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A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites.

Authors
  • Dodd, Dylan1, 2
  • Spitzer, Matthew H1, 2
  • Van Treuren, William2
  • Merrill, Bryan D2
  • Hryckowian, Andrew J2
  • Higginbottom, Steven K2
  • Le, Anthony1
  • Cowan, Tina M1
  • Nolan, Garry P2
  • Fischbach, Michael A3
  • Sonnenburg, Justin L2
  • 1 Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.
  • 2 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA.
  • 3 California Institute for Quantitative Bioscience and Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco 94143, California, USA.
Type
Published Article
Journal
Nature
Publisher
Springer Nature
Publication Date
Nov 30, 2017
Volume
551
Issue
7682
Pages
648–652
Identifiers
DOI: 10.1038/nature24661
PMID: 29168502
Source
Medline
License
Unknown

Abstract

The human gut microbiota produces dozens of metabolites that accumulate in the bloodstream, where they can have systemic effects on the host. Although these small molecules commonly reach concentrations similar to those achieved by pharmaceutical agents, remarkably little is known about the microbial metabolic pathways that produce them. Here we use a combination of genetics and metabolic profiling to characterize a pathway from the gut symbiont Clostridium sporogenes that generates aromatic amino acid metabolites. Our results reveal that this pathway produces twelve compounds, nine of which are known to accumulate in host serum. All three aromatic amino acids (tryptophan, phenylalanine and tyrosine) serve as substrates for the pathway, and it involves branching and alternative reductases for specific intermediates. By genetically manipulating C. sporogenes, we modulate serum levels of these metabolites in gnotobiotic mice, and show that in turn this affects intestinal permeability and systemic immunity. This work has the potential to provide the basis of a systematic effort to engineer the molecular output of the gut bacterial community.

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