For years, we’ve thought our gut bacteria primarily munched on fiber, the roughage we can’t digest ourselves. It’s a tidy picture: you eat your veggies, your friendly microbes break them down, and everyone benefits. But a groundbreaking study from Kobe University in Japan has thrown a delicious wrench into that understanding, revealing something truly astonishing: a direct pipeline of sugar, glucose, flowing from your bloodstream straight into your intestines, where your gut microbes are eagerly waiting to gobble it up.
This isn’t just a quirky scientific detail; it’s a game-changer. This new discovery doesn’t just reshape our view of how our internal ecosystem works, but it also casts a fresh light on how a common diabetes drug, metformin, might actually do its job. It even hints at entirely new ways we could treat various health problems by influencing our gut bugs directly. So, next time you feel a sugar rush, consider that some of it might be heading straight to your microbial friends.
Uncovering a Hidden Highway
The journey to this discovery began with a puzzling observation by Dr. Wataru Ogawa, an endocrinologist at Kobe University. He had noticed that people taking metformin, a widely used medication for type 2 diabetes, seemed to excrete glucose into their guts. This was odd, as glucose is typically absorbed much higher up in the digestive system, not passed through to the lower intestines. Dr. Ogawa stated, “If glucose is indeed excreted into the gut, it is conceivable that this could affect the symbiotic relationship between the gut microbiome and the host.” This intriguing thought set his team on a quest to understand this previously hidden flow of sugar.
To trace this invisible sugar trail, the researchers had to get creative. They developed new ways to “see” and measure how much glucose was entering the intestines and what happened to it. Dr. Ogawa explained that they “had to develop unprecedented bioimaging methods and establish novel analytical techniques for the products of the gut microbial metabolism.” Their innovative approach involved a special imaging system called PET-MRI. Think of it as a super-powered camera that combines detailed body pictures with a way to track specific substances like glucose as they move through the body. This allowed them to precisely visualize and count how much sugar was going where.
Tracking Sugar in Humans and Mice
To get a full picture, the researchers conducted studies in both people and mice, giving us a comprehensive view of how this glucose excretion works and its impact.
In the human studies, they looked at individuals with type 2 diabetes, some taking metformin and some not. They injected a special, traceable form of glucose and then used their PET-MRI system to follow its journey. What they saw was remarkable: the tracer appeared in the small intestine very quickly and then moved through the large intestine, showing a clear path for glucose along the digestive tract. The middle part of the small intestine, called the jejunum, appeared to be the main point where glucose was entering the gut.
For a more precise measurement, they compared ten individuals with type 2 diabetes, half on metformin and half not. The results were quite revealing: those taking metformin had three to four times more of the traceable glucose in their gut contents compared to those not on the drug. Specifically, individuals on metformin excreted about 1.65 grams of glucose into their intestines every hour. Even in those not on metformin, a significant amount – about 0.41 grams per hour – was still excreted. This indicates our bodies are constantly sending some sugar to our guts, even without medication.
The researchers also performed experiments on mice to dive deeper into how this excreted glucose was used by gut microbes. They gave mice a traceable sugar and then analyzed their droppings. These mouse studies confirmed what they saw in humans: metformin significantly increased the amount of traceable glucose in the gut. More importantly, they found that this excreted glucose was being turned into beneficial short-chain fatty acids (SCFAs) by the gut bacteria. This process was even more active in mice treated with metformin. This is a crucial finding because it directly shows that the sugar being sent into the gut is becoming food for our helpful gut bacteria, directly affecting the “symbiosis” or cooperative relationship between us and our microbes.
A New Chapter for Metformin and Gut Health
This research significantly changes how we understand metformin. While we’ve known it lowers blood sugar by reducing how much glucose the liver produces, this study adds another important piece to the puzzle: metformin actively pushes glucose into the intestines. Once there, this sugar becomes a direct meal for our beneficial gut bacteria. This could contribute to metformin’s ability to lower blood sugar and might even explain some of its other positive effects on our health.
Beyond metformin, this discovery highlights a fundamental biological process: our bodies are consistently providing our gut microbes with sugar from our bloodstream. This newly identified “glucose flux” is a vital part of the close partnership between humans and their gut microbes, playing a role in producing essential SCFAs. It’s a remarkable example of the complex and often surprising ways our bodies interact with the trillions of tiny organisms living inside us.
The findings from this study open up exciting possibilities for new treatments. Dr. Ogawa highlights this potential, stating, “Intestinal glucose excretion represents a previously unrecognized physiological phenomenon. Understanding the underlying molecular mechanisms and how drugs interfere with this process could lead to the development of novel therapeutics aimed at the regulation of gut microbiota and their metabolites.” By understanding how glucose moves into the gut and how medications like metformin influence this process, scientists could unlock new therapies specifically aimed at managing our gut microbiota and the beneficial compounds they produce. This isn’t just about managing diabetes; it’s about harnessing the power of our internal living communities to improve health in ways we are only just beginning to grasp.
Paper Summary
Methodology
The study used [F]FDG PET-MRI to quantify intestinal glucose excretion in humans with type 2 diabetes, both on and off metformin. Mouse experiments with ¹³C-labeled glucose and fecal analysis determined glucose metabolism by gut microbiota into short-chain fatty acids (SCFAs).
Results
Glucose is excreted into the intestinal lumen, increasing significantly with metformin treatment (1.65 g/h vs. 0.41 g/h without metformin). This excreted glucose is metabolized by gut microbiota into SCFAs, a process enhanced by metformin.
Limitations
Human studies involved small sample sizes (5-10 participants). Mouse experiments used only male mice. Assumptions were made regarding [F]FDG dynamics and glucose metabolism in intestinal cells.
Funding and Disclosures
Funding was provided by organizations including the Japan Society for the Promotion of Science, Japan Science and Technology Agency, Japan Diabetes Society, and Nippon Boehringer Ingelheim Co. Ltd. Clinical studies were approved by the Ethics Committee of Kobe University Hospital.
Publication Information
The paper, “Metformin-regulated glucose flux from the circulation to the intestinal lumen,” was published in Communications Medicine (a Nature Portfolio journal), Volume 5, Article 44 (2025). The authors include Kazuhiko Sakaguchi and Wataru Ogawa, among others. The DOI is 10.1038/s43856-025-00755-4.