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The ecology and environment of the microbes that inhabit the mammalian intestine undergoes several changes as the host ages. Here, we ask if the selection pressure experienced by a new strain colonizing the aging gut differs from that in the gut of young adults. Using experimental evolution in mice after a short antibiotic treatment, as a model for a common clinical situation, we show that a new colonizing E. coli strain rapidly adapts to the aging gut via both mutation accumulation and bacteriophage-mediated horizontal gene transfer (HGT). The pattern of evolution of E. coli in aging mice is characterized by a larger number of transposable element insertions and intergenic mutations compared to that in young mice, which is consistent with the gut of aging hosts harboring a stressful and iron limiting environment. [ABSTRACT FROM AUTHOR]