Lycopene Attenuates T2 Mycotoxin-Induced Hepatotoxicity and Dysbiosis by Activating PPAR Signaling

Simple SummaryT-2 toxin, a widespread mycotoxin, induces hepatotoxicity and gut dysbiosis, with limited mitigation strategies. This study demonstrates that lycopene protects against T-2 mycotoxicosis in mice by integrating microbiota restoration with hepatic metabolic reprogramming. Lycopene suppressed pro-inflammatory cytokines, alleviated oxidative stress, and enriched beneficial Muribaculum while suppressing pathogenic Escherichia. Mechanistically, lycopene de-repressed Peroxisome proliferator-activated receptor (PPAR) signaling and restored fatty acid oxidation and phase I detoxification gene expression. A hormetic dose–response was evident: low-dose lycopene outperformed high-dose lycopene, underscoring non-linear efficacy. These findings position lycopene as a candidate feed additive targeting the gut–liver–PPAR axis, though dose optimization remains critical for translation.Exposure to T2 toxin is known to induce hepatotoxicity and gut dysbiosis, yet effective dietary interventions remain underexplored. This study investigates the hepatoprotective and microbiota-modulating effects of lycopene against T2 toxin-induced toxicity in mice. Mice were exposed to T2 toxin with or without lycopene supplementation at low and high doses. The hepatic function, oxidative stress markers, inflammatory gene expression, detoxification pathway activity, and gut microbiota composition were assessed using histological, biochemical, and molecular analyses. T2 toxin exposure resulted in significant weight loss, oxidative liver damage, and gut dysbiosis—marked by a decline in beneficial phyla and an increase in pathogenic bacteria. Hepatic injury was accompanied by upregulated pro-inflammatory genes and downregulated PPAR pathway genes, leading to impaired lipid metabolism and disrupted liver histology. Lycopene supplementation effectively attenuated these effects: it reduced oxidative stress, enhanced antioxidant defense, lowered inflammatory markers, and restored gut microbial balance. Furthermore, lycopene upregulated PPAR pathway and phase I detoxification genes. Notably, the low-dose lycopene regimen demonstrated superior efficacy compared to the high-dose regimen. In conclusion, lycopene, particularly at a low dose, confers significant protection against T2 toxin-induced hepatotoxicity and gut dysbiosis, highlighting its potential as a dietary strategy for mitigating mycotoxin-induced health risks.