4 June 2019 – Farmers know that stress is decreasing their animals’ productivity like a dozen tiny straws sipping away at biological resources that should be dedicated to growth or reproduction. But it is intensely difficult to prevent entirely; stress can come from handling, from heat or sudden environmental changes, from shifts in the diet, from disease challenges at a clinical or subacute level, from the vaccines used to prevent those diseases, from toxins, including mycotoxins, or from multiple other sources. And at the same time, it is hard to make a business case for treating something that is so difficult to pin down.

Belgian company Innovad, however, argues that it is possible to combat both abiotic and biotic stress with a multifaceted approach, and obtain quantifiable results. Dr. Christos Gougoulias, Head of Innovation at Innovad, told Feedinfo of his conviction that the market needs not only a holistic and easy to deploy solution for non-specific stress, but also analytical tools that can be deployed at the point of need to measure the impact of this stress— and describes his company’s vision for a way forward.

[Feedinfo News Service] Can you start by explaining the interactions between stress, inflammation, and the health of the animal?

[Dr. Christos Gougoulias] We know that animals possess limited natural resistance and immunity against such cumulative stress leading often to oxidative stress.

Dr. Christos Gougoulias
Head of Innovation
Innovad

As a consequence it is believed that animals raised in modern intensive production systems experience gut dysbiosis or defective host defense towards invasive bacteria, triggering the immune response of the gut, which most probably is in a constant inflammatory response. The key organ recipients of such cumulative stressors are the liver and kidneys.

The impact of such multiple stress factors is worsened and amplified in the presence of toxins (not only mycotoxins) as an additional and major stress factor.

[Feedinfo News Service] To what extent is measurement of stress levels facing animals, and the measurement of these stressors’ effects on the body, even possible?

[Dr. Christos Gougoulias] One key is to establish the necessary analytical tools that are sensitive, cheap and easy to operate at the point of need to objectively establish the “stress baseline” the animals are confronted with. Only this way can we proceed to informed decisions on stress mitigation strategies with a true impact under real farming conditions across all species.

But it is also important to address how we think about these stressors. Today, the focus is mainly on mycotoxins. But even when attention is paid to mycotoxins, the main emphasis is on field surveys, i.e. surveying the levels of mycotoxins in crop/feed production globally every year. There is nothing wrong with this, except that the discussion on the impact of mycotoxins on animal health remains pretty much theoretical. There is a lack of evaluation of the true impact of detoxifier products on systemic levels of mycotoxins in animals and little correlation with their health status.

[Feedinfo News Service] What would serve as the basis for evaluating a different approach to mycotoxin and stress control?

[Dr. Christos Gougoulias] We believe that a relevant solution must demonstrate:

Prevention of oxidative stress. This should be confirmed by the measurement of relevant biomarkers in blood or other non-invasive biofluids in animals, such as saliva.

Strengthening the animal’s natural immune response. Evaluating this in an easy manner is critical, though. For example with the measurement of antibody titres of key vaccines routinely used on each species.

Liver & kidney support, by providing evidence e.g. via functional biomarkers of these two key organs or other histology/ immunohistochemistry indices.

[Feedinfo News Service] How is Escent® S more than a mycotoxin solution? What makes it a stress control solution?

[Dr. Christos Gougoulias] It is both a mycotoxin and a stress control solution. In fact, the Escent® S includes five different modes of action:

  1. Preventing against oxidative stress with a blend of natural and synthetic antioxidants. For example, blood data in pigs suggest it causes a significant reduction of malondialdehyde (a product/biomarker of oxidation).
  2. Supporting the liver function with a special combination of natural plant extracts. In vivo trials in chickens, rabbits and pigs indicate enhanced improvement of liver function under acute stress conditions.
  3. Stimulation of the animal’s immune system with a complex mix of yeast extracts and β-glucans. Measurement of antibody titres of the main vaccines routinely used for each animal species indicated significant increases when animals were challenged with high levels of toxic contaminants.
  4. Triggering biotransformation processes within the liver able to modify toxic contaminants into less harmful polar components.
  5. Adsorbing and binding. Following extensive research at the Veterinary Medical Diagnostic Laboratory of the University of Missouri, we have included in our Escent S Technology a selected cocktail of ingredients exhibiting optimum binding against five different toxic contaminants at two different pHs.

However, at Innovad we do know that this, on its own, is not sufficient. Not all toxic contaminants are polar and therefore will not bind onto a good binder. Hence, the complex technology of Escent® S with the additional four modes of action.

[Feedinfo News Service] Farmers aren’t used to quantifying the stress levels of their herds. How can they know the appropriate level of Escent® S for their particular situations?

[Dr. Christos Gougoulias] Innovad offers a speedy and comprehensive Risk Assessment system for the evaluation of toxic contaminants in feed based on state-of-the-art LC-MS/MS analysis. The only thing that the end user needs to do is to post a feedstuff sample through our rapid, prepaid envelope and within a couple of days he gets informed about the right level of application of Escent® S. What is of great importance, though, is that the analysis takes into account not only the “usual suspects” but also derivatives or conjugates of toxic contaminants.

The feedback from Innovad’s Risk Assessment Service has been great as it provides a valued service to nutritionists and their clients. I can describe the experience from the North East USA dairy market. In 2018 alone we performed 650 tests. Depending on the level of toxins, a follow-up sample of individual feedstuffs might be needed to discover the largest contributor of toxins. Systematic collection of reports of symptoms at the farm level forms an integral part of the process: rough hair coat, lethargic eyes, excess drooling, cud expulsion, inconsistent manure, reproductive issues and lower milk production – all symptoms are manifestations of stress.

The Escent® S technology has a profound impact when a high toxin level is encountered in less than 7 days—but only when fed at the proper level. Impressive results were seen after feeding Escent S for as little as 5 days when toxin levels are high.

Bear in mind that 2017 and 2018 were two of the worst years in the dairy economy in the USA. Escent® S sales have continued to grow each month. That speaks volumes.

[Feedinfo News Service] What kind of evidence do you have proving the efficacy of Escent® S?

[Dr. Christos Gougoulias] At Innovad we are coming to the end of a four-year PhD research with the University of Ghent in Belgium. For the first time we tested the efficacy of our Escent S Technology against blends of mycotoxins as a stress factor in poultry and pigs by following biomarkers for exposure in different biological matrices.

In other words, using sensitive analytical methods, we initially validated which mycotoxins or their derivatives should be measured for each biological fluid per animal species (i.e. excreta and blood for chickens; faeces, urine and blood for pigs). More importantly, we then demonstrated the ability of the Escent® S Technology to significantly reduce the systemic absorption of mycotoxins.

To give an example of what we saw: in chickens challenged with high doses of a blend of DON, aflatoxin B1 (AFB1) and ochratoxin A (OTA), we noticed a 50% reduction of DON and 40% reduction of AFB1 in plasma. These findings are of great importance when taking into account the direct toxicity of DON and fumonisins as a predisposing role in Necrotic Enteritis in chickens as well as a variety of diseases in different animal species.

Succeeding in reducing systemically the levels of such important stress factors could hopefully mean less loss on performance and less disease.

We are really proud that both pieces of research have been published very recently through the peer reviewed process in the highly ranked journal Toxins. We are also glad that Toxins is an Open View Journal, which means free access to everyone.

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Figure 1. (a) Mean high resolution mass spectrometry (HRMS) peak area-time curves (+SD) of deoxynivalenol- sulphate (DON-S) and, (b) Mean concentration–time curves (+SD) of AFB1 in plasma of broiler chickens after oral administration of a bolus of DON (5 mg/kg feed), OTA (2.5 mg/kg feed), and AFB1 (20 mg/kg feed) mix, either with the Escent® group, (n = 8, blue curve) or without (control group, n = 8, orange curve). Adapted from Lauwers et al, Toxins 2019, 11, 187; doi:10.3390/toxins11040187

[Feedinfo News Service] What are the different species and applications where Escent® S has been successful?

[Dr. Christos Gougoulias] Well, the Escent® S Technology is also available as a drinking water application, to support the animal’s own immune system against abiotic and biotic stress as a short intervention during critical periods.

We have seen great results spanning from poultry in Bangladesh to pigs in Spain and even shrimp ponds in Vietnam. The Escent® S Technology has helped shrimp producers in Vietnam to control ammonia levels and other poisonous residues that accumulate within production ponds.

In other words, we have seen a great response in the field given very diverse practices, climatic conditions, geographic territories and animal species.

The water application of the Escent ® technology provides further evidence that its performance is not dependent solely on the binding capacity of toxin contaminants as that capacity does not exist in the liquid format! The systemic effect of the Escent ® technology is attributed to the extra components besides clay, namely, yeast cell wall extracts and a proprietary blend of plant extracts amongst others also evidenced by our novel in vivo research.

To give an example of how the product could be applied: suppose I am a farmer, veterinarian or nutritionist in a big poultry house and this morning I discovered that the ventilation system is not working effectively when the outside temperature has risen to 40°C, while at the same time my new batch of feed is showing increased levels of two mycotoxins I have been struggling with in the past, and to top it all off, my 8-day old chicks were vaccinated three days ago with a combined Newcastle/Infectious Bronchitis live vaccine. What are my options and solutions? What can I do to combat all these stress factors? Fixing each of the above stress factors individually is not an option under real farming conditions. The answer could thus be innovative technologies such as Escent® S.

[Feedinfo News Service] What is the next step for this technology?

[Dr. Christos Gougoulias] We are in the middle of a large-scale field trial in sows where we are testing the efficacy of our Escent® S Technology to systemically lower the levels of key toxic contaminants; more importantly, we are aiming to correlate the findings with the animal health status by implementing key biomarkers.

At the same time, we are working towards the development of robust, sensitive, cheap and easy to operate analytical tools at the farm level i.e. the point of need (PON) for measuring several biomarkers of animal health. These PON tools would enable us to pick up changes at an early stage, hopefully when the animals start getting stressed above physiological levels.

Published in association with Innovad