Hokkaido UniversityThe Sonoyama Lab
Laboratory of Gut Physiology, Graduate School of Life Science
Laboratory of Food Biochemistry, Faculty of Agriculture

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Research Projects

- Prevention and treatment of allergic disease by use of prebiotic non-digestible oligosaccharides.

Given that gut microbiota is an environmental factor for the development of allergic diseases, modulation of gut microbiota may prevent the allergic diseases. Indeed, we have demonstrated that dietary non-digestible oligosaccharides such as fructo-oligosaccharides modulate gut microbiota and reduce allergic inflammation of atopic dermatitis and contact hypersensitivity in mice. Prebiotics are defined as non-digestible food ingredients, that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improve host health. Therefore, non-digestible oligosaccharides are regarded as prebiotics for allergy prevention. We are now investigating the cellular and molecular mechanisms for the allergy-preventing action of non-digestible oligosaccharides.

Selected Publications:

Sasajima N, Ogasawara T, Takemura N, Fujiwara R, Watanabe J, Sonoyama K. Role of intestinal Bifidobacterium pseudolongum in dietary fructo-oligosaccharide inhibition of 2,4-dinitrofluorobenzene-induced contact hypersensitivity in mice. Br J Nutr 2010; 103: 539-548.

Fujiwara R, Takemura N, Watanabe J, Sonoyama K. Maternal consumption of fructo-oligosaccharide diminishes the severity of skin inflammation in offspring of NC/Nga mice. Br J Nutr 2010; 103: 530-538.

Sonoyama K, Ogasawara T, Goto H, Yoshida T, Takemura N, Fujiwara R, Watanabe J, Ito H, Morita T, Tokunaga Y, Yanagihara T. Comparison of gut microbiota and allergic reactions in BALB/c mice fed different cultivars of rice. Br J Nutr 2010; 103: 218-226.

Watanabe J, Sasajima N, Aramaki A, Sonoyama, K. Consumption of fructo-oligosaccharide reduces 2,4-dinitrofluorobenzene-induced contact hypersensitivity in mice. Br J Nutr 2008; 100: 339-346.

- Gut colonization by Candida albicans as a risk factor for allergic disease.
It has been postulated that excessive colonization by C. albicans, part of the gut microbiota of healthy humans, may be triggering and/or aggravating factor for allergic diseases. In order to test this, we established a mouse model of chronic and latent gut colonization by C. albicans. Using this model, we have demonstrated that gut colonization by C. albicans promotes oral sensitization by food antigens and aggravates inflammation in allergic and autoimmune diseases, not only in the gut but also in the extra-gut tissues. The next step of our study is to establish the cellular and molecular mechanisms.

Selected Publications:
Sonoyama K, Miki A, Sugita R, Goto H, Nakata M, Yamaguchi N. Gut colonization by Candida albicans
inflammation in the gut and extra-gut tissues in mice. Med Mycol 2011; 49: 237-247.

Yamaguchi N, Sugita R, Miki A, Takemura N, Kawabata J, Watanabe J, Sonoyama K. Gastrointestinal Candida colonisation promotes sensitisation against food antigens by affecting the mucosal barrier in mice. Gut 2006; 55: 954-960.

Yamaguchi N, Sonoyama K, Kikuchi H, Nagura T, Aritsuka T, Kawabata J. Gastric colonization of Candida albicans differs in mice fed a commercial stock diet and a purified diet. J Nutr 2005; 135: 109-115.

- Prevention and treatment of obesity and metabolic syndrome by use of probiotics.

Recent studies suggest a link between gut microbiota and host adiposity. If it holds true, modulation of gut microbiota would be a potent preventive and/or therapeutic approach to the obesity and related diseases. We recently observed a reduction of adipocyte size by oral administration of a specific strain of lactic acid bacteria, i.e., Lactobacillus plantarum strain No.14, in high-fat diet-induced obese mice. Thus, this strain could be a possible candidate for obesity-preventing probiotics. We are currently studying this action more in detail.

Selected Publications:
Takemura N, Hagio M, Ishizuka S, Ito H, Morita T, Sonoyama K. Inulin prolongs survival of intragastrically administered Lactobacillus plantarum No. 14 in the gut of mice fed a high-fat diet. J Nutr 2010; 140: 1963-1969.

Takemura N, Okubo T, Sonoyama K. Lactobacillus plantarum strain No. 14 reduces adipocyte size in mice fed high-fat diet. Exp Biol Med (Maywood) 2010; 235: 849-856.

- Mutualism between gut microbiota and host in hibernating mammals (e.g., Syrian hamsters and Japanese black bears).

Hibernation essentially involves periods of fasting that is known to affect both the gut microbiota and the gut mucosal barrier function in non-hibernating mammals such as mice and rats. Specifically, long-lasting deprivation of oral feeding by total parenteral nutrition increases the risk of bacterial translocation due to reduced gut mucosal barrier in rats. In contrast, there are no evidence that hibernation increases the risk of bacterial translocation. It is therefore of interest to investigate the changes in the gut microbiota and gut epithelial structure and function that may take place during hibernation. We are investigating it by using Syrian hamsters and Japanese black bears as models of hibernators.

Selected Publications:

Sonoyama K, Fujiwara R, Takemura N, Ogasawara T, Watanabe J, Ito H, Morita T. Response of gut microbiota to fasting and hibernation in Syrian hamsters. Appl Environ Microbiol 2009; 75: 6451-6456.