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

• Published in: Neurogastroenterology and motility Vol. 35; no. 7; pp. e14575 - n/a
• Main Authors: Cuff, Callie, Lin, Lisa D., Mahurkar‐Joshi, Swapna, Jacobs, Jonathan P., Lagishetty, Venu, Jaffe, Nancee, Smith, Janelle, Dong, Tien, Sohn, Jessica, Chang, Lin
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2023
• Subjects: Adult; Constipation; Diet; Disaccharides; Female; Fermentation; FODMAP Diet; Fructose; fructose reintroduction; fructose tolerance; Glucose; Humans; Intestine; Irritable bowel syndrome; Irritable Bowel Syndrome - diagnosis; low FODMAP diet; Male; Mannose; Metabolism; Metagenomics; Microbiomes; Monosaccharides; Nutrient deficiency; Oligosaccharides; Pilot Projects; Polyols; Reintroduction; low FODMAP diet; fructose reintroduction; irritable bowel syndrome; fructose tolerance
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.14575

Background 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. Methods 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. Results 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. Conclusions 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. Non‐constipated, LFD‐responsive IBS patients reintroduced to different solutions (glucose/fructose/glucose + fructose) in increasing dosages up to 15 g demonstrated no significant difference in mean sugar dose tolerated, suggesting fructose reintroduction should use doses >15 g to assess tolerance. LFD was associated with significant changes in microbial composition and bacterial genes involved in FODMAP metabolism.