Mycotoxin And Its Effects On Human Health

*Debtanu Barman¹, Sagar C. Mandal² & Vikash Kumar³

¹Laboratory of Aquaculture & Artemia Reference Center, Ghent University, Belgium

²College of Fisheries, Central Agricultural University, Lembucherra, Tripura-799210, India

³Central Institute of Fisheries Education (Deemed University), Seven Bungalows, Mumbai-400061, India

*Corresponding author: debtanu08@gmail.com, Mobile- +32488191632

Introduction

Mycotoxins are small-molecular weight byproducts that are produced by fungi - essentially the mycotoxins are a type of waste product of the fungi. These fungi typically cause problems for animals and man because they contaminate grain and protein ingredients that we eat. The fungi may die off, but the mycotoxin remains behind and some of the 400 different kinds of toxins from fungi are very deadly. For example, aflatoxin is very deadly and can cause liver cancer etc. in animals that eat it, and in large amounts it can kill quickly. Over 400 mycotoxins have been identified by scientists. The three major mycotoxin-producing fungi are Aspergillus, Fusarium and Penicillium. Four key mycotoxins that are generally recognized as dangerous are aflatoxin B-1, Fusarium Tricinctum (T-2), Zearalenone and Vomitoxin (Don).

The toxicity of mycotoxins to animals ranges from feed refusal to acute death. Common problems are liver damage, gizzard erosion, cancer, anemia, vomiting, diarrhea, intestinal hemorrhage, conception, ovulation, fetal development, abortion and newborn viability. Other problems include reduced immune response feed consumption, feed efficiency and milk and egg production. Toxin metabolites are secreted in milk and will affect the nursing animals and humans consuming the milk.

History of Mycotoxin

The term mycotoxin was coined in 1962 in the aftermath of an unusual veterinary crisis near London, England, during which approximately 100,000 turkey poults died. When this mysterious turkey X disease was linked to a peanut (groundnut) meal contaminated with secondary metabolites from Aspergillus flavus (aflatoxins), it sensitized scientists to the possibility that other mold metabolites might be deadly. Soon, the mycotoxin rubric was extended to include a number of previously known fungal toxins (e.g., the ergot alkaloids), some compounds that had originally been isolated as antibiotics (e.g., patulin), and a number of new secondary metabolites revealed in screens targeted at mycotoxin discovery (e.g., ochratoxin A). The period between 1960 and 1975 has been termed the mycotoxin gold rush because so many scientists joined the well-funded search for these toxigenic agents. Depending on the definition used and recognizing that most fungal toxins occur in families of chemically related metabolites, some 300 to 400 compounds are now recognized as mycotoxins, of which approximately a dozen groups regularly receive attention as threats to human and animal health.

Major Mycotoxins

Aflatoxins

Aflatoxins are difuranocoumarin derivatives produced by a polyketide pathway by many strains of Aspergillus flavus and A. parasiticus in particular; A. flavus is a common contaminant in agriculture. A. bombycis, A. ochraceoroseus, A. nomius, and A. pseudotamari are also aflatoxin-producing species, but they are encountered less frequently. From the mycological perspective, there are great qualitative and quantitative differences in the toxigenic abilities displayed by different strains within each aflatoxigenic species. Natural contamination of cereals, figs, oilseeds, nuts, tobacco and a long list of other commodities is a common occurrence. Aflatoxin is associated with both toxicity and carcinogenicity in human and animal populations. The diseases caused by aflatoxin consumption are generally called aflatoxicoses. Acute aflatoxicosis results in death; chronic aflatoxicosis results in cancer, immune suppression and other slow pathological conditions. The liver is the primary target organ, with liver damage occurring when poultry, fish, rodents and nonhuman primates are fed aflatoxin B1.

Citrinin

Citrinin was first isolated from Penicillium citrinum prior to World War II; subsequently, it was identified in over a dozen species of Penicillium and several species of Aspergillus (e.g., A. terreus and A. niveus), including certain strains of P. camemberti (used to produce cheese) and A. oryzae (used to produce sake, miso and soy sauce). Recently, citrinin has also been isolated from Monascus ruber and M. purpureus, industrial species used to produce red pigments. Citrinin has been associated with yellow rice disease in Japan. It has also been implicated as a contributor to porcine nephropathy. Citrinin acts as a nephrotoxin in all animals.

Ergot Alkaloids

The ergot alkaloids are among the most fascinating of fungal metabolites. They are classified as indole alkaloids and are derived from a tetracyclic ergoline ring system. Lysergic acid, a structure common to all ergot alkaloids, was first isolated in 1934. These compounds are produced as a toxic cocktail of alkaloids in the sclerotia of species of Claviceps, which are common pathogens of various grass species. The human disease acquired by eating cereals infected with ergot sclerotia, usually in the form of bread made from contaminated flour is called ergotism or St. Anthony's fire. Two forms of ergotism are usually recognized, gangrenous and convulsive. The gangrenous form affects the blood supply to the extremities, while convulsive ergotism affects the central nervous system.

Fumonisins

Fumonisins were first described and characterized in 1988. The most abundantly produced member of the family is fumonisin B₁. They are thought to be synthesized by condensation of the amino acid alanine into an acetate-derived precursor. Fumonisins are produced by a number of Fusarium species, notably Fusarium verticillioides, F. proliferatum and F. nygamai, as well as Alternaria alternata. Although it is phytotoxic, fumonisin B₁ is not required for plant pathogenesis. In humans, there is a probable link with esophageal cancer.

Ochratoxin

Ochratoxin was discovered as a metabolite of A. ochraceus in 1965 during a large screen of fungal metabolites that was designed specifically to identify new mycotoxins. Members of the ochratoxin family have been found as metabolites of many different species of Aspergillus, including A. alliaceus, A. auricomus, A. carbonarius, A. glaucus, A. melleus, and A. niger. Although the role of ochratoxin A in human disease is still speculative, its acute nephrotoxicity, immunosuppressive actions and teratogenic effects in animal models, coupled with its ability to be carried through the food chain, merit concern.

Patulin

Patulin, 4-hydroxy-4H-furo [3,2c] pyran-2 (6H)-one, is produced by many different molds but was first isolated as an antimicrobial active principle during the 1940s from Penicillium patulum (later called P. urticae, now P. griseofulvum). Now a day, P. expansum, the blue mold that causes soft rot of apples, pears, cherries, and other fruits, is recognized as one of the most common offenders in patulin contamination. Patulin is regularly found in unfermented apple juice, although it does not survive the fermentation into cider products. Patulin is toxic at high concentration.

Trichothecenes

The trichothecenes constitute a family of more than sixty sesquiterpenoid metabolites produced by a number of fungal genera, including Fusarium, Myrothecium, Phomopsis, Stachybotrys, Trichoderma, Trichothecium, and others. The term trichothecene is derived from trichothecin, which was the one of the first members of the family identified. All trichothecenes contain a common 12, 13-epoxytrichothene skeleton and an olefinic bond with various side chain substitutions. They are commonly found as food and feed contaminants, and consumption of these mycotoxins can result in alimentary hemorrhage and vomiting; direct contact causes dermatitis. Fusarium is the major genus implicated in producing the nonmacrocylic trichothecenes. The macrocyclic trichothecenes are produced largely by Myrothecium, Stachybotrys, and Trichothecium species. Glutinosin, a mixture of the macrocyclic trichothecenes verrucarin A and B was originally identified as an antimicrobial agent.

Poisonous Mushrooms and Other Fleshy Fungi

It was estimated that there are at least 400 species of poisonous mushrooms. Complicated to the medical profession, most doctors are untrained in the identification of mushrooms. Different mushrooms have various types of toxins with different modes of activity. There are 8 basic groups of toxic mushrooms based upon their mode of activity. These are Monomethylhydrazine (MMH), Cyclopeptides (amanitoxins & phyllotoxins), Orellanine or cortinarin, Coprine (the antabuse reaction), Muscarine (sweating/salivation), Pantherine (psychotropic), Psilocybin and Psilocin (psychotropic) and Gastrointestinal irritants (few toxins identified, but found in a large number of mushrooms and puffballs).

Factors affecting Mycotoxins production

Each fungus requires special conditions like substrate, moisture, temperature, etc. for its growth and other conditions for its toxin(s) production which are different than those of the other fungi and toxins.  However, the main affecting factors on toxin production are genetic factors viz. related to the fungus, its strain and its genetic capability and environmental factors including the substrate (on which fungus will grow) and its nutritious content. Toxin production also dependant on water content of the substrate and ambient relative humidity, temperature, oxygen content, carbon dioxide, mechanical damage (enable fungal invasion and mycotoxin production), insects invasion (enable fungal invasion and mycotoxin production). Also the increased count of fungal spores accumulates the produced mycotoxin. The growth of non-toxic fungal strains inhibits the production from the toxigenic fungi. Presence of specific biota inhibits growth of fungi and mycotoxin production. Low layer thickness of a crop (< 50 cm) during drying strongly decreases mycotoxin production.

Toxicology and Human Health

Mycotoxicoses, like all toxicological syndromes, may be either acute or chronic. Acute toxicity generally has a rapid onset and an obvious toxic response, while chronic toxicity is characterized by low-dose exposure over a long time period, resulting in cancers and other generally irreversible effects. The main human and veterinary health burden of mycotoxin exposure is related to chronic exposure (e.g., cancer induction, kidney toxicity, immune suppression). However, the best-known mycotoxin episodes are manifestations of acute effects. In general, mycotoxin exposure is more likely to occur in parts of the world where poor methods of food handling and storage are common, where malnutrition is a problem and where few regulations exist to protect exposed populations. Mold spores are of great concern and when inhaled, the spores can cause the lungs to become abnormally sensitive to these particular spores. Chronic respiratory disease and even death can occur if exposure to the moldy feedstuff is continued. The spores are doubly dangerous because farmers can develop sensitivity known as "Farmers Lung." Symptoms appear four to eight hours after exposure to spores and can include headache, loss of appetite, fever and chills.

Conclusion

The fungi cause human illness in different ways. Mycoses are the best-known diseases of fungal etiology, but toxic secondary metabolites produced by saprophytic species are also an important health hazard. The mycotoxin are produced in a strain-specific way and elicit some complicated and overlapping toxigenic activities in sensitive species that include carcinogenicity, inhibition of protein synthesis, immunosuppression, dermal irritation and other metabolic perturbations. It is difficult to prove that a disease is a mycotoxicosis. Molds may be present without producing any toxin. Even when mycotoxins are detected, it is not easy to show that they are the etiological agents for human health problem. Thus, it concludes that mycotoxins pose an important danger to human and animal health and in the absence of appropriate investigative criteria and reliable laboratory tests; the mycotoxicoses will remain diagnostically daunting diseases.