Randomized controlled pilot study assessing fructose tolerance during fructose reintroduction in non‐constipated irritable bowel syndrome patients successfully treated with a low FODMAP diet

Limited data exist to guide FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) reintroduction to assess tolerance following a low FODMAP diet (LFD). Fructose reintroduction is often stepwise up to 7.5 g fructose (e.g., three tsp of honey). We aimed to determine the fructose tolerance threshold in non-constipated, LFD-responsive patients with irritable bowel syndrome (IBS) and assess whether stool microbiome predicted LFD response or fructose tolerance.Thirty-nine non-constipated IBS patients (51% women, mean age 33.7 years) completed a 4-week LFD. LFD responders were defined as those who reported adequate relief of IBS symptoms following the LFD. Responders were randomized to one of the three solution groups (100% fructose, 56% fructose/44% glucose, or 100% glucose) and received four doses (2.5, 5, 10, 15 g) for 3 days each. Patients reached their tolerance dose if their mean daily IBS symptom severity (visual analog scale [VAS], 0-100 mm) was >20 mm higher than post-LFD VAS. Stool samples before and after LFD were analyzed using shotgun metagenomics.Seventy-nine percent of patients were LFD responders. Most responders tolerated the 15 g sugar dose. There was no significant difference in mean dose tolerated between solution groups (p = 0.56). Compared to baseline, microbiome composition (beta diversity) significantly shifted and six bacterial genes in fructose and mannose metabolism pathways decreased after LFD, irrespective of LFD response or the solution group.Non-constipated, LFD-responsive IBS patients should be reintroduced to fructose in higher doses than 15 g to assess tolerance. LFD is associated with significant changes in microbial composition and bacterial genes involved in FODMAP metabolism.