Ginsenoside Rb1 Improves Metabolic Disorder in High-Fat Diet-Induced Obese Mice Associated With Modulation of Gut Microbiota

Hong Zou; Man Zhang; Xiaoting Zhu; Liyan Zhu; Shuo Chen; Mingjing Luo; Qinglian Xie; Yue Chen; Kangxi Zhang; Qingyun Bu; Yuchen Wei; Tao Ye; Qiang Li; Xing Yan; Zhihua Zhou; Chen Yang; Yu Li; Haokui Zhou; Chenhong Zhang; Xiaoyan You; Guangyong Zheng; Guoping Zhao

doi:10.3389/fmicb.2022.826487

Ginsenoside Rb1 Improves Metabolic Disorder in High-Fat Diet-Induced Obese Mice Associated With Modulation of Gut Microbiota

Front Microbiol. 2022 Apr 19:13:826487. doi: 10.3389/fmicb.2022.826487. eCollection 2022.

Authors

Hong Zou^{1

2}, Man Zhang³, Xiaoting Zhu⁴, Liyan Zhu⁴, Shuo Chen⁵, Mingjing Luo⁵, Qinglian Xie², Yue Chen³, Kangxi Zhang³, Qingyun Bu³, Yuchen Wei⁶, Tao Ye⁴, Qiang Li⁷, Xing Yan⁸, Zhihua Zhou⁸, Chen Yang⁸, Yu Li², Haokui Zhou⁵, Chenhong Zhang⁹, Xiaoyan You^{3

10}, Guangyong Zheng¹¹, Guoping Zhao^{1

3

5

6

7

8

11}

Affiliations

¹ State Key Laboratory of Genetic Engineering, Department of Microbiology and Immunology, School of Life Sciences, Fudan University, Shanghai, China.
² Engineering Laboratory for Nutrition, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
³ Master Lab for Innovative Application of Nature Products, National Center of Technology Innovation for Synthetic Biology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
⁴ Zhejiang Hongguan Bio-Pharma Co., Ltd., Jiaxing, China.
⁵ CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
⁶ Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, China.
⁷ Suzhou BiomeMatch Therapeutics Co., Ltd., Shanghai, China.
⁸ CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.
⁹ State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
¹⁰ College of Food and Bioengineering, Henan University of Science and Technology, Luoyang, China.
¹¹ Bio-Med Big Data Center, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.

Abstract

Gut microbiota plays an important role in metabolic homeostasis. Previous studies demonstrated that ginsenoside Rb1 might improve obesity-induced metabolic disorders through regulating glucose and lipid metabolism in the liver and adipose tissues. Due to low bioavailability and enrichment in the intestinal tract of Rb1, we hypothesized that modulation of the gut microbiota might account for its pharmacological effects as well. Here, we show that oral administration of Rb1 significantly decreased serum LDL-c, TG, insulin, and insulin resistance index (HOMA-IR) in mice with a high-fat diet (HFD). Dynamic profiling of the gut microbiota showed that this metabolic improvement was accompanied by restoring of relative abundance of some key bacterial genera. In addition, the free fatty acids profiles in feces were significantly different between the HFD-fed mice with or without Rb1. The content of eight long-chain fatty acids (LCFAs) was significantly increased in mice with Rb1, which was positively correlated with the increase of Akkermansia and Parasuttereller, and negatively correlated with the decrease of Oscillibacter and Intestinimonas. Among these eight increased LCFAs, eicosapentaenoic acid (EPA), octadecenoic acids, and myristic acid were positively correlated with metabolic improvement. Furthermore, the colonic expression of the free fatty acid receptors 4 (Ffar4) gene was significantly upregulated after Rb1 treatment, in response to a notable increase of LCFA in feces. These findings suggested that Rb1 likely modulated the gut microbiota and intestinal free fatty acids profiles, which should be beneficial for the improvement of metabolic disorders in HFD-fed mice. This study provides a novel mechanism of Rb1 for the treatment of metabolic disorders induced by obesity, which may provide a therapeutic avenue for the development of new nutraceutical-based remedies for treating metabolic diseases, such as hyperlipidemia, insulin resistance, and type 2 diabetes.

Keywords: fecal metabolome; free fatty acid receptor; ginsenoside Rb1; gut microbiota; lipidomics; long-chain fatty acids; metabolic disorder.