The projected growth of Aquaculture requires continuous optimisation of feeding regimes, especially in enhancing disease resilience through immunostimulating feed supplements. Seaweed has been introduced as a promising supplement due to its proposed immunostimulant effects, while mitigating carbon emissions and marine eutrophication. Two separate growth trials were performed to evaluate the effects of a seaweed supplement, focusing on a closed land-based RAS system with fish growing from ∼300–600 g and an open water net-based trial with fish growing from ∼500–2500 g. A multi-omics approach was taken to investigate the effect of using up to 2 % fermented sugar kelp (Saccharina latissima) as a supplement on the growth performance and gut health of Atlantic salmon (Salmo salar L.). Standard growth metrics and quality indicators were coupled with multi-omics data for the host intestinal transcriptome, intestinal metabolome, and intestinal microbiome. Levels of iodine and heavy metals in the fish fillets resulting from seaweed inclusion were evaluated. Seaweed additives up to 2 % had no negative impact on the salmon growth performance or other health parameters. While concentration of iodine increased with seaweed addition, all levels remain below recommended thresholds. Furthermore, gut transcriptome analyses of 179 individuals revealed multiple indications for an immunostimulant effect of seaweed, including overexpression of the mucin biosynthesis and pyrimidine metabolism pathways related to mucus production and intestinal homeostasis. Genome-resolved metagenomics revealed a core microbiome dominated by Mycoplasma, Photobacterium, and Brevinema species. Interestingly, the assembled genomes of these three core species had consistently higher levels of genome erosion and gene loss compared to other present species suggesting host adaptation. Further, reduced prevalence of known pathogens such as Aliivibrio highlights a potential protective effect of seaweed by impeding growth of opportunistic pathogens. Results suggest that supplementation of up to 2 % fermented seaweed can increase feed efficiency, stabilise the intestinal microbiome and potentially increase resistance against known pathogenic bacteria including Aliivibrio species.
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