Bovine milk-derived extracellular vesicles prevent gut inflammation by regulating lipid and amino acid metabolism.

Inflammatory bowel disease (IBD) is a global health problem in which metabolite alteration plays an important pathogenic role. Bovine milk-derived extracellular vesicles (mEVs) have been shown to regulate nutrient metabolism in healthy animal models. This study investigated the effect of oral mEVs on metabolite changes in DSS-induced murine colitis. We performed metabolomic profiling on plasma samples and measured the concentrations of lipids and amino acids in both fecal samples and colonic tissues. Plasma metabolome analysis found that mEVs significantly upregulated 148 metabolite levels and downregulated 44 metabolite concentrations (VIP > 1, and p < 0.05). In the fecal samples, mEVs significantly increased the contents of acetate and butyrate and decreased the levels of tridecanoic acid (C13:0), methyl cis-10-pentadecenoate (C15:1) and cis-11-eicosenoic acid (C20:1). Moreover, the concentrations of eicosadienoic acid (C20:2), eicosapentaenoic acid (C20:5), and docosahexaenoic acid (C22:6) were decreased in colonic tissues with mEV supplementation. In addition, compared with the DSS group, mEVs significantly increased the content of L-arginine, decreased the level of L-valine in the fecal samples, and also decreased the levels of L-serine and L-glutamate in the colonic tissues. Collectively, our findings demonstrated that mEVs could recover the metabolic abnormalities caused by inflammation and provided novel insights into mEVs as a potential modulator for metabolites to prevent and treat IBD.

Supplementation with Milk-Derived Extracellular Vesicles Shapes the Gut Microbiota and Regulates the Transcriptomic Landscape in Experimental Colitis.

Harboring various proteins, lipids, and RNAs, the extracellular vesicles (EVs) in milk exert vital tissue-specific immune-protective functions in neonates via these bioactive cargos. This study aims to explore the anti-inflammatory effects of bovine milk-derived EVs on a dextran sulfate sodium (DSS)-induced colitis model and to determine the underlying molecular mechanisms. Sixty C57BL/6 mice were divided into the NC group (normal control), DSS group (DSS + PBS), DSS + LOW group (DSS + 1.5 × 108 p/g EVs), DSS + MID group (DSS + 1.5 × 109 p/g EVs), and DSS + HIG group (DSS + 1.0 × 1010 p/g EVs). Histopathological sections, the gut microbiota, and intestinal tissue RNA-Seq were used to comprehensively evaluate the beneficial functions in mitigating colitis. The morphology exhibited that the milk-derived EVs contributed to the integrity of the superficial epithelial structure in the intestine. Additionally, the concentrations of IL-6 and TNF-α in the colon tissues were significantly decreased in the EVs-treated mice. The abundances of the Dubosiella, Bifidobacterium, UCG-007, Lachnoclostridium, and Lachnospiraceae genera were increased in the gut after treatment with the milk-derived EVs. Additionally, the butyrate and acetate production were enriched in feces. In addition, 1659 genes were significantly down-regulated and 1981 genes were significantly up-regulated in the EVs-treated group. Meanwhile, 82 lncRNAs and 6 circRNAs were also differentially expressed. Overall, the milk-derived EVs could attenuate colitis through optimizing gut microbiota abundance and by manipulating intestinal gene expression, implying their application potential for colitis prevention.