Published in Nature Communications, the findings showed that berberine (BBR) alone or berberine with probiotics is more effective in reducing the amount of glycated haemoglobin as compared to taking probiotics alone.
The trial randomised 409 participants into four groups.
One group took BBR pills plus probiotics powder, the other took BBR pills alone, the third group took probiotics powder alone, and the last group took placebo.
By the end of the trial, the group which took in berberine and probiotics had greatest reduction in the amount of glycated haemoglobin, HbA1c.
The percentage of HbA1c found in their blood dropped from 7.66 ± 0.82 to 6.62 ± 0.66, which was a 1.04 drop.
The next most effective outcome was seen in the group that took BBR alone, where the percentage of HbA1c fell from 7.68 ± 0.76 to 6.71 ± 0.77, which was a 0.99 decrease.
The groups which took placebo or probiotics did not see significant reduction in their level of HbA1c, since their HbA1c only dropped by 0.59 and 0.53 respectively.
Reasons
The two most effective interventions led to changes in the relative abundance of 78 bacteria species.
For instance, BBR depleted the bacteria species that mainly produce single sugar or short chain fatty acids (SCFAs) that from fermenting polysaccharides or oligosaccharides. These include bacteria such as Roseburia spp., Ruminococcus bromii, Faecalibacterium prausnitzii and Bifidobacterium spp.
Further metagenomics and metabolomic studies found that the BBR’s blood sugar lowering effect is due to the bacteria ruminococcus bromii – which plays a key role in degrading starch.
The bacteria inhibit production of bile acids key in regulating metabolic homeostasis. In this case, it inhibited the production of the deoxycholic acid species (DCAs).
“R. bromii could be the target of BBR in the gut microbiome to reduce the microbial production of secondary bile acid that is associated with the effective glycaemic control achieved with BBR.
“The study thus reports a human microbial related mechanism underlying the anti-diabetic effect of BBR on type II diabetes,” the researchers said.
BBR also elevated the bacterial response functions similar to the diabetes treatment medicine metformin, said the researchers.
BBR’s good and bad
On the other hand, the groups which took BBR saw improvements in other metabolic parameters, such as a lower fasting plasma glucose, blood triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels.
Yet, at the same time, the BBR treatment also induced more gastrointestinal side effects.
“More participants experienced gastrointestinal adverse events in the BBR-treated groups than that in the placebo or probiotics groups.
“(However), the adverse events did not affect the antidiabetic effect of BBR or gut microbiome features in this study with a 3-month treatment, again the concern needs to be addressed in trials with longer intervention duration,” the researchers said.
Probiotics’ role
Probiotics supplementation played a more significant role in controlling blood sugar level in older participants age 50 and above.
“Our study failed to find significant metabolic improvement with probiotic supplementation in type II diabetic patients, except when it was used in combination with BBR in the older participants.
“This was consistent with the conclusion from preponderant literatures that probiotics have limited effects in the treatment of metabolic diseases,” the researchers said.
However, they also said that such findings could be the result of bacteria strain-specific functional variations, hence the need for a more precise strategy for probiotics treatment.
The study was funded by grants from China’s national research funds, such as the National Key R&D Program of China.
Source: Nature Communications
Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)
doi: 10.1038/s41467-020-18414-8
Authors: Yifei Zhang et al
