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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]

Aging is a complex process, with many associated time-dependent phenotypes. The gut microbiota have long been postulated as an important factor in shaping healthy aging [ 1 , 2 ]. During aging, changes in the microbiota composition occur, with taxa that are rare in adults becoming dominant in the elderly [ 3 , 4 ]. Increased inflammation associated with aging is also known to modulate and be modulated by the microbiota [ 5 ]. Ecological interactions are known to affect the evolution of bacteria both in vitro [ 6 ] and in vivo [ 7 ], but the extent to which these and the host age-dependent inflammatory environment can alter the pattern of evolutionary change of a gut commensal lineage is still unknown [ 8 ]. Here, we provide the first genomic analysis of such evolution in cohorts of old mice, under controlled host genetics and lifestyle conditions. We find that Escherichia coli evolution when colonizing the gut of old mice significantly differs from its evolution in young mice. Evolution toward metabolic adaptation is slower in old than young mice, and mutational targets concerning stress-related functions were found specifically in the inflamed gut of old mice. Taking the genetic basis of E. coli short-term evolution as a reflection of the environment it experiences, the sequencing data indicate that aging imposes a more stressful environment to this important colonizer of the mammalian gut. • New commensal lineages colonizing the inflamed gut of aged mice evolve within weeks • The emergence of bacterial metabolic adaptations is delayed in old versus young mice • Stress-related genetic adaptations are a signature of bacterial evolution in old mice The gut microbiota is thought to play a role in aging. Barreto et al. show that E. coli evolves rapidly in both old and young mice. However, in old mice, metabolic adaptations emerge more slowly and exhibit a distinct stress-related genetic signature, suggesting a more inflammatory environment in the gut of older animals. [ABSTRACT FROM AUTHOR]