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

• Published in: Nature communications Vol. 11; no. 1; pp. 1 - 12
• Main Authors: Zhang, Yifei, Gu, Yanyun, Ren, Huahui, Wang, Shujie, Zhong, Huanzi, Zhao, Xinjie, Ma, Jing, Gu, Xuejiang, Xue, Yaoming, Huang, Shan, Yang, Jialin, Chen, Li, Chen, Gang, Qu, Shen, Liang, Jun, Qin, Li, Huang, Qin, Peng, Yongde, Li, Qi, Wang, Xiaolin, Kong, Ping, Hou, Guixue, Gao, Mengyu, Shi, Zhun, Li, Xuelin, Qiu, Yixuan, Zou, Yuanqiang, Yang, Huanming, Wang, Jian, Xu, Guowang, Lai, Shenghan, Li, Junhua, Ning, Guang, Wang, Weiqing
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06-10-2020; Nature Portfolio
• Subjects: 13/106; 45/23; 631/326/2565/2142; 692/163/2743/137/773; 82/58; 96/1; Humanities and Social Sciences; multidisciplinary; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-18414-8

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).
The gut microbiome affects systemic metabolism and is a therapeutic target for type 2 diabetes. Here the authors demonstrate in a randomized controlled trial that effects of berberine, a plant alkaloid known to lower blood glucose, may be explained by the inhibition of
Ruminococcus bromii
mediated biotransformation of the bile acid deoxycholic acid.