title: Shotgun metaproteomics of the human distal gut microbiota.
abstract: The human gut contains a dense, complex and diverse microbial community, comprising the gut microbiome. Metagenomics has recently revealed the composition of genes in the gut microbiome, but provides no direct information about which genes are expressed or functioning. Therefore, our goal was to develop a novel approach to directly identify microbial proteins in fecal samples to gain information about the genes expressed and about key microbial functions in the human gut. We used a non-targeted, shotgun mass spectrometry-based whole community proteomics, or metaproteomics, approach for the first deep proteome measurements of thousands of proteins in human fecal samples, thus demonstrating this approach on the most complex sample type to date. The resulting metaproteomes had a skewed distribution relative to the metagenome, with more proteins for translation, energy production and carbohydrate metabolism when compared to what was earlier predicted from metagenomics. Human proteins, including antimicrobial peptides, were also identified, providing a non-targeted glimpse of the host response to the microbiota. Several unknown proteins represented previously undescribed microbial pathways or host immune responses, revealing a novel complex interplay between the human host and its associated microbes.
authors.affiliation: Oak Ridge National Laboratory, Chemical and Life Sciences Divisions, Oak Ridge, TN, USA.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Verberkmoes
authors.forename: Alison L
authors.initials: AL
authors.lastname: Russell
authors.forename: Manesh
authors.initials: M
authors.lastname: Shah
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.forename: Magnus
authors.initials: M
authors.lastname: Rosenquist
authors.forename: Jonas
authors.initials: J
authors.lastname: Halfvarson
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lefsrud
authors.forename: Juha
authors.initials: J
authors.lastname: Apajalahti
authors.forename: Curt
authors.initials: C
authors.lastname: Tysk
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hettich
authors.forename: Janet K
authors.initials: JK
authors.lastname: Jansson
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000032:analysis; D001419:Bacteria / Q000276:immunology; D001426:Bacterial Proteins / Q000032:analysis*; D002853:Chromatography, Liquid; D005243:Feces / Q000737:chemistry*; D005260:Female; D006801:Humans; D007420:Intestine, Large / Q000382:microbiology*; D013058:Mass Spectrometry; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*
chemical_list: D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D020543:Proteome