Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)

Yifei Zhang; Yanyun Gu; Huahui Ren; Shujie Wang; Huanzi Zhong; Xinjie Zhao; Jing Ma; Xuejiang Gu; Yaoming Xue; Shan Huang; Jialin Yang; Li Chen; Gang Chen; Shen Qu; Jun Liang; Li Qin; Qin Huang; Yongde Peng; Qi Li; Xiaolin Wang; Ping Kong; Guixue Hou; Mengyu Gao; Zhun Shi; Xuelin Li; Yixuan Qiu; Yuanqiang Zou; Huanming Yang; Jian Wang; Guowang Xu; Shenghan Lai; Junhua Li; Guang Ning; Weiqing Wang

doi:10.1038/s41467-020-18414-8

Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)

Yifei Zhang, Yanyun Gu, Huahui Ren, Shujie Wang, Huanzi Zhong, Xinjie Zhao, Jing Ma, Xuejiang Gu, Yaoming Xue, Shan Huang, Jialin Yang, Li Chen, Gang Chen, Shen Qu, Jun Liang, Li Qin, Qin Huang, Yongde Peng, Qi Li, Xiaolin WangPing Kong, Guixue Hou, Mengyu Gao, Zhun Shi, Xuelin Li, Yixuan Qiu, Yuanqiang Zou, Huanming Yang, Jian Wang, Guowang Xu, Shenghan Lai, Junhua Li, Guang Ning, Weiqing Wang

School of Medicine

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], −1.04[−1.19, −0.89]%) and BBR-alone group (−0.99[−1.16, −0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (−0.59[−0.75, −0.44]%, −0.53[−0.68, −0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).

Original language	English (US)
Article number	5015
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-18414-8
State	Published - Dec 1 2020

ASJC Scopus subject areas

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.1038/s41467-020-18414-8

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Zhang, Y., Gu, Y., Ren, H., Wang, S., Zhong, H., Zhao, X., Ma, J., Gu, X., Xue, Y., Huang, S., Yang, J., Chen, L., Chen, G., Qu, S., Liang, J., Qin, L., Huang, Q., Peng, Y., Li, Q., ... Wang, W. (2020). Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nature communications, 11(1), Article 5015. https://doi.org/10.1038/s41467-020-18414-8

Zhang, Y, Gu, Y, Ren, H, Wang, S, Zhong, H, Zhao, X, Ma, J, Gu, X, Xue, Y, Huang, S, Yang, J, Chen, L, Chen, G, Qu, S, Liang, J, Qin, L, Huang, Q, Peng, Y, Li, Q, Wang, X, Kong, P, Hou, G, Gao, M, Shi, Z, Li, X, Qiu, Y, Zou, Y, Yang, H, Wang, J, Xu, G, Lai, S, Li, J, Ning, G & Wang, W 2020, 'Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)', Nature communications, vol. 11, no. 1, 5015. https://doi.org/10.1038/s41467-020-18414-8

@article{c037e1de7eb44857a2314f4dc0a473d9,

title = "Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)",

abstract = "Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], −1.04[−1.19, −0.89]%) and BBR-alone group (−0.99[−1.16, −0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (−0.59[−0.75, −0.44]%, −0.53[−0.68, −0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).",

author = "Yifei Zhang and Yanyun Gu and Huahui Ren and Shujie Wang and Huanzi Zhong and Xinjie Zhao and Jing Ma and Xuejiang Gu and Yaoming Xue and Shan Huang and Jialin Yang and Li Chen and Gang Chen and Shen Qu and Jun Liang and Li Qin and Qin Huang and Yongde Peng and Qi Li and Xiaolin Wang and Ping Kong and Guixue Hou and Mengyu Gao and Zhun Shi and Xuelin Li and Yixuan Qiu and Yuanqiang Zou and Huanming Yang and Jian Wang and Guowang Xu and Shenghan Lai and Junhua Li and Guang Ning and Weiqing Wang",

note = "Funding Information: We thank all the patients whose participation made this study possible. We thank Drs. Dalong Zhu (Nanjin Drum Tower Hospital, Nanjing University Medical School, Jiangsu Province, China), Tao Yang (Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing University Medical School, Nanjing Jiangsu, China), Yanbing Li (The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China), Li Yan (Sun Yat-sen Memory Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China), Wei Gu (The Second Affiliated hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China), Lulu Chen (Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China), Fan Zhang (Peking University Shenzhen Hospital, Shenzhen, Guangdong, China), Qian Zhang (Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China), Lili Xia (Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China), Yujuan Fan (Central Hospital of Minhang district, Shanghai, China), Junping Wen (Fujian Provincial Hospital, Fuzhou, Fujian, China), Wei Xu (Xuzhou Central Hospital, Xu Zhou, Jiangsu, China), Yanyan Hu (Chang Hai Hospital, Second Military Medical University, Shanghai, China), Yufan Wang (Shanghai First People{\textquoteright}s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) and Xi Xia (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) for their collection of data and blood samples, and taking care of patients. We thank Zhiyun Zhao, Min Xu (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) and Karsten Kristiansen (Department of Biology, University of Copenhagen, Denmark; BGI-Shenzhen, Shenzhen, China) for all discussion of clinical, metagenomics data and multi-omics analysis. We thank the Northeast Pharmaceutical Group Co., Ltd, Shenyang, Liaoning, and Shanghai Jiaoda Onlly Co., Ltd, Shanghai, China, for providing BBR, probiotics and the Placs as courtesies. This study was funded by grants from the Fund of the Prevention and control of major chronic non-communicable diseases research of China (2018YFC1313804); the National Key R&D Program of China (2016YFC0901200); the Fund of the Shanghai Science and Technology Committee (number 16431900501); the National Nature Science Foundation of China (91857205, 81870555, 81930021); and the Fund of the Shenzhen Municipal Government of China (No. JCYJ20170817145809215). Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-18414-8",

language = "English (US)",

volume = "11",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)

AU - Zhang, Yifei

AU - Gu, Yanyun

AU - Ren, Huahui

AU - Wang, Shujie

AU - Zhong, Huanzi

AU - Zhao, Xinjie

AU - Ma, Jing

AU - Gu, Xuejiang

AU - Xue, Yaoming

AU - Huang, Shan

AU - Yang, Jialin

AU - Chen, Li

AU - Chen, Gang

AU - Qu, Shen

AU - Liang, Jun

AU - Qin, Li

AU - Huang, Qin

AU - Peng, Yongde

AU - Li, Qi

AU - Wang, Xiaolin

AU - Kong, Ping

AU - Hou, Guixue

AU - Gao, Mengyu

AU - Shi, Zhun

AU - Li, Xuelin

AU - Qiu, Yixuan

AU - Zou, Yuanqiang

AU - Yang, Huanming

AU - Wang, Jian

AU - Xu, Guowang

AU - Lai, Shenghan

AU - Li, Junhua

AU - Ning, Guang

AU - Wang, Weiqing

N1 - Funding Information: We thank all the patients whose participation made this study possible. We thank Drs. Dalong Zhu (Nanjin Drum Tower Hospital, Nanjing University Medical School, Jiangsu Province, China), Tao Yang (Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing University Medical School, Nanjing Jiangsu, China), Yanbing Li (The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China), Li Yan (Sun Yat-sen Memory Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China), Wei Gu (The Second Affiliated hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China), Lulu Chen (Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China), Fan Zhang (Peking University Shenzhen Hospital, Shenzhen, Guangdong, China), Qian Zhang (Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China), Lili Xia (Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China), Yujuan Fan (Central Hospital of Minhang district, Shanghai, China), Junping Wen (Fujian Provincial Hospital, Fuzhou, Fujian, China), Wei Xu (Xuzhou Central Hospital, Xu Zhou, Jiangsu, China), Yanyan Hu (Chang Hai Hospital, Second Military Medical University, Shanghai, China), Yufan Wang (Shanghai First People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) and Xi Xia (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) for their collection of data and blood samples, and taking care of patients. We thank Zhiyun Zhao, Min Xu (Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China) and Karsten Kristiansen (Department of Biology, University of Copenhagen, Denmark; BGI-Shenzhen, Shenzhen, China) for all discussion of clinical, metagenomics data and multi-omics analysis. We thank the Northeast Pharmaceutical Group Co., Ltd, Shenyang, Liaoning, and Shanghai Jiaoda Onlly Co., Ltd, Shanghai, China, for providing BBR, probiotics and the Placs as courtesies. This study was funded by grants from the Fund of the Prevention and control of major chronic non-communicable diseases research of China (2018YFC1313804); the National Key R&D Program of China (2016YFC0901200); the Fund of the Shanghai Science and Technology Committee (number 16431900501); the National Nature Science Foundation of China (91857205, 81870555, 81930021); and the Fund of the Shenzhen Municipal Government of China (No. JCYJ20170817145809215). Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

Y1 - 2020/12/1

N2 - Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], −1.04[−1.19, −0.89]%) and BBR-alone group (−0.99[−1.16, −0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (−0.59[−0.75, −0.44]%, −0.53[−0.68, −0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).

AB - Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], −1.04[−1.19, −0.89]%) and BBR-alone group (−0.99[−1.16, −0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (−0.59[−0.75, −0.44]%, −0.53[−0.68, −0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).

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SN - 2041-1723

VL - 11

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 5015

ER -

Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)

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