Roundtable: Realising the Promise of Phytogenic Feed Additives — INDUSTRY PERSPECTIVES

Interest in the field of phytogenics, or feed additives derived from plants, was stepped up as animal nutrition began seeking alternatives to in-feed antibiotics to keep animals healthy and productive. Over the last 15 years or so, observers of this space have seen a blossoming of research papers, as well as an increase in the efficacy of the products on offer.

Today, in Feedinfo’s first-ever INDUSTRY PERSPECTIVES Roundtable, we are joined by three leading names in the phytogenic feed additives sector — ADM’s Sebastien Constantin, Herbonis’s Jan Dirk Van der Klis, and Liptosa’s Ewa Sujka. The three discuss considerations in applying and formulating with phytogenic feed additives, future areas of scientific exploration, the legislative/regulatory situation, and emerging trends and innovations.

[Feedinfo] Let’s start by quickly introducing what benefits can phytogenics bring to animal diets.

[Ewa Sujka, Liptosa] Today, the functional applications for phytogenics can be divided into three groups. The first group is [addressing] different health issues. Traditionally, phytogenics were used, or indicated for use, as promoters of intestinal health, gut health. But now we can talk about phytogenics used, for example, to support respiratory health, or to support reproductive health.

The second application for products based on plants – extracts, essential oils – is to improve feed efficiency, so we can maximise nutrient uptake from the feed, reducing production costs as well as reducing environmental impact.

[Feedinfo] What are the key factors to consider when formulating with these additives?

Another point is that it has to be designed and formulated for the respective animal physiology. A monogastric is not like a ruminant, so we need to think about how to manage the targeted release, think about encapsulation, for example.

Third, we need to have a formulation adapted to the technologies of the diet, mixing requirements, etc. We need to think about whether it has to be included in a milk replacer or a pellet, for example, because then we will need to think about the technology of encapsulation again.

Finally, probably the most important point: it has to show efficacy in the application target. So we need to rely on in vitro but also in vivo trials, in published and peer reviewed research, to be sure that we will have the efficacy for specific applications, specific targeted species.

[Jan Dirk Van der Klis, Herbonis] When we are sourcing active components from natural feed ingredients, of course it means variation. Variation comes from different growth conditions like the weather, the area where it comes from, different plants or plant varieties. So, using these natural ingredients means that standardization is extremely important when we’re using those natural ingredients.

For applications like antibacterial effects, often phytogenics are used in combination with other feed additives that have synergistic effects, like monoglycerides, which make the application even more complex.

[Ewa Sujka, Liptosa] I think that one very important point about formulation that many end users will not pay attention to or are not aware of the possibility of, is that by overlapping of different substances of natural origin, it's possible to overdose. There are overlapping effects in phytogenics and we should pay a lot of attention to this.

[Feedinfo] What are the main limitations or bottlenecks in the application of phytogenics?

[Jan Dirk Van der Klis, Herbonis] It's clear that the wealth of active ingredients that we have in nature, on the one hand is a blessing, because we have a lot of active ingredients to choose from, but I also consider it as one of the bottlenecks, as so many different ingredients are used in all kinds of different combinations while the efficacy of these combinations can vary based on the choices made by the manufacturer.

So it's a bit difficult for the end user to weigh the potential performance of one compared to another phytogenic feed additive. The efficacy should therefore be demonstrated for each commercially-available combination of additives, especially for the more complex products, based on a plausible mode of action…

Other bottlenecks would be: pricing, which should generally be covered by the return on investment that should be shown; variation in response based on the animal’s health status and production phase, and the acceptance of the animal of the concentrations of actives which might be the most effective combinations, but which can result in taste effects.

[Ewa Sujka, Liptosa] Additionally, there is another factor that can be seen both as a bottleneck, for sure, but also as an advantage- it is our EU legislation. It is very strict and under constant evolution. So we need to be continuously monitoring all the updates about the authorised ingredients and their definitions, maximum allowed doses, etc.
But at the end of the day, as a reference for quality standards and quality control, European Union manufacturers, we are the worldwide gold standard.

[Sebastien Constantin, ADM] Indeed, the understanding of this type of molecule is just quite new, finally, and it will continually grow over time, and the main bottleneck for me is regulation. There is often a long time between the discovery of a new molecule, for example, and the ability to register it as a new phytogenic solution. There is a need for acceleration, because this type of product could be a great alternative in the fight against antimicrobial resistance.

[Feedinfo] What are the critical research gaps and areas of scientific exploration that need to be addressed to further advance the understanding and application of phytogenic feed additives in animal nutrition?

[Jan Dirk Van der Klis, Herbonis] I would say that it's essential to understand the mode of action of those secondary plant metabolites, including the synergies and the antagonistic effects.

For simple effects, we see that in vitro methods might be available to predict in vivo response. For instance, antioxidant effects, you can [demonstrate efficacy] in vitro, showing the capturing of the oxygen radicals. But many phytogenics work, for instance, via nuclear transcription factors in the cell, meaning they have a physiological response that you cannot mimic in vitro, or else they might work via the activation of cellular receptors, like the vitamin D receptor that is present in many different cell types. This implies that you have to do a lot of the trials on live animals, or maybe if it's possible, on lab scale tissue models.
New research techniques like nutrigenomics, proteomics, metabolomics, can help to understand and optimize the composition, based on proper understanding of the mode of action. Because you study the animal as a whole and you can see which effects are up- or down-regulated, meaning that it helps to understand the pathways, how the different phytogenics or combinations of phytogenics work in the live animal. Such analysis has helped us a lot to understand how the bioactive form of vitamin D, for instance, can improve immunocompetence or epithelial integrity or muscle growth.

Being able to study the animal as a whole is certainly something where I see a big gap [and potential for future research].

[Ewa Sujka, Liptosa] Completely agree with you, [and would emphasize] once again mechanism of action, because the mechanism of action of plant-based ingredients are so broad and so complex that further studies should be done to understand better why certain phytogenics work in one species and in another not, in one application and in another not, or, for example, why one product works in sows but not in boars.
And, really, further study is needed on interactions between the ingredients of phytogenic compounds, but also between phytogenics and other ingredients from the diet.

[Sebastien Constantin, ADM] I also [agree with what has been said about translating in vitro to in vivo understanding, looking at animal-level impacts of phytogenics, and examining synergistic effects with other parts of the diet].

I think another important area to expand our knowledge in is to better understand the role of the gastrointestinal tract and the gut microbiome. There, with the cross talk, maybe phytogenics can have a novel impact on wellness also.

So just, for example, to develop a deeper knowledge of the integrated response of the gut receptors to sensory information, because beyond this sensory flavouring effect, we [might find] that we will tweak some receptor and that will induce a response. And this is exactly where the nutrigenomic will be of interest.

This information transmitted by the phyto molecules to the animals could have beneficial effect, and could be a novel solution…that's where nutrigenomic is an important [frontier for research], nutrigenomics and this link or this bridge between the microbiome and, finally, the host response.

[Feedinfo] What are the emerging trends and innovations in phytogenic feed additives, and how do they impact the future of the sector?

[Jan Dirk Van der Klis, Herbonis] If you talk, for instance, about antibacterial effects of phytogenics, being evident at low inclusion levels through quorum sensing inhibition, the effect can be demonstrated in vitro, but it’s very difficult to also prove in vivo. Still, you need those in vitro data to come up with a plausible mode of action. And the translation from in vitro to in vivo can be done, as said before, using the different -omics techniques to show the full animal response, giving insight in the physiology of the animal and helping explain differences in response between different animals, breeds, and management.

[Ewa Sujka, Liptosa] In our case, a lot of R&D is focusing on the protection and delivery system of active compounds, including how to make it so that active compounds are positioned in the target organ or the important part of the target organ. It's not the same to position the active compounds in the distal part of the large intestine than to position the active compound in the ileum. So how to get the active compound to travel through the organism, how to make this active compound available for the animal in the place where you want the product to work, is very important. Protection systems will allow you to get an active compound in the place where you would like to position it.

And also the stability of active compounds in the feed production plant or the farm, regardless of whether it will be going into feed for a livestock species or for fish, shrimp, or pet food, because we know that the production standards of aquaculture are completely different than for swine or poultry. The challenges are bigger: extrusion, different temperatures, different velocity of processing. So the techniques and technology that allow us to protect active compound are very important to study.

[Sebastien Constantin, ADM] Across the livestock industry, we are talking a lot about environmental sustainability and efficient use of resources for food security, and phytogenics additives can support both of these. We have some phytogenic compounds now that have demonstrated effects to reduce methane emissions in ruminants, for example, minimizing the impact of greenhouse gasses. We have recent studies that have demonstrated some potential effects from phytogenics on ammonia emission in livestock, too.

Moreover, thinking about food security, which is also an important point of sustainability, we know that phytogenics have shown some benefits on how to digest or to use more of the nutrients coming from the diet. Improving digestibility means that animals will optimize performance with fewer resources. We have even seen some benefits to support animal health, overall animal health status, and reducing mortality or morbidity will also support the global food security.