Zearalenone enhances TSST-1 production by intestinal Staphylococcus and increases uterine immune stress in rats

Zearalenone (ZEA), a mycotoxin prevalent in food crops, poses significant health risks, particularly through its impact on the gut-uterus axis. This study assessed the effects of a 5 mg/kg body weight ZEA dosage in female SD rats, focusing on gut microbiota alterations, inflammatory responses, and uterine changes. Our findings revealed substantial shifts in microbial composition, including significant reductions in beneficial genera such as Akkermansia and Ruminococcaceae and marked increases in pathogenic staphylococci, which correlated with elevated levels of toxic shock syndrome toxin-1 (TSST-1) in serum and uterine tissue. RNA sequencing of uterine samples indicated activation of the extracellular matrix (ECM) pathway, along with significant upregulation of MMP-2 and TIMP-2, enzymes associated with ECM remodelling. Correlation analysis showed a strong link between staphylococcal proliferation and ECM pathway activation, suggesting that ZEA-induced gut dysbiosis contributes to uterine inflammation and structural alterations. These results reveal how ZEA disrupts gut and uterine health, highlighting critical pathways that could serve as targets for future preventive and therapeutic strategies against mycotoxin exposure.