Introduction
The pig is a species of significant importance within the livestock sector and the global economy, in addition to being one of the most sensitive animals to mycotoxins, especially those produced by the Fusarium fungus. Mycotoxins are toxic, low-molecular-weight secondary metabolites produced by certain genera of fungi, which can contaminate feed during harvesting, processing, or storage.
There are well-known and highly dangerous mycotoxins for which the European Union (EU) has established maximum permitted levels in raw materials and feed. However, there is growing concern about other secondary fungal metabolites whose regulation is still under development: emerging mycotoxins. The term «emerging mycotoxins» refers to those mycotoxins that are neither routinely monitored nor legislatively regulated, despite existing evidence of their adverse effects on human and animal health (Arroyo-Manzanares et al., 2019; Khoshal et al., 2019; Krug et al., 2018). These compounds are gaining more attention due to their high frequency of contamination in feed and raw materials for animal nutrition (Hasuda et al., 2023).
Among the most globally prevalent emerging mycotoxins, especially in feed, are: enniatins (ENNs), beauvericin (BEA), apicidin (API), emodin (EMO), aurofucarin (AFN), and sterigmatocystin (STC).
Occurrence and co-contamination
The high incidence of mycotoxins, both regulated and emerging, in animal feed, especially in swine feed, is a constant phenomenon (Arroyo-Manzanares et al., 2019; Khoshal et al., 2019). Given the high proportion of cereals in the swine diet, pigs are one of the animal species most exposed to these toxins (Arroyo-Manzanares et al., 2019).
Various comprehensive occurrence studies in swine feed have confirmed the high prevalence of emerging mycotoxins. Arroyo-Manzanares et al. (2019) analyzed 228 samples of swine feed in Spain and found that enniatin B (ENN B) was present in 100% of the samples at an average concentration of 118 µg/kg reaching a maximum of 1222 µg/kg. BEA was detected in 93.4% of these samples at an average concentration of 20.7 µg/kg and a maximum of 747 µg/kg. Additionally, 40% of the samples were contaminated by more than 5 mycotoxins (including prevalent and emerging mycotoxins).
Khoshal et al. (2019) conducted a global study, analyzing 524 samples of swine feed, and demonstrated that 88% of the samples were co-contaminated with deoxynivalenol (DON) and other regulated or emerging mycotoxins. The most prevalent emerging mycotoxins co-occurring with DON globally were ENN B (91%; average concentration: 32 µg/kg), ENN B1 (92%; average concentration: 37 µg/kg), BEA (89%; average concentration: 7 µg/kg), API (65%; average concentration: 7 µg/kg), EMO (90%; average concentration: 5 µg/kg) and AFN (89%; average concentration: 211 µg/kg).
The simultaneous presence of mycotoxins in swine feed is a very frequent phenomenon and a critical risk factor, as the combined toxicity of multiple fungal metabolites can exacerbate adverse effects on animal health and performance. The toxicity of compounds when they occur together cannot be predicted based on their individual toxicity, as they can lead to additive, antagonistic, or synergistic effects (Khoshal et al., 2019; Muñoz-Solano et al., 2024).
Effects of emerging mycotoxins in swine
Swine exposure to emerging mycotoxins represents a systemic and organic risk which is complicated by the phenomenon of co-contamination (Khoshal et al., 2019; Novak et al., 2021).
The most critical impact of combined exposure is observed in swine performance, especially during the weaning phase, a period already critical for piglets (Novak et al., 2021). An in vivo 14-day study in weaned piglets (28 to 29 days of age) demonstrated that contamination with BEA, ENN B, and ENN B1 along with DON led to a significant decrease in the animals’ body weight gain compared to the control group. This performance effect was not observed in the group exposed only to the emerging metabolites, which underscores that the decrease in performance was not caused by the emerging metabolites in isolation, but by the synergistic or additive effect with DON (Novak et al., 2021). Furthermore, this decrease in growth correlated with a tendency toward reduced feed intake. On an organic level, all contaminated diets induced moderate to severe histological lesions in the jejunum, liver, and lymph nodes (Novak et al., 2021).
At the intestinal level, evaluation of individual toxicity in porcine epithelial cells (IPEC-1) showed that API and enniatin A1 (ENN A1) are more toxic than DON on their own (Khoshal et al., 2019). In porcine liver samples analyzed in ex vivo studies, ENN B1 induced significant changes in hepatic morphology following acute exposure, characterized by cytoplasmic vacuolation, megalocytosis, and nuclear vacuolation of hepatocytes (Hasuda et al., 2023).
In the context of potential neurotoxicity, ENN B and ENN B1 demonstrated the ability to be transported across the blood-brain barrier (in vitro), suggesting possible neurotoxic effects in the animal’s cerebral parenchyma (Krug et al., 2018).
Exposure to the combination of BEA and ENNs significantly impacted the fecal microbiota of piglets, especially in combination with DON. This combination of mycotoxins resulted in significantly lower microbial diversity (as measured by the Shannon index) (Novak et al., 2021). Regarding toxicity interaction, the co-occurrence with DON produces effects that differ depending on the tissue. While in vitro studies with porcine intestinal cells (IPEC-1) suggested the toxicity of the DON mixtures with emerging mycotoxins was generally similar or inferior to DON alone, indicating an antagonistic or additive effect (Khoshal et al., 2019), the in vivo effect zproved to be systemically detrimental, with the BEA + ENNs + DON mixture causing a significant decrease in weight gain (Novak et al., 2021). This contrast underscores the critical need to investigate the complex interactions of mycotoxins within a complete organic context (Novak et al., 2021).
Conclusion
Emerging mycotoxins are a growing concern for swine health and productivity. However, there are few in vivo studies that confirm laboratory findings, and this lack of information limits the creation and enforcement of clear regulations. Current rules do not fully address the risks of emerging mycotoxins or the dangers of combined exposure to mycotoxins.
