Gut-liver-hypothalamus axis dysfunction in mycotoxin toxicity: mechanisms and protective roles of natural compounds

Mycotoxins, secondary toxic metabolites produced by filamentous fungi, pose significant health risks through contamination of food commodities such as grains. Major mycotoxins, including T-2 toxin, aflatoxins, and ochratoxin, are associated with a range of adverse health effects, particularly gastrointestinal disorders and hepatotoxicity. Increasing attention has been directed toward the gut-liver axis, which plays a critical role in mediating the systemic impact of these toxins, alongside growing interest in natural products as potential therapeutic agents. Natural compounds, including probiotics and antioxidants, have demonstrated the ability to mitigate mycotoxin toxicity through multiple mechanisms, such as toxin binding, inhibition of intestinal absorption, and biotransformation, mediated by pathways including Nrf2-ARE signaling and modulation of antioxidant enzyme activities. This review highlights the complex molecular mechanisms and signaling networks involved in mycotoxin toxicity, with particular emphasis on the gut-liver-hypothalamus axis. Disruption of gut microbiota homeostasis is recognized as a key initial event that compromises intestinal barrier integrity, facilitating toxin translocation to the liver and subsequent effects on hepatic function and hypothalamic hormonal regulation. Emerging evidence supports the potential of natural products as promising therapeutic strategies for restoring the balance of the gut-liver-hypothalamus axis and improving overall health outcomes; however, further research is needed to better elucidate their mechanisms of action and expand their application in the prevention and management of mycotoxin-related diseases.