Alleviation of DSS-induced colitis via bovine colostrum-derived extracellular vesicles with microRNA let-7a-5p is mediated by regulating Akkermansia and β-hydroxybutyrate in gut environments

Abstract

ABSTRACT Inflammatory bowel disease (IBD) is an inflammatory disease caused by the interaction of environmental and genetic factors, including diet and microbiota. Recent studies have suggested the effects of extracellular vesicles (EVs) on controlling host intestinal immune responses, although the specified mechanisms have not yet been fully elucidated. In the current study, we investigated the effects of EVs isolated from bovine colostrum on attenuating dextran sodium sulfate-induced colitis in mice. Multiomic approaches were used to assess host gene expression and gut microbiota profiles and to explain the roles of EVs in modulating the host immune system. Transcriptomic analyses suggested a possible immunoregulatory mechanism mediated by the cell cycle regulator CDK6 and pro-inflammatory responses. The gut microbiome composition and fecal metabolite profiles showed that EV supplementation promoted the microbial abundance of Akkermansia and short-chain fatty acid production in mice with colitis. Further in vivo analysis revealed that β-hydroxybutyrate and Akkermansia muciniphila, which are elevated by the administration with EVs, are involved in lessening colitis through modulating the immune system. Additionally, the bta-let-7a-5p, one of the most abundant microRNAs in bovine colostrum-derived EVs, alleviated the indications of colitis in mice by modulating their intestinal immunity and by regulating the cell cycle-related target gene Cdk6. Overall, these results suggest that bovine colostrum EVs and bta-let-7a-5p could be promising alternative strategies for preventing the onset of IBD. IMPORTANCE Even though studying on the possible involvement of extracellular vesicles (EVs) in host-microbe interactions, how these relationships mediate host physiology has not clarified yet. Our current findings provide insights into the encouraging benefits of dietary source-derived EVs and microRNAs (miRNAs) on organic acid production and ultimately stimulating gut microbiome for human health, suggesting that supplementation of dietary colostrum EVs and miRNAs is a novel preventive strategy for the treatment of inflammatory bowel disease.

Keywords

• bovine colostrum
• extracellular vesicles
• microbiome
• metabolome
• bta-let-7a-5p