Review: Strategies and technologies in preventing regulated and emerging mycotoxin co-contamination in forage for safeguarding ruminant health.

Ruminants are often considered less susceptible to mycotoxins than monogastrics, owing to rumen microflora converting mycotoxins to less toxic compounds or several compounds present in the rumen-reticulum compartment, being able to bind the mycotoxin "mother" molecule that make them unavailable for absorption process in the gastro-intestinal tract of host animals. However, if ruminants consume feed contaminated by mycotoxins for long periods, their growth, development, and fertility can be compromised. Among regulated mycotoxins, the most studied and known for their effects are aflatoxins (AFs) AFB1, AFB2, AFG1 and AFG2, as well as the AFM1 for its high importance in dairy sector, deoxynivalenol (DON) and its metabolites 3/15 acetyl-DON and 3-glucoside DON, T-2 and HT-2 toxins, zearalenone, fumonisins, in particular that belong to the B class, and ochratoxin A. Furthermore, because of the emergence of multiple emerging mycotoxins that are detectable in feed utilised in ruminant diets, such as ensiled forage, there is now a growing focus on investigating these compounds by the scientific community to deepen their toxicity for animal health. Despite the enhancement of research, it is remarkable that there is a paucity of in vivo trials, as well as limited studies on nutrient digestibility and the impact of these molecules on rumen and intestinal functions or milk yield and quality. In this review, recent findings regarding the occurrence of regulated and emerging mycotoxins in forage and their possible adverse effects on dairy cattle are described, with special emphasis on animal performance and on rumen functionality.

[Mycotoxin intoxication in 54 dogs after ingestion of walnuts]. / Mykotoxinvergiftung nach Walnussaufnahme bei 54 Hunden.

OBJECTIVE: The aim of this retrospective study was to decribe the intoxication with tremorgenic mycotoxins subsequent to the ingestion of walnuts in a large population of dogs and the evaluation of the development of the clinical signs under the initiated treatment. MATERIAL AND METHODS: The study included 54 dogs exhibiting signs of tremor, hyperesthesia, hyperthermia and ataxia, in particular a few hours following observed ingestion of walnuts or its justified suspicion. RESULTS: The patients were presented to the clinic mostly during winter and spring. Fifty-three of 54 dogs were hospitalized for symptomatic, decontaminating and eliminating therapy (98%). Symptomatic treatment comprised of anticonvulsant therapy in 14 dogs (26%) and an antiemetic therapy in for half of the patients (n=27; 50%). A forced emesis for decontamination was undertaken in only 6 patients due to the severity of their neurological symptoms (11%). For further decontamination, an oral administration of activated charcoal after improvement of clinical signs (n=39; 72%). The majority of dogs (n=45; 83%) additionally received an intravenous lipid therapy for toxin elimination and isotonic crystalloid solution to compensate fluid losses. There were no side effects observed following the administration of intravenous lipid therapy. The majority of dogs were hospitalized for a duration of 2 days (n=44; 81%). In most dogs, examination was unremarkable on the day of their release (n=39; 72%). Potential long-term sequelae of the intoxication were not recorded in any patient. CONCLUSION: Due to the lipophilic nature of mycotoxins, the use of intravenous lipid therapy may considered for toxin elimination purposes. The prognosis of mycotoxin intoxication following walnut ingestion is good with decontamination and elimination measures. CLINICAL RELEVANCE: In the case of unspecific neurological signs such as tremor, ataxia and hyperesthesia as well as a corresponding preliminary report, an intoxication with mycotoxin-containing walnuts should be considered.

Impact of enniatins and beauvericin on lipid metabolism: Insights from a 3D HepaRG spheroid model.

Emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) pose potential health risks to humans through dietary exposure. However, research into their mechanisms of toxicity is limited, with a lack of comprehensive toxicological data. This study investigates from a hepatic lipid metabolism perspective, establishing a more precise and reliable 3D HepaRG hepatocyte spheroid model as an alternative for toxicity assessment. Utilizing physiological indices, histopathological analyses, lipidomics, and molecular docking techniques, it comprehensively elucidates the effects of ENNs and BEA on hepatic lipid homeostasis and their molecular toxicological mechanisms. Our findings indicate that ENNs and BEA impact cellular viability and biochemical functions, significantly altering lipid metabolism pathways, particularly those involving glycerophospholipids and sphingolipids. Molecular docking has demonstrated strong binding affinity of ENNs and BEA with key enzymes in lipid metabolism such as Peroxisome Proliferator-Activated Receptor α (PPARα) and Cytosolic Phospholipase A2 (cPLA2), revealing the mechanistic basis for their hepatotoxic effects and potential to impair liver function and human health. These insights enhance our understanding of the potential hepatotoxicity of such fungal toxins and lay a foundation for the assessment of their health risks.

Effects of isochlorogenic acid A on mitochondrial dynamics imbalance and RLR damage in PAM cells induced by combined mycotoxins.

Mycotoxins have strong immunotoxicity and can induce oxidative stress and mitochondrial dynamics imbalance. Mitochondrial antiviral signaling protein (MAVS) in the RIG-I like receptor (RLR) pathway of innate immunity is located on mitochondria, and whether it is affected by mycotoxins has not been reported yet. This experiment used porcine alveolar macrophages (PAM) to evaluate the antagonism of three isomers of chlorogenic acid (chlorogenic acid, isochlorogenic acid A, and neochlorogenic acid) against combined mycotoxins (Aflatoxin B1, Deoxynivalenol, and Ochratoxin A) induced mitochondrial damage and their effects on the RLR pathway, providing assistance for further elucidating the mechanism of mycotoxin immunotoxicity. Western blotting, enzyme linked immunosorbent assay (ELISA), and flow cytometry were used to detect relevant indicators. All three types of chlorogenic acid treatment can antagonize the cytotoxicity induced by combined mycotoxins, especially isochlorogenic acid A, which can protect cells from mycotoxins damage by maintaining mitochondrial dynamic homeostasis and improving innate immune function related to the RLR pathway.

Discovery of Two Novel Phthalide Phytotoxins from the Wheat Tan Spot Fungal Pathogen Pyrenophora tritici-repentis.

The Dothideomycete fungal pathogen Pyrenophora tritici-repentis (Ptr) is the causal agent of the tan spot disease of wheat. The proteinaceous necrotrophic effectors ToxA and ToxB are well characterized. A nonproteinaceous effector called ToxC has also been partially characterized. Ptr produces a number of other small molecular weight compounds, but these remain poorly characterized. In this study, two novel compounds, designated ToxE1 and ToxE2, capable of inducing chlorotic symptoms on wheat leaves in a cultivar-specific manner, were purified from Ptr liquid cultures. There is no evidence that these compounds correspond to ToxC. Most isolates produced ToxE1, ToxE2, or both, and both compounds were detected in infected wheat leaves. The structures of both analogues were elucidated by NMR spectroscopy and comprise a phthalide core structure with an amide moiety. We postulate that these compounds have a general phytotoxic effect and may have an ancillary role in disease development.

Association between spectrum of mycotoxins and semen quality: A cross-sectional study in Beijing, China.

Exposure to mycotoxins is unavoidable in daily life through ingestion, dermal, and inhalation routes. Toxicological studies found that exposure to mycotoxins might affect male reproductive function. However, there is still a lack of population evidence. We aimed to assess the association of individual and joint exposure to spectrum of mycotoxins with semen quality. The present study included 192 participants in Beijing, China. We measured conventional semen parameters and assessed semen quality. Sixty-seven traditional or emerging mycotoxins were determined to describe the spectrum of mycotoxins. The participants were widely exposed to multiple mycotoxins, and nearly half were simultaneously exposed to more than six mycotoxins. After adjusting potential confounders, logistic regression indicated that the number and concentration of plasma mycotoxin were correlated to the risk of low semen quality. Plasma beauvericin and citrinin concentrations were associated with lower semen quality. The least absolute shrinkage and selection operator regression showed similar results to logistic regression. Quantile-based g-computation and Bayesian kernel machine regression models found that the mixture of mycotoxins was harmful to semen quality, especially in sperm motility. In conclusion, both individual and mixture of mycotoxin exposure were correlated with lower semen quality. More regulations and measures should be taken to reduce mycotoxin contamination.

Mycotoxins in food: Occurrence, health implications, and control strategies-A comprehensive review.

Mycotoxins are secondary metabolites produced by various filamentous fungi, including Aspergillus, Fusarium, Penicillium, Alternaria, Claviceps, Mucor, Trichoderma, Trichothecium, Myrothecium, Pyrenophora, and Stachybotrys. They can contaminate various plants or animal foods, resulting in a significant loss of nutritional and commercial value. Several factors contribute to mycotoxin production, such as humidity, temperature, oxygen levels, fungal species, and substrate. When contaminated food is consumed by animals and humans, mycotoxins are rapidly absorbed, affecting the liver, and causing metabolic disorders. The detrimental effects on humans and animals include reduced food intake and milk production, reduced fertility, increased risk of abortion, impaired immune response, and increased occurrence of diseases. Therefore, it is imperative to implement strategies for mycotoxin control, broadly classified as preventing fungal contamination and detoxifying their toxic compounds. This review aims to discuss various aspects of mycotoxins, including their occurrence, and risk potential. Additionally, it provides an overview of mycotoxin detoxification strategies, including the use of mycotoxin absorbents, as potential techniques to eliminate or mitigate the harmful effects of mycotoxins and masked mycotoxins on human and animal health while preserving the nutritional and commercial value of affected food products.

Rats exposed to Alternaria toxins in vivo exhibit altered liver activity highlighted by disruptions in riboflavin and acylcarnitine metabolism.

Natural toxins produced by Alternaria fungi include the mycotoxins alternariol, tenuazonic acid and altertoxins I and II. Several of these toxins have shown high toxicity even at low levels including genotoxic, mutagenic, and estrogenic effects. However, the metabolic effects of toxin exposure from Alternaria are understudied, especially in the liver as a key target. To gain insight into the impact of Alternaria toxin exposure on the liver metabolome, rats (n = 21) were exposed to either (1) a complex culture extract with defined toxin profiles from Alternaria alternata (50 mg/kg body weight), (2) the isolated, highly genotoxic altertoxin-II (ATX-II) (0.7 mg/kg of body weight) or (3) a solvent control. The complex mixture contained a spectrum of Alternaria toxins including a controlled dose of ATX-II, matching the concentration of the isolated ATX-II. Liver samples were collected after 24 h and analyzed via liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Authentic reference standards (> 100) were used to identify endogenous metabolites and exogenous compounds from the administered exposures in tandem with SWATH-acquired MS/MS data which was used for non-targeted analysis/screening. Screening for metabolites produced by Alternaria revealed several compounds solely isolated in the liver of rats exposed to the complex culture, confirming results from a previously performed targeted biomonitoring study. This included the altersetin and altercrasin A that were tentatively identified. An untargeted metabolomics analysis found upregulation of acylcarnitines in rats receiving the complex Alternaria extract as well as downregulation of riboflavin in rats exposed to both ATX-II and the complex mixture. Taken together, this work provides a mechanistic view of Alternari toxin exposure and new suspect screening insights into hardly characterized Alternaria toxins.

A 19-year longitudinal assessment of gyromitrin-containing (Gyromitra spp.) mushroom poisonings in Michigan.

Mushroom poisonings are common in the United States. Gyromitrin (acetaldehyde N-methyl-N-formylhydrazone) is a clinically significant mycotoxin primarily associated with the lorchel (i.e. the false morel) Gyromitra esculenta. Resemblance between 'true and false morels' has resulted in misidentification of Gyromitra spp. as edible and sought after Morchella spp., resulting in toxicity. Despite literature evidence outlining toxic sequalae, Gyromitra spp. mushrooms are commonly consumed and prepared for culinary purposes. Classic clinical teachings emphasize significant neurotoxicity, including seizures, associated with ingestion of gyromitrin-containing mushrooms, stemming from gyromitrin's terminal metabolite monomethylhydrazine. We performed a longitudinal descriptive review of the clinical toxicity associated with ingestion of mushroom species known or suspected to contain gyromitrin in cases reported to the Michigan Poison & Drug Information Center between January 1, 2002, to December 31, 2020. Our 19-year descriptive case series of gyromitrin-containing mushroom ingestions reported to our Center demonstrated a preponderance of gastrointestinal signs and symptoms, including hepatotoxicity. Of 118 identified cases, 108 (91.5%) of the reported ingestions involved Gyromitra esculenta. The most frequent clinical findings associated with symptomatic ingestions (n = 83) were the aforementioned gastrointestinal symptoms (n = 62; 74.7%). Neurological symptoms were less frequent (n = 22, 26.5%) while hepatotoxicity occurred in fewer patients (n = 14; 16.9%). Of symptomatic patients, most were treated with symptomatic and supportive care (n = 58; 70%). Pyridoxine was used in a total of seven patients (n = 7; 8.4%) with either hepatotoxicity or neurotoxicity. Medical outcomes ranged from minor to major, with no reported deaths. Patient presentations (i.e. GI vs. neurotoxic symptoms) following ingestion of gyromitrin-containing mushrooms may be highly variable and multifactorial, owing to differences in dose ingested, geographical distribution, genetic variability of both patient and mushroom species, and species-specific differences in toxin composition. Future research warrants species-level identification of ingested gyromitrin-containing mushrooms and investigating the contribution of genetic polymorphisms to differences in clinical toxidromes.

A review on mycotoxins and mycotoxicoses in ruminants and Equidae in South America.

Of the mycotoxicoses caused by molds contaminating grains or their byproducts, leukoencephalomalacia of horses and less frequently aflatoxicosis in cattle have been reported in South America. However, the most important group of mycotoxins in the region are those caused by fungi that infect forages and other types of plants and have regional distribution. In this group, ergotism is important, both caused by Claviceps purpurea infecting grains or by Epichloë coenophiala infecting Schedonorus arundinaceus. Other important mycotoxicoses are those caused by indole-diterpenes produced by Clavicipitaceous fungi including Claviceps paspali in Paspalum spp., Claviceps cynodontes in Cynodon dactylon, and by Periglandula a seed transmitted symbiont associated with the tremorgenic plant Ipomoea asarifolia. The latter is an important poisoning in the northeastern and northern Brazil. Other important mycotoxicoses are those caused by swainsonine containing plants. It was demonstrated that swainsonine contained in Ipomoea carnea var. fistulosa is produced by an epibiotic fungus of the order Chaetothyriales whose mycelia develop on the adaxial surface of the leaves. Swainsonine is also produced by the symbiotic, endobiotic fungi Alternaria section Undifilum spp., which is associated with Astragalus spp. in the Argentinian Patagonia causing poisoning. Another form of mycotoxicosis occurs in poisoning by Baccharis spp., mainly B. coridifolia, a very important toxic plant in South America that contains macrocyclic trichothecenes probably produced by an endophytic fungus that has not yet been identified. Pithomycotoxicosis caused by Pithomyces chartarum used to be an important mycotoxicosis in the region, mainly in cattle grazing improved pastures of legumes and grasses. Slaframine poisoning, diplodiosis and poisoning by barley contaminated by Aspergillus clavatus has been rarely diagnosed in Brazil, Uruguay and Argentina.

Neurotoxic mechanisms of mycotoxins: Focus on aflatoxin B1 and T-2 toxin.

Aflatoxin B1 (AFB1) and T-2 toxin are commonly found in animal feed and stored grain, posing a serious threat to human and animal health. Mycotoxins can penetrate brain tissue by compromising the blood-brain barrier, triggering oxidative stress and neuroinflammation, and leading to oxidative damage and apoptosis of brain cells. The potential neurotoxic mechanisms of AFB1 and T-2 toxin were discussed by summarizing the relevant research reports from the past ten years. AFB1 and T-2 toxin cause neuronal damage in the cerebral cortex and hippocampus, leading to synaptic transmission dysfunction, ultimately impairing the nervous system function of the body. The toxic mechanism is related to excessive reactive oxygen species (ROS), oxidative stress, mitochondrial dysfunction, apoptosis, autophagy, and an exaggerated inflammatory response. After passing through the blood-brain barrier, toxins can directly affect glial cells, alter the activation state of microglia and astrocytes, thereby promoting brain inflammation, disrupting the blood-brain barrier, and influencing the synaptic transmission process. We discussed the diverse effects of various concentrations of toxins and different modes of exposure on neurotoxicity. In addition, toxins can also cross the placental barrier, causing neurotoxic symptoms in offspring, as demonstrated in various species. Our goal is to uncover the underlying mechanisms of the neurotoxicity of AFB1 and T-2 toxin and to provide insights for future research, including investigating the impact of mycotoxins on interactions between microglia and astrocytes.

Mycotoxicoses in Veterinary Medicine: Fusarium Toxins, Grass Staggers, and Neothyphodium Toxins.

Fungi are a large group of eukaryotic microorganisms that can readily adapt to diverse environments and occur in almost all climatic zones and continents. Although some fungi are inevitable in the environment for the decay and recycling of organic material, many species are known to produce secondary metabolites, and these mycotoxins, when ingested with food or feed materials, can adversely affect animal and human health. Among the toxigenic fungi, Fusarium species are recognized as so-called field fungi, invading crops and producing mycotoxins predominantly before harvest. Fusarium produces a wide array of mycotoxins, causing different plant diseases. Fusariosis causes significant economic losses in a wide range of crops. Fusarium secondary metabolites, particularly trichothecenes, are potent toxins in mammalian species and cause diverse adverse effects in humans and animals. Other prominent Fusarium toxins with entirely different chemical structures are zearalenone and its derivatives and fumonisins. With an entirely different life cycle, toxins of endophytes belonging to the genus Epichloë and Neothyphodium coenophialum and Neothyphodium lolii comprise an animal health risk, particularly for grazing animals. This review aimed to summarize the adverse effects of selected Fusarium and Epichloë toxins, with a special emphasis on their occurrence in roughages and their mechanisms of action, and describe their effect on animal health and welfare and the potentially related public health risks.

Exposure to a Combination of Fusarium Mycotoxins Leads to Lipid Peroxidation and Influences Antioxidant Defenses, Fatty Acid Composition of Phospholipids, and Renal Histology in Laying Hens.

The effects of combined short-term (3 days) exposure to Fusarium mycotoxins at both the EU recommended limit (T-2/HT-2 toxin: 0.25 mg/kg; DON/3-AcDON/15-AcDON: 5 mg/kg; FB1: 20 mg/kg) and twice the dose (T-2/HT-2 toxin: 0.5 mg/kg, DON/3-AcDON/15-AcDON: 10 mg/kg, and FB1: 40 mg/kg feed) on the kidneys of laying hens were examined. Our study aimed to investigate how these mycotoxins interacted with membrane lipid fatty acid (FA) composition and lipid peroxidation processes. It was observed that the levels of conjugated dienes and trienes were higher than the control in the low-mix group on day 3, and malondialdehyde concentration was higher on days 2 and 3. The proportion of phospholipid (PL) FAs showed that saturated and monounsaturated FAs increased. Still, both n3 and n6 polyunsaturated FAs decreased significantly on day 2 of exposure in the high-mix group. Among the n3 FAs, the level of docosahexaenoic (C22:6 n3) and among n6 FAs, arachidonic (C20:4 n6) acids decreased mainly on day 2 in the high-mix group. The results suggest that the combined exposure to Fusarium mycotoxins induced lipid peroxidation in the kidneys of laying hens, which resulted in marked changes in the PL FA profile. Histological examination revealed time- and dose-dependent increases as consequences of mycotoxin exposure.

PI3K/Akt/FoxO Pathway Mediates Antagonistic Toxicity in HepG2 Cells Coexposed to Deoxynivalenol and Enniatins.

The emerging mycotoxins enniatins (ENNs) and the traditional mycotoxin deoxynivalenol (DON) often co-contaminate various grain raw materials and foods. While the liver is their common target organ, the mechanism of their combined effect remains unclear. In this study, the combined cytotoxic effects of four ENNs (ENA, ENA1, ENB, and ENB1) with DON and their mechanisms were investigated using the HepG2 cell line. Additionally, a population exposure risk assessment of these mycotoxins was performed by using in vitro experiments and computer simulations. The results showed that only ENA at 1/4 IC50 and ENB1 at 1/8 IC50 coexposed with DON showed an additive effect, while ENB showed the strongest antagonism at IC50 (CI = 3.890). Co-incubation of ENNs regulated the signaling molecule levels which were disrupted by DON. Transcriptome analysis showed that ENB (IC50) up-regulated the PI3K/Akt/FoxO signaling pathway and inhibited the expression of apoptotic genes (Bax, P53, Caspase 3, etc.) via phosphorylation of FoxO, thereby reducing the cytotoxic effects caused by DON. Both types of mycotoxins posed serious health risks, and the cumulative risk of coexposure was particularly important for emerging mycotoxins.

Evaluating the human neurotoxicity and toxicological interactions impact of co-occurring regulated and emerging mycotoxins.

Mycotoxins can inflict harmful effects on diverse organs, and mounting evidence indicates their potential involvement in human neurodegenerative diseases. Given the common occurrence of these toxins in food, there is an increasing demand for a comprehensive assessment of their combined toxicity to enhance our understanding of their potential hazards. This research investigates mycotoxin exposure from widely consumed cereal-based products, including enniatin B (ENNB), sterigmatocystin (STG), aflatoxin B1 (AFB1), cyclopiazonic acid (CPZ), citrinin (CIT), and ochratoxin A (OTA). Employing the median-effect equation based on Chou and Talalay's mass-action law, we assessed their cytotoxicity in human SH-SY5Y neuronal cells. Notably, ENNB displayed the highest neurotoxicity (IC50 = 3.72 µM), followed by OTA (9.10 µM) and STG (9.99 µM). The combination of OTA + STG exhibited the highest toxicity (IC50 = 3.77 µM), while CPZ + CIT showed the least detrimental effect. Approximately 70 % of tested binary combinations displayed synergistic or additive effects, except for ENNB + STG, ENNB + AFB1, and CPZ + CIT, which showed antagonistic interactions. Intriguingly, the senary combination displayed moderate antagonism at the lowest exposure and moderate synergism at higher doses. OTA exhibited predominantly synergistic interactions, comprising approximately 90 %, a noteworthy finding considering its prevalence in food. Conversely, ENNB interactions tended to be antagonistic. The most remarkable synergy occurred in the STG and CIT combination, enabling a 50-fold reduction in CIT dosage for an equivalent toxic effect. These findings highlight the biological relevance of robust synergistic interactions, emphasizing the need to assess human exposure hazards accurately, particularly considering frequent mycotoxin co-occurrence in environmental and food settings.

New insight into mycotoxins and bacterial toxins: Toxicity assessment, molecular mechanism and food safety (preface to the special issue of food and chemical toxicology on the outcomes of Myco & bacterial toxin).

The special issue "New Insight into Mycotoxins and Bacterial Toxins: Toxicity Assessment, Molecular Mechanism and Food Safety" in Food and Chemical Toxicology contains 19 articles on current hot topics in mycotoxins and bacterial toxins. Dietary exposure to mycotoxins and risk assessments are reported in this issue. Molecular mechanisms of multiple mycotoxins and emerging mechanisms of toxicity are especially concerned by researchers. Moreover, mycotoxin-detoxifying substances and antimicrobial agents are also fully investigated in the context. This special issue will help to further understand the mycotoxins and bacterial toxins, casting new light for the control of food safety.

Meta-Analysis of the Effects of Yeast Cell Wall Extract Supple-Mentation during Mycotoxin Challenges on the Performance of Laying Hens.

A random-effects meta-analysis was conducted to investigate the effect of mycotoxins (MT) without or with the inclusion of yeast cell wall extract (YCWE, Mycosorb®, Alltech, Inc., Nicholasville, KY, USA) on laying hen performance. A total of 25 trials were collected from a literature search, and data were extracted from 8 of these that met inclusion criteria, for a total of 12 treatments and 1774 birds. Laying hens fed MT had lower (p < 0.05) body weight (BW) by -50 g, egg production by -6.3 percentage points, and egg weight by -1.95 g than control fed hens (CTRL). Inclusion of YCWE during the mycotoxin challenges (YCWE + MT) resulted in numerically greater (p = 0.441) BW by 12.5 g, while egg production and egg weight were significantly (p < 0.0001) higher by 4.2 percentage points and 1.37 g, respectively. Furthermore, economic assessment calculations indicated that YCWE may not only support hen performance but also resulted in a positive return on investment. In conclusion, mycotoxins can play a role in negatively impacting laying hen performance and profitability. Inclusion of YCWE in feed with mycotoxin challenges provided benefits to egg production and egg weight and may support profitability. As such, the inclusion of YCWE could play an important role in minimizing mycotoxin effects and in turn aid farm efficiency and profitability.

Fumonisins alone or mixed with other fusariotoxins increase the C22-24:C16 sphingolipid ratios in chicken livers, while deoxynivalenol and zearalenone have no effect.

Poultry feed is often contaminated with fumonisins, deoxynivalenol, and zearalenone, which can result in oxidative damage, inflammation and change in lipid metabolism. Although sphingolipids play key roles in cells, only the effects of fumonisins on the sphingolipidome are well-documented. In chickens, fumonisins have been shown to increase the sphinganine to sphingosine ratio and the C22-24:C16 sphingolipid ratio, which has been proposed as a new biomarker of toxicity. In this study, we used UHPLC-MSMS targeted analysis to measure the effect of fusariotoxins on sphingolipids in the livers of chickens fed with diets containing fusariotoxins administered individually and in combination, at the maximum levels recommended by the European Commission. Chickens were exposed from hatching until they reached 35 days of age. This study revealed for the first time that fumonisins, deoxynivalenol, and zearalenone alone and in combination have numerous effects on the sphingolipidome in chicken livers. A 30-50 % decrease in ceramide, dihydroceramide, sphingomyelin, dihydrosphingomyelin, monohexosylceramide and lactosylceramide measured at the class level was observed when fusariotoxins were administered alone, whereas a 30-100 % increase in dihydroceramide, sphingomyelin, dihydrosphingomyelin, and monohexosylceramide was observed when the fusariotoxins were administered in combination. For these different variables, strong significant interactions were observed between fumonisins and zearalenone and between fumonisins and deoxynivalenol, whereas interactions between deoxynivalenol and zearalenone were less frequent and less significant. Interestingly, an increase in the C22-24:C16 ratio of ceramides, sphingomyelins, and monohexosylceramides was observed in chickens fed the diets containing fumonisins only, and this increase was close when the toxin was administered alone or in combination with deoxynivalenol and zearalenone. This effect mainly corresponded to a decrease in sphingolipids with a fatty acid chain length of 16 carbons, whereas C22-24 sphingolipids were unaffected or increased. In conclusion the C22-24:C16 ratio emerged as a specific biomarker, with variations dependent only on the presence of fumonisins.

Endotoxin Translocation Is Increased in Broiler Chickens Fed a Fusarium Mycotoxin-Contaminated Diet.

Broiler chickens in livestock production face numerous challenges that can impact their health and welfare, including mycotoxin contamination and heat stress. In this study, we aimed to investigate the combined effects of two mycotoxins, deoxynivalenol (DON) and fumonisins (FBs), along with short-term heat stress conditions, on broiler gut health and endotoxin translocation. An experiment was conducted to assess the impacts of mycotoxin exposure on broilers, focusing on intestinal endotoxin activity, gene expression related to gut barrier function and inflammation, and the plasma concentration of the endotoxin marker 3-OH C14:0 either at thermoneutral conditions or short-term heat stress conditions. Independently of heat stress, broilers fed DON-contaminated diets exhibited reduced body weight gain during the starter phase (Day 1-12) compared to the control group, while broilers fed FB-contaminated diets experienced decreased body weight gain throughout the entire trial period (Day 1-24). Furthermore, under thermoneutral conditions, broilers fed DON-contaminated diets showed an increase in 3-OH C14:0 concentration in the plasma. Moreover, under heat stress conditions, the expression of genes related to gut barrier function (Claudin 5, Zonulin 1 and 2) and inflammation (Toll-like receptor 4, Interleukin-1 beta, Interleukin-6) was significantly affected by diets contaminated with mycotoxins, depending on the gut segment. This effect was particularly prominent in broilers fed diets contaminated with FBs. Notably, the plasma concentration of 3-OH C14:0 increased in broilers exposed to both DON- and FB-contaminated diets under heat stress conditions. These findings shed light on the intricate interactions between mycotoxins, heat stress, gut health, and endotoxin translocation in broiler chickens, highlighting the importance of understanding these interactions for the development of effective management strategies in livestock production to enhance broiler health and welfare.

Effects of a Curcumin/Silymarin/Yeast-Based Mycotoxin Detoxifier on Redox Status and Growth Performance of Weaned Piglets under Field Conditions.

The aim of this in vivo study was to investigate the effects of a novel mycotoxin detoxifier whose formulation includes clay (bentonite and sepiolite), phytogenic feed additives (curcumin and silymarin) and postbiotics (yeast products) on the health, performance and redox status of weaned piglets under the dietary challenge of fumonisins (FUMs). The study was conducted in duplicate in the course of two independent trials on two different farms. One hundred and fifty (150) weaned piglets per trial farm were allocated into two separate groups: (a) T1 (control group): 75 weaned piglets received FUM-contaminated feed and (b) T2 (experimental group): 75 weaned piglets received FUM-contaminated feed with the mycotoxin-detoxifying agent from the day of weaning (28 days) until 70 days of age. Thiobarbituric acid reactive substances (TBARSs), protein carbonyls (CARBs) and the overall antioxidant capacity (TAC) were assessed in plasma as indicators of redox status at 45 and 70 days of age. Furthermore, mortality and performance parameters were recorded at 28, 45 and 70 days of age, while histopathological examination was performed at the end of the trial period (day 70). The results of the present study reveal the beneficial effects of supplementing a novel mycotoxin detoxifier in the diets of weaners, including improved redox status, potential hepatoprotective properties and enhanced growth performance.