Double blind placebo-controlled trial for the prevention of ulcerative colitis relapses by β-fructan prebiotics: efficacy and metabolomic analysis

Abstract

BackgroundUlcerative colitis (UC) is associated with altered intestinal microbiome (‘dysbiosis’), most significantly, reduced strict butyrate-producing anaerobes and increased facultative anaerobes. Inulin-type prebiotics appear to reduce and prevent colitis in preclinical studies and small clinical trials. However, these results need to be validated in randomized controlled clinical trial (RCT) studies.AimsThe aim of this RCT study was to assess the efficacy of β-fructans (oligofructose and inulin) in preventing relapses in UC patients in clinical remission as well as identify potential mechanisms of activity.MethodsAdult UC patients in clinical remission (total Mayo score ≤ 2) were randomized to supplement their diet with 15g/d of either β-fructans (oligofructose and inulin; Synergy1/Prebiotin) or placebo (maltodextrin) for 6 months. Partial Mayo scores, medications, adverse events and intervention compliance were monitored monthly. Fecal specimens were collected throughout the study to measure fecal calprotectin (FCP), along with stool metabolites.ResultsEighty-nine UC patients in clinical remission were randomized to β-fructans (n=43) or placebo (n=46). Of those, 11 participants never started, 2 were withdrawn, and 76 were included in the study population (β-fructans n=35; placebo n=41). Although there was no difference in symptomatic clinical flare (β-fructans n=11 flare; placebo n=10 flare, P=0.60), patients randomized to oligofructose and inulin showed only a 3-fold median FCP increase versus 17-fold in the placebo group (P=0.038). Interestingly, antibiotics and serotonin reuptake inhibitors significantly increased the relative risk (RR) of flare (RR 3.321, 95% Cl 2.005 to 5.344, P < 0.0001). β-Fructan intake significantly increased anti-inflammatory fecal metabolites (arabinose, L-arabitol, 5-oxo-D-proline).ConclusionsAlthough oligofructose and inulin did not prevent symptomatic relapses in UC patients, their oral administration significantly reduced the severity of biochemical relapse compared to placebo which was further associated with increased anti-inflammatory metabolites.