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Abstract

Host-associated microbiotas normally guide the trajectory of intrinsically encoded developmental programs, and dysbiosis is linked to neurodevelopmental disorders such as autism spectrum disorder. Recent work suggests that microbiotas modulate social phenotypes associated with these disorders, though developmental mechanisms linking microbiotas to social behavior are not well understood. We discovered that the zebrafish microbiota is required for normal social behavior. Using this model to examine neuronal features modulated by the microbiota during early development, we found that the microbiota restrains neurite complexity and targeting of specific forebrain neurons required for normal social behavior. The microbiota is also required for normal forebrain infiltration of microglia, the brain’s resident phagocytes that remodel neuronal arbors, suggesting the microbiota modulates arborization via a neuro-immune route. Our work establishes a foundation for study of microbial and host mechanisms that link the microbiota and social behavior in an experimentally tractable model vertebrate.