July 9, 2025
Kitasato University
Keio University
A research group from Kitasato University and Keio University has developed a novel dietary intervention method that selectively reshapes the gut microbiota in a short period by administering carbohydrates metabolizable by gut bacteria (Microbiota-Accessible Carbohydrates [MACs]) during fasting. This research is the result of a team led by Kensuke Sato (then in the Doctoral Programs at the Graduate School of Media and Governance and the Institute for Advanced Biosciences, Keio University), Project Professor Shinji Fukuda of the Institute for Advanced Biosciences, Keio University, Visiting (Guest) Professor Jo Inoue of the Department of Biochemistry, Faculty of Pharmacy, Keio University and the Department of Microbiology, Faculty of Pharmacy, Kitasato University, and Professor Tomoki Nakanishi of the Department of Microbiology, Faculty of Pharmacy, Kitasato University (then a professor at the Center for Drug Discovery, Faculty of Pharmacy, Keio University).
The composition of the gut microbiota is strongly influenced by the nutrients in our daily diet. However, intentional dietary interventions aimed at selectively promoting the growth of specific gut bacteria in a short period have been difficult to achieve, as they are strongly limited by the homeostasis (robustness) of the gut environment. Within the gut, bacteria engage in complex interactions over host-derived nutrients and metabolites, and this network allows the gut microbial community to maintain a high degree of stability.
In this study, we successfully created an environment where specific bacteria could preferentially grow by introducing fasting as a means to temporarily break down this homeostatic barrier and then administering microbiota-accessible carbohydrates (MACs) in that state. MACs are carbohydrates that are not broken down by human digestive enzymes and are metabolized only by gut bacteria. Typical examples include dietary fiber and oligosaccharides.
In experiments using mice, we confirmed that administering MACs during fasting caused a significant change in the composition of the gut microbiota within a single day. It also became clear that in addition to different bacteria proliferating depending on the type of MACs consumed, the production of IgA antibodies—the primary immune antibodies in the intestinal mucosa that play a crucial role in protecting against infection—was significantly enhanced in the intestinal tract. Furthermore, a major advantage of this method is its ability to achieve effects such as the selective proliferation of specific gut bacteria and an increase in IgA without relying on antibiotics or strong pharmaceutical interventions.
It should be noted that this study was conducted using mice as an animal model, and further clinical verification and research toward practical application are necessary for its use in humans.
The results of this research were published in the international academic journal "BMC Microbiology" (Springer Nature Publishing Group) on July 5, 2025.
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