Multi-omics suggest diverse mechanisms for response to biologic therapies in IBD

The intestinal microbiome is a key determinant of response to biologic therapy in inflammatory bowel disease. We conducted a prospective study, profiling baseline stool and blood samples, in patients with moderate-to-severe Crohn's disease or ulcerative colitis initiating anti-TNF, anti-IL12/23 (grouped as anti-cytokine therapy), or anti-intergrin therapy. Patients were assessed at 14 weeks for clinical remission and 52 weeks for clinical and endoscopic remission. Baseline microbial richness was a key feature indicating preferential response to anti-cytokine therapy. Increase diversity of baseline samples could be attributed to increased abundance of microbial specific competent in the 7-alpha/beta-dehydroxylation of primary to secondary bile acids. Paired serum metabolomic analysis reaffirmed the readouts of microbial-derived secondary bile acids. Serum signatures of immune-proteins reflective of microbial diversity identify a subset of patients who were more likely to achieve remission with anti-cytokine therapy. Twenty seven unique serum immune-proteins profiles associated with remission in this study were unique to specific therapeutic classes. The multi -omic profiles identified from this study could aid physicians to determine a. priori the therapeutic class most likely to benefit patients, as well as potentially serve as novel targets for newer therapies to treat IBD.