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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\u2014marked 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.<\/jats:p>","DOI":"10.3390\/biology15040347","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:37:28Z","timestamp":1771245448000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lycopene Attenuates T2 Mycotoxin-Induced Hepatotoxicity and Dysbiosis by Activating PPAR Signaling"],"prefix":"10.3390","volume":"15","author":[{"given":"Wael","family":"Ennab","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3722-7220","authenticated-orcid":false,"given":"Saber Y.","family":"Adam","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"},{"name":"Biomedical Research Institute, Darfur University College, South Darfur State, Nyala 155, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8529-1147","authenticated-orcid":false,"given":"Hao-Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghaid J.","family":"Al-Rabadi","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, Mutah University, Karak 61710, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Hu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiome Abdelmaguid","family":"Baiome","sequence":"additional","affiliation":[{"name":"Parasitology and Animal Diseases Institute, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5898-845X","authenticated-orcid":false,"given":"Kaiqi","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4015-2845","authenticated-orcid":false,"given":"Abdelkareem A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute, Darfur University College, South Darfur State, Nyala 155, Sudan"},{"name":"Department of Physiology and Biochemistry, Faculty of Veterinary Sciences, University of Nyala, Nyala 155, Sudan"},{"name":"Department of Veterinary Sciences, Faculty of Animal and Veterinary Sciences, Botswana University of Agriculture and Natural Resources, Gaborone 0027, Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6652-2504","authenticated-orcid":false,"given":"In Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Animal Resource and Science, Dankook University, Cheonan 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madesh","family":"Muniyappan","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0500-5292","authenticated-orcid":false,"given":"Demin","family":"Cai","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112027","DOI":"10.1016\/j.fct.2021.112027","article-title":"The nephrotoxicity of T-2 toxin in mice caused by oxidative stress-mediated apoptosis is related to Nrf2 pathway","volume":"149","author":"Zhang","year":"2021","journal-title":"Food Chem. 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