FIGURE 5.

Mechanisms that mediate translocation of microbiota‐derived BEVs across the intestinal epithelium. The processes are numbered and indicated in red. BEVs released by gut microbes are taken up by intestinal epithelial cells (IECs) via endocytosis (1). Internalized BEVs can reach the basolateral membrane of IECs and be translocated into the lamina propria by transcytosis (2). In addition, the paracellular route (3) also allows passage of luminal BEVs to the underlying submucosa. This route is favoured under conditions of gut dysbiosis. Once in the lamina propria, translocated BEVs directly interact with resident gut immune cells, triggering suitable immune responses. Direct sampling and phagocytosis of luminal BEVs by DCs also mediate passage of luminal BEVs into the internal milieu (4). There is evidence that BEVs cross endothelial barriers and reach blood vessels, thus being distributed to distal organs