Prediction and quantification of bioactive microbiota metabolites in the mouse gut.
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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.
author list (cited authors)
Sridharan, G. V., Choi, K., Klemashevich, C., Wu, C., Prabakaran, D., Pan, L. B., ... Jayaraman, A.
complete list of authors
Sridharan, Gautham V||Choi, Kyungoh||Klemashevich, Cory||Wu, Charmian||Prabakaran, Darshan||Pan, Long Bin||Steinmeyer, Shelby||Mueller, Carrie||Yousofshahi, Mona||Alaniz, Robert C||Lee, Kyongbum||Jayaraman, Arul