Researchers mobilise to combat antimicrobial resistance

COPENHAGEN, Denmark, May 5, 2022 /PRNewswire/ -- Worldwide antibiotic use is increasing, which is a major driver of antimicrobial resistance (AMR). The WHO predicts that in just 30 years antimicrobial resistance will become the third leading cause of death globally. Pig production is a major, global consumer of antibiotics, however, with DKK 150 million (€20.1 million) of funding from the Novo Nordisk Foundation, scientists in Denmark, the United States and the Netherlands aim to reduce the need for antibiotic use through the PIG-PARADIGM research project.

Antibiotics are used to treat or prevent some types of bacterial infection, for example in the airways or digestive tract of humans and pigs. However, the current overuse of antibiotics leads to bacteria developing resistance and thus creating a lack of antibiotic efficacy and, worst case, a complete lack of therapeutic options to treat bacterial infections. Currently, more than 700,000 people die each year from infections that are resistant to most, or all antibiotics, and the number is increasing. New approaches to prevent common infections in agriculture can help reduce the need for antibiotics and reduce the spread of antibiotic resistance.

Researchers from universities in Denmark, the United States and the Netherlands are therefore joining forces in a new project, PIG-PARADIGM, collecting 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. The Novo Nordisk Foundation is funding the project with DKK 150 million.

"Antimicrobial resistance is one of the greatest global threats to our health. 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," says Mads Krogsgaard Thomsen, CEO, Novo Nordisk Foundation.

Research on pig intestines will save people's lives

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. If this can be improved, the incidence of diarrhoeal diseases can be reduced and thus the need for antibiotics," says the grant recipient, Charlotte Lauridsen, Professor and Head of the Department of Animal Science at Aarhus University.

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. 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," says Charlotte Lauridsen.

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," she adds.

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. He says: "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."

Associate Professor Mani Arumugam from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen, who is responsible for leading the data integration, says: "Many factors affect a pig's risk of developing infections, from their microbiome and genetics to their diet and environment. 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."

Merete Fredholm, Professor of Animal Genetics, Department of Veterinary and Animal Sciences, University of Copenhagen second 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. She says, "integrative analyses are instrumental for establishing knowledge about the role of host-microbiome interaction on robustness towards intestinal disease."

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. 

Facts about the PIG-PARADIGM project

• The project is called Preventing Infection in the Gut of developing Piglets – and thus Antimicrobial Resistance – by disentAngling the interface of DIet, the host and the Gastrointestinal Microbiome (PIG-PARADIGM).
• The duration of the project is five years: from 2022 to 2027.
• The Novo Nordisk Foundation is enabling the research with a grant of DKK 150 million.
• The five key collaborators in the project are Aarhus University, the University of Copenhagen, Aalborg University, the University of California, Davis in the United States and Wageningen University & Research in the Netherlands.