Open-Label Trial of a Prebiotic Preparation Containing Inulin and Oligofructose (Synergy-1) for the Treatment of Mild to Moderate Acute Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the colon which manifests as mucosal inflammation and ulceration. The disease affects various lengths of the colon. It cycles through periods of symptomatic relapse and asymptomatic remission. During relapse, patients suffer from frequent passage of watery diarrhea which may contain blood and mucous. Currently pharmacological treatments of mild to moderate UC consist of 5 amino salicylic acid (5 ASA), corticosteroids, and immunosuppressive agents such as azathioprine (Imuran), its metabolite 6-mercaptopurine (6-MP) and cyclosporine. Although 5-ASA medications are well-tolerated and relatively safe, systematic reviews have shown that they are successful in inducing remission in 50% of patients. Systemic corticosteroids and immunosuppressive such as cyclosporine, azathioprine and 6-MP have considerable toxicity which can limit their use in some patients. Therefore alternatives to the current standard therapy are in search.

The pathogenesis of UC is thought to be due to a combination of genetic, environmental and immunological factors. Several studies have shown that among the environmental factors, commensal intestinal bacteria play an important role in the etiology of UC. Patients with UC demonstrate a general increase in bacterial mucosal adherence and inter-epithelial cell penetration. Mucosal biopsies from UC showed increased concentrations of potentially pathogenic strains of enterobacteria (Escherichia coli group), Bacteroides and Clostridium species, and a relative decrease in protective organisms such as Faecalibacterium and Bifidobacteria, as compared to healthy individuals.

In the search for treatments of UC that have a direct influence on bacterial factors, efforts have been directed at altering the composition of the intestinal microflora to favour more protective organisms such as Lactobacilli and Bifidobacteria, also called probiotic bacteria. Several probiotic formulas (VSL#3 and Mutaflor - E. coli Nissle 1917) have shown efficacy as induction or maintenance therapy for UC or pouchitis.

As an alternative to oral supplementation with probiotic bacteria, prebiotics are more easily produced and cost-effective substitute. Prebiotics are oligosaccharides that cannot be enzymatically hydrolyzed in the small intestine, however serve as substrates for fermentation by probiotic bacteria in the colon. Prebiotics occur in nature; inulin is derived from chicory and oligosaccharides are present in edible plants. Human studies with healthy volunteers consuming diet supplemented with oligofructose or inulin demonstrated significant increase in luminal bifidobacteria and the strict anaerobe Faecalibacterium prausnitzii. These colonic bacterial groups are shown to alter cytokine production toward a more anti-inflammatory profile such as stimulating dendritic cell IL-10 production. In addition fructo-oligosaccharides fermentation in the colon results in improved short-chain fatty acids (SCFA) production, and in particular butyrate, which is important for the energy metabolism, cell differentiation and regulation of the immune response in the colon. Ulcerative colitis (UC), a subset of Inflammatory Bowel Disease (IBD) is characterized by disturbed microbial community (dysbiosis) with marked decrease of strict anaerobes, in particular Faecalibacterium spp. and Roseburia ssp. in addition to lower production of SCFA. Based on these findings oligofructose-enriched inulin (Beneo™ Synergy1) was chosen to be used in this trial.

Primary Hypothesis: Synergy-1 is a prebiotic food ingredient that can be used safely in the treatment of mild to moderate UC, and daily oral administration of Synergy-1 will result in the clinical improvement and/ or remission of disease.