Metabolic Profiling of the Impact of Oligofructose-Enriched Inulin in Crohn's Disease Patients: A Double-Blinded Randomized Controlled Trial

OBJECTIVES: Although intestinal dysbiosis is well established in Crohn's disease (CD), little is known about the microbial metabolic activity of CD patients. In this study, we compared the metabolite patterns of the CD patients with profiles from healthy controls (HCs) and correlated them to disease activity and bacterial composition. In addition, the influence of the prebiotic oligofructose-enriched inulin (OF-IN) on the CD metabolites profile was evaluated. METHODS: Sixty-seven inactive and moderately active CD patients were included in a double-blinded randomized placebo controlled trial (RCT). Patients consumed either 10 g OF-IN or 10 g placebo twice per day for 4 weeks. They collected a fecal sample before the start of the study (baseline) and after the treatment period. In addition, fecal samples were obtained from 40 HCs. The metabolite profile was assessed using gas chromatography–mass spectrometry. RESULTS: The number of fecal metabolites was significantly higher in HCs than in CD patients (P<0.001). Forty compounds differed between CD patients and HCs. When correlating the metabolite levels to disease activity, significantly lower levels of butyrate, pentanoate, hexanoate, heptanoate, and p-cresol were found in active patients as compared with HCs. In the RCT, no significant changes in the metabolite pattern were found in patients randomized to placebo. In patients receiving OF-IN (per protocol; n=21), the relative levels of acetaldehyde (P=0.0008) and butyrate (P=0.0011) were significantly increased as compared with baseline. CONCLUSIONS: We identified medium chain fatty acids and p-cresol as differentiating metabolites toward CD disease status and as compared with HCs. In addition, OF-IN intake primarily increased the carbohydrate fermentation metabolites butyrate and acetaldehyde.