INTERVIEW: Ambitious International Project to Decode Interactions Between Piglet Gut, Feed, and Microbiome

13 June 2022 by Shannon Behary

Why do some piglets get sick while others, exposed to the same conditions, do not?

It is a question at the heart of improving swine health, productivity, the efficacy of feed additives, and the reduction of antimicrobial resistance (AMR). But the answer to this question is as complex as the porcine digestive system, and involves an understanding of several moving parts, from the microbiome, to the feed, to the intestines themselves.

Last month, the Novo Nordisk Foundation announced it would be funding a project to take on all three elements simultaneously. The DKK 150 million (€20 million) grant will support PIG-PARADIGM, a fundamental research project spanning five years and five universities located not only in Denmark, but also in the Netherlands and the US. Aarhus University is coordinating the consortium.

As per the press release announcing the grant, researchers will investigate how different elements of the intestinal microbiome, including bacteria, fungi, archaea and viruses, interact, as well as whether changes in dietary composition or the environment can affect the intestinal microbiome in order to reduce the use of antibiotics in young swine and thus avoid contributing further to the development of AMR.

The dietary research pillar will be headed by a researcher at the University of California Davis, and the microbiome pillar at Wageningen, while the pillar related to host (pig) intestinal and systemic health will headed at the University of Copenhagen, which also hosts the head of the data integration pillar. Two other Danish institutions—Aarhus University and Aalborg University—are also deeply involved.

Fundamental research necessary to unpack GI issues

According to Professor Charlotte Lauridsen, project coordinator for PIG-PARADIGM and Head of the Department of Animal Science at the University of Aarhus, “around 85% of the use of antibiotics in [Danish ] pig production is for treating gastrointestinal diseases in newly weaned piglets.”

Therefore, improving our understanding of what distinguishes a healthy young pig’s GI tract from an unhealthy one is critical to any effort to reduce overall usage of antibiotics (or of medicinal use of zinc oxide). Professor Lauridsen claims that the need for more expansive fundamental research in this area has been apparent “for a long time”.
“This is why the Novo Nordisk Foundation [got involved] in such a project. They’re typically funding more fundamental and strategic research,” she asserts.

“This project is certainly not just for improving pig gut health. It’s about reducing AMR.”
Among the tasks ahead for the PIG-PARADIGM researchers are: sampling a large number of pigs in a cohort study, then trying to characterise the pig and its microbiome. This will be followed by “more intensive experiments where we are looking, from a mechanistical point of view, for knowledge which can lead to nutritional solutions,” by which she means feed formulation concepts such as low protein diets, the use of fatty acids and carbohydrates, etc.

When it comes to the dietary aspect, Professor Lauridsen says they will be looking at inflammation, oxidative stress, and understanding what conditions lead to a morphologically-changed gut: “why does one gut look like this when in other circumstances it looks different? And the metabolome of the pig—how does it respond to what we observe in the gut?”

In other words, the dietary research is not immediately focused on treatment of gut issues through dietary intervention, but on understanding how different conditions-- oxidative stress, for example-- are influenced by different diets. Beyond that, there is even the hope that biomarkers can be identified in order to make this information actionable, to be able to identify which piglets are at risk for diarrhoea and why.

What it aims to achieve

From sequencing the microbiomes to carrying out intensive nutrition studies, the different elements of the PIG-PARADIGM project will be generating a huge amount of data, which will be put into what Professor Lauridsen refers to as the data integration pillar. In her words, this data, connecting what is seen in the gut with the pig (host) responses and allowing for deep analysis, will enable microbiome targeted dietary interventions that improve and/or support intestinal development and health by reducing the risk of infectious diarrhea.

While gut health has been a main focus of nutrition-related swine research for years, this project is primarily distinct from others in the scope of what it hopes to capture. “Sometimes, [with] smaller projects, you are not capable of going into the mechanisms, and going in-depth to provide the knowledge base we are looking for” she observes .

And for something as complex as the gut, studying a small piece of the whole means eliminating a lot of detail. “[Analysing the gut microbiome] along the whole gastrointestinal tract, you’ll see a lot of microbial societies, but also you have microbial societies which are changing from the lumen of the gastrointestinal tract to the inner compartment,” she explains. Given that diversity, “there are really a lot of ways to tackle [gut health analysis], and very seldom you have one project where you can do [the whole thing.]”

Professor Lauridsen is also hopeful about the insight in different facets of AMR reduction that this project will provide to the next generation of scientists, the PhD’s and postdocs who will be participating. “We are also going to study what we call the resistome. This is highly centred around the pig microbiome. There is a lot of knowledge being generated on the bacteria that’s in the intestine, but we also have viruses and other microbial species. Learning about the communication between these different microbial species, and also being able to study the resistome, that is also what our data integration pillar is all about.”

Finally, PIG-PARADIGM aspires to generate knowledge which will be used as a resource for the industry to develop new nutritional tools to preserve gut health. In some cases, it could even help refine our understanding of tools, which have been in use for a while, but perhaps without a full understanding of the conditions under which they work best. As Professor Lauridsen puts it, even in the context of Danish producers who have been working on AGP-free production for years, “some farms say they can simply manage and do without any medical zinc, and any antibiotics, and so on. But there are also farms where it is very difficult.” Indeed, as many in the industry can attest, the variability in responses to even well-developed feed additives can present a real challenge to their wider adoption.

Professor Lauridsen emphasises that the project, though not in itself concerned with feed additive development, is very much intended to be a foundation upon which future innovation in the area can build. “I really hope that this project will also generate a lot of other collaborative projects,” she says. “It’s really a platform for developing a lot of knowledge that will hopefully be used as a starting point for other, maybe more applied projects with industrial partners.”