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Holistic solution to improve animal food production through deconstructing the biomolecular interactions between feed, gut microorganisms and animals in relation to performance parameters

Periodic Reporting for period 3 - HoloFood (Holistic solution to improve animal food production through deconstructing the biomolecular interactions between feed, gut microorganisms and animals in relation to performance parameters)

Reporting period: 2022-01-01 to 2023-04-30

Ensuring food production remains sustainable while meeting the needs of a growing population is a key challenge that needs to be met. Gut microorganisms play pivotal roles in the health and well-being of animals, and a balanced gut microbiota is essential for optimal food production. Feed additives have proven effective at modulating microbiomes in many systems, although their efficiency often exhibits variation. A likely reason underlying such inconsistency is the limited knowledge we have about their specific means of action. In the best case, companies producing feed additives might employ both in vitro and in vivo experiments to test the properties and benefits of the additive. However, the information capacity of these approaches is limited, as the in vivo response of microorganisms can be radically different to in vitro conditions, as the microorganisms of interest are under different physico-chemical conditions and might interact with hundreds of other microbial taxa as well as the host. Therefore improvement of feed additives often relies on trial and error approaches, which limits development of a full understanding of reasons behind the success or failure of the additives. Consequently, procedures to improve feed additive products are inefficient, and it is unlikely that truly optimal products can be found without drastically modifying the approach taken. HoloFood overcomes these limitations by leveraging state-of-the-art laboratory and computational developments, to provide direct insights into the effects of the biomolecular interactions between feed additives, gut microorganisms and hosts in food production. This was achieved by implementing a novel holo-omic framework, that exploits decreases in the price of generating ‘omic datasets, coupled with cutting-edge biomolecular and statistical methods. HoloFood is based on two observations:i) Animals and their associated microorganisms behave differently depending on the environment and developmental stage of the animal, and ii) many biological processes of animals and their associated microorganisms are affected, or even conditioned, by the other partner of the symbiosis. This implies that the effect of any feed additive could differ based on the genomic background and developmental stage of the animal, microbiome composition, and the production environment. Our framework analyses the genomes, transcriptomes and metabolomes of animals and their associated gut microorganisms, then links this to animal health and physiology, as well as food production performance parameters. To showcase the potential in different food production systems, and measure the commercial and societal impact of our approach, HoloFood performed commercial-scale trials for poultry and salmon in which the biomolecular interactions between microorganisms and animals fed with different feed additives were analysed in relation to food production parameters relating to the the quantity, quality and safety of the food, as well as the sustainability of food production and welfare. By understanding the physiological effects of the biomolecular interactions that occurred when administering different feed additives, HoloFood optimised their use by tailoring their administration to the genomic background and gut microbiome of the animals, as well as the farming environment. As such the aim was to increase the efficiency of feed additives and thereby improve final food products. In the future we believe that other food production systems could be optimised through such holo-omic approaches. Hence, HoloFood will act as a paradigm for approaches and in doing so foster the creation of jobs related to scientific research and the food sector, both with the production companies and associated industries. Moreover, the open resources and data availability resulting from the HoloFood project will be of value for research and industry stakeholders beyond the project's timespan.
We developed a novel framework for sustainable salmon feeds utilising a full hologenomic approach. With this in place, our integrative holo-omic analyses elucidated hidden links between metabolic capacities of bacteria and animal growth, and identified mechanistic links between microbiome development and Campylobacter spread in chicken. In addition, for salmon we have made two major discoveries including the first thorough metagenomic mapping of the complete functional potential and core composition of their intestinal microbiota. Second, we demonstrated the value of analysing the metatranscriptome, to reveal functional differences between microbiome communities that are otherwise identical by species composition. Our industrial partners are undertaking new studies to leverage on the findings in the context of chicken and salmon production. With regards to dissemination and exploitation, a number of peer review publications are completed or under preparation, and our active media presence including newsletters and information videos, and participation in local, European and Global dissemination events enabled wide dissemination of the findings. We also developed a HoloFood Data portal and workbook - two major public resources allowing further exploration of the datasets or design of new experiments beyond the scope of this IA. Additionally we held in September 2022 the first Applied Hologenomics Conference, attracting 300 participants from across academia and industry, and are planning a follow up in 2024 in Copenhagen.
HoloFood introduced a novel applied hologenome concept to the terrestrial and marine animal production and feed additive sectors. The design and implementation of Holo-omic animal trials for both salmon and chicken farming and the information and data types collected provide a huge and unique resource not only for the objectives of HoloFood but for any future holo-omic study aiming to improve any other animal farmed system. All trial designs, laboratory and data generation protocols and data analysis pipelines and integrations so far created and executed are included into the public HoloFood workbook and all omic datasets are organised within the public HoloFood data portal. The close collaboration of experts from all HoloFood beneficiaries, both from research institutions and industry partners means that outcomes from the HoloFood project are already being utilised, particularly within the salmon farming industry. This project goes beyond the state of the art as it introduces and implements the latest technologies and know-how and integrates interdisciplinary expertise across all work packages to achieve its goals. In this regard HoloFood has demonstrated immense innovation potential in both the chicken and salmon systems by uncovering biological insights that were both unknown and unexpected by the onset of the HoloFood project. Future strategies to optimise microbiome functions in chickens have to take the novel HoloFood insights on the direct interaction between certain bacterial species and the overall growth of the host chicken. Similarly for salmon, we have now mapped the naturally occurring bacteria in the unexpected low diversity salmon microbiomes. As such, our results for salmon provide a whole new repository for identifying and developing better pre and/or probiotics in the future that are in line with the naturally occurring species more likely to establish healthy colonies in the salmon intestinal environment.
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