Microbiome’s missing link? Research reveals how glucose effects gut health

Gut microbes, which were previously thought to feed on dietary fiber, actually feed on glucose excreted by the host, according to new research from Kobe University in Japan. The scientists explain that, as a result, these bacteria produce short-chain fatty acids (SCFA) that are essential to several body functions. They suggest the symbiotic relationship gives a nod to new therapeutics.

The study observed that glucose is excreted in the small intestine and transported to the large intestine and rectum. Nutrition Insight speaks to Kobe University endocrinologist Ogawa Wataru to learn about the discovery, fiber, and gut health.

“It has been known that individuals taking metformin [diabetes drug] show an accumulation of glucose in the intestine compared to non-users. A few years ago, we clarified that this accumulation occurs not in the intestinal wall but in the lumen, indicating that metformin promotes the excretion of glucose into the intestinal lumen.” 

“However, in that earlier study, while we demonstrated that glucose excretion into the gut was greater in metformin users than in controls, it remained unclear whether the control group exhibited no excretion at all or a certain baseline level,” he explains.

In this mouse study, the researchers created a new method that can accurately measure how much glucose is released into the gut. Using this method, they discovered that even people who are not taking the diabetes drug metformin still release some glucose into their intestines — about 20–30% of the levels in people on the drug. This means that glucose excretion into the gut happens naturally in healthy people, not just in those taking medication.

“Intestinal glucose excretion is an entirely novel physiological phenomenon, and the method for its quantitative evaluation was developed for the first time in this study,” says Wataru. 

The body’s natural excretion of glucose may be the source of food for gut bacteria (Image credit: Kobe University).“By comparing intestinal glucose excretion levels with various physiological parameters, we believe new insights will emerge. We are currently undertaking such a project to further explore these relationships.”

Is fiber still important?

Wataru discusses whether the discovery that gut bacteria can thrive on host-derived glucose challenges current dietary guidelines that emphasize fiber as their main fuel.

“The relative contributions of SCFA derived from dietary fiber versus those produced from glucose excreted into the gut remain an open question for future investigation.”

“However, there is robust epidemiological evidence supporting the wide-ranging health benefits of dietary fiber intake. Therefore, despite our recent findings, the importance of consuming dietary fiber remains unchanged,” he states.

The WHO recommends a dietary fiber intake of at least 25 grams daily, but research indicates many people don’t reach that goal. We examined this dietary fiber gap in the global population and opportunities for fortified foods to improve public health with Tate & Lyle, COMET, Alland & Robert, and Sensus.

Wataru adds: “Much remains to be elucidated about the distinct impacts of glucose excreted into the intestinal lumen versus those of nutrients derived from dietary intake on the gut environment.”

New research shows this hidden fuel source helps microbes produce health-boosting compounds, reshaping our understanding of diet and digestion.The paper, published in Communications Medicine, explains that SCFAs are generated by the gut microbiota when metabolizing indigestible dietary fiber. “Our findings suggest that, even in the absence of such fiber, glucose excreted into the intestine serves as a source for SCFA production.”

Enhancing glucose excretion 

According to Wataru, enhancing glucose excretion can be a strategy not just for diabetes but for modulating the gut microbiome in other conditions. “Metformin is known not only for its glucose-lowering effect but also for a variety of health benefits, including anti-atherosclerotic, anti-inflammatory, anti-tumor, and anti-aging effects.”

“While the mechanisms underlying these pleiotropic effects are not yet fully understood, one prevailing hypothesis is that they are mediated, at least in part, through alterations in the gut microbiota. Intestinal glucose excretion may be one of the factors contributing to these broader effects of metformin.”

“On the other hand, a common side effect of metformin is gastrointestinal disturbance, including diarrhea and loose stools. Although it remains unclear whether there is a direct link between intestinal glucose excretion and these symptoms, increased glucose excretion into the gut lumen could potentially alter the intestinal environment in ways that contribute to such gastrointestinal side effects,” he explains.

Dependency on symbiosis

Wataru explains what the newly discovered mechanism reveals about the fine line between symbiosis and dependency in our microbiome.

“Some of which are thought to arise from alterations in the gut environment, including changes in the gut microbiota. We believe that metformin’s ability to promote glucose excretion into the intestinal lumen may also influence both the composition and functional activity of gut bacteria.”

“In the future, if the mechanisms underlying intestinal glucose excretion are fully elucidated, it may become possible to develop new agents — distinct from metformin — that enhance this pathway. Such agents would not only offer novel therapeutic options but also help further clarify the physiological and metabolic significance of intestinal glucose excretion,” he concludes.