ORAL SODIUM BUTYRATE ADMINISTRATION SIGNIFICANTLY IMPROVES CLINICAL OUTCOME AND QUALITY OF LIFE IN PATIENTS WITH CROHN’S DISEASE BY MODIFYING THE GUT MICROBIOTA – RESULTS FROM A RANDOMISED PLACEBO-CONTROLLED STUDY

Background and Objectives: Butyrate, a short-chain fatty acid (SCFA), is crucial as the primary energy source for colonocytes. The deficiency of SCFAs has been theorized to lead to mucosal hypoplasia and colitis. In this monocentric randomized, placebo-controlled trial, we investigated changes in microbiome composition induced by microencapsulated sodium butyrate (BLM) treatment in patients with inflammatory bowel disease (IBD) and its impact on disease activity.
Methods: One hundred forty IBD patients (60 with Crohn's disease, CD, and 80 with Ulcerative Colitis, UC) were randomly assigned to receive oral administration of BLM or placebo( PBO) for three months, in addition to conventional therapy. Stool samples and the Firmicutes/Bacteroidota(F/B) ratio enterotypes were assessed using 16S sequencing. Clinical disease activity was evaluated using the Harvey Bradshaw Index (HBI) for CD and partial-Mayo Score (pMS) for UC. Quality of life (QoL)was assessed using the Inflammatory Bowel Disease Questionnaire 32 (IBDQ-32), and adherence to dietary recommendations was evaluated before (T0=0 day) and after treatment (T1=90 days).
Results: Two primary enterotypes were identified for both CD and UC patients. The first was characterized by a prevalence of Bacteroidota, and the second by a prevalence of Firmicutes. Changes in the F/B ratio served as a macroscopic representation of alterations in microbiota composition. BLM had a more pronounced effect on Enterotype 1, increasing taxa associated with improving gut health and immunomodulation (Clostridia, Ruminococcus, Lachnospiraceae, [Eubacterium]). Conversely, taxa associated with intestinal inflammation (Escherichia-Shigella, Klebsiella, and Morganella) decreased. Significantly greater improvements in QoL, as measured by IBDQ, were observed in the BLM-treated group compared to the PBO group in both UC and CD patients (p = 0.029 in CD and p = 0.086 in UC). Calprotectin levels also significantly reduced in CD patients treated with BLM compared to PBO (p = 0.047 vs p = 0.7). A similar trend was observed in UC patients, with a slightly less significant reduction in the BLM group (BLM: p = 0.09 vs PBO: p = 0.14). Clinical disease activity showed a significant improvement in the BLM-treated group compared to placebo in CD patients (BLM: p = 0.013 vs PBO: p > 0.9). While not statistically significant in UC patients, an encouraging trend favoring the BLM-treated group was observed (BLM: p = 0.13 vs PBO: p = 0.72).

Conclusions: Sodium butyrate supplementation significantly improves the clinical activity and quality of life in IBD patients. Furthermore, our data indicate that the differential response to BLM treatment is based on enterotype, suggesting that Enterotype-1 patients may experience greater clinical benefits and improvements in quality of life compared to Enterotype-2 patients in both UC and CD populations.