Clinical Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-Gu 34054, Daejeon, Republic of Korea.
Non-clinical Collaboration Team, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-Gu 34054, Daejeon, Republic of Korea.
Phytomedicine. 2020 Dec;79:153354. doi: 10.1016/j.phymed.2020.153354. Epub 2020 Sep 21.
Gut microbiota play important roles in insulin homeostasis and the pathogenesis of non-alcoholic fatty liver diseases (NAFLD). Yijin-Tang (YJT), a traditional Korean and Chinese medicine, is used in the treatment of gastrointestinal diseases and obesity-related disorders such as insulin resistance (IR) and NAFLD.
Our aim was to identify the microbiome-mediated effects of YJT on IR and associated NAFLD by integrating metagenomics and hepatic lipid profile.
C57BL/6J mice were fed a normal chow diet (NC) or high-fat/high-cholesterol (HFHC) diet with or without YJT treatment. Hepatic lipid profiles were analyzed using liquid chromatography/mass spectrometry, and the composition of gut microbiota was investigated using 16S rRNA sequencing. Then, hepatic lipid profiles, gut microbiome, and inflammatory marker data were integrated using multivariate analysis and bioinformatics tools.
YJT improved NAFLD, and 39 hepatic lipid metabolites were altered by YJT in a dose-dependent manner. YJT also altered the gut microbiome composition in HFHC-fed mice. In particular, Faecalibaculum rodentium and Bacteroides acidifaciens were altered by YJT in a dose-dependent manner. Also, we found significant correlation among hepatic phosphatidylglycerol metabolites, F. rodentium, and γδ-T cells. Moreover, interleukin (IL)-17, which is secreted by the γδ-T cell when it recognizes lipid antigens, were elevated in HFHC mice and decreased by YJT treatment. In addition, YJT increased the relative abundance of B. acidifaciens in NC or HFHC-fed mice, which is a gut microbiota that mediates anti-obesity and anti-diabetic effects by modulating the gut environment. We also confirmed that YJT ameliorated the gut tight junctions and increased short chain fatty acid (SCFA) levels in the intestine, which resulted in improved IR.
These data demonstrated that gut microbiome and hepatic lipid profiles are regulated by YJT, which improved the IR and NAFLD in mice with diet-induced obesity.
肠道微生物群在胰岛素稳态和非酒精性脂肪性肝病（NAFLD）的发病机制中发挥重要作用。益津汤（YJT）是一种传统的韩中药物，用于治疗胃肠道疾病和肥胖相关疾病，如胰岛素抵抗（IR）和 NAFLD。
我们旨在通过整合宏基因组学和肝脂质谱来确定 YJT 对 IR 和相关 NAFLD 的微生物组介导作用。
C57BL/6J 小鼠喂食正常饮食（NC）或高脂肪/高胆固醇（HFHC）饮食，同时给予或不给予 YJT 治疗。使用液相色谱/质谱法分析肝脂质谱，使用 16S rRNA 测序研究肠道微生物群的组成。然后，使用多变量分析和生物信息学工具整合肝脂质谱、肠道微生物群和炎症标志物数据。
YJT 改善了 NAFLD，YJT 以剂量依赖的方式改变了 39 种肝脂质代谢物。YJT 还改变了 HFHC 喂养小鼠的肠道微生物群组成。特别是，YJT 以剂量依赖的方式改变了 Faecalibaculum rodentium 和 Bacteroides acidifaciens 的含量。此外，我们发现肝磷脂酰甘油代谢物、F. rodentium 和 γδ-T 细胞之间存在显著相关性。此外，当 γδ-T 细胞识别脂质抗原时分泌的白细胞介素（IL）-17 在 HFHC 小鼠中升高，并被 YJT 治疗降低。此外，YJT 增加了 NC 或 HFHC 喂养小鼠中 B. acidifaciens 的相对丰度，这种肠道微生物群通过调节肠道环境介导抗肥胖和抗糖尿病作用。我们还证实，YJT 改善了肠道紧密连接并增加了肠道中的短链脂肪酸（SCFA）水平，从而改善了 IR。
这些数据表明，肠道微生物群和肝脂质谱受 YJT 调节，改善了饮食诱导肥胖小鼠的 IR 和 NAFLD。
