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

Autor: Williams BB; Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Van Benschoten AH; Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Cimermancic P; Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Donia MS; Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Zimmermann M; ETH Zurich, Institute of Molecular Systems Biology, Zurich 8093, Switzerland., Taketani M; Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Ishihara A; Faculty of Agriculture, Tottori University, Koyama, Tottori 680-8550, Japan., Kashyap PC; Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA., Fraser JS; Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA., Fischbach MA; Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: fischbach@fischbachgroup.org.
Jazyk: angličtina
Zdroj: Cell host & microbe [Cell Host Microbe] 2014 Oct 08; Vol. 16 (4), pp. 495-503. Date of Electronic Publication: 2014 Sep 25.
DOI: 10.1016/j.chom.2014.09.001
Abstrakt: 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.
(Copyright © 2014 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE