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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 malab-sorption, 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 hypersensi-tivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis. At 50 days postinfection with G. duo-denalis (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 (vil-lus 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 trans-location 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.
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Marie Halliez, Jean-Paul Motta, Troy Feener, Gaëtan Guerin, Laetitia Legoff, et al.. Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity. AJP - Gastrointestinal and Liver Physiology, American Physiological Society, 2016, 310, pp.574 - 585. ⟨10.1152/ajpgi.00144.2015⟩. ⟨hal-02317886⟩

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