Dopaminergic signalling in gastrointestinal health and disease

Abstract

Enteric dopaminergic signalling has a critical role in gastrointestinal motility, maintaining mucosal integrity and modulating the gut microbiome. In this Review, we provide an overview of dopamine metabolism and signalling pathways in the central nervous system and periphery and their effects on gastrointestinal health and disease. We describe the physiological role of enteric dopamine, including a discussion of therapeutic opportunities and future research needs. With rising interest in the gut-first hypothesis of Parkinson disease, an area of great interest is how dopaminergic depletion in the gut could indicate future neurological dysfunction. In addition, dopamine signalling has been found to influence microbiome colonization resistance against enteric pathogens and immunoregulation. Emerging data on the effect of dopamine replacement therapy on gastrointestinal symptoms, across a range of conditions from neurodegenerative disease to inflammatory bowel disease, are also explored. In this Review, Pasricha and Kulkarni describe the role of dopaminergic signalling pathways in the central nervous system and periphery, and their role in gastrointestinal health and disease. In addition, they discuss emerging evidence and future directions.