Tryptophan Metabolism and Gut-Brain Homeostasis

Abstract

Tryptophan is an essential amino acid critical for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only precursor for the neurotransmitter serotonin, which is vital for the processing of emotional regulation, hunger, sleep, and pain, as well as colonic motility and secretory activity in the gut. Tryptophan catabolites from the kynurenine degradation pathway also modulate neural activity and are active in the systemic inflammatory cascade. Additionally, tryptophan and its metabolites support the development of the central and enteric nervous systems. Accordingly, dysregulation of tryptophan metabolites plays a central role in the pathogenesis of many neurologic and psychiatric disorders. Gut microbes influence tryptophan metabolism directly and indirectly, with corresponding changes in behavior and cognition. The gut microbiome has thus garnered much attention as a therapeutic target for both neurologic and psychiatric disorders where tryptophan and its metabolites play a prominent role. In this review, we will touch upon some of these features and their involvement in health and disease.

Do Gut Microbes Taste?

“…For example, tryptophan undergoing microbial degradation is taken up by serotonergic neurons and glia and convert it to serotonin, a neurotransmitter that processes high order brain functions such as emotion, learning and memory. Compelling evidence also demonstrate the influence of gut microbes and tryptophan metabolites in the development of several neurological disorders such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis and indole derivatives have been used for neuroprotection [ 48 ]. Together, these studies show how gut bacteria can control maturation and function of CNS specialized cells through SCFA, vagal transit and metabolite production that cross the blood–brain barrier.…”

Serotonin Pathway of Tryptophan Metabolism in Small Intestinal Bacterial Overgrowth—A Pilot Study with Patients Diagnosed with Lactulose Hydrogen Breath Test and Treated with Rifaximin

“…Small intestine bacterial overgrowth presents a problem in the gastrointestinal clinic, as there are not a consensus concerning the definition of SIBO and so its diagnostic criteria as well as therapeutic procedures. Tryptophan metabolism is involved in the pathogenesis of several gastrointestinal disorders, but little is known on Trp role in SIBO etiology [ 12 , 13 , 14 ]. Moreover, nutritional implications of SIBO are not completely known [ 8 ].…”

“…Tryptophan (Trp), an essential exogenous amino acid in humans, plays an important role in the GI tract homeostasis and disturbances in its metabolism are associated with intestinal diseases [ 12 ]. The vast majority of Trp is absorbed in the small intestine and the rest of it may be a metabolic substrate for colonic microbes so potential association of Trp metabolism with SIBO pathogenesis is rational (reviewed in [ 13 ]). Tryptophan metabolism in hosts proceeds via the kynurenine pathway or serotonin pathway to yield active metabolites.…”

“…Tryptophan metabolism in hosts proceeds via the kynurenine pathway or serotonin pathway to yield active metabolites. In gut microbes Trp is metabolized in the indole pathway (reviewed in [ 13 ]). Microbial Trp catabolites resulting from proteolysis influence host health (reviewed in [ 14 ]).…”

The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine

“…Trp is one of nine nutritionally essential AAs [ 19 ]. In addition to its role as a substrate for protein synthesis, Trp is an important precursor for many compounds such as 5-HT, melatonin, and kynurenine [ 20 ]. Correspondingly, Trp and its metabolites play a key role in nutrition, reproduction, immune system, and anti-stress responses [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”