BACKGROUND & AIMS: Colonic fermentation of carbohydrates is known to influence gastric and esophageal motility in healthy subjects. This study investigated the effects of colonic fermentation induced by oral administration of fructooligosaccharides (FOS) in patients with gastroesophageal reflux disease (GERD). METHODS: In the cross-over design used in the study, 9 patients with symptomatic GERD were administered a low-residue diet (i.e., 10 g fiber/day) during 2, 7-day periods, receiving either 6.6 g of FOS or placebo 3 times daily after meals. Each period was separated by a wash out of at least 3 weeks. On day 7, esophageal motility and pH were recorded in fasting conditions and after a test meal containing 6.6 g of FOS or placebo. Breath hydrogen concentrations (reflecting colonic fermentation) and plasma concentrations of glucagon-like peptide 1 (GLP-1), peptide YY, and cholecystokinin were monitored. RESULTS: Compared with placebo, FOS led to a significant increase in the number of transient lower esophageal sphincter relaxations (TLESRs) and reflux episodes, esophageal acid exposure, and the symptom score for GERD. The integrated plasma response of GLP-1 was significantly higher after FOS than placebo. CONCLUSIONS: Colonic fermentation of indigestible carbohydrates increases the rate of TLESRs, the number of acid reflux episodes, and the symptoms of GERD. Although different mechanisms are likely to be involved, excess release of GLP-1 may account, at least in part, for these effects.