Introduction

Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction often accompanied by psychiatric and/or somatic comorbidities. Intestinal barrier dysfunction has long been hypothesised to be a key player in IBS pathophysiology. However, it is unknown how psychiatric and somatic comorbidities affect intestinal barrier dysfunction. This study aims to assess intestinal barrier function in a large multicentric cohort of adult IBS patients with and without psychiatric/somatic comorbidities.

Aims & Methods

IBS patients (Rome IV) with (N=197) and without (N=171) comorbidities, and healthy volunteers (N=23), were included in six European hospitals. Intestinal permeability (IP) was assessed in vivo with the lactulose-mannitol-sucralose test (LMS) and ex vivo in colonic biopsies using Ussing chambers. Sugar concentrations in the urine were assessed through HPLC-ELSD and GC-MS. The L/M ratio after 2 hours was used as an estimation of the small intestinal permeability, and the %S excreted and the S/M ratio from 2 to 24 hours, for colonic permeability. Colonic biopsies were collected from 17 controls and 18 IBS patients and mounted in Ussing chambers to measure the paracellular permeability to FITC-dextran (4 kDa).

Results

When compared with healthy controls, L/M ratio did not differ in IBS patients with (p=0.33) or without comorbidities (p=0.44). Moreover, the %S excreted and S/M were not altered in IBS patients with (respectively p=0.3 and p=0.09) and without (p=0.14, p=0.1) comorbidities. Interestingly, when comparing results from IBS patients among recruiting hospitals in different parts of Europe, significant differences were found in L/M ratio (p<0.0001), %S (p<0.0001), and S/M ratio (p<0.0001). Lastly, paracellular permeability assessed ex vivo in colonic biopsies was not different between IBS patients and controls (p=0.46).

Conclusion

These results suggest that psychiatric and somatic comorbidities do not alter small intestinal and colonic permeability in IBS patients. Interestingly, our results highlight a strong variability between IBS patients from different countries, which may be explained by lifestyle, environmental, and genetic factors. Further investigations are needed to better understand these findings.

Disclosure

no conflicts of interest

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 T_1/2 (GE T_1/2), 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 T_1/2 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 T_1/2.

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

Introduction

Gastro-oesophageal reflux disease (GORD) is characterised by visceral pain hypersensitivity, manifesting as heartburn, and distal oesophageal inflammation. In the oesophageal mucosa of GORD patients, even without visible inflammation (non-erosive reflux disease; NERD) there is increased innervation of sensory nerve fibres containing Substance P (SP) (Xu et al., 2013). SP may be released in response to luminal refluxate or inflammatory mediators to potentiate neuro-immune pathways relevant to GORD pathogenesis. We aimed to investigate the contribution of SP and its receptor NK1R to GORD symptoms.

Aims & Methods

To assess expression of NK1R on native tissue epithelium, biopsies were collected from healthy controls (HC), functional heartburn (FH), NERD and erosive reflux disease (ERD) patients following informed consent (Royal London Hospital ethics number: 19/LO/1506) and prepared for immunohistochemistry. NK1R was co-stained with epithelial cell marker E-Cadherin, pan-leukocyte marker CD45, and general T lymphocyte marker CD3. NK1R protein level was determined by mean fluorescence intensity of 3 FOVs. Cells of the NE-1 oesophageal epithelial cell line were incubated with media containing 100 nM and 300 nM SP for 30 minutes. Cells were lysed and intracellular inflammatory pathway activation was determined by p-NF-κB/NF-κB ratio through Western blot. mRNA levels of the inflammatory cytokine CXCL8 were determined via qPCR with 18S rRNA as a housekeeping gene.

Results

Quantification of mucosal tissue samples showed NK1R mean fluorescence intensity was significantly higher in NERD (fold-change 1.52; p<0.05) and ERD (fold change 1.70; p<0.01) oesophageal mucosa compared to healthy control (n=6-8). Interestingly, NK1R was also found expressed in a sub-group of CD3+ T lymphocytes specifically in the papillae and epithelium of GORD patients. in NE-1 oesophageal epithelial cells, 30 minutes exposure to 100 nM (fold change 1.41; p<0.05) and 300 nM (fold change 1.92; p<0.0001) SP induced phosphorylation of NF-κB in a dose dependent manner (n=7-8). CXCL8 expression in NE-1 cells exposed to 30 nM, 100 nM, or 300 nM SP for 30 minutes resulted in significantly higher mRNA expression at the highest concentration (fold change 6.29; p<0.05), although a dose-dependent trend was observed at lower concentrations (n=3).

Conclusion

The significant increase in NK1R expression in NERD and ERD patients compared to healthy volunteers, combined with expression on T lymphocytes provides evidence, for the first time, that SP may have a critical role in potentiating pain sensation in the oesophagus. Indeed, SP directly induces NF-κB phosphorylation and increases transcription of inflammatory cytokine IL-8 in oesophageal epithelial cells. This demonstrates a novel neuroimmune pathway regulated by SP and NK1R that may be critical in GORD symptom generation.

References

Xu, X., Li, Z., Zou, D., Yang, M., Liu, Z., & Wang, X. (2013). High expression of calcitonin gene-related peptide and substance P in esophageal mucosa of patients with non-erosive reflux disease. Dig Dis Sci, 58(1), 53-60. doi:10.1007/s10620-012-2308-z

Introduction

Functional dyspepsia (FD) is a common yet complex gastrointestinal disorder, characterised by postprandial fullness, early satiety, epigastric pain, and burning. With growing evidence linking diet to inflammation and symptoms, our objective was to review the evidence for the impact of dietary factors on FD symptomatology.

Aims & Methods

A systematic review was conducted to identify dietary components influencing FD symptoms in adults. Databases searched included MEDLINE, EMBASE, PsycINFO, Scopus, and Cochrane, covering January 2000 to December 2024. A total of 14 studies met eligibility criteria, with findings synthesised through narrative analysis.

Results

The search strategy yielded 18,424 articles, of which 14 met the inclusion criteria. Analysis identified seven key dietary components associated with FD: (1) a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet significantly improved symptoms (p = 0.04), while gluten intake was linked to early satiety (p = 0.03); (2) probiotics or prebiotics provided symptom relief (RR 1.15, p = 0.52), with probiotics alone showing a trend toward improved FD scores (RR 1.35, p = 0.061); (3) capsaicin significantly exacerbated symptoms (p < 0.001), and spicy foods were associated with increased gastric fullness (p = 0.001); (4) both peppermint-caraway oil (p < 0.00001) and cinnamon oil (p < 0.001) demonstrated significant symptom relief; (5) ginseng-based herbal porridge led to a higher rate of epigastric symptom remission by day 90 compared to placebo (45.71% vs. 20.69%, p = 0.036), while the STW 5-II formulation (a nine-herb extract) also yielded significant improvement (p = 0.008); (6) prokinetic agents reduced symptom severity (RR 0.81, p < 0.0001), while amitriptyline outperformed both placebo (40%) and escitalopram (38%), relieving symptoms in 53% of patients—particularly those with ulcer-like FD; and (7) ginger/artichoke capsules improved symptoms within 14 days (p = 0.017), while ginger/perilla tablets offered progressive relief over one to two weeks (p < 0.05 and p < 0.01, respectively). Study quality was assessed using ROBIS, RoB 2.0, and ROBINS-I tools. Of the included studies, three were rated as low risk of bias, eight as moderate, and three as serious. Despite adherence to a standardised PRISMA-based search strategy, variability in outcome reporting limited direct comparability across studies.

Table 1

Conclusion

This review highlights dietary interventions as a promising strategy for managing FD. Our findings show that specific dietary components can be implicated in inducing inflammation and symptoms in FD. Since the symptoms are related to inflammation, we propose using “inflammatory dyspepsia” to represent the true presentation of this form of dyspepsia. Large-scale randomised trials are needed to confirm findings and refine dietary guidelines.