2. Academic Validation
  3. Melatonin mitigates aflatoxin B1-induced liver injury via modulation of gut microbiota/intestinal FXR/liver TLR4 signaling axis in mice

Melatonin mitigates aflatoxin B1-induced liver injury via modulation of gut microbiota/intestinal FXR/liver TLR4 signaling axis in mice

  • J Pineal Res. 2022 Sep;73(2):e12812. doi: 10.1111/jpi.12812.
Shuiping Liu 1 2 3,  Weili Kang 1 2 3,  Xinru Mao 1 2 3,  Lei Ge 1 2 3,  Heng Du 1 2 3,  Jinyan Li 1 2 3,  Lili Hou 1 2 3,  Dandan Liu 1 2 3,  Yulong Yin 4,  Yunhuan Liu 1 2 3,  Kehe Huang 1 2 3
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, China.
  • 2 Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing, Jiangsu, China.
  • 3 MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, China.
  • 4 College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, China.
PMID: 35652241 DOI: 10.1111/jpi.12812
Abstract

Aflatoxin B1 (AFB1) is a widespread contaminant in foods and feedstuffs, and its target organ is the liver. 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-induced liver injury remains unclear. In the present study, MT pretreatment markedly increased the expression of intestinal tight junction proteins (ZO-1, Occludin, and Claudin-1), decreased intestinal permeability, reduced production of gut-derived Lipopolysaccharide (LPS) and remodeled gut microbiota, ultimately alleviated AFB1-induced liver injury in mice. Interestingly, MT pretreatment failed to exert beneficial effects on the intestine and liver in antibiotic-treated mice. Meanwhile, MT pretreatment significantly increased the farnesoid X receptor (FXR) protein expression of ileum, and decreased the TLR4/NF-κB signaling pathway-related messenger RNA (mRNA) and proteins (TLR4, MyD88, p-p65, and p-IκBα) expression in livers of AFB1-exposed mice. Subsequently, pretreatment by Gly-β-MCA, an intestine-selective FXR inhibitor, blocked the alleviating effect of MT on liver injury through increasing the liver-specific expression of TLR4/NF-κB signaling pathway-related mRNA and proteins (TLR4, MyD88, p-p65, and p-IκBα). In conclusion, MT pretreatment ameliorated AFB1-induced 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-derived liver inflammation.

Keywords

TLR4/NF-κB signaling pathway; aflatoxin B1; farnesoid X receptor; gut-liver axis; intestinal barrier; liver inflammation; melatonin.

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