Milk Exosomes Prevent Intestinal Inflammation in a Genetic Mouse Model of Ulcerative Colitis: A Pilot Experiment

Abstract

Background: Milk is rich in nutrients and anabolic mediators rendering it essential for postnatal growth and metabolic programming. However, in adults, excessive consumption of milk is controversial as civilization disorders such as diabetes or prostate cancer may be promoted. A cytoprotective effect of milk could be utilized in inflammatory conditions, that is, chronic colitis. Objective: To evaluate the effect of bovine milk exosomes on intestinal inflammation in a genetic mouse model of ulcerative colitis. Methods: Intestinal-specific kindlin 2 knockout (KO) mice were exposed for 4 days to tamoxifen for induction of an ulcerative colitis phenotype. At the same time 4 other kindlin 2 KO mice were exposed to 33 μg/g cow milk derived exosomes in PBS by oral gavage. Both groups were compared to untreated wild-type controls. Results: Milk exosomes prevented the appearance of a severe ulcerative phenotype. The macroscopic colitis score dropped from a mean of 3.33 in untreated mice to 0.75 index points (p < 0.01) in exosome-treated mice, which included significant improvement of the subscores of stool improvement and colon weight and length. Treated mice featured a noninflamed appearance of the intestinal mucosa. Key Message: Milk exosomes have cytoprotective/anti-inflammatory activity in a genetic mouse model of ulcerative colitis. The mechanisms behind this need to be elucidated. This pilot study needs verification before a therapeutic strategy is developed.