Fatty Liver Disease Caused by High-Alcohol-Producing Klebsiella pneumoniae.

Abstract

The underlying etiology of nonalcoholic fatty liver disease (NAFLD) is believed to be quite varied. Changes in the gut microbiota have been investigated and are believed to contribute to at least some cases of the disease, though a causal relationship remains unclear. Here, we show that high-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) is associated with up to 60% of individuals with NAFLD in a Chinese cohort. Transfer of clinical isolates of HiAlc Kpn by oral gavage into mice induced NAFLD. Likewise, fecal microbiota transplant (FMT) into mice using a HiAlc-Kpn-strain-containing microbiota isolated from an individual with NASH induced NAFLD. However, selective elimination of the HiAlc Kpn strain before FMT prevented NAFLD in the recipient mice. These results suggest that at least in some cases of NAFLD an alteration in the gut microbiome drives the condition due to excess endogenous alcohol production.

• Authors: Jing Yuan, Chen Chen, Jinghua Cui, Jing Lu, Chao Yan, Xiao Wei, Xiangna Zhao, NanNan Li, Shaoli Li, Guanhua Xue, Weiwei Cheng, Boxing Li, Huan Li, Weishi Lin, Changyu Tian, Jiangtao Zhao, Juqiang Han, Daizhi An, Qiong Zhang, Hong Wei, Minghua Zheng, Xuejun Ma, Wei Li, Xiao Chen, Zheng Zhang, Hui Zeng, Sun Ying, JianXin Wu, Ruifu Yang, Di Liu
• Journal: Cell metabolism (Cell Metab) Vol. 30 Issue 4 Pg. 675-688.e7 (10 01 2019) ISSN: 1932-7420 [Electronic] United States
• PMID: 31543403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Ethanol

Topics

• Animals
• Ethanol (metabolism)
• Fecal Microbiota Transplantation
• Gastrointestinal Microbiome
• Hep G2 Cells
• Humans
• Klebsiella pneumoniae (metabolism, pathogenicity)
• Male
• Mice
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (microbiology)