Breaking the mold: The first report on germ-free adult marine medaka (Oryzias melastigma) models

The generation and application of germ-free (GF) fish models are mostly limited to the early life stages with innate immunity and without feeding. Marine medaka (Oryzias melastigma) is a critical animal for evaluating environmental toxicity and human disease models. The gut microbiota contributes to host growth and development, but GF model of this organism has not been successfully generated. In this study, we revealed for the first time the distribution of the gut microbiota in marine medaka during growth and generated GF fish from the larval to adult stages with GF Artemia provided daily as food. According to the basic indexes, weaker behavioral ability, smaller immune organs, reproductive system, intestinal tissues, and transcriptome, the delayed development and differences indicated the negative influences of the absence of the microbiota in GF medaka, compared to conventionally raised (CR) fish at the same life stages. All these results provided novel insights into the application of GF medaka models to define intestinal bacterial functions in the host.