Effects of mycotoxins in ruminants

RuminantsThe effects of mycotoxins in ruminants is a research area that highly depends on economic factors that arise when it comes to planning and conducting a trial.1 Effects of mycotoxins in ruminants are dependent upon multiple factors that include: type of mycotoxin and duration of exposure, type of diet (ruminant diets are quite complex and involve the use of different types of ingredient and protein sources), status of the animal (age, sex, breed, dry matter intake (DMI), general health, immune status, nutritional strategies), and environmental parameters (farm management, hygiene and biosecurity).1,2 Of relevance is the multiple unknown metabolites whose presence can increase the toxicity of other known mycotoxins via synergistic and additive interactions.1,3 Normally, ruminants are considered more resistant to mycotoxins due to the complexity of their gastrointestinal tract which is populated by a broad variety of different microorganisms, some of which are capable to biotransform mycotoxins.1,4,5 However, feed commodities are usually contaminated by more than one mycotoxin, and due to the composition of the diet, ruminants are more exposed to the a mixture of toxins that occur in the field and during storage.3

Aflatoxins, especially aflatoxin B1 (AfB1) are potent carcinogens for both animals and humans (listed as a group 1 carcinogens by the International Agency for Research on Cancer, IARC).1,6,7 AfB1 is rapidly absorbed and metabolized in the body, and appear in the bloodstream and milk after a minimum of five minutes.5,8,9,10,11 The main metabolite of AfB1 is aflatoxin M1 which is even more carcinogenic and contaminates milk and other dairy products, which is why the presence of AfB1 in dairy feed is strictly regulated in the majority of markets worldwide.1,5,10 The aflatoxin metabolite AFM1, is carried over into the milk from around 1 to 6% of the aflatoxin consumed.31 In addition, AfB1 demonstrates antimicrobial activities, as reported by some studies where cows fed AfB1 contaminated feed showed a reduction of gas production, ammonia and volatile fatty acid (VFA) concentrations, together with an increased bioavailability of AfB1 in the rumen fluid.5,6,10,12 Aflatoxins are highly immunosuppressive as well, and effects on animals such as sheep and dairy cows can be significant, even at low doses.1,5,10,11 In general, calves are more sensitive to aflatoxins than adult cattle.1  

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Ergot alkaloids may induce neurotoxic effects, leading to reduced feed intake because the birds are reluctant to move and may suffer from respiratory difficulties.34 Birds affected by ergot alkaloids showed poor growth and decreased egg production. The most obvious pathological changes are gangrenous lesions on the toes, beak and claws.35

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Fumonisins are poorly degraded in the rumen. Common symptoms in ruminants are diarrhea and hematological changes such as an increase in the serum cholesterol.1,5,20 Other symptoms reported in the literature include hepatocellular injuries and neoplasia in the biliary epithelial cells, changes in hematological parameters including an increase of serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin and cholesterol.5,20,21,22 One study conducted on calves reported on histological changes after feeding with 15, 31 and 148 mg fumonisins/kg diet for 31 days.20

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Ochratoxin A (OTA) is largely degraded by rumen microflora into OTα.13 The literature generally does not report the effects on nutrient digestibility and feed intake, suggesting that animals have developed tolerance mechanisms.14 Portions of ochratoxin A that are not degraded can however be transferred to the milk, although the concentration is usually too low to present a threat to consumers.5,15  

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Type A Trichothecenes

The effects of type A trichothecenes such as T-2 and HT-2 have been investigated in young ruminants.1,13 Their main effects include hemorrhages, lesions in the gastrointestinal tract, and changes in the immune status.1,13 Effects on the semen quality were observed in bulls, but no information is currently available on dairy cows or beef animals.19

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In the rumen, zearalenone (ZEN) is converted into α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL), with the α-metabolite (which is approximately ten times more estrogenic than the parental compound) being the predominant one.1,2,23 Common ZEN post-exposure symptoms include reproductive problems, such as edema and hypertrophy of the genitalia, decrease in embryo survival, alteration in uterine tissues morphology, decreased testosterone production and subsequent feminization in males, and infertility.2,24,25,26,27 

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Synergistic effects in ruminants

Although ruminants are thought to be less susceptible to the effects of mycotoxins, the protective effect of the rumen can be compromised when the health status of the animal is altered, or when the latter is exposed to mixtures of mycotoxins. A typical agricultural commodity contains on average 25-30 different bacterial and fungal secondary metabolites, thus mycotoxin mixtures can be quite heterogeneous.3

The literature reports that a mixture of deoxynivalenol and other Fusarium mycotoxins including zearalenone, nivalenol, and masked forms of deoxynivalenol (DON-3-glucoside) are able to interfere with the activity of cellulolytic bacteria, which are very important for ruminants.1,13,26 An increase in rumen ammonia concentration, and a reduced duodenal flow of microbial proteins suggesting alteration of microbial population, was also reported in cows consuming feed contaminated by mixtures of Fusarium mycotoxins.28 The latter, in combination with AfB1 were able to interfere with the dry matter intake and nutrient digestibility in lactating dairy cows, stressing the importance of synergistic interactions.1,5,27 Mycotoxins such as aflatoxins, deoxynivalenol, gliotoxin, fumonisins, roquefortine C and mycophenolic acid are quite stable in the rumen environment and can potentially reach the intestinal intact.29

Mixtures of Aspergillus mycotoxins can be harmful for ruminants. These include gliotoxin which exhibits antimicrobial, antiprotozoal and immunosuppressive effects (ROS and apoptosis of lymphocytes), and Kojic acid and cyclopiazonic acid, which both show antimicrobial activities (disruption of calcium homeostasis, degeneration and necrosis of liver).13,29,30

Strains of Penicillium such as P. roqueforti and P. paneum produce immunosuppressive and antibacterial secondary metabolites. Consumption of feed contaminated with these fungi can result in loss of appetite, impaired nutrient efficiency, ketosis, ulceration and gastroenteritis.2,13,29,30 In some cases, paralysis and abortion were observed as well.1 Some mycotoxins, and mixtures of them, produced by strains of Penicillium such as ochratoxin A, citrinin, patulin, mycophenolic acid, can inhibit macrophage proliferation, rendering cattle more susceptible to diseases.29 Other symptoms observed in animals consuming moldy silages were oxidative stress and dysfunction of lipid metabolism.25

Co-occurrence of Monascus ruber toxins such as citrinin and ochratoxin A are able to generate symptoms such as pruritus, pyrexia, and hemorrhages as well as fever and diarrhea. Moreover, citrinin shows antimicrobial effects and can have a negative impact on the rumen microflora.29

Effects of Mycotoxins in Ruminants

AFB1 – Aflatoxin B1 | AFM1 – Aflatoxin M1 | DON – Deoxynivalenol | FUM – Fumonisins | OTA – Ochratoxin A | T-2 – T-2 Toxin | HT-2 – HT-2 Toxin | ZEN - Zearalenone | Ergots – Ergot, Alkaloids

  1. Gallo, A., Giuberti, G., Frisvald, J.C., Bertuzzi, T. and Nielsen, K.F. (2015). Review on Mycotoxin Issues in Ruminants: Occurrence in Forages, Effects of Mycotoxin Ingestion on Health Status and Animal Performance and Practical Strategies to Counteract Their Negative Effects. Toxins, 7, 3057-3111.
  2. Jouany, J.P., and Diaz, D.E. (2005). Effects of mycotoxins in ruminants. In Mycotoxins Blue Book; Nottingham University Press: Thrumpton, Nottingham, UK. pp. 295–321. 134
  3. Kovalsky P, Kos g. Nährer K, Schwab C, Jenkins T, Schatzmayr G, Sulyok and Krska R. (2016). Co-occurrence of Regulated, Masked and Emerging Mycotoxins and Secondary metabolites in Finished Feed and Maize- An Extensive Survey. Toxins, 8, 363.
  4. Charmley, E., Trenholm, H.L., Thompson, B.K., Vudathala, D., Nicholson, J.W., Prelusky, D.B., and Charmley, L.L. (1993). Influence of level of deoxynivalenol in the diet of dairy cows on feed intake, milk production, and its composition. J. Dairy Sci. 76, 3580–3587. 176
  5. Fink-Gremmels, J. (2008). Mycotoxins in cattle feeds and carry-over to dairy milk: A review. Food Addit. Contam. A Chem. Anal. Control Expo. Risk Assess. 25, 172–180. 31
  6. Jiang, Y.H., Yang, H.J., and Lund, P. (2012). Effect of aflatoxin B1 on in vitro ruminal fermentation of rations high in alfalfa hay or ryegrass hay. Anim. Feed Sci. Technol. 175, 85–89. 144
  7. Mojtahedi, M. (2013). Effect of aflatoxin B1 on in vitro rumen microbial fermentation responses using batch culture. Annu. Rev. Res. Biol. 3, 686–693. 141
  8. Council for Agricultural Science and Technology (CAST). (2003). Mycotoxins: Risks in Plant, Animal, and Human Systems; CAST: Ames, IA, USA, 4
  9. Masoero, F., Gallo, A., Moschini, M., Piva, G., and Diaz, D. (2007). Carryover of aflatoxin from feed to milk in dairy cows with low or high somatic cell counts. Animal 1, 1344–1350. 169
  10. Pulina, G., Battacone, G., Brambilla, G., Cheli, F., Danieli, P.P., Masoero, F., Pietri, A., Ronchi, B. (2014). An update on the safety of foods of animal origin and feeds. Ital. J. Anim. Sci. 13, 845-856
  11. Tripathi, M.K., Mondal, D., and Karim, S.A. Growth, haematology, blood constituents and immunological status of lambs fed graded levels of animal feed grade damaged wheat as substitute of maize. J. Anim. Physiol. Anim. Nutr. Berl. 92, 75-85.
  12. Morgavi, D.P., and Riley, R.T. (2007). An historical overview of field disease outbreaks known or suspected to be caused by consumption of feeds contaminated with Fusarium toxins. Anim. Feed Sci. Technol. 137, 201–212. 241
  13. Fink-Gremmels, J. (2008). The role of mycotoxins in the health and performance of dairy cows. Vet. J. 176, 84–92. 3
  14. Battacone, G., Nudda, A., and Pulina, G. (2010). Effects of ochratoxin a on livestock production. Toxins 2, 1796–1824. 227
  15. Boudra, H., Saivin, S., Buffiere, C., and Morgavi, D.P. (2013). Short communication: Toxicokinetics of ochratoxin A in dairy ewes and carryover to milk following a single or long-term ingestion of contaminated feed. J. Dairy Sci. 96, 6690–6696. 233
  16. European Food Safety Authority (EFSA). (2004). Opinion of the Scientific Panel on contaminants in the food chain [CONTAM] related to Deoxynivalenol (DON) as undesirable substance in animal feed. EFSA J. 73, 1–42. 242
  17. Keese, C., Meyer, U., Rehage, J., Spilke, J., Boguhn, J., Breves, G., and Dänicke, S. (2008). On the effects of the concentrate proportion of dairy cow rations in the presence and absence of a fusarium toxin-contaminated triticale on cow performance. Arch. Anim. Nutr. 62, 241–262. 174
  18. Keese, C., Meyer, U., Rehage, J., Spilke, J., Boguhn, J., Breves, G., and Dänicke, S. (2008). Ruminal fermentation patterns and parameters of the acid base metabolism in the urine as influenced by the proportion of concentrate in the ration of dairy cows with and without Fusarium toxin-contaminated triticale. Arch. Anim. Nutr. 62, 287–302. 175
  19. Alm, K., Dahlbom, M., Säynäjärvi, M., Andersson, M.A., Salkinoja-Salonen, M.S., and Andersson, M.C. (2002). Impaired semen quality of AI bulls fed with moldy hay: A case report. Theriogenology 58, 1497–1502. 254
  20. Osweiler, G.D., Kehrli, M.E., Stabel, J.R., Thurston, J.R., Ross, P.F., and Wilson, T.M. (1993). Effects of fumonisin-contaminated corn screenings on growth and health of feeder calves. J. Anim. Sci. 71, 459–466. 186
  21. Baker, D.C., and Rottinghaus, G.E. (1999). Chronic experimental fumonisin intoxication of calves. J. Vet. Diagn. Investig. 11, 289–292. 23
  22. Richard, J.L., Meerdink, G., Maragos, C.M., Tumbleson, M., Bordson, G., Rice, L.G., and Ross, P.F. (1996). Absence of detectable fumonisins in the milk of cows fed Fusarium proliferatum (Matsushima) Nirenberg culture material. Mycopathologia 133, 123–126. 185
  23. Kennedy, D.G., Hewitt, S.A., McEvoy, J.D., Currie, J.W., Cannavan, A., Blanchflower, W.J., and Elliot, C.T. (1998). Zeranol is formed from Fusarium spp. toxins in cattle in vivo. Food Addit. Contam. 15, 393–400. 258
  24. Minervini, F., and Dell’Aquila, M.E. (2008). Zearalenone and reproductive function in farm animals. Int. J. Mol. Sci. 9, 2570–2584. 259
  25. Santos, R.R., Schoevers, E.J., Roelen, B.A.J., and Fink-Gremmels, J. (2013). Mycotoxins and female reproduction: In vitro approaches. World Mycotoxin J. 6, 245–253. 138
  26. Winkler, J., Kersten, S., Meyer, U., Engelhardt, U., and Dänicke, S. (2014). Residues of zearalenone (ZEN), deoxynivalenol (DON) and their metabolites in plasma of dairy cows fed Fusarium contaminated maize and their relationships to performance parameters. Food Chem. Toxicol. 65, 196–204. 182
  27. Zinedine, A., Soriano, J.M., Moltó, J.C., and Mañes, J. (2007). Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: An oestrogenic mycotoxin. Food Chem. Toxicol. 45, 1–18. 2
  28. Santos, R.R., and Fink-Gremmels, J. (2014). Mycotoxin syndrome in dairy cattle: Characterisation and intervention results. World Mycotoxin J. 7, 357–366. 16
  29. Oh, S.Y., Balch, C.G., Cliff, R.L., Sharma, B.S., Boermans, H.J., Swamy, H.V.L.N., Quinton, V.M., and Karrow, N.A. (2013). Exposure to Penicillium mycotoxins alters gene expression of enzymes involved in the epigenetic regulation of bovine macrophages (BoMacs). Mycotoxin Res. 29, 235–243.
  30. Nielsen, K.F., Sumarah, M.W., Frisvad, J.C., and Miller, J.D. (2006). Production of metabolites from the Penicillium roqueforti complex. J. Agric. Food Chem. 2006, 54, 3756–3763. 11
  31. Pettersson, H. (2004) Controlling mycotoxins in animal feed. In: Mycotoxins in food, detection and control (Magan, N. and Olsen, M., eds.), pp. 262-304. Woodhead Publishing Limited. Cambridge.