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

Ying-Ao Xie, Jian-Da Kong, Shuai Li, Dian-Fang Wei

Alpha Psychiatry - 2025;26(6):1-18

Withthedevelopmentofthebrain-gutaxis(GBA),thebidirectionalcommunicationbetweengutmicrobiotaandthebrainhasbecomecriticalinemotionregulationresearch,anddopamineD2receptorsandgutmicrobiotaplaykeyrolesinthisprocess,especiallyinneurologicalandpsychiatricdisorders.ThisnarrativereviewexplorestheimpactofdopamineD2receptorsintheGBA,focusingonhowgutmicrobiotamodulatesemotionandbehaviorviaD2receptors,analyzestheirimbalancecorrelation,andlooksforwardtoD2receptor-basedtherapies.ComprehensivesearcheswereconductedinPubMed,WebofScience,andGoogleScholar(2000-2025)usingkeywordslikedopamineD2receptor,brain-gutaxis,ande­motion­disorders,includinganimalandclinicalstudies.ResearchshowsgutmicrobiotaaffectsdopaminesystemactivityandD2receptorfunctionmainlyviametabolites,especiallyshort-chainfattyacids(SCFAs,suchasbutyricacidandpropionicacid).SCFAscrosstheblood-brainbarrier,bindtoGprotein-coupledreceptors(GPCRs)to­regulatedopaminesynthesis/release,enhancebrainimmunefunctionbyimprovingastrocyteactivityandblood-brainbarrierintegrity,andthuspromotedD2receptorsignaltransduction.GutmicrobiotaalsoindirectlyinfluencesD2receptorexpression/activitybyregulatingdopamineprecursor(suchastyrosine)metabolism.GutmicrobiotaimbalanceiscloselyassociatedwithD2receptordysfunction.Indepression,anxiety,schizophrenia,andParkinson'sdisease,D2receptorfunctionisreducedorabnormallyactivated;gutdysbiosis(suchasalteredFirmicutes/Bacteroidetesratio,increasedProteobacteria/Escherichiacoli)disruptsgutm­etabolites(suchasreducedSCFAs),aggravatessystemicinflammation,andimpairsthedopaminesystem.Overall,gutmicrobiotamodulatesD2receptoractivitythroughmultiplemechanisms,exertinganimportantroleinregulatingemotionandbehavior.