Metagenomic analysis of infant stool sample

Stool sample from a premature human infant (UC1). This study used metagenomic methods (community genomic analysis and sequencing of amplified 16S rRNA genes) to document microbial colonization of the gut of a premature infant born at 28 weeks gestation. Analysis of 16S rRNA gene sequences collected approximately daily revealed three compositional phases during colonization. We reconstructed genomes of the dominant organisms and intensively curated population genomic datasets from the third phase. In the third phase, the communities were dominated by a nearly clonal Serratia population, two Citrobacter strains sharing >99% nucleotide identity, and contained a lower abundance Enterococcus population, multiple plasmids and bacteriophage. The relative abundance of the Citrobacter strains changed significantly over time. Modeling of Citrobacter strain abundances suggests differences in growth rates and/or host colonization patterns. We identified genotypic variation potentially responsible for divergent strain ecologies, including hotspots of sequence variation in regulatory genes and intergenic regions, and in genes involved in transport, flagellar biosynthesis, substrate metabolism, and host colonization, as well as differences in the complements of these genes. Our results demonstrate that a community genomic approach can elucidate gut microbial colonization at the resolution required to discern medically relevant strain and species population dynamics, and hence improve our ability to diagnose and treat microbial community-mediated disorders.