Why the invisible bounds? A reflection upon the physiology of toxics

  The predoctoral period is not very special. Every day is special. At least, it should be so. The ordinary life offers us a vastity of gifts. They are out waiting for us. We have to discover them. To eliminate our blindness, we should close our eyes more often. One of these gifts of ordinary life was the connection of mycotoxins, gut microbiota changes and liver disease.

 Mycotoxins are toxic secondary metabolites produced by filamentous fungi and are estimated to contaminate up to 80% of global diets [1. Although they are synthesized by a wide range of fungal species, the genera Aspergillus, Fusarium, and Penicillium are recognized as the principal producers. Exposure to mycotoxins poses significant risks to both human and animal health, being associated with neurotoxicity, hepatotoxicity, nephrotoxicity, teratogenicity, carcinogenicity, reproductive disorders, and immunosuppression. As dietary intake represents the primary route of human exposure, continuous monitoring of mycotoxin levels in food and feed is essential to ensure food safety [2].

  To mitigate these risks, the European Union has established maximum permissible levels for several mycotoxins in food through Commission Regulation (EU) 2023/915 of 25 April 2023. This regulation covers aflatoxins (AFB1, AFB2, AFG1, AFG2, and AFM1), citrinin (CIT), deoxynivalenol (DON), ergot sclerotia and ergot alkaloids, fumonisins (FB1 and FB2), HT-2 and T-2 toxins, ochratoxin A (OTA), patulin, and zearalenone (ZEN) (European Commission, 2023). In contrast, a growing group of compounds referred to as emerging mycotoxins remains largely unregulated [3].

  Beyond their direct toxic effects, mycotoxins are now recognized as important modulators of the gut microbiota, a complex and dynamic microbial community essential for host health [4]. The gut microbiota is increasingly considered an “emerging organ,” shaped by factors such as diet, stress, physical activity, medication use, and exposure to environmental contaminants, including mycotoxins [5].

  Disruptions in gut microbiota composition and function have been linked to a wide range of diseases, including inflammatory bowel disease, neurodegenerative disorders, metabolic diseases, mental health disorders, and cancer. These effects are mediated through bidirectional gut microbiota–host communication networks, known as microbiota-related axes, such as the gut–brain, gut–immune system, and gut–liver axes [6]. Among these, the gut microbiota–liver axis is particularly relevant in the context of mycotoxin exposure, as the liver plays a central role in metabolism, immune regulation, and detoxification of xenobiotics, including dietary toxins [7] Knowing all this information, a scoping review was conducted to provide insight into the relationship between mycotoxins, gut microbiota, and liver disease in animals. The results are the following:

  Across many animal species, including chickens, rabbits, sheep, rodents, and several fish species, mycotoxin exposure was consistently linked to signs of liver stress, oxidative damage, and inflammation. Scientists observed changes in key liver health markers and increases in molecules associated with cellular stress and immune activation.

  Mycotoxins also disrupted the gut microbiota, the community of microorganisms living in the digestive system. Important bacterial groups changed both at the broad level (major phyla such as Firmicutes, Bacteroidetes, and Proteobacteria) and at the finer genus level, including beneficial microbes like Lactobacillus and Bifidobacterium as well as potentially harmful bacteria.

  Despite the fact that more than 400 mycotoxins are known to exist, research on their effects on the gut–liver connection has focused on only a few well-studied compounds — mainly aflatoxin B1, ochratoxin A, deoxynivalenol, zearalenone, enniatins, and T-2 toxin. This highlights a major gap in current knowledge and suggests that the health impacts of many mycotoxins remain poorly understood. Overall, the findings emphasize that mycotoxins can influence both gut microbes and liver health at the same time, reinforcing the importance of studying the body as an interconnected system rather than isolated organs [8].

  This interdisciplinarity should be more common in the world of science. I know that, even unconsciously, researchers delve into interdisciplinarity without knowing it. For instance, investigating mycotoxins requires knowledge not only about toxicology, but also nutrition, molecular biology, physiology, microbiology, chemistry and food safety. If we thought of this interconnection more often, we would be more likely to be possessed by reality.

 Reality is a gift. Could we have ever imagined it? I do not think so. The effects of mycotoxins and gut microbiota and the consequences on liver physiology is not an invention, but a discovery. It is not a human creation. Our creativity participates in this work of art. There are invisible bindings to be discovered. We could think that bread – containing considerable quantity of mycotoxins – could be related to liver disease in livestock. We are talking about appearances. Reality is another issue.

  Yes, it is partially true. However, it is not about bread, but mycotoxins. And, what about the gut microbiota-liver axis? Our central nervous system (CNS) is connected to the walls of our intestine. Every signal from microbiota or their metabolites can be sent to our CNS.

  Our mind is so limiting to understand the whole existence. A binding is a synonym of a bound. We have to use our reason, but also our heart. Close your eyes and see the vast garden opening before your soul. Some visible connection may appear to you and transform your destiny.

1. Eskola M, Kos G, Elliott CT, Hajšlová J, Mayar S, Krska R. Worldwide contamination of food-crops with mycotoxins: Validity of the widely cited “FAO estimate” of 25. Crit Rev Food Sci Nutr. 2020;60(16):2773–2789. https://doi.org/10.1080/10408398.2019.1658570

2. Awuchi, C. G., Ondari, E. N., Nwozo, S., Odongo, G. A., Eseoghene, I. J., Twinomuhwezi, H., Ogbonna, C. U., Upadhyay, A. K., Adeleye, A. O., & Okpala, C. O. R. (2022). Mycotoxins’ toxicological mechanisms involving humans, livestock and their associated health concerns: A review. Toxins, 14(3), 167. https://doi.org/10.3390/toxins14030167

3. Lázaro Á, Vila-Donat P, Manyes L. Emerging mycotoxins and preventive strategies related to gut microbiota changes: probiotics, prebiotics, and postbiotics - a systematic review. Food Funct. 2024b;15(18):8998–9023. https://doi.org/10.1039/d4fo01705f

4. Thursby, E., & Juge, N. (2017). Introduction to the human gut microbiota. Biochem. J. 474(11), 1823–1836. https://doi.org/10.1042/BCJ20160510

5. Donati Zeppa S, Agostini D, Gervasi M, Annibalini G, Amatori S, Ferrini F, et al. Mutual interactions among exercise, sport supplements and microbiota. Nutrients. 2019;12(1):17. https://doi.org/10.3390/nu12010017

6. Yang Y, Lv L, Shi S, Cai G, Yu L, Xu S, et al. Polysaccharide from walnut green husk alleviates liver inflammation and gluconeogenesis dysfunction by altering gut microbiota in ochratoxin A-induced mice. Carbohydr Polym. 2023;322:121362. https://doi.org/10.1016/j.carbpol.2023.121362

7. Trefts E, Gannon M, Wasserman DH. The liver. Curr Biol. 2017;27(21):R1147–R1151. https://doi.org/10.1016/j.cub.2017.09.019

8. Lázaro, Á., Frangiamone, M., de Las Heras, M., & Ruiz, M. J. (2026b). Mycotoxins, gut microbiota alterations and liver disease in animals: A scoping review. Cell Biology and Toxicology. https://doi.org/10.1007/s10565-026-10156-5

Acknowledgements

The author would like to thank Massimo Frangiamone, Marcelo de las Heras and María José Ruiz for their contributions to the original research on which this article is based, as well as for the valuable academic discussions that helped contextualize the results.

*This article has been adapted for academic purposes, with the inclusion of bibliographic references formatted according to APA style. It is derived from a research study published in the Cell Biology and Toxicology journal entitled “Mycotoxins, gut microbiota alterations and liver disease in animals: A scoping review”, and it is used as teaching material.