• Drug-bacteria interplay
• Human study
What is already known on this topic
The gut microbiota, together with several nutrients, is thought to influence the host’s response to drugs. For example, the effects of metformin—a widely used drug for type 2 diabetes—are regulated by the host microbiota and diet, but the exact mechanisms by which gut microbes regulate these effects are unclear.What this research adds
Researchers developed an automated screen to investigate how diet, drugs and the microbiota interact to influence host physiology. Using the roundworm Caenorhabditis elegans colonized with the human gut bacteria Escherichia coli, the team found that metformin altered the metabolism and lifespan of the worm, and that specific nutrients influenced these effects.Conclusions
The findings could help to inform dietary guidelines that increase drug efficacy and reduce side effects.
Researchers developed a rapid method to investigate how diet, drugs and the microbiota interact to influence host health. The study, published in Cell, could help to inform dietary guidelines that increase drug efficacy and reduce side effects.
The gut microbiota, as well as several nutrients, are thought to influence the host’s response to drugs. For example, the effects of metformin—a widely used drug for treating type 2 diabetes and aging—are regulated by the host microbiota and diet, but the exact mechanisms by which gut microbes regulate these effects are unclear.
So Rosina Pryor at the MRC London Institute of Medical Sciences and her colleagues set out to devise a screen that allowed them to quickly test all possible interactions between diet, drugs, microbiota, and host.
Drug-bacteria interplay
As a simplified host-microbiota model, the researchers used the roundworm Caenorhabditis elegans colonized with the human gut bacteria Escherichia coli. Then, they exposed the worm to metformin in the presence of hundreds of different nutrients.
The team found that metformin influenced the worm’s physiology by altering the type of metabolites that the microbiota produced. Metabolite analysis revealed that sugars blocked the activation of a gene whose product regulates the host metabolism in response to the nutritional environment. On the other hand, nutrients such as amino acids helped activate the downstream effects induced by the drug.
The team found that bacteria were able to rewire their own metabolism depending on the nutrient and metformin signals they were exposed to. The microbes did so by accumulating a metabolite called agmatine.
Human study
To investigate whether the results found in C. elegans could also apply to people, the researchers compared the microbiota, diet, and medication status of type-2 diabetic patients with that of healthy people.
In individuals with type-2 diabetes, metformin treatment was associated with an increased capacity of gut bacteria to produce agmatine. And the bacterial species that produce most agmatine were increased in the gut microbiota of people treated with metformin. Those people were also able to produce compounds that help improve overall host health.
Although the biological target of metformin is still unknown, the study uncovered how the drug influences metabolic and bacterial signaling pathways that regulate host physiology, the scientists say.
