title: Dietary intervention with serum-derived bovine immunoglobulins protects barrier function in a mouse model of colitis.
abstract: Dietary supplementation with immunoglobulins from animal plasma has anti-inflammatory effects on intestinal and lung models of acute inflammation. Here, we aimed to establish whether dietary intervention with serum-derived bovine immunoglobulin (SBI) can prevent alterations in intestinal barrier function in a mouse model with a genetic predisposition to inflammatory bowel disease (IBD). Wild-type (WT) mice and mice lacking the mdr1a gene (KO) were fed diets supplemented with either SBI (2% wt/wt) or milk proteins (control diet), from day 21 (weaning) until day 56. The epithelial permeability of distal colon crypts was measured by confocal microscopy using a fluorescent marker. The expression of junctional epithelial E-cadherin and β-catenin proteins were determined by Western blot and zonula occludens-1 (ZO-1) by immunofluorescence. Mucins (MUC1, MUC2, MUC4), TFF3, cytokines (TNF-α, IFN-γ), and inducible nitric oxide synthase RNA expression were quantified by real-time PCR. SBI blocked the increase in colon crypt permeability and partially prevented the reduction in E-cadherin and ZO-1 expression that characterize the KO mouse model (both P < 0.05). SBI inclusion also reduced the mucosal expression of the inflammatory markers TNF-α, IFN-γ, and inducible nitric oxide synthase (all P < 0.005). The number of goblet cells in the colon of KO mice was low and correlated well with MUC2 and TFF3 expression (P < 0.001), whereas dietary supplementation with SBI attenuated these effects (all P < 0.05). In short, dietary SBI ameliorated colonic barrier alterations and reduced the expression of mucosal inflammatory markers in a genetic model of IBD.
authors.forename: Anna
authors.initials: A
authors.lastname: Pérez-Bosque
authors.forename: Lluïsa
authors.initials: L
authors.lastname: Miró
authors.forename: Mònica
authors.initials: M
authors.lastname: Maijó
authors.forename: Javier
authors.initials: J
authors.lastname: Polo
authors.forename: Joy
authors.initials: J
authors.lastname: Campbell
authors.forename: Louis
authors.initials: L
authors.lastname: Russell
authors.forename: Joe
authors.initials: J
authors.lastname: Crenshaw
authors.forename: Eric
authors.initials: E
authors.lastname: Weaver
authors.forename: Miquel
authors.initials: M
authors.lastname: Moretó
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002417:Cattle; D003092:Colitis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D007136:Immunoglobulins / Q000276:immunology* / Q000627:therapeutic use; D018345:Mice, Knockout; D020011:Protective Agents / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015820:Cadherins; D007136:Immunoglobulins; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha