Published online Jun 21, 2018. doi: 10.3748/wjg.v24.i23.2468
Peer-review started: March 1, 2018
First decision: March 15, 2018
Revised: March 27, 2018
Accepted: May 11, 2018
Article in press: May 11, 2018
Published online: June 21, 2018
The contributing role of the gut microbiota in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been extensively studied.
Gut microbiota dysbiosis in NASH is mainly depicted as an endpoint, and little is known regarding the microbiota disturbances during NASH progression.
Our goal was to investigate dynamic changes in the gut microbiota and its metabolism during the progression from simple hepatic steatosis to NASH in mice fed a methionine-choline-deficient (MCD) diet.
C57BL/6J mice were equally divided into four groups and fed either a methionine-choline-sufficient diet for 2 or 4 wk (the Control 2w group and Control 4w group, respectively) or the MCD diet for 2 or 4 wk (the MCD 2w group and MCD 4w group, respectively) (n = 6 per group). Liver injury, fibrosis, intestinal barrier function, and the fecal microbiome and metabolome were studied.
The mice fed with the MCD diet for 2 wk developed simple hepatic steatosis, which progressed to prominent NASH with liver fibrosis after 4 wk. Compared with the control diet, the MCD diet induced gradual intestinal barrier impairment and gut microbiota dysbiosis; the fecal metabolomic profile was also substantially altered by the MCD diet.
The MCD diet induced persistent alteration of the gut microbiota and metabolome.
We may have for the first time shown that an MCD diet induced persistent gut microbiota and metabolome deterioration. Fundamental observations of these alterations will provide new insight into NASH-associated intestinal disorder and gut-targeted therapies for NASH.