Mycotoxins – Part 4: Mycotoxins threaten the immune system

Mycotoxins are a diverse group of fungal products that are harmful to animals, plants and humans. They cause different pathologies according to the specific toxin structure, leading to difficulties in diagnosis due to the multiple symptoms shown in affected individuals. To date, around 500 different mycotoxin compounds have been identified, which are present in more than 30% of the cereals produced worldwide.

 

The main challenge in studying and controlling mycotoxicosis is the difficulty in accurately diagnosing this disease. Diligent poultry producers, however, know that they are often involved in causing poor bird performance. The main areas to be considered when diagnosing mycotoxicosis include clinical history, outward symptoms, and observation of liver lesions, as this organ is the most vulnerable for attack by fungal toxins. It remains a challenge to detect mycotoxins in poultry feed that cause immune suppression, poor performance or classical lesions.

 

From an epidemiological point of view, fungal growth occurs in different phases of plant and animal production. Spores can infect seeds before harvest while the crop is still in the field, during storage time at the feed mill, or whilst being processed. Particularly vulnerable times are when the grain is exposed to warmth and humidity, which favours fungal growth. Contamination within grain stores, feed mills and on farms is common as spores can remain in bins and feeders if they are inadequately cleaned and monitored.

 

Fungal growth causes damage to and losses in nutritional quality in grain, and multiple contamination has a cumulative effect in terms of the severity of the mycotoxicosis. Metabolic activity within moulds is associated with aerobic respiration, so grain deterioration results from fat and carbohydrate oxidation, resulting in carbonic acid, water, heat, and an increase in fungal growth. Moreover, the fat content of grain is markedly reduced in those batches infected by fungi, and is in turn related to a reduction in available energy when included in animal feed. This may have a further influence on the performance of the birds exposed to contaminated feed if the energy levels are not suitably corrected by a nutritionist. For this reason, the most correct concept regarding affected birds is not only mycotoxicosis per se, but is better described as a ‘poor quality cereal syndrome’. This syndrome causes a reduction in health status and performance due to consumption of feed produced by cereal damaged by fungi, whether through exposure to mycotoxins or due to a reduction in nutritional quality of the final feed.

 

Understanding the effects of individual mycotoxin compounds is very important. The interaction between mycotoxins and poor nutritional quality of feeds related to fungal damage will increase the severity of clinical signs, even at low levels of mycotoxins regarded as generally safe for single mycotoxin contamination. An important effect of this interaction is immune suppression, which is due to mycotoxin genotoxicity and the cytotoxic effects on immune cells.

 

Mycotoxins cause deterioration and cellular depletion in lymphoid organs. In the case of aflatoxin and ochratoxin exposure, interference in protein synthesis is thought to be the principal cause of immune suppression. To conserve the immune response in the body, animals need higher protein synthesis. When this is not possible, the immune system falters. A study with mycotoxins revealed a reduction in mitotic cell number in the bursa organ in broilers. Contaminated feed reduced the humoral immune response to Newcastle Disease Virus (NDV) vaccine. In a commercial situation, this effect would reduce vaccine efficiency. The trial suggested that, for broiler breeders, a reduction in the transfer of maternal immunity in broiler chicks may result, causing lower liveability of day-old birds.

 

The discovery that fumonisins are potent inhibitors of the enzyme sphinganine N-acyl transferase identified another aspect of their biological activity, i.e. that cellular membranes may be a principal target for fumonisins in vivo, which is potentially important for the integrity and function of immune cells. Ledoux and co-workers reported that fumonisin exposure in chickens decreased humoral immunity, suppressed lymphocyte proliferation and reduced bacterial clearance. Some unpublished studies have shown a linear interference of fumonisin on vaccine titres against NDV in broilers, whereby the higher the fumonisin levels, the lower the titre.

 

Genetic ‘down regulation’ of the immune system and its responses is one of the best known aspects of mycotoxicosis. An interesting experiment, conducted by Petska, showed that the mycotoxin DON and other tricothecenes affected both cellular and molecular immune modulation. Low doses of trichothecenes caused transcriptional and post-transcriptionally up-regulation of cytokines, chemokines and inflammatory genes, which was associated with immune stimulation. However, high levels of exposure promoted leukocyte apoptosis with concomitant immune suppression. Those results should be examined more closely to best understand how these mechanisms occur. If lower doses of trichothecenes cause immune stimulation, this is not necessarily a good response in terms of bird health or performance. In fact, each time the immune response is activated this system becomes energetically expensive for the animal, and as a result draws on many tissue reserves, limiting growth and other cellular and tissue functions. From a practical point of view, the response of the animal to occasional pathogenic attack will be very strong, and stored resources will be used to facilitate this, resulting in reduction in feed conversion, for example.

 

Field cases of immune suppression have been related to reductions in vaccine titres, increases in the occurrence of opportunistic infection (e.g. E. coli or Clostridium spp.) and increases in downgrades at the slaughterhouse due to septicaemic lesions. On the other hand, an increase in unspecific immune responses within the intestine and mouth mucosa, or a strong vaccine reaction and poorer feed conversion rate, may be associated with the up-regulation of the immune system.

 

The evaluation of cereal mycotoxins under commercial conditions is not easy, but there appears to be a high correlation between damaged grains, nutritional losses and mycotoxin levels. The higher the percentage of damaged grains, the higher the probability for mycotoxin contamination and the lower the nutritional value of the grain. Applying constant monitoring for identifying the percentage of physically-damaged grains (broken and mouldy grains for example) makes it easier to evaluate quality and, if monitored over a suitable period, predict the times when such problems arise (Figure 1). If the trends follow the example given in Figure 1, it is possible to predict an increase in the number of damaged grains, and reduction of fat content within the grain from December to February. This period can then be classified as being most critical in terms of potential mycotoxin problems in poultry that have been fed the grain. This is shown in Figure 2, where the occurrence of lesions reported from necropsy of commercial birds in field are correlated to the grain characteristics reported in Figure 1, confirming the critical period for mycotoxin exposure. From this, it is possible to conclude that the increase in lesion problems in the field is highly influenced by both the presence of mycotoxins and fungi growth on cereal.

 

 

 

 

The first point of control for preventing mycotoxicosis in poultry is to avoid fungi growth in feed ingredients or feed, as the detection of contaminated feedstuff s is the primary defense against mycotoxins. Affected ingredients or consignments should be rejected to prevent contamination within stores, mills or feeders. Identifying potential contamination should not only rely on analysis of the mycotoxin levels present, but should also include the physical condition of the grain. From a practical point of view, it is good practice to analyse grains before accepting them on site at the mill, and to establish a maximum tolerated level of damaged grain. To establish a safe percentage of damaged grains in the field mill, it is important to monitor the correlation between increases in damaged grains and the observance of symptoms in birds. If the percentage of damaged grain is higher than the maximum permitted level, it is important to correct the formulation of diet according to the nutritional losses.

 

During storage of grains, it is important to monitor humidity and temperature inside the bins. The inclusion of fungal inhibitors, such as organic acids, can suppress fungal growth and hence control the production of toxins. Dilution of contaminated grain with clean grain is often used to reduce the level of mycotoxins to below toxic levels. This practice may reduce the risk; however, it makes it impossible to know exactly how many mycotoxins are present and what toxic effects may result from their synergy. Furthermore, this practice is not permitted in some regions of the world, such as in the European Union.

 

During feed processing or on the farm, it is important to clean equipment to avoid accumulation of dust that harbours spores or toxins, allowing fungal growth and mycotoxin production. When mycotoxins are already present in the feed, good practice is to include a sequestering agent, such as that produced by Alltech, which has been proven effective in feed applications and can bind a diverse range of toxins effectively. Nutritional enhancement of feeds with anti-oxidant compounds, such as vitamin E and Se, has been actively used to improve the animal’s defenses against mycotoxins and can decrease the severity of exposure. A combination of natural antioxidants and organic adsorbents could be the best way to combat mycotoxicosis in poultry production and animal health.