Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling

Abstract

Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vital functions such as cognition, reward, satiety, voluntary motor movements, pleasure, and motivation. Optimal dopamine bioavailability is essential for normal brain functioning and protection against the development of neurological diseases. Emerging evidence shows that gut microbiota have significant roles in maintaining adequate concentrations of dopamine via intricate, bidirectional communication known as the microbiota-gut-brain axis. The vagus nerve, immune system, hypothalamus–pituitary–adrenal axis, and microbial metabolites serve as important mediators of the reciprocal microbiota-gut-brain signaling. Furthermore, gut microbiota contain intrinsic enzymatic activity that is highly involved in dopamine metabolism, facilitating dopamine synthesis as well as its metabolite breakdown. This review examines the relationship between key genera of gut microbiota such as Prevotella, Bacteroides, Lactobacillus, Bifidobacterium, Clostridium, Enterococcus, and Ruminococcus and their effects on dopamine. The effects of gut dysbiosis on dopamine bioavailability and the subsequent impact on dopamine-related pathological conditions such as Parkinson’s disease are also discussed. Understanding the role of gut microbiota in modulating dopamine activity and bioavailability both in the periphery and in the central nervous system can help identify new therapeutic targets as well as optimize available methods to prevent, delay, or restore dopaminergic deficits in neurologic and metabolic disorders.

Gut Microbiota: A Novel Therapeutic Target for Parkinson’s Disease

“…Dopamine, a major neurotransmitter, plays a critical role in vital functions such as cognition, motivation, and voluntary motor movements both peripherally and centrally. Optimal dopamine bioavailability is essential for normal brain functioning and protection against the development of neurological diseases (142). Levodopa is widely used in the treatment of PD, which can cross the blood-brain barrier and can be transformed into dopamine in the brain, thereby alleviating the symptoms of PD (143).…”

“…The gut microbes belonging to the genera of Bacteroides, Prevotella, Bifidobacterium, Lactobacillus, Enterococcus, Clostridium, and Ruminococcus can regulate dopaminergic activity (142). van Kessel et al also demonstrated that the TDC genes (tdc) can be found in more than 50 Enterococcus strains (mainly E. faecalis and E. faecium) and several Staphylococcus and Lactobacillus species, while lower plasma levels of levodopa in rats treated with levodopa/carbidopa correlated with the level of bacterial tdc in the jejunum (147).…”

Impact of Nutrition, Microbiota Transplant and Weight Loss Surgery on Dopaminergic Alterations in Parkinson’s Disease and Obesity

“…RYGB surgery also increases levels of ghrelin and GLP-1, which have been positively associated with obesity, dietary interventions, and dopamine production [ 182 ]. The specific mechanisms on how the complex microbiota and/or the abundance or absence of single bacterial strains impact the dopaminergic system in the gut and the brain have been recently reviewed elsewhere [ 14 ].…”

“…The dopaminergic system, in particular, plays a significant role in regulating satiety, food-seeking behaviors, and the motivational drive to eat [ 25 , 26 ]. It is also known that gut microbiota plays significant roles in modulating processes that influence dopamine bioavailability via gut-brain signaling [ 14 ]. Different dietary patterns, such as increased intake of animal meat or protein and plant-based carbohydrates, influence the composition of gut microbiota.…”

“…The protective effect of the Mediterranean diet is attributed, in part, to increased diversity and favorable enterotypes of gut microbiota, such as a decrease in the Firmicutes/Bacteroidetes ratio, which has been associated with many disease states when elevated [ 12 , 13 ]. Additionally, certain gut microbial species are associated with neurotransmitter availability and can exert neuroprotective effects against PD or exacerbate its pathophysiology [ 14 ]. These complex processes are regulated by crosstalk between the gut and the brain via the so-called microbiota–gut–brain axis.…”