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Current concepts in feed-borne mycotoxins and the potential for dietary prevention of mycotoxicoses

Published: September 13, 2006
By: Trevor K. Smith - Ewen J. MacDonald - Swany Haladi - ALLTECH INC.
The most commonly recognized feed-borne mycotoxins are the aflatoxinsand the Fusarium mycotoxins. Our understanding of the etiology ofaflatoxicosis is far more complete than our corresponding understanding ofFusarium mycotoxicoses. This is perhaps because of the large volume ofliterature fueled by the acutely carcinogenic nature of aflatoxins. Analyticalmethodology for aflatoxins in feedstuffs is also simple, sensitive andreproducible. This is due, in part, to the natural fluorescence of aflatoxinmolecules. Even though Fusarium mycotoxins are likely the mosteconomically significant grain mycotoxins (Wood, 1992), the complex mixtureof chemically-unrelated compounds has slowed advances in the study ofFusarium mycotoxicoses. Complete analysis of feedstuffs for Fusariummycotoxins is a daunting, time-consuming and prohibitively expensive task.It is also now clear that toxicological synergism between differentFusarium mycotoxins can increase the toxicity of a given diet (Smith et al.,1997) and incomplete analysis can, therefore, give false security as to thepotential hazard posed by the feeding of contaminated grains. It is important,also, to remember that many different components of a complete feedcan be vectors for mycotoxin contamination. The studies of Smith andSousadias (1993, Table 1) indicated that the fusaric acid content of completefeeds can exceed that found in individual feedstuffs. This has sincebeen attributed to fusaric acid contamination of soybean meal. Fusaric acidhas been found in soybean plants and is considered to be a phytotoxin invarious vegetable species (Matsui and Watanabe, 1988). Since almost allstrains of Fusarium fungi produce fusaric acid, it has been suggested thatthis compound be used as a marker compound for Fusarium contaminationof grains (Bacon et al., 1996). It is therefore important that complete feeds,and not just suspect individual ingredients, be analyzed when mycotoxincontamination is suspected.


Current concepts in feed-borne mycotoxins

Current concepts in feed-borne mycotoxins and the potential for dietary prevention of mycotoxicoses - Image 1

Several trends have tended to increase the severity and economic importanceof mycotoxicoses in animal and poultry agriculture in recent years. One keyfactor in minimizing fungal infestation in field crops and mycotoxinaccumulation in feedstuffs is moisture content during the growing andharvesting periods. Stored grains should contain less that 15% moisture toensure fungal stability. Recent global weather patterns, however, have beenirregular with heavy rainfall and flooding in some areas coupled with droughtand unusual frosts in other regions. Drought stress can also lead to increasedfungal penetration of grains. The result has been an increased frequency ofreports of mycotoxin contamination of feed grains. Some tropical and semitropicalcountries are reporting Fusarium contamination of crops whereonly aflatoxin was previously detected. It is not clear, however, if this isalsothe result of increasingly frequent testing for compounds that wereerroneously assumed to be absent in the past.
Another trend contributing to the frequency of mycotoxin contaminationof feeds is improved global grain transportation systems and global tradingof agricultural commodities. This allows more extensive shipping of grainsand other feed components throughout the world. The result is that completefeeds are likely a more complex blend of feedstuffs with more widelyvarying geographic origins than was seen in the past. The potential foraflatoxins and mixtures of Fusarium mycotoxins to be co-contaminants infeeds is, therefore, enhanced.

The concept of mycotoxin binders

Mycotoxin binders are large molecular weight polymers that, when addedto feed, are capable of forming irreversible complexes with mycotoxinmolecules in the intestinal lumen. Such complexes are not digestible, passdown the digestive tract and are excreted in the feces. The net effect is toreduce the dose of absorbed toxin to the point that it is below the biologicalthreshold. This allows contaminated feed to be fed with minimal losses inperformance. The challenge is to identify compounds capable of effectivelybinding a mixture of mycotoxins with widely varying molecular structuresand polarities. The binder must also be effective at low levels of inclusionsince these non-nutritive additives are diluents that will reduce the nutrientdensity of the diet. An example of a toxin binder that has been widely usedin veterinary medicine to treat accidental acute poisonings is activatedcharcoal.
Mycotoxin binders can be silica-based inorganic polymers or carbon-basedorganic polymers. The inorganic polymers currently on the market includenatural clay products as well as synthetic polymers. The advantage of theclay-based products is their low price. Unfortunately these products alsooffer low specificity and so must be used at a relatively high level of inclusionto be effective. We found this to be the case for both bentonite (Carsonand Smith, 1983a) and spent canola oil bleaching clays (Smith, 1984) whenovercoming T-2 toxicosis. Synthetic inorganic polymers have usually beendesigned to effectively bind one specific mycotoxin. This is usually aflatoxin.Such specific products are, therefore, much less effective against amixture of mycotoxins of varying molecular weight and polarity. Syntheticproducts are also inevitably more expensive than naturally-produced materials.

Organic toxin binders are derived from plant or microorganism fibers.Studies in our laboratory indicated that lignin-rich alfalfa fiber was quiteeffective at overcoming the toxicity of T-2 toxin (Carson and Smith, 1983b)and zearalenone (James and Smith, 1982; Stangroom and Smith, 1984). Anadvantage of using organic fibers as mycotoxin binders is that feedstuffssuch as dehydrated alfalfa meal have some dietary energy and protein contentand do not act as dietary diluents in the manner of inorganic polymers.Alfalfa fiber, however, like clay-based products, is an effective mycotoxinbinder at only high levels of dietary inclusion. This makes such materialsimpractical when added to livestock and poultry diets.
An innovation in mycotoxin binders is the concept of organic polymersderived from yeast cell wall fractions. This material has a high surface areaand enough specificity to allow effective mycotoxin binding at a low level ofdietary inclusion. This is the basis of the product Mycosorb (Alltech, Inc.).A series of experiments was therefore conducted to determine the effectivenessof yeast cell wall polymers in overcoming Fusarium mycotoxicosesin broiler chickens and swine.


Response to Mycosorb
FEEDING TRIALS WITH BROILER CHICKENS


Broiler chicks of a commercial strain (Cobb, Big Four Hatchery) were fedsoybean meal, corn and wheat-based diets for eight weeks at the ArkellPoultry Research Station of the University of Guelph. The diets included:(1) control (2) same diet formulated with a low level of contaminated cornand wheat (3) a diet containing higher levels of contaminated corn andwheat (4) the highly contaminated diet + 0.2% Mycosorb. Three replicatepens of 30 birds were fed each diet. Weight gain and feed consumption

Current concepts in feed-borne mycotoxins

were determined weekly. Diets were adjusted for protein levelscorresponding to starter (0-3 weeks), grower (4-6 weeks) and finisher (7-8weeks) phases. Diets were analyzed for deoxynivalenol, fusaric acid,zearalenone and T-2 toxin. Blood samples were taken at the end of thestarter and finisher phases and a clinical screen of serum metabolites wasconducted. At the end on the experiment, samples of breast, thigh and legtissue were tested for discoloration using a Minolta colorimeter.
Results of the trial are given in Tables 2 and 3. Growth rate, feed consumption,feed efficiency and serum parameters were largely unaffectedby diet with the exception of the finisher phase. In the finisher phase, eedingof increasing levels of contaminated grains significantly depressed ingrowth rates. This effect was overcome by the feeding of 0.2% Mycosorb.It was also observed that red blood cell counts and concentrations of hemoglobinand uric acid increased with the feeding of increasing amounts ofcontaminated grains. An increasing redness of breast meat was also observed,as has been reported for turkey poults fed Fusarium culture material(Wu et al., 1994). The discoloration may be due to the effect of fusaricacid, which acts as a hypotensive agent. It was concluded that Fusariummycotoxicoses can be observed in broiler chickens with the feeding of naturally-contaminated grains. Such toxicoses can be reversed with the feedingof 0.2% Mycosorb.

Table 2. Effect of feeding blends of Fusarium mycotoxin-contaminated grains ongrowthperformance of broiler chickens.

Current concepts in feed-borne mycotoxins and the potential for dietary prevention of mycotoxicoses - Image 2


Table 3. Effect of feeding blends of Fusarium mycotoxin contaminated grains onbloodmetabolites and breast meat coloration of broiler chickens.


Current concepts in feed-borne mycotoxins and the potential for dietary prevention of mycotoxicoses - Image 3




FEEDING TRIALS WITH STARTER PIGS


In the summer of 2000, an experiment was conducted at the University ofGuelph Arkell Swine Research Centre to determine the potential forMycosorb to overcome the toxicity of diets containing blends of grainsnaturally contaminated with deoxynivalenol and fusaric acid. PurebredYorkshire pigs (average initial weight 8.1 kg) were fed diets formulated tocontain 3.0 mg deoxynivalenol/kg and 20.0 mg fusaric acid/kg for 21 days.Diets included: (1) control (2) contaminated grains and (3) contaminatedgrains + 0.2% Mycosorb. There was a highly significant reduction in weightgain and feed intake of pigs fed contaminated grains compared to controls(Table 4). These differences were too large, however, to be prevented with0.2% dietary Mycosorb. Higher levels of the product might have been moreeffective; however adding the standard dosage of Mycosorb to the diet didprevent the significant depression in liver weight seen with the feeding ofcontaminated grains.


Table 4. Effect of feeding blends of Fusarium mycotoxin-contaminated grains ongrowthperformance and liver weights of starter pigs.

Current concepts in feed-borne mycotoxins and the potential for dietary prevention of mycotoxicoses - Image 4

At the end of the study, a subgroup of 12 pigs fed each diet was euthanizedand brains were excised and dissected into frontal cortex, pons andhypothalamus. Brain regional neurochemistry was determined by highperformance liquid chromatography with electrochemical detection. Effectsof diet were seen in the hypothalamus and pons (Figures 1 and 2). Feedingcontaminated grains reduced pons norepinephrine concentrations. This islikely due to the inhibitory effect of fusaric acid on the activity of dopaminebetahydroxylase, the enzyme that catalyzes the synthesis of norepinephrinefrom dopamine. Also seen was an increase in the ratio of 5-hydroxyindoleacetic acid to serotonin (HIAA/5HT). This ratio can be used,with caution, as an index of serotonergic neuronal firing and related behaviorssuch as loss of appetite, lethargy and loss of muscle coordination. In thehypothalamus, the HIAA/5HT ratio was also increased by feedingcontaminated grains while concentrations of dopamine were reduced.Addition of 0.2% Mycosorb to the diet prevented all of the neurochemicalchanges seen when contaminated grains were fed.


Figure 1.
Effect of deoxynivalenol (DON) and Mycosorb on norepinephrineand dopamine concentrations in starter pigs (Means without common letters differ,P<0.05).

Current concepts in feed-borne mycotoxins and the potential for dietary prevention of mycotoxicoses - Image 5


Figure 2. Effect of deoxynivalenol (DON) and Mycosorb on 5-hydroxyindoleaceticacid:serotonin ratios in pons and hypothalamic tissues of starter pigs (Meanswithoutcommon letters differ, P<0.05).

Current concepts in feed-borne mycotoxins and the potential for dietary prevention of mycotoxicoses - Image 6



Conclusions

The active component of choice in commercial preparations for overcomingmycotoxin contamination of feeds is a mycotoxin binding agent. In theabsence of an effective binding agent, feeding grains contaminated with
Fusarium mycotoxins results in harmful metabolic changes that reduceproduction efficiency of broilers, pigs and other species. Our studies haveshown that Mycosorb effectively prevents such metabolic changes bypreventing intestinal absorption of a mixture of mycotoxins of widely varyingmolecular weights and charges. It is an efficient and cost effective solutionto the problem of feeding mycotoxin-contaminated feeds and forages.


TREVOR K. SMITH1, EWEN J. MACDONALD2 AND SWAMYHALADI1

1Department of Animal and Poultry Science, University of Guelph,Ontario, Canada
2Department of Pharmacology and Toxicology, University ofKuopio, Kuopio, Finland




References

Bacon, C.W., J.K. Porter, W.P. Norred and J.F. Leslie. 1996. Production offusaric acid by Fusarium species. Appl. Environ. Microbiol. 62:4039.
Carson, M.S. and T.K. Smith. 1983a. Role of bentonite in the prevention ofT-2 toxicosis in rats. J. Anim. Sci. 57:1498.
Carson, M.S. and T.K. Smith. 1983b. Effect of feeding alfalfa and refinedplant fibres on the toxicity and metabolism of T-2 toxin in rats. J. Nutr.113:304.
James, L.J. and T.K. Smith. 1982. Effect of dietary alfalfa on zearalenonetoxicity and metabolism in rats and swine. J. Anim. Sci. 55:110.
Matsui, Y. and M. Watanabe. 1988. Quantitative analysis of fusaric acid inthe cultural filtrate and soybean plants innoculated with Fusariumoxysporum var. redolens. J. Rakuno Gakuen Univ. Nat. Sci. 13:159.
Smith, T.K. 1984. Spent canola oil bleaching clays: potential for treatmentof T-2 toxicosis in rats and short-term inclusion in diets for immatureswine. Can. J. Anim. Sci. 64:725.
Smith, T.K., E.G. McMillan and J.B. Castillo. 1997. Effect of feeding blendsof Fusarium mycotoxin-contaminated grains containing deoxynivalenoland fusaric acid on growth and feed consumption of immature swine. J.Anim. Sci. 75:2184.
Smith, T.K. and M.G. Sousadias. 1993. Fusaric acid content of swine feedstuffs.
J. Agr. Food Chem. 41:2296.
Stangroom, K.E. and T.K. Smith. 1984. Effect of whole and fractionateddietary alfalfa meal on zearalenone toxicosis in rats and swine. Can. J.Physiol. Pharmacol. 62:1219.
Wood, G.E. 1992. Mycotoxins in foods and feeds in the United States. J.Anim. Sci. 70:3941.
Wu, W., D. Jerome and R. Nagaraj. 1994. Increased redness in turkeybreast meat induced by Fusarial culture materials. Poultry Sci. 73:331.
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