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Shotgun Metaproteomics of the Human Distal Gut Microbiota

Journal Article · · Nature Methods
 [1];  [1];  [1];  [2];  [3];  [4];  [5];  [6];  [3]
  1. ORNL
  2. Burnham Institute for Medical Research, La Jolla, CA
  3. Swedish University of Agricultural Sciences, Upsalla, Sweden
  4. Orebro University Hospital, Orebro, Sweden
  5. McGill University, Montreal, Quebec
  6. Alimetrics Ltd,

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 what genes were 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 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.

Research Organization:
Oak Ridge National Laboratory (ORNL)
Sponsoring Organization:
SC USDOE - Office of Science (SC)
DOE Contract Number:
AC05-00OR22725
OSTI ID:
958920
Journal Information:
Nature Methods, Journal Name: Nature Methods Journal Issue: 2 Vol. 3
Country of Publication:
United States
Language:
English

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