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 lifethreatening intestinal disease. To study variability in the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first three months of life from 35 premature infants, 14 of which developed NEC, and metaproteomic measurements were made on 87 samples. Microbial proteomic profiles and community composition remained relatively stable on the time scale of a week, but the proteome was more variable than community composition. 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 find that organism proteomes correlate with overall community composition. Thus, this genome-resolved proteomics study demonstrates that the contributions of individual organisms to microbiome development depend on microbial community context.

A Robust and Universal Metaproteomics Workflow for Research Studies and Routine Diagnostics Within 24 h Using Phenol Extraction, FASP Digest, and the MetaProteomeAnalyzer

“…However, the number of identifications was heavily dependent on the sample type. First, a literature comparison (Supplementary Table S9) confirmed that soil metaproteome studies (Keiblinger et al, 2012; Bagnoud et al, 2016; Bastida et al, 2016; Thorn et al, 2018) identified less proteins and peptides than studies of Hgut (Tanca et al, 2016; Brown et al, 2018; Zhang et al, 2018a; Rechenberger et al, 2019) and BGP (Bize et al, 2015; Hagen et al, 2017; Joyce et al, 2018). Second, it became obvious that sacrificing the fractionation before or after (Hinzke et al, 2019) tryptic digestion resulted in lower number of identifications.…”

Effects of early life NICU stress on the developing gut microbiome

“…However, studies investigating the developing microbiome of preterm infants have revealed conflicting and sometimes counterintuitive results. For the first 3 months of life, Brown et al () examined the gut microbiome of 35 preterm infants and found high variability within infants. In subsequent sampling, some infants had microbial community abundance as unique as those from other infants, and no species were strongly associated with necrotizing enterocolitis (NEC) (Brown et al, ).…”

“…For the first 3 months of life, Brown et al () examined the gut microbiome of 35 preterm infants and found high variability within infants. In subsequent sampling, some infants had microbial community abundance as unique as those from other infants, and no species were strongly associated with necrotizing enterocolitis (NEC) (Brown et al, ). Dobbler et al () identified low microbial diversity and chaotic succession for infants who developed NEC.…”

A phylogenetic model for the recruitment of species into microbial communities and application to studies of the human microbiome

“…phylogenetic overdispersion). However, overdispersion is far from universal, and multiple studies have shown that extremely close relatives can coexist within the human microbiome [26; 27; 28], and may even be preferentially recruited [29]. Indeed, Darwin's pre-adaptation hypothesis predicts that species with a close relative present in a community will be preferentially recruited, because they are likely to already be adapted to the new environment [23].…”