P859 Sodium Butyrate supplementation significantly improved clinical outcomes and quality of life in patients with Crohn’s Disease – results from a randomized placebo-controlled study

Abstract

Abstract Background Butyrate has shown anti-inflammatory effects and plays an important role in maintaining gut homeostasis, providing symptomatic relief when orally supplemented in patients suffering from various colonic diseases. Methods In this randomised, double-blind, placebo-controlled study 140 IBD patients in remission or with mild disease (n=60 Crohn's disease, CD and n=80 Ulcerative Colitis, UC) were randomized to oral administration of BLM/placebo for 90 days in addition to conventional therapy. As primary aim: changes in microbiome composition induced by BLM treatment. Fecal microbiota from stool samples was assessed by 16S sequencing. Clinical disease activity assessed by using Harvey Bradshaw Index (HBI) for CD and partial-Mayo Score (pMS) for UC, quality of life assessed by using Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32) and adherence-dietary-raccomandation( WCRF) were evaluated before and after treatment. Results Demographics, clinical and dietary characteristics were similar between the two populations. The microbiota sequencing highlighted two different enterotypes in CD population: the first one was characterized by a low F/B ratio (with a genus prevalence of Fusobacteriota, Alistipes, and Blautia). The second enterotype was characterized by a higher F/B ratio (with a genus prevalence of Escherichia-Shigella and Lachnoclostridium)(Fig1). BLM had a more pronounced effect on enterotype-1 where the taxa associated with intestinal comfort, SCFA production, increased after treatment, while the taxa associated with CRC and intestinal inflammation, decreased. After treatment was observed: a)improved quality of life (IBDQ-32: CD: treat. 170/184 vs Pb. 188/197 p<0.001 vs p=0.021; UC: treat.185/195 vs Pb.188/188 p=0.003 vs p=0.4), b)lower disease activity in CD patients (the HBI score, showed a significant improvement for those treated with BLM as compared to placebo (McNemar’s p=0.013 vs p>0.9).c) reduced Calprotectin levels (Table1.) Finally, a significant separation was observed in samples from patients who have undergone minor surgery (ileo-colon), compared to non-surgery patients. The variable "surgery" seems to be associated with the enterotype-1. Conclusion Sodium butyrate supplementation significantly improved clinical outcomes and quality of life in patients with CD. Our data showed that the differential response to BLM treatment is based on enterotype, suggesting that Enterotype-1 patients may experience greater clinical benefits and improvements in QoL compared to Enterotype-2 patients in both UC and CD populations.