Endogenous ethanol produced by intestinal bacteria induces mitochondrial dysfunction in non-alcoholic fatty liver disease.

Journal of Gastroenterology and Hepatology
Xiao ChenJing Yuan

Abstract

A causal relationship between changes of the gut microbiome and non-alcoholic fatty liver disease (NAFLD) remains unclear. We demonstrated that endogenous ethanol (EnEth) produced by intestinal microbiota is likely a causative agent of NAFLD. Two mutants with different alcohol-producing abilities, namely, W14-adh and W14Δadh, were constructed using the clinical high alcohol-producing (HiAlc) Klebsiella pneumoniae strain W14 as a parent. Damage to hepatocytes caused by bacteria with different alcohol-producing capacities was evaluated (EtOH group as positive control). The ultrastructural changes of mitochondria were assessed via transmission electron microscopy (TEM). Hepatic levels of mitochondrial reactive oxygen species (ROS), DNA damage, and adenosine triphosphate were examined. The results illustrated that steatosis was most severe in the W14-adh group, followed by the W14 group, whereas the W14Δadh group had few fatty droplets. TEM and examination of related protein expression revealed that the mitochondrial integrity of HepG2 hepatocytes was considerably damaged in the EtOH and bacteria treatment groups. The impaired mitochondrial function in HepG2 hepatocytes was evidenced by reduced adenosine triphosphate content and in...Continue Reading

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Citations

Jul 29, 2020·International Journal of Molecular Sciences·Jiezhong Chen, Luis Vitetta
Apr 23, 2021·United European Gastroenterology Journal·Ahmed B BayoumyMaarten E Tushuizen
May 13, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Tingshuai WangDewen Mao
May 25, 2021·Archives of Toxicology·Joost BoeckmansTamara Vanhaecke
Jun 3, 2021·International Journal of Molecular Sciences·Agostino Di CiaulaPiero Portincasa

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