For millennia, humans have had an unwritten trade deal with the microbes that inhabit our guts. We feed them fiber, and they reward us with short-chain fatty acids — compounds that help regulate our metabolism and inflammation. But a new study suggests we may be giving them more than just fiber, and they might be offering more as well.

A team of Japanese researchers has uncovered a hidden sugar pipeline that funnels glucose from our bloodstreams into our intestines, where microbes eagerly consume it. Even more surprising, this may explain how a popular diabetes drug works so well.

You and your microbes

Humans and microbes have shaped each other’s biology in ways we are only beginning to understand. The trillions of bacteria in our gut don’t just passively inhabit us — they influence everything from digestion to immune function, even producing molecules that affect our metabolism and brain chemistry.

But the more researchers look into this relationship, the more they find intriguing things. The new finding focuses on a compound called metformin.

Metformin is a common drug used against type 2 diabetes. It’s often used as a first-line treatment. The drug, derived from a plant used in folk medicine for centuries, has been hailed as a safe and effective way to lower blood sugar levels. But, despite its widespread use, scientists have never fully understood how it works.

The findings, published in Communications Medicine, suggest that metformin doesn’t just regulate blood sugar by acting on the liver — as long believed — but also by interacting with the gut, where it reshapes the relationship between humans and their microbiome.

Sugar in the gut

The study started when researchers noticed something odd in medical imaging studies. Patients on metformin who underwent PET scans often showed unexpected buildups of sugar in their intestines. PET scans are sensitive to glucose levels, which made the researchers wonder why there’s more glucose in these people’s guts than in their blood.

To find out, researchers used PET-MRI scans to track glucose in people with type 2 diabetes. Half of the participants were taking metformin, while the other half were not. The scans revealed a stark difference: in those taking metformin, glucose was flowing into the intestines at nearly four times the normal rate. Yet, even people who weren’t taking metformin had high levels of sugar in their guts.

“It was surprising to find that even individuals not taking metformin exhibited a certain level of glucose excretion into the intestine. This finding suggests that intestinal glucose excretion is a universal physiological phenomenon in animals, with metformin acting to enhance this process,” explains Kobe University endocrinologist Ogawa Wataru.

Researchers confirmed a very similar mechanism in mice, suggesting it wasn’t something unique to humans. So, they set out to investigate it more.

Helpful bacteria

The team looked at what was happening to the glucose. To track the fate of this sugar, they turned to mice. They injected the animals with glucose labeled with carbon-13 (a rare form), which allowed them to follow its path.

At first the glucose was excreted in the jejunum, a part of the small intestine. From there, it was transported inside to the large intestine. In mice treated with metformin, more of this labeled glucose ended up in short-chain fatty acids, the metabolic byproducts of gut bacteria. In other words, bacteria inside their gut was using this sugar to create short-chain fatty acids — products of bacterial fermentation that are important for gut health and may help prevent disease.

“The production of short-chain fatty acids from the excreted glucose is a huge discovery. While these compounds are traditionally thought to be produced through the fermentation of indigestible dietary fibers by gut microbiota, this newly identified mechanism highlights a novel symbiotic relationship between the host and its microbiota.”

One possibility is that it’s a side effect of how the drug works in intestinal cells. Another is that it’s an evolutionary adaptation — one that takes advantage of the gut’s microbes to help regulate metabolism.

This raises intriguing questions: Could other drugs — or even dietary interventions — mimic metformin’s effect? If we better understood how the body decides to “pay” its microbial partners in sugar, could we develop new ways to improve metabolic health?

For now, one thing is clear: Our metabolism isn’t only about us. Our gut bacteria have been helping all along. And, thanks to metformin, they might just be getting a raise.

The study was published in Nature: Communications Medicine.