In a new journal, Cell Systems, Mimee et al. report that in their M.I.T. lab they succeeded in modulating the constitutive gene expression of the mammalian commensal bacterium Bacteroides thetaiotaomicron. They used the CRISPR interference methodology and validated the results of various gene modifications, from knockdown genes to repression, in mice colonized with the modified strain after antibiotic treatment. These results present a new way to explore cellular sensing, learn more about the host-microbe interface in the gut, and potentially change the gut ecosystem.