Nutrigeonomics: Evaluating Mycotoxin Control Strategies

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Introduction
Mycotoxins are metabolites produced by molds (fungi) that can infest crops pre-harvest and can continue to flourish under sub-optimal storage conditions. Grains with a high moisture content are particularly unstable and prone to mold proliferation and possible mycotoxin production. Excess rainfall at harvest and at key periods during the growing season can be a major promoter of mycotoxin contamination of feedstuffs. These are the same conditions which have affected much of the 2009 American corn crop.
 
The most significant species of mycotoxin-producing fungi that have an impact on poultry production would include Aspergillus and Fusarium. The most significant mycotoxin produced by Aspergillus fungi are the aflatoxins. The fungi that synthesize aflatoxins, A. flavus and A. parasiticus, are considered to be tropical or semi-tropical molds that thrive under conditions of high moisture and temperature. The effects of feedborne aflatoxin on poultry production have been extensively studied and we have a good understanding of the tolerance of various classes of poultry. This is partly due to concern for human health and food safety issues arising from contamination of poultry products with aflatoxin since aflatoxin is a potent hepatocarcinogen. Analytical techniques for aflatoxin analysis in feeds are very practical due to the small number of different compounds which allows their simultaneous analysis. 
 
Fusarium fungi flourish in more temperate climates including much of the American corn belt. Our understanding of Fusarium mycotoxicoses in poultry is much less complete than our understanding of aflatoxicosis. This is in part because of the very large number of Fusarium mycotoxins, more than one hundred have been chemically characterized, which makes a complete analysis of feedstuffs for Fusarium mycotoxins impractical, if not impossible. The most commonly recognized Fusarium mycotoxins include the trichothecenes, a large family of structurally-related compounds including deoxynivalenol (DON, vomitoxin), T-2 toxin, nivalenol, diacetoxyscirpenol (DAS) and over 100 others; zearalenone, an estrogenic compound; fumonisins and fusaric acid.
 
Analyzing Mycotoxins in Poultry Feeds
A major source of error in mycotoxin analysis is inadequate sampling of feedstuffs. Proper sampling protocols have been developed and published in an effort to minimize this source of error. Another source of error is the potential presence of different chemical forms of mycotoxins which may escape routine analysis. Attention has been focused on the presence of conjugated forms of mycotoxins that are produced by plants. This may be the result of detoxification of mycotoxins by plant metabolism and it has been suggested that the presence of conjugated mycotoxins might be used in making genetic selection of plant resistance to fungal invasion (Liu et al., 2005). Although conjugated forms of deoxynivalenol (DON, vomitoxin) were identified many years ago (Sewald et al., 1992), little information is available about the relative significance of conjugated and free mycotoxins in poultry diets. Schneweis et al. (2002) identified glucose conjugated zearalenone in samples of wheat. Naturally-contaminated wheat and corn samples from Slovakia have been found to contain glucose-conjugated DON with up to 29% of deoxynivalenol in a glucose conjugated form (Berthiller at al., 2005). More recently, Zhou et al. (2007) reported an increase in DON concentrations of up to 88% when barley samples from North Dakota were treated with trifluoroacetic acid prior to analysis. Such acid treatment would hydrolyze all different conjugates of DON. Similar acid treatment of different barley samples showed up to 21% of total DON found in conjugated forms (Zhou et al., 2008). Most recently, Zachariasova et al. (2008) have found even higher levels of bound DON in barley and beer using a variety of analytical techniques. The frequency of bound fumonisin routinely exceeded free fumonisin in samples of European corn and corn-based foods (Dall’Asta et al., 2008). It is not yet clear if the conjugated forms of mycotoxins are as harmful to poultry as the parent compounds, but it has been shown that some conjugated mycotoxins can be hydrolyzed in the digestive tracts of animals (Gareis et al., 1990).
 
It must be concluded that until we have a better understanding of the frequency, toxicity and nature of conjugated mycotoxins, current mycotoxin analysis of poultry feeds should often be considered to be an underestimate of correct values. It is necessary at this time, therefore, to consider mycotoxin analysis of feeds as offering only an approximation of the true hazard posed by the feeding of contaminated materials to poultry 
 
The Effects of Feeding Blends of Grains Naturally Contaminated With Fusarium Mycotoxins to Poultry
A series of studies has been conducted to determine the effects of feeding blends of naturally-contaminated feedstuffs, largely corn and wheat, to different types of poultry. The findings have been reviewed by Girgis and Smith (2010). These experiments were conducted in an effort to mimic conditions seen in commercial poultry production where diets contain multiple vectors of mycotoxin contamination. The mycotoxins in such diets were determined to be mainly DON with lesser amounts of zearalenone and 15-acetyl DON in addition to fusaric acid. Four different modes of action of the mycotoxins fed were identified: (1) reductions in cellular protein synthesis (2) reduced immunity (3) alterations in brain neurochemistry (4) damage to the intestinal epithelium. 
 
Reductions in cellular protein synthesis result in lesions of the gastrointestinal tract including necrosis, gizzard erosion, hemorrhaging, and malabsorption of nutrients. Reduced hepatic protein synthesis can decrease utilization of dietary amino acids resulting in increased uric acid synthesis as amino acids are oxidized for energy purposes.
 
Many Fusarium mycotoxins, as well as aflatoxin, have been shown to be immunosuppressive. This results in increased susceptibility to disease, lingering health problems in the flock and possible failure of vaccination programs. The disease symptoms arising from immunosuppression, moreover, are not symptoms characteristic of mycotoxins. They are only indirectly caused by mycotoxins and this makes certain identification of mycotoxins as the causative agent of reduced flock health very difficult.   
 
Combinations of feed-borne Fusarium mycotoxins are pharmacologically active. This means they have drug-like properties due to their effects on brain neurochemistry. The most reproducible effects observed are elevations in brain regional concentrations of serotonin. Such changes alter behavior including reductions in feed intake, loss of muscle coordination and increased lethargy.
 
Broilers
The feeding of a blend of ingredients naturally-contaminated with a combination of Fusarium mycotoxins resulted in reduced growth in the grower phase, elevations in blood uric acid levels, discoloration of breast meat and immunosuppression (Swamy et al., 2002, Swamy et al., 2004a). Changes in brain neurochemistry were also seen (Swamy et al., 2004b).   
 
Broiler Breeders
The feeding of a similar combination of Fusarium mycotoxin contaminated materials to broiler breeders significantly reduced hatchability due to reduced shell thickness of fertile eggs (Yegani et al., 2006a).Changes in brain neurochemistry were also observed (Yegani et al., 2006b). There were no effects of diet on sperm quality. In a parallel study with broiler breeder pullets, immunosuppression was observed (Girgis et al., 2008) as well as changes in intestinal morphology (Girgis et al., 2010). 
 
Layers
Laying hens were very sensitive to the feeding of combinations of Fusarium mycotoxins. Egg production and feed efficiency were reduced while major increases in blood uric acid concentrations were seen (Chowdhury and Smith, 2004). The elevations in blood uric acid levels were likely due to a reduction in hepatic fractional protein synthesis rates (Chowdhury and Smith, 2005). Immunosuppression was also observed (Chowdhury and et al., 2005a).   
 
Turkeys
Turkeys were very sensitive to the feeding of high levels of Fusarium mycotoxin contaminated feeds. Growth rates were significantly reduced even in the starter phase (Chowdhury and Smith, 2007) and some indices of immunosuppression were seen (Chowdhury et al., 2005b). The feeding of lower concentrations of Fusarium mycotoxins also reduced growth rates, elevated blood uric acid levels and caused immunosuppression (Girish et al., 2008a). This was coupled with morphological changes in the small intestine (Girish and Smith, 2008) and changes in brain neurochemistry (Girish et al., 2008b).   
 
Ducks
Ducks were quite resistant to the feeding of combinations of grains naturally contaminated with Fusarium mycotoxins (Chowdhury et al., 2005c). Indices of immunosuppression, however, were observed. 
 
Conclusions
It can be concluded that poultry are sensitive to combinations of feed-borne Fusarium mycotoxins and that the feeding of contaminated materials should be minimized. It appears that the frequency of mycotoxin contamination of poultry feeds is increasing. This may be due in part to adverse weather conditions pre-harvest in many parts of the world arising from global climate change. The complex nature of modern poultry rations including the increasing use of potentially contaminated by-products such distillers’ dried grains adds to the possibility of toxicological synergy between combinations of mycotoxins thereby increasing the severity of the response of poultry to contaminated feeds. Many of the adverse effects seen in the studies reviewed above could be prevented by the simultaneous feeding of a polymeric glucomannan mycotoxin adsorbent. The use of an appropriate mycotoxin adsorbent is likely the best short term strategy available for minimizing the adverse effects of feed-borne mycotoxins in poultry feeds. It is hoped that long-term strategies such as improved quality control measures arising from advances in analytical methodology and plant breeding strategies to reduce the susceptibility of plants to fungal invasion will help to minimize mycotoxin challenges to the poultry industries in the future.
 
References
Berthiller, F., Dall’Asta, C., Schuhmacher, R., Lemmens, M., Adam, G. and Krska, R. 2005. Masked mycotoxins: Determination of a deoxynivalenol glucoside in artificially and naturally contaminated wheat by liquid chromatography – tandem mass spectrometry. J. Agri. Food Chem. 53: 3421-3425. 
 
Chowdhury, S.R. and Smith, T.K. 2004. Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on performance and metabolism of laying hens. Poult. Sci. 83: 1849-1856.   
 
Chowdhury, S.R. and Smith, T.K. 2005. Effects of feeding grains naturally contaminated with Fusarium mycotoxins on hepatic fractional protein synthesis rates of laying hens and the efficacy of a polymeric glucomannan mycotoxin adsorbent. Poult. Sci. 84: 16711674.   
 
Chowdhury, S.R. and Smith, T.K. 2007. Effect of feed-borne Fusarium mycotoxins on performance, plasma chemistry and hepatic fractional protein synthesis rates of turkeys. Can. J. Anim. Sci. 87: 543-551.   
 
Chowdhury, S.R., Smith, T.K., Boermans, H.J. and Woodward, B. 2005a. Effects of feed-borne Fusarium mycotoxins on hematology and immunology of laying hens. Poult. Sci. 84: 1841-1850. 
 
Chowdhury, S.R., Smith, T.K., Boermans, H.J. and Woodward, B. 2005b. Effects of feed-borne Fusarium mycotoxins on hematology and immunology of turkeys. Poult. Sci. 84: 1698-1706.  
 
Chowdhury, S.R., Smith, T.K., Boermans, H.J., Sefton, A.E., Downey, R. and Woodward, B. 2005c. Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on performance, metabolism, hematology, and immunocompetence of ducklings. Poult. Sci. 84: 1179-1185. 
 
Dall’Asta, C., Galaverna, G., Aureli, G., Dossena, A. and Marchelli, R. 2008. A LC/MS/MS method for the simultaneous quantification of feww and masked fumonisins in maize and maize-based products. World Mycotoxin J. 1: 237-246.
 
Gareis, M., Bauer, J., Thiem, J., Plank, G., Grabley, S. and Gedek, B. 1990. Cleavage of zearalenone-glycoside, a “masked” mycotoxin, during digestion in swine. Zentralbl. Veterinarmed., Reihe B 37: 236-240.  
 
Girgis, G.N., Sharif, S., Barta, J.R., Boermans, H.J. and Smith, T.K. 2008. Immunomodulatory effects of feed-borne Fusarium mycotoxins in chickens infected with coccidia. Exper. Biol. Med. 233: 1411-1420. 
 
Girgis, G.N, Barta, J.R., Brash, M. and Smith, T.K. 2010. Morphologic changes in the intestine of broiler breeder pullets fed diets naturally contaminated with Fusarium mycotoxins with or without coccidial challenge.  Avian. Dis. 54: 67-73. 
 
Girgis, G.N. and Smith, T.K. 2010. Comparative aspects of Fusarium mycotoxicoses in poultry fed diets containing naturally contaminated grains.  World’s Poult. Sci. J. 66: 6586.      
 
Girish, C.K. and Smith, T.K. 2008. Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on small intestinal morphology of turkeys. Poult. Sci. 87: 1075-1082. 
 
Girish, C.K., Smith, T.K., Boermans, H.J. and Karrow, N.A. 2008a. Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on performance, hematology, metabolism, and immunocompetence of turkeys. Poult. Sci. 87: 421-432. 
 
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Liu, Y., Walker, F., Hoeglinger, B. and Buchenauer, H. 2005. Solvolysis procedures for the determination of bound residues of the mycotoxin deoxynivalenol in Fusarium species infected grain of two winter wheat cultivars preinfected with barley yellow dwarf virus. J. Agric. Food Chem. 53: 6864-6869. 
 
Schneweis, I., Meyer, K., Engelhardt, G. and Bauer, J. 2002. Occurrence of zearalenone4-beta-D-glucopyranoside in wheat. J. Agric. Food Chemn. 50: 1736-1738. 
 
Sewald, N., Lepschy von Gleissenthall, J., Schuster, M., Muller, G. and Aplin, R.T. 1992. Structure elucidation of a plant metabolite of 4-deoxynivalenol. Tetrahedron: Assymmetry. 3: 953-960.
 
Swamy, H.V.L.N., Smith, T.K., Cotter, P.F., Boermans , H.J. and Sefton, A.E. 2002. Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on production and metabolism in broilers. Poult. Sci. 81: 966-975. 
 
Swamy, H.V.L.N., Smith, T.K., Karrow, N.A. and Boermans, H.J. 2004a. Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on growth and immunological parameters of broiler chickens. Poult. Sci. 83: 533-543. 
 
Swamy, H.V.L.N., Smith, T.K. and MacDonald, E.J. 2004b. Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on brain regional neurochemistry of starter pigs and broiler chickens. J. Anim. Sci. 82: 2131-2139. 
 
Yegani, M., Smith, T.K., Leeson, S. and Boermans, H.J. 2006a. Effects of feeding grains naturally contaminated with Fusarium mycotoxins on performance and metabolism of broiler breeders. Poult. Sci. 85: 1541-1549.  
 
Yegani, M., Chowdhury, S.R., Oinas, N., MacDonald, E.J. and Smith, T.K. 2006b. Effects of feeding grains naturally contaminated with Fusarium mycotoxins on brain regional neurochemistry of laying hens, turkey poults, and broiler breeder hens. Poult. Sci. 85: 2117-2123. 
 
Zhou, B., Li, Y., Gillespie, J., He, G.-Q., Horsley, R. and Schwarz, P. 2007. Doehlert matrix design for optimization of the determination of bound deoxynivalenol in barley grain with trifluoroacetic acid (TFA). J. Agr. Food Chem. 55: 10141-10149. 
 
Zhou, B., Schwarz, P., He, G.-Q., Gillesie, J. and Horsley, R. 2008. Effect of enzyme pretreatments on the determination of deoxynivalenol in barley. J. Am. Soc. Brew. Chem. 66: 103-108.
 
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September 4, 2017
This publication has been of benefit to me and so I will like to reference it in my own PhD research write up. Please what is the appropriate citation for this publication? Thank you.
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