Posts

Mycotoxin kinetics: Did you know how quickly mycotoxins disappear?

Impacts of mycotoxins on farm animal performance and health are generally well known. However, what is often less well known are mycotoxin kinetics and the metabolism of mycotoxins, when they pass through the digestive tract. Based on the current scientific literature, this is also an area of research that still requires greater understanding.

Considering that most dietary mycotoxin solutions will act on mycotoxins in the gut, it is important to understand the time window for action available in the gut. Increasing knowledge of mycotoxin kinetics and metabolism highlights that speed can be a critical characteristic for the mode of action in mycotoxin solutions, as well as the location for mode of action in the animal’s body.

Pharmacokinetics

The pharmacokinetic behaviour of an orally ingested compound determines how readily it is absorbed from the gastrointestinal tract, which concentrations are reached in the various organs, and how long the agent and its metabolites will stay in the body. These aspects are of prime importance for the biological effects and risk assessment.

Mycotoxins have varying bio-availability. Some will be more rapidly absorbed, whilst others will travel further along the digestive tract. This is very important for a number of reasons:

1) Whether absorbed into the systemic circulation or not, the cells of the gastro intestinal tract (GIT) will potentially be exposed to the full range of ingested mycotoxins and in the highest concentrations.
2) Mycotoxins that are rapidly adsorbed can cause damage in other organs and their metabolism can result in more toxic metabolites as well as waste of metabolic energy.
3) The pace at which mycotoxins will be adsorbed from the gut, will affect the time window for dietary mycotoxin solutions to act on mycotoxins in the gut.

Intestinal absorption of mycotoxins in the gut

Mycotoxin uptake and subsequent tissue distribution is governed by GIT absorption. This passage across the intestinal barrier may be maximal, as with aflatoxins or very limited, as with fumonisins (Table 1). The rapid appearance of most mycotoxins in the circulation suggests, that the majority of the ingested toxin is absorbed in the proximal part of the GIT.

Absorption of deoxynivalenol (DON) is on average 55% in pigs, but very limited in poultry (Table 1). The relative tolerance of poultry to DON has been partly attributed to its low bioavailability. However, the potential impact of the remaining DON in the intestinal lumen is still unknown, and the tolerance level within the GIT might be different.

Further details on DON kinetics and metabolism are discussed later in the text.

mycotoxin absoprtion - gut

Kinetics and metabolism of zearalenone (ZEA)

In pigs zearalenone and its metabolites were found in the plasma of a pig less than 30 min after the beginning of feeding.

The first reported mammalian phase I metabolites of ZEA are the stereoisomers of zearalenol (ZOL) – α-ZOL and β-ZOL. α-ZOL is 92 times more oestrogenic than ZEA. β-ZOL is 2.5 times less oestrogenic than ZEA. The metabolization of ZON occurs primarily in the liver, but a variety of organs show metabolization activity, such as intestine, kidney, ovary and testis.

Observations in pigs indicate that ZEA is rapidly and efficiently absorbed after oral intake and metabolised to ZOL and glucuronides of ZEA and ZOL. The glucuronides are efficiently eliminated into the bile, but hydrolysed in the intestine and the aglycones reabsorbed, accounting for the secondary peaks in plasma level. The extensive enterohepatic circulation of ZEA and its metabolites slows the excretion and extends the half-life of this mycoestrogen in the pig. The enterohepatic recirculation of ZEA and α-ZOL was confirmed in a later study on the fate of a single dose of ZEA administered intravenously to young female pigs (Dänicke et al 2005).

In broilers, a large proportion of ZEA was changed into. α -ZOL and β -ZOL in the plasma and various tissues of broiler chickens following oral administration of ZEA. This suggests that ZEA was absorbed and metabolized rapidly. The absolute oral bioavailability of ZEA was 29.66% and was higher in broilers than in rats (2.7%) ZEA is excreted largely in the form of α -ZOL in the excreta of broiler chickens. (Buranatragool et al 2015).

In another study, the rate of reduction of zearalenone into α- and β-zearalenol was compared in geese, ducks, guinea-fowl, chickens, laying hens, and quail. Zearalenone reduction was lowest in geese and highest in quail. Although α-zearalenol was the main metabolite formed in all the avian species, the α:β ratio ranged from 1:8 in quail to 5:3 in chicken (Guerre 2015).

In ruminants, the nearly complete recovery of ingested ZON at the duodenum as a-ZOL, b-ZOL and ZON suggests only a minor complete degradation in the rumen under steady-state conditions or some interference with an intensive entero-hepatic cycling of these substances (Dänicke et al 2005b).

Studies in lactating dairy cows revealed that with daily doses of 50, 165 or 544 mg ZEA for 21 days, concentrations of 2.5 ng ZEA and 3.0 ng α-ZOL per ml milk were only detected as conjugated products in cows fed the highest dose of ZEA. Thus, even though minute amounts of ZEA and its metabolites are transmitted into the milk of cows from contaminated feed, this carry-over is minimal. (Metzler et al 2010)

Kinetics and metabolism of aflatoxin

Following ingestion, aflatoxin B1 (AFB1) more than 80% is rapidly absorbed in the intestinal tract in both poultry and pigs. The duodenum was found to be the major site of absorption. From the site of absorption, AFB1 enters the blood stream and is transported to the liver, the major site of metabolism.

Metabolism of AFB1 can be divided into three phases, bioactivation (phase I), conjugation (phase II) and deconjugation (phase III), all of which can occur directly at the site of absorption, in the blood, after entering the liver as the main metabolizing organ, or in several extra-hepatic tissues. Aflatoxin B1 itself is not a potent toxin, and phase I bioactivation is needed to exert toxic effects.
Phase I reactions are mainly oxidation of AFB1 to hydroxylated metabolites such as aflatoxin M1, aflatoxin Q1 and aflatoxin P1 and to the highly reactive AFB1-8,9-epoxide. Cytochrome P450 enzymes (CYPs) are known to play the major role in oxidation of AFB1 to the reactive epoxide in many tissues.

Phase II metabolism includes conjugation of phase I metabolites with glutathione or glucuronic acid and is considered detoxification to enhance water solubility and excretion. Conjugates of epoxide and hydroxylated AFB1 metabolites are readily excreted via the bile into the intestinal tract, where they might be subject to bacterial deconjugation as phase III reaction.
The major route of excretion of AFB1 and its metabolites is the biliary pathway, followed by the urinary pathway. In lactating animals, AFM1 and other metabolites are excreted in the milk.
(adapted from Gratz 2007)

Kinetics and metabolism of deoxynivalenol (DON)

After oral intoxication of pigs, DON starts to appear in the plasma after 30 min. A study on bioavailability of DON in pigs revealed that DON was rapidly absorbed following oral exposure and reached maximal plasma and serum concentrations after 99.1 min. The mean bioavailability of DON was 54%. DON was highly distributed and poorly metabolized. (Goyarts and Dänicke 2006).

In avian, species the levels of DON in plasma following oral administration are relatively low, recent results suggest that DON is highly metabolized, leading to the formation of sulfates, which are a detoxified form of the toxin. This metabolism differs from that observed in some mammal species, in which de-epoxidation is recognized to be the most important step. Although the persistence of DON in tissue and its transmission to eggs are limited, the metabolites of the toxin, especially 3α-sulfate, should be measured (Guerre 2015).

In ruminants, the low recovery of DON at the duodenum as de-epoxy-DON and DON would indicate either a nearly complete degradation of the molecule in the rumen and/or absorption at this site of the digestive tract (Dänicke et al 2005b). However, detoxification capacity for DON by rumen bacteria can be compromised in high producing dairy cows, which are fed greater amounts of concentrates and where feed passage rate is high. Both conditions will affect rumen pH and the time available to degrade DON into non-toxic metabolites. Low rumen pH has a negative impact on the rumen microbes that would otherwise detoxify DON. Jeong et al (2010) report that high concentrate to forage rations reduce the amount of DON detoxified by rumen bacteria by 14%. Similarly, Hildebrand et al (2012) observed that DON can negatively influence rumen fermentation and microbial protein synthesis to a greater extent in high concentrate rations than in low concentrate rations.

The rank order of sensitivity of animals to ingested DON is pigs > poultry/ruminants. Intestinal explants (cultured tissue samples) from poultry and pigs possess a similar ability to intestinally absorb DON, suggesting that the difference in their sensitivity to ingested DON does not rely on their ability to intestinally absorb DON.

It is more likely that the sensitivity of animals to oral DON relies on the localization of the intestinal bacteria in their gut in relation to their ability to generate 9,12-diene DON or DOM-1, the non-toxic de-epoxide derivative of DON (Maresca 2013). The presence of high bacterial contents that can convert toxic DON into its non-toxic de-epoxide metabolite DOM-1 before the small intestine in ruminants (rumen-associated bacteria) and poultry (crop-associated bacteria) hugely decreases the amount of native DON reaching the small intestine.

In pigs, due to the high absorption of DON by the small intestine, bacterial transformation of DON in DOM-1 could only be possible if a part of the ingested DON reaches the colon and/or in the case of intestinal/hepatic excretion of absorbed DON.

Differences between animal species

Mycotoxin metabolism can occur in both the liver and the digestive tract. Intestinal metabolism, be in the gut epithelium or by gut microorganisms, may limit the toxic effects of mycotoxins within the GIT. This is especially true for ruminants which can convert many mycotoxins into non-toxic metabolites. Greater resistance to zearalenone, DON or ochratoxin in ruminants has been attributed to the detoxifying role of the microbial population in the rumen. These mycotoxins are effectively transformed into non-toxic metabolites by rumen microorganisms before absorption. However, in non-ruminants, intestinal biotransformation of mycotoxins takes place predominantly in the large intestine and thus provides little detoxification prior to absorption. (Grenier and Applegate 2013)

Scientific data suggest that the toxicokinetics of fusariotoxins in avian species differs from those in mammals. The use of radio labelled DON, T2-toxin, and zearalenone revealed high biliary excretion of these toxins whereas the amount of the parent compound in plasma was low. This observation and the low level of radioactivity found in tissues led to the conclusion that fusariotoxins are weakly absorbed and rapidly eliminated in birds.

Metabolism appears to play a key role in avian species. For instance, the metabolic pathways of DON in avian species strongly differ from what was reported in rat, pig, cattle and sheep, which could contribute to the reported difference in sensitivity to DON. De-epoxidation of DON, which is the main detoxification mechanism in mammals, appears to play a less important role in avian species. In avian species, it seems that sulfation is a key protective mechanism. (Guerre 2015)

Speed matters

The message from the scientific literature is that the potential time window for action on some mycotoxins in the gut is short – for zearalenone in pigs 30 minutes or less, before they get absorbed into the blood system.
The consequence is that speed is of great importance, when it comes to solutions that act on mycotoxins in the gut to counteract their harmful effects. The alternative is that they also should be able to act on the mycotoxins or reduce their impact outside of the animal’s digestive tract, i.e. in the blood system or other target organs for mycotoxins in the animal.

Adapt vs attack – strategies for counteracting mycotoxins

Traditionally, feed additives have been developed to attack mycotoxins in the animal’s digestive tract directly to counteract harmful effects from mycotoxins in the animal. However, both mycotoxin binders and mycotoxin deactivators have their limitations.

It is well known that adsorption is not an effective strategy for most mycotoxins. Only certain bentonites work well with aflatoxins and some yeast cell wall components have been proven to bind zearalenone, based on specific structural fits. For other types of mycotoxins, particularly DON, binding strategies do not work effectively.

Biotransformation of mycotoxins is another strategy that directly attacks mycotoxins to transform their structure into non-toxic metabolites. Again, this strategy is very specific to certain target mycotoxins. On top of that, it takes time to complete the biotransformation of mycotoxins and time to do so in the digestive tract is limited. Find out how long it takes to transform mycotoxins in vitro in this scientific paper.

The question is, how does the animal deal with the mycotoxins left untouched by the highly specific feed solutions mentioned above?

A third and more cost-effective strategy to counteract mycotoxins focuses on disarming mycotoxins by supporting the animal’s resistance to the harmful effects of mycotoxins. This strategy empowers animals to adapt to nutritional stress factors such as mycotoxins and reduces the extent of the stress reactions generally seen in response to these stressors . Find out more about stress reactions

This strategy is not a direct attack on mycotoxins, but it helps the animal to shield itself efficiently from the negative effects of a broader range of mycotoxins, when challenged. It is non-specific for mycotoxins, but highly specific on the side effects of the most important mycotoxins.

References

Buranatragool et al (2015). Dispositions and tissue residue of zearalenone and its metabolites α-zearalenol and β-zearalenol in broilers. Toxicology Reports 2 ,351–356

Dänicke et al (2005). Kinetics and metabolism of zearalenone in young female pigs. Journal of Animal Physiology and Animal Nutrition 89, 268–276

Dänicke et al (2005b). Effects of Fusarium toxin-contaminated wheat grain on nutrient turnover, microbial protein synthesis and metabolism of deoxynivalenol and zearalenone in the rumen of dairy cows. Journal of Animal Physiology and Animal Nutrition 89, 303–315

Devreese et al (2013). Overview of the most important mycotoxins for the pig and poultry husbandry. Vlaams Diergeneeskundig Tijdschrift, 82

Goyarts and Dänicke (2006). Bioavailability of the Fusarim toxin deoxynivalenol (DON) from naturally contaminated wheat for the pigs. Toxicology Letters, Volume 163, Issue 3, Pages 171–182

Gratz (2007). Aflatoxin Binding by Probiotics, Experimental Studies on Intestinal Aflatoxin Transport, Metabolism and Toxicity, Doctorial Thesis; University of Kuopio, Finland

Grenier and Applegate (2013). Modulation of Intestinal Functions Following Mycotoxin Ingestion: Meta-Analysis of Published Experiments in Animals, Toxins 5, 396-430

Guerre (2015). Review: Fusariotoxins in Avian Species: Toxicokinetics, Metabolism and Persistence in Tissues, Toxins, 7, 2289-2305

Hildebrand et al (2012). Effect of Fusarium toxin-contaminated triticale and
forage-to-concentrate ratio on fermentation and microbial protein synthesis in the rumen. Journal of Animal Physiology and Animal Nutrition 96, 307–318

Jeong et al (2010), Effects of the Fusarium mycotoxin deoxynivalenol on in vitro rumen
fermentation, Animal Feed Science and Technology, 162, 144–148

Maresca (2013). From the Gut to the Brain: Journey and Pathophysiological Effects of the Food-Associated Trichothecene Mycotoxin Deoxynivalenol. Toxins (Basel); 5(4): 784–820.

Metzler et al (2010). Zearalenone and its metabolites as endocrine disrupting chemicals.
World Mycotoxin Journal, 3 (4): 385-401

Vekiru et al (2010). Cleavage of Zearalenone by Trichosporon mycotoxinivorans to a Novel Nonestrogenic Metabolite, Applied and environmental microbiology, vol. 76 no. 7 2353-2359

DON- How does deoxynivalenol (DON) affect feed intake in pigs

A well known response to the mycotoxin deoxynivalenol (DON) is a reduction in feed intake. This is particularly the case in pigs. According to a meta-analysis (Andretta et al 2012) DON reduces feed intake by 26% in pigs.
DON is globally the most prevalent mycotoxin in pig diets and there are signs that this year’s harvest of certain crops is contaminated with significant levels of this mycotoxin. Feed intakes at risk with DON in 2016/17 harvest

What controls appetite?

One constant physiological factor of appetite control are certain gut peptides, of which cholecystokinin (CCK) is one of them. CCK is released in response to feed intake and sends signals to the brain contributing to the sensation of satiety, when it binds to certain receptors, such as CCK1R.

Scientific studies show that CCK1R antagonists increase meal size and food intake in experimental animals, and they increase hunger, meal size, and caloric intake in humans.

Physiological effects of CCK include stimulation of gastric acid, gallbladder and pancreatic secretion, decreased gastric motility and suppression of energy intake.

Researchers studied the control of eating by CCK in pigs extensively. As in humans, carbohydrates, proteins and lipids all stimulate CCK secretion in pigs. Active immunization against CCK increased food intake and body weight in pigs (Pekas and Trout 1990) confirming the importance of CCK in feed intake.

How does DON affect appetite?

More recent studies carried out in mice show that the decreased feed intake in mice in response to DON in the diet corresponds with a significant increase in CCK in mice compared to a control diet. Studies with a relevant antagonist known to bind to the same receptors as CCK report that the negative impact of DON on feed intake in mice can be reduced through the antagonist.

The conclusion was that CCK plays a major role in feed intake reduction in response to DON. DON exposure also elicited higher proinflammatory cytokine responses in mice, which could be another cause of DON-induced anorexia.

Test your knowledge on mycotoxins

Agility for competitive animal production in the EU

Animal producers and animal feed companies in the EU are facing tough times in a highly competitive and rapidly changing environment. Agile nutrition concepts are the next step towards more agile operations, maintaining a competitive edge and increasing efficiency. By Gwendolyn Jones, Anco Animal Nutrition Competence GmbH

The European livestock sector contributes €130bn annually to Europe’s economy and represents 48% of total agricultural activity. With the rapid growth of efficient farming businesses outside the EU, growth in productivity is essential for EU livestock farmers in order to stay competitive. According to a whitepaper by the Animal Task Force (ATF) this requires imaginative and innovative system approaches.

The ATF announced that one of the top priorities for competitive animal production in Europe is to improve resource efficiency of animals. This means more efficient and robust animals that are healthier, more resilient, have an increased well-being and have a lower feed conversion rate. Key to this for genetic selection will be identifying appropriate indicator traits that reflect improved resource-use efficiency. Furthermore, feeding management can have a significant impact on robustness and resilience of animals.

Dealing with the unexpected

Brexit- nobody really thought it would happen, but on the 24th of June this year the EU woke up to a Brexit decision by the British people. What that really means for the future is still uncertain. One thing is for sure, it will mean significant change for both the UK and the EU. How this is going to affect businesses, farming and agriculture is most definitely also going to be down to decision makers in management of organizations and how they will respond and adapt to a changing business and trading environment.

Businesses that are going to complain, resist or deny the change and just carry on with the same procedure as every year, are probably not going to do very well. Others that think: “Shit happens, change happens, but OK let’ s make a plan and deal with it!” are most likely to find ways to efficiently adapt to a changing business and trading environment and even find opportunities to benefit from the change. This is what organizational agility really is all about.

Organizational agility key to survival

Under today’s levels of uncertainty, ambiguity, volatility in the markets, and globalization, it is critical to be agile and quickly respond to change. Organizational agility is the capacity to anticipate change, respond, adapt quickly and thrive in a changing environment.
Given the rapid pace of technological development and growth of global competition, agility is the ability to move quickly and effectively in anticipating and taking advantage of change. It is essential to pick out fast what matters and act accordingly. Agile companies in the modern business world can maintain a competitive edge, despite significant business change in their environments.
A study by McKinsey found that 9 out of 10 executives said organizational agility was critical to business success and growing in importance over time. Given the challenges for animal production to remain competitive in the EU, organizational agility is precisely a capability increasingly also required by animal producers and feed millers.

Taking steps towards an agile operation

The American change management company PROSCI carried out research on what attributes agile organizations share that make them agile. The attributes where respondents scored the highest were:
1. We encourage cross-organizational collaboration
2. We anticipate and plan for changes
3. We have enhanced risk management practices

This is a starting point to generate ideas for steps to take to increase the agility of your organization. Organizational change management capability also showed up prominently as a crucial enabler of agility. So another step could be to start developing the change management capability of your organization.

In this article the focus is on what you can do at the animal level to increase the agility of your operation.

Advanced operational agility with agile nutrition concepts

Feed is the largest and most important component to ensuring safe, abundant and affordable animal protein. Animal nutrition is a crucial means to influence animal performance, production costs, product quality, environmental impact, animal health and welfare, and food security. Needless to say animal feeding plays an important role in livestock production systems and the pressure is on to quickly adapt animal nutrition to the challenges ahead and find new ways to meet increasing demands more sustainably, efficiently and at the same time taking the well-being of animals into account. All of which play a key role for consumers in the EU.

Agile nutrition concepts are concerned with the question, whether the natural ability of animals to adapt to nutritional challenges and other stressors can be deliberately accelerated and optimized to benefit animal performance and the agility of animal production systems.

Research in genetic selection shows that improving the ability of animals to cope with stressors is a better way of improving performance than selecting only for increased growth potential. Genetic selection is certainly going to play an important role for advancement in this capability of the animal. However, nutritional strategies supporting the speed and efficacy with which the animal adapts to stressors will bring a more immediate competitive advantage in animal production.

Agile nutrition concepts are an advanced step towards greater operational agility in animal protein production. The reality of the animal is, that it too faces unexpected changes in diet composition, feed raw materials and stressors such as mycotoxin contamination of feed. This again will lead to stress reactions at the cellular level, which will result in a reduction in production efficiency and can make the animal more prone to disease. It can also lead to reduced feed intake, resulting in reduced growth performance particularly in young animals.

The purpose of agile nutritional concepts is to empower the animal to adapt to nutritional stressors in a more energy efficient response and cope in such a way that negative impacts on performance are reduced.

Feeding for gut agility

The gut is particularly responsive to different stressors. That is why it makes sense to focus on the gut to empower animals to cope with stressors. A new approach to nutrition is to support the agility of the gut, i.e. its ability to adapt to stress factors efficiently. The agile gut is quicker to respond to prevent negative stress reactions, such as oxidative stress, loss in appetite, increased gut permeability and inflammation, which can cause waste of metabolic energy and increased risk of disease. Agile nutritional concepts are designed to empower animals to adapt to a variety of nutritional stress factors for more robust and energy-efficient animals. They rely on bioactive substances derived from plants, known to prevent some of the negative stress reactions seen at the cellular levels in response to stressors.

OUTCOME: more robust and efficient animals

Applying agile nutritional concepts to feed to support gut agility leads to more robust animals and greater efficiency in performance in the face of nutritional challenges, that are difficult to control, but are part of the reality of the animal and impact performance. The animal becomes more agile in the face of dietary challenges, resulting in more consistent high performance and well-being. This also helps to support the overall demand for agility in animal production operations to stay competitive in safe animal protein production.

Relevant publications

Plant extracts: Take advantage of the agile power to manage mycotoxin challenges

Plants developed highly sophisticated mechanisms to cope with stressors, many of which are based on bioactive substances that can be extracted from plant material. One way of empowering animals to cope with stressors better is therefore to supplement their diets with relevant plant extracts and bioactive substances derived from plants.

Stress reactions to mycotoxins in animals

Many trials have proven the significant negative impact of mycotoxins on performance in pigs and poultry. Looking at the effects of mycotoxins at a cellular level, it is becoming obvious that many reactions seen to mycotoxins in animals are those commonly seen in response to other stressors.

One reaction to stressors is an increase in Reactive Oxygen Species (ROS). ROS are produced endogenously by normal metabolic processes, but amounts may be increased markedly by certain stressors, including mycotoxins. Deficiencies of natural protective substances or excess exposure to stimulators of ROS production may result in oxidative stress, which occurs when ROS exceed the capacity of antioxidants. Oxidative stress is a major factor related to the development of inflammatory diseases.

Consumption of DON-contaminated feed in pigs, not only increases oxidative stress, it has also shown to impact the gastrointestinal tract, causing epithelial injuries of the stomach and the intestine, leading to intestinal inflammatory response. In vitro and in vivo studies have also demonstrated that DON compromises the intestinal barrier function and increases gut permeability. Furthermore, it has been shown that mycotoxins modify the intestinal microbiota in pigs and in poultry. However, not all mycotoxins show this effect. For example, feeding pigs with fumonisin was not reported to induce any modification of the intestinal microbiota, whereas DON did. In the chicken a high dose of ochratoxin exhibited significant numbers of Salmonella typhimurium in the digestive tract when compared to non-administered birds. However, feeding birds with high levels of aflatoxin or T-2 toxin had no effect on incidence or severity of S. typhimurium colonization.

Taken all together these type of responses at the cellular level will predispose the animal to intestinal and systemic infections and impair efficient digestion and absorption of nutrients, with the associated effect on animal productivity and efficiency.

How plants adapt to stress factors

Plants are stressed by environmental changes that threaten their health, such as drought, pathogens and plant-eating insects. However, compared to animals and humans, plants have to be a lot more sophisticated with their response to stress since they are stuck where they grow and cannot run from the stress they are exposed to.
The exposure of plants to unfavorable environmental conditions increases the production of reactive oxygen species (ROS) and the ROS detoxification process in plants is essential for the protection of plant cells against the toxic effect of ROS. The ROS detoxification systems in plants include enzymatic and non-enzymatic antioxidant. Non-enzymatic antioxidants involved include phenolic compounds, flavonoids, alkaloids, tocopherol and carotenoids. The antioxidant defense systems work in concert to control the cascades of uncontrolled oxidation and protect plant cells from oxidative damage.

Apart from antioxidants, plants contain a multitude of bioactive substances, with a variety of proven properties such as anti-inflammatory, anti-microbial and aromatic, which are part of their mechanisms for survival and defense. The combination of the many substances makes plants polyvalent to different stressors and threats to survival and hence more agile.

Beat mycotoxins to the punch with plant extracts

As mentioned above mycotoxins can lead to a variety of stress reactions at the cellular level, which again will affect the animal’s performance, efficiency and susceptibility to disease.
Through a multitude of bioactive substances, with a variety of adaptive properties plants are very well equipped to be polyva¬lent to different stressors and to prevent their negative impact. Bioactive substances derived from plants have also shown to support humans and animals to adapt to stressors more ade¬quately and help counteract some of the negative physiological and metabolic side effects.

Since the stress reactions seen to mycotoxins are very similar to those commonly seen in response to other stressors, applying the right combination of plant extracts to animal feed can therefore help the animal become more robust and efficient in the face of mycotoxin challenges.

ANCO knowledge: 3 things to know about bentonites

Bentonite can be applied in animal nutrition to adsorb mycotoxins and reduce mycotoxin bioavailability from contaminated feeds in the animal’s gut. It is a fine clay material mined from the earth. Most bentonites are formed by the alteration of volcanic ash in marine environments and occur as layers sandwiched between other types of rocks (as can be seen in the image above).

Bentonite is defined as a naturally occurring material that is composed predominantly of the clay mineral smectite. The Cation Exchange Capacity (CEC) and the specific surface area of smectites are considerable larger than other families of clays. Their absorption capacity is as much as 8 times greater than other clays.

However, there are a few things to know before applying bentonite to animal feed:
1. Not all bentonites are the same
2. Best proof of efficacy is still in vivo
3. Only one type of bentonite is EU approved for the adsorption of mycotoxins

1. Not all bentonites are the same

Bentonites are colloidal and plastic clay materials composed largely of montmorillonite (a species of dioctahedral smectite). The properties of bentonites can vary considerably depending on geological origin and any post-extraction modification. Their individual characteristics have a marked bearing on their economic use.

Despite the generic nomenclature of commercially-available bentonite, several physicochemical properties have been identified as having a possible correlation with adsorption of mycotoxins and might therefore be used to categorize the different available types.

These characteristics comprise:
• cation exchange capacity (CEC), exchangeable K+, Na+, Mg++ and Ca++,
• pH
• linear swelling,
• mineral fraction
• relative humidity
• d-spacing

Role of d-spacing for zearalenone adsorption

Adsorption to clays is not limited to the surface of the clay particles, but extends also to the interlayer space of the clay. This interlayer space, characterized by the d-spacing, can be determined with X-ray diffraction (XRD) and is restrictive for the formation of one or more adsorbent layers. This space can increase if the clay swells, thereby increasing the number of binding sites.
In vitro adsorption tests have shown that there is a positive correlation between zearalenone adsorption and d-spacing in commercially available products based on bentonite, i.e. large d-spacing was associated with higher % adsorption of zearalenone. (De Mil et al 2015). The d-spacing ranged from 9.2 to 21.5 (10-10 m) in 16 different products containing bentonite material, showing the large variation in material out there.

Difference between cis- and trans-bentonites for aflatoxin adsorption

Recent scientific data (Vekiru et al 2015) evaluating different types of bentonites for the in vitro adsorption efficacy relating to aflaxtoxin B1 has shown that most of the tested Ca- or Na-bentonites were effective. However, cis-bentonites were more effective than trans-bentonites.
Dioctahedral smectites that are found in bentonite have one vacant position in the octahedrons because one of the three symmetrically independent octahedral positions is not occupied by cations, resulting in a vacant site. The disposition of the hydroxyl groups in the octahedral sheet with respect to this vacancy defines the configuration cis- or trans-vacant.

2. Best proof of efficacy is still in vivo

In vitro experiments have been developed as a way to effectively pre-screen adsorption agents before testing in animals. However, results between in vitro and in vivo efficacy can vary significantly. Even among bentonites with high in vitro adsorption efficacy, there are differences in in vivo efficacy indicating that in vitro testing alone is not adequate for evaluation of adsorbents.

3. Only one type of bentonite is EU approved for the adsorption of mycotoxins

Currently 1m 558 bentonite has been approved as a substance for reduction of the contamination of feed by mycotoxins (aflatoxin B1) for pigs, poultry and ruminants according to EU regulation in the EU register for feed additives. The approval is based on safety of using the product and proven in vitro and in vivo adsorption efficacy of Aflatoxin.

This bentonite meets the following characteristics:
• Bentonite: ≥ 70 % smectite (dioctahedral montmorillonite)
• < 10 % opal and feldspar
• < 4 % quartz and calcite
• AfB 1-binding capacity (BC AfB1) above 90 %

At current recommended maximum inclusion level of this bentonite in animal feed, the binding of vitamins and minerals is insignificant.

Read ANCO’s first publication in All About Feed, June 2016

As plants evolved, they developed very sophisticated coping mechanisms to stressors, helping plants to be more agile in the face of stressors and threats to survival. It is therefore right to think that new agile concepts developed for nutritional strategies to empower animals to adapt to stressors rely partly on the power of plants.

Several meta-analysis studies have proven the negative impact of mycotoxins in pig and poultry diets on animal performance. What is also becoming apparent with greater knowledge of the impact of mycotoxins on animals is, that mycotoxins will cause very similar physiological and metabolic reactions in the animals as seen in response to more common stressors. Those reactions will again increase cell damage, waste metabolic energy, increase the susceptibility to disease and reduce appetite. Through a multitude of bioactive substances, with a variety of adaptive properties plants are very well equipped to be polyvalent to different stressors and to prevent their negative impact. Bioactive substances derived from plants have also shown to support humans and animals to adapt to stressors more adequately and help counteract some of the negative physiological and metabolic side effects. Applying the right combination of plant extracts to feed can therefore help the animal become more robust and reach performance potential more efficiently in the face of stressors, including mycotoxins.

Read more in Disarm mycotoxins with the agile power of plants, by Gwendolyn Jones, June 2016 digital All About Feed issue, Vol 24/5, page 24-26
http://www.allaboutfeed.net/All-About-Feed-Digital-Magazine/

Aflatoxin: How big is the threat of aflatoxins in poultry diets?

Aflatoxin is a secondary metabolite produced by toxigenic strains of A. flavus and A. parasiticus. Chemically, aflatoxins belong to the bifuranocoumarin group, with aflatoxins B1 (AFB1), B2 (AFB2), G1 (AFG1) and G2 (AFG2) being the most toxic. Liver is the main organ affected by these toxins.

Poultry is considered as the most susceptible animal species to aflatoxins. A meta-analysis (Andretta et al 2011) carried out on broiler performance in response to mycotoxins showed that aflatoxin (average concentration 0.95mg/kg of feed) and ochratoxin had the biggest effects on broiler performance. Aflatoxins on average significantly reduced feed intake by 10% and growth rate by 12%. Aflatoxins also significantly increased liver weight by 22% and the weight of kidneys, lungs, gizzard and the heart. Aflatoxins presented the most important effects of all mycotoxins on organ weight in broilers.

Occurrence of aflatoxins in feed ingredients

Global mycotoxin surveys for 2015 feed and feed ingredient samples revealed that 20% of complete diets were contaminated with Aflatoxin of which 5% at a level of Aflatoxins above risk threshold. The feed ingredient most frequently contaminated with aflatoxin above risk threshold level was corn.

Aflatoxin production occurs primarily in regions with tropical or subtropical climates. Hence, from a European perspective, imported feed such as peanut cake, palm kernel, copra and corn gluten meal (depending of origin) is considered to be the most common source of exposure.

A recent review (Pinotti et al 2016) on the global occurrence of mycotoxins states that aflatoxins are most often detected in Southern Europe, Africa, South Asia and Southeast Asia (average values of positive samples higher than 30%).
Aflatoxin Occurrence_2016

Regulatory guidelines for aflatoxin limits in poultry diets

In Brazil, the presence of aflatoxins in corn is regulated by the Ministry of Agriculture through Decree 183 of March 21, 1996 and Resolution 274 of October 15, 2002 of the National Sanitary Surveillance Agency, which established a maximum limit of 20 μg/kg for the sum of aflatoxins B1, B2, G1 and G2.

In the EU the presence of undesirable substances (chemical contaminants) in feed is controlled by EC Directive 2002/32 (as amended). The Directive sets maximum permitted levels (MPLs) for substances that are present in, or on, animal feed that pose a potential danger to animal or human health or to the environment, or could adversely affect livestock production. Currently, aflatoxin B1 is the only mycotoxin with MPLs. MPLs of aflatoxin B1 have been set as low as reasonably achievable in order to protect animal and public health. The aflatoxin B1 limit for poultry diets in the EU is 20 μg/kg.

In the US the Food and Drug Administration (FDA) has established guidelines for the maximum toxin level that can be safely fed to the animal. See table below.

FDA’s action levels for aflatoxin in poultry feed
FDA aflatoxin guidelines
FDA aflatoxin guidelines

FeedInfo interviews ANCO on gut agility and company strategy

Feedinfo News Service spoke to Gwendolyn Jones at Anco, to find out more about gut agility and what the company’s strategic objectives are.

Read about where ANCO is heading in the following link:
Anco Animal Nutrition Competence and the Emergence of Gut Agility

Mayor eficiencia en el rendimiento de los cerdos con agilidad intestinal

La aplicación de agilidad a la nutrición de los cerdos es un enfoque totalmente nuevo para una mayor rentabilidad en la producción animal competitive

Por Gwendolyn Jones
Traducción: Viviana Schroeder R

Los requerimientos nutricionales de cerdos con genotipo moderno están bien investigados. Sin embargo, muchos cerdos no alcanzan su potencial de rendimiento, a pesar de las dietas cuidadosamente formuladas. Esto puede ser debido a factores de gestión y / o medioambientales. Pero también hay factores nutricionales sobre los que tenemos menos control. Pueden dar lugar a toda una serie de reacciones de estrés en el animal y a eficacia subóptima en el rendimiento del cerdo. El hecho es que el cerdo estará sometido a factores estresantes durante toda su vida productiva.

grafik_stoppschild_spanisch
Existe evidencia científica que sugiere que para la selección genética, mejorar la capacidad de los cerdos para hacer frente a los factores de estrés puede ser una mejor manera de mejorar el rendimiento de los cerdos que seleccionar sólo para un mayor potencial de crecimiento. Por lo tanto, el aumento de la capacidad del cerdo para adaptarse a los factores de estrés de manera más adecuada mediante la nutrición también ofrece una alternativa a la mejora de rendimiento de los animales. Lo más importante es que la capacidad del animal para hacer frente a los estresores también tendrá un impacto en el retorno de la inversión (ROI, por sus siglas en inglés) de la formulación de dietas y la rentabilidad del productor.

Ataque los estresores nutricionales
Tradicionalmente, los aditivos se han desarrollado para atacar posibles factores de estrés directamente en el tracto digestivo del animal. Por ejemplo, las enzimas degradan componentes no digeribles específicos como fitato y polisacáridos no amiláceos (NSP, por sus siglas en inglés) en el cerdo para liberar nutrientes atrapados y también reducir los posibles efectos secundarios negativos de estos componentes. ¿Qué pasa con componentes menos digeribles presentes en las dietas que no son blanco específico de las enzimas para alimentación animal?

Antibióticos promotores del crecimiento se han usado por su efecto anti-bacteriano contra ciertas bacterias patógenas. Sin embargo, en muchos países los antibióticos ya han sido prohibidos para uso rutinario en la alimentación animal. Más países están haciendo lo mismo, y hay una mayor necesidad de alternativas eficaces. El ágil intestino le ayuda al animal a adaptarse a los factores de estrés de manera más eficiente y a ser más robusto en vista de los desafíos dietéticos y los estresores.
Adsorbentes de micotoxinas y desactivadores de micotoxinas se están aplicando a las dietas para contrarrestar los efectos nocivos de las micotoxinas en el animal. Sin embargo, es bien sabido que la adsorción no es una estrategia eficaz para todas las micotoxinas. La biotransformación de micotoxinas en metabolitos no tóxicos solamente se dirigirá a ciertos tipos de micotoxinas y es poco probable que sea completa en el tracto digestivo del animal.

Adaptarse a los factores de estrés nutricional
La pregunta es, ¿Qué hace el animal con los factores estresantes que quedan al margen de las soluciones de alimentación altamente específicos mencionados anteriormente? El cerdo tiene que ser más ágil. Como se mencionó con antelación, se pueden lograr mayores resultados en el rendimiento de los cerdos mediante la mejora de la habilidad del cerdo para hacer frente a los estresores. Eso significa que el cerdo tiene que ser capaz de adaptarse más rápido y más adecuadamente a cambios en la dieta y a los factores de estrés para un rendimiento eficiente. La selección genética va a jugar un papel importante para avanzar en esta capacidad del cerdo. Las estrategias nutricionales que apoyan la velocidad y la eficacia con la que el cerdo se adapta a los estresores traerá una ventaja competitiva más inmediata en la producción porcina.

La agilidad en el negocio
Cuando la medida del rendimiento es la rentabilidad, unas pocas empresas grandes en todas las industrias superan constantemente a sus iguales durante períodos prolongados, e incluso mantienen esa ventaja encarando cambios empresariales significativos en sus entornos competitivos. El único factor que tienen en común es la agilidad – se adaptan con éxito. La agilidad es una capacidad que permite a una organización para responder de manera oportuna, eficaz y sostenible cuando las circunstancias cambiantes así lo requieran. Las investigaciones realizadas en el Instituto de Tecnología de Massachusetts sugieren que las empresas ágiles generan 30 por ciento más ganancias que las empresas no ágiles. Otro estudio identificó una mayor eficiencia como un beneficio significativo de una mayor agilidad de la organización.

Agilidad intestinal en los cerdos
La aplicación del concepto de agilidad en el cerdo puede ayudar a desarrollar aún más la eficiencia en la producción porcina. El intestino y el sistema inmunológico son particularmente sensibles a los factores de estrés, de ahí que el énfasis está en el intestino cuando se habla de mejorar la respuesta adaptativa del animal. La agilidad intestinal es un nuevo término acuñado para describir la capacidad del cerdo para adaptarse a los estresores nutricional con una respuesta más eficiente energéticamente y más rápido de lo normal.

Lo que funciona
A medida que las plantas evolucionaron desarrollaron muy sofisticados mecanismos de adaptación a los factores estresantes y las amenazas potenciales para mejorar la supervivencia. Contienen una multitud de sustancias bioactivas, con una variedad de propiedades, tales como anti-oxidantes, anti-inflamatorias, anti-microbianas, anti-virales y aromáticas. La combinación de las muchas sustancias hace que las plantas sean polivalentes ante diferentes factores de estrés. Por tanto, es lógico pensar en la aplicación de extractos de plantas con las estrategias nutricionales desarrolladas para capacitar a los cerdos para adaptarse a los factores de estrés. Las sustancias derivadas de las plantas ya han demostrado ser muy eficaz en la naturaleza, ayudando a las plantas a ser más ágiles para hacer frente a los estresores y amenazas a la supervivencia. Sin embargo, la velocidad de la agilidad intestinal, con el apoyo de sustancias bioactivas en la alimentación, dependerá de encontrar la combinación óptima adecuada para el cerdo y sus desafíos.

Conclusiones
La combinación de estrategias nutricionales con parámetros de selección genética de interés para mejorar la agilidad del tracto gastrointestinal del cerdo podría contribuir a la producción de carne más segura y más rentable en vista de la creciente presión de los consumidores para las dietas libres de antibióticos.

Read ANCO´s first publication in WATT Pig International, May/June 2016

Agile concepts are known to drive the speed of growth and competitive advantage in the modern business world. The application of agility to animal nutrition is an entirely new approach for more profitability in competitive animal production.

Gut agility is a new term coined to describe the animal’s ability to adapt to nutritional stressors in a faster and more energy-efficient response than it normally would.

Gwendolyn Jones writes about applying agile concepts in pig nutrition in the following article, published by WATT Pig International May/June issue and WATT Feed Management May/June

http://www.feedmanagement-digital.com/#&pageSet=0

Higher efficiency in pig performance with gut agility