As the primary author, how was this almost 100-page report initiated?

The FAO invited four experts from around the world, including me, to write a paper focused on how nutrition can help reduce antibiotic use. I welcomed this opportunity to collaborate with co-authors Prof. John Patience from the Iowa State University in the USA, Prof. Defa Li from the China Agricultural University in China and Prof. Leo den Hartog from Wageningen University. World Organization for Animal Health (OIE) and the FAO clearly are committed to improving food security, food safety, sustainable agriculture, and working with animal health to reduce the risk of antimicrobial resistance. They asked us to develop a report that could be used as a guide for what the possibilities are from the nutrition side.

It is important to note that the key to reducing antibiotic use in animals is a multidisciplinary approach requiring an investment in a strong biosecurity plan, a well-designed animal vaccine program that is tailor-made for the farm and the specific pathogen challenges they face, implementing best farming practices, especially related to health and welfare, and utilizing nutrition to prevent animal diseases in swine, poultry and ruminants.

What are three takeaways about the state of antibiotic reduction efforts in herds and flocks in 2021?

In the past decade, we have made really good progress worldwide in reducing antibiotic use in farm animals. This clearly demonstrates that it is feasible to reduce antibiotic use significantly. The other good news is that in those countries where it’s combined with good monitoring of antimicrobial resistance, like in the Netherlands, Denmark and a few other countries, they also see a reduction in antimicrobial resistance with the same or even better technical results.

The first takeaway is that we’re making progress. However, as demand for animal protein increases, production levels are also expected to increase. Therefore, the use of veterinary antimicrobials in the world is predicted to increase by 11.5% from 2017 to 2030 in swine, poultry and ruminants (Tiseo et al, 2020). Thus, we are not there yet, and more work is needed. Of note, a similar trend in antimicrobial use is predicted for humans, including a 15% increase from 2015 to 2030.

Secondly, we should expect to see variation in reduction between countries. Some countries have reached the Netherland’s state of very low antibiotic use. Now, it’s much more difficult to further reduce antibiotic use than when we started about 10 years ago. We have already reduced antibiotic use in swine and poultry by 70%, so additional reduction will be difficult. If animals are sick, we do need to be able to apply antibiotics in a responsible way to ensure their health and wellbeing. However, there are still many countries where it can be expected that animal protein demand will increase significantly over the coming years and where we need to establish best practices to control the use of antibiotics, especially critically important antibiotics for human health. In these countries, antibiotic use is often neither reported nor tracked nationwide, so there are still opportunities to lower use there.

Lastly, there are many opportunities to work on animal health with prophylactic nutrition to help prevent diseases and infections. Nutrition should be a targeted approach towards the animal species and subspecies you're working with that is tailormade to the specific farm. Start with the most important - having high feed and water quality and biosecurity in place to control microbial quality. Next, focus on nutritional composition to prevent disorders in swine and poultry. For example, work to reduce the risk for diarrhea in piglets or wet litter in broilers by reducing the protein level, which is a risk factor for both. We can also modify the starch, fat and fiber levels in the feed. Starch is usually safer in a diet because it is less susceptible to impaired digestibility when animals are exposed to a disease or gastrointestinal disorder. Coarse particles and coarse fibers are important in the diet because they have bulking properties that stimulate the gastrointestinal tract. The area of feed additives, like organic acids, prebiotics, probiotics, phytogenics, and other functional ingredients have been shown to contribute to health. We can reduce the need for antibiotics in a profitable way by combining feed, farm and health advice into an antibiotic reduction program, working in close collaboration with the customer.

What are some practices from nations such as Denmark and the Netherlands that can be practically applied in regions seeking to reduce antibiotics?

Denmark and the Netherlands have secured a significant commitment from all stakeholders to work on antibiotic reduction together. In the Netherlands, the government, industry, veterinarians, farmers and scientific groups came together and committed to reduce antibiotic use. Then they started to build several programs to reduce antibiotic use. It became all about the measures - investing in biosecurity, in well-designed and targeted vaccine programs, and applying best farming and health practices across different areas and nutritional measures that support the gastrointestinal defense system. A more radical measure in the Netherlands was the agreement made by the feed industry to ban the use of medicated feed.

During the first few years of the program, it was not easy to maintain the same technical performance of the animals. But now we have adjusted and can keep productivity and animal health high with the antibiotic reduction program that we have implemented. In the first five years, the Netherlands achieved a reduction of 60% of antibiotics in swine and poultry. Since 2015, we’ve added another 10%, so we're now 70% below the reference year of 2009. Other countries have followed a similar approach a few years later and are now very successful as well. China, the US and many EU countries have realized significant reductions in antibiotic use in the range of 30% to 60% in recent years.

How has research on functional nutrition contributed to reducing antibiotic consumption in livestock production?

We have made fantastic progress over the last few decades by enabling new technologies. For example, the 16S rRNA sequencing technology, and nowadays even whole genome sequencing, are giving us much more insight into the composition of the gastrointestinal microbiota. Trouw Nutrition was among the first in animal nutrition research to use this technology about 14 years years ago. It provides a profile or picture of the whole microbiota composition in the gut of a chicken, pig or calf or a human. We started this work together with a human medical group at an academic hospital, a food research institute and Wageningen University. The technology has given us much more insight in recent years about what is a good microbiota and what's the picture of a bad or compromised microbiota. It tells us what kind of bacteria pop up that you don't want to see and which are beneficial groups typically seen in healthy, well performing animals. From a nutrition standpoint, this information has been hugely important in steering our microbiota research efforts.

A second area of research is around a better understanding of the critical factors of good barrier function. Normally, the gut wall acts as a highly selective barrier, taking up nutrients and keeping potentially harmful bacteria outside. New insights have been found to enforce the barrier function by nutrition and prevent ‘leakages’. Furthermore, we are exploring the immune system in terms of immune competence. We are trying to avoid an overreacting immune system because that will create inflammation. So, we are learning about the balance between giving the right stimulus and not overstimulating.

The insights have led on our side to a well balanced and effective feed additive program to improve the microbial quality of feed and water, prevent uptake of harmful bacteria, support digestibility, strengthen gut barrier function, stabilize microbiota and support the natural defense system. There is no silver bullet feed additive. A synergistic approach has proven to be most successful.

Trouw Nutrition also created the LifeStart program, using the premise that early life sets life performance and health. We have seen that the first hours, days and weeks after the hatch of a chick or the birth of a piglet or calf are very critical for the development of the intestinal microbiota and the development of the immune competence of animals. With special nutrition in the first days or weeks of life, we can steer the animal in a desired direction that allows it to become more competent and productive later. Animals will perform better, and they will have better immunity, leading them to fight diseases and infections more efficiently and fall ill less often during their lifetime. Imprinting is also occurring even before birth. We are actively studying what the impact of the mother and her nutrition on the viability and the health of the offspring

What emerging areas are researchers focusing on to develop interventions that manage poultry, pig, beef and dairy production challenges without antibiotics?

In emerging research, there are opportunities to look at nutritional ways to reduce the need for antibiotics for respiratory diseases, not only for gastrointestinal diseases. Research groups are looking at the communication between the gut, the immune system and the lungs. If we can mobilize the immune competence in the gut using nutrition solutions, what might benefit the health of the lungs? This is a very interesting, new area where we believe the industry can make important progress. The same counts for nutritional measures to reduce stress, as stress impacts the functioning of the defense system in the gut and lungs.

Another emerging research area is rapid diagnostics. We now see many more opportunities for on-farm diagnostics that allow farmers and veterinarians to diagnose more effectively a specific health challenge on the farm and link that with nutritional advice or a strategy to improve the situation in that particular farm. This is very positive for antibiotic reduction programs.

From a growth phase perspective, what are some life stages that present an opportunity to reduce the need for antibiotics throughout an animal's life?

In pig and poultry production, we mainly apply antibiotics in young animals since they are the most prone to falling sick, but there are also specific diseases occurring later in life that also need to be tackled. A piglet or chick is typically born with some disease protection from the mother. Piglets receive immunoglobulins from the sow’s colostrum, and in birds, the yolk sac contains immunoglobulins. However, this disease protection disappears after a few days, while the animal is not fully capable of fighting off bacteria or viruses just yet. This period is called the immunity gap in young animals. It's essentially when the animal loses its protection from the mother and is not immune-competent enough in development to tackle disease risks.

During this immunity gap, it is critical to manage everything well in terms of best farming practices, nutrition and health care. The immunity gap in chicks occurs about two to three weeks post-hatch. In piglets, the immunity gap is at three to six weeks of age which is exactly when piglets are weaned. From an economic point and productivity point of view, it might be the right time to wean, but from an animal health and disease resistance point of view, it's not an ideal time. In calves, the immunity gap occurs in a similar period after birth as in piglets. The immunity gap not only counts for gastrointestinal diseases, but also for respiratory infections. In the Netherlands, we have experienced that it's more challenging to reduce antibiotic use in calves than in swine and in poultry because calves are more exposed to respiratory health issues.

What species present the greatest opportunities to reduce antibiotics using nutritional interventions?

Young animals are key, but if you zoom in, there are still some diseases which we have difficulties solving with nutrition. Thus, we need to focus on possible interventions for those specific diseases. I'll mention two examples:

1. Streptococcus suis in piglets: This is an important disease worldwide in piglets which is still very difficult to find successful nutritional intervention methods. Quite a lot of antibiotics are used to combat this disease, even critically important antibiotics.
2. Dysbacteriosis and necrotic enteritis (NE) in broiler chickens: While the two conditions are distinct with different symptoms and effects on animal health, they are often confused. NE is an enteric disease characterized by patches of necrotic tissue on the intestinal epithelium and is caused by specific types of Clostridium perfringens, producing the toxins responsible for the necrotic lesions. While the prevalence of NE is low worldwide (with a slightly higher prevalence in some regions), its presence always causes high economic losses due to necrotic lesions or even higher mortality. The term NE has been widely misused to describe dysbacteriosis without any necrotic lesions. Dysbacteriosis, also called dysbiosis, is defined as the imbalance of microbiota in the intestine, e.g. a shift in composition or distribution of the microbiota. The prevalence of dysbacteriosis is high, and its severity varies around the world. It is causing significant performance losses worldwide, mainly due to its high prevalence. It is a multifactorial disease and triggers can range from an infectious change (coccidiosis, viral enteritis, …) to management issues such as oversupplying nutrients. This is an interesting research area because often, you have preceding, primary subclinical infections or other intestinal stress factors that lead to an imbalance in the microbiota – a dysbacteriosis. This situation may affect the gut barrier function and impair performance. In turn, this imbalance may trigger specific pathogenic Clostridium perfringens bacteria to cause an infection that leads to NE. While some dietary interventions can help, it’s a health problem we still need to learn more about.

What are some promising research efforts underway to accelerate efforts to reduce antibiotics in livestock production?

The industry has quite a bit of research underway on novel feed additives or functional ingredients in general, including novel probiotics, prebiotics, phytogenics or synergistic combinations thereof for example organic acids or medium chain fatty acids. I briefly would like to mention postbiotics which are receiving more attention nowadays. Postbiotic includes a preparation or fermented material with beneficial microbes and then the microbes are inactivated, so it’s no longer a live microorganism. The bioactives produced by the microbes exert gut health-promoting effects. This is an interesting new functional ingredient space to further explore.

Another exciting area is controlled-release technology. Such targeted delivery technologies enable bioactives to be released at the site where you want it delivered. We have, for example, one slow-release medium chain fatty acid that is specifically released in the second half of the small intestine. Normally, medium chain fatty acids are absorbed in the first part of the small intestine. The technology is enabling us to stabilize the microbiota in the lower parts of the gastrointestinal tract.

How does the current regulatory framework help or hinder the use of nutritional interventions?

Animal nutrition is generally regulated by animal feed legislation, and animal health interventions are regulated by veterinary legislation. A fine line separates the two. Animal nutrition solutions intended to prevent, cure, treat or mitigate disease conditions are considered drugs under veterinary legislation in most jurisdictions. This is a significant limitation due to the cost and time required to receive veterinary registration of new products.

The adoption of existing and new dietary interventions will undoubtedly reduce the need for antibiotics. Regulatory recognition of the preventive effects of feed additives used in animal health should further contribute toward reducing antibiotic resistance. A new regulatory environment is needed that is balanced and encourages the implementation of new technologies. New legislation should be considered.

One regulatory option to consider that is currently being explored in the European Union would be to establish a regulatory framework that allows feed additives to make claims about their beneficial effects on animal health and welfare. This approach to feed regulation would avoid overlaps with veterinary legislation and would be more agile for the adoption of innovations and solutions in animal nutrition that contribute to animal health.

Click here to read the report “Animal nutrition strategies and options to reduce the use of antimicrobials in animal production”.

Cited works:

Ema.Europa.Eu. 2021. Sales of veterinary antimicrobial agents in 31 European countries in 2018. https://www.ema.europa.eu/en/documents/report/sales-veterinary-antimicrobial-agents-31-european-countries-2018-trends-2010-2018-tenth-esvac-report_en.pdf.

Tiseo K, Huber L, Gilbert M, Robinson TP, Van Boeckel TP. Global Trends in Antimicrobial Use in Food Animals from 2017 to 2030. Antibiotics (Basel). 2020 Dec 17;9(12):918. doi: 10.3390/antibiotics9120918. PMID: 33348801; PMCID: PMC7766021.