State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
Department of Chemotherapy 2, Wenzhou Central Hospital, Wenzhou 325000, Zhejiang Province, China.
World J Gastroenterol. 2018 Jun 21;24(23):2468-2481. doi: 10.3748/wjg.v24.i23.2468.
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, = 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.
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 and 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 probiotic levels and markedly promoted abundance ( < 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.
The MCD diet induced persistent alterations in the gut microbiota and metabolome.
研究蛋氨酸-胆碱缺乏（MCD）饮食诱导的非酒精性脂肪性肝炎（NASH）发展过程中肠道微生物群和代谢物的变化。
将 24 只雄性 C57BL/6J 小鼠等分为 4 组，分别给予蛋氨酸-胆碱充足饮食 2 周（对照组 2w 组，n = 6）或 4 周（对照组 4w 组，n = 6），或 MCD 饮食 2 周（MCD 2w 组，n = 6）或 4 周（MCD 4w 组，n = 6）。喂养 2 周和 4 周后，评估肝损伤、纤维化和肠道屏障功能。采用 16s rRNA 深度测序和气相色谱-质谱联用技术研究粪便微生物群和代谢组。
MCD 饮食喂养 2 周后，小鼠出现单纯性肝脂肪变性和轻微的肠道屏障恶化。然而，喂养 MCD 饮食 4 周后，小鼠发展为明显的 NASH 伴肝纤维化，肠道屏障受损更为严重。与对照饮食相比，MCD 饮食诱导逐渐的肠道微生物群失调，表现为双歧杆菌和拟杆菌属丰度显著降低（ < 0.001 和 < 0.05，分别），而 Ruminococcaceae UCG 014 丰度显著增加（ < 0.05）。在 4 周时，MCD 饮食显著降低了有前途的益生菌双歧杆菌属丰度，并显著增加了肠杆菌科丰度（ < 0.05 和 < 0.01，分别）。MCD 饮食还显著改变了粪便代谢组谱：在 2 周时，花生四烯酸、十六烷、棕榈酸和二十四烷被选为与相应对照组有显著差异的潜在生物标志物，而在 4 周时，胆酸、胆固醇、花生四烯酸、二十四烷和硬脂酸被选为潜在生物标志物。
MCD 饮食诱导肠道微生物群和代谢组的持续改变。
