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Nutritional Immunology

Isomalto-Oligosaccharides Polarize Th1-Like Responses in Intestinal and Systemic Immunity in Mice

Hiroyuki Mizubuchi^*,,1, Toshiki Yajima^*, Noriaki Aoi^*, Tetsuji Tomita and Yasunobu Yoshikai^*

^* Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan and Research and Development Center, Bio Science Laboratory, Showa Sangyo, Tsukuba, Ibaraki 305-0003, Japan

¹To whom correspondence should be addressed. E-mail: hiroyuki_mizubuchi{at}showa-sangyo.jp.

ABSTRACT

Isomalto-oligosaccharides (IMO) belong to a group of prebiotics that significantly increase the number of protective gut microflora. In the present study, we investigated the effects of IMO on intestinal and systemic immunity in mice. When mice were fed a diet supplemented with 20% IMO for 4 wk, the number of lactobacilli and the levels of IgA in feces were greater than those of mice fed the control diet (P < 0.05). Interferon- (IFN-) production by intestinal intraepithelial lymphocytes (i-IEL) in response to T-cell receptor (TCR) triggering was greater in mice fed IMO than in controls (P < 0.05), indicating T helper-1 (Th1) polarization of intestinal immunity by IMO. The proportion of natural killer (NK) T cells in the liver mononuclear cells (MNC), and the production of IFN- by the liver MNC in response to TCR triggering were greater in mice fed IMO than in controls (P < 0.05), suggesting that the Th1/Th2 balance was shifted toward the Th1 lineage by IMO in systemic immunity. Furthermore, the proportion and activity of NK cells were greater in the spleens of the mice fed IMO than in the controls. Dietary IMO protected the mice from -irradiation–induced lethality, accompanied by an inhibition of the translocation of Enterobacteriaceae. Notably, when mouse macrophage-like J774.1 cells were cultured with Lactobacillus gasseri in the presence of IMO, interleukin (IL)-12 production was greater than in the absence of IMO. These results suggest that IMO, in synergy with lactobacilli, upregulate the Th1 response and beneficially modulate host defense.

KEY WORDS: • isomalto-oligosaccharides • lactobacilli • mucosal immunity • systemic immunity • mice