title: Enhanced natural killer cell activation by exopolysaccharides derived from yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1.
abstract: Yogurt is generally recognized as a beneficial food for our health, but research into its physiological effects has focused mainly on intestinal dysfunctions such as constipation and diarrhea. We previously found yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (hereafter OLL1073R-1) could reduce risks of catching the common cold and flu in human trials. It was assumed that immunostimulatory exopolysaccharide (EPS) produced from OLL1073R-1 play an important role in this context. However, few studies have examined the immunostimulatory effects of traditional Bulgarian yogurts fermented with different strains of lactobacilli and their metabolites. Therefore, we screened 139 L. delbrueckii ssp. bulgaricus strains and identified OLL1073R-1 as the most robust producer of EPS. This strain was also the only strain that induced the production of IFN-γ in vitro. Oral administration of the EPS or yogurt fermented with OLL1073R-1 and Streptococcus thermophilus OLS3059 (OLL1073R-1 yogurt) augmented natural killer (NK) cell activity and induced IFN-γ production in spleen cells in mice, whereas 2 other yogurts fermented with other strains had no effect on NK cell activity. Cellular preparations of the OLL1073R-1 strain also slightly augmented NK cell activity, but were less effective than EPS itself. The EPS-dependent stimulation of NK cell activity was abrogated in IFN-γ knockout mice and in myeloid differentiation factor 88 knockout mice. Furthermore, IFN-γ production from spleen cells stimulated with EPS was completely blocked with both anti-IL-12 and anti-IL-18 antibodies in vitro. These findings suggest that NK cell activation by OLL1073R-1 yogurt is EPS-dependent, occurs via IL-12- and IL-18-mediated IFN-γ production, and requires myeloid differentiation factor 88. We showed that traditional Bulgarian yogurt could exert immunostimulatory effects by selecting starter strains and part of the mechanisms depend on IFN-γ inducible EPS produced from L. delbrueckii ssp. bulgaricus. Further investigations on processes of fermentation to increase of the EPS may lead to the development of new functional foods that keep our immune functions stable.
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co. Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan. Electronic address: seiya.makino@meiji.com.
authors.forename: Seiya
authors.initials: S
authors.lastname: Makino
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co. Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Sato
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co. Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Goto
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co. Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
authors.forename: Marie
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co. Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co. Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
authors.forename: Yoshika
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co. Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hemmi
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co. Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kano
authors.affiliation: Division of Cell Biology, Biomedical Research Center, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Biofunctional Microbiota, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Biofunctional Microbiota, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan; Atopy (Allergy) Research Center, Graduate School of Medicine, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Food Science Research Laboratories, R&D Division, Meiji Co. Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Asami
mesh_terms: D000818:Animals; D019149:Bioreactors; D005285:Fermentation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D007778:Lactobacillus / Q000378:metabolism; D048668:Lactobacillus delbrueckii / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D048249:Streptococcus thermophilus / Q000378:metabolism; D015014:Yogurt / Q000032:analysis* / Q000382:microbiology
chemical_list: D011135:Polysaccharides, Bacterial; D007371:Interferon-gamma
keywords: exopolysaccharide; interferon-γ; natural killer; yogurt