Tags

Type your tag names separated by a space and hit enter

Gluten-induced symptoms in diarrhea-predominant irritable bowel syndrome are associated with increased myosin light chain kinase activity and claudin-15 expression.
Lab Invest. 2017 01; 97(1):14-23.LI

Abstract

The mechanisms underlying diarrhea-predominant irritable bowel syndrome (IBS-D) are poorly understood, but increased intestinal permeability is thought to contribute to symptoms. A recent clinical trial of gluten-free diet (GFD) demonstrated symptomatic improvement, relative to gluten-containing diet (GCD), which was associated with reduced intestinal permeability in non-celiac disease IBS-D patients. The aim of this study was to characterize intestinal epithelial tight junction composition in IBS-D before and after dietary gluten challenge. Biopsies from 27 IBS-D patients (13 GFD and 14 GCD) were examined by H&E staining and semiquantitative immunohistochemistry for phosphorylated myosin II regulatory light chain (MLC), MLC kinase, claudin-2, claudin-8 and claudin-15. Diet-induced changes were assessed and correlated with urinary mannitol excretion (after oral administration). In the small intestine, epithelial MLC phosphorylation was increased or decreased by GCD or GFD, respectively, and this correlated with increased intestinal permeability (P<0.03). Colonocyte expression of the paracellular Na+ channel claudin-15 was also markedly augmented following GCD challenge (P<0.05). Conversely, colonic claudin-2 expression correlated with reduced intestinal permeability (P<0.03). Claudin-8 expression was not affected by dietary challenge. These data show that alterations in MLC phosphorylation and claudin-15 and claudin-2 expression are associated with gluten-induced symptomatology and intestinal permeability changes in IBS-D. The results provide new insight into IBS-D mechanisms and can explain permeability responses to gluten challenge in these patients.

Links

Authors+Show Affiliations

Department of Pathology, The University of Chicago, Chicago, IL, USA. Department of Pathology and Laboratory Medicine, Jackson Memorial Hospital, University of Miami, Miami, FL, USA.

Vazquez-Roque MI

Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, College of Medicine, Mayo Clinic, Rochester, MN, USA.

Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, College of Medicine, Mayo Clinic, Rochester, MN, USA.

Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, College of Medicine, Mayo Clinic, Rochester, MN, USA.

Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, College of Medicine, Mayo Clinic, Rochester, MN, USA.

Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research, College of Medicine, Mayo Clinic, Rochester, MN, USA.

Department of Pathology, The University of Chicago, Chicago, IL, USA. Departments of Pathology and Medicine (GI), Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27869798

Citation

Wu, Richard L., et al. "Gluten-induced Symptoms in Diarrhea-predominant Irritable Bowel Syndrome Are Associated With Increased Myosin Light Chain Kinase Activity and Claudin-15 Expression." Laboratory Investigation; a Journal of Technical Methods and Pathology, vol. 97, no. 1, 2017, pp. 14-23.

Wu RL, Vazquez-Roque MI, Carlson P, et al. Gluten-induced symptoms in diarrhea-predominant irritable bowel syndrome are associated with increased myosin light chain kinase activity and claudin-15 expression. Lab Invest. 2017;97(1):14-23.

Wu, R. L., Vazquez-Roque, M. I., Carlson, P., Burton, D., Grover, M., Camilleri, M., & Turner, J. R. (2017). Gluten-induced symptoms in diarrhea-predominant irritable bowel syndrome are associated with increased myosin light chain kinase activity and claudin-15 expression. Laboratory Investigation; a Journal of Technical Methods and Pathology, 97(1), 14-23. https://doi.org/10.1038/labinvest.2016.118

Wu RL, et al. Gluten-induced Symptoms in Diarrhea-predominant Irritable Bowel Syndrome Are Associated With Increased Myosin Light Chain Kinase Activity and Claudin-15 Expression. Lab Invest. 2017;97(1):14-23. PubMed PMID: 27869798.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Gluten-induced symptoms in diarrhea-predominant irritable bowel syndrome are associated with increased myosin light chain kinase activity and claudin-15 expression. AU - Wu,Richard L, AU - Vazquez-Roque,Maria I, AU - Carlson,Paula, AU - Burton,Duane, AU - Grover,Madhusudan, AU - Camilleri,Michael, AU - Turner,Jerrold R, Y1 - 2016/11/21/ PY - 2016/08/23/received PY - 2016/09/26/revised PY - 2016/10/01/accepted PY - 2016/11/22/pubmed PY - 2017/6/22/medline PY - 2016/11/22/entrez SP - 14 EP - 23 JF - Laboratory investigation; a journal of technical methods and pathology JO - Lab Invest VL - 97 IS - 1 N2 - The mechanisms underlying diarrhea-predominant irritable bowel syndrome (IBS-D) are poorly understood, but increased intestinal permeability is thought to contribute to symptoms. A recent clinical trial of gluten-free diet (GFD) demonstrated symptomatic improvement, relative to gluten-containing diet (GCD), which was associated with reduced intestinal permeability in non-celiac disease IBS-D patients. The aim of this study was to characterize intestinal epithelial tight junction composition in IBS-D before and after dietary gluten challenge. Biopsies from 27 IBS-D patients (13 GFD and 14 GCD) were examined by H&E staining and semiquantitative immunohistochemistry for phosphorylated myosin II regulatory light chain (MLC), MLC kinase, claudin-2, claudin-8 and claudin-15. Diet-induced changes were assessed and correlated with urinary mannitol excretion (after oral administration). In the small intestine, epithelial MLC phosphorylation was increased or decreased by GCD or GFD, respectively, and this correlated with increased intestinal permeability (P<0.03). Colonocyte expression of the paracellular Na+ channel claudin-15 was also markedly augmented following GCD challenge (P<0.05). Conversely, colonic claudin-2 expression correlated with reduced intestinal permeability (P<0.03). Claudin-8 expression was not affected by dietary challenge. These data show that alterations in MLC phosphorylation and claudin-15 and claudin-2 expression are associated with gluten-induced symptomatology and intestinal permeability changes in IBS-D. The results provide new insight into IBS-D mechanisms and can explain permeability responses to gluten challenge in these patients. SN - 1530-0307 UR - https://www.unboundmedicine.com/medline/citation/27869798/Gluten_induced_symptoms_in_diarrhea_predominant_irritable_bowel_syndrome_are_associated_with_increased_myosin_light_chain_kinase_activity_and_claudin_15_expression_ DB - PRIME DP - Unbound Medicine ER -