Impact of mycotoxins on the intestine: are mucus and microbiota new targets?

There is an increasing awareness of the deleterious effects attributed to mycotoxins during their fate within the gut, particularly for deoxynivalenol (DON), zearalenone (ZEN), ochratoxin A (OTA), fumonisin B1 (FB1), aflatoxin B1 (AFB1), and patulin (PAT). Evidence indicates that disruption of the epithelial barrier is well established. However, intestinal barrier function on its luminal side involves two other partners, mucus and microbiota, which have rarely been considered in the context of mycotoxin exposure. The current review aimed at providing a summary of DON, ZEN, OTA, FB1, AFB1, and PAT effects on intestinal barrier function, with special focus on mucus and microbiota. DON, ZEN, OTA, FB1, AFB1, and PAT are known to markedly affect epithelial cell integrity and functions. Regarding mucus, DON is the most documentated mycotoxin. In vivo, toxicological impact of DON generally has only been assessed through goblet cell number. Evaluation of the mycotoxins/mucus interplay considering other indicators such as composition, thickness, and penetrability of mucus, mucin O-glycosylation thus warrants further attention. With respect to microbiota, few short-term studies to date have been reported indicating deleterious effects. However, long-term exposure to mycotoxins may also produce significant changes in microbiota composition and metabolic activity, which requires further experimentation. In conclusion, mucus and microbiota are key targets for dietary mycotoxins although assessment of induced effects is preliminary. A significant research effort is now underway to determine the adverse consequences of mycotoxins on mucus and microbiota considered as individual but also as tightly connected gut players.

EGFR-mediated Akt and MAPKs signal pathways play a crucial role in patulin-induced cell proliferation in primary murine keratinocytes via modulation of Cyclin D1 and COX-2 expression.

Patulin (PAT), a present day major contaminant of commercial apple and apple products is reported to be carcinogenic, embryotoxic, and immunotoxic. While oral and inhalation are considered to be the most prevalent routes of exposure to this toxin, exposure through skin is now being extensively investigated. Our previous study showed that short-term dermal exposure to PAT resulted in toxicological injury to the skin, while long-term exposure induced skin tumorigenesis. In this study, we explore the mechanism involve in proliferation of mouse keratinocytes by PAT. Our study revealed that PAT rapidly induces phosphorylation of EGFR, activation of the Ras/MAPKs, and Akt pathways. This in-turn leads to the activation of NF-κB/AP-1 transcription factors which then binds to the promoter region of the cell growth regulatory genes Cyclin D1 and COX-2 inducing their expression leading ultimately to PMKs proliferation. Inhibition of EGFR or the Ras/MAPKs, PI3/Akt pathways with different pharmacological inhibitors or knockdown of NF-κB, c-jun, c-fos, Cyclin D1, and COX-2 with siRNA inhibited PAT-induced PMKs proliferation.

[Nutritional health aspects of mycotoxins]. / Mikotoxinok táplálkozás-egészségügyi vonatkozásai.

Mycotoxins produced by mould fungi can enter into the human food chain directly through foods of plant origin (cereal grains), consumer goods (coffee and bear) and indirectly through foods of animal origin (kidney, liver, milk and eggs). Mycotoxins occur in small amount in the foods; however their continuous intake even in microdoses can result in accumulation in the organism. Synergic effects of the mycotoxins as well as their possible additive multi-toxic effects seem to be especially dangerous. Mycotoxin problems are very important in Hungary because these natural toxins occur mainly in those cereals (e.g. wheat, maize) that amount to high proportion of the sowing area in Hungary and provide the main foods to the inhabitants. Public health risks of the toxins accumulating in the human and animal bodies during the long term consumption of the mycotoxins containing foods--even in small doses--have not been evaluated yet as thoroughly as their importance would require. However, there are more and more direct and indirect expressions of the danger resulting from the toxins. The most frequently observed human health effects are carcinogen effects (aflatoxin, ochratoxin A, fumonisins, patulin); effects causing developmental abnormalities (zearalenon, ochratoxin); effects harmful to the reproduction (zearalenon, and trichotecenes), effects decreasing the resistance; immunosuppressive effects (trichotecenes), and effects causing injury of the nervous system (ochratoxin A, fumonisins). Prevention of the injury of the health caused by mycotoxins can be completed by joint and integrated activity of the various disciplines only and requires a comprehensive interdisciplinary cooperation. This paper gives a discussion on health injuring effects of the most frequently occurring mycotoxins that are very important from human health aspects in Hungary; on their occurrence in the foods and on their human risk.

Selenium supplementation shows protective effects against patulin-induced brain damage in mice via increases in GSH-related enzyme activity and expression.

AIMS: This study was designed to investigate the protective effects of selenium supplementation on patulin-induced neurotoxicity. MAIN METHODS: Mice were subjected to patulin for 8 weeks. Sodium selenite (Na2SeO3) and selenium-methionine (Se-Met) were supplemented with the diet, and we investigated the effects of selenium on patulin-induced neurotoxicity. The animals were randomly divided into 4 groups containing 6-8 mice each. The first group was used as a control, and only physiological saline (0.9%) was injected. The second group was treated with patulin (1mg/kg) intraperitoneally. The third group was treated with patulin (1mg/kg) along with a dietary supplementation of Na2SeO3 (0.2mg Se/kg of diet). The fourth group was treated with patulin (1mg/kg) plus Se-Met (0.2mg Se/kg of diet). KEY FINDINGS: Patulin treatment increased oxidative damage in the brain, as evidenced by a decrease in non-protein thiol and total thiol groups, along with significant increases in GSSG, reactive oxygen species, thiobarbituric acid reactive substances and protein carbonyl levels. Moreover, the activities of glutathione peroxidase (GPx) and glutathione reductase were inhibited with patulin treatment. Selenium supplementation significantly ameliorated these biological parameter changes. In addition, selenium treatments significantly increased the mRNA levels of GPx-1, GPx-4 and thioredoxin reductase. SIGNIFICANCE: Our data show that selenium supplementation increases the activity and expression of glutathione-related enzymes and offers significant protection against brain damage induced by patulin.

Reduction of patulin in aqueous solution by lactic acid bacteria.

This study aims to investigate the ability of lactic acid bacteria (LAB) to remove patulin (PAT) from aqueous solution with respect to the bacterial viability, initial PAT concentration, incubation time, temperature, and pH. The removal of PAT determined by high-performance liquid chromatography (HPLC) coupled with UV detector. The maximum PAT uptake was achieved by Bifidobacterium bifidum 6071 and Lactobacillus rhamnosus 6149 strains (52.9% and 51.1%) for viable and (54.1% and 52.0%) for nonviable cells after 24 h incubation. The highest removal of PAT was at pH 4.0 and 37 °C and increased with decreasing of toxin levels. The removal ability of selected strains could represent new strategies for a possible application in contaminated food products and animal feed.

[Carcinogenic fungi (author's transl)]. / I funghi tumorigeni.

An association of carcinogenicity of toxic substances with fungi is shortly documented and discussed. The actions of the aflatoxin B1 (AFB1) are particularly examined; but it is emphasized that other carcinogenic mycotoxins are more frequent and therefore more dangerous. The man is unable to live estranged from them, because they are a great part in ecological systems and in the work-place, resulting a potentially major threat. The range of food and feedstuffs potentially affected has been increased in recent years. In effect contamination is liable to occur during transport, storage and food processing. These studies demand organized cooperation among mycologists, chemists, pathologists, pharmacologists, physicians. In Japan such extensive collaboration has a long history.

[Danger to health caused by mycotoxins in foods]. / Gesundheitsgefährdung durch Mykotoxine in Lebensmitteln.

The toxicological effects of some mycotoxins are described. The results of own analyses of aflatoxin and patulin in food are reported.

Identification of risk groups for intake of food chemicals.

This paper summarizes by four recent examples the procedure of the characterization of groups at risk for ingestion of food chemicals and its limitations. The examples concern two food additives (sulfites and aspartame), one nutrient (calcium), and one food contaminant (patuline). On the one hand, results show that the empirical description of a group at risk is nowadays the best way to provide to risk managers information useful for consumer protection. On the other hand, these examples show that in any case if risk 0 does not exist, it is impossible to completely avoid any group at risk. The responsibility of risk managers is to decide what is the minimum size of the population to protect as a function of the risk and of the cost of the protection.