Researchers from universities in Denmark, the United States and the Netherlands are joining forces in a new project, PIG-PARADIGM, to collect data on how to improve intestinal resilience in developing piglets, with the aim of advancing knowledge on how to prevent bacterial infections and reducing the need for antimicrobial use. Novo Nordisk Foundation is funding the project with DKK150 million (USD $21.2 million).

"Antimicrobial resistance is one of the greatest global threats to our health," said Mads Krogsgaard Thomsen, CEO, Novo Nordisk Foundation. "By supporting the project, the Novo Nordisk Foundation wants to contribute to generating new knowledge that can help to reduce the use of antibiotics in the pig farming industry and thereby counteract the development of resistant bacteria."

Like humans, pigs develop a complex intestinal microbiome shortly after birth. However, many piglets get diarrhoea at weaning when they are separated from the sow and adapt to the challenge of a new environment and a new diet. At this time piglets become vulnerable to enteric infections which require the use of antibiotics to prevent disease transmission, and the suffering and death of piglets.

"In PIG-PARADIGM, we will gather knowledge about how to increase the pigs' natural defences and immunity in the gut," said grant recipient Charlotte Lauridsen, professor and head of the Department of Animal Science at Aarhus University. "If this can be improved, the incidence of diarrhoeal diseases can be reduced and thus the need for antibiotics."

Antibiotics are designed to kill or reduce the growth of the bacteria that make pigs sick, but they can also eliminate the natural intestinal microbiome, which is important for development of immunity in early life. In PIG-PARADIGM, the researchers will investigate how members of the intestinal microbiome, including bacteria, fungi, archaea and viruses, interact and whether changes in dietary composition or the environment can affect the intestinal microbiome so that less antibiotics are required and thereby that microbial resistance is avoided.

"We know that diet and nutrition strongly affect the composition and function of the gut microbiome among both humans and pigs," said Lauridsen. "Obtaining knowledge about what characterises a healthy and an unhealthy gut will enable us to design the optimal feed-induced gut microbiome, which can strengthen the immune response and the health of the pigs. This will avoid the need for antibiotics."

International collaboration and wide-ranging interest

Extensive data collected from studying pigs will be analysed in detail by researchers in Denmark (Aarhus University, University of Copenhagen and Aalborg University) and internationally (University of California, Davis in the United States and Wageningen University & Research in the Netherlands). The collaboration across institutions and borders will bring together the necessary expertise, technologies and animal studies to find innovative solutions to the problem.

"Through interdisciplinary research supported by the Novo Nordisk Foundation we are positioned to decode the complexities of the digestive tract which have thus far eluded researchers," said Maria Marco, professor in the Department of Food Science and Technology at UC Davis who will be leading the research to understanding how pig diets can be improved. "With this knowledge, we will be able to innovate to provide new approaches needed to prevent antibiotic resistance spread."

Hauke Smidt, personal chair at the Laboratory of Microbiology and Scientific Director of the UNLOCK Research Infrastructure, Wageningen University & Research, will lead efforts towards understanding the processes driving early assembly and functioning of the intestinal microbiome and its interactions with the host.

"This exciting project with its unique combination of expertises opens up entirely new perspectives for the understanding of the interactions of the developing pig, its diet and its intestinal microbiome, and to turn that knowledge into new strategies for healthier pigs," he said.

"Many factors affect a pig's risk of developing infections, from their microbiome and genetics to their diet and environment," said associate professor Mani Arumugam from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen. "So it is vital that we take a holistic approach to understand how these factors influence that risk in order to develop guidelines that can help reduce antibiotic use. Data scientists with a background in biology, who can integrate and analyse the different data, will therefore play a crucial role in this project."

Arumagam is responsible for leading the data integration.

Merete Fredholm, Professor of Animal Genetics, Department of Veterinary and Animal Sciences, University of Copenhagen seconded this opinion. She will be leading the research clarifying the individual and combined impact of the pig host factors and the microbiome on intestinal and systemic health.

"Integrative analyses are instrumental for establishing knowledge about the role of host-microbiome interaction on robustness towards intestinal disease," said Fredholm.

Real-world data

Pork and feed producers all over the world will also follow from the sidelines, and key companies will be invited to join PIG-PARADIGM. The companies will continually use the researchers' new knowledge in their daily work and will provide the project with real-world data. They will eventually be able to implement the knowledge the project generates as specific solutions that can reduce the need for antibiotics in the pig farming industry – thereby helping to reduce the spread of antimicrobial resistance.

The research project thus has great potential for global health, and if the researchers behind PIG-PARADIGM succeed in determining how to reduce the need for antibiotics in pig production, they can help to overcome one of the greatest health threats of our era.