Tryptophan metabolism and gut-brain homeostasis

William Roth, Kimia Zadeh, Rushi Vekariya, Yong Ge, Mansour Mohamadzadeh

Research output: Contribution to journalReview articlepeer-review

118 Scopus citations


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 neurotrans-mitter 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 kynure-nine 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.

Original languageEnglish (US)
Article number2973
Pages (from-to)1-23
Number of pages23
JournalInternational journal of molecular sciences
Issue number6
StatePublished - Mar 2 2021
Externally publishedYes


  • Anxiety
  • Cerebrovascular disease
  • Depression
  • Gut microbiota
  • Inflammation
  • Inflammatory bowel disease
  • Kynurenic acid
  • Kynurenine
  • Quinolinic acid
  • Serotonin
  • Tryptophan

ASJC Scopus subject areas

  • Molecular Biology
  • Spectroscopy
  • Catalysis
  • Inorganic Chemistry
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry


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