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

By B. B. Williams, Andrew H. Van Benschoten, Peter Cimermancic, Mohamed S. Donia, Michael Zimmermann, Mao Taketani, A. Ishihara, P. Kashyap, James S. Fraser, Michael A. Fischbach. Cell Host and Microbe, 2014

609 citations recorded by the source corpus.

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.

Subfields: Biological Psychiatry, Molecular Biology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/f5d1434ff4ab50942a1915cbbde4eafad33bf534

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biological Psychiatry

1. S. Mazmanian

In Molecular Biology

1. Harry Sokol
2. Kyongbum Lee
3. A. Farzi
4. S. Mazmanian
5. J. Cryan
6. June L. Round

Citations in the corpus

• Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism (2018, background): “The common gut Firmicutes C. sporogenes and Ruminococcus gnavus are capable of decarboxylating Trp to tryptamine (Williams et al., 2014).”
• Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis (2015, positive): “HT in culture (Roshchina, 2010), but this is believed to occur independently of Tph, by decarboxylation of tryptophan to tryptamine (Williams et al., 2014), as seen in plants (Oleskin et al.”
• Tryptophan Metabolism: A Link Between the Gut Microbiota and Brain. (2019, background): “A previous study demonstrated that at least 10% of the human population harbors at least 1 bacterium encoding a TrpD in their gut community (40).”
• Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders (2021, background): “Tryptamine Tryptophan Staphylococcus [32] Ruminococcus gnavus [33] Clostridium sporogenes [33] Induce serotonin secretion by enterochromaffin cells [51] Promote gastrointestinal transit and colonic secretion [52]”
• Gut Microbiota-Derived Tryptophan Metabolites Modulate Inflammatory Response in Hepatocytes and Macrophages (2018, positive): “Enzymes for producing TA (Williams et al., 2014) and I3A (Sridharan et al., 2014) from tryptophan have been characterized in the gut microbiota, whereas such enzymes have not yet been identified for XA.”
• Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. (2018, positive): “Trp metabolizing pathways have been identified in some members of the human gut microbiota such as Clostridium sporogenes which is able to decarboxylate Trp leading to the production of the neurotransmitter tryptamine (Williams et al., 2014).”
• Control of Brain Development, Function, and Behavior by the Microbiome (2015, neutral): “sporogenes and Ruminococcus gnavus are capable of producing the neurotransmitter tryptamine through decarboxylation of tryptophan (Williams et al., 2014).”