Abstract
ABSTRACT The intestinal microbiota is involved in ulcerative colitis (UC) pathogenesis. Prebiotics are hypothesized to improve health through alterations to gut microbiota composition and/or activity. Our aim was therefore to determine if inulin-type fructans induce clinical benefits in UC, and identify if benefits are linked to compositional and/or functional shifts of the luminal (fecal) and mucosal (biopsy) bacterial communities. Patients (n = 25) with mild/moderately active UC received 7.5 g (n = 12) or 15 g (n = 13) daily oral oligofructose-enriched inulin (Orafti®Synergy1) for 9 weeks. Total Mayo score, endoscopic activity and fecal calprotectin were assessed. Fecal and mucosal bacterial communities were characterized by 16S rRNA tag sequencing, and short chain fatty acids (SCFA) production were measured in fecal samples. Fructans significantly reduced colitis in the high-dose group, with 77% of patients showing a clinical response versus 33% in the low-dose group (P = 0.04). Fructans increased colonic butyrate production in the 15 g/d dose, and fecal butyrate levels were negatively correlated with Mayo score (r = −0.50; P = 0.036). The high fructan dose led to an increased Bifidobacteriaceae and Lachnospiraceae abundance but these shifts were not correlated with improved disease scores. In summary, this pilot study revealed that 15 g/d dose inulin type fructans in UC produced functional but not compositional shifts of the gut microbiota, suggesting that prebiotic-induced alterations of gut microbiota metabolism are more important than compositional changes for the benefits in UC. The findings warrant future well-powered controlled studies for the use of β-fructans as adjunct therapy in patients with active UC.
Highlights
Crohn’s disease (CD) and ulcerative colitis (UC), collectively called inflammatory bowel disease (IBD), are chronic inflammatory conditions of the intestine
The clinical response, changes in the inflammatory stool marker fecal calprotectin, the composition of fecal and mucosal microbiota, the fecal short-chain fatty acids production and butyrate metabolism were analyzed, and associations between the parameters were systematically tested. In this pilot exploratory clinical study assessing the efficacy, safety and tolerability of inulin type β-fructans (Synergy[1], Orafti) in active UC, 53 patients were screened of which 31 were eligible for the study based on the inclusion and exclusion criteria
The same short chain fatty acids (SCFA) and BCFAs that differed between responders and non-responders were identified to be significantly altered through the high β-fructan dose. These findings suggest that the prebiotic activity of β-fructans is based on a metabolic effect of the intestinal microbiota in UC patients reflected by changes in fecal SCFA patters towards increased butyrate production
Summary
Crohn’s disease (CD) and ulcerative colitis (UC), collectively called inflammatory bowel disease (IBD), are chronic inflammatory conditions of the intestine. Probiotic bacteria have shown efficacy in the treatment of UC and chronic pouchitis.[11] Inulin-type β-fructans are non-digestible carbohydrates that beneficially alter activity of gut microbiota[12] and are classified as prebiotics.[13] β-Fructans, were shown to reduce intestinal inflammation in rodent colitis models.[14] Their efficacy in managing inflammation in IBD, is not as well documented as the effect of probiotics and it remains disputed whether their activity relates to the stimulation of specific members of the intestinal microbiota, or metabolic alterations such as an increased production of short chain fatty acids (SCFAs).[12,13,15]
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