title: Stress disrupts intestinal mucus barrier in rats via mucin O-glycosylation shift: prevention by a probiotic treatment.
abstract: Despite well-known intestinal epithelial barrier impairment and visceral hypersensitivity in irritable bowel syndrome (IBS) patients and IBS-like models, structural and physical changes in the mucus layer remain poorly understood. Using a water avoidance stress (WAS) model, we aimed at evaluating whether 1) WAS modified gut permeability, visceral sensitivity, mucin expression, biochemical structure of O-glycans, and related mucus physical properties, and 2) whether Lactobacillus farciminis treatment prevented these alterations. Wistar rats received orally L. farciminis or vehicle for 14 days; at day 10, they were submitted to either sham or 4-day WAS. Intestinal paracellular permeability and visceral sensitivity were measured in vivo. The number of goblet cells and Muc2 expression were evaluated by histology and immunohistochemistry, respectively. Mucosal adhesion of L. farciminis was determined ex situ. The mucin O-glycosylation profile was obtained by mass spectrometry. Surface imaging of intestinal mucus was performed at nanoscale by atomic force microscopy. WAS induced gut hyperpermeability and visceral hypersensitivity but did not modify either the number of intestinal goblet cells or Muc2 expression. In contrast, O-glycosylation of mucins was strongly affected, with the appearance of elongated polylactosaminic chain containing O-glycan structures, associated with flattening and loss of the mucus layer cohesive properties. L. farciminis bound to intestinal Muc2 and prevented WAS-induced functional alterations and changes in mucin O-glycosylation and mucus physical properties. WAS-induced functional changes were associated with mucus alterations resulting from a shift in O-glycosylation rather than from changes in mucin expression. L. farciminis treatment prevented these alterations, conferring epithelial and mucus barrier strengthening.
authors: Université de Toulouse; INSA, UPS, INP; LISBP, Toulouse, France; INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, France; CNRS, UMR5504, Toulouse, France; INRA, EI-Purpan, UMR 1331 TOXALIM, Equipe de NeuroGastroentérologie et Nutrition, Toulouse, France;
authors: Stéphanie
authors: S
authors: Da Silva
authors: Université de Lille 1, Unité de Glycobiologie Structurale et Fonctionnelle, UGSF, Villeneuve d'Ascq, France; CNRS, UMR 8576, Villeneuve d'Ascq, France; and.
authors: Catherine
authors: C
authors: Robbe-Masselot
authors: INRA, EI-Purpan, UMR 1331 TOXALIM, Equipe de NeuroGastroentérologie et Nutrition, Toulouse, France; Lallemand SA, Blagnac, France;
authors: Afifa
authors: A
authors: Ait-Belgnaoui
authors: Université de Lille 1, Unité de Glycobiologie Structurale et Fonctionnelle, UGSF, Villeneuve d'Ascq, France; CNRS, UMR 8576, Villeneuve d'Ascq, France; and.
authors: Alessandro
authors: A
authors: Mancuso
authors: Université de Toulouse; INSA, UPS, INP; LISBP, Toulouse, France; INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, France; CNRS, UMR5504, Toulouse, France;
authors: Myriam
authors: M
authors: Mercade-Loubière
authors: INRA, EI-Purpan, UMR 1331 TOXALIM, Equipe de NeuroGastroentérologie et Nutrition, Toulouse, France;
authors: Christel
authors: C
authors: Salvador-Cartier
authors: INRA, EI-Purpan, UMR 1331 TOXALIM, Equipe de NeuroGastroentérologie et Nutrition, Toulouse, France;
authors: Marion
authors: M
authors: Gillet
authors: INRA, EI-Purpan, UMR 1331 TOXALIM, Equipe de NeuroGastroentérologie et Nutrition, Toulouse, France;
authors: Laurent
authors: L
authors: Ferrier
authors: Université de Toulouse; INSA, UPS, INP; LISBP, Toulouse, France; INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, France; CNRS, UMR5504, Toulouse, France;
authors: Pascal
authors: P
authors: Loubière
authors: CNRS; LAAS; Toulouse, France; CNRS; ITAV-UMS3039; F31106 Toulouse, France; and Université de Toulouse; UPS, INSA, INP, ISAE; UT1, UTM, LAAS, ITAV; Toulouse, France.
authors: Etienne
authors: E
authors: Dague
authors: INRA, EI-Purpan, UMR 1331 TOXALIM, Equipe de NeuroGastroentérologie et Nutrition, Toulouse, France; vtheodor@toulouse.inra.fr.
authors: Vassilia
authors: V
authors: Theodorou
authors: Université de Toulouse; INSA, UPS, INP; LISBP, Toulouse, France; INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, France; CNRS, UMR5504, Toulouse, France;
authors: Muriel
authors: M
authors: Mercier-Bonin
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D006031:Glycosylation; D020397:Goblet Cells / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D007778:Lactobacillus / Q000378:metabolism; D008297:Male; D055262:Mucin-2 / Q000096:biosynthesis*; D009093:Mucus / Q000378:metabolism; D010539:Permeability; D019936:Probiotics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D055262:Mucin-2; D003345:Corticosterone
keywords: L. farciminis; gut permeability; mucus layer; water avoidance stress