The interactions between a host and its resident microbes form complicated networks that can affect host physiology. Disentangling these host-microbe interactions can help us better understand mechanisms by which bacteria affect hosts, while also defining the integral commensal protection that host-associated microbiota offer to promote health. Here we utilize a tractable genetic model organism, Caenorhabditis elegans, to study the effects of host environments on bacterial gene expression and metabolic pathways. First, we compared the transcriptomic profiles of E. coli OP50 in vitro (on agar plates) versus in vivo (fed to C. elegans host). Our data revealed that 110 biosynthetic genes were enriched in host-associated E. coli. Several of these expressed genes code for the precursors and products needed for the synthesis of lipopolysaccharides (LPS), which are important for innate immune and stress responses, as well as pathogenicity. Secondly, we compared the transcriptomic profiles of E. coli fed to hosts with different genetic backgrounds, including the long-lived daf-2/insulin like growth factor (IGF) receptor and short lived daf-16/FOXO transcription factor mutants. We find that hosts genetics also alters bacterial metabolic pathways. Given that bacteria influence host health, this transcriptomics approach can elucidate genes mediating host aging.