skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles

Abstract

During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants.more » In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context.« less

Authors:
ORCiD logo [1]; ORCiD logo [2];  [1];  [3];  [4];  [5];  [6]; ORCiD logo [7];  [8]
  1. Univ. of California, Berkeley, CA (United States). Department of Plant and Microbial Biology
  2. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Biosciences Division
  3. Univ. of California, Berkeley, CA (United States). Department of Earth and Planetary Science
  4. Magee-Womens Hospital of UPMC, Pittsburgh, PA (United States)
  5. University of Pittsburgh School of Medicine, Pittsburgh, PA (United States). Department of Surgery
  6. University of Pittsburgh School of Medicine, Pittsburgh, PA (United States). Department of Surgery; Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States). Division of Pediatric General and Thoracic Surgery
  7. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Chemical Sciences Division
  8. Univ. of California, Berkeley, CA (United States). Department of Earth and Planetary Science and Department of Environmental Science, Policy, and Management; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Earth Sciences Division
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1474619
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
mBio (Online)
Additional Journal Information:
Journal Volume: 9; Journal Issue: 2; Journal ID: ISSN 2150-7511
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Brown, Christopher T., Xiong, Weili, Olm, Matthew R., Thomas, Brian C., Baker, Robyn, Firek, Brian, Morowitz, Michael J., Hettich, Robert L., and Banfield, Jillian F. Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles. United States: N. p., 2018. Web. doi:10.1128/mBio.00441-18.
Brown, Christopher T., Xiong, Weili, Olm, Matthew R., Thomas, Brian C., Baker, Robyn, Firek, Brian, Morowitz, Michael J., Hettich, Robert L., & Banfield, Jillian F. Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles. United States. doi:10.1128/mBio.00441-18.
Brown, Christopher T., Xiong, Weili, Olm, Matthew R., Thomas, Brian C., Baker, Robyn, Firek, Brian, Morowitz, Michael J., Hettich, Robert L., and Banfield, Jillian F. Tue . "Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles". United States. doi:10.1128/mBio.00441-18. https://www.osti.gov/servlets/purl/1474619.
@article{osti_1474619,
title = {Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles},
author = {Brown, Christopher T. and Xiong, Weili and Olm, Matthew R. and Thomas, Brian C. and Baker, Robyn and Firek, Brian and Morowitz, Michael J. and Hettich, Robert L. and Banfield, Jillian F.},
abstractNote = {During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context.},
doi = {10.1128/mBio.00441-18},
journal = {mBio (Online)},
issn = {2150-7511},
number = 2,
volume = 9,
place = {United States},
year = {2018},
month = {4}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 4 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

IDBA-UD: a de novo assembler for single-cell and metagenomic sequencing data with highly uneven depth
journal, April 2012


Temporal bacterial and metabolic development of the preterm gut reveals specific signatures in health and disease
journal, December 2016

  • Stewart, Christopher J.; Embleton, Nicholas D.; Marrs, Emma C. L.
  • Microbiome, Vol. 4, Issue 1
  • DOI: 10.1186/s40168-016-0216-8

Clinical Benefits of Lactoferrin for Infants and Children
journal, June 2016


Bacterial Community Variation in Human Body Habitats Across Space and Time
journal, November 2009


Strain-resolved analysis of hospital rooms and infants reveals overlap between the human and room microbiome
journal, November 2017


Shifting the genomic gold standard for the prokaryotic species definition
journal, October 2009

  • Richter, Michael; Rosselló-Móra, Ramon
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 45
  • DOI: 10.1073/pnas.0906412106

Peripheral education of the immune system by colonic commensal microbiota
journal, September 2011

  • Lathrop, Stephanie K.; Bloom, Seth M.; Rao, Sindhuja M.
  • Nature, Vol. 478, Issue 7368
  • DOI: 10.1038/nature10434

edgeR: a Bioconductor package for differential expression analysis of digital gene expression data
journal, November 2009


Development of the Human Infant Intestinal Microbiota
journal, June 2007


Time series community genomics analysis reveals rapid shifts in bacterial species, strains, and phage during infant gut colonization
journal, August 2012

  • Sharon, I.; Morowitz, M. J.; Thomas, B. C.
  • Genome Research, Vol. 23, Issue 1
  • DOI: 10.1101/gr.142315.112

A metagenome-wide association study of gut microbiota in type 2 diabetes
journal, September 2012


Gut bacteria are rarely shared by co-hospitalized premature infants, regardless of necrotizing enterocolitis development
journal, March 2015


Evidence for persistent and shared bacterial strains against a background of largely unique gut colonization in hospitalized premature infants
journal, June 2016

  • Raveh-Sadka, Tali; Firek, Brian; Sharon, Itai
  • The ISME Journal, Vol. 10, Issue 12
  • DOI: 10.1038/ismej.2016.83

Necrotizing Enterocolitis
journal, January 2011

  • Neu, Josef; Walker, W. Allan
  • New England Journal of Medicine, Vol. 364, Issue 3
  • DOI: 10.1056/NEJMra1005408

Measurement of bacterial replication rates in microbial communities
journal, November 2016

  • Brown, Christopher T.; Olm, Matthew R.; Thomas, Brian C.
  • Nature Biotechnology, Vol. 34, Issue 12
  • DOI: 10.1038/nbt.3704

UniRef: comprehensive and non-redundant UniProt reference clusters
journal, March 2007


Estimating the number of clusters in a data set via the gap statistic
journal, May 2001

  • Tibshirani, Robert; Walther, Guenther; Hastie, Trevor
  • Journal of the Royal Statistical Society: Series B (Statistical Methodology), Vol. 63, Issue 2, p. 411-423
  • DOI: 10.1111/1467-9868.00293

KEGG: Kyoto Encyclopedia of Genes and Genomes
journal, January 2000

  • Kanehisa, Minoru; Goto, Susumu
  • Nucleic Acids Research, Vol. 28, Issue 1, p. 27-30
  • DOI: 10.1093/nar/28.1.27

Fast gapped-read alignment with Bowtie 2
journal, March 2012

  • Langmead, Ben; Salzberg, Steven L.
  • Nature Methods, Vol. 9, Issue 4
  • DOI: 10.1038/nmeth.1923

IDPicker 2.0: Improved Protein Assembly with High Discrimination Peptide Identification Filtering
journal, August 2009

  • Ma, Ze-Qiang; Dasari, Surendra; Chambers, Matthew C.
  • Journal of Proteome Research, Vol. 8, Issue 8
  • DOI: 10.1021/pr900360j

Community-wide analysis of microbial genome sequence signatures
journal, January 2009

  • Dick, Gregory J.; Andersson, Anders F.; Baker, Brett J.
  • Genome Biology, Vol. 10, Issue 8
  • DOI: 10.1186/gb-2009-10-8-r85

Unravelling the pathogenesis of inflammatory bowel disease
journal, July 2007


Basic local alignment search tool
journal, October 1990

  • Altschul, Stephen F.; Gish, Warren; Miller, Webb
  • Journal of Molecular Biology, Vol. 215, Issue 3, p. 403-410
  • DOI: 10.1016/S0022-2836(05)80360-2

dRep: a tool for fast and accurate genomic comparisons that enables improved genome recovery from metagenomes through de-replication
journal, July 2017

  • Olm, Matthew R.; Brown, Christopher T.; Brooks, Brandon
  • The ISME Journal, Vol. 11, Issue 12
  • DOI: 10.1038/ismej.2017.126

Intestinal Microbial Ecology in Premature Infants Assessed with Non–Culture-Based Techniques
journal, January 2010


Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis
journal, March 2017


Fecal Microbiota in Premature Infants Prior to Necrotizing Enterocolitis
journal, June 2011


Microbial metaproteomics for characterizing the range of metabolic functions and activities of human gut microbiota
journal, May 2015


KEGG for integration and interpretation of large-scale molecular data sets
journal, November 2011

  • Kanehisa, M.; Goto, S.; Sato, Y.
  • Nucleic Acids Research, Vol. 40, Issue D1
  • DOI: 10.1093/nar/gkr988

Antibiotics, birth mode, and diet shape microbiome maturation during early life
journal, June 2016

  • Bokulich, Nicholas A.; Chung, Jennifer; Battaglia, Thomas
  • Science Translational Medicine, Vol. 8, Issue 343
  • DOI: 10.1126/scitranslmed.aad7121

Prodigal: prokaryotic gene recognition and translation initiation site identification
journal, March 2010


An efficient algorithm for large-scale detection of protein families
journal, April 2002


somoclu : An Efficient Parallel Library for Self-Organizing Maps
journal, January 2017

  • Wittek, Peter; Gao, Shi Chao; Lim, Ik Soo
  • Journal of Statistical Software, Vol. 78, Issue 9
  • DOI: 10.18637/jss.v078.i09

CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes
journal, May 2015

  • Parks, Donovan H.; Imelfort, Michael; Skennerton, Connor T.
  • Genome Research, Vol. 25, Issue 7
  • DOI: 10.1101/gr.186072.114

MyriMatch:  Highly Accurate Tandem Mass Spectral Peptide Identification by Multivariate Hypergeometric Analysis
journal, February 2007

  • Tabb, David L.; Fernando, Christopher G.; Chambers, Matthew C.
  • Journal of Proteome Research, Vol. 6, Issue 2
  • DOI: 10.1021/pr0604054

Lactoferrin in the Preterm Infants' Diet Attenuates Iron-Induced Oxidation Products
journal, December 2002


Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants
journal, April 2013

  • Morrow, Ardythe L.; Lagomarcino, Anne J.; Schibler, Kurt R.
  • Microbiome, Vol. 1, Issue 1
  • DOI: 10.1186/2049-2618-1-13

Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
journal, October 2009

  • Maslowski, Kendle M.; Vieira, Angelica T.; Ng, Aylwin
  • Nature, Vol. 461, Issue 7268
  • DOI: 10.1038/nature08530

Search and clustering orders of magnitude faster than BLAST
journal, August 2010


Gut Microbiome Metagenomics Analysis Suggests a Functional Model for the Development of Autoimmunity for Type 1 Diabetes
journal, October 2011


Mash: fast genome and metagenome distance estimation using MinHash
journal, June 2016


UniFrac: a New Phylogenetic Method for Comparing Microbial Communities
journal, December 2005