Using lacI DNA-binding domain and LXRbeta ligand-binding domain, we made an artificial bile acid receptor which can regulate expression of target gene within a natural lacI operon. As proof of principle, we demonstrate that regulation of bacteria gene expression by host eukaryocyte metabolites is achievable using chimeric nuclear receptors. Through directed molecular evolution, a harmonious signal network regulating metabolism of both prokaryocytes and their host eukaryocytes in the digestive tract is feasible.