Shedding of microbial extracellular vesicles constitutes a universal mechanism for inter-kingdom and intra-kingdom communication that is conserved among prokaryotic and eukaryotic microbes. Here, researchers from MD Anderson Cancer Center delineate fundamental aspects of bacterial extracellular vesicles (BEVs) including their biogenesis, cargo composition, and interactions with host cells. They critically examine the evidence that BEVs from the host gut microbiome can enter the circulatory system to disseminate to distant organs and tissues. The potential involvement of BEVs in carcinogenesis is evaluated and future research ideas explored. The researchers further discuss the potential of BEVs in microbiome-based liquid biopsies for cancer diagnostics and bioengineering strategies for cancer therapy.
Bacterial extracellular vesicles (BEVs) in the gut lumen can gain access to the systemic blood circulation
Microbial dysbiosis can lead to disruption of tight junctions in the luminal epithelium leading to passive paracellular transport of BEVs into the underlying submucosa, where BEVs can interact with resident immune cells or enter the circulatory system/portal vein and lymphatics (via trans-endothelial migration) for systemic dissemination. Active transcytosis through an intact gut luminal epithelium during steady state is thought to result in a smaller number of BEVs escaping to the submucosal compartment with subsequent blood-borne dissemination.