Mycotoxins are biological poisons produced by fungi when they experience stressful conditions to try to reduce the challenge from competing microbes.
The presence of fungi on feeds does not necessarily mean that mycotoxins are present (because the conditions had not been right to stimulate the production of mycotoxins) and the absence of visible fungi on feeds does not mean they are free from mycotoxins (because the fungi could have been stressed to the point of elimination but the mycotoxins remain).
Pigs are more sensitive to mycotoxins than ruminants because the microbial population in the rumen has a neutralizing effect on many of the mycotoxins they consume.
Pigs are considered highly susceptible to mycotoxin contamination, with young animals and female breeders being the most sensitive groups. Mycotoxin can cause clinical symptoms or subclinical decreasing animal performance leading to great economic losses.
Mycotoxins are toxic substances produced by molds and fungi on plants, on the field or during the storage.
Careful storage of ingredients, complex formulations that spread the risk of a single ingredient dominating a diet and manufacturing protocols further reduce the risk that compound feeds might contain mycotoxins when fed, provided it has been stored as recommended.
In the event that mycotoxins are believed to be affecting pigs, the suspected feeds should be removed from the diet. Mycotoxin binders are available, which can be mixed with feeds if they really have to be fed.
It is very important for farmers to understand that Mycotoxins are secondary fungal metabolites that can reduce performance and alter metabolism and reproduction in swine production. They are unavoidable contaminants in foods and feeds and are a major problem all over the world.
Mould growth and the subsequent mycotoxin production is determined by several environmental factors that markedly affect the composition of the mycoflora in feeds.
Of particular importance are temperature, composition of the gas atmosphere, substrate properties including moisture content and water activity (aw), pH and chemical composition, as well as biotic factors (insects, vertebrates and other microorganisms).
The pathological states arising from the consumption of feeds contaminated with mycotoxins are referred to as mycotoxicoses.
The majority of the known mycotoxin-producing fungal species fall into three recognised genera. These genera are Aspergillus, Penicillium and Fusarium. The major classes of mycotoxins are aflatoxins, trichothecenes, fumonisins, zearalenone, ochratoxin A, and ergot alkaloids.
According to research, Zearalenone, ochratoxin, fumonisins and the deoxynivalenol (vomitoxin) are the most often reported mycotoxins in swine feed.
The Major Toxins found in Pig Feeds / Swine Feeds
Zearalenone is a commonly occurring mycotoxin that is often found in co-contamination with deoxynivalenol and other trichothecenes. The primary effect of zearalenone is oestrogenic and prepubertal female pigs are clearly the most sensitive farm animal. Clinical signs include swelling (vulvovaginitus) and reddening of the vulva and exposure may also result in tenesmus and rectal and vaginal prolapse (Rainey et al., 1991).
Effects on prepubertal boars have also been reported and include reduced libido, plasma testosterone and other effects (Osweiller, 1986). Dietary levels of three to 10ppm zearalenone can induce anoestrus in sows, reduced litter size, foetal resorption and implantation failure (Smith et al. 2005). The basis for the oestrogenic effect is due to a structural similarity between zearalenone (and many of its metabolites) and oestradiol (Osweiller, 2000).
Zearalenone is rapidly absorbed and eliminated. It is metabolised in the liver and excreted in urine and faeces as the glucuronide after considerable enterohepatic recirculation. In pigs, the zearalenone metabolites are conjugated with glucuronic acid and recycled via the bile. There is some evidence that the intestinal mucosa is also active in reducing zearalenone to α-zearalenol and conjugation with glucuronic acid (Biehl et al., 1993).
The glucuronide conjugates can also be detected in urine and liver (CAST, 2003; Zollner et al., 2002). In pigs, the α-zearalenol metabolite is more frequently detected than the ß-zearalenol, zeranol, α-zearalenol, zearalenol and zearalenona metabolites (Zollner et al., 2002). Toxicologically, zearalenone, like phytoestrogens and environmental oestrogens, passively cross the cell membrane and bind to the cytosolic estrogen receptor.
The receptor-zearalenone complex is rapidly transferred into the nucleus where it binds to specific nuclear receptors and generates oestrogenic responses via gene activation. This results in the production of mRNAs that code for proteins that are normally expressed by receptor-oestrogen complex binding (Riley and Pestka, 2005).These glucoronide conjugates could have potential as a biochemical marker of exposure in suspected field outbreaks.
Due to the higher oestrogenic activity of α-zearalenol (three times more) compared to zearalenone and the relative binding affinity for oestrogen receptors in pigs as compared to other species; pigs show a much higher inter-species differences in sensitivity to the oestrogenic effects (Fitzpatrick et al., 1989). Clinical signs of oestrus can be induced in ovariectomised sows and doses as low as 1 to 5ppm (Osweiller, 1986).
The oestrogenic effect of feeding less than 1.1mg zearalenone per kg feed to gilts, gestating sows and lactating sows on reproductive performance was examined by Kordic et al. (1990). Vulvovaginitis was observed in 0.24 per cent of gilts and this syndrome receded with time. Similarly, Friend et al (1990) concluded that 0.5 mg zearalenone per kg of feed would have no serious effects on reproductive efficiency of young gilts.
Interestingly, zearalenone consumption of 10mg zearalenone per kg of feed in prepubertal animals did not delay attainment of puberty or adversely affect subsequent reproduction pointing to the quick detoxification and reversibility of the toxins effect (Green et al. 1990). On the other hand, feeding high levels of zearalenone (up to 22mg per kg) to breeding gilts had an significant harmful effects on reproductive performance including decreased number of corpora lutea, decreased weight of ovaries, decreased number of live embryos and increased number of stillbirths (Kordic et al., 1992).
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Ochratoxin A is produced by a several species of both Penicillium and Aspergillus. Ochratoxicosis is characterised by nephropathy, enteritis and immuno-suppression (Terao and Ohtsubo, 1991). Nephrotoxicity in pigs is manifested with affected tubules and the discoloration and enlargement of the kidney. Typically, large increases in proteins excreted in urine that are indicative of glomerular proteinuria and have been correlated with histological observations of renal damage are observed (Riley and Petska 2005).
Exposure to lower levels of ochratoxin can result in altered performance including reduced feed consumption and weight gain and at higher levels delayed response to immunisation, and increased susceptibility to infection (Stoev et al., 2000). Lippold et al., 1992 showed reductions in weight gain, feed intake and feed efficiency when borrows were fed up to 2.5mg per kg of ochratoxin A. Impaired renal function, however, was noted at even 0.5mg per kg ochratoxin A.
More recently, interest has centered on the immunosuppressive effects of ochratoxin A in pigs and on ochratoxin A stimulating effect on lipid peroxidation. For example, it has been shown that feeding 2.5mg per kg ochratoxin A to growing gilts for 35 days suppresses cell-mediated immune responses (Harvey et al., 1992). Additionally, lipid peroxidation due to OTA consumption may be implicated in DNA damage (Surai and Dvorska, 2005).
The mechanism of action of ochratoxin is unclear but its structural similarity to phenylalanine and the fact that it inhibits many enzymes and processes that are dependent on phenylalanine strongly suggest that ochratoxin A acts by disrupting phenylalanine metabolism (CAST, 2003).
Numerous studies have shown that ochratoxin A can alter processes that require phenylalanine and many of the biological effects of ochratoxin can be at least partially prevented by supplementation with phenylalanine or phenylalanine analogues (Zanic-Grubisic et al., 2000; Baudrimont et al., 2001). The half-life in plasma is dependent on the extent of binding to plasma proteins. It is widely distributed and is accumulated in kidney and other tissues in pigs, and can occur in edible tissues.
Because ochratoxin binds tightly to albumin and serum proteins, and is rapidly and well absorbed, the ochratoxin protein adduct in serum is a useful biomarker for exposure in pigs. There have been attempts to correlate field pig blood concentrations of ochratoxin A with contamination of the feed. For example, the Danish swine industry uses renal ochratoxin A residues as an effective quality control system to minimize potentially harmful residues in pork products (Jorgensen and Peteresen, 2002).
Deoxynivalenol belongs to the trichothecene group which contains over 150 mycotoxins produced by primarily by Fusarium species. Other important toxins in this group include T-2 toxin, HT-2 toxin, diacetoxyscripenol (DAS) and nivalenol.
Deoxynivalenol is one of the most common Fusarium trichothecene mycotoxins and is the most commonly encountered trichothecene worldwide. Deoxynivalenol is considered to be a major cause of economic loss due to reduced performance. Food concentrations as low as 0.5 to 1ppm have been associated in the field with feed refusal and reduced feed intake in pigs (Smith et al., 2005).
Typically, concentrations above 2 to 5ppm are required for decreased feed intake and reduced weight gain and concentration of over 20ppm for vomiting and complete feed refusal (Haschek et al., 2002; Trenholm et al., 1988).
Feed refusal and emesis appear to be due to neurochemical imbalances in the brain, which have been shown to not be due to taste or learned responses (Prelusky, 1997). Other clinical signs include digestive problems, like soft stools, diarrhea, and an increased susceptibility to other diseases. In pigs, mild renal nephrosis, reduced thyroid size, gastric mucosal hyperplasia, increased albumin/ α-globulin ratio, and sometimes mild changes in other hematological parameters have been reported (JECFA 56th, 2001).
Numerous studies in laboratory animals demonstrate alterations in immune function induced by deoxynivalenol (Riley and Pestka, 2005) but there is little conclusive evidence that deoxynivalenol induces altered resistance to infectious diseases in the field or in farm animals experimentally (Osweiller, 2000). Nonetheless, the mechanism of action in laboratory animals suggests the potential for involvement in altered immune response in farm animals.
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Laboratory animal studies have demonstrated that, depending on dose and exposure regimen, trichothecenes can be both immunosuppressive and immune-stimulatory (Riley and Pestka, 2005). For example, increased serum IgA concentrations were seen in response to feeding up to 1.2mg per kg deoxynivalenol to piglets for eight weeks (Drochner et al., 2004) while a dose-dependent reduction in secondary antibody response to tetanus toxoid was observed when growing pigs were fed up to 4.7mg per kg deoxynivalenol for nine weeks (Overnes et al., 1997).
The seemingly paradoxical effects of trichothecenes can be explained by their cellular and molecular modes of action. Exposure to low levels of trichothecenes appears to promote expression of a diverse array of cytokines and pro-inflammatory genes in vitro and in vivo, while high doses of trichothecenes promote rapid onset of leukocyte apoptosis, which is manifested as immuno-suppression (Pestka et al., 2004).
Trichothecene-induced cellular damage also occurs in tissues of the gastrointestinal tract including the gastric mucosa, gastric glandular epithelium and intestinal crypt cell epithelium (Pestka et al., 2004). The damage in these tissues might result in the breakdown of non-specific mucosal defence mechanisms such as the epithelial barrier and mucus secretion and thus result in increased translocation of gut bacteria and endotoxin (Zhou et al., 2003).
Toxicologically, deoxynivalenol and other trichothecenes enter the cell via diffusion and bind to active ribosomes which transduce a signal to RNA–activated protein kinase (PKR) and haematopoietic cell kinase Hck. Subsequent phosphorylation of mitogen–activated protein kinases drives transcription factor activation and resultant chronic and immunotoxic effects (Riley and Pestka, 2005 and Pestka et al., 2004).
The transition between these two effects occurs with increasing concentration/dose of trichothecene, which explains the resulting immune stimulation or suppression, respectively. Intravenous infusion of deoxynivalenol to pigs resulted in peak concentrations in cerebral spinal fluid 30 to 60 minutes following infusion (Prelusky et al., 1990).
It was observed that there was no extensive uptake or retention by any tissue, suggesting that accumulation of residues in swine would not happen upon chronic consumption of deoxynivalenol (Prelusky and Trenholm, 1991). This was confirmed by subsequent long-term (up to seven weeks) swine feeding trials (Prelusky and Trenholm, 1992). A urinary biomarker using ß-glucuronidase treatment has been developed to estimate the daily intake of deoxynivalenol in people (Meky et al., 2003) and may also be useful in suspected field outbreaks in farm animals.
In growing swine, deoxynivalenol feeding up to 1 to 4mg per kg resulted in decreased weight gain, feed intake and feed efficiency (Bergsjo et al., 1992). Feeding diets with up to 3.5mg per kg deoxynivalenol to growing pigs increased liver weights, decreased serum protein and albumin concentrations (Bergsjo et al., 1993). In grower pigs, feeding up to 3mg per kg of naturally contaminated grains resulted in more severe feed refusal than was seen when an equivalent amount of purified deoxynivalenol was fed (Prelusky et al., 1994).
This could be explained by the co-contamination with other trichothecenes or other mycotoxins in the naturally contaminated feed. More recently, a naturally contaminated diet with dietary concentration of 2mg per kg deoxynivalenol was fed to growing and finishing pigs to market weight, which did not reduce growth rates or alter carcass composition of barrows (House et al., 2002).
This again demonstrates the difficulty in comparison between naturally contaminated and synthetic contaminated diets based on the potential of co-contaminants that are difficult to account for.
The fumonisins are a group of mycotoxins that are produced mainly by Fusarium moniliforme. In swine, fumonisin exposure is characterised primarily by pulmonary oedema (Haschek et al., 2002) and the effects on swine immunity (Riley and Petska, 2005). Clinical signs indicative of porcine pulmonary oedema syndrome typically occur soon (two to seven days) after pigs consume diets containing large amounts of fumonisins over a short period of time.
Clinical signs usually include decreased feed consumption, dyspnoea, weakness, cyanosis and death. At necropsy, the animals exhibit varying degrees of interstitial and interlobular oedema, with pulmonary oedema and hydrothorax. Hepatic toxicity commonly occurs concurrently with porcine pulmonary oedema and is sometime observed in animals that consume high levels of fumonisins but do not develop porcine pulmonary oedema.
Two studies have reported nodular hyperplasia in the pig liver (JECFA 56th, 2001). Fazekas et al., (1998) showed that feeding a diet containing 330mg per kg fumonisin B1 to weaned piglets resulted in hydrothorax and pulmonary oedema and mortality infive to six days. In a more chronic study, up to 10mg per kg fumonisin B1 was fed to starter pigs for eight weeks (Rotter et al., 1996). Average daily gain was reduced by 11 per cent when the maximum dose of fumonisin was fed.
Daily intravenous injections of fumonisin B1 to pigs indicated that cardiovascular function is altered and that fumonisin-induced pulmonary oedema is caused by left-sided heart failure and not by altered endothelial permeability (Smith et al., 2000). Constable et al. (2003) further noted that this was due to decreased cardiac output and characteristic impedance.
There is considerable evidence that the underlying mechanism by which fumonisins cause toxicity to animals is disruption of lipid metabolism (JECFA 56th, 2001). Most notably, fumonisins are specific inhibitors of ceramide synthase (sphinganine and sphingosine N-acyltransferase), a key enzyme in the pathway leading to formation of ceramide and more complex sphingolipids.
Porcine pulmonary oedema, liver and kidney toxicity that result from fumonisin exposure are closely correlated with the degree of disruption of sphingolipid metabolism (Riley and Petska, et al., 2005). Tissue and serum sphinganine:sphingosine ratios can be used as an early index of consumption of fumonisin-contaminated feeds (Riley et al., 1993).