High Alcohol-Producing Klebsiella Pneumonia is a Bacterial Culprit of Fatty Liver Disease

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.