Nonalcoholic fatty liver disease (NAFLD), a prelude to cirrhosis and hepatocellular carcinoma, was considered to be associated with gut microbiota. However, causal relationship between microbiota and NAFLD remains unclear. We showed that high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) was significantly associated with up to 60% of NAFLD patients. Gavage administration of HiAlc Kpn induced typical pathological changes of hepatic steatosis and similar gene expression profiles in NAFLD murine, compared to those of alcohol intake. Comprehensive investigations in mice including gnotobiotic gavage and microbiota transplant demonstrated that HiAlc Kpn strains are the causative agents of NAFLD and lead to mitochondrial dysfunction and steatosis through 2,3-butanediol pathway. Feeding with high-fat diet and HiAlc Kpn aggravated disease progression and severity, while glucose intake promoted detectable blood alcohol concentration, which represents a promising marker for clinical diagnosis. All these findings augmented our current knowledge of NAFLD.
Yuan, Jing and Wei, Xiao and Zhao, Xiangna and Chen, Chen and Lu, Jing and Cheng, Weiwei and Li, Boxin and Li, Huan and Lin, Weishi and Tian, Changyu and Zhao, Jiangtao and Han, Juqiang and An, Daizhi and Wei, Hong and Zheng, Minghua and Ma, Xuejun and Li, Wei and Wang, Xuesong and Chen, Xiao and Zhang, Zheng and Zeng, Hui and Ying, Sun and Wu, JianXin and Yang, Ruifu and Liu, Di, High Alcohol-Producing Klebsiella Pneumonia is a Bacterial Culprit of Fatty Liver Disease. Available at SSRN: https://ssrn.com/abstract=3376661 or http://dx.doi.org/10.2139/ssrn.3376661
This version of the paper has not been formally peer reviewed.
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