Adaptive evolution within the gut microbiome of individual people

Individual bacterial lineages stably persist for years in the human gut microbiome 1–3 . However, the potential of these lineages to adapt during colonization of healthy people is not well understood 2,4 . Here, we assess evolution within individual microbiomes by sequencing the genomes of 602 Bacteroides fragilis isolates cultured from 12 healthy subjects. We find that B. fragilis within-subject populations contain substantial de novo nucleotide and mobile element diversity, which preserve years of within-person evolutionary history. This evolutionary history contains signatures of within-person adaptation to both subject-specific and common selective forces, including parallel mutations in sixteen genes. These sixteen genes are involved in cell-envelope biosynthesis and polysaccharide utilization, as well as yet under-characterized pathways. Notably, one of these genes has been shown to be critical for B. fragilis colonization in mice 5 , indicating that key genes have not already been optimized for survival in vivo . This lack of optimization, given historical signatures of purifying selection in these genes, suggests that varying selective forces with discordant solutions act upon B. fragilis in vivo . Remarkably, in one subject, two B. fragilis sublineages coexisted at a stable relative frequency over a 1.5-year period despite rapid adaptive dynamics within one of the sublineages. This stable coexistence suggests that competing selective forces can lead to B. fragilis niche-differentiation even within a single person. We conclude that B. fragilis adapts rapidly within the microbiomes of individual healthy people, providing a new route for the discovery of key genes in the microbiome and implications for microbiome stability and manipulation.