Intra- and inter-species interactions drive early phases of invasion in mice gut microbiota

The stability and dynamics of ecological communities are dictated by interaction networks typically quantified at the level of species.^1–10But how such networks are influenced by intra-species variation (ISV) is poorly understood.^11–14Here, we use ~500,000 chromosomal barcodes to track high-resolution intra-species clonal lineages ofEscherichia coliinvading mice gut with the increasing complexity of gut microbiome: germ-free, antibiotic-perturbed, and innate microbiota. By co-clustering the dynamics of intra-species clonal lineages and those of gut bacteria from 16S rRNA profiling, we show the emergence of complex time-dependent interactions betweenE. coliclones and resident gut bacteria. With a new approach, dynamic covariance mapping (DCM), we differentiate three phases of invasion in susceptible communities: 1) initial loss of community stability asE. colienters; 2) recolonization of some gut bacteria; and 3) recovery of stability withE. colicoexisting with resident bacteria in a quasi-steady state. Comparison of the dynamics, stability and fitness from experimental replicates and different cohorts suggest that phase 1 is driven by mutations inE. colibefore colonization, while phase 3 is byde novomutations. Our results highlight the transient nature of interaction networks in microbiomes driven by the persistent coupling of ecological and evolutionary dynamics.