Introduction
The pig is a species of critical 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. 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).
The most prevalent emerging mycotoxins worldwide, particularly in feed, include: enniatins (ENNs), beauvericin (BEA), apicidin (API), emodin (EMO), aurofusarin (AFN), and sterigmatocystin (STE).
Occurrence and co-contamination
Mycotoxins, including both regulated and emerging compounds, occur frequently in animal feed (Arroyo-Manzanares et al., 2019; Khoshal et al., 2019). As swine diets are largely cereal-based, pigs are among the animal species most exposed to these toxins (Arroyo-Manzanares et al., 2019).
Studies on mycotoxin occurrence in swine feed report a high prevalence of emerging compounds. Arroyo-Manzanares et al. (2019) analysed 228 swine feed samples in Spain and reported that enniatin B (ENNB) was detected in 100% of samples, with a mean concentration of 118 µg/kg and a maximum of 1222 µg/kg. BEA was detected in 93.4% of samples, with a mean concentration of 20.7 µg/kg and a maximum of 747 µg/kg. Up to 40% of samples were co-contaminated with more than five mycotoxins, including both regulated and emerging compounds.
Khoshal et al. (2019) analysed 524 swine feed samples in a global study and reported that 88% were co-contaminated with deoxynivalenol (DON) and other regulated or emerging mycotoxins. The most prevalent emerging mycotoxins co-occurring with DON worldwide were ENN B (91%; mean concentration: 32 µg/kg), ENN B1 (92%; mean concentration: 37 µg/kg), BEA (89%; mean concentration: 7 µg/kg), API (65%; mean concentration: 7 µg/kg), EMO (90%; mean concentration: 5 µg/kg), and AFN (89%; mean concentration: 211 µg/kg).
Co-occurrence of mycotoxins in swine feed is frequent and represents a critical risk factor, as the combined toxicity of multiple fungal metabolites may exacerbate adverse effects on animal health and performance. The toxicity of these compounds in combination cannot be predicted from their individual effects, as interactions may be additive, antagonistic, or synergistic (Khoshal et al., 2019; Muñoz-Solano et al., 2024).
Effects of emerging mycotoxins in swine
As previously described, exposure of swine to emerging mycotoxins represents a systemic risk that is further exacerbated by co-contamination (Khoshal et al., 2019; Novak et al., 2021).
The most significant impact of combined exposure is observed in swine performance, particularly during the weaning phase, which is already a highly vulnerable period for piglets (Novak et al., 2021). A 14-day in vivo study in weaned piglets (28-29 days old) showed that co-contamination with BEA, ENN B, and ENN B1 in combination with DON resulted in a significant reduction in body weight gain compared with the control group. This effect was not observed in animals exposed only to emerging mycotoxins, indicating that the reduction in performance was not attributable to these compounds alone, but rather to additive or synergistic interactions with DON (Novak et al., 2021). The reduction in growth performance was also associated with a trend towards decreased feed intake. At the organ level, 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 ENN A1 exhibit greater toxicity than DON (Khoshal et al., 2019). In ex vivo studies using porcine liver samples, ENN B1 induced significant morphological alterations following acute exposure, including cytoplasmic vacuolation, megalocytosis, and nuclear vacuolation of hepatocytes (Hasuda et al., 2023).
With regard to potential neurotoxicity, ENN B and ENN B1 have been shown to cross the blood–brain barrier in vitro, suggesting potential neurotoxic effects on the cerebral parenchyma (Krug et al., 2018).
Exposure to a mixture of BEA and ENNs significantly affected the faecal microbiota of piglets, particularly when combined with DON. This co-exposure resulted in a significant reduction in microbial diversity, as measured by the Shannon index (Novak et al., 2021).
The interaction between DON and co-occurring mycotoxins varies across tissues. In vitro studies using porcine intestinal epithelial cells (IPEC-1) have shown that mixtures of DON with emerging mycotoxins generally exhibit toxicity comparable to or lower than that of DON alone, suggesting antagonistic or additive effects (Khoshal et al., 2019). However, in vivo exposure has been shown to be systemically detrimental, with the combination of BEA, ENNs, and DON significantly reducing weight gain (Novak et al., 2021). This discrepancy highlights the need to investigate mycotoxin interactions within a whole-organism 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.