Li Xiuxia, Wang Yanping, Xing Yilan, Xing Renxin, Liu Yongsheng, Xu Yinsheng
Eastern Hospital, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.
Hepatol Res. 2020 Jan;50(1):5-14. doi: 10.1111/hepr.13444. Epub 2020 Jan 5.
Gut microbiota are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Silybin (Sil), a naturally occurring hepatoprotective agent, is widely used for treating NAFLD. Whether Sil affects gut microbiota during its actions in treating NAFLD is unknown. We aimed to examine the effect of Sil on intestinal flora dysbiosis induced by a high-fat diet (HFD).
After 10 weeks of feeding normal chow diet or HFD, mice were given a daily gavage for 8 weeks. Cecal contents were harvested for study of short-chain fatty acids, bile acids, and gut microbiota alteration.
Sil showed protective effects against dietary-induced obesity and liver steatosis; accordingly, gut microbiota composition changed. At the phylum level, compared with the HFD group, mice in the Sil-treated group had significantly lower levels of Firmicutes, and the ratio of Firmicutes-to-Bacteroidetes was lower (P < 0.05). At the genus level, the Sil-treated group have significantly lower levels of Lachnoclostridium, Lachnospiraceae_UCG-006, and Mollicutes_RF9, which were reported to be potentially related to diet-induced obesity, and increased levels of Blautia (P < 0.05), Akkermansia (P < 0.05), and Bacteroides (P < 0.05), which are known to have a beneficial effect on improving NAFLD. Sil also showed an inhibitory effect on well-known beneficial bacteria, such as Alloprevotella and Lactobacillus. Furthermore, the production of acetate, propionate, and butyrate increased, whereas the generation of formate and conversion of cytotoxic secondary metabolites (lithocholic acid and deoxy-cholic acid) decreased in mice treated with Sil.
Sil might have beneficial effects on ameliorating NAFLD and mediating HFD-induced change of gut microbiota composition, followed by major changes in secondary metabolites, such as short-chain fatty acids and bile acids.
肠道微生物群参与非酒精性脂肪性肝病（NAFLD）的发病机制。水飞蓟宾（Sil）是一种天然存在的肝脏保护剂，广泛用于治疗NAFLD。Sil在治疗NAFLD的过程中是否会影响肠道微生物群尚不清楚。我们旨在研究Sil对高脂饮食（HFD）诱导的肠道菌群失调的影响。
在给予正常饲料或HFD喂养10周后，小鼠每天接受灌胃8周。收集盲肠内容物用于研究短链脂肪酸、胆汁酸和肠道微生物群的变化。
Sil对饮食诱导的肥胖和肝脏脂肪变性具有保护作用；相应地，肠道微生物群组成发生了变化。在门水平上，与HFD组相比，Sil治疗组小鼠的厚壁菌门水平显著降低，厚壁菌门与拟杆菌门的比例更低（P<0.05）。在属水平上，Sil治疗组的毛螺菌属、毛螺菌科_UCG-006和柔膜菌纲_RF9水平显著降低，据报道这些与饮食诱导的肥胖潜在相关，而布劳特氏菌属（P<0.05）、阿克曼氏菌属（P<0.05）和拟杆菌属（P<0.05）水平升高，已知这些对改善NAFLD有有益作用。Sil对诸如别普雷沃菌属和乳杆菌属等知名有益细菌也有抑制作用。此外，Sil治疗的小鼠中乙酸、丙酸和丁酸的产生增加，而甲酸产生和细胞毒性次级代谢产物（石胆酸和脱氧胆酸）的转化减少。
Sil可能对改善NAFLD和介导HFD诱导的肠道微生物群组成变化有益，随后短链脂肪酸和胆汁酸等次级代谢产物发生重大变化。
