Original Article

Subject Category: Microbe-microbe and microbe-host interactions

The ISME Journal (2009) 3, 179–189; doi:10.1038/ismej.2008.108; published online 30 October 2008

Shotgun metaproteomics of the human distal gut microbiota

Nathan C Verberkmoes1,7, Alison L Russell1,7, Manesh Shah1, Adam Godzik2, Magnus Rosenquist3,8, Jonas Halfvarson4, Mark G Lefsrud1,9, Juha Apajalahti5, Curt Tysk4, Robert L Hettich1 and Janet K Jansson3,6

  1. 1Oak Ridge National Laboratory, Chemical and Life Sciences Divisions, Oak Ridge, TN, USA
  2. 2Department of Bioinformatics and Systems Biology, Burnham Institute for Medical Research, La Jolla, CA, USA
  3. 3Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden
  4. 4Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden
  5. 5Alimetrics Ltd, Helsinki, Finland
  6. 6Department of Ecology, Earth Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

Correspondence: JK Jansson, Earth Science Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA. E-mail: jrjansson@lbl.gov

7These authors contributed equally to this work.

8Current address: Department of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, Uppsala, Sweden.

9Current address: Bioresource Engineering, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada.

Received 2 September 2008; Revised 7 October 2008; Accepted 8 October 2008; Published online 30 October 2008.

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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.

Keywords:

microbiome, human gut, metaproteome, shotgun proteomics, metagenomics, antimicrobial peptide

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