The occurrence of mycotoxin-producing fungi in foods and feeds has become a significant global concern [1]. Mycotoxins are toxic metabolites produced by fungi such as Aspergillus, Fusarium, and Penicillium, which can lead to life-threatening health conditions, collectively known as mycotoxicosis [2]. The health implications of mycotoxins are profound, as they are carcinogenic, teratogenic, nephrotoxic, mutagenic, immunotoxic, and allergenic [3]-[6]. These toxic compounds can cause acute and chronic toxic effects on the cardiovascular system, liver, and central nervous system of humans and animals [7][8].

The key mycotoxins of major concern include aflatoxins, fumonisins, ochratoxin A, zearalenone, and trichothecenes. These mycotoxins are known to contaminate a wide range of agricultural products, including cereals, nuts, spices, cocoa, and coffee beans [3][9]. The global impact of mycotoxin contamination is substantial, with approximately 4.5 - 5 billion individuals facing a significant risk of long-term exposure to harmful mycotoxins [10]. This risk is particularly pronounced in underdeveloped countries, where limited resources and infrastructure lead to poor agricultural practices, inadequate storage, and a lack of regulatory enforcement, resulting in higher mycotoxin contamination rates.

The challenges posed by mycotoxin contamination are multifaceted, contributing to food loss, reduced food availability, and heightened risks of hunger and malnutrition. Furthermore, the carry-over of mycotoxins in livestock products, such as meat, can lead to chronic or acute toxicity in humans [6][11]. Given the severity of these issues, it is crucial to understand the classification and occurrence of mycotoxins, their toxicological effects, methods for their detection, and strategies for prevention. This review, titled “Overview of Mycotoxins in Food and Animal Feed: Recent Advances”, aims to provide a comprehensive overview of these aspects, offering insights into the current state of mycotoxin research and future directions for mitigating this global health threat.

Aflatoxins (Afs), being secondary metabolites of certain strains of fungi such as Aspergillus flavus and A. parasiticus, and the less common A.nomius[19], are very dangerous to health when consumed. The name “aflatoxin” was derived from the name of the genus and species of the microorganism from which it was first identified (i.e., “a” from Aspergillus and “fla” from flavus). The B and G classes indicate the blue and green light fluorescence emitted by these metabolites when viewed under ultraviolet (UV) light, and the sub-types 1 and 2 refer to the major and minor compounds, respectively. A. flavusis a producer of the type B aflatoxin, while the other two fungal species produce both types of aflatoxins, B and G [20].

Aflatoxins contaminate a wide variety of important foodstuffs including cereals, and aflatoxins could cause cancer, behave as mutagens, teratogens, and can be immunosuppressive. Aflatoxins can cause both acute toxicity and chronic carcinogenicity in humans and animals [21]. Aflatoxin B1 is classified by the International Agency of Research on Cancer (IARC) as a Group 1 carcinogen, with high risks for hepatocellular carcinoma (HCC) in individuals exposed to aflatoxins, while AFM1 is listed in Group 2B; possibly carcinogenic to humans [22]. Acute toxicosis, though rare in developed countries, is common in some developing countries such as Africa [23]. The toxic effects of AFB1 are principally due to the binding of bioactivated AFB1-8,9-epoxide to cellular macromolecules, particularly mitochondrial and nuclear nucleic acids and nucleoproteins, resulting in general cytotoxic effects [21]. Due to the toxicity of aflatoxins to humans and animals, many countries have established regulations and regulatory limits for their control in foods meant for human and animal consumption [24].

Recent studies have highlighted the importance of understanding the molecular mechanisms of aflatoxin toxicity, including the role of miRNAs in regulating gene expression [25]. The classification of aflatoxin B1 as a Group 1 carcinogen by [26] underscores the need for stringent regulations and controls to minimize exposure. Novel approaches, such as the use of nanotechnology-based detection methods [24], may enhance our ability to detect and mitigate aflatoxin contamination.

Ochratoxins are products of moulds, most especially AspergillusandPenicillium. Among the ochratoxin family A, B, and C, ochratoxin A (OTA) is the most dangerous to health [27]. Cereals such as maize, oats, barley, wheat, groundnuts, dried fruits, and coffee are the main sources of OTA contamination. These were reported to have been infected by A. ochraceus, A. niger, A. carbonarius, A. flavus, A. auricomus, A. glaucus, A. melleus, A. alliaceus, P. verrucosum, and P. virridicatumn [21].

The International Agency for Research on Cancer (IARC) has classified OTA as a group 2B carcinogen because of its nephrotoxic, hepatotoxic, immunosuppressive, teratogenic, and carcinogenic effects on animals and humans [26]. Several countries have established regulatory bodies for the detection and control of OTA because of its toxicity and frequent occurrence in feed and foodstuffs [28]. The average range/limit for OTA is between 3 - 50 µg/kg [28]. The European Commission (EC) regulation maximum limits for OTA in unprocessed cereals are 5 µg/kg and 3 µg/kg for unprocessed cereal products as published in Commission Regulation No. 1881/2006 [29].

Ochratoxin A (OTA) can negatively impact the productivity of food-producing animals by decreasing feed efficiency, leading to weight loss, and reducing egg production [30]. Due to its fat-soluble nature, OTA tends to accumulate in animal tissues, particularly in pigs [31]. OTA disrupts the activity of the enzyme phenylalanine hydroxylase in the kidneys and liver, hindering proper protein synthesis at the molecular level. Furthermore, OTA also inhibits the synthesis of RNA and DNA [32], leading to a range of harmful effects on animal health and productivity.

Fumonisins are produced by several species of Fusarium, which include F. verticillioides, F. proliferatum,andF. nygamai. The most commonly produced toxin is Fumonisin B1, which is of Fusarium verticillioides origin. The F. verticillioides is of great economic importance and can be found in maize. Fumonisins, produced by Fusarium species, interfere with sphingolipid metabolism [33] and are associated with various syndromes in animals, including leukoencephalomalacia in horses and hepatotoxicity in rats [34]; pulmonary oedema and hydrothorax in pigs [35]; carcinogenicity and apoptosis [36] in the liver of rats. This, if consumed in large amounts, may also lead to cancer of the lungs in humans [37]. It can also lead to serious diseases in rats, horses, and cattle and could cause liver, kidney, and lung damage in rats, and equine leukoencephalomalacia, a neurological disease, in horses [38]. Fumonisins are also linked to pulmonary inflammation in swine and liver cancer in rodents [38].

Zearalenone (ZEN), like fumonisin, is also produced by some species of Fusarium, the most common being F. graminearum, and others such as Fusarium crookwellense, Fusarium culmorum, and Fusarium equiseti, may also be a cause. Cereal crops such as maize are the main target [39]. Biologically, they cause reproductive problems in animals and also affect oestrogen, resulting in abortion, infertility, and other reproductive malformations in many animal species such as sheep, cattle, and pigs. It has lesser toxicity compared to fumonisin in swine, cattle, and sheep [40].

Zearalenone is absorbed by the intestinal tract and undergoes metabolism, leading to the production of some metabolites, some of which are even more potent than their parent toxin [41]. ZEN binds to estrogen receptors to cause hyperestrogenic effects, thereby disrupting endocrine systems [42]. Increased levels of ZEN may induce toxicity, which may give rise to oxidative stress and cytotoxicity. Zearalenone affects reproductive systems, based on the research on pigs, leading to hyperplasia of the reproductive tract, infertility, and hormonal dysfunctions. For humans, exposure to ZEN is linked to the development of breast cancer and endometrial hyperplasia. Conclusively, ZEN could affect various organs such as the liver, kidneys, immune cells, and intestines [39].

Trichothecenes are mycotoxins produced by a number of fungal genera, including Fusarium, Myrothecium, Trichothecium, Trichoderma, and Cephalosporium among others [21]. The name “trichothecenes” was given as a result of the first member of the family identified. The almost 180 different structures are grouped into four distinct groups, A to D. Cereals such as maize, oats, barley, etc. are the primary source of trichothecene. The type-A and type-B trichothecenes are less toxic and are commonly circulated by means of the mentioned crops. The type-C and type-D are more toxic and rarely occur in food and feed.

The genus Fusarium comprises numerous field fungi adapted to infect plants, including wheat, corn, barley, oats, and forages. Fusarium affects plants in temperate regions, and this has led to most outbreaks.

Trichothecenes prevent protein build-up and are toxic to molds, bacteria, plants, and animals [43]. Trichothecenes are established food and feed contaminants, and their consumption may lead to irritation of the intestines, which may result in alimentary hemorrhage, vomiting, and diarrhea. Direct contact with trichothecenes can cause dermatitis, while chronic exposure in animals can lead to immune system suppression [38].

Patulin, produced by Aspergillus, Penicillium, and Byssochlamys fungi, is toxic to both plants and animals. It is present in rotten apples and apple products, grains, and other foods. Despite the antibacterial, antiviral, and antiprotozoal properties of patulin, it is reported to be toxic to both plants and animals [44]. The toxicity of patulin has masked its clinical uses as antibiotics [45]. Patulin is associated with the following acute symptoms in animal species: liver, spleen, and kidney damage, and immune system toxicity, while in humans it is responsible for nausea, gastrointestinal disorders, and vomiting.

The US FDA limits patulin to 50 ppb as an action level in food for human consumption. The EU committee has set a maximum level of 50 ppb for fruit juices and concentrated fruit juices, 25 ppb for solid apple products, and 10 ppb for juices and foods consumed by babies [46].

Deoxynivalenol (DON) is produced by fungi of the genus Fusarium, and they can be found in several grains and products of animal origin. Ingestion of food contaminated by DON may cause nausea, emesis, diarrhoea, abdominal and head pain, dizziness, fever, and eventually death. The severity of the disease depends on the concentration of the ingested toxin. The chronic effects of DON are mainly felt on the immune, reproductive, and gastrointestinal systems [47][48]. Ingestion of DON, in addition to its acute effects, can lead to genotoxicity in human lymphocytes, which may later lead to DNA damage by oxidative stress [49]. Deoxynivalenol (DON) exposure is associated with emetic effects in humans, and animal research has demonstrated a range of detrimental effects, including immunosuppression, anorexia, reduced nutritional efficiency, and impaired reproductive capacity [50].

Enniatins (ENN) are made up of different groups, of which ENB1, despite being less studied, is the most widely relevant and prevalent ENN contaminant of agricultural produce [51]. ENN occurs in cereals such as maize, barley, oats, etc., but to a lesser extent in potatoes, eggs, apples, etc. [52]. In a study conducted on about 4000 food, feed, and unprocessed grain samples in Europe between 2000 and 2013, ENNs were detected in 37%, 68%, and 76% of food, feed, and unprocessed grain samples, respectively [53]. As high as 5720 μg/kg was reported in grains, 980 μg/kg was reported in cereal-based food, and 5441 μg/kg in feed and feed raw materials [54]. [55] reported these contaminants in Nordic countries, which include Norway, Sweden, Iceland, North America (Canada), Asia (Iran, China), as well as Africa (Egypt, Mozambique, Cameroon, etc.). Because of its wide distribution across the globe, it can be deduced that the formation of this toxin by Fusarium spp. is not affected by any climatic condition but may be modified, which in turn has an impact on its toxicity [55]. Biological contamination of crops by this fungus results from the crops’ compatibility with the fungus, harvesting, and storage methods and conditions, which make ingestion of the fungus by plants and animals very easy and rampant [51].

Most ENNs exhibit both antifungal and antibacterial characteristics against organisms such as Candida albicans, Cryptococcus neoformans, Escherichia coli, Yersinia enterocolitica, etc. [18]. Recently, De Felice et al., 2023, reported ENN B₁ to have the ability to permeabilize the lysosomal membrane by destabilizing the LAMP-2 complex at a concentration close to the EC50 (1.5 - 1.7 µmol/L). ENNs have also been found to inhibit drug efflux pumps and enzymes, which has stimulated interest in these molecules for use in medicine. ENNs were proven to inhibit ABC (ATP-binding cassette) transporters and, therefore, have started to be considered for their utility in cancer therapy [52]. Understanding the molecular mechanisms of enniatin toxicity is crucial for developing effective strategies to minimize its impact on human and animal health.

Beauvericin (BEA) is composed of cyclic hexadepsipeptides consisting of alternating D-α-hydroxy-isovaleryl-(2-hydroxy-3-methylbutanoic acid) and amino acid units. This compound was first isolated from the culture of Beauverina bassiana, a pathogen of insects [56], and several other Fusarium species such as F. acuminatum, F. acutatum, and F. anthophilum [57], have been reported to produce beauvericin. Beauvericin was one of the active constituents of B. bassiana, and despite its toxicity to human cells, it was confirmed to have antimicrobial and anti-tumor activities [57].

Beauvericin is used as a commercial insecticidal agent because of the ability of the entomopathogenic fungus to become established and spread widely by insect movement, leading to its efficiency and the assurance that beauvericin production will remain within the threshold limits as stipulated by the EPA [58].

BEA has been reported to be a common contaminant of grains throughout the world, although the results from surveys reported thus far are dominated by data from Europe. Although the reported concentrations are highly variable, the maximum concentration was 520 mg/kg in a sample of visibly infected maize [59].

Bioaccumulation of mycotoxins due to continuous intake of low levels of mycotoxins in food can result in chronic toxicity [93]. The aflatoxins B1 (AFB1), B2 (AFB2), G1 (AFG1), and G2 (AFG2) are of great toxicological importance due to the resulting metabolite from the hepatic metabolism of these toxins [94]. AFB1 is the most prevalent toxin in human and animal food/feed, and it is also the most dangerous hepatocarcinogen in mammals [95]. Common types of cancer induced by AFB1 include hepatocellular carcinoma (HCC), and liver cancer. AFB1 is metabolized by cytochrome P450 enzymes in the liver into a reactive intermediate called AFB1-8,9-exo-epoxide, which forms DNA adducts. These adducts lead to genetic mutations, particularly in the p53 tumor suppressor gene, resulting in carcinogenesis. The DNA adducts disrupt normal cellular processes, including DNA repair, and increase the risk of liver cancer [96].

Even though DON has been reported to be non-carcinogenic, acute toxicity can lead to severe health implications if contaminated food/feed is consumed over a long period of time (Table 7). In addition, cases of chronic toxicity have been reported to affect the gastrointestinal, immune, and reproductive systems [97].

Ochratoxins can disrupt some biological processes in the body, such as the production of protein, metabolism of calcium, lipid peroxidation, metabolism of sugars, and mitochondrial respiration [98]. Exposure of humans and animals to OTA-contaminated foods/feed over a short and long period could result in acute and chronic toxicity with resulting health impact (Table 7).

Fumonisins (FMNs) are hepatotoxic, immunotoxic, carcinogenic, and nephrotoxic [99]. FMNs have been reported to have a strong toxic effect on the lungs, liver, and kidneys of rats, cattle, and horses. FMNs caused leukoencephalomalacia (ELEM) in horses and pulmonary inflammation in pigs [100].

Trichothecenes (T-2/HT-2) negatively affect the synthesis of protein, thereby resulting in membrane dysfunction, immunosuppression, and cell death [101]. T-2/ HT-2 toxins have negative effects on the gastrointestinal tract and the epithelium of the skin, thereby resulting in nausea, diarrhea, vomiting, burns, blisters, redness of the skin, and necrosis [90]. Long-term exposure to trichothecenes can weaken the immune system, making individuals more susceptible to infections. In swine, the conversion of T-2 to HT-2 has been shown to have detrimental effects on blood cells and immune function [102].

Zearalenone (ZEA) is similar to an estrogenic hormone which is naturally produced in the body [103]. ZEA has been reported to have toxic effects on the blood, immune system, liver, and DNA [104]. ZEA is a non-steroidal estrogenic mycotoxin and has been reported as the likely cause of hyper-estrogenic syndromes in humans, and reproductive disorders in animals such as cattle, sheep, and swine [105]. Further information on the effects on human health is shown in Table 7 below.

Table 7. Acute and chronic toxicities of mycotoxins and their health impacts.

Emerging mycotoxins (EMs) like nivalenol (NIV), enniatins (ENNs), beauvericin (BEA), diacetoxyscirpenol (DAS), fusaric acid (FUS), patulin (PAT), moniliformin (MON), and sterigmatocystin (STG) contaminate grains and feed commodities globally. These EMs, often overlooked and not routinely monitored, are increasingly recognized for their presence and impact. Fusarium species, such as F. sambucinum, F. subglutinans, and F. tricinctum, produce NIV, ENNs, BEA, DAS, FUS, and MON, while Aspergillus and Penicillium species produce STG and PAT.

Studies have shown that EMs co-occur with regulated mycotoxins, exacerbating adverse effects such as reproductive issues, immune system disorders, and impaired intestinal morphology [118][119]. For example, enniatin B was found at concentrations of up to 13,335 µg/kg in triticale grown in France [120], while diacetoxyscirpenol was detected at 70 µg/kg in grains from Japan [121]. A recent metadata study revealed that NIV, ENNs, and BEA are the most predominant toxins, frequently contaminating cereal grains [122].

Climate change is significantly influencing the emergence of new mold species, further complicating food safety and biodiversity [123]. Rising temperatures, changing precipitation patterns, and increased CO₂levels are altering the distribution and prevalence of mycotoxigenic fungi, such as Aspergillus and Fusarium species [124]. These changes are expected to increase mycotoxin contamination in crops, particularly in tropical and subtropical regions. Changing climate patterns are projected to alter host-pathogen interactions, fungal ecology, and mycotoxin production. For example, studies suggest that Aspergillus flavus may outcompete other species, increasing aflatoxin risks in Europe [124]. Similarly, warmer temperatures and drought conditions may favor Fusarium species, leading to increased fumonisin contamination. To manage these emerging risks, effective mitigation strategies are necessary, including cumulative risk assessments, multi-screening methods, and climate-smart agricultural practices.