Tryptophan Metabolism and the Microbiome-Gut-Brain Axis

Abstract The capacity of the gut microbiome to influence communication along the gut-brain axis relies in part on the microbial influence on neurotransmitter systems. Recent years have seen increasing surveillance of tryptophan in this regard, an essential amino acid and building block for a number of host-produced and microbial-derived bioactives. An appreciation of the important role for tryptophan in supporting microbiome-gut-brain axis signaling requires a reframing of what is currently known about this important precursor to integrate with newer concepts around the gut microbiota. The fate, distribution, metabolism, absorption, and distal availability of tryptophan for these pathways following dietary consumption is heavily influenced by the action of the gastrointestinal microbiota. This in turn has implications for local gastrointestinal enteric circuits and the neurobiology of a range of central nervous system and gastrointestinal disorders in which compositional and functional microbiota alterations have now been reported. Further research is required to bridge the knowledge gaps surrounding microbial regulation of tryptophan metabolism and availability. Mechanistic advances in our understanding of these important aspects of host–microbe dialogue offer the possibility of therapeutic targeting of the gut microbiome to fine-tune tryptophan metabolism in multiple pathways that contribute to symptom expression in disorders associated with the microbiome-gut-brain axis.