Deactivating Mycotoxins

Zearalenone (ZEN) can have a significant impact on reproductive performance, as pigs are among the most sensitive species to this mycotoxin. Negative effects are due to the interaction of ZEN and its metabolites with estrogen receptors, disturbing hormonal homeostasis. 

ZEN can cause abortions, light litters and stillbirths In addition, ZEN contaminated feed induces the swelling and reddening of vulva (hypoestrogenism), false heats and pseudopregnancy. Studies investigating the carry-over of ZEN into meat and other edible tissues showed that there is only limited tissue deposition of this mycotoxin.

Pigs are very sensitive to zearalenone (ZEN). ZEN increases the frequency of abortions and stillbirths in pregnant sows. In general, ZEN-contaminated pig feed induces:

• swelling and reddening of the vulva 
• false heats
• false pregnancy

Due to their undeveloped endocrine system, gilts are even more sensitive to ZEN’s estrogenic effect. The results of ZEN ingestion are hyperaemia and vulva swelling (hyperestrogenism); uterus mass increase; ovarian follicle atresia and atrophic ovaries; vaginal or rectal prolapse. Hyperestrogenism would delay oestrus onset and would compromise fertility in subsequent reproductive life of gilt.

• hyperaemia and vulva swelling (hyperestrogenism)
• uterus mass increase
• ovarian follicle atresia and atrophic ovaries
• vaginal or rectal prolapse.

Aflatoxins can cause death when administered at high levels, but the greatest impact comes from reduced reproductive and performance capabilities, suppressed immune function and various pathological effects on organs and tissues.

Piglets fed aflatoxin-contaminated diets which were vaccinated with ovalbumin, showed decreased cell-mediated immunity and impaired lymphocyte activation. Thymus weight and histopathology, as well as viable alveolar macrophages were negatively influenced. In addition, cases of aflatoxin carry-over in swine have been reported with residues found in porcine liver and muscle tissues.

Hepatotoxic effects, decreased performance parameters, nephrotoxicity and necrosis are the major toxic effects caused by Ochratoxin A. In addition, pigs showed a significant and linear reduction of daily gain with increasing doses of ingested ochratoxin A. This mycotoxin was observed to suppress cell-mediated immune response in pigs, resulting in reduced macrophage activity and weakened stimulation of lymphocytes. Furthermore, ochratoxin A tends to accumulate in kidneys, liver and muscle tissues, as well as in blood serum and, therefore, it represents a potential hazard in the human food chain.

Reduced milk production results from several factors, including a decrease in intake or feed refusal, commonly caused by trichothecenes (e.g. DON, NIV, T-2, etc.). Many mycotoxins can alter rumen function due to their antimicrobial effect, such as trichothecenes, zearalenone, fumonisins, as well as many emerging mycotoxins. They can alter the microbial populations and reduce feed digestibility, therefore reducing volatile fatty acid and microbial protein production, which finally limits nutrient availability for milk synthesis.

1. Reduced milk production
2. Toxic contaminants in milk, especially Aflatoxin M1
3. Increased risk of mastitis
4. Altered milk composition
5. Reduced milk to cheese yield

• Ruminants can only partly degrade aflatoxin in the rumen, the rest is converted into Aflatoxin M1, which is excreted in milk, representing a public health concern
• Aflatoxins are known to be the most carcinogen substance found in nature, it causes multiple negative effects to the animal’s health
• Most countries established strict limits for aflatoxins in milk (Table 2), but it is important to note that also other mycotoxins can negatively affect profitability and animal health and welfare

One of the most commonly occurring mycotoxins in livestock feeds is deoxynivalenol (DON), better known as ‘vomitoxin’. Deoxynivalenol is a member of the trichothecene family of mycotoxins, specifically Type B trichothecenes. Several species of Fusarium molds are capable of producing trichothecenes. Additionally, some Fusarium mold species can produce the mycotoxins zearalenone and fumonisins. It is not uncommon to detect more than one toxin in a feed sample since molds can produce more than one type of mycotoxin and since more than one mold can infect a plant.

Additionally, other organs may be exposed to pathogens or toxins which enter the bloodstream, increasing the possibility for disease. Disruption of the intestinal mucosa can also lead to diarrhea. A large portion of the immune system is located in the gastrointestinal tract. Immune function can be impaired by disruption of the gut mucosa.  

DON can impair production of the white blood cells, which help fight infection. Deoxynivalenol can also weaken the immune system by negatively impacting cytokine and antibody production. The animal’s natural immune response to vaccinations may also be reduced, leaving them susceptible to disease despite vaccination. All of these factors can lead to immune dysfunction in cattle, increasing vulnerability to infections. 

• ZEN shares a very similar structure with estrogen, therefore it binds to estrogen receptors and causes hormonal imbalances and reproductive failure
• ZEN is not detoxified by ruminal microbiota, instead its estrogenic effect is increased by being transformed largely into α-ZEL, a molecule with an estrogenic effect 60 times higher than ZEN (Figure 5)
• Reproductive efficiency in dairy farms represents massive economic losses

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• Ruminants have a well-known susceptibility to the effects of ergot alkaloids
• Ergots are produced by fungi growing on cereals or by endophyte fungi within tall fescue grass
• One of their main effects is vasoconstriction (restricting blood flow) which has a visible impact on extremities (Figure 6), but can also cause lameness, reproductive failure and it worsens heat stress. 

• It is commonly detected in maize silages
• Rumen microbes allow FUM to bypass the rumen mostly intact (Figure 7) FUM can cause hepatic damage in calves, dairy cows and beef cattle as well as impair the immune system
• FUM can lead to decreased milk production and milk quality in dairy cattle and lower weight gain in beef cattle, especially when co-occurring with other mycotoxins

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Aflatoxins 

Aflatoxin B1 is the most toxic Aflatoxin. It is highly carcinogenic and hepatotoxic and its concentration is strictly regulated in several markets worldwide. Each year numerus cases of aflatoxicosis breakouts occur globally. It is a strong immune suppressor thus predisposing animals to disease. Further, aflatoxins affect growth and feed efficiency.

This mycotoxin can accumulate in tissues (including liver, muscles, ovary) making it a risk to human or animals consuming the fish.

Sensitivity differs a lot between aquatic species. Some species are extremely sensitive: In sea bream (Sparus aurata), ‘low’ aflatoxin B1 (AFB1) levels caused hepatocytes damage and cell death, additionally uncontrolled cell proliferation and tumoral foci was caused by the exposure to AFB1.

The feed conversion ratio (FCR) and weight gain of Beluga (Huso huso) are negatively affected by concentrations of AFB1 ranging from 20 to 100 ppb. Other symptoms such as liver necrosis can be observed as well.

In tilapia, AFB1 affects the growth rate and FCR at concentrations ranging from 100 to 2500 ppb, however studies showed how already 50 ppb were enough to cause liver necrosis. A very comprehensive study exposed Nile tilapia to 50 ppb aflatoxins for 45 days and reported various negative impacts ranging from gasping, severe fin rot, skin darkness over enlarged liver and spleen, tissue damage in liver and kidney, distended gall bladder, increased mucus in intestines, decrease in immunological parameters (lysozyme activity) to increased mortality.

Summing up, aflatoxins have a strong impact on fish farming production by causing disease with high mortality and a gradual decline of reared fish stock quality.

Deoxynivalenol 

Some aquatic species are sensitive to deoxynivalenol (DON), especially salmonids such as rainbow trout and Atlantic salmon. Both species show sensitivity at low levels (300-500 ppb). The main symptoms observed in several studies were significant decreases in: 

• Growth  
• Feed intake  
• Feed efficiency 
• Protein efficiency ratio (weight gain (g)/ protein intake (g))
• Energy utilization  

A reciprocal decrease in feed conversion efficiency and weight gain was also observed in red tilapia exposed to moderate levels (300-500 ppb) over 8 weeks.

Zearalenone 

Studies on the effects of zearalenone (ZEN) in farm animals have mainly focused on dysfunction or structural disorders of the reproductive tract. Several studies have confirmed that ZEN modulates estrogen receptor-dependent gene expression in aquatic species, thus affecting the reproduction of fish.  

Effects of feed contaminated with ZEN at EU guidance value (2 mg/kg feed) on reproductive health and performance was investigated in rainbow trout. Long-term exposure, particularly during sexual maturation affected viability of the offspring. ZEN exposure may have interfered with sex differentiation and caused morphological anomalies in gonads. Apart from the reproductive system, also immunomodulatory/immunotoxic effects were detected.

These findings raise concerns about the safety of the current guidance value for ZEN in feed used in aquaculture.

Fumonisins 

In aquaculture species, fumonisin B1 (FB1) has been generally associated with reduced growth rate, feed consumption and feed efficiency ratio, as well as impaired sphingolipid metabolism. In rainbow trout, FB1 has been shown to induce changes in the liver’s sphingolipid metabolism at levels lower than 100 ppb and was able to induce liver cancer in 1-month-old trout.

According to the literature, ingestion of FB1 by carp resulted in lesions in liver and pancreas already at concentrations as low as 500 ppb. Performance parameters such as average weight gain and body weight dropped after dietary administration of moderate doses of FB1. FB1 affected the performance of Nile tilapia and might have promoted formation of liver tumors in co-occurrence with Afla B1.

An internal trial with Asian seabass indicated a negative influence already at moderate levels of FUM (500 ppb) with and without DON (250 ppb DON, 250 ppb FUM). Contamination negatively impacted survival, performance, liver size (HSI) and immune response (predisposing to diseases).

Ochratoxins 

Studies on the toxicity of ochratoxin A (OTA) in aquatic animals are very scarce. However, this mycotoxin is known to have a carryover character making it a risk to human or animals consuming the fish. In addition, a few studies reported effects such as severe degeneration and necrosis of kidney and liver leading to inferior weight gain, poorer FCR, lower survival rates and hematocrit levels. OTA is also immunosuppressive, and a study conducted on catfish showed how animals exposed to this mycotoxin become more susceptible to pathogenic infections.

Carp (Cyprinus carpio) seem to be very sensitive as a natural contamination with 15 ppb OTA resulted in decreased growth performance and feed utilization parameters.

Aflatoxins 

Impact of mycotoxins in shrimp are less investigated than for fish. However, evidence in the literature suggests that shrimp can be highly sensitive to certain mycotoxins.

In Pacific white shrimp (Litopenaeus vannamei) exposure to AFB1 is usually associated with increased mortality, damages to hepatopancreas, immune suppression and ultimately, drop in performance parameters.

Black tiger shrimp (Penaeus monodon Fabricius) was reported to be susceptible to levels of AFB1 as low as 5 to 20 ppb. The main effects are damage to hepatopancreas and reduction on weight gain up to 50% compared to the control group.

Deoxynivalenol 

Regarding the impact of DON on shrimp, those are mostly related to performance, where concentrations as little as 200 ppb have been associated with reduced body weight and/or growth rate. A study exposing Pacific white shrimp (Litopenaeus vannamei) to DON observed detrimental effects at levels between 300 to 1000 ppb DON. Weight gain and survival were negatively influenced. The gastrointestinal system, mucus and intestinal epithelial cell structure, were harmed by dietary DON already at moderate concentrations. Furthermore, effects on immune system were indicated. This can negatively impact nutrient utilization and pathogen exposure of the animals.

Zearalenone 

Still little is known about the impact of ZEN in shrimp. Some studies investigated its impact on black tiger shrimp (Penaeus monodon Fabricius). The observed effects were abnormalities in the development of the hepatopancreas, with consequences for the immune system and growth performance. Direct toxicity of ZEN was evaluated in species of Artemia brine shrimp, lethality was observed in concentration starting as low as 10 ppb and was increasing with time and toxin concentration.

Fumonisins 

The effects of FUM in shrimp have not been extensively investigated. However, there is some evidence suggesting that moderate doses of these mycotoxins (500 ppb to 1000 ppb) can affect the hepatopancreas tissue as well as the muscle structure, with implications on the quality of the product during ice storage.

Ochratoxins 

OTA is probably the least investigated mycotoxin in shrimp. The few available studies reported atrophy, severe necrosis and degeneration of the hepatopancreas and disruption of the hematopietic tissue and lymphoid organs after oral administration of OTA.