An integrated gene catalog of the zebrafish gut microbiome reveals significant homology with mammalian microbiomes

Gut microbiome research increasingly utilizes zebrafish (Danio rerio) given their amenability to high-throughput experimental designs. However, the utility of zebrafish for discerning translationally relevant host-microbiome interactions is constrained by a paucity of knowledge about the biological functions that zebrafish gut microbiota can execute, how these functions associate with zebrafish physiology, and the degree of homology between the genes encoded by the zebrafish and human gut microbiomes. To address this knowledge gap, we generated a foundational catalog of zebrafish gut microbiome genomic diversity consisting of 1,569,102 non-redundant genes from twenty-nine individual fish. We identified hundreds of novel microbial genes as well as dozens of biosynthetic gene clusters of potential clinical interest. The genomic diversity of the zebrafish gut microbiome varied significantly across diets and this variance associated with altered expression of intestinal genes involved in inflammation and immune activation. Zebrafish, mouse, and human fecal microbiomes shared > 50% of their total genomic diversity and the vast majority of gene family abundance for each individual metagenome (~99%) was accounted for by genes that comprised this shared fraction. These results indicate that the zebrafish gut houses a functionally diverse microbial community that manifests extensive homology to that of humans and mice despite substantial disparities in taxonomic composition. We anticipate that the gene catalog developed here will enable future mechanistic study of host-microbiome interactions using the zebrafish model.