Goat Milk-Derived Extracellular Vesicles Alleviate Colitis Potentially Through Improved Gut Microbiota in Mice

Ulcerative colitis (UC) is characterized clinically by intestinal inflammation and gut microbiota dysbiosis. The consumption of biologics, although effective in inflammation control, may lead to adverse effects and is inconvenient for at-home administration. Goat milk-derived extracellular vesicles (GMEVs) have been proposed as a supplement to prevent intestinal inflammation. However, their therapeutic potential for colitis remains elusive. This study aimed to explore the preventive effect of GMEVs on colitis and its underlying mechanisms through the microbiota-immune axis using a dextran sodium sulfate (DSS)-induced colitis mouse model. We found that a pre-treatment of 20 mg/kg/d GMEVs effectively prevented body weight loss, colon shortening, the depletion of colonic goblet cells, and the disappearance of crypts, while enhancing the intestinal mucosal barrier. Consistent with these phenotypes, GMEV pre-treatment increased levels of IL-22 and IL-10 and decreased levels of IL-1β, TNF-α, IL-6, and iNOS. However, GMEVs themselves had no effect on normal mice. Paralleling the alleviation of intestinal inflammation, GMEV pre-treatment also restored the reduction in <i>unclassified Muribaculaceae</i>, <i>Dubosiella</i>, and <i>Lactobacillus</i> and suppressed the expansion of <i>Alistipes</i> and <i>Proteobacteria</i> following DSS treatment. Additionally, GMEV intake significantly downregulated the expression of proteins in the NF-κB signaling pathway induced by DSS. In summary, GMEVs could prevent colitis by regulating intestinal inflammation, the intestinal mucosal barrier, gut microbiota, organ damage, and the immune microenvironment. This study demonstrated that GMEVs have potential application prospects for UC prevention.