The most successful treatment for type 2 diabetes may work by changing the makeup of gut bacteria.
Metformin is commonly prescribed to help people with type 2 diabetes control their blood sugar. It is also being tested as an anti-ageing treatment.
The drug is generally believed to work by reducing the amount of glucose made in the liver, which would in turn lower blood sugar levels. But some observations suggest this isn’t the whole story.
For instance, a slow-release version of the drug appears to be just as effective, even though only small amounts of it ever reach the liver. And metformin works just as well in people with genetic variants that stop it from getting to the liver.
Fredrik Bäckhed at the University of Gothenburg, Sweden, and José Manuel Fernàndez-Real at the University of Girona, Spain, wondered if gut bacteria might play a role in the drug’s action. After all, the trillions of bugs that line our intestines have been linked to a range of diseases, and are known to influence drug metabolism.
The pair and their colleagues recruited 40 volunteers who were newly diagnosed with type 2 diabetes. Each person was randomly assigned to take metformin or a placebo for four months. All of them were placed on a low-calorie diet.
During the study period, the collection of gut bacteria changed much more dramatically in those taking metformin. In particular, the drug seemed to encourage the growth of strains of bacteria called Akkermansia and Bifidobacterium. Lab experiments revealed that both types also grew faster in the presence of metformin.
The researchers then took stool samples from three people before and after a course of metformin and fed them to mice that were on a high-fat diet, to mimic human type 2 diabetes. The technique, known as a faecal transplant, is thought to pass beneficial bacteria from the gut of a healthy individual to a sickly one.
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Faeces taken from metformin-treated individuals seemed to improve glucose tolerance – a measure of how well animals can control blood sugar levels – in mice that received samples from two of the three donors. But faeces taken from people before their treatment had no effect on any of the mice.
Together, the results suggest that metformin at least partly works by encouraging the growth of gut bacteria such as Akkermansia, which can influence blood sugar levels. However, the researchers still don’t know how the bacteria might be doing this.
Bäckhed hopes that some people with diabetes might get similar benefits by modifying their diets to change the makeup of their gut bacteria – for example by encouraging the growth of Akkermansia and Bifidobacterium.
Journal reference: Nature Medicine, DOI: 10.1038/nm.4345