A research team from OUC’s College of Food Science and Engineering, led by Professor YI Huaxi, and a research team from the National University of Singapore led by Professor Jiong-Wei Wang, have jointly made new progress in improving intestinal inflammation and non-alcoholic fatty liver disease (NAFLD) using milk-derived extracellular vesicles (mEVs). The findings were published in Science Advances under the title of Milk-derived Extracellular Vesicles Protect Intestinal Barrier Integrity in Gut-liver Axis”.

Maintaining the integrity of the gastrointestinal barrier is crucial for nutrient absorption and preventing harmful substances from entering the body's circulation. Gastrointestinal barrier dysfunction can cause leaky gut and increase the incidence of metabolic diseases such as inflammatory bowel disease and NAFLD/NASH. Therefore, maintaining gastrointestinal barrier integrity is an effective strategy for preventing and treating metabolic diseases. Extracellular vesicles (EVs) are nano-sized vesicles secreted by cells containing various immune-regulatory proteins and microRNAs, and they play an essential role in various physiological and metabolic processes. mEVs derived from breast milk and cow's milk can tolerate the digestive environment of the gastrointestinal tract, have good biocompatibility and low immunogenicity, and can regulate the gastrointestinal tract's function at various sites. Previous studies have shown that mEVs can not only enhance the intestinal immune environment and maintain the intestinal flora in healthy mice but can also repair the intestinal barrier dysfunction in malnourished mice. However, the role and mechanism of mEVs in the gastrointestinal tract and metabolic diseases remain uncertain.

This study isolated and purified mEVs from breast milk and cow's milk and analyzed miR-148a, which has potential anti-inflammatory activity and intestinal epithelial barrier protection functions, through RNA-seq sequencing and bioinformatics. In addition, the study evaluated the integrity and biological activity of mEVs after passing through the digestive tract in vitro and in vivo and found that mEVs could effectively resist gastrointestinal digestion and reach the colon smoothly, where they are taken up by colon epithelial and immune cells. Based on a mouse model of acute and chronic colitis induced by DSS, oral administration of mEVs protected the intestines from acute and chronic colitis induced by DSS and effectively repaired induced immune barrier, physical barrier, and mucosal barrier dysfunction. Additionally, by constructing a mouse model of NASH induced by MCD diet, the study further demonstrated the role of oral administration of mEVs in regulating liver disease through the gut-liver axis and intestinal barrier protection. mEVs were found to repair intestinal barrier integrity and reduce liver fat accumulation, inflammation, and fibrosis induced by MCD diet in NASH mice, effectively inhibiting liver disease via the gut-liver axis. This research clarifies the role of oral administration of mEVs in protecting gastrointestinal barrier integrity and confirms the potential preventive and therapeutic effects of mEVs in gastrointestinal- and liver axis-related diseases such as inflammatory bowel disease and NAFLD/NASH. It provides theoretical support for further research and development of special functional dietary supplements based on mEVs.