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).

Analysis of the effect of okra extract on the diversity of intestinal flora in diabetic rats based on 16S rRNA sequence

“…On the contrary, there were negatively correlated with diabetic indexes (FBG, AUGG, TC, TG, HDL-C, Food) and Firmicutes_bacterium_ASF500, Streptococcus_sp_GDLAMI.SD2, Ruminococcus_sp_YE281, indicating that these bacteria were anti-diabetes. Metagenomics and metabonomics studies found that the hypoglycaemic effect of berberine was mediated the activity of intestinal farnesoid X receptor (FXR) by inhibiting the biotransformation of deoxycholic acid (DCA) by Ruminococcus bromii (Zhang et al, 2020). California Stanford University School of Medicine (Sinha et al, 2020) found that Ruminococcaceae converting primary bile acids into secondary bile acids, which played a key role in the treatment of ulcerative colitis.…”

Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes

“…Berberine, a natural plant alkaloid extracted from Berberis aristata and Coptis chinensis , is reported to be an effective remedy for T2D ( 155 ). A recent randomized, double-blind, placebo-controlled trial conducted in China demonstrates that administration of berberine with probiotics improves HbA1C levels compared to the group treated with berberine alone ( 156 ). A meta-analysis of randomized controlled trials reported that diets supplemented with either prebiotics or symbiotics improved fasting blood glucose and HbA1C in patients with T2D ( 157 ).…”

Intestinal Microbiota—A Promising Target for Antiviral Therapy?

“…Given the potential risk of administering conventional medications, such as antibiotics, TCM has attracted increasing interest for many disease treatments, such as diabetes ( 153 ), ulcerative colitis (UC) ( 154 ) and kidney diseases ( 155 ), the mechanisms of which have been further demonstrated to be associated with the intestinal microbiota. The treatment of diabetes mellitus is one of the most typical examples showing that TCM’s regulatory effect on the intestinal flora exerts a therapeutic role ( 153 , 156 ). Berberine (BBR), which is extracted from a traditional Chinese herb, is used to alleviate symptoms of type 2 diabetes mellitus.…”