Differences in gut microbiome composition are linked with health, disease and ultimately host fitness; however, the molecular mechanisms underlying that relationship are not well characterized. Here, we modified the fish gut microbiota using antibiotic and probiotic feed treatments to address the effect of host microbiome on gene expression patterns. Chinook salmon (Oncorhynchus tshawytscha) gut gene expression was evaluated using whole transcriptome sequencing (RNA-Seq) on hindgut mucosa samples from individuals treated with antibiotic, probiotic and control diets to determine differentially expressed (DE) host genes. Fifty DE host genes were selected for further characterization using nanofluidic qPCR chips. We used 16S rRNA gene metabarcoding to characterize the rearing water and host gut microbiome bacterial communities. Daily administration of antibiotics and probiotics resulted in significant changes in fish gut and aquatic microbiota as well as more than 100 DE genes in the antibiotic and probiotic treatment fish, relative to healthy controls. Normal microbiota depletion by antibiotics mostly led to downregulation of different aspects of immunity and upregulation of apoptotic process. In the probiotic treatment, genes related to post-translation modification and inflammatory responses were up-regulated relative to controls. Our qPCR results revealed significant effects of treatment (antibiotic and probiotic) on rabep2, aifm3, manf, prmt3 gene transcription. Moreover, we found significant associations between members of Lactobacillaceae and Aeromonadaceae with host gene expression patterns. Overall, our analysis showed that the microbiota had significant impacts on many host signaling pathways, specifically targeting immune, developmental, and metabolic processes. Our characterization of some of the molecular mechanisms involved in microbiome-host interactions will help develop new strategies for preventing/ treating microbiome disruption-related diseases.

The microbiome community consists of microbes living in or on an organism and has been implicated in both host health and function. Environmental and host-related drivers of the microbiome have been studied in many fish species, but the role of the host genetic architecture across populations and among families within a population is not well characterized. Here, Chinook salmon (Oncorhynchus tshawytscha) were used to determine inter-population differences and additive genetic variation within populations for gut microbiome diversity and composition. Specifically, hybrid stocks of Chinook salmon were created by crossing males from eight populations with eggs from an inbred line created from self-fertilized hermaphrodite salmon. Based on high-throughput sequencing of the 16S rRNA gene, significant gut microbiome community diversity and composition differences were found among the hybrid stocks. These differences likely reflect divergent selection shaping the gut microbiome and its co-evolution with the host. Furthermore, additive genetic variance components varied among hybrid stocks, indicative of population-specific heritability patterns, suggesting the potential to select for specific gut microbiome composition for aquaculture purposes. Determining the role of host genetics in shaping their gut microbiome has important implications for predicting population responses to environmental changes and will thus impact conservation efforts for declining populations of Chinook salmon.