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.