Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis

Abstract

Neurotransmitters, including catecholamines and serotonin, play a crucial role in maintaining homeostasis in the human body. Studies on these neurotransmitters mainly revolved around their role in the "fight or flight" response, transmitting signals across a chemical synapse and modulating blood flow throughout the body. However, recent research has demonstrated that neurotransmitters can play a significant role in the gastrointestinal (GI) physiology. Norepinephrine (NE), epinephrine (E), dopamine (DA), and serotonin have recently been a topic of interest because of their roles in the gut physiology and their potential roles in GI and central nervous system pathophysiology. These neurotransmitters are able to regulate and control not only blood flow, but also affect gut motility, nutrient absorption, GI innate immune system, and the microbiome. Furthermore, in pathological states, such as inflammatory bowel disease (IBD) and Parkinson's disease, the levels of these neurotransmitters are dysregulated, therefore causing a variety of GI symptoms. Research in this field has shown that exogenous manipulation of catecholamine serum concentrations can help in decreasing symptomology and/or disease progression. In this review article, we discuss the current state-of-the-art research and literature regarding the role of neurotransmitters in regulation of normal GI physiology, their impact on several disease processes, and novel work focused on the use of exogenous hormones and/or psychotropic medications to improve disease symptomology. J. Cell. Physiol. 232: 2359-2372, 2017. © 2016 Wiley Periodicals, Inc.

Figure 1. Biochemical pathway for serotonin synthesis with inhibitors of serotonin receptors

Synthesis pathway for serotonin (5-hydroxytryptamine, 5-HT) is depicted here with enzymes responsible for each step as well as known inhibitors of these enzymes. Serotonin will then bind to one of seven 5-HT receptors (5-HT_1-7) at the nerve ending. A few known drug inhibitors of specific 5-HT receptors are also portrayed.

Figure 2. Biochemical pathway for catecholamine synthesis with inhibitors of different dopaminergic and adrenergic receptors

Synthesis pathway for catecholamines dopamine, norepinephrine, and epinephrine are depicted here with enzymes responsible for each step as well as known inhibitors of these enzymes. Dopamine will then bind to one of five dopaminergic receptors (D₁ to D₅) at the nerve ending. Norepinephrine and epinephrine will then bind one of four adrenergic receptors (α1, α2, β1, or β2). A few known drug inhibitors of some of these receptors are also portrayed.

Figure 3. Neurotransmitters affect microbiota in the gut

Neurotransmitters including serotonin alter the microbiota in the gut that can modulate the production of cytokines and bacterial byproducts leading to either heathy or diseased state.