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. 2025 Aug 28:gutjnl-2024-334156.
doi: 10.1136/gutjnl-2024-334156. Online ahead of print.

Outcome of a FODMAP restriction diet with subsequent blinded reintroduction in functional dyspepsia/postprandial distress syndrome

Karen Van den Houte  1 , Bert Broeders  1 , Joran Tóth  1 , Karen Routhiaux  1 , Zoë Mariën  1 , Jasmien Van den Bergh  2   3 , Julie Vanderstappen  2   3 , Nelle Pauwels  2   3 , Ann Meulemans  2   4 , Christophe Matthys  2   4 , Tim Vanuytsel  1   3 , Florencia Carbone  1   3 , Jan Tack  5   3
Affiliations

Outcome of a FODMAP restriction diet with subsequent blinded reintroduction in functional dyspepsia/postprandial distress syndrome

Karen Van den Houte et al. Gut. .

Abstract

Background: Recent studies have shown increased duodenal mucosal permeability as a possible key player in the pathophysiology of functional dyspepsia (FD). Adverse reaction to nutrients is an important candidate underlying mechanism. Intragastric infusion of fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) induced symptoms reminiscent of FD with a rapid onset.

Objective: We evaluated the effect of a low FODMAP diet (LFD) and individual FODMAP-triggers on symptom severity and duodenal mucosal permeability in FD.

Design: Patients with FD followed a 6-week LFD and filled out the validated Leuven Postprandial Distress Syndrome (LPDS) daily diary, Short Form-Nepean Dyspepsia Index (SF-NDI) Questionnaire, patient assessment of upper gastrointestinal symptoms (PAGI-SYM) and Patient Health Questionnaire (PHQ). Patients underwent an endoscopy with duodenal biopsies to define mucosal integrity by quantifying transepithelial electrical resistance (TEER) and dextran flux. LFD was followed by a blinded reintroduction during which patients were challenged by 7 powders (fructans, fructose, galacto-oligosaccharides (GOS), lactose, mannitol, sorbitol, glucose).

Results: 36 FD patients entered the study. LPDS improved significantly at the end of the LFD in 73%. In addition, SF-NDI, PAGI-SYM and PHQ improved significantly. Dextran flux and TEER were not significantly different, but delta TEER correlated positively with delta LPDS. A large variety of FODMAP powders was able to induce recurrence with mannitol as the most prevalent triggering FODMAP (23%). Surprisingly, 27% showed higher LPDS scores during intake of glucose.

Conclusions: A LFD significantly improved PDS symptoms, but this was not associated with altered mucosal integrity. Powder reintroduction identified a large variety in individual FODMAPs and glucose as triggers.

Keywords: DIET; FUNCTIONAL DYSPEPSIA; MUCOSAL BARRIER.

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Conflict of interest statement

Competing interests: JTa has given Scientific advice to AlfaWassermann, Allergan, Christian Hansen, Danone, Grünenthal, Ironwood, Janssen, Kiowa Kirin, Menarini, Mylan, Neutec, Novartis, Noventure, Nutricia, Shionogi, Shire, Takeda, Theravance, Tramedico, Truvion, Tsumura, Zealand and Zeria pharmaceuticals, has received research support from Shire, Sofar and Tsumura and has served on the Speaker bureau for Abbott, Allergan, AstraZeneca, Janssen, Kyowa Kirin, Menarini, Mylan, Novartis, Shire, Takeda, Truvion and Zeria. Funding was provided by a Methusalem grant from Leuven University to JTa and a koor grant from University Hospitals Leuven. TV has given scientific advice to VectivBio, Shire, Dr Falk Pharma, Takeda and Baxter; has received research support from Danone, MyHealth and VectivBio; and has served on the Speaker bureau for Abbott, Tramedico, Truvion, Will Pharma, My Health, Kyowa Kirin, Menarini, Biocodex, Remedus, Fresenius Kabi, Dr Falk Pharma. TV is funded by a senior clinical research fellowship of the Flanders Research Foundation (FWO Vlaanderen; 1830517N) CM has served on the Speaker bureau for Coca-Cola and Zespri and received travel/conference grants from Danone, Nestlé Health Sciences, Fresenius-Kabi. KVdH is funded by FWO Flanders, Belgium (12B1B24N).

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