Hospitalized premature infants are colonized by related bacterial strains with distinct proteomic profiles

Christopher T. Brown, Weili Xiong, Matthew R. Olm, Brian C. Thomas, Robyn Baker, Brian Firek, Michael J. Morowitz, Robert L. Hettich, Jillian F. Banfield

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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. 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. IMPORTANCE Humans are colonized by microbes at birth, a process that is important to health and development. However, much remains to be known about the fine-scale microbial dynamics that occur during the colonization period. We conducted a genomeresolved study of microbial community composition, replication rates, and proteomes during the first 3 months of life of both healthy and sick premature infants. Infants were found to be colonized by similar microbes, but each underwent a distinct colonization trajectory. Interestingly, related microbes colonizing different infants were found to have distinct proteomes, indicating that microbiome function is not only driven by which or-ganisms are present, but also largely depends on microbial responses to the unique set of physiological conditions in the infant gut.

Original languageEnglish
Article numbere00441-18
JournalmBio
Volume9
Issue number2
DOIs
StatePublished - Mar 1 2018

Funding

Funding was provided by National Institutes of Health grants R01-AI-092531 and R01-GM-103600. Sample collection was approved by the University of Pittsburgh Institutional Review Board (PRO10090089). Funding was provided by National Institutes of Health grants R01-AI-092531 and R01-GM-103600. M.J.M. oversaw sample collection, R.B. collected all samples and managed metadata, and B.F. coordinated sample processing for DNA sequencing and proteomics analysis. C.T.B. and M.R.O. assembled and annotated the metagenome data. C.T.B. and J.F.B. carried out the genome binning and curation. C.T.B. conducted the microbial community time series abundance and iRep analyses. W.X. and R.L.H. generated the proteomics data, which was analyzed by C.T.B. C.T.B., M.R.O., and B.C.T. provided bioinformatics support. C.T.B. and J.F.B. wrote the paper, and all of us provided input to the final text.

Keywords

  • Human microbiome
  • Metagenomics
  • Metaproteomics
  • Microbial colonization
  • Microbial genomics
  • Necrotizing enterocolitis
  • Neonates
  • iRep

Fingerprint

Dive into the research topics of 'Hospitalized premature infants are colonized by related bacterial strains with distinct proteomic profiles'. Together they form a unique fingerprint.

Cite this