Effects of Milk-Derived Extracellular Vesicles on the Colonic Transcriptome and Proteome in Murine Model

Abstract

Evidence shows that effective nutritional intervention can prevent or mitigate the risk and morbidity of inflammatory bowel disease (IBD). Bovine milk extracellular vesicles (mEVs), a major bioactive constituent of milk, play an important role in maintaining intestinal health. The aims of this study were to assess the effects of mEV pre-supplementation on the colonic transcriptome and proteome in dextran sulphate sodium (DSS)-induced acute colitis, in order to understand the underlying molecular mechanisms of mEV protection against acute colitis. Our results revealed that dietary mEV supplementation alleviated the severity of acute colitis, as evidenced by the reduced disease activity index scores, histological damage, and infiltration of inflammatory cells. In addition, transcriptome profiling analysis found that oral mEVs significantly reduced the expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-17A and IL-33), chemokine ligands (CXCL1, CXCL2, CXCL3, CXCL5, CCL3 and CCL11) and chemokine receptors (CXCR2 and CCR3). Moreover, oral mEVs up-regulated 109 proteins and down-regulated 150 proteins in the DSS-induced murine model, which were involved in modulating amino acid metabolism and lipid metabolism. Collectively, this study might provide new insights for identifying potential targets for the therapeutic effects of mEVs on colitis.

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

“…1B) in DSS-induced colitis. 21 Histological analysis found that mEVs significantly decreased the infiltration of inflammatory cells, mucosal injury, and overall histology score 21 (Fig. 1C and D).…”

“…Isolation of bovine mEVs was carried out as previously described. 21 All centrifugation was performed at 4 °C. Whole milk samples were centrifuged at 3000 g for 30 min and subsequently at 12 000 g for 60 min to remove fat globules, casein aggregates, and residual chymosin.…”

“…The particle size and concentration were measured by nanoparticle tracking analysis (NTA) with ZetaView PMX 110 and ZetaView v8.04.02 SP2 software (Particle Metrix, Meerbusch, Germany). The results of WB, TEM, and NTA 21 are presented in Fig. S1 †.…”

Extracellular Vesicles from Animal Milk: Great Potentialities and Critical Issues

“…Furthermore, the EVs effectively upregulated the expression of anti-inflammatory genes and downregulated the expression of proinflammatory genes on a total of 1659 down-regulated and 1981 up-regulated genes, including 82 long noncoding RNAs and 6 circRNAs with regulatory functions 0/0/0000 0:00:00 AM. A similar transcriptome and proteome profiling analysis revealed a significantly reduced expression of proinflammatory cytokines (IL-1β, IL-6, IL-17A, and IL-33), chemokine ligands (CXCL1, CXCL2, CXCL3, CXCL5, CCL3, and CCL11), and chemokine receptors (CXCR2 and CCR3), as well as 109 upregulated and 150 downregulated proteins involved in modulating amino acid metabolism and lipid metabolism [ 170 ].…”

Plasma proteome responses in zebrafish following λ-carrageenan-Induced inflammation are mediated by PMN leukocytes and correlate highly with their human counterparts

“…The first challenge to overcome is the selection of appropriate animal models to achieve the desired goal. Vertebrate animal models have proven their efficacy in screening inflammatory responses and determining specific molecular therapeutic targets in human medicine ( 23 – 25 ). In this context, zebrafish (ZF) emerged as an outstanding genetically tractable and practical model for screening the biological process of inflammation in vivo ( 26 , 27 ).…”