High-resolution lineage tracking of within-host evolution and strain transmission in a human gut symbiont across ecological scales

Abstract

SummaryGut bacteria rapidly evolvein vivo, but their long-term success requires dispersal across hosts. Here, we quantify this interplay by tracking >50,000 genomically barcoded lineages of the prevalent commensalBacteroides thetaiotaomicron(Bt) among co-housed mice. We find that adaptive mutations rapidly spread between hosts, overcoming the natural colonization resistance of residentBtstrains. Daily transmission rates varied >10-fold across hosts, but shared selection pressures drove predictable engraftment of specific lineages over time. The addition of a 49-species community shifted the adaptive landscape relative to mono-colonizedBtwithout slowing the rate of evolution, and reduced transmission while still allowing specific mutants to engraft. Whole-genome sequencing uncovered diverse modes of adaptation involving complex carbohydrate metabolism. Complementaryin vitroevolution across 29 carbon sources revealed variable overlap within vivoselection pressures, potentially reflecting synergistic and antagonistic pleiotropies. These results show how high-resolution lineage tracking enables quantification of commensal evolution across ecological scales.