Emergence of Caenorhabditis elegans as a Model Organism for Dissecting the Gut–Brain Axis

Accumulating evidence links the gut microbiome to neuronal functions in the brain. Given the increasing prevalence of brain disorders, there is a critical need to understand how gut microbes impact neuronal functions so that targeted therapeutic interventions can be developed. In this commentary, we discuss what makes the nematode Caenorhabditis elegans a valuable model for dissecting the molecular basis of gut microbiome-brain interactions. With a fully mapped neuronal circuitry, C. elegans is an effective model for studying signaling of the nervous system in a context that bears translational relevance to human disease. We highlight C. elegans as a potent but underexploited tool to interrogate the influence of the bacterial variable on the complex equation of the nervous system. We envision that routine use of gnotobiotic C. elegans to examine the gut–brain axis will be an enabling technology for the development of novel therapeutic interventions for brain diseases.