Dynamic alterations in the gut microbiota and metabolome during the development of methionine-choline-deficient diet-induced nonalcoholic steatohepatitis

Jun 23, 2018World journal of gastroenterology

Changes in gut bacteria and metabolism during the development of diet-induced fatty liver disease

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Abstract

The MCD diet induced persistent alterations in gut microbiota and metabolome in mice.

Mice on the MCD diet exhibited simple liver fat accumulation and slight gut barrier impairment after 2 weeks.
After 4 weeks on the MCD diet, mice developed pronounced nonalcoholic steatohepatitis (NASH) and more severe gut barrier damage.
The MCD diet caused significant gut microbiota changes, including decreased levels of certain beneficial bacteria and increased levels of others.
Fecal metabolomic profiles were significantly altered by the MCD diet, with specific fatty acids identified as potential biomarkers at both 2 and 4 weeks.

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AIM: To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis (NASH) development in mice fed a methionine-choline-deficient (MCD) diet.

METHODS: 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,= 6) or 4 wk (Control 4w group,= 6) or the MCD diet for 2 wk (MCD 2w group,= 6) or 4 wk (MCD 4w group,= 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. n n n n

RESULTS: 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 ofand the ()group (< 0.001 and< 0.05, respectively) and a significant increase in Ruminococcaceae UCG 014 abundance (< 0.05) after 2 wk. At 4 wk, the MCD diet significantly reduced the promising probioticlevels and markedly promotedabundance (< 0.05, and< 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. Alistipes Eubacterium coprostanoligenes P P P Bifidobacterium Bacteroides P P

CONCLUSION: The MCD diet induced persistent alterations in the gut microbiota and metabolome.

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Dynamic alterations in the gut microbiota and metabolome during the development of methionine-choline-deficient diet-induced nonalcoholic steatohepatitis

Abstract

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