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Melatonin (MT) has been shown to alleviate inflammation in organs and remodel gut microbiota in animals and humans. However, the underlying mechanism by which MT alleviates AFB1\u2010induced liver injury remains unclear. In the present study, MT pretreatment markedly increased the expression of intestinal tight junction proteins (ZO\u20101, Occludin, and Claudin\u20101), decreased intestinal permeability, reduced production of gut\u2010derived Lipopolysaccharide (LPS) and remodeled gut microbiota, ultimately alleviated AFB1\u2010induced liver injury in mice. Interestingly, MT pretreatment failed to exert beneficial effects on the intestine and liver in antibiotic\u2010treated mice. Meanwhile, MT pretreatment significantly increased the farnesoid X receptor\u00a0(FXR) protein expression of ileum, and decreased the TLR4\/NF\u2010\u03baB signaling pathway\u2010related messenger RNA\u00a0(mRNA) and proteins (TLR4, MyD88, p\u2010p65, and p\u2010I\u03baB\u03b1) expression in livers of AFB1\u2010exposed mice. Subsequently, pretreatment by Gly\u2010\u03b2\u2010MCA, an intestine\u2010selective FXR inhibitor, blocked the alleviating effect of MT on liver injury through increasing the liver\u2010specific expression of TLR4\/NF\u2010\u03baB signaling pathway\u2010related mRNA and proteins (TLR4, MyD88, p\u2010p65, and p\u2010I\u03baB\u03b1). In conclusion, MT pretreatment ameliorated AFB1\u2010induced liver injury and the potential mechanism may be related to regulate gut microbiota\/intestinal FXR\/liver TLR4 signaling axis, which provides a strong evidence for the protection of gut\u2010derived liver inflammation.<\/jats:p>","DOI":"10.1111\/jpi.12812","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T03:31:41Z","timestamp":1654140701000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":168,"title":["Melatonin mitigates aflatoxin B1\u2010induced liver injury via modulation of gut microbiota\/intestinal FXR\/liver TLR4 signaling axis in mice"],"prefix":"10.1111","volume":"73","author":[{"given":"Shuiping","family":"Liu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Nanjing Agricultural University Nanjing Jiangsu China"},{"name":"Institute of Animal Nutritional Health Nanjing Agricultural University 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