The bidirectional pathways of the microbiota–gut–brain axis (MGBA) involving the microbiota, the intestine, and the brain. Intestinal dysbiosis and derived metabolites in neuropathological conditions induce the barrier permeability defects and local inflammation with increased pro-inflammatory cytokines, MAMPs (e.g., LPS), and activation of immune cells in the gastrointestinal tract. These signaling mediators as well as microbial metabolites (e.g., SCFAs and Trp derivatives) and hormones (e.g., GLP-1, PYY) can distantly affect the brain function via the humoral pathway. In addition, dysregulated regulation of the vagus nerve can also directly modulate the brain function. Together, these MGBA pathways culminate in regulating neuroinflammation and neuronal defects of the brain and behavioral abnormalities. Refer to the text for details. 5-HT; 5-hydroxyltryptamine; LPS, lipopolysaccharides; MAMPs, microbe-associated molecular patterns; SCFAs, short chain fatty acids; Trp; tryptophan.

Key advantages of the zebrafish model for studying the MGBA. Refer to the text for details.