title: Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity.
abstract: Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis [then termed postinfectious IBS (PI-IBS)], the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field.
authors.affiliation: Protozooses transmises par l'alimentation, Rouen University Hospital, University of Rouen and University of Reims Champagne-Ardennes, and Institute for Biomedical Research, Rouen and Reims, France; Department of Biological Sciences, Inflammation Research Network, Host-Parasite Interaction NSERC-CREATE, University of Calgary, Calgary, Alberta, Canada;
authors.forename: Marie C M
authors.initials: MC
authors.lastname: Halliez
authors.affiliation: Department of Biological Sciences, Inflammation Research Network, Host-Parasite Interaction NSERC-CREATE, University of Calgary, Calgary, Alberta, Canada;
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Motta
authors.affiliation: Department of Biological Sciences, Inflammation Research Network, Host-Parasite Interaction NSERC-CREATE, University of Calgary, Calgary, Alberta, Canada;
authors.forename: Troy D
authors.initials: TD
authors.lastname: Feener
authors.affiliation: Protozooses transmises par l'alimentation, Rouen University Hospital, University of Rouen and University of Reims Champagne-Ardennes, and Institute for Biomedical Research, Rouen and Reims, France;
authors.forename: Gaetan
authors.initials: G
authors.lastname: Guérin
authors.affiliation: Protozooses transmises par l'alimentation, Rouen University Hospital, University of Rouen and University of Reims Champagne-Ardennes, and Institute for Biomedical Research, Rouen and Reims, France;
authors.forename: Laetitia
authors.initials: L
authors.lastname: LeGoff
authors.affiliation: Protozooses transmises par l'alimentation, Rouen University Hospital, University of Rouen and University of Reims Champagne-Ardennes, and Institute for Biomedical Research, Rouen and Reims, France; Service d'Anatomie et de Cytologie Pathologique CHU Rouen, Rouen cedex, France; and.
authors.forename: Arnaud
authors.initials: A
authors.lastname: François
authors.affiliation: Service d'Anatomie et de Cytologie Pathologique CHU Rouen, Rouen cedex, France; and.
authors.forename: Elodie
authors.initials: E
authors.lastname: Colasse
authors.affiliation: Protozooses transmises par l'alimentation, Rouen University Hospital, University of Rouen and University of Reims Champagne-Ardennes, and Institute for Biomedical Research, Rouen and Reims, France;
authors.forename: Loic
authors.initials: L
authors.lastname: Favennec
authors.affiliation: Protozooses transmises par l'alimentation, Rouen University Hospital, University of Rouen and University of Reims Champagne-Ardennes, and Institute for Biomedical Research, Rouen and Reims, France;
authors.forename: Gilles
authors.initials: G
authors.lastname: Gargala
authors.affiliation: Snyder Institute for Chronic Diseases, Inflammation Research Network, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Tamia K
authors.initials: TK
authors.lastname: Lapointe
authors.affiliation: Snyder Institute for Chronic Diseases, Inflammation Research Network, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Christophe
authors.initials: C
authors.lastname: Altier
authors.affiliation: Department of Biological Sciences, Inflammation Research Network, Host-Parasite Interaction NSERC-CREATE, University of Calgary, Calgary, Alberta, Canada; aburet@ucalgary.ca.
authors.forename: André G
authors.initials: AG
authors.lastname: Buret
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D004926:Escherichia coli / Q000472:pathogenicity / Q000502:physiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D005873:Giardiasis / Q000150:complications* / Q000382:microbiology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000209:etiology* / Q000382:microbiology / Q000469:parasitology; D008297:Male; D059225:Nociception; D051381:Rats; D017207:Rats, Sprague-Dawley; D062725:Tight Junction Proteins / Q000378:metabolism; D057688:Transcellular Cell Migration
chemical_list: D062725:Tight Junction Proteins
keywords: Giardia; bacterial translocation; irritable bowel syndrome; tight junctions; visceral hypersensitivity