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Title: Genome-resolved metaproteomic characterization of preterm infant gut microbiota development reveals species-specific metabolic shifts and variabilities during early life

Establishment of the human gut microbiota begins at birth. This early-life microbiota development can impact host physiology during infancy and even across an entire life span. But, the functional stability and population structure of the gut microbiota during initial colonization remain poorly understood. Metaproteomics is an emerging technology for the large-scale characterization of metabolic functions in complex microbial communities (gut microbiota). We applied a metagenome-informed metaproteomic approach to study the temporal and inter-individual differences of metabolic functions during microbial colonization of preterm human infants’ gut. By analyzing 30 individual fecal samples, we identified up to 12,568 protein groups for each of four infants, including both human and microbial proteins. With genome-resolved matched metagenomics, proteins were confidently identified at the species/strain level. The maximum percentage of the proteome detected for the abundant organisms was ~45%. A time-dependent increase in the relative abundance of microbial versus human proteins suggested increasing microbial colonization during the first few weeks of early life. We observed remarkable variations and temporal shifts in the relative protein abundances of each organism in these preterm gut communities. Given the dissimilarity of the communities, only 81 microbial EggNOG orthologous groups and 57 human proteins were observed across all samples. Thesemore » conserved microbial proteins were involved in carbohydrate, energy, amino acid and nucleotide metabolism while conserved human proteins were related to immune response and mucosal maturation. We also identified seven proteome clusters for the communities and showed infant gut proteome profiles were unstable across time and not individual-specific. By applying a gut-specific metabolic module (GMM) analysis, we found that gut communities varied primarily in the contribution of nutrient (carbohydrates, lipids, and amino acids) utilization and short-chain fatty acid production. Overall, this study reports species-specific proteome profiles and metabolic functions of human gut microbiota during early colonization. In particular, our work contributes to reveal microbiota-associated shifts and variations in the metabolism of three major nutrient sources and short-chain fatty acid during colonization of preterm infant gut.« less
ORCiD logo [1] ;  [2] ;  [3] ;  [2] ; ORCiD logo [4]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biosciences Division
  2. Univ. of California, Berkeley, CA (United States). Dept. of Earth and Planetary Science
  3. Univ. of Pittsburgh, PA (United States). School of Medicine
  4. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Chemical Sciences Division
Publication Date:
Grant/Contract Number:
AC05-00OR22725; 1R01-GM-103600
Accepted Manuscript
Journal Name:
Additional Journal Information:
Journal Volume: 5; Journal Issue: 1; Journal ID: ISSN 2049-2618
BioMed Central
Research Org:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org:
USDOE; National Institutes of Health (NIH)
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; metaproteomics; human infant gut; shotgun proeomics; genome resolved; microbial metabolic functions
OSTI Identifier: