Dietary intervention with serum-derived bovine immunoglobulins protects barrier function in a mouse model of colitis

• Published in: American journal of physiology: Gastrointestinal and liver physiology 2015-06, Vol.308 (12), p.G1012-G1018
• Main Authors: Pérez-Bosque, Anna, Miró, Lluïsa, Maijó, Mònica, Polo, Javier, Campbell, Joy, Russell, Louis, Crenshaw, Joe, Weaver, Eric, Moretó, Miquel
• Format: Article
• Language: English
• Subjects: Animals; Biosynthesis; Cadherins - metabolism; Cattle; Colitis - drug therapy; Colitis - immunology; Colitis - prevention & control; Dietary Supplements; Disease Models, Animal; Gene expression; Immunoglobulins; Immunoglobulins - immunology; Immunoglobulins - therapeutic use; Inflammatory bowel disease; Mice, Knockout; Protective Agents - pharmacology; Real-Time Polymerase Chain Reaction - methods; RNA-protein interactions; Rodents; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00378.2014

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.