ROLE OF TOXIN BINDERS IN POULTRY

Mycotoxins are toxic metabolites that synthesized by a variety of fungal species and can be produced in feed, feedstuffs and foods in suitable conditions, such as moisture, temperature, oxygen and duration .The most common mycotoxin found in poultry feed and foodstuffs is aflatoxins (AFs) because it is produced rapidly and more toxic than the others . Mycotoxin binders are feed additives that aim to adsorb mycotoxins in the gastrointestinal tract of animals, making them unavailable for systemic absorption.

AFs are a major concern in poultry production and public health because of serious economic losses and health problems. AF contamination causes reduced feed quality and reduced animal efficiency either through poor conversion of nutrients or problems such as reproductive abnormalities .Aflatoxicosis in poultry also causes listlessness, anorexia with lowered growth rate; poor feed utilization, decreased egg production and increased mortality. Additionally, anemia, reduction of immune function , hepatotoxicosis, hemorrhages .teratogenesis, carcinogenesis and mutagenesis are associated with aflatoxicosis . The problem of aflatoxicosis is not so easy to solve and requires constant attention throughout the entire process of grain harvest, shipping, storage, feed manufacturing, and its formulation. Nevertheless, complete avoidance of mycotoxins is not possible. Prevention of feed, feedstuffs and foods from AF contamination and utilization of AF-contaminated feed and feedstuffs presents a major problem. Detoxification as well as routine, AF analysis of feed ingredients is an important step in a control program at field level. Detoxification is defined as neutralization, elimination or mitigation of toxic effects of mycotoxins including AFs. Still, this is quite difficult because AFs are resistant molecules. Conventionally, detoxification strategies are based on chemical, physical or microbiological methods .One of the important approaches to the prevention of mycotoxicosis in livestock is the addition of nonnutritional adsorbents in the diet that bind mycotoxins in the gastrointestinal tract, and that are capable of reducing their bioavailability. These binding agents do not undergo any changes in the digestive system, and when used to feed in different levels they prevent mycotoxins from being absorbed through the digestive system and thereby generation of toxic effects on animals and transmission of toxins into animal products. They also bind AF molecules and reduce their toxic effects .Both inorganic and organic absorbers are used to control of mycotoxins including AF. Inorganic mycotoxin binders include commonly aluminosilicate minerals (clays) that are the largest class of mycotoxin binders, and most of the studies on the alleviation of mycotoxicosis by the use of adsorbents have been focused on these clays .The organic binders or biopolymers are complex indigestible carbohydrates (cellulose, polysaccharides in the cell walls of yeast, and bacteria such as glucomannans, peptidoglycans, and others), and synthetic polymers such as cholestyramine can adsorb mycotoxins .Saccharomyces cerevisiae initially used as a growth promoter in the early 1990s, was also found to induce beneficial effects on weight gain and immune response in broilers exposed to mycotoxins. The beneficial effects of yeast have been attributed to mannan in the yeast cell wall. By using only yeast cell walls (composed of betaglucans and mannan oligosaccharides) instead of the whole cell, mycotoxin binding can be enhanced .The properties of adsorbents, mycotoxins and feed/food components play an important function in binding of mycotoxins and adsorbent activity. The physicochemical properties of the adsorbents such as total charge, charge distribution, size of the pores on the surface and surface area, iodine number, methylene blue index and pH as well take on an important function in binding effectively .On the other hand, the properties of mycotoxins such as polarity, solubility, form and size of the mycotoxin to be adsorbed and the presence of ionized compounds in the environment are other effective factors. It has also been mentioned that the high fiber content of the feed/food substrate increased the mycotoxin affinity to adsorbent . European Food Safety Authority (EFSA) stated that along with efficacy testing of mycotoxin binders; their safety should also be investigated because the toxin binders added to the feeds are thought to make non-specific bindings

Hundreds of different mycotoxins exist, and they vary in their chemistry and mode of action on animals. The molds that are most common in animal feed are Aspergillus, Fusarium, and Penicillium. Consequently, the mycotoxins of greatest concern are produced by these molds and include aflatoxin (produced by Aspergillus); deoxynivalenol, zearalenone, T-2 toxin, and fumonisin (produced by Fusarium); and ochratoxin and PR toxin (produced by Penicillium). Ergot is another mycotoxin commonly present in animal feed.

Even with excellent management, low levels of mycotoxins may exist in poultry feed. Several mycotoxin binders have been developed that prevent the toxic effects of mycotoxins on animals consuming contaminated feed. These materials bind with the mycotoxin(s) and prevent the negative effects on the animals consuming them. Potential mycotoxin binders include activated carbon; aluminosilicates (e.g., clay, bentonite, montmorillonite, zeolite, phyllosilicates); and complex indigestible carbohydrates (e.g., cellulose, polysaccharides in the cell walls of yeast and bacteria) as well as some synthetic polymers. The diversity in chemistry of mycotoxins influences the effectiveness of mycotoxin binders. Mycotoxin control measures may require multiple approaches to solve the problems associated with mycotoxin consumption. More recent approaches include the use of a combination of binders, microbial enzymes, yeast cell walls, and natural antioxidants.

Livestock enterprises faces the maximum loss is owed to the contamination of animal feed ingredients and compounded feeds by moulds and its toxic metabolites known as mycotoxin. Some of the primary toxigenic moulds and mycotoxins are indicated as following:

Moulds Fusarium spp. Aspergillus spp. Penicillium spp.

Mycotoxins Deoxynivalenol, Zearalenone, T-2 Toxin, Fumonisin, Moniliformin, Diacetoxyscirpenol, Fusaric acid, etc. Aflatoxin, Ochratoxin, Sterigmatocystin, Cyclopiazonoic acid, etc. Ochratoxin, PR Toxin, Citrinin, Cyclopiazonic acid, etc.

Among these, the most thoroughly studied and best understood of the mycotoxins are the aflatoxins. The aflatoxins (AF), a class of mycotoxins produced by the common mould Aspergillus flavus Link and Aspergillus parasiticus Speare. Major forms of aflatoxin include B1, B2, G1, and G2, with aflatoxin B1 being the most common and biologically active component (1). All four have been detected as contaminants of crops before harvest, between harvesting and drying, during storage, and after processing and manufacturing (2).

The primary mechanisms through which mycotoxins affect animals are (3):

• 1. Reduction of feed intake

• 2. Reduced nutrition (reduced nutrient content of the feed, reduced nutrient absorption and altered nutrient metabolism)

• 3. Immunosuppression

• 4. Mutagenicity

• 5. Teratogenicity

• 6. Cellular death

Chronic exposure to the mycotoxins may significantly alter productivity, which can mean the difference between profit and loss to the livestock industry. Consequently, practical and effective methods to detoxify toxins-containing feedstuffs are in great demand. Various physical (grain cleaning/seperation, heating, irradiation), chemical (ammoniation, sodium bisulfite) and biological approaches (microbial, non-toxic strains) to counteract the mycotoxins problem have been reported (4 & 5) but these methods have certain limitations like they are impractical, ineffective and potentially unsafe.

Nowadays there are a variety of products available on the market for animal feed with a ‘toxin binder’ capacity, and the risk of mycotoxins in the animal organism is reduced or avoided. For practical purposes, these products minimize the risk of mycotoxicosis that could be derived from the use of contaminated feeds. The active substances in these products are distinctly different. Their functions are described as follows:

Phylosilicates, tectosilicates and diatomea sands —————

Phylosilicates are commonly named “clays”, which are broadly defined as mineral components with a diameter less than 2 μm. The most common used clays for animal feeding are smectite, kaolin, talc, sepiolite and atapulgite. The latter are classified according to structure and mineral composition. They normally show laminate structure, except sepiolite and atapulgite, which are pseudo-laminate or tubular. There are non-clay based silicates, such as zeolite (tectosilicates), diatomea sand (from organic origin), perlite and vermiculite (from volcanic origin), which are used as toxin binders. Indirectly, such molecules are able to bind the toxins’ reactive polar groups, therefore avoiding their diffusion into the medium. The anti-aflatoxin effect has been proven the combined by their capacity to bind β-cetolactone or αbislactone groups contained in the aflatoxin molecule. Equally, they can bind other mycotoxins depending on their chemical structure. There are several hydroscopic clays, which reduce the available water and delay the growth of the alfatoxin-productive fungi.

– POLYSACCHARIDES They are glucomannanes components obtained from the structural wall of yeasts. Their surface is very reactive against active mycotoxin groups and improves the animal’s immune system. Natural compositions present a huge capacity for resistance to digestive degradation; therefore bonded mycotoxins are not reabsorbed inside the animal.

– ENZYMES

Oxidases, catalases, lactonases and sterases can all potentially reduce mycotoxins to inactive forms. Unfortunately there is only a small amount of scientific literature to prove their efficiency. –

There are certain distinct absorbents capable complexing molecules with phenol rings, and acid or alkaline toxin complexes such as mycotic toxins, thanks to the reactivity and amphoteric properties of their molecular structure. Some of the latter molecules can be especially effective against toxins of bacterial origin, e.g. botulinus toxin. PVPP is one of the absorbents authorized by the European Pharmaceutical Association for use in humans and effective at low inclusion rates. All the above components are able to significantly reduce the mycotoxin concentration in feed. Additionally, it is widely recommended to include antioxidants and hepatic protective elements (organic selenium, vitamin E, ascorbic acid, glutathione, methionine and cystine, etc.) in order to minimize the residual toxins’ negative and toxic impact.

Recent studies have shown that the addition of certain adsorbents to contaminated diets can greatly reduce the bioavailability of toxins in the gastrointestinal tract . Some mycotoxin adsorbents are given below:

1) Silicate Products:

• Phyllosilicates (silicate sheets): Clays [Montmorillonite, bentonite and Hydrated Sodium Calcium Aluminosilicate (HSCAS)].

• Tectosilicate (silicate frameworks): Zeolites and Clinoptilolite.

2) Carbon Products:

• Activated or superactivated charcoal.

3) Glucan products

4) Inorganic polymers:

• Cholestyramine.

• Polyvinylpyrrolidone (PVP).

Impact of mycotoxins ———-

• Direct health challenges

Reduced immune response (vaccinations)

Toxicity

Skeletal health

• Reduced feed intake

• Reduced nutrient absorption

Excretion of lipids

• Residues in meat / Eggs

• Condemnations / Downgrading

Bruising

Loss of salable product (i.e.: liver, gizzard erosion)

• Reproduction (loss in fertility & hatchability)

Impact of aflatoxins on the immune system ———–

• Reduction in size of bursa of Fabricius and thymus

• Reduction in T-lymphocyte, B-lymphocyte and white blood cell counts

• Reduction in total serum proteins and immunoglobulins

• Reduction in antibody titers

• Reduction in serum concentration of antibiotics

Mycotoxin adsorbents Factors to be considered————-

• Able to adsorb a wide range of mycotoxins

• Low inclusion rate Reduce cost, dilution effect, but harder to mix evenly

• Easy to mix uniformly

• Heat and storage stability

• No affinity for vitamins, minerals, etc.

• Functional under pH ranging from 2-7

• Biodegradability after excretion

• Safe for animals and humans

• Palatability

• No potential for other sources of contaminants

Adsorbents:

Mineral clays ————

• Many products available Bentonites

(used as a pellet binder, but require >4%) Zeolites

Aluminosilicates

Hydrated sodium calcium aluminosilicate (HSCAS)

Activated charcoal

• Adsorption depends on the chemical structure Capacity can vary from 0 to 87%

Adsorbents:

Mineral clays

• Mostly effective for aflatoxins, but little efficacy for: Zearalenone

T-2 toxin

Ochratoxin

Diacetoxyscirpenol

Fescue Toxin

• Mineral clays reduce the utilization of Mn, Zn, Mg, Cl, Cu and Na

Adsorbents:

Yeast cell wall

• Yeast cell wall derived and/or modified glucomannan (Mycosorb / Alltech Inc)

• Biorigin (Brazil)

• Biomin (Germany)

• Pros and Cons Lower inclusion levels than clays (1 vs 40kg / MT) o Costs/MT similar, but less dilution of diet Broader claims for different types of mycotoxins

Efficacy often variable

• Saccharomyces cerevisiae is a yeast species which has been domesticated for at least 3,000 years

• Not live yeast, rather the yeast cell wall Manno-oligo saccharides

It is alternative attachement place 1-3, 1-6 β glucans

Diverse molecule

Strong immune stimulator effect

SOME TOXIN BINDERS BRAND NAME————-

B.I.O.Tox Activ8

B.i.o.Tox^®Z

MYCOFIX®

TOXIMAR Powder for Poultry

BIO-BANTOX™

Inta-O-Tox

Toxiwin-ES

Bio-bantoxplus Toxin Binders

Unitox-zm Plus Toxin Binder

Detox Toxin Binder

Tox-nil Toxin Binder For Poultry

Anfatox – Feed Toxin Binder

Reference-On Request