The study investigates the molecular mechanisms underlying host-microbial interactions in the zebrafish (Danio rerio) gut using gnotobiotic (germ-free) zebrafish. Gnotobiotic zebrafish were developed and reared through late juvenile stages, allowing for the analysis of gene expression in the digestive tract. DNA microarray comparisons revealed 212 genes regulated by the microbiota and 59 conserved responses in the mouse intestine, including those involved in epithelial proliferation, nutrient metabolism, and innate immune responses. The microbial ecology of the digestive tracts of conventionally raised and conventionalized zebrafish was characterized by sequencing 16S rDNA amplicons. Monoassociation experiments with individual bacterial species showed bacterial species specificity in host responses. These findings establish gnotobiotic zebrafish as a valuable model for studying the molecular foundations of host-microbial interactions in the vertebrate digestive tract.The study investigates the molecular mechanisms underlying host-microbial interactions in the zebrafish (Danio rerio) gut using gnotobiotic (germ-free) zebrafish. Gnotobiotic zebrafish were developed and reared through late juvenile stages, allowing for the analysis of gene expression in the digestive tract. DNA microarray comparisons revealed 212 genes regulated by the microbiota and 59 conserved responses in the mouse intestine, including those involved in epithelial proliferation, nutrient metabolism, and innate immune responses. The microbial ecology of the digestive tracts of conventionally raised and conventionalized zebrafish was characterized by sequencing 16S rDNA amplicons. Monoassociation experiments with individual bacterial species showed bacterial species specificity in host responses. These findings establish gnotobiotic zebrafish as a valuable model for studying the molecular foundations of host-microbial interactions in the vertebrate digestive tract.