title: Prediction and quantification of bioactive microbiota metabolites in the mouse gut.
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.
authors.affiliation: Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts 02155, USA.
authors.forename: Gautham V
authors.initials: GV
authors.lastname: Sridharan
authors.affiliation: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Kyungoh
authors.initials: K
authors.lastname: Choi
authors.affiliation: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Klemashevich
authors.affiliation: Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts 02155, USA.
authors.forename: Charmian
authors.initials: C
authors.lastname: Wu
authors.affiliation: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Darshan
authors.initials: D
authors.lastname: Prabakaran
authors.affiliation: Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts 02155, USA.
authors.forename: Long Bin
authors.initials: LB
authors.lastname: Pan
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College Station, Texas 77843, USA.
authors.forename: Shelby
authors.initials: S
authors.lastname: Steinmeyer
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College Station, Texas 77843, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Mueller
authors.forename: Mona
authors.initials: M
authors.lastname: Yousofshahi
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College Station, Texas 77843, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Alaniz
authors.affiliation: Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts 02155, USA.
authors.forename: Kyongbum
authors.initials: K
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Arul
authors.initials: A
authors.lastname: Jayaraman
mesh_terms: D000818:Animals; D002432:Cecum / Q000378:metabolism* / Q000382:microbiology; D013058:Mass Spectrometry; D055442:Metabolome; D051379:Mice; D064307:Microbiota