Neuroactive metabolites modulated by the gut microbiota in honey bees

Honey bees have emerged as a new model to study the gut–brain axis, as they exhibit complex social behaviors and cognitive abilities, while experiments with gnotobiotic bees have revealed that their gut microbiota alters both brain and behavioral phenotypes. Furthermore, while honey bee brain functions supporting a broad range of behaviors have been intensively studied for over 50 years, the gut microbiota of bees has been experimentally characterized only recently. Here, we combined six published datasets from metabolomic analyses to provide an overview of the neuroactive metabolites whose abundance in the gut, hemolymph and brain varies in presence of the gut microbiota. Such metabolites may either be produced by gut bacteria, released from the pollen grains during their decomposition by bacteria, or produced by other organs in response to different bacterial products. We describe the current state of knowledge regarding the impact of such metabolites on brain function and behavior and provide further hypotheses to explore in this emerging field of research. The gut microbiota of honeybees increases the abundance of several classes of neuroactive metabolites in the gut, the hemolymph, and the brain. Combining datasets from previous studies, we identify such metabolites and discuss how their deficiency might be responsible for the behavioral alterations reported in microbiota‐free honeybees.