Maturation of the medaka immune system depends on reciprocal interactions between the microbiome and the intestinal tract
Interaction between host immune system and intestinal microorganisms have been studied in many animals including fish. However, detailed analysis has not been done in medaka, one of the established fish models biological studies. Here we investigate effect of immunodeficiency on microbiota composition and effect of gut bacteria on intestinal epithelial development and immune responses.  Chronological analysis of intestinal metagenome of il2rg mutant medaka shows gradual decrease of evenness of OTUs, mainly caused by overwhelm by Aeromonadaceae family. Infection of wild type medaka with high dose of this opportunistic bacteria causes sign of inflammatory response, suggesting harmful effect of Aeromonadaceae on adult il2rg mutant. In addition, we establish germfree condition of larval medaka and observe large absorptive vacuoles in intestinal epithelial cells, indicating block of epithelial maturation. Transcriptome analysis shows decrease of expression of genes involved in defense response including antimicrobial peptide gene hepcidin which were expressed upon LPS stimulation in normal larvae. These results show that reciprocal interactions between the microbiome and the intestinal tract are required for the maturation of the medaka immune system.