Cited by 283Gastrointestinal motility and disordersGut microbiota and healthInflammatory Bowel Disease

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Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier

Martínez, Cristina, Lobo, Beatriz, Pigrau, Marc, Ramos, Laura, González-Castro, Ana Maria, Alonso, Carmen, Guilarte, Mar, Guilá, Meritxell, de Torres, Ines, Azpiroz, Fernando, Santos, Javier, Vicario, María·2013·Gut

DOI 10.1136/gutjnl-2012-302093

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Abstract

Objective: Recently, the authors demonstrated altered gene expression in the jejunal mucosa of diarrhoea-predominant irritable bowel syndrome patients (IBS-D); specifically, the authors showed that genes related to mast cells and the intercellular apical junction complex (AJC) were expressed differently than in healthy subjects. The aim of the authors here was to determine whether these alterations are associated with structural abnormalities in AJC and their relationship with mast cell activation and IBS-D clinical manifestations. Design: A clinical assessment and a jejunal biopsy were obtained in IBS-D patients (n=45) and healthy subjects (n=30). Mucosal mast cell number and activation were determined by quantifying CD117 + cells/hpf and tryptase expression, respectively. Expression and distribution of AJC specific proteins were evaluated by western blot and confocal microscopy. AJC ultrastructure was assessed by transmission electron microscopy. Results: Compared with healthy subjects, IBS-D patients exhibited: (a) increased mast cell counts and activation; (b) increased protein expression of claudin-2, reduced occludin phosphorylation and enhanced redistribution from the membrane to the cytoplasm; and (c) increased myosin kinase expression, reduced myosin phosphatase and, consequently, enhanced phosphorylation of myosin. These molecular alterations were associated with ultrastructural abnormalities at the AJC, specifically, perijunctional cytoskeleton condensation and enlarged apical intercellular distance. Moreover, AJC structural alterations positively correlated both with mast cell activation and clinical symptoms. Conclusion: The jejunal mucosa of IBS-D patients displays disrupted apical junctional complex integrity associated with mast cell activation and clinical manifestations. These results provide evidence for the organic nature of IBS-D, a heretofore model disease of functional gastrointestinal disorders.

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Authors: Martínez, C., Lobo, B., Pigrau, M., Ramos, L., González-Castro, A. M., Alonso, C., Guilarte, M., Guilá, M., de Torres, I., Azpiroz, F., Santos, J., & Vicario, M.
Affiliations: Universitat Autònoma de Barcelona (ES)
Department of Gastroenterology, Digestive System Research Unit, Hospital Universitari Vall d'Hebron and Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona (Departmento de Medicina), Barcelona, Spain
Pathology Department, Hospital Universitari Vall d'Hebron and Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona (Departmento de Medicina), Barcelona, Spain
Corresponding author: Vicario, María
ORCID: Martínez, Cristina
Lobo, Beatriz
Pigrau, Marc
Ramos, Laura
Alonso, Carmen
Guilarte, Mar
Azpiroz, Fernando
Santos, Javier
Vicario, María
Venue: Gut
Publisher: BMJ
Published: 2012-05-25
Volume: 62
Issue: 8
Pages: 1160-1168
ISSN: 0017-5749 (ISSN-L)
1468-3288
DOI: 10.1136/gutjnl-2012-302093
OpenAlex: W2111819970
Cited by: 283
References: 44
Citations by year: 2026: 8 · 2025: 12 · 2024: 15 · 2023: 11 · 2022: 26 · 2021: 20 · 2020: 24 · 2019: 23 · 2018: 15 · 2017: 26 · 2016: 32 · 2015: 20 · 2014: 30 · 2013: 18 · 2012: 3
FWCI: 22.12
Type: journal article
Language: en
Open access: closed
Locations: Gut (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Topics: Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
Keywords: diarrhea-predominant irritable bowel syndrome, mast cell activation, claudin-2, occludin phosphorylation, myosin phosphatase, tryptase, CD117, jejunal mucosa, functional gastrointestinal disorders
MeSH terms: Adolescent, Adult, Biopsy, Diarrhea, Female, Humans, Intercellular Junctions, Intestinal Mucosa, Jejunum, Male, Mast Cells, Middle Aged, Phosphorylation, Prospective Studies, Sex Factors, Stress, Psychological, Myosin Light Chains, Irritable Bowel Syndrome, Young Adult, Tight Junction Proteins

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Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier

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