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.
