The Effects of Fermentable Dietary Fibre Supplementation on Intestinal Barrier Function, Intestinal Microbiome, and Inflammation in Microscopic Colitis Patients—A Randomised, Triple-Blinded, Placebo-Controlled Trial ^†

Abstract

Background: Microscopic colitis (MC) is a chronic inflammatory disease of the colon that primarily manifests as chronic watery diarrhoea. The aetiology of MC is still unknown, but the current hypothesis states that MC results from an abnormal immune response to luminal antigens in predisposed individuals. Studies have also shown that MC patients often display an increased intestinal permeability and alterations in the intestinal microbiota, which likely contribute to sustained intestinal inflammation. In this study, we aimed to examine how a dietary fibre known to promote luminal butyrate production affects intestinal homeostasis and gastrointestinal symptoms in MC patients. Methods: A total of 24 participants with a confirmed MC diagnosis were randomised into 2 study arms: The active treatment arm consumed 24 g of a wheat-based dietary fibre supplement daily for 6 weeks. The placebo arm consumed 24 g of maltodextrin daily. Blood and faecal samples were collected both at baseline and at the end of the intervention period. In vivo intestinal permeability was assessed with a multi-sugar test that allows the simultaneous measurement of gastroduodenal, small intestinal, and colonic permeability. The composition of the faecal microbiome was analysed with shotgun sequencing using the Illumina NextSeq2000 platform. The plasma concentrations of several inflammatory cytokines and chemokines were analysed using commercially available assays. The study protocol is registered at clinicaltrials.gov (NCT05058131). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 896263 and from Lantmännens Forskningsstiftelse. Results: A total of 22 (7 males, 16 females) participants completed both study visits. The median age of the participants was 65.6 (32–75). The study remains blinded, and the analyses are ongoing. Our preliminary group-wise analyses showed a statistically significant increase in the relative abundance of butyrate-producing bacteria in group A compared to group B. However, we did not observe any group-level differences in the measured cytokines or in the severity of gastrointestinal symptoms. The urinary excretion of the sugar probes assessing intestinal permeability will be measured with UPLC/MS/MS. Conclusions: The increase of butyrate-producing bacteria does not appear to lead to any significant improvements in the clinical symptoms of MC.