How gut microbes can regulate the enteric nervous system and gut-brain communications is a field of intense research. Dr. Lihua Ye and colleagues in Drs. John Rawls and Rodger Liddle’s labs at Duke University have demonstrated that bacteria can control intestinal motility and vagal neuronal activation via tryptophan catabolites through the receptor TrpA1 expressed on enteroendocrine cells within the gut epithelium. Identified initially using zebrafish, this pathway was also shown to exist in humans and mice suggesting an ancient mechanism by which gut bacteria can influence the host nervous system. This Research article was recently published in Cell Host and Microbe accompanied by a Preview article by Harry Sokol and colleagues in the same issue.