Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

Abstract

The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis.

Keywords: gut-brain axis; mood and cognition; serotonin; tryptophan.

Figure 1

The brain-gut axis and the bi-directional system of communication. The brain-gut axis is a bi-directional system of communication between the brain and the gastrointestinal tract. This links emotional and cognitive centres of the brain with peripheral control and function of the gut and its resident microbiota. Serotonin is a key element of this axis, acting as a neurotransmitter in the CNS and in the enteric nervous system that is present in the wall of the gut. A. Neural communication between the gut and brain is via the vagus (stomach and rectum) and dorsal root ganglia (DRG-small and large intestine), via projections from the enteric nervous system to sympathetic ganglia and parasympathetic innervation of the gut. B. Humeral communication is via release of bacterial factors, production of cytokines and circulating hormones. An important advance for future studies will be testable models of a potential mechanism of action (e.g., cutting the vagus can block some effects of changing the gut microbiota in rodent models).