2. Academic Validation
  3. Aflatoxin B1 Induces Intestinal Barrier Dysfunction by Regulating the FXR-Mediated MLCK Signaling Pathway in Mice and in IPEC-J2 Cells

Aflatoxin B1 Induces Intestinal Barrier Dysfunction by Regulating the FXR-Mediated MLCK Signaling Pathway in Mice and in IPEC-J2 Cells

  • J Agric Food Chem. 2022 Dec 29. doi: 10.1021/acs.jafc.2c06931.
Shuiping Liu 1 2 3,  Jinyan Li 1 2 3,  Weili Kang 1 2 3,  Yun Li 1,  Lei Ge 1 2 3,  Dandan Liu 1 2 3,  Yunhuan Liu 1 2 3,  Kehe Huang 1 2 3
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
  • 2 Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
  • 3 MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu Province, China.
PMID: 36579420 DOI: 10.1021/acs.jafc.2c06931
Abstract

Aflatoxin B1 (AFB1) is a widespread mycotoxin in food and feed. Although the liver is the main target organ of AFB1, the intestine is the first exposure organ to AFB1. However, the mechanism by which AFB1 induced intestinal barrier dysfunction via regulating the farnesoid X receptor (FXR)-mediated Myosin light chain kinase (MLCK) signaling pathway has rarely been studied. In vivo, AFB1 exposure significantly decreased the small intestine length and increased the intestinal permeability. Meanwhile, AFB1 exposure markedly suppressed the protein expressions of FXR, ZO-1, occludin, and claudin-1 and enhanced the protein expression of MLCK. In vitro, AFB1 exposure induced intestinal barrier dysfunction by the elevation in the FITC-Dextran 4 kDa flux and inhibition in the transepithelial electrical resistance in a dose-dependent manner. In addition, AFB1 exposure downregulated the mRNA and protein expressions of FXR, ZO-1, occludin, and claudin-1, redistributed the ZO-1 protein, and enhanced the protein expressions of MLCK and p-MLC. However, fexaramine (Fex, FXR Agonist) pretreatment markedly reversed the AFB1-induced FXR activity reduction, MLCK protein activation, and intestinal barrier impairment in vitro and in vivo. Moreover, pretreatment with the inhibition of MLCK with ML-7 significantly alleviated the AFB1-induced intestinal barrier dysfunction and tight junction disruption in vitro. In conclusion, AFB1 induced intestinal barrier impairment via regulating the FXR-mediated MLCK signaling pathway in vitro and in vivo and provided novel insights to prevent mycotoxin poisoning in the intestine.

Keywords

aflatoxin B1; farnesoid X receptor; intestinal barrier; myosin light chain kinase.

Figures
Products