People often take probiotics to supplement the community of microbes living in their gut and maintain their digestive health. But can gut microbes also have an important effect on the brain? New evidence indicates that they can, with possible key roles in neurologic disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). While treatment with antibiotics to manipulate the gut microbiota has been shown to improve neurologic symptoms, it can worsen them in SOD1 mice, which are often used to study ALS. To better understand the role of gut microbes in ALS, scientists either depleted the gut microbiota of SOD1 mice with antibiotics or augmented it by housing SOD1 with non-SOD1 mice to encourage microbial transfer. The antibiotic treatment decreased motor function and survival in the SOD1 mice, while cohabitation with non-SOD1 mice had no effect. The antibiotics also reduced the abundance of potentially beneficial bacteria and induced changes in the microglia, which are the primary immune cells of the central nervous system. These results suggest that interactions between the microbiota and microglia may help drive ALS progression and highlight the important yet unexpected role of the gut microbiota in overall health.