What is the Impact of Dopamine D2 Receptor in the Brain-Gut Axis? A Narrative Review of the Mechanism Based on Gut Microbiota in Modulating Emotion and Behavior

With the development of the brain-gut axis (GBA), the bidirectional communication between gut microbiota and the brain has become critical in emotion regulation research, and dopamine D2 receptors and gut microbiota play key roles in this process, especially in neurological and psychiatric disorders. This narrative review explores the impact of dopamine D2 receptors in the GBA, focusing on how gut microbiota modulates emotion and behavior via D2 receptors, analyzes their imbalance correlation, and looks forward to D2 receptor-based therapies.Comprehensive searches were conducted in PubMed, Web of Science, and Google Scholar (2000-2025) using keywords like "dopamine D2 receptor", "brain-gut axis", and "emotional disorders", including animal and clinical studies. Research shows gut microbiota affects dopamine system activity and D2 receptor function mainly via metabolites, especially short-chain fatty acids (SCFAs, such as butyric acid and propionic acid). SCFAs cross the blood-brain barrier, bind to G protein-coupled receptors (GPCRs) to regulate dopamine synthesis/release, enhance brain immune function by improving astrocyte activity and blood-brain barrier integrity, and thus promote D2 receptor signal transduction. Gut microbiota also indirectly influences D2 receptor expression/activity by regulating dopamine precursor (such as tyrosine) metabolism. Gut microbiota imbalance is closely associated with D2 receptor dysfunction. In depression, anxiety, schizophrenia, and Parkinson's disease, D2 receptor function is reduced or abnormally activated; gut dysbiosis (such as <i>altered Firmicutes</i>/<i>Bacteroidetes ratio</i>, increased <i>Proteobacteria</i>/<i>Escherichia coli</i>) disrupts gut metabolites (such as reduced SCFAs), aggravates systemic inflammation, and impairs the dopamine system. Overall, gut microbiota modulates D2 receptor activity through multiple mechanisms, exerting an important role in regulating emotion and behavior.