Research on human-associated E. coli tends to focus on pathogens, such as enterotoxigenic E. coli (ETEC) strains, which are a leading cause of diarrhea in developing countries. However, the severity of disease caused by these pathogens is thought to be influenced by the microbiome. The nonpathogenic E. coli community that resides in the human gastrointestinal tract may play a role in pathogen colonization and disease severity and may become a reservoir for virulence and antibiotic resistance genes. Our study used whole-genome sequencing of E. coli before, during, and after challenge with an archetype ETEC isolate, H10407, and antibiotic treatment to explore the diversity and resiliency of the resident E. coli population in response to the ecological disturbances caused by pathogen invasion and antibiotic treatment.