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).
Highlights
Human gut microbiome is a promising target for managing type 2 diabetes (T2D)
Similar to metformin, the specific in vivo target of BBR has barely been clarified and its poor oral bioavailability has suggested a potential effect on the gut microbiome. 16S rRNA genesequencing studies in rodents have shown significant gut microbiota alterations induced by BBR and several microbialrelated mechanisms, including the potential to alter short-chain fatty acids (SCFAs) and bile acids (BAs) metabolism, have been found to underlie the metabolic benefits of BBR28–31
To determine which commensal bacteria affected by BBR might mediate its inhibitory effect on microbial BA metabolism, we further examined the correlations of the post-treatment relative abundances (RAs) of key BBR responsive species (Supplementary Fig. 2) with the changes in clinical outcomes and the changes in plasma BA levels
Summary
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. The key role of gut microbiota in regulating host metabolism and the associations of gut microbial dysbiosis with the development of obesity and diabetes has been extensively explored[4,5,6,7,8,9,10] Evidence from both human and animal studies has suggested that the gut microbiome serves as the common route to mediate the therapeutic effects of bariatric surgery, diet control and antidiabetic medications[4,11,12,13,14,15]. Comprehensive metagenomics and metabolomics analyses are employed to investigate the potential for regulating the gut microbiome of BBR and/or probiotics treatments, and how these gut microbial changes correlated with the antidiabetic effect after a 7-day antibiotic pretreatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
