Small study reveals metformin-induced changes in the gut microbiota of diabetes patients

The findings of a recent study suggest that metformin regulates glucose metabolism by altering specific gut bacteria rather than by causing a general increase in microbial diversity.
Table of Contents

What is already known
Metformin is mainly used to control high blood sugar in people with type 2 diabetes. The drug helps lower blood sugar levels, thus preventing complications related to diabetes such as kidney damage and vision issues. Previous studies suggested that metformin alters the composition of the gut microbiota, which in turn may contribute to its glucose-lowering effects. But the drug’s effects on gut microbes are still unclear.

What this research adds
Researchers analyzed the gut microbiota of 25 diabetes patients who received a daily dose of metformin for the first time. After 3 months of treatment, the variety and abundance of bacterial species in the gut microbiota decreased, with a reduction in the Firmicutes to Bacteroidetes ratio. Metformin treatment was linked to an increase in Escherichia-Shigella bacteria and a decrease in Romboutsia and Pseudomonas. The treatment also altered 17 metabolic pathways, including that of amino acids.

Conclusions
The findings suggest that metformin regulates glucose metabolism by altering specific gut bacteria rather than by causing a general increase in microbial diversity.

Metformin is mainly used to lower blood sugar levels in people with type 2 diabetes, thus preventing complications related to diabetes such as kidney damage and vision issues. Now, researchers have found that metformin may regulate glucose metabolism by altering specific gut bacteria.

The findings, published in Endocrine, may inform future work on the effects of metformin on gut bacteria. 

Previous research suggested that the drug alters the composition of the gut microbiota, which in turn may contribute to its glucose-lowering effects. “The influence of the microbiota on hypoglycemic agents is becoming more apparent,” the researchers say. However, they add, metformin’s effects on gut microbes are still unclear.

So, researchers led by Yuting Gao at the Chinese Academy of Medical Science and Peking Union Medical College in Beijing, China, set out to analyze the gut microbiota of 25 diabetes patients who received metformin for the first time.

Metformin-induced changes

Each study participant received a daily dose of 1500 mg of metformin, and the composition of their microbiota was analyzed at the start and after 1, 3 and 6 months of treatment.

After 3 months of treatment, the researchers observed a decrease in the variety and abundance of bacterial species in the gut microbiota — or the alpha-diversity. However, the beta-diversity, or the microbial diversity between samples from different patients, didn’t change. 

Metformin treatment was associated with a reduction in the Firmicutes to Bacteroidetes ratio as well as an increase in Escherichia-Shigella bacteria and a decrease in Romboutsia and Pseudomonas, the researchers also found.

Altered metabolism

The analysis revealed three different types of microbial alterations following metformin treatment: some bacterial genera only experienced temporary changes; others, such as Bacteroides, decreased steadily in abundance, whereas genera such as Lachnospiraceae and Faecalibacterium increased in abundance. 

The abundance of some of these gut bacteria was linked to the levels of triglycerides in the patients’ blood and other clinical parameters. Metformin treatment also appeared to alter 17 metabolic pathways, including that of amino acids.

The findings indicate that metformin regulates glucose metabolism by altering specific gut bacteria rather than by causing a general increase in microbial diversity, the authors say. “This may suggest gut microbiota targets in future studies on metabolic abnormalities caused by metformin.”