September 27, 2021
Keio University Faculty of Pharmacy
Kaigen Pharma Co., Ltd.
The Keio University Faculty of Pharmacy and Kaigen Pharma Co., Ltd. (Headquarters: Chuo-ku, Osaka; President: Nobuo Nakagiri; hereinafter "Kaigen Pharma") have revealed that sodium alginate (hereinafter "SA"), a dietary fiber found in seaweed, suppresses metabolic syndrome (hereinafter "MS") via gut microbiota. This research is the result of a research group centered on Ryuta Ejima, a sixth-year student in the Department of Pharmacy at the Keio University Faculty of Pharmacy; Masahiro Akiyama, a Project Lecturer at the same faculty; Professor Yun-Gi Kim; Shinji Fukuda, a Project Professor at the Institute for Advanced Biosciences, Keio University; and Hiroki Sato of Kaigen Pharma Co., Ltd.
SA is a polysaccharide found in brown algae such as kombu, wakame, hijiki, and mozuku. In addition to being widely used as a food quality improver, such as a "thickener" or "gelling agent," SA is also used as a soluble dietary fiber. Furthermore, studies using obese animal models have also reported its effects on MS, such as suppressing weight gain and reducing cholesterol. It has also become clear that some gut bacteria can use SA as a nutritional source. In recent years, it has been known that gut microbiota affect our metabolic functions, but the contribution of gut microbiota to the MS-suppressing action of SA remained unclear.
In this study, by using mice whose gut microbiota were disrupted with antimicrobial agents and performing omics analysis, we clarified that gut microbiota are essential for the MS-suppressing effect of SA. We also found that when mice fed a high-fat diet were given SA, bacteria of the genus Bacteroides increased significantly. Since intestinal inflammatory macrophages (hereinafter "MΦ") were known to be deeply involved in the onset of diet-induced MS, we next observed the quantitative and qualitative changes in intestinal MΦ after SA intake. As a result, we found that giving SA to mice on a high-fat diet decreased the proportion of inflammatory MΦ in the large intestine and, conversely, increased the proportion of anti-inflammatory MΦ. This decrease in the proportion of inflammatory MΦ by SA was no longer observed with the administration of antimicrobial agents that eliminate gut microbiota, including bacteria of the genus Bacteroides . Furthermore, intestinal metabolome analysis identified metabolites that showed a positive correlation with the increased Bacteroides bacteria due to SA, including B vitamins such as nicotinic acid, pantothenic acid, riboflavin, and pyridoxal, as well as amino acid derivatives and nucleic acids.
From the above, it has become clear that SA suppresses MS by reducing intestinal inflammatory MΦ via gut microbiota. Previously, the effect of SA on MS was thought to be due to physical actions, such as adsorbing lipids in food and making them less likely to be absorbed into the body. The results of this study have newly revealed that SA suppresses MS by suppressing intestinal inflammation through changes in the composition and metabolites of the gut microbiota. In the future, it is expected that the concept that "MS can be prevented by maintaining a healthy gut environment" will become widespread, and that foods and pharmaceuticals that alter the gut environment for the purpose of preventing and improving MS will be developed. The results of this research were published in the international academic journal "Nutrients" (online edition) on August 16, 2021.
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