Hay mycotoxins linked to liver disease in horses in British study

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Findings do not prove that the identified mycotoxins caused liver disease, but they provide a basis for further investigation of possible links.
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Certain mycotoxins identified in stored hay have been tied to some cases of liver disease in horses.

While the British study, reported in the Journal of Veterinary Internal Medicine, did not prove that the mycotoxins caused liver disease in horses, the findings provide a basis for further investigation of possible links.

Study author Professor Andy Durham, clinical director at the Liphook Equine Hospital in England, noted that, in most liver disease outbreaks in horses, the cause remains elusive.

“Many fungi produce metabolites that possess antibacterial, antiviral, anthelmintic, antifungal, herbicidal, and insecticidal properties, which may provide a competitive advantage,” he said.

Some fungal products are also toxic to mammals. More than 500 such mycotoxins have been identified, mostly from fungi of the genera Aspergillus, Penicillium, Alternaria, and Fusarium. Mycotoxins are also a major human health concern, with around 25% of global crop production being contaminated, he noted.

Monogastric species, including horses, are considered more susceptible to mycotoxins than ruminants, with the main groups endangering animal health comprising alflatoxins, ochratoxins, trichothecenes, fumonisins, and zearalenone.

Several mycotoxins are known to be associated with liver disease, he said.

In his study, Durham set out to examine the association between outbreaks of liver disease in horses and the presence of mycotoxins in forage stored on the same premises.

Premises were identified where four or more horses were affected by liver disease around the same time, and a control group was formed from premises where at least four horses had been examined and found, on the basis of serum analysis, to have no evidence of liver disease.

To meet the study criteria, the cases of liver disease in affected horses had to be confirmed contemporaneously through either serum biochemistry or liver biopsy, and with no cause identified.

Forage was collected from 29 premises that met the case criteria and 12 control premises.

The forage was analyzed for mycotoxins using liquid chromatography/mass spectrometry, targeting 54 mycotoxins. The presence and distribution of mycotoxins between case and control samples were compared.

Mycotoxins were found in 23 of the 29 hay samples from properties affected by liver disease, representing 79% of the samples; and 10 of the 12 control samples, representing 83% of samples. Median total mycotoxin concentrations were similar between the two sample groups.

However, 10 mycotoxins were found, alone or in combination, exclusively in case premises: Fumonisin B1, 15-acetyldeoxynivalenol, deoxynivalenol, zearalenone, aflatoxins B1 and G1, methylergonovine, nivalenol, verruculogen, and wortmannin. Several of them have known potential to cause liver disease.

The findings, he said, are consistent with the hypothesis that forage-associated mycotoxicosis may be a cause of outbreaks of liver disease in horses in Britain.

Durham said mycotoxins were present in more than 80% of the tested hay samples across all premises, although neither the overall prevalence nor total mycotoxin concentrations differed between hay fed to horses with liver disease versus those from control premises.

The difference lay in the 10 mycotoxins found exclusively on premises with liver disease, indicating they might be considered as potential causes.

Of these, fumonisin B1 was the most prevalent and differed significantly between case and control samples.

The most common mycotoxins identified across the hay samples were fusaric acid, ochratoxin A, fumonisin B1, penicillic acid, and neosolaniol. However, the only mycotoxin found in forage from case premises in significantly higher concentrations than in control samples was fumonisin B1.

“In contrast, fusaric and penicillic acids were found in significantly larger amounts in control hay samples, with ochratoxin A almost reaching significance.”

This finding may reflect storage and growth factors favoring the production of specific mycotoxins with and without the potential to cause liver disease.

Mycotoxin contamination, he said, is known to vary significantly for the same crop in different years, depending on factors such as local temperature and humidity.

Interestingly, despite fusaric acid, penicillic acid or ochratoxin A being present in 20 of 41 hay samples, only one of the nine samples positive for fumonisin B1 contained fusaric acid (the lowest detected amount of all samples) and none contained penicillic acid or ochratoxin A. This perhaps suggested important differences in storage parameters for hay on case and control premises.

Durham said adverse health consequences of mycotoxins can be complex and unpredictable. They depend on a range of factors, including the animal species, bioavailability and co-exposure to other mycotoxins.

“In addition to the association of fumonisin B1 with liver disease in our study, it is possible that other mycotoxins also might have pathogenetic relevance.”

Durham raised several limitations to his study but said the findings provide a basis for further study of certain mycotoxins.

He said those found more commonly in control premises would appear unlikely to have relevance to outbreaks of liver disease. Instead, a focus on the other mycotoxins, such as fumonisin B1, would appear more logical.

Durham, A. E., Association between forage mycotoxins and liver disease in horses. J Vet Intern Med. 2022; 36( 4): 1502- 1507. doi:10.1111/jvim.16486

The study, published under a Creative Commons License, can be read here

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