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
To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis (NASH) development in mice fed a methionine-choline-deficient (MCD) diet.
Twenty-four male C57BL/6J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk (Control 2w group, n = 6) or 4 wk (Control 4w group, n = 6) or the MCD diet for 2 wk (MCD 2w group, n = 6) or 4 wk (MCD 4w group, n = 6). Liver injury, fibrosis, and intestinal barrier function were evaluated after 2 and 4 wk of feeding. The fecal microbiome and metabolome were studied using 16s rRNA deep sequencing and gas chromatography-mass spectrometry.
The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk. After 4 wk of feeding with the MCD diet, however, the mice developed prominent NASH with liver fibrosis, and the intestinal barrier was more impaired. Compared with the control diet, the MCD diet induced gradual gut microbiota dysbiosis, as evidenced by a marked decrease in the abundance of Alistipes and the (Eubacterium) coprostanoligenes group (P < 0.001 and P < 0.05, respectively) and a significant increase in Ruminococcaceae UCG 014 abundance (P < 0.05) after 2 wk. At 4 wk, the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance (P < 0.05, and P < 0.01, respectively). The fecal metabolomic profile was also substantially altered by the MCD diet: At 2 wk, arachidic acid, hexadecane, palmitic acid, and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group, and at 4 wk, cholic acid, cholesterol, arachidic acid, tetracosane, and stearic acid were selected.
The MCD diet induced persistent alterations in the gut microbiota and metabolome.
Core tip: Nonalcoholic steatohepatitis (NASH) is increasingly prevalent as a remarkable problem worldwide. Increased evidence indicates the critical role of gut microbiota in NASH progression. We aimed to investigate the dynamic alterations in the gut microbiota and the related metabolites during NASH development in mice fed a methionine-choline-deficient (MCD) diet. We for the first time find that the MCD diet may induce persistent gut microbiota and metabolome deterioration.