Dietary beta-fructans reduce inflammation in patients with mild to moderate Ulcerative Colitis

A relative lack of protective versus disease-inducing intestinal bacteria in genetically susceptible individuals is important for pathogenesis of ulcerative colitis (UC). Non-digestible, fermentable carbohydrates (prebiotics) are able to stimulate the growth and activity of specific protective microbiota. Our previous work showed that a mixture of prebiotic inulin and fructo-oligosaccharides (FOS) reduce chronic colitis in HLA-B27 transgenic rats, a validated colitis model. THE AIM of the present study is to assess if this prebiotic combination can reduce inflammation in patients with mild to moderate UC and to analyze microflora changes induced by these prebiotics. Patients with mild to moderate active UC, on stable doses of oral 5-ASA or no medication, were randomized to 7.5g or 15g daily oral inulin plus FOS (1:1) for 9 weeks. At the start and at wk 9 patients were assessed for disease activity (UCDAI) and endoscopic activity. Stool and biopsies were collected for fecal calprotectin, microbiota and gene expression analyses. Multiplex pyrosequencing of 16S rRNA tags based on Titanium platform was employed to identify the bacterial community at different taxonomic units. Statistical analysis using the Mann-Whitney test was performed in order to identify differences in the fecal and biopsy microbiota composition. Spermann test was used to reveal possible correlations between bacterial groups and inflammation. A total of 570,000 sequences were employed for statistical analysis. Colonic monocarboxylate transporter 1 (MCT1)-mRNA expression was also quantified. 24 patients completed the trial and 2 patients withdrew. Fifty percent of the patients who completed the treatment showed clinical response (12/24), of which 10 patients (42%) entered remission. The prebiotic showed a dose-dependent effect; patients on 15g dose had an average decrease in UCDAI of 2.5 versus 1.2 in the 7.5g dose. The clinical response was associated with an increase of bacterial biodiversity, as assessed by Shannon's and Simpson's diversity indices. The prebiotic treatment altered the ratio between Bacteroides and Firmicutes with a relative increase of Firmicutes. The high dose inulin plus FOS stimulated Incertae Sedis XIV and Lachnospiraceae (butyrate-producers), and Bifidobacteriaceae. Veillonellaceae, Erysipelotrichaceae and Coriobacteriaceae were also significantly elevated, but their function remains to be identified. Colitis reduction was associated with higher numbers of mucosal Faecalibacterium, Roseburia, Dialister and Lactobacillus. In contrast, specific mucosa-associated bacteria, including Leuconostoc, Enterococcus, Flavobacterium and genera from beta- and gamma-Proteobacteria were positively correlated with inflammation. The clinical response was associated with improved butyrate metabolism in the colon demonstrated by increase butyrate levels, increased bacterial butyryl-CoA-transferase gene copy numbers and upregulation of MCT1 gene expression. This suggests that improved butyrate metabolism mediates colitis reduction. Modulation of the gut microbiota by a mixture of inulin and FOS can improve chronic inflammation and alter the composition and metabolic function of colonic bacteria in UC patients. This small open prospective study indicates that these prebiotics show promise as adjunctive therapy to induce a clinical response in UC.