July 8, 2025
Kitasato University
Keio University
A research group from Kitasato University and Keio University has revealed that the consumption of sorbitol, a sugar alcohol widely used as an artificial sweetener, exacerbates colitis by activating the intestinal inflammatory immune response via the gut microbiota and its metabolites.
This research is the result of work by a team led by Professor Tomoki Kimbara of the Department of Microbiology, Faculty of Pharmacy, Kitasato University (at the time of the research: Professor at the Center for Drug Discovery, Faculty of Pharmacy, Keio University), Kensuke Sato, a third-year student in the Doctoral Programs at the Graduate School of Media and Governance and the Institute for Advanced Biosciences, Keio University (at the time of the research), and Miwa Tomioka, a sixth-year student in the Department of Pharmacy, Faculty of Pharmacy, Keio University (at the time of the research).
FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, And Polyols), a collective term for fermentable short-chain carbohydrates, are not absorbed in the digestive tract and reach the large intestine, where they are utilized and fermented by gut bacteria. This process can cause gas production, abdominal pain, and bloating, and it has been suggested that FODMAPs may worsen symptoms in patients with Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD). In recent years, a "low-FODMAP diet" has gained attention as an effective dietary therapy. Among these, sorbitol, a type of polyol (sugar alcohol) widely used as a sweetener, has been reported to have higher fecal concentrations in patients with active IBD compared to healthy individuals or patients in remission, suggesting a link to intestinal inflammation. However, it remained unclear whether sorbitol itself could induce inflammation in the gut and how the gut microbiota and immune cells were involved in this process.
In this study, we analyzed in detail the effects of sorbitol on the gut environment and immune response through experiments in which mice were fed sorbitol. The results showed that sorbitol intake exacerbated experimental colitis. Furthermore, it was revealed that continuous intake of sorbitol promoted the production of inflammatory cytokines such as IL-1β and the differentiation of inflammatory M1-type macrophages in the large intestine. Additionally, changes were observed in the composition of the gut microbiota, with a particularly high proportion of bacteria from the family Prevotellaceae. These inflammatory changes were eliminated by the administration of antibiotics, suggesting that the effects of sorbitol are dependent on the gut microbiota. Moreover, fecal tryptamine concentrations were significantly elevated in the sorbitol-fed group, and in cell experiments where tryptamine was added, differentiation into M1 macrophages and increased expression of IL-1β were also confirmed.
These findings reveal a novel mechanism by which polyols affect the composition and metabolism of the gut microbiota and the immune response, thereby exacerbating intestinal inflammation. This suggests that a low-FODMAP diet may contribute to symptom relief during the acute phase of IBD. On the other hand, some sugars within the FODMAP group have been reported to be involved in suppressing enteritis. Therefore, from a long-term perspective of maintaining the diversity and function of the gut microbiota, it is also important to consider the intake of beneficial sugars for the gut, such as soluble dietary fiber.
This research provides a new perspective on inflammation control by focusing on the interplay between gut bacteria, metabolites, and immune cells, and is expected to contribute to the development of personalized nutritional therapy and therapeutic strategies targeting the microbiome.
The findings of this research were published online in the international scientific journal "iScience" (Cell Press) on June 19, 2025.
For the full press release, please see below.