γ-Aminobutyric acid (GABA) activates neuronal cells by inducing the secretion of exosomes from intestinal cells

The oral administration of gamma-aminobutyric acid (GABA) has been shown to affect brain functions. However, the molecular mechanisms underlying GABA-induced gut-brain interactions have not yet been fully elucidated. As the blood-brain barrier is impermeable to GABA, we hypothesized that the gut-brain interaction might be stimulated by some secretory factors derived from the gut. Then we focused on exosomes as a secretory mediator. In the present study, we investigated whether exosomes derived from GABA-treated intestinal cells activate neuronal cells. Our results revealed that secretory factors derived from GABA-treated intestinal cells (Caco-2) activated neuronal cells (SH-SY5Y). Further investigation revealed that exosomes derived from GABA-treated Caco-2 cells were responsible for activating the SH-SY5Y cells. These results suggested that GABA-activated intestinal cells induce the secretion of exosomes that activate neuronal cells. MicroRNAs in the exosomes derived from GABA-treated intestinal cells may play a key role in the activation of neuronal cells.