High alcohol-producing causes fatty liver disease through 2,3-butanediol fermentation pathway .

High alcohol-producing (HiAlc ) in the gut microbiota had been demonstrated to be the causative agent of fatty liver disease (FLD). However, the catabolic pathways for alcohol production remain unclear. Here, we characterized the genome of HiAlc and medium alcohol-producing (MedAlc) and constructed an (an essential gene encoding alcohol dehydrogenase) knock-out HiAlc W14 strain (W14) using CRISPR-Cas9 system. Subsequently, we established the mouse model gavage administration of HiAlc W14 and W14 strains, respectively. Proteome and metabolome analysis showed that 10 proteins and six major metabolites involved in the 2,3-butanediol fermentation pathway exhibited at least a three-fold change or greater during intestinal growth. Compared with HiAlc W14-fed mice, W14-fed mice with weak alcohol-producing ability did not show apparent pathological changes at 4 weeks, although some steatotic hepatocytes were observed at 12 weeks. Our data demonstrated that carbohydrate substances are catabolized to produce alcohol and 2,3-butanediol the 2,3-butanediol fermentation pathway in HiAlc , which could be a promising clinical diagnostic marker. The production of high amounts of endogenous alcohol is responsible for the observed steatosis effects in hepatocytes .