Multi-omics reveal microbial determinants impacting responses to biologic therapies in inflammatory bowel disease.

The intestinal microbiome is a key determinant of responses to biologic therapy in inflammatory bowel disease (IBD). However, diverse therapeutics and variable responses among IBD patients have posed challenges in predicting clinical therapeutic success. In this prospective study, we profiled baseline stool and blood in patients with moderate-to-severe Crohn's disease or ulcerative colitis initiating anti-cytokine therapy (anti-TNF or -IL12/23) or anti-integrin therapy. Patients were assessed at 14 weeks for clinical remission and 52 weeks for clinical and endoscopic remission. Baseline microbial richness indicated preferential responses to anti-cytokine therapy and correlated with the abundance of microbial species capable of 7α/ß-dehydroxylation of primary to secondary bile acids. Serum signatures of immune proteins reflecting microbial diversity identified patients more likely to achieve remission with anti-cytokine therapy. Remission-associated multi-omic profiles were unique to each therapeutic class. These profiles may facilitate a priori determination of optimal therapeutics for patients and serve as targets for newer therapies.

Vedolizumab Therapy Is Associated with an Improvement in Sleep Quality and Mood in Inflammatory Bowel Diseases.

INTRODUCTION: Poor sleep, depression, and anxiety are common in patients with inflammatory bowel diseases (IBD) and associated with increased risk of relapse and poor outcomes. The effectiveness of therapies in improving such psychosocial outcomes is unclear but is an important question to examine with increasing selectivity of therapeutic agents. METHODS: This prospective cohort enrolled patients with moderate-to-severe CD or UC starting biologic therapy with vedolizumab or anti-tumor necrosis factor α agents (anti-TNF). Sleep quality, depression, and anxiety were measured using validated short-form NIH PROMIS questionnaires assessing sleep and mood quality over the past 7 days. Disease activity was assessed using validated indices. Improvement in sleep and mood scores from baseline was assessed, and regression models were used to identify determinants of sleep quality. RESULTS: Our study included 160 patients with IBD (49 anti-TNF, 111 Vedolizumab) among whom half were women and the mean age was 40.2 years. In the combined cohort, we observed a statistically significant and meaningful decrease in mean scores from baseline (52.8) by week 6 (49.8, p = 0.002). Among vedolizumab users, sleep T-score improved from baseline (53.6) by week 6 (50.7) and persisted through week 54 (46.5, p = 0.009). Parallel reductions in depression and anxiety were also noted (p < 0.05 by week 6). We observed no difference in improvement in sleep, depression, and anxiety between vedolizumab and anti-TNF use at week 6. CONCLUSIONS: Both vedolizumab and anti-TNF biologic therapies were associated with improvement in sleep and mood quality in IBD.