Figure 1.

Neurotransmitter modulation by gut microbiota (schematic illustration). Bacterial metabolites, such as short-chain fatty acids (SCFAs), secondary bile acids, and indole, are able to stimulate the production of neurotransmitters, including glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT). They act through G-protein coupled receptors (GPCRs) FFAR2, FFAR3, and TGR5 that are coupled to different types of G proteins (G_αs, G_αq, and G_αi) and activate different pathways known to regulate gene expression and promote exocytosis by raising intracellular Ca²⁺ levels. SCFAs are recognized by FFAR2 and FFAR3. Enteroendocrine L-cells express both of these proteins, whereas enterochromaffin (EC) cells have been reported to express FFAR2. Bile acids are recognized by TGR5 receptors expressed in L-cells and EC cells. The sensing of indole remains elusive, although it is thought to act through GPCR. G_αs stimulates adenylate cyclase and elevates cyclic adenosine monophosphate (cAMP), which activates protein kinase A (PKA). G_αi inhibits the cAMP pathway. G_αq stimulates phospholipase C (PLC), resulting in the generation of diacylglycerol (DAG) and inositol triphosphate (IP₃), which activate protein kinase C (PKC) and induce intracellular Ca²⁺ release[23,138-140]. SCFA: Short-chain fatty acids; GLP-1: Glucagon-like peptide-1; PYY: Peptide YY.