Introduction
Functional dyspepsia (FD) is one of the most frequent disorders of the gut-brain interaction with a worldwide prevalence of around 7%.1 Our group showed that a diet excluding fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) improved symptoms in the majority of FD patients.2 FODMAPs have been studied in irritable bowel syndrome, where poor intestinal absorption may lead to osmotic effects and fermentation, contributing to symptoms. However, this has not been studied in FD to date. In this study, we assessed pathophysiological parameters after ingestion of mannitol and a control meal in FD patients and healthy volunteers (HV).
Aims & Methods
FD patients (N=11) that responded to the low FODMAP diet and showed symptom triggers by mannitol during reintroduction were recruited. Also, 11 HV participated in this trial. FD and HV had a similar age (47 (24-55) vs. 25 (21-46), p=0.14) and BMI (22 (21-31) vs. 23 (21-25), p=0.85), but FD cohort included more females (100% vs 55%, p=0.04). After an overnight fast, abdominal magnetic resonance imaging (MRI) was performed in patients and HV. MRI images, gastrointestinal (GI) symptoms and blood samples were collected at baseline and at six separate time points after a challenge meal (0, 15, 30, 45, 60, 120, 240 min). The meal was an oat porridge breakfast containing either mannitol or glucose, as a control, in a randomized, double blind cross-over fashion. MRI images were analyzed for gastric emptying T1/2 (GE T1/2), duodenal volume, small bowel water content (SBWC) and colonic gas volume. Blood samples were analyzed for glucose like peptide-1 (GLP-1), peptide YY (PYY), and GIP.
Results
FD patients exhibited more FD symptoms compared to HV after consuming both the glucose-rich meal (54 ± 10 vs 24 ± 7, p=0.02) and the mannitol-rich meal (64±13 vs 23±7, p=0.01). No differences were found for GE T1/2 in FD and HV, as indicated in Table 1. Colonic gas volume was significantly increased in patients compared to HV. Duodenal volumes tended to increase more after intake of mannitol compared to glucose in both groups, but reached significance only in HV. SBWC was increased after mannitol in both HV (p=0.01) and FD (p=0.01). After intake of mannitol, postprandial GLP-1 levels were significantly lower in FD compared to HV, after 15 (p=0.02) and 30 min (p=0.001). Also, the AUC of GLP-1 was significantly lower in FD versus HV after mannitol (p=0.04), as well as after glucose-rich (p=0.04) meal. In FD, AUC of GIP levels was significantly lower after mannitol versus glucose (p=0.002). GI symptom scores did not correlate with PYY, GLP-1, and GIP levels. GLP-1 and GIP values did not correlate with GE T1/2.
| FD mannitol | FD glucose | HV mannitol | HV glucose |
| Gastric emptying T1/2 | 46 (36-58)
| 54 (45-65)
| 48 (44-58)
| 53 (48-62)
|
Δ Colonic gas (mL)
| 15.45 ±4.18*
| -0.35 ±4.38*
| 7.27 ±7.91
| 10.53 ±4.12
|
Δ duodenum volume (AUC mL*min)
| 1272 ± 520
| 469 ±271
| 1167 ±366*
| 643 ±221*
|
Δ small bowel water content (AUC mL*min)
| 154 ±16*
| 103 ±8*
| 167 ±16¶
| 119 ±4¶
|
AUC GLP-1 (pmol/L *min)
| 358±35*
| 344±34¶
| 504±52*
| 458±34¶
|
AUC GIP (pmol/L *min)
| 81,875±9,631*
| 109,554±9,362*
| 189,929±86,981
| 205,771±65,071
|
AUC PYY (pmol/L *min)
| 20,910±2680
| 19,651±2445
| 23,501±3656
| 23,170±3427
|
GE T1/2: Gastric emptying half time, FD: Functional dyspepsia, HV healthy volunteers. * or ¶ indicating pairs of values that are significantly (p<0.05) different after correction for multiple testing. Volumes were compared using a two-way ANOVA. AUC values (4 hours postprandially) were compared using multiple T-tests. GE T1/2 was compared using multiple Mann Whitney U test.
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Conclusion
In this pilot study no difference in symptom triggering in FD was observed between mannitol and glucose (control) supplemented meals, but compared to HV the meals were associated with higher symptom burden, lower release of GLP-1 and GIP, and larger colonic gas volumes. The mechanisms underlying decreased peptide hormone release and their relevance to symptom generation deserve further studies.
References
1. Sperber AD, Bangdiwala SI, Drossman DA, Ghoshal UC, Simren M, Tack J, Whitehead WE, Dumitrascu DL, Fang X, Fukudo S, Kellow J, Okeke E, Quigley EMM, Schmulson M, Whorwell P, Archampong T, Adibi P, Andresen V, Benninga MA, Bonaz B, Bor S, Fernandez LB, Choi SC, Corazziari ES, Francisconi C, Hani A, Lazebnik L, Lee YY, Mulak A, Rahman MM, Santos J, Setshedi M, Syam AF, Vanner S, Wong RK, Lopez-Colombo A, Costa V, Dickman R, Kanazawa M, Keshteli AH, Khatun R, Maleki I, Poitras P, Pratap N, Stefanyuk O, Thomson S, Zeevenhooven J, Palsson OS. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology. 2021 Jan;160(1):99-114.e3. doi: 10.1053/j.gastro.2020.04.014. Epub 2020 Apr 12. PMID: 32294476.
2. Van den Houte K. et al. OUTCOME OF A LOW FODMAP ELIMINATION DIET WITH BLINDED REINTRODUCTION IN FUNCTIONAL DYSPEPSIA / POSTPRANDIAL DISTRESS SYNDROME. Under review Gut 2025