Effect of ingesting yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 on influenza virus-bound salivary IgA in elderly residents of nursing homes: a randomized controlled trial.

Objective: The purpose of this study was to clarify the influence of consuming yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (1073R-1-yogurt) on influenza virus-bound salivary immunoglobulin A (IgA) levels, in the elderly residents of nursing homes. Methods: A double-blind, parallel-group, randomized controlled trial was conducted with 96 elderly volunteers residing in 2 nursing homes. During the trial, participants consumed 100 g of 1073R-1-yogurt every morning for 12 weeks, whereas the control participants consumed yogurt fermented with a different Lactobacillus strain (control yogurt). Saliva was collected before the trial and after 4, 8 and 12 weeks of yogurt ingestion. Results: Our data indicated that consumption of 1073R-1-yogurt affected influenza A virus subtype H3N2-bound IgA levels in saliva (p = .001). In addition, saliva flow rate and total IgA levels increased in response to the yogurt intake period in both the 1073R-1 and control yogurt groups (p = .04). Conclusions: Our study suggests that continuous daily ingestion of 1073R-1-yogurt may help prevent infection with influenza A virus subtype H3N2 in elderly subjects with weakened immunity, by increasing the production of influenza A virus subtype of H3N2-bound salivary IgA.

Enhanced natural killer cell activation by exopolysaccharides derived from yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1.

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.

Consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 augments serum antibody titers against seasonal influenza vaccine in healthy adults.

Seasonal influenza is a major upper respiratory tract infection occurring in winter. Vaccination is the best method for preventing this infection. We conducted two randomized, double-blind, placebo-controlled trials to examine whether consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1, which has been reported to reduce the risk of catching the common cold, augments serum antibody titers against seasonal influenza vaccines. In the first trial, which included university students, serum antibody titers against influenza A (H3N2) and B viruses were significantly higher in the yogurt group than in the placebo group. According to the guidelines established by the European Medicines Agency (EMA) for the assessment of vaccines, the seroconversion rate and mean geometric increase of influenza A (H3N2) and seroprotection of influenza B met the criteria only in the yogurt group. In the second trial, which included healthy adults, serum antibody titers against influenza A (H1N1) and B viruses were significantly higher in the yogurt group than in the placebo group. The seroconversion rate and mean geometric increase of influenza B met the EMA criteria only in the yogurt group. Furthermore, the cumulative days of ill health, such as throat complaints, upper respiratory inflammation, and cold, were significantly lower in the yogurt group than in the placebo group. Therefore, daily intake of yogurt fermented with L. bulgaricus OLL1073R-1 could reduce the duration of symptoms caused by respiratory infections and act as a mucosal adjuvant enhancing acquired immune responses against vaccines, leading to the improvement of public health.

Anti-Fatigue Effects of Yogurt Fermented with Lactobacillus delbureckii subsp. bulgaricus OLL1073R-1 in Healthy People Suffering from Summer Heat Fatigue: A Randomized, Double-Blind, Placebo-Controlled Trial.

Fatigue caused by summer heat is a typical indefinite complaint along with anorexia, loss of sleep, stress, lack of motivation and, in some cases, catching a cold. Yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 has been shown to stimulate the immune system and reduce the risk of catching colds. Here, we conducted a randomized, double-blinded, placebo-controlled trial to investigate whether ingesting this yogurt could ameliorate summer heat fatigue in 49 healthy males (median age 40.0 ± 6.0 years; 30⁻49 years) who felt fatigued every summer. Fatigue was evaluated by visual analogue scales (VAS) and the balance of sympathetic/parasympathetic nervous systems. After 12 weeks of ingestion in early autumn, the VAS fatigue scores in the yogurt group were lower than those of the placebo group. These results indicate that yogurt fermented with L. bulgaricus OLL1073R-1 can ameliorate summer heat fatigue lasting up to early autumn.

Induction of Colonic Regulatory T Cells by Mesalamine by Activating the Aryl Hydrocarbon Receptor.

BACKGROUND & AIMS: Mesalamine is a first-line drug for treatment of inflammatory bowel diseases (IBD). However, its mechanisms are not fully understood. CD4+ Foxp3+ regulatory T cells (Tregs) play a potential role in suppressing IBD. This study determined whether the anti-inflammatory activity of mesalamine is related to Treg induction in the colon. METHODS: We examined the frequencies of Tregs in the colons of wild-type mice, mice deficient for aryl hydrocarbon receptor (AhR-/- mice), and bone marrow-chimeric mice lacking AhR in hematopoietic cells (BM-AhR-/- mice), following oral treatment with mesalamine. We also examined the effects of mesalamine on transforming growth factor (TGF)-ß expression in the colon. RESULTS: Treatment of wild-type mice with mesalamine increased the accumulation of Tregs in the colon and up-regulated the AhR target gene Cyp1A1, but this effect was not observed in AhR-/- or BM-AhR-/- mice. In addition, mesalamine promoted in vitro differentiation of naive T cells to Tregs, concomitant with AhR activation. Mice treated with mesalamine exhibited increased levels of the active form of TGF-ß in the colon in an AhR-dependent manner and blockade of TGF-ß signaling suppressed induction of Tregs by mesalamine in the colon. Furthermore, mice pretreated with mesalamine acquired resistance to dextran sodium sulfate-induced colitis. CONCLUSIONS: We propose a novel anti-inflammatory mechanism of mesalamine for colitis: induction of Tregs in the colon via the AhR pathway, followed by TGF-ß activation.