Hologenomic Approach to Understanding Cestode Infections in Farmed Atlantic Salmon

Background and aims: Cestodes represent a major health concern for both human and animal populations. The cestode Eubothrium, which parasitises the gut of Atlantic salmon (Salmo salar), impacts salmon health and is of significant economic burden to the salmon aquaculture industry. There is growing recognition that both host- and parasite-associated microbes participate in host-parasite interactions to affect disease outcomes. The role of microbes in cestode-salmon interactions are currently unclear. We use a hologenomic approach to characterise cestode-associated and salmon-associated microbiomes and investigate how these microbiomes influence host phenotype at multiple -omics levels. Methods: Host genomes, mRNA transcriptomes, metabolomes, metagenomes and 16S profiles were generated from gut tissue and gut content samples from 420 harvest-aged at a seafarm in Bergen, Norway. These -omics datasets were integrated into a hologenomic framework using Multi-Omic Factor Analysis. Cestode infection levels in the salmon gut were scored at time of sampling. For 20 parasitised individuals, one cestode was sampled at the same time and the cestode-associated microbiome characterised with metagenomic and 16S amplicon sequencing. Results: Salmon weight significantly decreased as level of cestode infection increased. Both the cestode-associated and salmon-associated microbiomes were dominated by bacteria of the family Mycoplasmataceae (the mycoplasmas). However, the prevalent mycoplasma phylotype at each site was phylogenetically and functionally different between cestodes and salmon. Comparison of parasitised and non-parasitised salmon revealed that the salmon gut microbiome was disrupted during cestode infection, with increased alpha diversity and decreased abundance of the dominating salmon-associated mycoplasma phylotype. Instead, we observed increases in alternative mycoplasma phylotypes, including those associated with the cestode microbiome. Preliminary results from the multi-omics analysis suggest that the shift in the salmon gut microbiome was accompanied by changes in salmon gut metabolic and gene expression profiles. Microbiome GWAS results also hint at underlying associations between genetic variation, cestode infection and microbiome composition. Conclusions: Our results indicate that cestode infection is associated with gut dysbiosis in the salmon host, which correlates with shifts in host functional profiles. Future work will determine the biological significance/meaning of these shifts. Our study highlights the importance of a hologenomic approach to understanding parasite infections, taking into account both host- and parasite-associated microbes. Such approaches further our understanding of host-parasite interactions and may reveal novel targets to improve fish welfare and sustainable aquaculture practices.