Discovery and Characterization of Gut Microbiota Decarboxylases that Can Produce the Neurotransmitter Tryptamine

Abstract

Summary 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 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 demonstrates 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.

Trace Amines and Their Receptors

“…Prokaryotes contain a large array of decarboxylase enzymes, many of which include L-amino acids in their substrate profile (Zheng et al, 2011;Nelson et al, 2015). Indeed, the production of PEA, TYR, and TRP by commensal prokaryotes has been established (Marcobal et al, 2006;Irsfeld et al, 2013;Williams et al, 2014;Yang et al, 2015a), and bacterial production of these compounds was the original basis of Nencki's studies on putrefaction and fermentation (see Grandy, 2007). With TAARs established to be present throughout the body, it is expected that the role of trace amines and their receptors in mediating host-microbiota interactions will become a growing area of interest.…”

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

“…In fact, an unbalanced diet that is poor in dietary fiber content (and thus does not require complex metabolic interactions between the microbial members) would result in lower microbial diversity and in the imbalanced host-microbial relationship that is observed in the emerging Western lifestyle-associated human diseases. 80 In a recent attempt to unravel which bacterial metabolites can bring about the host-microbial balance, Williams et al 81 used a combination of genetics and biochemistry to identify a key microbial enzyme that converts dietary tryptophan to the neuropeptide tryptamine (ie, tryptophan decarboxylase enzyme, which was found to be present in several bacteria that colonize 10% of the human population). This finding suggests that the gut microbiota can sequester tryptophan from the diet and alter its metabolites in the host, eventually resulting in altered brain levels of the neuropeptide serotonin, which ultimately affects brain function.…”

Biological underpinnings of psychogenic nonepileptic seizures: directions for future research

“…In a recent study, researchers using a combination of genetics, biochemistry, and crystallography identified and characterized two phylogenetically distinct enzymes in the human microbiome that decarboxylate tryptophan to form the b-arylamine neurotransmitter tryptamine. Their results uncovered previously unrecognized enzymatic activity that can give rise to host-modulatory compounds and showed how gut microbiota can influence host physiology, including behavior [47].…”