View More View Less
  • 1 Puyang Oilfield General Hospital, P. R. China
  • | 2 Shandong University, P. R. China
Restricted access

Purchase article

USD  $25.00

1 year subscription (Individual Only)

USD  $752.00

Objectives

Impaired intestinal barrier function has been demonstrated in the pathophysiology of diarrhea-predominant irritable bowel syndrome (IBS-D). This study aimed to describe the intestinal ultrastructural findings in the intestinal mucosal layer of IBS-D patients.

Methods

In total, 10 healthy controls and 10 IBS-D patients were analyzed in this study. The mucosa of each patient’s rectosigmoid colon was first assessed by confocal laser endomicroscopy (CLE); next, biopsied specimens of these sites were obtained. Intestinal tissues of IBS-D patients and healthy volunteers were examined to observe cellular changes by transmission electron microscopy (TEM).

Results

CLE showed no visible epithelial damage or inflammatory changes in the colonic mucosa of IBS-D compared with healthy volunteers. On transmission electron microscopic examination, patients with IBS-D displayed a larger apical intercellular distance with a higher proportion of dilated (>20 nm) intercellular junctional complexes, which was indicative of impaired mucosal integrity. In addition, microvillus exfoliation, extracellular vesicle as well as increased presence of multivesicular bodies were visible in IBS-D patients. Single epithelial cells appeared necrotic, as characterized by cytoplasmic vacuolization, cytoplasmic swelling, and presence of autolysosome. A significant association between bowel habit, frequency of abdominal pain, and enlarged intercellular distance was found.

Conclusion

This study showed ultrastructural alterations in the architecture of intestinal epithelial cells and intercellular junctional complexes in IBS-D patients, potentially representing a pathophysiological mechanism in IBS-D.

  • 1.

    Bertiaux-Vandaele N , Youmba SB , Belmonte L , Lecleire S , Antonietti M , Gourcerol G , Leroi AM , Dechelotte P , Menard JF , Ducrotte P , Coeffier M : The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am. J. Gastroenterol. 106, 21652173 (2011)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Bruewer M , Samarin S , Nusrat A : Inflammatory bowel disease and the apical junctional complex. Ann. N. Y. Acad. Sci. 1072, 242252 (2006)

  • 3.

    Buning J , Von Smolinski D , Tafazzoli K , Zimmer KP , Strobel S , Apostolaki M , Kollias G , Heath JK , Ludwig D , Gebert A : Multivesicular bodies in intestinal epithelial cells: responsible for MHC class II-restricted antigen processing and origin of exosomes. Immunology 125, 510521 (2008)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Chang FY , Lu CL : Irritable bowel syndrome in the 21st century: perspectives from Asia or South-east Asia. J. Gastroenterol. Hepatol. 22, 412 (2007)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Demaude J , Salvador-Cartier C , Fioramonti J , Ferrier L , Bueno L : Phenotypic changes in colonocytes following acute stress or activation of mast cells in mice: implications for delayed epithelial barrier dysfunction. Gut 55, 655661 (2006)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Dourmashkin RR , Davies H , Wells C , Shah D , Price A , O’morain C , Levi J : Epithelial patchy necrosis in Crohn’s disease. Hum. Pathol. 14, 643648 (1983)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Fritscher-Ravens A , Schuppan D , Ellrichmann M , Schoch S , Rocken C , Brasch J , Bethge J , Bottner M , Klose J , Milla PJ : Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology 147, 10121020.e1014 (2014)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Groschwitz KR , Hogan SP : Intestinal barrier function: molecular regulation and disease pathogenesis. J. Allergy Clin. Immunol. 124, 320; quiz 21–22 (2009)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Gunther C , Neumann H , Neurath MF , Becker C : Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium. Gut 62, 10621071 (2013)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Gwee KA , Bak YT , Ghoshal UC , Gonlachanvit S , Lee OY , Fock KM , Chua AS , Lu CL , Goh KL , Kositchaiwat C , Makharia G , Park HJ , Chang FY , Fukudo S , Choi MG , Bhatia S , Ke M , Hou X , Hongo M : Asian consensus on irritable bowel syndrome. J. Gastroenterol. Hepatol. 25, 11891205 (2010)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Hartsock A , Nelson WJ : Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim. Biophys. Acta. 1778, 660669 (2008)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Jeon MK , Klaus C , Kaemmerer E , Gassler N : Intestinal barrier: molecular pathways and modifiers. World J. Gastrointest. Pathophysiol. 4, 9499 (2013)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Kiesslich R , Burg J , Vieth M , Gnaendiger J , Enders M , Delaney P , Polglase A , Mclaren W , Janell D , Thomas S , Nafe B , Galle PR , Neurath MF : Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo. Gastroenterology 127, 706713 (2004)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Kiesslich R , Duckworth CA , Moussata D , Gloeckner A , Lim LG , Goetz M , Pritchard DM , Galle PR , Neurath MF , Watson AJ : Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease. Gut 61, 11461153 (2012)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Krug SM , Schulzke JD , Fromm M : Tight junction, selective permeability, and related diseases. Semin. Cell Dev. Biol. 36, 166176 (2014)

  • 16.

    Lewis SJ , Heaton KW : Stool form scale as a useful guide to intestinal transit time. Scand. J. Gastroenterol. 32, 920924 (1997)

  • 17.

    Liu L , Xiao QF , Zhang YL , Yao SK : A cross-sectional study of irritable bowel syndrome in nurses in China: prevalence and associated psychological and lifestyle factors. J. Zhejiang Univ. Sci. B. 15, 590597 (2014)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Longstreth GF , Thompson WG , Chey WD , Houghton LA , Mearin F , Spiller RC : Functional bowel disorders. Gastroenterology 130, 14801491 (2006)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Mallegol J , Van Niel G , Heyman M : Phenotypic and functional characterization of intestinal epithelial exosomes. Blood Cells Mol. Dis. 35, 1116 (2005)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Maloy KJ , Powrie F : Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 474, 298306 (2011)

  • 21.

    Martinez C , Lobo B , Pigrau M , Ramos L , Gonzalez-Castro AM , Alonso C , Guilarte M , Guila M , De Torres I , Azpiroz F , Santos J , Vicario M : Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut 62, 11601168 (2013)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Perez-Moreno M , Jamora C , Fuchs E : Sticky business: orchestrating cellular signals at adherens junctions. Cell 112, 535548 (2003)

  • 23.

    Piche T , Barbara G , Aubert P , Bruley Des Varannes S , Dainese R , Nano JL , Cremon C , Stanghellini V , De Giorgio R , Galmiche JP , Neunlist M : Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 58, 196201 (2009)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Potten CS , Loeffler M : Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development 110, 10011020 (1990)

    • Search Google Scholar
    • Export Citation
  • 25.

    Than UTT , Guanzon D , Leavesley D , Parker T : Association of extracellular membrane vesicles with cutaneous wound healing. Int. J. Mol. Sci. 18, 956 (2017)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Tompkins AJ , Chatterjee D , Maddox M , Wang J , Arciero E , Camussi G , Quesenberry PJ , Renzulli JF : The emergence of extracellular vesicles in urology: fertility, cancer, biomarkers and targeted pharmacotherapy. J. Extracell. Vesicles 4, 23815 (2015)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Turcotte JF , Kao D , Mah SJ , Claggett B , Saltzman JR , Fedorak RN , Liu JJ : Breaks in the wall: increased gaps in the intestinal epithelium of irritable bowel syndrome patients identified by confocal laser endomicroscopy (with videos). Gastrointest. Endosc. 77, 624630 (2013)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Vanheel H , Vicario M , Vanuytsel T , Van Oudenhove L , Martinez C , Keita AV , Pardon N , Santos J , Soderholm JD , Tack J , Farre R : Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut 63, 262271 (2014)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Xu R , Greening DW , Zhu HJ , Takahashi N , Simpson RJ : Extracellular vesicle isolation and characterization: toward clinical application. J. Clin. Invest. 126, 11521162 (2016)

    • Crossref
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 227 220 11
Full Text Views 53 5 0
PDF Downloads 31 3 0