Genetics and Pharmacogenetics of Aminergic Transmitter Pathways in Functional Gastrointestinal Disorders

Abstract

Functional gastrointestinal disorders (FGIDs) are highly prevalent syndromes, without evident underlying organic causes. Their pathogenesis is multifactorial in nature, with a combination of environmental and genetic factors contributing to their clinical manifestations, for which most of current treatments are not satisfactory. It is acknowledged that amine mediators (noradrenaline, dopamine and serotonin) play pivotal regulatory actions on gut functions and visceral sensation. In addition, drugs of therapeutic interest for FGIDs act on these transmitter pathways. The present article reviews current knowledge on the impact of genetics and pharmacogenetics of aminergic pathways on FGID pathophysiology, clinical presentations, symptom severity and medical management, in an attempt of highlighting the most relevant evidence and point out issues that should be addressed in future investigations.

SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization

“…Not only the classical neurotransmitters, but TAs as well can exert pronounced pharmacological effects in many species; they can affect uptake or release of catecholamines or serotonin activity at nerve endings (Raiteri et al, 1977), and they might also act as neuromodulators through direct actions on receptors for catecholamines or serotonin (Jones, 1982;Paterson and Boulton, 1988). TAs are attracting attention as neurotransmitters because they are believed to play a role in human disorders (Branchek and Blackburn, 2003;Martinucci et al, 2015).…”

Visceral sensitivity modulation by faecal microbiota transplantation: the active role of gut bacteria in pain persistence

“…83,94 Physiological studies suggest that dopaminergic mechanisms are important in the regulation of gastrointestinal motility, 87,89 directly or after its metabolism to noradrenaline. 48,63,67 The gut levels of dopamine were reduced also in DNBS donors, which reported alterations in the gastrointestinal motility. 2 Further study needs to evaluate the impact of dopamine reduction in the gut of animals receiving the FMT.…”

Salsolinol: an Unintelligible and Double-Faced Molecule—Lessons Learned from In Vivo and In Vitro Experiments

“…The same should apply for the peripheral tissues, therefore boosting further advances in this field. Because the enteric nervous system and gut microbiota are the major sources of serotonin and dopamine in the human body (Martinucci et al 2015 ), the results might be of clinical relevance not only in terms of prodromal Parkinson’s disease but also gastrointestinal and gut-brain axis disorders.…”