Prediction and quantification of bioactive microbiota metabolites in the mouse gut. Academic Article uri icon

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.

published proceedings

  • Nat Commun

altmetric score

  • 85.1

author list (cited authors)

  • Sridharan, G. V., Choi, K., Klemashevich, C., Wu, C., Prabakaran, D., Pan, L. B., ... Jayaraman, A.

citation count

  • 160

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

publication date

  • November 2014