damage were evaluated, and the expression of intestinal interferon-stimulated genes (ISGs) was detected by qPCR. The expression of FXR was detected by WB, and the expressions of colonic β-catein and Ki-67 were detected by immunofluorescence. A DSS-induced IFNAR1-/-acute colitis mouse model was constructed with intestinal flora altered by IFX treatment, and disease activity, colon length, and histopathological damage was evaluated.

Results

The colitis mice treated with IFX treated with the fecal suspension of colitis mice showed obvious disease remission. IFX-treated colitis mice fecal suspension induced the expression of ISGs, up-regulated the expression of FXR, and promoted the proliferation of colonic epithelial cells. IFX treatment in remission stage CD children’s fecal suspension alleviates weight loss, DAI, colon shortening, and pathological damage in DSS-induced acute colitis mice, induces the expression of ISGs, increases the expression of FXR, and promotes the proliferation of colonic epithelial cells. IFX treatment altered intestinal flora and intestinal bacterial metabolites could not ameliorate DSS-induced weight loss, colon shortening, and pathological damage in IFNAR1-/- mice. Bifidobacterium longum CECT 7894 increases the expression of colonic tight junction protein and colonic FXR, improves the composition of colonic flora and bile acid metabolism, and improves the efficacy of IFX in treating acute colitis mice.

Conclusions

The gut microbiota altered by IFX treatment activates FXR, induces the expression of ISGs, promotes the proliferation of intestinal epithelial cells, and reduces the expression of inflammatory factors in acute colitis mice.