The gut microbiome harbors astonishing genetic diversity, with over 22 million genes sequenced from human gut microbial populations, and an immense pool of unique enzymes capable of producing and modifying a wide array of chemical structural groups. Influence of this dense community, with its dynamic metabolic activity and bidirectional flux of molecules between microbe and host, extends beyond the gut into the entire body, including the brain. In fact, integration of molecular inputs from within the gut can shape animal health and behavior, with recent examples showing that an altered gut microbiota is sufficient to affect neurological and psychological symptoms in many mouse models, including multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, and autism spectrum disorder (ASD). However, the mechanisms mediating gut-brain interactions remain poorly defined. Deeper understanding of the molecular communication between gut microbes and the central nervous system will uncover critical features of behavioral, psychiatric, and neurodegenerative diseases. Decoding the chemical messages between gut microbes and the host is the foundation of our research program.