ArticleGut2020
Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS.
Article in Gut, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 98 citations in OpenAlex.
- Trial
- Trial
- Pro-Inflammatory Cytokines as Core Mediators of Colonic Epithelial Barrier Dysfunction: Roles of TNF-α, IFN-γ, IL-1β, and IL-6.International journal of molecular sciences · 2026Review
- The Mast Cell-PAR2-TRP Axis: A Convergent Mechanism for Visceral Hypersensitivity Independent of Divergent Motility in IBS.Biomolecules · 2026Review
- [Niranthin ameliorates Crohn's disease-like colitis in mice via antagonizing intestinal epithelial cell apoptosis and regulating intestinal Th1/Th2 immune homeostasis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Tongxie Yaofang ameliorates IBS-D by targeting the gut microbiota-derived tryptophan metabolites and AhR signaling axis.Frontiers in microbiology · 2026Article
- Thymosin β4 released by mast cells under stress conditions impairs intestinal epithelial barrierWorld journal of gastroenterology · 2025Article
- Unraveling the Pathophysiology of Irritable Bowel Syndrome: Mechanisms and Insights.International journal of molecular sciences · 2025Review
- A Bacteroides fragilis protease activates host PARCell host & microbe · 2025Article
- Review
- Proteomics of Bacterial and Mouse Extracellular Vesicles Released in the Gastrointestinal Tracts of Nutrient-Stressed Animals Reveals an Interplay Between Microbial Serine Proteases and Mammalian Serine Protease Inhibitors.International journal of molecular sciences · 2025Article
- Microbial dipeptidyl peptidases of the S9B family as host-microbe isozymes.Science advances · 2025Review
- Rome Foundation Working Team Report on overlap in disorders of gut-brain interaction.Nature reviews. Gastroenterology & hepatology · 2025Review
- The role of the gut microbiome in disorders of gut-brain interaction.The FEBS journal · 2025Review
- Identification of a secreted protease frombioRxiv : the preprint server for biology · 2025Article
- Mucus and mucin: changes in the mucus barrier in disease states.Tissue barriers · 2025Review
- Proteomic analysis across aged tissues reveals distinct signatures and the crucial involvement of midgut barrier function in the regulation of aging.Aging cell · 2025Article
- Energy metabolism and the intestinal barrier: implications for understanding and managing intestinal diseases.Frontiers in microbiology · 2025Review
- Microbiome Shifts and Their Impact on Gut Physiology in Irritable Bowel Syndrome.International journal of molecular sciences · 2024Review
- Serine proteases and metalloproteases are highly increased in irritable bowel syndrome Tunisian patients.Scientific reports · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveThe intestinal lumen contains several proteases. Our aim was to determine the role of faecal proteases in mediating barrier dysfunction and symptoms in IBS.
design39 patients with IBS and 25 healthy volunteers completed questionnaires, assessments of in vivo permeability, ex vivo colonic barrier function in Ussing chambers, tight junction (TJ) proteins, ultrastructural morphology and 16 s sequencing of faecal microbiota rRNA. A casein-based assay was used to measure proteolytic activity (PA) in faecal supernatants (FSNs). Colonic barrier function was determined in mice (ex-germ free) humanised with microbial communities associated with different human PA states.
resultsPatients with IBS had higher faecal PA than healthy volunteers. 8/20 postinfection IBS (PI-IBS) and 3/19 constipation- predominant IBS had high PA (>95th percentile). High-PA patients had more and looser bowel movements, greater symptom severity and higher in vivo and ex vivo colonic permeability. High-PA FSNs increased paracellular permeability, decreased occludin and increased phosphorylated myosin light chain (pMLC) expression. Serine but not cysteine protease inhibitor significantly blocked high-PA FSN effects on barrier. The effects on barrier were diminished by pharmacological or siRNA inhibition of protease activated receptor-2 (PAR-2). Patients with high-PA IBS had lower occludin expression, wider TJs on biopsies and reduced microbial diversity than patients with low PA. Mice humanised with high-PA IBS microbiota had greater in vivo permeability than those with low-PA microbiota.
conclusionA subset of patients with IBS, especially in PI-IBS, has substantially high faecal PA, greater symptoms, impaired barrier and reduced microbial diversity. Commensal microbiota affects luminal PA that can influence host barrier function.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.