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

Publisher: Baishideng Publishing Group Country of Publication: United States NLM ID: 100883448 Publication Model: Print Cited Medium: Internet ISSN: 2219-2840 (Electronic) Linking ISSN: 10079327 NLM ISO Abbreviation: World J Gastroenterol Subsets: MEDLINE

Publication: 2014- : Pleasanton, CA : Baishideng Publishing Group
Original Publication: Beijing : WJG Press, c1998-

Dysbiosis/*metabolism ; Gastrointestinal Microbiome/*physiology ; Liver Cirrhosis/*metabolism ; Non-alcoholic Fatty Liver Disease/*microbiology; Animals ; Choline Deficiency/metabolism ; Disease Models, Animal ; Dysbiosis/microbiology ; Feces/chemistry ; Feces/microbiology ; Gastrointestinal Microbiome/genetics ; Humans ; Intestines/microbiology ; Intestines/pathology ; Liver Cirrhosis/microbiology ; Liver Cirrhosis/pathology ; Male ; Metabolome ; Methionine/deficiency ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/metabolism ; RNA, Ribosomal, 16S/isolation & purification

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, 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.
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 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.
Conclusion: The MCD diet induced persistent alterations in the gut microbiota and metabolome.
Competing Interests: Conflict-of-interest statement: There is no conflict of interest in this study.

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Keywords: Gut microbiota; Metabolome; Methionine-choline deficient diet; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis

0 (RNA, Ribosomal, 16S)
AE28F7PNPL (Methionine)

Date Created: 20180623 Date Completed: 20181024 Latest Revision: 20181114

20231215

PMC6010937

10.3748/wjg.v24.i23.2468

29930468