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ERGOT ALKALOIDS IN ANIMAL NUTRITION

What are ergot alkaloids?

The ergot alkaloids are a parasitic fungus belonging to the genus Claviceps, which are distributed worldwide and have a significant ability to inhibit grain growth and reducing its quality. The most prevalent member of this genus is Claviceps purpurea, named for its characteristic transformation of cereal grains into hard purple bodies (Arcella et.al, 2017). Ergot contamination occurs during extended periods of cold and humidity and infects when the seed coat is open. Among its effects, ergot is responsible for the production of a group of mycotoxins commonly found in cereals, known as ergot alkaloids. These alkaloids are highly toxic compounds both for animals and humans. If consumed in sufficient quantities, they can lead to a disease called ergotism. A large number of countries have imposed restrictions on the consumption of ergot-contaminated and redirect its use towards livestock feed. Despite the misconception that livestock are less susceptible to the effects of alkaloids, regulations tend to be less strict when alkaloid contamination is present in animal feed (Coufal et.al, 2016).

Stages of ergot alkaloids

The ergot has two stages in its life cycle: germination and the molasses phase. Ergot germination is a process by which it develops structures that enable it to produce spores (known as ascospores), which are carried by the wind and infect the ovaries of the cereal flower. Ergot invades cereal grains, depositing structures called sclerotia that can germinate after an incubation period. The species C. purpurea takes 4 to 8 weeks to initiate germination with the optimal temperature range estimated to be 18 to 20 °C. However, germination time may decrease under cold and humid conditions. On the other hand, the molasses phase consists of the propagation of a contaminated sticky conidia through insects. Once this stage is over, the infected ovary hardens and is replaced by the ergot body. The infected grain can fall, leading to contamination of the field or the rest of the crop. It should be noted that, if the flowers of the cereal grains are fertilized before the infection by ergot, the plants would present greater resistance against the fungus (Coufal et.al, 2016).

Types of ergot alkaloids

So far, more than 50 different types of ergot alkaloids have been identified in grains infected by Claviceps spp. These alkaloids have been categorized into two significant subfamilies: ergopeptine and ergoline alkaloids. Furthermore, Ergot alkaloids have been biogenetically divided into three classes: clavinet, derivatives of simple lysergic acid derivatives, and peptide alkaloids (Arcella et.al, 2017). The classification of alkaloids is still not completed and it is a complex challenge as new alkaloids continue to be discovered. What is clear is that the type of alkaloid and its concentration vary based on the fungal species, the type of cereal grain and the environment. Consequently, alkaloid production tends to be higher during periods of heavy rainfall and in humid soils. With the aforementioned, it has been reported that the concentration of alkaloids present in the sclerotia of the ergot fungus can reach up to 0.75% of the dry matter (Coufal et.al, 2016). 

As predominant ergot alkaloids bodies are: ergotamine, ergosine, ergocristine, ergocriptine and ergocornine. The alkaloids known as ergovaline and ergine are produced by endophytic fungi of forage. The amount of alkaloids produced by endophytic fungi is vastly lower than the concentration of alkaloids found in the sclerotia of Claviceps spp. (Coufal et al, 2016).

Mechanism of action of ergot alkaloids

Ergot alkaloids disrupt various biological processes, leading to the development of multiple effects in both human and animal organisms. This disruption is attributed to the fact that the alkaloids structurally have an ergorline tetracyclic ring, similar to the ring structure of common neurotransmitters such as norepinephrine, serotonin, and dopamine. As is known, these biogenic amines have receptors located throughout the body, and unfortunately, ergot alkaloids can bind to or interact with these receptors. The interaction of the alkaloids with the amine receptor is extremely complex (even the activity changes between alkaloids). This complexity results in the toxins acting as agonists (stimulants), partial agonists or antagonists of the receptors. Consequently, a variety of issues attributed to ergot alkaloid poisoning arise (Klotz, 2015).

Exposure of animals to ergot alkaloids

There is significant controversy surrounding the permissible concentration of ergot alkaloids in cattle feed. The toxicity associated with these molecules will depend on their individual absolute concentration, the type of alkaloid and the interactions that may develop with other types of mycotoxins present in the feed. Each country has established legislation regarding the tolerable concentration of ergotamine compounds in human and animal food. Both, the European Union and North America allow levels of 0-0.05% ergot contamination in cereal grains intended for human consumption. While, for cattle, the tolerable concentration is 0.1 and 0.3 ppm of total ergot. Cereals are prohibited from exceeding these concentration ranges (Coufal et.al, 2016).

Impact on health and productive performance of ergot alkaloids in animal production

Ergot poisoning can manifest within a few hours or even emerge several months later. The variability of response to intoxication can be attributed to the type and concentration of this mycotoxin. Furthermore, the diagnosis of ergot poisoning is frequently mistaken for other conditions, often of a respiratory nature (Coufal et.al, 2016). Ergot poisoning manifests in the form of convulsive, gangrenous, or other clinical symptoms. In the convulsive form, animals experience convulsions, staggering, temporary paralysis, and muscle spasms. This type of poisoning is more common to observe in sheep, horses, and unusually in cattle. On the other hand, the gangrenous type of poisoning is more prevalent in cattle and pigs. Due to disruptions in circulation and blood supply, the animals suffer from lameness followed by the loss of extremities such as tails, ears, and hooves. This condition, also known as gangrenous ergotism, may take up to 3 months to become clinically evident. Early indicators include gradual weight loss, an increased respiratory rate, diminished milk production, and decreased reproductive performance. Other clinical signs of ergotism, though less severe, encompass vomiting, fever, and endocrine disruption (Coufal et al., 2016). There are significant variations in tolerance levels among species, along with differences in absorption rates and detoxification capacities. Birds according to their species can be tolerant or extremely sensitive (like ducks). Compared to mammals, poultry appear to possess a more efficient alkaloid detoxification capacity.  However, prolonged exposure to these toxins can lead to adverse effects such as loss of appetite, diarrhea, increased thirst, vomiting, and weakness (Coufal et. al, 2016).

 

Symptoms in animals after ergot alkaloid intoxication

The clinical symptoms presented in the different animal species after intoxication with ergot alkaloids are explained below. 

Ruminants 

Gangrene linked to alkaloid intoxication is the main pathology observed in cattle and commonly affects the ears, tail and hooves. The loss of extremities due to compromised of blood circulation associated with the disease is relatively common in ruminants, unlike pigs and birds, since they often do not have a temperature-controlled environment. In sheep, the effects of ergotism are usually milder than in other cattle and they more frequently show convulsive signs. In addition to the pathology observed due to reduced blood flow, low conception rates, shortened gestation periods, miscarriages, reduced growth, and impaired sperm quality are also reported. Ruminants also suffer from agalactia, a loss or dysfunction in milk production. It is suggested that the animals suffer from this pathology after consuming the food infected with ergot; and after depriving contaminated food, prolactin takes months to return to normal concentrations (Thompson, 2017). 

Once an animal develops ergotism, veterinary guidance entails monitoring and promptly transitioning to an ergot-free diet. However, in cases where peripheral gangrene is clinically identified in cattle, removing the contaminated feed will not result in recovery (Coufal et.al, 2016). 

Pigs 

The effects observed in pigs are similar to those seen in ruminants. The clinical signs in pigs include reduced growth, decreased feed consumption, reproductive losses (smaller litters, premature birth, repeated heat, mastitis and metritis). Additionally, there is a decrease in milk production due to the inhibition of prolactin. In some cases, hindquarter lameness and limb necrosis are also reported. However, controlled environment production helps mitigate the impact of gangrene (Thompson, 2017).

 •Birds

 Birds that ingest feed contaminated with ergot alkaloids show reduced growth, lower feed conversion, dyspnea, reduced feed intake, and may present with diarrhea. Furthermore, a high mortality is reported. Decreased prolactin concentrations are also observed in birds, affecting incubation and behavior. The reduction of the hormone prolactin causes the circulating levels of gonadotropins to be low, leading to evident ovarian regression. Similar to other species, birds are also susceptible to gangrene, primarily affecting areas such as the legs, beaks, and crests (Thompson, 2017). 

Horses 

Gangrene effects are not commonly observed in horses. However, when the exposure period becomes chronic or prolonged, the condition can manifest. Primarily, horses tend to exhibit convulsive symptoms along with other secondary changes, including reproductive ones. Females may experience abortions, prolonged gestation periods, increased frequency of dystocia, retained placenta, and diminished mammary development resulting in reduced milk production. Many of these reproductive issues are associated with the depression of hormones such as progesterone, estradiol, and prolactin, due to the impact of ergot alkaloids (Thompson, 2017).

 

How to prevent contamination by ergot alkaloids?

Due to the widespread and adaptable nature of fungi, predicting the occurrence of their contamination in food is challenging. The multitude of factors influencing the origin and growth of fungi is highly diverse and variable, wherein alterations in climatic conditions or harvest management can lead to fungal or mycotoxin contamination. Toxins can infiltrate crops at various stages, including harvesting, transportation, and storage. Consequently, the mitigation of ergot mycotoxins contamination in cereals will primarily target both pre-harvest and post-harvest phases. Management of mycotoxins revolves around adopting Good Agricultural Practices, Good Manufacturing Practices, and implementing Hazard Analysis and Critical Control Points (Agriopoulou, 2021). 

Pre-harvest control 

The application of pesticidal and fungicidal agents has traditionally been the focus for the control of phytopathogenic fungi and their derived metabolites in food crops However, the current focus is on exploring more environmentally sustainable strategies that effectively combat contamination in agricultural production. One of the possible tools to be used is biological control. The use of biological agents has a limited spectrum of action compared to chemical fungicides, however, biological media can also work quite well if used in conjunction with chemical fungicides. Biological control employs various agents such as yeasts, fungi, bacteria, and enzymes, which can degrade and absorb diverse mycotoxins. When it comes to ergot alkaloids, limited published studies have explored biological control methods. Among these studies, bacteria and fungi like Pseudomonas aureofaciens and Trichoderma lignorum, respectively, have been employed. However, these agents did not yield a significant effect on sclerotia germination (Agriopoulou, 2021). 

Similar to fungicides and pesticides, good agricultural practices are employed as techniques to manage fungi and their metabolites in crops. Within the life cycle of fungi belonging to the Claviceps genus, sclerotia play a crucial role. In brief, these structures serve as shelters for the pathogen during hibernation. As the cold spring season approaches, these structures germinate and disperse into the environment (Agriopoulou, 2021). As a beneficial agricultural practice, the use of calcium cyanamide as a fertilizer has been found to reduce ergot germination by 40-50%. Other related practices such as crop rotation, deep ploughing, weed control, and herbicides contribute favorably to the control of ergot alkaloids; because the crops are more robust and less vulnerable to infection with pathogenic fungi. Finally, one of the main preventive actions is the use of non-infected seeds. Numerous sclerotia can accumulate within seeds, and upon germination, they generate a substantial quantity of ascospores that disperse across the soil and the surrounding environment. Consequently, adopting the use of pathogen-free seeds proves pivotal in averting contamination and safeguarding crop yields (Agriopoulou, 2021). 

Harvest and post-harvest control 

As the grains of the crop mature, control of the sclerotia tends to be more effective, because the visibility of crop contamination increases. A late harvest improves obtaining crops with low sclerotia indices. In cases where sclerotia contamination is highly visible, it is preferred not to mix the contaminated seed with the non-infected one, nor to use it as animal feed. A practical solution to mitigate moderate contamination loads involves the use of gravity or color sorting methods. These techniques serve as effective alternatives for post-harvest sclerotia removal (Agriopoulou, 2021). 

There are several crop decontamination techniques that apply or focus on two directions. The first approach centers on degrading mycotoxins into less harmful compounds, whereas the second aims to safeguard the nutritional content of agricultural products from deterioration (Agriopoulou, 2021). 

An essential distinction to emphasize is that decontamination should not be confused with detoxification, as the degradation process can result in the creation of products with unknown toxicity. Among the decontamination processes, there is heating, which is a physical form capable of converting the toxic form of an alkaloid such as ergotamine into a less toxic product. Among the ergot alkaloids, ergotamine and ergosine are quite stable to heat treatments and, on the other hand, ergocristine, ergokriptine, ergocornine and ergometrine are the most susceptible to heat, leading to a reduction in their concentration when subjected to heat treatment (Agriopoulou, 2021). 

When faced with a reduced mycotoxins content, additional physical decontamination methods can be employed. These include techniques such as sorting, grinding, and flotation. Furthermore, grain processing plays a role in eliminating ergot alkaloids. However, it’s important to note that conventional practices like boiling, baking, cooking, pasteurizing, and frying generally do not significantly diminish stable mycotoxins (Agriopoulou, 2021). 

Use of mycotoxins binder 

Mycotoxin binders have proven to be an effective strategy to counteract the detrimental effects of ergot alkaloids once animals have ingested contaminated feed. Mycotoxin binders are compounds that are added to animal diets to effectively bind and neutralize mycotoxins present in the feed. This strategy is also applicable to ergots, since the mycotoxins binder have the ability to bind to these metabolites and reduce their absorption in the gastrointestinal tract of animals. Through the reduction of ergot intake, mycotoxin binders play a significantly role in mitigating the adverse consequences of ergot alkaloids on animal welfare and performance. This, in turn, ensures the safety and welfare of livestock (Sillué et al., 2021).


Ergot alkaloids, a growing challenge in animal production

In summary, ergot alkaloids, produced by the fungus Claviceps purpurea, are toxic and can cause adverse effects on human health and animal nutrition. Grains contaminated with these compounds can induce symptoms such as seizures, gangrene, disruptions in reproductive functions among consuming animals. Prevention and control of this contamination are crucial to ensure food safety and animal performance. This involves proper agricultural practices, identifying and eliminating sclerotia, and incorporating mycotoxin binders in animal feed to counteract the harmful effects of ergot alkaloids. In general, understanding these compounds and applying appropriate strategies is essential to ensure safe and healthy animal production.