Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine

Cell Host Microbe. 2014 Oct 8;16(4):495-503. doi: 10.1016/j.chom.2014.09.001. Epub 2014 Sep 25.


Several recent studies describe the influence of the gut microbiota on host brain and behavior. However, the mechanisms responsible for microbiota-nervous system interactions are largely unknown. Using a combination of genetics, biochemistry, and crystallography, we identify and characterize two phylogenetically distinct enzymes found in the human microbiome that decarboxylate tryptophan to form the β-arylamine neurotransmitter tryptamine. Although this enzymatic activity is exceedingly rare among bacteria more broadly, analysis of the Human Microbiome Project data demonstrate that at least 10% of the human population harbors at least one bacterium encoding a tryptophan decarboxylase in their gut community. Our results uncover a previously unrecognized enzymatic activity that can give rise to host-modulatory compounds and suggests a potential direct mechanism by which gut microbiota can influence host physiology, including behavior.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacteria / enzymology
  • Bacteria / genetics
  • Biotransformation
  • Carboxy-Lyases / chemistry
  • Carboxy-Lyases / genetics*
  • Carboxy-Lyases / metabolism
  • Crystallography, X-Ray
  • Gastrointestinal Tract / microbiology*
  • Humans
  • Metagenome*
  • Microbiota*
  • Models, Molecular
  • Molecular Sequence Data
  • Neurotransmitter Agents / metabolism*
  • Phylogeny
  • Protein Conformation
  • Sequence Homology
  • Tryptamines / metabolism*
  • Tryptophan / metabolism


  • Neurotransmitter Agents
  • Tryptamines
  • tryptamine
  • Tryptophan
  • Carboxy-Lyases

Associated data

  • PDB/4OBU
  • PDB/4OBV