Abstract
The management of the dysbiosed gut microbiota in inflammatory bowel diseases (IBD) is gaining more attention as a novel target to control this disease. Probiotic treatment with butyrate-producing bacteria has therapeutic potential since these bacteria are depleted in IBD patients and butyrate has beneficial effects on epithelial barrier function and overall gut health. However, studies assessing the effect of probiotic supplementation on microbe-microbe and host-microbe interactions are rare. In this study, butyrate-producing bacteria (three mono-species and one multispecies mix) were supplemented to the fecal microbial communities of ten Crohn’s disease (CD) patients in an in vitro system simulating the mucus- and lumen-associated microbiota. Effects of supplementation in short-chain fatty acid levels, bacterial colonization of mucus environment and intestinal epithelial barrier function were evaluated. Treatment with F. prausnitzii and the mix of six butyrate-producers significantly increased the butyrate production by 5–11 mol%, and colonization capacity in mucus- and lumen-associated CD microbiota. Treatments with B. pullicaecorum 25-3T and the mix of six butyrate-producers improved epithelial barrier integrity in vitro. This study provides proof-of-concept data for the therapeutic potential of butyrate-producing bacteria in CD and supports the future preclinical development of a probiotic product containing butyrate-producing species.
Highlights
Inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by a chronic, relapsing intestinal inflammation
At the end of the incubation, the average concentration of Lachnospiraceae members in non-treated samples tended to be lower in both lumen- (p = 0.08) and mucus(p = 0.07) associated microbiota of active CD compared to remissive CD (Fig. 1C)
Patients with CD were selected as there is a major shift in their butyrate-producing gut microbial community, especially in active CD13
Summary
Inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by a chronic, relapsing intestinal inflammation. The decreased abundance of Firmicutes bacteria belonging to the families Ruminococcaceae ( referred as clostridial cluster IV) and Lachnospiraceae ( referred as clostridial cluster XIVa) as opposed to healthy control samples is one of the major signatures of the microbial dysbiosis in IBD, especially in (active) CD12–15. Both families are important functional members of the human gut microbiota since most butyrate-producing bacteria from the human gut belong to them. There is a lack of studies assessing the functional effect of supplementation of butyrate-producing bacteria to dysbiosed human IBD microbiota on microbial interactions (e.g. SCFA production) and host-microbe interactions (e.g. epithelial barrier integrity). Caco-2 monolayers were exposed to samples derived from in vitro CD microbiota supplemented with butyrate-producers to assess the host-microbiome interactions
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