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A recent investigation has unveiled that certain gut microorganisms, previously believed to thrive solely on dietary fiber, also metabolize sugars sourced from within the gastrointestinal tract. This interaction leads to the production of short-chain fatty acids, which are vital for various bodily functions. Researchers from Kobe University have made a significant breakthrough in understanding this symbiotic relationship, paving the way for potential new therapeutic strategies.
Gut microbiota are responsible for generating numerous substances essential for bodily functions, including short-chain fatty acids. These fatty acids serve as the primary energy source for intestinal epithelial cells but also play various other critical roles. Traditionally, it was thought that these metabolites were solely derived from the fermentation of undigested fiber by gut bacteria. However, a previous observation by OGAWA Wataru, an endocrinologist at Kobe University, indicated that individuals taking the diabetes medication metformin excrete glucose into their intestines. “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,” Ogawa stated.
To deepen their understanding of glucose excretion and its effects on gut microbiota, Ogawa and his team undertook innovative research, developing advanced bioimaging techniques and analytical methods to scrutinize gut microbial metabolism products. Through these methods, they successfully tracked how glucose is released into the gut and transformed, using both human and mouse models to assess the influence of metformin.
The findings, published in the journal Communications Medicine, revealed that glucose is primarily excreted in the jejunum, a segment of the small intestine. From there, it is transported down the gut to the large intestine and rectum. “We were surprised to discover that even individuals not on metformin displayed some level of glucose excretion into their intestines, suggesting that this phenomenon is a universal physiological process in animals, with metformin enhancing this activity,” Ogawa explained. Notably, metformin increased glucose excretion nearly fourfold in both humans and mice, regardless of diabetic status.
Furthermore, the research indicated that the excreted glucose is subsequently converted into short-chain fatty acids during its passage through the intestines. Ogawa remarked, “The discovery of short-chain fatty acid production from excreted glucose represents a pivotal finding. Traditionally, these compounds were believed to arise solely from the fermentation of indigestible dietary fibers, but this newly recognized mechanism underscores an important symbiotic relationship between the host and its microbiota.”
The Kobe University research team is now expanding its studies to further elucidate how various diabetes medications, including metformin, influence glucose excretion and the specific interactions with the gut microbiome and its metabolic outputs. Ogawa emphasized, “Intestinal glucose excretion signifies an overlooked physiological occurrence. Gaining insight into the molecular mechanisms that govern this process and how pharmaceuticals impact it could lead to the creation of innovative therapeutics aimed at modulating gut microbiota and their metabolites.”
This research was supported by various organizations including the Japan Society for the Promotion of Science and involved collaboration with teams from multiple universities and research facilities.
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