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TEMPORAL STABILITY OF FECAL METABOLOMIC PROFILES IN IRRITABLE BOWEL SYNDROME

Cristina Iribarren 1, Otto Savolainen 2, Maria Sapnara 1, Hans Törnblom 3, Magnus Simrén 3,4, Maria K. Magnusson 1, Lena Öhman 1

Affiliations

1 University of Gothenburg, Institute of Biomedicine, Dept. of Microbiology and Immunology, Gothenburg, Sweden

2 Chalmers University of Technology, Chalmers Mass Spectrometry Infrastructure, Dept. of Biology and Biological Engineering, Gothenburg, Sweden

3 University of Gothenburg, Institute of Medicine, Dept. of Molecular and Clinical Medicine, Gothenburg, Sweden

4 University of North Carolina at Chapel Hill, Center for Functional GI and Motility Disorders, Chapel Hill, United States

Summary

AI Generated

Fecal metabolite profiles remain stable over time within individual IBS patients regardless of fluctuations in stool consistency, suggesting potential as a non-invasive diagnostic tool.

Two cohorts of healthy subjects and IBS patients (Rome III/IV criteria) provided fecal samples analyzed by mass spectrometry, with Cohort A collecting daily samples over 5 days and Cohort B at baseline and 4 weeks.
Within individual IBS patients, fecal metabolome dissimilarity was low and stable over both 5-day and 4-week periods, despite significant changes in stool consistency measured by Bristol Stool Form scale.
Between-individual metabolome variation was significantly higher than within-individual variation in both healthy subjects and IBS patients across all time periods measured.
At baseline, IBS patients showed higher metabolome dissimilarity compared to healthy subjects in Cohort B, but individual IBS patient profiles remained consistent between week 0 and week 4.
This work addresses a knowledge gap regarding fecal metabolite stability in IBS and may inform development of metabolite-based diagnostic approaches for the condition.

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This summary was generated by an AI large language model based on the content transcript. It is for informational purposes only and should not be considered a substitute for clinical judgment. Always rely on your professional expertise and the full clinical context when making clinical decisions.

Abstract

Introduction

Previous studies indicate that patients with irritable bowel syndrome (IBS) may present with altered fecal microbiota and metabolite profiles. While changes in bowel habits seem to not influence the microbiota dynamics, the stability of fecal metabolites in IBS patients has not been addressed yet.

Aims & Methods

This study aimed to assess the stability of the fecal metabolite profile over time, and its link with fluctuations of stool consistency. It used fecal samples from two cohorts (A and B) comprising healthy subjects and patients with IBS diagnosed according to either Rome III (Cohort A) or Rome IV (Cohort B) and subtyped using the Bristol Stool Form (BSF) scale. Cohort A collected fecal samples for 5 consecutive days that were analyzed by gas chromatography-tandem mass spectrometry (GC-MS/MS). Additionally, IBS patients collected up to 3 additional samples within one of those days. Cohort B collected fecal samples at week 0 (healthy and IBS) and week 4 (only IBS), later analyzed by liquid chromatography-MS (LC-MS). All participants reported stool consistency using BSF scale. Metabolome variation based on the metabolite intensity signals was assessed by Bray-Curtis dissimilarity in R (version 4.2.1). Additional statistical analyses were conducted in GraphPad (version 9.4.1).

Results

Cohort A (7 healthy subjects and 8 IBS patients with mixed bowel habits, IBS-M) provided 66 fecal samples. Twenty-nine samples were collected from Cohort B (7 healthy subjects, 3 IBS-M, and 8 IBS patients with predominant diarrhea). The metabolome of Cohort A (n=155 spectral features) at day 1 showed similar composition with a tendency towards a higher Bray-Curtis dissimilarity in the IBS group (0.026 (0.023-0.028) vs 0.028(0.025-0.032); p=0.10). Over a period of 5 days, metabolome dissimilarities were higher between- than within- individuals (Table 1) and fluctuated minimally over time for both healthy subjects and IBS patients. The stool type however changed more over time in the IBS than the healthy group (p<0.001). Consecutive samples taken within the same day showed higher compositional variance between- than within- IBS patients (Table 1). At individual level, the metabolomic profiles remained stable despite changes in the BSF score. In Cohort B, the metabolome profile comprised 6 999 spectral features. The metabolome dissimilarity was higher in IBS patients as compared to healthy subjects at week 0 (0.045(0.040-0.048) vs 0.048(0.042-0.054); p<0.05). In the IBS group, the metabolome was stable between week 0 and week 4 regardless of stool form and differed more between- than within-patients (Table 1).

Table 1. Fecal metabolome variation in healthy subjects and IBS patients using Bray-curtis dissimilarity analysis. Dissimilarity index ranges from 0 (identical composition) to 1 (totally different composition).
Cohort A		Within-individuals	Between-individuals	P value
Healthy	Over 5 days	0.020 (0.018-0.024)	0.028 (0.025-0.32)	<0.0001
IBS	Over 5 days	0.021 (0.016-0.029)	0.029 (0.026-0.033)	<0.0001
IBS	Within a day	0.017 (0.015-0.033)	0.034 (0.031-0.036)	<0.01
Cohort B: IBS	Over 4 weeks	0.028 (0.023-0.038)	0.048 (0.042-0.054)	<0.0001

Conclusion

The metabolite profile of fecal samples remains stable over time within an individual IBS patient independently of the variation in stool consistency. This study suggests the use of fecal metabolites as a potential non-invasive diagnostic tool in IBS.

Conference

UEG Week Copenhagen 2023

Topics

Colorectal

Submission format

Abstract

Session

PP 06 Other lower GI disorders (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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OVERDIAGNOSIS OF SUPERIOR MESENTERIC ARTERY SYNDROME: LIMITED DIAGNOSTIC CONCORDANCE BETWEEN IMAGING MODALITIES AND LIMITED BENEFIT OF SURGERY

Tim Vanuytsel

COLONIC MAST CELL ACTIVATION IS LINKED TO MENTAL AND SOMATIC SYMPTOM SEVERITY IN IRRITABLE BOWEL SYNDROME: RESULTS FROM THE DISCOVERIE PROJECT (EU-FUNDED PROJECT Nº: 848228)

Carmen Alonso-Cotoner

TRANSCRIPTOMIC AND PROTEOMIC PROFILING OF COLONIC MUCOSA IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH OR WITHOUT MENTAL/SOMATIC COMORBIDITIES: RESULTS FROM THE EUROPEAN MULTICENTER DISCOVERIE STUDY

Carmen Alonso-Cotoner

MAST CELLS AS KEY PLAYERS OF VISCERAL HYPERSENSITIVITY TRIGGERED BY MICROBIAL HISTAMINE

Giada De Palma

Diagnosis and management of IBS: Past, present and future

Christopher Black

Are bowel disorders with diarrhoea really a separate entity from bile acid malabsorption?

Giovanni Barbara

UEG Presentation

New

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OVERDIAGNOSIS OF SUPERIOR MESENTERIC ARTERY SYNDROME: LIMITED DIAGNOSTIC CONCORDANCE BETWEEN IMAGING MODALITIES AND LIMITED BENEFIT OF SURGERY

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OVERDIAGNOSIS OF SUPERIOR MESENTERIC ARTERY SYNDROME: LIMITED DIAGNOSTIC CONCORDANCE BETWEEN IMAGING MODALITIES AND LIMITED BENEFIT OF SURGERY

Christian von Muhlenbrock 1,2,3, Sandrien Abbeel 4, Thomas Debrouwere 1, Dirk Vanbeckevoort 1, Jan Tack 1, Tim Vanuytsel 1

Affiliations

1 KU Leuven, Leuven, Belgium

2 Universidad de Chile, Santiago, Chile

3 Universidad de los Andes, Santiago, Chile

4 KU Leuven, Eppegem, Belgium

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Abstract

Introduction

Superior mesenteric artery (SMA) syndrome is traditionally described as a rare vascular cause of duodenal obstruction. However, overlapping symptoms with functional gastrointestinal disorders and variable radiological criteria raise concerns regarding overdiagnosis.

Aims & Methods

We aimed to evaluate diagnostic concordance across modalities and clinical outcomes following medical and surgical treatment in patients referred for suspected SMA syndrome.We retrospectively analyzed 49 consecutive patients undergoing hypotonic barium duodenography (HBD) for suspected SMA syndrome based on symptoms and standard imaging (ultrasound or CT) in a tertiary neurogastroenterology center (2003–2023). SMA syndrome was defined by the combination of fixed abrupt narrowing of the third duodenum and proximal duodenal dilatation on HBD, the gold standard for the diagnosis in our center, in the absence of a more plausible diagnosis. CT-based aortomesenteric angle (AMA) and distance (AMD), intestinal manometry findings, gastric emptying, and treatment outcomes were also assessed.

Results

Only 11/49 patients (22%) met strict HBD criteria for SMA syndrome. Clinical presentation, BMI, and weight loss were indistinguishable between HBD-confirmed cases and controls (Table 1). CT criteria lacked specificity: 4 patients with positive CT findings had negative HBD and were ultimately diagnosed with alternative disorders of gut–brain interaction. AMA was lower in confirmed cases (18.8° vs 26.5°, p=0.05), whereas AMD did not significantly differ. Conservative medical management (n=6) led to symptom improvement in 50%. In contrast, despite >5% weight gain in 80% of patients undergoing a duodenojejunostomy (n=4) or gastroenterostomy (n=1) , meaningful symptom improvement occurred in only one patient, with procedure-related complications observed (dumping syndrome in 2 and worsening of gastroparesis-like symptoms in 1 patient).

Parameters	Patients with SMA syndrome on HBD (N=11)	Control group (N=38)	p-value
Age (years)	30.5 ± 3.2	34.0 ± 1.9	0.37
Body mass index (kg/m2)	17.5 (16.2, 19.3)	17.5 (16.4, 19.1)	1.00
Gender Male Female	1 (9%) 10 (91%)	7 (18%) 31 (82%)	0.66
Patients reporting weight loss	10 (91%)	32 (84%)	1.00
Weight loss (kg)	8.7 ± 1.6	9.8 ± 1.5	0.96
Weight loss of >10%	8 (73%)	22 (58%)	0.49
Aortamesenteric angle (°)	18.8 ± 2.52	26.5 ± 2.11	0.05
Aortamesenteric distance (mm)	5 (4.5, 7.5)	7.0 (6, 9)	0.13
Gastric emptying study: t1/2 (minutes)	70 (64.5, 85.5)	119 (74, 159)	0.02

Conclusion

In a tertiary referral setting, most patients suspected of SMA syndrome do not meet strict diagnostic criteria on HBD. Standard radiological findings alone may overestimate the condition, and surgical intervention frequently fails to improve symptoms. These findings question whether SMA syndrome represents a distinct clinical entity in most cases and support a highly restrictive, conservative management strategy.

Event

UEG Week Barcelona 2026

Topics

Small Intestine & Nutrition Endoscopy

Submission format

Abstract

Session

Small intestine diseases: Inside the black box

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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OVERDIAGNOSIS OF SUPERIOR MESENTERIC ARTERY SYNDROME: LIMITED DIAGNOSTIC CONCORDANCE BETWEEN IMAGING MODALITIES AND LIMITED BENEFIT OF SURGERY

Tim Vanuytsel

COLONIC MAST CELL ACTIVATION IS LINKED TO MENTAL AND SOMATIC SYMPTOM SEVERITY IN IRRITABLE BOWEL SYNDROME: RESULTS FROM THE DISCOVERIE PROJECT (EU-FUNDED PROJECT Nº: 848228)

Carmen Alonso-Cotoner

TRANSCRIPTOMIC AND PROTEOMIC PROFILING OF COLONIC MUCOSA IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH OR WITHOUT MENTAL/SOMATIC COMORBIDITIES: RESULTS FROM THE EUROPEAN MULTICENTER DISCOVERIE STUDY

Carmen Alonso-Cotoner

MAST CELLS AS KEY PLAYERS OF VISCERAL HYPERSENSITIVITY TRIGGERED BY MICROBIAL HISTAMINE

Giada De Palma

Diagnosis and management of IBS: Past, present and future

Christopher Black

Are bowel disorders with diarrhoea really a separate entity from bile acid malabsorption?

Giovanni Barbara

UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

COLONIC MAST CELL ACTIVATION IS LINKED TO MENTAL AND SOMATIC SYMPTOM SEVERITY IN IRRITABLE BOWEL SYNDROME: RESULTS FROM THE DISCOVERIE PROJECT (EU-FUNDED PROJECT Nº: 848228)

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COLONIC MAST CELL ACTIVATION IS LINKED TO MENTAL AND SOMATIC SYMPTOM SEVERITY IN IRRITABLE BOWEL SYNDROME: RESULTS FROM THE DISCOVERIE PROJECT (EU-FUNDED PROJECT Nº: 848228)

Ana Maria González 1,2, Núria Vilaplana 1, Beatriz Lobo Alvarez 1,2,3, Elba Expósito 1, Marc Pigrau Pastor 3, Irina Midenfjord 4, Magnus Simrén 4, Andrei Pop 5, Ricard Farré 6, Giovanni Barbara 7, Amanda Rodriguez 8,9, Javier Santos 3,2,1, Carmen Alonso-Cotoner 3,2,1

Affiliations

1 Vall d’Hebron Institut de Recerca, Barcelona, Spain

2 Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBER-EHD), Madrid, Spain

3 Hospital Universitari Vall d'Hebron, Barcelona, Spain

4 Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

5 University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania

6 KU Leuven, Leuven, Belgium

7 University of Bologna and IRCCS Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy

8 University Hospital Vall d’Hebron, Barcelona, Spain

9 CIBERSAM, Madrid, Spain

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Abstract

Introduction

Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction in which low‑grade mucosal inflammation, particularly involving mast cells (MCs), has emerged as a key mechanism linking epithelial barrier dysfunction, immune activation, visceral hypersensitivity and symptom generation. Mental comorbidities such as anxiety and depression, as well as somatic comorbidities including fibromyalgia and chronic fatigue syndrome, are highly prevalent in IBS. However, the specific role of MC in IBS patients with and without comorbidities remains unknown.

Aims & Methods

To characterize MC activation in the colonic mucosa of patients with IBS with or without mental comorbidities (depression, anxiety) and/or somatic comorbidities (fibromyalgia and/or chronic fatigue), and to evaluate its role in clinical severity. We included healthy volunteers (HV, n=10) and IBS patients fulfilling Rome IV criteria were prospectively recruited across five European hospitals: IBS without comorbidity (IBS-A, n=9); IBS with mental comorbidity (IBS-Co, n=10) and IBS with both mental and somatic comorbidities (IBS-Mco, n=10). Colonic mucosal biopsies and clinical information were obtained from all participants. Validated questionnaires were used to assess IBS severity (IBS-SSS), depression (PHQ‑9), anxiety (GAD‑7), fibromyalgia (FIQ), chronic fatigue (MFI), and other physical symptoms (PHQ‑15). Mast cell activation was characterized by anti‑tryptase immunohistochemistry and transmission electron microscopy (TEM). Tryptase+ cells were quantified per high‑power field, and the percentage of tryptase‑stained area in the lamina propria was analyzed using QuPath software. MC ultrastructure, including granule morphology, degranulation profile, and proximity to nerve fibres, was evaluated by TEM.

Results

All groups showed similar MC infiltration in the lamina propria and epithelium. However, IBS-Co and IBS-Mco groups exhibited higher % of tryptase-stained area compared to IBS-A (p=0.038, p=0.021, respectively). Ultrastructurally, HV-MCs showed more electrodense core pattern granules, while IBS groups showed a predominant scroll pattern. IBS-Mco showed higher % of MCs with a very high activation profile (vesicles fusion and piecemeal) compared to HV (p=0.009) and IBS-A (p=0.031). Furthermore, IBS-Co and IBS-Mco groups had higher % of MCs in close proximity (<5 μm) to nerve fibres compared to HV (p=0.013). Notably, the % of tryptase-stained area correlated with PHQ15 (r=0.352; p=0.04), MFI Mental (r=0.438; p=0.01) and MFI physical fatigue (r=0.376; p=0.03); and the % of MC <5 μm to nerve fibres with IBS-SSS (r=0.56; p=0.03).

Conclusion

Mast cell activation, regardless of mast cell count, is a clinical marker of abdominal pain and of greater severity of both mental and somatic symptoms in IBS, indicating the involvement of MCs in the pathophysiology of IBS with comorbidities. Further studies are needed to characterize the interaction between MCs and the symptoms associated with disorders of the brain–gut axis.

Event

UEG Week Barcelona 2026

Topics

Small Intestine & Nutrition Primary Care Colorectal

Submission format

Abstract

Session

Insights into IBS

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

OVERDIAGNOSIS OF SUPERIOR MESENTERIC ARTERY SYNDROME: LIMITED DIAGNOSTIC CONCORDANCE BETWEEN IMAGING MODALITIES AND LIMITED BENEFIT OF SURGERY

Tim Vanuytsel

COLONIC MAST CELL ACTIVATION IS LINKED TO MENTAL AND SOMATIC SYMPTOM SEVERITY IN IRRITABLE BOWEL SYNDROME: RESULTS FROM THE DISCOVERIE PROJECT (EU-FUNDED PROJECT Nº: 848228)

Carmen Alonso-Cotoner

TRANSCRIPTOMIC AND PROTEOMIC PROFILING OF COLONIC MUCOSA IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH OR WITHOUT MENTAL/SOMATIC COMORBIDITIES: RESULTS FROM THE EUROPEAN MULTICENTER DISCOVERIE STUDY

Carmen Alonso-Cotoner

MAST CELLS AS KEY PLAYERS OF VISCERAL HYPERSENSITIVITY TRIGGERED BY MICROBIAL HISTAMINE

Giada De Palma

Diagnosis and management of IBS: Past, present and future

Christopher Black

Are bowel disorders with diarrhoea really a separate entity from bile acid malabsorption?

Giovanni Barbara

UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

TRANSCRIPTOMIC AND PROTEOMIC PROFILING OF COLONIC MUCOSA IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH OR WITHOUT MENTAL/SOMATIC COMORBIDITIES: RESULTS FROM THE EUROPEAN MULTICENTER DISCOVERIE STUDY

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TRANSCRIPTOMIC AND PROTEOMIC PROFILING OF COLONIC MUCOSA IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH OR WITHOUT MENTAL/SOMATIC COMORBIDITIES: RESULTS FROM THE EUROPEAN MULTICENTER DISCOVERIE STUDY

Juan Manuel Garcia 1, Ana Maria Gonzalez-Castro 1,2, Beatriz Lobo Alvarez 1,2,3, Elba Exposito 1, Marc Pigrau Pastor 4,3, Amanda Rodriguez 1,3,5, Ricard Farré 6, Magnus Simrén 7, Giovanni Barbara 8,9, Maria Raffaella Barbaro 9,8, Maaike Van Den Houte 10, Andrei Pop 11, Daisy Mae Jonkers 12, Javier Santos 1,2,3, Carmen Alonso-Cotoner 1,2,3

Affiliations

1 Vall d’Hebron Research Institute, Barcelona, Spain

2 CIBEREHD, Madrid, Spain

3 Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain

4 Universitat Autonoma de Barcelona, Barcelona, Spain

5 CIBERSAM, Madrid, Spain

6 University of Leuven, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium

7 Sahlgrenska University Hospital - Dept of Internal Medicine, Sahlgrenska University Hospital ; Gothe, Gothenburg, Sweden

8 University of Bologna, Bologna, Italy

9 Università di Bologna, Bologna, Italy

10 Laboratory for Brain-Gut Axis Studies, Translational Research in Gastrointestinal Disorders (TARGID), Leuven, Belgium

11 Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania

12 Maastricht University Medical Center, Maastricht, Netherlands

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Abstract

Introduction

Irritable bowel syndrome (IBS) is a chronic, relapsing disorder frequently associated with psychiatric and/or somatic comorbidities, including depression, anxiety, fibromyalgia, and chronic fatigue. Although its pathogenesis is multifactorial, dysfunction of the gut-brain axis is considered a key underlying mechanism. However, the specific molecular alterations and pathways involved remain poorly characterized.

Aims & Methods

We aimed to characterize the transcriptomic and proteomic profiles of colonic mucosa in irritable bowel syndrome (IBS) patients with or without mental and/or somatic comorbidities compared with healthy subjects. Methods: Within the European DISCOvERIE project, IBS patients and healthy volunteers (HV) were recruited across five European centers. Colonic biopsies and demographic and clinical variables, including symptom severity scores for IBS (IBS-SSS), depression (PHQ-9), anxiety (GAD-7), somatic symptoms (PHQ-15), fibromyalgia (FIQ), and fatigue (MFI) were collected. RNA was extracted and analyzed by RNA sequencing (RNA-seq). Libraries were prepared using TruSeq Stranded mRNA (Illumina) and sequenced on a NovaSeq 6000 platform. Differential gene expression (DE) analysis was performed using the DESeq2 package in R, with gene-level validation by qPCR. Proteomic analysis was performed through LC-MS/MS and quantified using Proteome Discoverer 2.5. Protein DE was assessed using the limma package in R.

Results

A total of 174 subjects (131 IBS patients and 43 HV) were included. For transcriptomic analysis, a subset was randomly selected comprising 20 HV (10 male/10 female) and 60 IBS patients (17 M/43 F), stratified into IBS without comorbidities (IBS-A: n=20), IBS with anxiety and/or depression (IBS-Co:N=20), and IBS with both mental and somatic comorbidities (IBS-MCo; N=20). Symptom severity scores for IBS, depression, anxiety, somatic symptoms, fibromyalgia, and fatigue increased progressively along with the number of comorbidities (p<0.001). In colonic mucosa, seven DE genes were identified between HV and IBS-MCo (FDR<0.1), two of which were related to barrier function and immune response. qPCR confirmed increased expression of both genes in IBS (p=0.023 and p=0.083). Proteomic analysis identified 271 DE proteins in IBS-MCo compared with HV. These proteins were enriched in pathways related to DNA/RNA processing and extracellular matrix-receptor interaction, oxidative phosphorylation, and thermogenesis. Additionally, 18, 12, and 3 DE proteins were identified in IBS-A, IBS-Co, and IBS-MCo, respectively. Interestingly, 46 DE proteins were identified in HV compared with IBS, of which 4 were consistently DE across all three IBS subgroups.

Conclusion

Integrated transcriptomic and proteomic analysis of colonic mucosa reveals distinct molecular alterations in IBS patients, depending on comorbidity burden. Several potential diagnostic biomarkers emerged from this analysis. Further validation studies are required to confirm these findings.

References

EU-FUNDED PROJECT Nº: 848228

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine Immunology Digestive Oncology Colorectal

Submission format

Abstract

Session

The gut talks back

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

OVERDIAGNOSIS OF SUPERIOR MESENTERIC ARTERY SYNDROME: LIMITED DIAGNOSTIC CONCORDANCE BETWEEN IMAGING MODALITIES AND LIMITED BENEFIT OF SURGERY

Tim Vanuytsel

COLONIC MAST CELL ACTIVATION IS LINKED TO MENTAL AND SOMATIC SYMPTOM SEVERITY IN IRRITABLE BOWEL SYNDROME: RESULTS FROM THE DISCOVERIE PROJECT (EU-FUNDED PROJECT Nº: 848228)

Carmen Alonso-Cotoner

TRANSCRIPTOMIC AND PROTEOMIC PROFILING OF COLONIC MUCOSA IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH OR WITHOUT MENTAL/SOMATIC COMORBIDITIES: RESULTS FROM THE EUROPEAN MULTICENTER DISCOVERIE STUDY

Carmen Alonso-Cotoner

MAST CELLS AS KEY PLAYERS OF VISCERAL HYPERSENSITIVITY TRIGGERED BY MICROBIAL HISTAMINE

Giada De Palma

Diagnosis and management of IBS: Past, present and future

Christopher Black

Are bowel disorders with diarrhoea really a separate entity from bile acid malabsorption?

Giovanni Barbara

UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

MAST CELLS AS KEY PLAYERS OF VISCERAL HYPERSENSITIVITY TRIGGERED BY MICROBIAL HISTAMINE

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MAST CELLS AS KEY PLAYERS OF VISCERAL HYPERSENSITIVITY TRIGGERED BY MICROBIAL HISTAMINE

Anushka Patel 1, Cynthia Lopez-Lopez 2, Josue Jaramillo Polanco 2, Yun Shi 2, Julien Pujo 1, Camila E. Perete de Freitas 1, Andy Jiang 1, Jun Lu 1, Graham Dinniwell 1, Stephen Collins 1, Stephen Vanner 2, Premysl Bercik 1, David E. Reed 2, Giada De Palma 1

Affiliations

1 McMaster University/Farncombe Institute, Hamilton, Canada

2 Queen's University/GIDRU, Kingston, Canada

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Abstract

Introduction

Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction characterized by abdominal pain and altered motility. Although visceral hypersensitivity is a core feature of IBS, its pathophysiology is not fully understood but both mast cells and altered gut microbiota have been implicated. Clinical studies in IBS patients showed that colonic mast cells co-localize with nerve endings, and that histamine and tryptase are involved in pain regulation. We demonstrated in a mouse model of IBS that bacterial histamine drives visceral hypersensitivity through mast cell hyperplasia via histamine receptor 4 pathways. However, it is unclear whether microbial histamine acts only through the mast cells or can also act directly on sensory afferents.

Aims & Methods

The aim of this study is to investigate whether mast cells are required in induction of visceral hypersensitivity in mice colonized with high histamine (HH) producing microbiota from IBS patients.
Methods:We used 1) germ free (GF) NIH Swiss mice colonized with stool samples of IBS patients with high (IBS-HH) or low histamine (IBS-LH) producing microbiota treated or not (vehicle) with the mast cell stabilizer cromolyn (100mg/kg ip once daily for one week, starting 3 weeks after colonization), and 2) mast cell deficient (Cpa3-Cre;Mcl-1fl/fl; C57BL6 background) or WT (C57BL6) mice treated with antibiotics and colonized with stool samples of IBS-HH patients. Visceral motor responses (VMRs) to colorectal distension (CRD) were evaluated in all mice 4 weeks after colonization. Mice were euthanized thereafter, and serum, cecum content, and intestinal tissues were collected for further analyses. Absence of mast cells in Cpa3-Cre;Mcl-1fl/fl homozygous mice was verified through tryptase staining. Neuronal excitability of dorsal root ganglia (DRG) neurons from naïve mice exposed to colonic supernatants were measured.

Results

The mast cell stabilizer cromolyn decreased visceral hypersensitivity in mice colonized with IBS-HH microbiota but not in mice with IBS-LH microbiota (P=0.037; IBS-HH vehicle vs IBS-HH cromolyn). These results were mirrored by decrease of serum mast cell protease 1 in IBS-HH mice after cromolyn treatment (P=0.001; IBS-HH vehicle vs IBS-HH cromolyn). Neuronal excitability was decreased after incubating DRG neurons with colonic supernatants of IBS-HH mice treated with cromolyn (P=0.02 vs IBS-HH vehicle). Mast cell deficient mice, particularly females, colonized with IBS-HH microbiota displayed a reduction in visceral hypersensitivity compared to WT IBS-HH mice (P=0.05).

Conclusion

Our data suggest mast cells are key players in visceral hypersensitivity but only in mice colonized with IBS microbiota with high histamine production. Thus, mast cells directed treatment might be effective mainly in a subset of patients with evidence of high bacterial histamine production.

Disclosure

Nothing to disclose.

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine Immunology Digestive Oncology Colorectal

Submission format

Abstract

Session

The gut talks back

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

OVERDIAGNOSIS OF SUPERIOR MESENTERIC ARTERY SYNDROME: LIMITED DIAGNOSTIC CONCORDANCE BETWEEN IMAGING MODALITIES AND LIMITED BENEFIT OF SURGERY

Tim Vanuytsel

COLONIC MAST CELL ACTIVATION IS LINKED TO MENTAL AND SOMATIC SYMPTOM SEVERITY IN IRRITABLE BOWEL SYNDROME: RESULTS FROM THE DISCOVERIE PROJECT (EU-FUNDED PROJECT Nº: 848228)

Carmen Alonso-Cotoner

TRANSCRIPTOMIC AND PROTEOMIC PROFILING OF COLONIC MUCOSA IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH OR WITHOUT MENTAL/SOMATIC COMORBIDITIES: RESULTS FROM THE EUROPEAN MULTICENTER DISCOVERIE STUDY

Carmen Alonso-Cotoner

MAST CELLS AS KEY PLAYERS OF VISCERAL HYPERSENSITIVITY TRIGGERED BY MICROBIAL HISTAMINE

Giada De Palma

Diagnosis and management of IBS: Past, present and future

Christopher Black

Are bowel disorders with diarrhoea really a separate entity from bile acid malabsorption?

Giovanni Barbara

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Diagnosis and management of IBS: Past, present and future

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Diagnosis and management of IBS: Past, present and future

Christopher Black 1

Affiliations

1 Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom

Summary

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Summary is not available for this content yet.

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Abstract

Event

UEG Week Barcelona 2026

Topics

Neurogastroenterology & Motility Primary Care

Session

Controversies in lower GI: disorders of gut–brain interaction

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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COLONIC MAST CELL ACTIVATION IS LINKED TO MENTAL AND SOMATIC SYMPTOM SEVERITY IN IRRITABLE BOWEL SYNDROME: RESULTS FROM THE DISCOVERIE PROJECT (EU-FUNDED PROJECT Nº: 848228)

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TRANSCRIPTOMIC AND PROTEOMIC PROFILING OF COLONIC MUCOSA IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH OR WITHOUT MENTAL/SOMATIC COMORBIDITIES: RESULTS FROM THE EUROPEAN MULTICENTER DISCOVERIE STUDY

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MAST CELLS AS KEY PLAYERS OF VISCERAL HYPERSENSITIVITY TRIGGERED BY MICROBIAL HISTAMINE

Giada De Palma

Diagnosis and management of IBS: Past, present and future

Christopher Black

Are bowel disorders with diarrhoea really a separate entity from bile acid malabsorption?

Giovanni Barbara

UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

Are bowel disorders with diarrhoea really a separate entity from bile acid malabsorption?

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

Not sure what you can access? Learn more about account types.

Are bowel disorders with diarrhoea really a separate entity from bile acid malabsorption?

Giovanni Barbara 1

Affiliations

1 University of Bologna, Bologna, Italy

Summary

AI Generated

Summary is not available for this content yet.

Download PDF

Was this helpful?

Thanks for your feedback.

Abstract

Event

UEG Week Barcelona 2026

Topics

Neurogastroenterology & Motility Primary Care

Session

Controversies in lower GI: disorders of gut–brain interaction

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

OVERDIAGNOSIS OF SUPERIOR MESENTERIC ARTERY SYNDROME: LIMITED DIAGNOSTIC CONCORDANCE BETWEEN IMAGING MODALITIES AND LIMITED BENEFIT OF SURGERY

Tim Vanuytsel

COLONIC MAST CELL ACTIVATION IS LINKED TO MENTAL AND SOMATIC SYMPTOM SEVERITY IN IRRITABLE BOWEL SYNDROME: RESULTS FROM THE DISCOVERIE PROJECT (EU-FUNDED PROJECT Nº: 848228)

Carmen Alonso-Cotoner

TRANSCRIPTOMIC AND PROTEOMIC PROFILING OF COLONIC MUCOSA IN PATIENTS WITH IRRITABLE BOWEL SYNDROME WITH OR WITHOUT MENTAL/SOMATIC COMORBIDITIES: RESULTS FROM THE EUROPEAN MULTICENTER DISCOVERIE STUDY

Carmen Alonso-Cotoner

MAST CELLS AS KEY PLAYERS OF VISCERAL HYPERSENSITIVITY TRIGGERED BY MICROBIAL HISTAMINE

Giada De Palma

Diagnosis and management of IBS: Past, present and future

Christopher Black

Are bowel disorders with diarrhoea really a separate entity from bile acid malabsorption?

Giovanni Barbara