title: The effect of microbial colonization on the host proteome varies by gastrointestinal location.
abstract: Endogenous intestinal microbiota have wide-ranging and largely uncharacterized effects on host physiology. Here, we used reverse-phase liquid chromatography-coupled tandem mass spectrometry to define the mouse intestinal proteome in the stomach, jejunum, ileum, cecum and proximal colon under three colonization states: germ-free (GF), monocolonized with Bacteroides thetaiotaomicron and conventionally raised (CR). Our analysis revealed distinct proteomic abundance profiles along the gastrointestinal (GI) tract. Unsupervised clustering showed that host protein abundance primarily depended on GI location rather than colonization state and specific proteins and functions that defined these locations were identified by random forest classifications. K-means clustering of protein abundance across locations revealed substantial differences in host protein production between CR mice relative to GF and monocolonized mice. Finally, comparison with fecal proteomic data sets suggested that the identities of stool proteins are not biased to any region of the GI tract, but are substantially impacted by the microbiota in the distal colon.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Joshua S
authors.identifier: http://orcid.org/0000-0002-5256-6773
authors.initials: JS
authors.lastname: Lichtman
authors.affiliation: Department of Computer Science, Stanford University, Stanford, CA, USA.
authors.forename: Emily
authors.identifier: http://orcid.org/0000-0002-5370-1746
authors.initials: E
authors.lastname: Alsentzer
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: Jaffe
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sprockett
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Masutani
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA, USA.
authors.forename: Elvis
authors.initials: E
authors.lastname: Ikwa
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Gabriela K
authors.identifier: http://orcid.org/0000-0001-9703-2591
authors.initials: GK
authors.lastname: Fragiadakis
authors.affiliation: The Climate Corporation, San Francisco, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Clifford
authors.affiliation: Digital Productivity Flagship, Commonwealth Scientific and Industrial Research Organization, Dutton Park, Queensland, Australia.
authors.forename: Bevan Emma
authors.initials: BE
authors.lastname: Huang
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Sonnenburg
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.|Department of Bioengineering, Stanford University, Stanford, CA, USA.
authors.forename: Kerwyn Casey
authors.initials: KC
authors.lastname: Huang
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Joshua E
authors.identifier: http://orcid.org/0000-0002-8063-3259
authors.initials: JE
authors.lastname: Elias
mesh_terms: D000818:Animals; D002432:Cecum / Q000382:microbiology; D016000:Cluster Analysis; D005243:Feces; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007082:Ileum / Q000382:microbiology; D007583:Jejunum / Q000382:microbiology; D013058:Mass Spectrometry; D051379:Mice; D020543:Proteome / Q000378:metabolism*; D013270:Stomach / Q000382:microbiology
chemical_list: D020543:Proteome