Ammonia is a waste product of urea metabolism. In the human body, it is maintained at a low serum concentration, and when levels are too high, ammonia can cause neurological dysfunctions, due to its neurotoxic properties. In the gut, ammonia is generated by urease-positive bacteria like harmful Helicobacter pylori or beneficial Streptococcus thermophilus and Streptococcus salivarius, which hydrolyse host-derived urea into ammonia and carbon dioxide. It is known that the gut can communicate with the brain via bacterium-derived metabolites. However, whether intestinal ammonia can act as a bacterium-derived metabolite to modulate brain function is unknown. In this study, Wang et al. show that bacterium-derived intestinal ammonia modulates astrocytes in the mouse brain to produce glutamine and reduce stress-induced depressive-like behaviours.