Jung-Eun Lee1, So Min Lee2, Jeeyoun Jung3. 1. Clinical Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-Gu 34054, Daejeon, Republic of Korea. Electronic address: steineun@kiom.re.kr. 2. Non-clinical Collaboration Team, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-Gu 34054, Daejeon, Republic of Korea. Electronic address: dasonya@kiom.re.kr. 3. Clinical Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-Gu 34054, Daejeon, Republic of Korea. Electronic address: jjy0918@kiom.re.kr.
Abstract
BACKGROUND: 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. PURPOSE: Our aim was to identify the microbiome-mediated effects of YJT on IR and associated NAFLD by integrating metagenomics and hepatic lipid profile. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. PURPOSE: Our aim was to identify the microbiome-mediated effects of YJT on IR and associated NAFLD by integrating metagenomics and hepatic lipid profile. METHODS: 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. RESULTS: 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. CONCLUSION: 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.