P0906Melatonin Intervention Improves Clinical Prognosis in Patients with Inflammatory Bowel Disease: A Randomized Controlled Study Running Title: Melatonin and IBD Prognosis

Background Inflammatory bowel disease (IBD) is a chronic relapsing intestinal disorder, and sleep plays a significant role in its progression. The impact of sleep intervention, particularly melatonin, on disease activity remains unclear. We aim to evaluate the effects of melatonin on the prognosis of IBD. Methods This was a randomized, double-blind, placebo-controlled study. IBD patients in remission or with mild activity were randomly assigned, with half receiving a 3-month melatonin supplementation. The primary outcome was disease activity defined by patient reported outcomes (PRO). Secondary outcomes included disease progression, health-related quality of life, disability, and sleep quality. Gut microbiota were accessed at baseline and follow-up as exploratory outcomes. Results 53 participants completed this study, with 26 in the melatonin group. There were 38 participants with UC and 29 of 53 participants were in remission. The melatonin group showed significantly lower PRO2 scores at follow-up, and sustained remission rate was also higher (88.5% vs. 59.3%, P = 0.036). Placebo group experienced a significant increase in PRO2 scores at follow-up, while no changes were observed in melatonin group. The risk of relapse was lower in the melatonin group (HR: 0.23, 95% CI: 0.06 - 0.83, P = 0.03). No significant differences were observed in secondary outcomes. The relative abundance of Faecalibactrium and Ruminococcaceae showed significant changes before and after melatonin intervention. Conclusion Melatonin supplementation may facilitate sustained remission in IBD patients by modulating the gut microbiota, increasing SCFAs production. These findings provide a new perspective and evidence for the comprehensive management of IBD. Conflict of interest: Dr. Yu, Ziqing: No conflict of interest He, Xidong: No conflict of interest Yinghao, Sun: No conflict of interest Ruan, Gechong: No conflict of interest Bai, Xiaoyin: No conflict of interest Yang, Hong: No conflict of interest