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Nat Commun. 2014 Nov 20;5:5492. doi: 10.1038/ncomms6492.

Prediction and quantification of bioactive microbiota metabolites in the mouse gut.

Author information

1
Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts 02155, USA.
2
Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843, USA.
3
Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College Station, Texas 77843, USA.
4
1] Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843, USA [2] Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College Station, Texas 77843, USA.

Abstract

Metabolites produced by the intestinal microbiota are potentially important physiological modulators. Here we present a metabolomics strategy that models microbiota metabolism as a reaction network and utilizes pathway analysis to facilitate identification and characterization of microbiota metabolites. Of the 2,409 reactions in the model, ~53% do not occur in the host, and thus represent functions dependent on the microbiota. The largest group of such reactions involves amino-acid metabolism. Focusing on aromatic amino acids, we predict metabolic products that can be derived from these sources, while discriminating between microbiota- and host-dependent derivatives. We confirm the presence of 26 out of 49 predicted metabolites, and quantify their levels in the caecum of control and germ-free mice using two independent mass spectrometry methods. We further investigate the bioactivity of the confirmed metabolites, and identify two microbiota-generated metabolites (5-hydroxy-L-tryptophan and salicylate) as activators of the aryl hydrocarbon receptor.

PMID:
25411059
DOI:
10.1038/ncomms6492
[Indexed for MEDLINE]

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