Blueberry-derived exosome like nanovesicles carry RNA cargo into HIEC-6 cells and down-regulate LPS-induced inflammatory gene expression: A proof-of-concept study

Exosome-like nanovesicles (ELNs) of food origin have received great attention in the last decade, due to the hypothesis that they contain bioactive molecules. ELNs purified from edible species have been shown to be protective and are able to regulate intestinal homeostasis. Despite ELNs being potential rising stars in modern healthy diets and biomedical applications, further research is needed to address underlying knowledge gaps, especially related to the specific molecular mechanism through which they exert their action. Here, we investigate the cellular uptake of blueberry-derived ELNs (B-ELNs) using a human stabilized intestinal cell line (HIEC-6) and assess the ability of B-ELNs to modulate the expression of inflammatory genes in response to lipopolysaccharide (LPS). Our findings show that B-ELNs are internalized by HIEC-6 cells and transport labeled RNA cargo into them. Pretreatment with B-ELNs reduces LPS-induced ROS generation and cell viability loss, while modulating the expression of 28 inflammatory genes compared to control. Pathway analysis demonstrates their ability to suppress inflammatory responses triggered by LPS. In conclusion, our data indicate that B-ELNs are up taken by HIEC-6 cells and can modulate inflammatory responses after LPS stimulation, suggesting a therapeutic potential. This study demonstrates the role of B-ELNs in regulating crucial biological processes, like anti-inflammatory responses, which could support intestinal health.