title: Delivery of a mucin domain enriched in cysteine residues strengthens the intestinal mucous barrier.
abstract: A weakening of the gut mucous barrier permits an increase in the access of intestinal luminal contents to the epithelial cells, which will trigger the inflammatory response. In inflammatory bowel diseases, there is an inappropriate and ongoing activation of the immune system, possibly because the intestinal mucus is less protective against the endogenous microflora. General strategies aimed at improving the protection of the intestinal epithelium are still missing. We generated a transgenic mouse that secreted a molecule consisting of 12 consecutive copies of a mucin domain into its intestinal mucus, which is believed to modify the mucus layer by establishing reversible interactions. We showed that the mucus gel was more robust and that mucin O-glycosylation was altered. Notably, the gut epithelium of transgenic mice housed a greater abundance of beneficial Lactobacillus spp. These modifications were associated with a reduced susceptibility of transgenic mice to chemically induced colitis. Furthermore, transgenic mice cleared faster Citrobacter rodentium bacteria which were orally given and mice were more protected against bacterial translocation induced by gavage with adherent-invasive Escherichia coli. Our data show that delivering the mucin CYS domain into the gut lumen strengthens the intestinal mucus blanket which is impaired in inflammatory bowel diseases.
authors.affiliation: 1] LIRIC - UMR 995 Inserm; Université de Lille, Lille, France [2] CHRU de Lille, Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Gouyer
authors.affiliation: LIRIC - UMR 995 Inserm; Université de Lille, Lille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Dubuquoy
authors.affiliation: CNRS, UMR 8576; Université de Lille, Villeneuve d'Ascq, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Robbe-Masselot
authors.affiliation: LIRIC - UMR 995 Inserm; Université de Lille, Lille, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Neut
authors.affiliation: LIRIC - UMR 995 Inserm; Université de Lille, Lille, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Singer
authors.affiliation: LIRIC - UMR 995 Inserm; Université de Lille, Lille, France.
authors.forename: Ségolène
authors.initials: S
authors.lastname: Plet
authors.affiliation: Department of Pathology, UZ Gent, De Pintelaan, 185, 9000 Gent, Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.affiliation: 1] LIRIC - UMR 995 Inserm; Université de Lille, Lille, France [2] CHRU de Lille, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
authors.affiliation: 1] LIRIC - UMR 995 Inserm; Université de Lille, Lille, France [2] CHRU de Lille, Lille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gottrand
authors.affiliation: LIRIC - UMR 995 Inserm; Université de Lille, Lille, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Desseyn
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium / Q000276:immunology; D003545:Cysteine / Q000737:chemistry; D004847:Epithelial Cells; D004926:Escherichia coli / Q000276:immunology; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D006031:Glycosylation; D020397:Goblet Cells; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D007422:Intestines / Q000382:microbiology; D007778:Lactobacillus / Q000302:isolation & purification; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008863:Microspheres; D018396:Mucin-1 / Q000378:metabolism; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism*; D055263:Mucin-3 / Q000378:metabolism; D055272:Mucin-6 / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D019108:Tight Junctions / Q000502:physiology*
chemical_list: C524626:Muc2 protein, mouse; C524641:Muc3 protein, mouse; C524735:Muc6 protein, mouse; D018396:Mucin-1; D055262:Mucin-2; D055263:Mucin-3; D055272:Mucin-6; C577056:muc1 protein, mouse; D003545:Cysteine