Structural Alteration of Gut Microbiota during the Amelioration of Human Type 2 Diabetes with Hyperlipidemia by Metformin and a Traditional Chinese Herbal Formula: a Multicenter, Randomized, Open Label Clinical Trial
Xiaolin Tong,
Jia Xu,
Fengmei Lian,
Xiaotong Yu,
Yufeng Zhao,
Lipeng Xu,
Menghui Zhang,
Xiyan Zhao,
Jian Shen,
Shengping Wu,
Xiaoyan Pang,
Jiaxing Tian,
Chenhong Zhang,
Qiang Zhou,
Linhua Wang,
Bing Pang,
Feng Chen,
Zhiping Peng,
Jing Wang,
Zhong Zhen,
Chao Fang,
Min Li,
Limei Chen,
Liping Zhao
Affiliations
Xiaolin Tong
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Jia Xu
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Fengmei Lian
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Xiaotong Yu
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Yufeng Zhao
Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Lipeng Xu
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Menghui Zhang
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Xiyan Zhao
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Jian Shen
Shanghai Centre for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Shengping Wu
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Xiaoyan Pang
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Jiaxing Tian
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Chenhong Zhang
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Qiang Zhou
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Linhua Wang
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Bing Pang
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Feng Chen
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Zhiping Peng
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Jing Wang
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Zhong Zhen
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Chao Fang
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Min Li
Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China
Limei Chen
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Liping Zhao
State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
ABSTRACT Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement. The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients. They significantly increased a coabundant group represented by Blautia spp., which significantly correlated with the improvements in glucose and lipid homeostasis. However, AMC showed better efficacies in improving homeostasis model assessment of insulin resistance (HOMA-IR) and plasma triglyceride and also exerted a larger effect on gut microbiota. Furthermore, only AMC increased the coabundant group represented by Faecalibacterium spp., which was previously reported to be associated with the alleviation of T2DM in a randomized clinical trial. Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria, such as Blautia and Faecalibacterium spp. IMPORTANCE Metabolic diseases such as T2DM and obesity have become a worldwide public health threat. Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases, and thus the gut microbiota serves as a promising target for disease control. In this study, we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs: metformin and a specifically designed Chinese herbal formula (AMC) for diabetic patients with hyperlipidemia. Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota. Blautia spp. were identified as being associated with improvements in glucose and lipid homeostasis for both drugs. AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels, which were associated with the enrichment of Faecalibacterium spp. In brief, these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula.
