ArticleJournal of Crohn's & colitis2023
Long-Term Use of Proton Pump Inhibitors Disrupts Intestinal Tight Junction Barrier and Exaggerates Experimental Colitis.
Article in Journal of Crohn's & colitis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The impact of proton pump inhibitor exposure on pneumonia: an updated meta-analysis based on randomized controlled trials.Frontiers in pharmacology · 2025Pooled it
- From signals to systems: the epigenetic-microbiome-mitochondrial axis in IBD pathogenesis.Gut microbes · 2026Review
- Chronic proton pump inhibitor exposure aggravates intestinal injury by impairing intestinal stem cell self-renewal through the microbiota-7-ketolithocholic acid Axis.Journal of translational medicine · 2026Article
- Fusobacterium nucleatum regulates nicotinamide metabolism via the upregulation of NNMT to activate PARP1/MAPK signalling in colitis-associated cancer.Cellular and molecular life sciences : CMLS · 2026Article
- The gut-lung axis in ARDS: beyond microbial translocation.Respiratory research · 2026Review
- Association of Proton Pump Inhibitor and Potassium-Competitive Acid Blocker Use With Discontinuation and Intolerance of Oral 5-Aminosalicylic Acid in Patients With Ulcerative Colitis.JGH open : an open access journal of gastroenterology and hepatology · 2026Article
- Association between proton pump inhibitor use and muscle mass: a US population-based study.Aging clinical and experimental research · 2026Article
- Inflammatory bowel diseases: pathological mechanisms and therapeutic perspectives.Molecular biomedicine · 2026Review
- Proton pump inhibitor increases intestinal epithelial paracellular permeability via the p38-MAPK/NF-κB signaling pathway.Molecular biology reports · 2025Article
- The association of proton pump inhibitors and inflammatory bowel disease from the perspective of gut microbiota perturbation.NPJ biofilms and microbiomes · 2025Review
- Restoration of colonic barrier function by tofacitinib in experimental colitis: anti-inflammatory effects and decreased expression of claudins-2 and claudin-15.Intestinal research · 2025Article
- Intact glycoconjugates from Taenia crassiceps excreted/secreted products ameliorate chemically induced colitis by modulating inflammation and strengthening adherens junctions.Inflammopharmacology · 2025Article
- Intestinal Epithelial Tight Junction Barrier Regulation by Novel Pathways.Inflammatory bowel diseases · 2025Review
- The effect of proton-pump inhibitor therapy on disease outcomes in inflammatory bowel disease: a population-based cohort study.Therapeutic advances in gastroenterology · 2025Article
- OralJournal of oral microbiology · 2025Article
- Effect of tegoprazan, a novel potassium-competitive acid blocker, on non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy.Scientific reports · 2024Article
- Elevated risk of adverse effects from foodborne contaminants and drugs in inflammatory bowel disease: a review.Archives of toxicology · 2024Review
- Effects of proton pump inhibitors on inflammatory bowel disease: An updated review.World journal of gastroenterology · 2024Review
- Rabeprazole suppressed gastric intestinal metaplasia through activation of GPX4-mediated ferroptosis.Frontiers in pharmacology · 2024Article
- Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundProton pump inhibitors [PPIs] are widely used to treat a number of gastro-oesophageal disorders. PPI-induced elevation in intragastric pH may alter gastrointestinal physiology. The tight junctions [TJs] residing at the apical intercellular contacts act as a paracellular barrier. TJ barrier dysfunction is an important pathogenic factor in inflammatory bowel disease [IBD]. Recent studies suggest that PPIs may promote disease flares in IBD patients. The role of PPIs in intestinal permeability is not clear.
aimThe aim of the present study was to study the effect of PPIs on the intestinal TJ barrier function.
methodsHuman intestinal epithelial cell culture and organoid models and mouse IBD models of dextran sodium sulphate [DSS] and spontaneous enterocolitis in IL-10-/- mice were used to study the role of PPIs in intestinal permeability.
resultsPPIs increased TJ barrier permeability via an increase in a principal TJ regulator, myosin light chain kinase [MLCK] activity and expression, in a p38 MAPK-dependent manner. The PPI-induced increase in extracellular pH caused MLCK activation via p38 MAPK. Long-term PPI administration in mice exaggerated the increase in intestinal TJ permeability and disease severity in two independent models of DSS colitis and IL-10-/- enterocolitis. The TJ barrier disruption by PPIs was prevented in MLCK-/- mice. Human database studies revealed increased hospitalizations associated with PPI use in IBD patients.
conclusionsOur results suggest that long-term use of PPIs increases intestinal TJ permeability and exaggerates experimental colitis via an increase in MLCK expression and activity.
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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.