Leveraging microbiota services through hologenomic analyses to improve gut health in farmed salmon

Atlantic salmon aquaculture is one of the most profitable and technologically advanced fish production industries in the world. However, improved practices are imperative if the industry is to sustainably meet future global production demands. Ongoing industry challenges include frequent disease outbreaks, inefficient feed conversion and losses due to unpredictable variation in fish size at harvest, even in fish from the same genetic broodstock raised in identical environmental conditions. We investigated whether a hologenomic approach could identify novel pathways linking the salmon gut microbiome, gut metabolism, and host genetic variability to the observed phenotypes, focusing on fish size at harvest. Genomes, transcriptomes, epigenomes, metabolomes, and metagenomes were generated from the guts of 460 harvest-aged Norwegian salmon (gutted weights: 0.8–7.8 kg), from the same broodstocks and open-water pens. Consistent with previous studies, the salmon gut microbiota was characterised by low microbial biomass and low alpha diversity, with most individuals dominated by a species of Mycoplasma specific to salmonids. As expected, host genetic variation was low, and a GWAS found only weak evidence for a host genetic link to microbiota composition. However, we identified subtle shifts in the microbiota that were associated with fish size, including increased abundance of Mycoplasma in larger, healthier fish. Multi-omic factor analysis revealed that these fish were also characterised by shifts in gene expression and metabolic profiles, including changes in fatty acid and lipid metabolism, concordant with the higher levels of omega-3 fatty acids observed in the muscle of these larger fish. We also identified links between Mycoplasma genome functions and host gut metabolism, specifically in prenol-associated pathways of both, suggesting host-specific adaptation of Mycoplasma to the salmon gut. Our results demonstrate the value of a hologenomic approach to more fully understand how complex host–microbe interactions shape growth and health performance in farmed salmon.