Anti-diabetic Effects of Algae with a Sustainable Society in View: In Focus on Regulatory T Cells and the Flora of Intestinal Bacteria

Due to the lifestyle changes caused by mechanization and urbanization, high nutrient availability and an energy dense diet along with decreasing physical activity levels have predisposed people to obesity and type 2 diabetes. This drastic change of life style in Asia also increased the onset of allergic diseases, and changed the type of tumors. For example, the world prevalence of diabetes has been reported on and it is estimated that more than 400 million adults will suffer from diabetes by 2030. Health organizations also reported that the prevalence of type 2 diabetes has reached epidemic levels in Asia and that this epidemic threatens to overwhelm health-care systems in the region. It has been suggested that certain changes in lifestyle can be effective in the prevention of type 2 diabetes, especially for those with impaired glucose tolerance. This is also true for allergies and tumors. In Asian countries, various species of algae have traditionally been considered as foods good for health. In Japan, for example, the Ecklonia species have been thought to improve the properties of blood. The precise function of these algae, however, has not been well analyzed. Here, we have focused on the following two topics. 1) The regulatory effect of algae on the development of type 2 diabetes. At first, we examined the effects of various algae on the blood glucose level in leptin receptor deficient db/db mice and found that gametophytes of Ecklonia kurome (E. kurome) down-regulate blood levels of glucose and triacylglycerol. Sporophytes of E. kurome did not have any effects on these levels. Since we administered the algae homogenates orally, we examined the bacterial flora in the intestine by using 16S rRNA nucleotides as a probe. We found the increase of Lactobacillus species and Bacteroides species in the mice administered with gametophytes of E. kurome. Interestingly, we found that regulatory T lymphocytes (Treg) had decreased in the mice administered with gametophytes of E. kurome. 2) We also examined the effect of gametophytes of E. kurome in wild type mice. We established prediabetic status in C57BL/6J by administrating a high fat diet (HFD) containing 32% fatty acids. We found that gametophytes of E. kurome down-regulated the blood glucose in prediabetic C57BL/6J wild type mice. We found that a cytokine, interferon-γ (IFN-γ) involved in the thermogenesis is also engaged in the regulation of blood levels of glucose and triacylglycerol. We also noted that Treg cells had increased in the absence of interferon-γ. Although we found that both gametophytes and sporophytes of E. kurome down-regulated the Treg cells in prediabetic mice of wild type strain, only gametophytes of E. kurome down-regulated the blood glucose in pre-diabetic wild type mice. This result suggests that Treg cells are down-regulated by substances contained in both sporophytes and gametophytes of E. kurome and that the level of blood glucose is not simply controlled by Treg cells. We summarize the recent advances in the area of regulation of immune responses by edible algae in view of a sustainable society.