Fig. 1

Schematic presentation of EV derived miRNA acting as a novel regulatory system for bi-directional communication in gut-brain-microbiota axis. A proposed regulatory system consisting of extracellular vesicles (EVs) derived from the brain, gut and gut microbiota which modulate bi-directional communication in gut-brain-microbiota axis (GBMAx) via intercellular transfer of microRNAs (miRNAs). Brain-derived EVs may modulate the gut and gut microiota via a “top-down” manner by migrating from brain to gut and regulating the expression of gut miRNAs and fecal miRNAs. Fecal miRNAs entrapped within EVs can enter bacteria and shape gut microbiota via targeting bacterial nucleic acid sequences. Alternatively, or in parallel, microbiota derived-EVs (bacterial membrane vesicles) may modulate the brain via a “bottom-up” manner by crossing the blood brain barrier and exerting a direct effect on the central nervous system. Microbiota derived-EVs can also potentially modulate gut barrier function and the immune response directly