In recent years, biologic agents such as infliximab, vedolizumab, and ustekinumab have demonstrated tremendous potential in the treatment of inflammatory bowel disease (IBD), altering the traditional treatment paradigm for IBD. Despite their significant efficacy, there remains a subset of patients who do not respond to biologic agents, necessitating research into the response mechanisms of biologic therapy to explore more precise treatment strategies. Preliminary work by the principal investigator has identified multiple potential responder cell subtypes to biologic agents, which may be influenced by the gut and oral microbiota. Therefore, this project proposes to investigate the mechanisms of response to biologic agents, aiming to explore more precise treatment strategies, through the integration of single-cell transcriptomics, 16S rRNA, and other multi-omics technologies on tissue samples, feces, saliva, peripheral blood, etc., from IBD patients before and after treatment. This will involve integrating bioinformatics analysis and in vitro/in vivo functional validation to elucidate the roles of treatment-responsive cell subtypes and gut and oral microbiota in the inflammatory microenvironment of the intestine, with the aim of uncovering the mechanisms of biologic agent therapy and providing new clues for the development of next-generation drug targets.

Inclusion Criteria:

• Patients aged 18 years or older; diagnosed with inflammatory bowel disease according to the 2019 European ECCO-ESGAR guidelines; who have not previously received any biologic therapy or, based on the treating physician's judgment, require treatment with infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), or ustekinumab (UST) after 3 months of medication.

Exclusion Criteria:

• Patients who refuse treatment with infliximab, adalimumab, vedolizumab, or ustekinumab for various reasons, or those with contraindications; patients currently using antibiotics or who have been in contact with probiotics/antibiotics in the past month; those with concomitant active autoimmune diseases, active tumors, etc.; those with severe oral diseases; patients experiencing other diseases unrelated to inflammatory bowel disease during treatment but may affect the efficacy of inflammatory bowel disease treatment; pregnant or lactating women; those deemed unsuitable for participation in this study by the investigator's judgment.

based on the treating physician's judgment, The patients require biologic therapy with infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), or ustekinumab (UST) after 3 months of medication. Patients were then divided into two groups based on whether primary non-response occurred or not.