IL-22 from enteroendocrine cells promotes early-life gut motility in zebrafish through the microbiota

The gut microbiota, immune system, and enteric nervous system interact to regulate adult gut physiology. However, the mechanisms establishing gut physiology during development remain unknown. We report that in developing zebrafish, enteroendocrine cells produced interleukin-22 (IL-22) in response to microbial signals before lymphocytes populated the gut. In larvae, IL-22 shaped the gut microbiota, increasing Lactobacillaceae abundance and ghrelin expression to promote gut motility. Impaired motility and ghrelin expression were restored in il22^-/- zebrafish by transfer of microbiota from wild-type zebrafish or by introducing only Lactobacillus plantarum. IL-22-deficient mice also had impaired gut motility and reduced ghrelin expression in early life, indicating a conserved function. Thus, before immune system maturation, enteroendocrine cells regulate early-life gut function by controlling the microbiota through IL-22.