RCUK-CONICYT Mucosal health and microbiota during sea lice parasitism: effect of oral delivery of immunomodulants

The mucosal surfaces (skin, intestine and gills) of fish are constantly interacting with a wide range of pathogens and, in
concert with the resident mucosal microbiota, are the first line of host defence. Several immune factors have been
described in fish mucus and their presence and abundance can be affected by pathogen infection. As a consequence, the
mucosa-associated microbiota can be affected and this may lead to dysbiosis, a microbial imbalance on or inside the body,
which reduces the beneficial role of microbiota on the innate immune system and may lead to secondary infections by
opportunistic microbes. Sea lice (Lepeophtheirus salmonis and Caligus spp.) infections are the most economically
important causative agents of disease in marine-farmed salmonids worldwide. Caligus rogercresseyi is the main
ectoparasite affecting the Chilean salmon industry with estimated costs of up to $120 million annually. This parasite
damages external surfaces of the integument providing portal of entry for secondary infectious pathogens, and infected fish
also become stressed which leads to immunosuppression with consequent increased susceptibility to the secondary
infections. Other Caligid parasites (Caligus rogercresseyi and other Caligus spp.) have detrimental impacts on mariculture
operations in both developing and developed parts of the world which causes economic losses of US$ 100's millions
annually. The development of novel methods to prevent or reduce sea lice infection is therefore a high priority for the
industry. An essential prerequisite for improved treatments strategies is a better understanding of relationship between
host-microbiome-parasite at the epidermal interface. Therefore, the aim of this research programme is to evaluate the
influence of sea lice parasitism on mucosal health, including aspects of the immune response and host microbiota. We will
evaluate the effect of immunomodulants on susceptibility to sea lice infection, and on gut and mucus quality by determining
epidermal mucus proteomic responses, microbiota changes and mucosal transcriptomic changes. We will correlate the
responses of the host and the sea lice during the early stages of parasitism in order to develop new strategies (i.e. identify
antigens for vaccines, targets for RNAi, probiotics, prebiotics, immunomodulants) for sea ice control.

Copepod parasites (sea lice) are a major factor limiting growth in the global salmonid aquaculture sector. Economic losses associated with Caligid infections cost the Chilean aquaculture industry in excess of US$100 million per year. This has detrimental socioeconomic impacts and reduces food security. Caligid sea lice infection is also an emergent threat to nonsalmonid
finfish mariculture in the developing blue economies of North Africa and the Middle East. New therapies and approaches to louse control are urgently required and such strategies can be developed by providing a better understanding of the host-immune-microbiome-parasite interactions. Our main goal is to elucidate the relationship between mucosal health, diet and microbiota in salmon, with knowledge then being transferred to other aquaculture species in the North African/Middle Eastern aquaculture sectors - including Egypt, Turkey, Morocco, Tunisia and Greece where sustainable non-salmonid mariculture is increasingly impacted by Caligid sea lice.

The primary beneficiary of the research is the Chilean aquaculture industry where there is an urgent requirement to develop new approaches to control Caligus, however to develop such therapies basic biology of the interaction between the mucosal immune system and the host mucosal microbiota and the interaction with parasite is urgently required. The findings will have direct impact on the research against the salmon louse Lepeophtheirus salmonis that is a major pest in Northern European salmon aquaculture in UK.

Benefits to the aquaculture sectors of beneficiary regions will come in the form of new potential therapeutics and/or new targets for therapeutics to alleviate the burden of louse infection on fish. Provision of new therapeutics will improve economic growth and sustainability (via improved survival and feed conversion efficiency) in the sector, as well as improve the welfare of the animals themselves.

Consumers will benefit from this research via improvements to fish welfare and associated improvements to food quality. The Atlantic salmon, and other marine finfish, are excellent sources of protein and Omege-3 oils. Improved volumes of these high quality food products on the market will benefit consumers, particularly those of developing countries where the consumption of seafood is below internationally recommended levels. One primary aim is to explore the impact of dietary immunomodulants on louse pathobiology, especially in reducing susceptibility to secondary bacterial infections. Our fundamental research on host-microbe-parasite interactions will generated data which will reveal targets for future treatment strategies. By limiting secondary infections in farmed salmonids we hope to reduce the reliance of Chilean producers on antimicrobials, driving down the prevalence of such drugs and antimicrobial resistant bacteria (and antibiotic residues) in the food chain.

Finally, by identifying tools to reduce the prevalence and abundance of C. rogercresseyi on farmed fish, we hope to reduce the transmission of these organisms to wild fish, and so fishing industries and downstream seafood processing industries (for both farmed and wild fish products) are also potential beneficiaries of this research.

The results from the project will be disseminated via the Marine Alliance for Science and Technology for Scotland (MASTS) aquaculture forum and the Scottish Aquaculture Innovation Centre (SAIC). These are both avenues through which the impact of our project targets key governmental, industrial and strategic plans for aquaculture research. Through our industrial partners (BioMar), who are a sponsor of several major international meetings organised by the World and European Aquaculture Societies, we will reach additional audiences.Through these mechanisms, and as described comprehensively in our "Pathways to Impact Plan", these impacts will be ensured.