Figure.

Bidirectional interactions between gut microbiota, gut permeability and central nervous system (CNS). Increased gut permeability can lead to translocation of gut microbiota or metabolic products such as lipopolysaccharides through the intestinal barrier. Exposure of epithelial cells or mucosal immune cells to bacterial or metabolic products can lead to activation of an immune response and release of pro-inflammatory cytokines. Additionally, metabolic products can directly affect the function of enteric neurons, spinal sensory neurons and vagus nerve through activation to Toll-like receptors or translocation and release of neuroactive peptides and hormones. On the other hand, stress can lead to activation of the hypothalamus-pituitary axis and excessive release of the corticotropin-releasing factor. This hormone along with altered vagal activity can modulate the local activation of mast cells in the intestinal wall and release of cytokines, causing increased gut permeability. ENS, enteric nervous system.