Impact of oral butyrate on clinical and biochemical parameters in IBD: A randomized placebo-controlled study targeting gut microbiota.

BACKGROUND AND AIMS: We performed a randomized, double-blind, placebo-controlled, trial to investigate the changes in microbiome composition induced by Butyrate-Lsc-Microincapsulated (BLM) supplementation in IBD patients and its impact on disease activity. METHODS: 140 IBD patients (n=60 Crohn's disease, CD and n=80 Ulcerative Colitis, UC) were randomized to oral administration of BLM, plus conventional therapy. Stool samples were assessed by 16S sequencing and fecal calprotectin (fCal) analysis. For the microbiota analysis, the Firmicutes/Bacteroidota (F/B) ratio was used. Clinical disease activity was assessed by using the Harvey-Bradshaw-Index (HBI) for CD and partial-Mayo-Score for UC, Quality-of-life (QoL) by using Inflammatory-Bowel-Disease-Questionnaire-32 (IBDQ) and adherence-dietary-recommendation was evaluated before and after supplementation RESULTS: microbiota analysis revealed two principal enterotypes, defined by the F/B ratio, in both CD and UC patients. BLM exerted a more pronounced effect on Enterotype 1 (low F/B ratio), resulting in greater clinical and biochemical improvements and potentially identifying a target population. After supplementation, clinical disease activity (p=0.013) and fCal (p=0.047) improved significantly in CD, while fCal showed a marginal reduction in UC (p=0.09). QoL increased significantly in both CD (p<0.001) and UC (p=0.003). CONCLUSIONS: Supplementation with BLM, by modulating the gut microbiota, significantly improved disease outcomes and QoL in patients with IBD. GOV REGISTRATION: NCT04879914.