Yet at lower taxonomic levels, and at early stages of development, our knowledge of this process is incomplete. The dynamic process of colonization has been well studied at high taxonomic levels ( Palmer et al., 2007) and seems predictable based on competitive interactions between and within the dominant phyla ( Trosvik et al., 2010). In infants, early assembly of the gut microbiota has been linked to development of innate immune responses and terminal differentiation of intestinal structures ( Hooper et al., 2001).
Although the adult gut microbiota is highly variable between individuals, it displays limited diversity at the phylum level: only two bacterial phyla ( Bacteroidetes and Firmicutes) contribute ~90% of all microbes ( Eckburg et al., 2005). Intestinal microbes influence human health through harvesting of energy from dietary substrates, production of essential nutrients, and protection against colonization by pathogens ( Dethlefsen et al., 2007 Hooper et al., 2002). 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. 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. Modeling of Citrobacter strain abundance suggests differences in growth rates and host colonization patterns. The relative abundance of two Citrobacter strains sharing ~99% nucleotide identity changed significantly over time within a community dominated by a nearly clonal Serratia population and harboring a lower abundance Enterococcus population and multiple plasmids and bacteriophage. We observed three compositional phases during colonization, and reconstructed and intensively curated population genomic datasets from the third phase. Here, we document strainlevel genomic divergence during the first 3 wk of life within the fecal microbiota of an infant born at 28-wk gestation. Increasing evidence suggests that strain-level genomic variation may underpin distinct ecological trajectories within mixed populations, yet there have been few strain-resolved analyses of genotype–phenotype connections in the context of the human ecosystem. Alterations in its composition have been correlated with chronic disorders, such as obesity and inflammatory bowel disease in adults, and may be associated with neonatal necrotizing enterocolitis in premature infants.
E-mail: intestinal microbiome is a critical determinant of human health. To whom correspondence should be addressed.
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