title: Targeting immunoproteasome and glutamine supplementation prevent intestinal hyperpermeability.
abstract: Intestinal hyperpermeability has been reported in several intestinal and non-intestinal disorders. We aimed to investigate the role of the ubiquitin proteasome system in gut barrier regulation in two mice models: the water avoidance stress model (WAS) and a post-inflammatory model (post-TNBS).
  
  
  
  Both models were applied in C57BL/6 male mice (n=7-8/group); Proteasome was targeted by injection of a selective proteasome inhibitor or by using knock-out mice for β2i proteasome subunit. Finally, glutamine supplementation was evaluated.
  
  
  
  In both models (WAS at day 10, post-TNBS at day 28), we observed an increase in proteasome trypsin-like activity and in inducible β2/constitutive β2 subunit protein expression ratio, associated with an increase in intestinal permeability. Moreover, intestinal hyperpermeability was blunted by intraperitoneal injection of selective proteasome inhibitor in WAS and post-TNBS mice. Of note, knock-out mice for the β2i subunit exhibited a significant decrease in intestinal permeability and fecal pellet output during WAS. Glutamine supplementation also improved colonic permeability in both models.
  
  
  
  In conclusion, the proteasome system is altered in the colonic mucosa of WAS and post-TNBS mice with increased trypsin-like activity. Associated intestinal hyperpermeability was blunted by immunoproteasome inhibition.
authors.affiliation: Normandie Univ, INSERM unit 1073, Nutrition, Inflammation and Gut-brain axis, Rouen, France; Rouen University, Institute for Research and Innovation in Biomedicine, Rouen, France.
authors.forename: Ibtissem
authors.initials: I
authors.lastname: Ghouzali
authors.affiliation: Normandie Univ, INSERM unit 1073, Nutrition, Inflammation and Gut-brain axis, Rouen, France; Rouen University, Institute for Research and Innovation in Biomedicine, Rouen, France; Department of Gastroenterology, Rouen University Hospital, Rouen, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lemaitre
authors.affiliation: Normandie Univ, INSERM unit 1073, Nutrition, Inflammation and Gut-brain axis, Rouen, France; Rouen University, Institute for Research and Innovation in Biomedicine, Rouen, France.
authors.forename: Wafa
authors.initials: W
authors.lastname: Bahlouli
authors.affiliation: Normandie Univ, INSERM unit 1073, Nutrition, Inflammation and Gut-brain axis, Rouen, France; Rouen University, Institute for Research and Innovation in Biomedicine, Rouen, France.
authors.forename: Saïda
authors.initials: S
authors.lastname: Azhar
authors.affiliation: Normandie Univ, INSERM unit 1073, Nutrition, Inflammation and Gut-brain axis, Rouen, France; Rouen University, Institute for Research and Innovation in Biomedicine, Rouen, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bôle-Feysot
authors.affiliation: Normandie Univ, INSERM unit 1073, Nutrition, Inflammation and Gut-brain axis, Rouen, France; Rouen University, Institute for Research and Innovation in Biomedicine, Rouen, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Meleine
authors.affiliation: Normandie Univ, INSERM unit 1073, Nutrition, Inflammation and Gut-brain axis, Rouen, France; Rouen University, Institute for Research and Innovation in Biomedicine, Rouen, France; Department of Gastroenterology, Rouen University Hospital, Rouen, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ducrotté
authors.affiliation: Normandie Univ, INSERM unit 1073, Nutrition, Inflammation and Gut-brain axis, Rouen, France; Rouen University, Institute for Research and Innovation in Biomedicine, Rouen, France; Department of Nutrition, Rouen University Hospital, Rouen, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
authors.affiliation: Normandie Univ, INSERM unit 1073, Nutrition, Inflammation and Gut-brain axis, Rouen, France; Rouen University, Institute for Research and Innovation in Biomedicine, Rouen, France; Department of Nutrition, Rouen University Hospital, Rouen, France. Electronic address: moise.coeffier@univ-rouen.fr.
authors.forename: Moïse
authors.initials: M
authors.lastname: Coëffier
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000503:physiopathology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005973:Glutamine / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007422:Intestines / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D062793:Occludin / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000276:immunology* / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D062793:Occludin; D061988:Proteasome Inhibitors; D005973:Glutamine; D014302:Trinitrobenzenesulfonic Acid; D046988:Proteasome Endopeptidase Complex
keywords: Glutamine; Intestinal permeability; Post-inflammatory model; Proteasome; Water avoidance stress