Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain

Abstract

The gut-brain axis (GBA) is a bilateral communication network between the gastrointestinal (GI) tract and the central nervous system. The essential amino acid tryptophan contributes to the normal growth and health of both animals and humans and, importantly, exerts modulatory functions at multiple levels of the GBA. Tryptophan is the sole precursor of serotonin, which is a key monoamine neurotransmitter participating in the modulation of central neurotransmission and enteric physiological function. In addition, tryptophan can be metabolized into kynurenine, tryptamine, and indole, thereby modulating neuroendocrine and intestinal immune responses. The gut microbial influence on tryptophan metabolism emerges as an important driving force in modulating tryptophan metabolism. Here, we focus on the potential role of tryptophan metabolism in the modulation of brain function by the gut microbiota. We start by outlining existing knowledge on tryptophan metabolism, including serotonin synthesis and degradation pathways of the host, and summarize recent advances in demonstrating the influence of the gut microbiota on tryptophan metabolism. The latest evidence revealing those mechanisms by which the gut microbiota modulates tryptophan metabolism, with subsequent effects on brain function, is reviewed. Finally, the potential modulation of intestinal tryptophan metabolism as a therapeutic option for brain and GI functional disorders is also discussed.

Gut dysbiosis in Huntington’s disease: associations among gut microbiota, cognitive performance and clinical outcomes

“…These changes may be important, because methionine links to oxidative stress ( Campbell et al , 2016 ), and these pathways are related to glutamate release, tryptophan metabolism and synthesis of serotonin and melatonin production ( O'Mahony et al , 2015 ; Yu and Lau, 2018 ; Hoglund et al , 2019 ). The finding of differences in these pathways in our Huntington’s disease sample supports previous observations showing abnormal handling of tryptophan metabolism in Huntington’s disease, resulting in higher levels of oxidative stress, which may contribute to neuroinflammation and brain dysfunction, as well as depressive symptoms and memory difficulties ( Stoy et al , 2005 ; Mendelsohn et al , 2009 ; Bourassa et al , 2016 ; Kałużna-Czaplińska et al , 2019 ; Gao et al , 2020 ). Furthermore, at the enzyme level, significantly lower levels of glutathione transferase have been found in Parkinson’s disease and Alzheimer’s disease, and these changes are linked to increased oxidative stress and neuroinflammation ( Mazzetti et al , 2015 ).…”

Dynamics of Tryptophan Metabolic Pathways in Human Placenta and Placental-Derived Cells: Effect of Gestation Age and Trophoblast Differentiation

“…Recently, the importance of gut microbiome metabolism of TRP for gut–brain axis has been described ( Kaur et al, 2019 ; Gao et al, 2020 ). Similarly, placental metabolism of TRP might form a crucial component of the placenta–brain axis ( Rosenfeld, 2020a , b ).…”

The Urine Metabolome of Young Autistic Children Correlates with Their Clinical Profile Severity

“…Second, at least two major pathways of the tryptophan metabolism were perturbed in ASD children. On the one hand, the direct metabolism of tryptophan by gut microorganisms led to a significant increase in indole-3-acetic acid, with effects on gut permeability and host immunity [ 38 ]. On the other hand, perturbations in the kynurenine pathway were confirmed by an increase in quinolinic acid (+36%, p = n.s.)…”