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miXscience Talks Science Behind Its New ‘One-of-a-Kind’ Biotoxin Eliminator – INDUSTRY PERSPECTIVES


Source: miXscience via Feedinfo

As climate change continues to affect global temperatures, mycotoxins are now more widespread than ever and have become a common health challenge that production animals are faced with. One that can sometimes overlap with other health threats, resulting in even more pressure being placed on an animal’s immune system and its ability to perform.

French premixer, miXscience, is looking to ease some of this pressure with its new biotoxin eliminator, Multiprotect Up. Created using the company’s patented NOLIVADE Bacillus bacteria strains, the product – which miXscience is marketing as a one-of-a-kind solution – targets and degrades a wide spectrum of mycotoxins as well as endo- and exotoxins produced by common bacteria, like Escherichia coli and Clostridium perfringens. The product also defends against mycotoxin metabolites, which the company explained can sometimes be up to 60 times more dangerous than the parent mycotoxin itself and that this remains relatively unknown in the industry.

So, for more on the science behind miXscience’s Multiprotect Up, how its development came about and its efficacy against common mycotoxins, their metabolites, and bacterial toxins, Feedinfo recently sat down with Product Manager, Anne-Laure Tournay and Research Innovation Development Manager, Clarisse Techer.

 

[Feedinfo] Ms, Tournay, let’s kick off with a quick introduction to biotoxins. What is the definition of biotoxins within miXscience?

[Anne-Laure Tournay] When we talk about biotoxins, we are really referring to naturally occurring toxins, of which there are different kinds. They can be from plants, from animals (such as venin) or from algae. The biotoxins that we are targeting within miXscience, however, are:

- Mycotoxins, which come from fungi,
- Bacterial toxins, of which there are 2 different types:
               - endotoxins, that are released when the membrane of Gram-negative                              bacteria is lysed (e.g., LPS from Escherichia coli)
               - and exotoxins, which are produced and excreted directly by the bacteria                        (e.g., α toxin from Clostridium perfringens)

These different toxins separately have direct negative effects on animal health and production. But what is becoming more evident and reported more in scientific literature is that the interaction and synergistic effects between these two kinds of biotoxins is an important but probably often underestimated risk that needs to be considered.

Our new Multiprotect range is especially developed to counteract adverse effects of all of these biotoxins.

[Feedinfo] Let’s look at mycotoxin contamination. Am I right when I say that this is the norm rather than the exception? And then what does the bacterial toxin contamination landscape currently look like?

Anne-Laure Tournay
Product Manager
miXscience

[Anne-Laure Tournay] Absolutely! You can definitely say that mycotoxin contamination is ubiquitous with 80% of crops worldwide being contaminated. And on top of that, we can also say that mycotoxin co-contamination is the rule rather than the exception. In fact, most contaminations are multiples, with samples being contaminated by at least 2 mycotoxins in almost 50% of the cases!

Furthermore, it is now clearly acknowledged that multiple contaminations have synergistic effects, even if the contamination is low (or under the regulatory/recommended values of the testing institution)!

Mycotoxins contamination is impacted by different factors:

FEED: type of mycotoxin, raw materials origin, mycotoxin quantities, possible synergy between mycotoxins in animal feed

ANIMAL: species, physiological stage, level of ingestion and duration of exposure, stress level, overall health, immune status

BREEDING PRACTICE: hygiene, production density, temperature, building ventilation

LOCATION: climate, different pre- and post-harvest practices. Also, seasonal and local weather conditions may vary in the future due to climate change.

But climate change and co-contamination are not the only challenges that we are facing nowadays. We also have to consider emerging mycotoxins, which are new mycotoxins showing toxicity or metabolites from main families of mycotoxins. Some of these metabolites can sometimes be more dangerous than the parent mycotoxins itself.

With regard to bacterial toxins, it is difficult to accurately assess their presence and contamination levels. This is also linked to environmental and sanitary conditions. However, it is well-known that animals are constantly challenged by high Lipopolysaccharides (LPS) levels, especially ruminants.

 

[Feedinfo] Okay, so let’s zoom in on these mycotoxin metabolites. What can you share with us on their prevalence and how dangerous are they really?

[Anne-Laure Tournay] To start it is important to understand that   mycotoxins themselves are secondary metabolites produced by several fungi, more specifically those of the genera Aspergillus, Fusarium and Penicillium with the main types/families being aflatoxins, ochratoxin A, fumonisins, trichothecenes and zearalenone. But there are a number of different mycotoxins that are also able to produce mycotoxin metabolites themselves when degraded. And while knowledge on the pathogenic potential of mycotoxins has been increasing in recent years (co-contamination, impact on animal health and productivity, interactions in the gut), the adverse effects of their associated metabolites are not totally well known.

This is due to the fact that these metabolites are mostly formed inside the animal, making their monitoring very difficult. But research into the side effects of these metabolites has highlighted their toxicity. For example, zearalenone (ZEA) is known for its oestrogenic effect. But ZEA and its modified forms have different toxicities, with some ZEA metabolites such like α-ZEL, α-ZEL14Glc, other α-ZELGlc’s and α-ZELSulfs sometimes being 60 times more dangerous than ZEA itself.

[Feedinfo] You are putting forward Multiprotect Up as a possible solution to help counteract the adverse effects of mycotoxins, their metabolites, and bacterial toxins in animal production. How long has the product been in development and why are you calling it one of a kind on the market?

[Anne-Laure Tournay] Multiprotect Up is the result of extensive development based on numerous in vitro and in vivo trials on different animal species. It combines our know-how of biotoxins and the action of our patented NOLIVADE bacterial strains.

The story of Multiprotect Up began 10 years ago, when Bacillus strains were initially used to control Salmonella gallinarum in layers. Field observations reported better than expected results, noting interesting effects on the clinical signs related to mycotoxins. Thus, we put forward the following hypothesis: are the Bacillus strains able to counteract the adverse effects of mycotoxins? Knowing that mycotoxin pressure was particularly high at that time, we decided to verify this hypothesis by testing our Bacillus strain in vitro at the Institute of Sciences of Food Production (ISPA, Italy). The first results were astonishing, giving us proof that Bacillus are effective in degrading mycotoxins (ZEA and metabolites, etc.).

To expand on this research, we conducted an in vivo trial on piglets at the Institute of Agrifood Research and Technology (IRTA, Spain) and, this time, were able to prove Bacillus efficiency for limiting the adverse effects of more mycotoxins, such as DON and FUM.

All this research led to us using our NOLIVADE Bacillus strains to develop an innovative and complete solution, which is Multiprotect Up. It combines three modes of action to counteract the effects of biotoxins in two main ways:

- The first is reducing the bioavailability of biotoxins in the gut thanks to an adsorption and degradation action on a wide spectrum of mycotoxins throughout the digestive tract of the host animal
- The second uses a bio-protection action to help the animal eliminate absorbed mycotoxins and limit their adverse effects on different key organs

 

[Feedinfo] Ms Techer, let’s talk about the degradation action of Multiprotect Up a bit more. Ms Tournay briefly mentioned the different mycotoxins miXscience found Bacillus strains to be effective against. But how effective are we talking? What findings can you share with us?

[Clarisse Techer] The degradation action of Multiprotect Up is directly correlated to our NOLIVADE Bacillus bacteria, which can naturally degrade mycotoxins (only few Bacillus strains have this capability).

Our NOLIVADE Bacillus have been rigorously selected and identified, they are natural strains, non-GMO and safe. And this specific action of the bacteria to degrade mycotoxins is patented!

As Anne-Laure said, we in vitro tested the capacity of NOLIVADE Bacillus to degrade mycotoxins and their metabolites, with result showing a degradation percentage of 80 to 100% on ZEA and its associated metabolites! This activity was also demonstrated, to a lesser extent, on fumonisins and ochratoxins.

Figure 1. Zearalenone (ZEA) and its metabolites reduction (%) by Bacillus strains from Multiprotect Up

[Feedinfo] What about the adsorption action of Multiprotect Up? What are the active components being employed to adsorb mycotoxins and how effective is it against common mycotoxins? How does it differ from binders currently on the market?

[Clarisse Techer] The biotoxin binding capabilities can differ significantly from one active ingredient to another due to the complex and diverse structure of adsorbing materials and the chemical diversity of the different mycotoxins.

Aflatoxins have historically received a lot of research attention due to their frequent occurrence in agricultural commodities and related health issues in human and animals. However, as we have touched on, the occurrence and negative impact of various other mycotoxins and the reality of co-contamination necessitates that a product be able to bind a wide number of mycotoxins.

To ensure that Multiprotect Up was the most complete product, we ran a large selection of ingredients through in vitro trials to test their capacity to bind different biotoxins. We selected only the best for our formula to get the most relevant and effective blend, which gives Multiprotect Up its wide spectrum adsorption effect.

Moreover, the physiological conditions of the action site of the product were also important to consider. For example, pH values vary greatly along the digestive tract of animals, from acidic conditions (pH 3 or 4) to more alkaline ones (pH 6 or 7). Binding capacities of products may be influenced by pH changes, leading to the risk that the toxins are adsorbed in one part of the digestive tract but released in another part. This was taken into consideration when we developed our Multiprotect Up solution, to ensure that it will be effective all along the digestive tract of the animal.

 

Clarisse Techer
Research Innovation Development Manager
miXscience

[Feedinfo] What about adsorbing endotoxins and exotoxins? What are the active components being employed here and how effective are they? How were you able to prove this?

[Clarisse Techer] Bacterial toxins, which can be involved in various diseases such as colibacillosis and necrotic enteritis in poultry or neonatal diarrhoea in piglets, can also be bound by some of our active ingredients. But considering the ability of bacteria to develop resistance, we target the metabolites of the bacteria and not the bacteria themselves.

During our in vitro studies, we checked the adsorption capacity of various active ingredients on several types of microbial toxins and in different pH conditions to create our Multiprotect Up formula. We then tested its biotoxin adsorption capacity against other binders on the market. Each was tested at the maximum recommended dosage on the main bacterial toxins encountered in animal issues (toxins from Escherichia coli, from Clostridium perfringens and other problematic bacterial toxins). Multiprotect Up showed the highest toxin adsorption capacity and the widest spectrum of activity.

 

[Feedinfo] As we know it is difficult to bind DON and it is also one of the most common mycotoxins. How does Multiprotect Up fare against this particular mycotoxin? And how does it go about safeguarding animal health when faced with DON?

[Clarisse Techer] Since DON has a complex molecular structure that does not allow it to be easily de-activated by an adsorption mechanism, Multiprotect Up will act against it by indirect means.

The first action is to limit the transfer of DON in the animal body. Bacillus strains have the ability to act on the tight junctions in the intestine, strengthening their barrier effect which limits the transfer of biotoxins. We were able to confirm this by measuring the quantity of DON in the blood of piglets during our in vivo trial with IRTA in Spain. The group supplemented with Multiprotect UP showed a significant (p<0.05) lower amount of DON in the blood compared to the control group, highlighting the Bacillus of Multiprotect Up was able to limit the bioavailability of DON in the organism. This result was associated with better animal performance in the supplemented group.

Multiprotect Up will also contribute to the elimination of biotoxins, such as DON and their main metabolites through the bio-protection effect discussed earlier. Biotoxins (mycotoxins and endotoxins) can destroy liver cells, resulting in an increase in the level of liver cell enzymes (e.g., transaminases, etc.) in the blood. If the hepatic cells are lysed, the liver is less functional and therefore has difficulties to perform its numerous functions. Multiprotect Up contains specific compounds that increase enzymes activity involved in detoxification pathways. It can also provide specific chemical radicals that can bind to toxic molecules, rendering these more hydrosoluble and less toxic, and promoting better elimination from the body. As a result, liver cells are less exposed to toxic molecules and less “destroyed/lysed”. We have been able to confirm these beneficial effects by looking at liver health biomarkers in different trials that were recently performed in dairy cows in Europe and broilers in Africa.

 

[Feedinfo] So now let’s look at where Multiprotect Up is currently available. What are your priorities for expanding the product’s reach? Where are you focusing your efforts?  

[Anne-Laure Tournay] Currently, Multiprotect Up is available outside the European Union. The targeted markets are those confronted with multi-contamination, but ones that may also be interested to protect species sensitive to bacterial toxins in particular. This new solution responds to customers’ demands facing multiple issues related to biotoxins and who are looking for an innovative, effective and broad-spectrum solution against them.

 

Published in association with miXscience

 

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