Dynamics of within-host evolution and strain replacement in the human gut microbiome

The human gut contains trillions of rapidly reproducing bacteria, making it a potential hotbed of within-host evolution. While the species-level dynamics in the gut have been extensively studied, we currently know very little about the evolutionary dynamics that take place within individual species. In this talk, I will discuss our recent efforts to measure the statistical properties of within-host evolution from a large panel of human gut metagenomes. Our analysis shows that on short timescales, genetic differences are only rarely caused by the invasion of distantly related strains. Resident strains more commonly acquire putative evolutionary changes, in which small numbers of nucleotide variants or gene content differences rapidly sweep to high frequency within a host. However, comparisons of adult twins suggest that strain replacement eventually overwhelms evolution over multi-decade timescales, hinting at fundamental limits to the extent of local adaptation. Together, our results show that gut bacteria can evolve on human-relevant timescales, and they provide key empirical constraints necessary for future modeling efforts.