Cell-type-specific responses to the microbiota across all tissues of the larval zebrafish

Animal development proceeds in the presence of intimate microbial associations, but the extent to which different host cells across the body respond to resident microbes remains to be fully explored. Using the vertebrate model organism, the larval zebrafish, we assessed transcriptional responses to the microbiota across the entire body at single-cell resolution. We find that cell types across the body, not limited to tissues at host-microbe interfaces, respond to the microbiota. Responses are cell-type-specific, but across many tissues the microbiota enhances cell proliferation, increases metabolism, and stimulates a diversity of cellular activities, revealing roles for the microbiota in promoting developmental plasticity. This work provides a resource for exploring transcriptional responses to the microbiota across all cell types of the vertebrate body and generating new hypotheses about the interactions between vertebrate hosts and their microbiota. [Display omitted] •The Larval Zebrafish Gnotobiotic Atlas: a resource of microbiota-responsive genes•The microbiota induces transcriptional responses across all tissues of the body•The microbiota stimulates widespread transcriptional signatures of ATP production•The microbiota promotes exocrine pancreas growth and functional plasticity The Larval Zebrafish Gnotobiotic Atlas provides a comprehensive resource of microbiota-dependent transcriptomes across the entire body at single-cell resolution. Massaquoi et al. show gene expression changes between conventionalized and germ-free cell types to the microbiota, not limited to tissues in direct contact with resident microbes.