title: Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis.
abstract: Elafin, a natural protease inhibitor expressed in healthy intestinal mucosa, has pleiotropic anti-inflammatory properties in vitro and in animal models. We found that mucosal expression of Elafin is diminished in patients with inflammatory bowel disease (IBD). This defect is associated with increased elastolytic activity (elastase-like proteolysis) in colon tissue. We engineered two food-grade strains of lactic acid bacteria (LAB) to express and deliver Elafin to the site of inflammation in the colon to assess the potential therapeutic benefits of the Elafin-expressing LAB. In mouse models of acute and chronic colitis, oral administration of Elafin-expressing LAB decreased elastolytic activity and inflammation and restored intestinal homeostasis. Furthermore, when cultures of human intestinal epithelial cells were treated with LAB secreting Elafin, the inflamed epithelium was protected from increased intestinal permeability and from the release of cytokines and chemokines, both of which are characteristic of intestinal dysfunction associated with IBD. Together, these results suggest that oral delivery of LAB secreting Elafin may be useful for treating IBD in humans.
authors.affiliation: INSERM, U1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse F-31300, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Motta
authors.forename: Luis G
authors.initials: LG
authors.lastname: Bermúdez-Humarán
authors.forename: Céline
authors.initials: C
authors.lastname: Deraison
authors.forename: Laurence
authors.initials: L
authors.lastname: Martin
authors.forename: Corinne
authors.initials: C
authors.lastname: Rolland
authors.forename: Perrine
authors.initials: P
authors.lastname: Rousset
authors.forename: Jérôme
authors.initials: J
authors.lastname: Boue
authors.forename: Gilles
authors.initials: G
authors.lastname: Dietrich
authors.forename: Kevin
authors.initials: K
authors.lastname: Chapman
authors.forename: Pascale
authors.initials: P
authors.lastname: Kharrat
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Vinel
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mas
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Sallenave
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000276:immunology* / Q000382:microbiology*; D053492:Elafin / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000517:prevention & control*; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D007413:Intestinal Mucosa; D051379:Mice
chemical_list: D053492:Elafin