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

Neurogastroenterol Motil. 2023 Apr 13;e14575. doi: 10.1111/nmo.14575. Online ahead of print.


Callie Cuff 1Lisa D Lin 2Swapna Mahurkar-Joshi 2 3Jonathan P Jacobs 2 4 5Venu Lagishetty 2 4Nancee Jaffe 2Janelle Smith 2Tien Dong 2 4Jessica Sohn 2Lin Chang 2 3


Author information

1University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, USA.

2Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, Los Angeles, California, USA.

3G Oppenheimer Center for Neurobiology of Stress and Resilience, Los Angeles, California, USA.

4UCLA Microbiome Center, David Geffen School of Medicine, Los Angeles, California, USA.

5Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System, Los Angeles, California, USA.


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.

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