Within-host evolution and transmission of a human gut symbiont across ecological scales

Gut bacteria rapidly evolve in vivo, but their long-term success requires dispersal across hosts. Here, we quantify this interplay by tracking ∼70,000 genomically barcoded lineages of the commensal Bacteroides thetaiotaomicron (Bt) among co-housed mice. Adaptive mutations rapidly spread between hosts, overcoming colonization resistance imposed by resident Bt strains. Daily transmission rates varied >10-fold across hosts, but shared selection pressures drove predictable engraftment of specific lineages. Spatially resolved sampling within hosts revealed emergent preferences among adaptive lineages. The addition of a highly diverse community shifted the adaptive landscape without slowing the rate of evolution and reduced transmission while allowing specific mutants to engraft. Whole-genome sequencing uncovered diverse modes of adaptation involving complex carbohydrate metabolism. In vitro evolution across 29 carbon sources revealed variable overlap with in vivo selection pressures, potentially reflecting synergistic and antagonistic pleiotropies. These results illustrate how high-resolution lineage tracking enables quantification of commensal evolution across ecological scales.