Trial reportGut2014
Characterisation of faecal protease activity in irritable bowel syndrome with diarrhoea: origin and effect of gut transit.
Trial report in Gut, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00745004 (Ondansetron for the Treatment of IBS With Diarrhoea), which is not on this map. Cited by 43 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Ondansetron for the Treatment of IBS With Diarrhoea (IBS-D): Identifying the "Responder"
Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- Serological and faecal markers of irritable bowel syndrome: a systematic review and meta-analysis.EBioMedicine · 2026Pooled it
- Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023.Digestion · 2024Guideline
- Abnormalities of mucosal serotonin metabolism and 5-HTAlimentary pharmacology & therapeutics · 2019Trial
- Trial
- Trial
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Unraveling the Pathophysiology of Irritable Bowel Syndrome: Mechanisms and Insights.International journal of molecular sciences · 2025Review
- A triad of gut dysbiosis, dysregulated immunity, and 'leaky' gut characterize HCMV associated neonatal cholestasis.Gut pathogens · 2024Article
- Impact of Enteric Nervous Cells on Irritable Bowel Syndrome: Potential Treatment Options.Microorganisms · 2024Review
- Review
- Activation of goblet cell Piezo1 alleviates mucus barrier damage in mice exposed to WAS by inhibiting H3K9me3 modification.Cell & bioscience · 2023Article
- A protease activity-based machine-learning approach as a complementary tool for conventional diagnosis of diarrhea-predominant irritable bowel syndrome.Frontiers in microbiology · 2023Article
- Immune activation in irritable bowel syndrome: what is the evidence?Nature reviews. Immunology · 2022Review
- Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome.Neurogastroenterology and motility · 2022Review
- Mucosal Serotonin Reuptake Transporter Expression in Irritable Bowel Syndrome Is Modulated by Gut Microbiota Via Mast Cell-Prostaglandin E2.Gastroenterology · 2022Article
- Gut microbial β-glucuronidases regulate host luminal proteases and are depleted in irritable bowel syndrome.Nature microbiology · 2022Article
- Inhibition of Serine Proteases as a Novel Therapeutic Strategy for Abdominal Pain in IBS.Frontiers in physiology · 2022Review
- Proteolytic Cleavage of Bioactive Peptides and Protease-Activated Receptors in Acute and Post-Colitis.International journal of molecular sciences · 2021Article
- Post-infection Irritable Bowel Syndrome.Gastroenterology clinics of North America · 2021Review
- Local Colonic Administration of a Serine Protease Inhibitor Improves Post-Inflammatory Visceral Hypersensitivity in Rats.Pharmaceutics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesFaecal serine proteases (FSPs) may play a role in irritable bowel syndrome with diarrhoea (IBS-D), but their origin is unclear. We aimed to structurally characterise them and define the impact of colonic cleansing and transit time.
designFaecal samples were obtained from 30 healthy volunteers (HV) and 79 patients with IBS-D participating in a trial of ondansetron versus placebo. Colonic transit was measured using radio-opaque markers. Samples were also obtained from 24 HV before and after colonic cleansing with the osmotic laxative MoviPrep. FSPs were purified from faecal extracts using benzamidine-Sepharose affinity chromatography. SDS-PAGE profiled components were identified using trypsinolysis and tandem mass spectrometry. Functional protease activity in faecal extracts was measured using a colorimetric assay based on the proteolysis of azo-casein.
resultsProtein analysis identified the most abundant FSPs as being of human origin and probably derived from pancreatic juice. Functional assays showed increased faecal protease (FP) and amylase in patients with IBS-D compared with HV. Those with higher amylase had significantly higher FP and greater anxiety. FP activity correlated negatively with whole gut transit in patients with IBS-D (Spearman r=-0.32, p=0.005) and HV (r=-0.55, p=0.014). Colon cleansing caused a significant rise in FP activity in HV from a baseline of median (IQR) 253 (140-426) to 1031 (435-2296), levels similar to those seen in patients with IBS-D. FSP activity correlated positively with days/week with urgency.
conclusionsThe most abundant FSPs are of human origin. Rapid transit through the colon and/or decreased (possibly bacterial) proteolytic degradation increases their faecal concentration and could contribute to visceral hypersensitivity in patients with IBS-D. CLINICALTRIALSGOV: NCT00745004.
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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.