A BENEO-Orafti Newsletter - Spring 2008 - Nr. 18:
Prebiotics and healthy ageing
Monitor
Inulin improves vaccination response in mice
Nutritional supplements that stimulate the immune system are estimated to improve the efficacy of vaccines. Prebiotics are well-known for their effect on the colonic microflora (e.g. improved growth of bifidobacteria) leading to a decrease in intestinal pH that contributes to the protection against pathogens. It is also assumed that direct modification of the gut microflora by prebiotics may affect immune functioning.
The aim of the study was to investigate the capacity of an inulin and oligofructose mixture to enhance murine immune responses to Salmonella vaccine and to evaluate its relevance for protection against Salmonella infection. In a first study, mice (Balb/c) (n=20 per group) were fed a diet with 5% of an inulin and oligofructose mixture (70% Orafti®P95 and 30% Orafti®HP) or cellulose (control) for 1 week before oral immunisation with a sub-optimal dose of live-attenuated Salmonella typhimurium vaccine (5 x 107 cfu). Four weeks after immunisation (corresponding to the peak of antibody response), mice were infected with LD100 of virulent S.typhimurium (3 x 107 cfu per mice) and immune parameters were measured (after 1 and 4 weeks post-immunisation). In a second study, mice were divided into 4 groups (n=20 per group) receiving a control diet, a control diet with vaccination (similar as in study 1), inulin and oligofructose mixture, and inulin and oligofructose mixture with vaccination. After infection (similar as in study 1), the survival rate was measured.
In study 1, specific anti-Salmonella antibody response significantly increased in both groups at 4 weeks post-immunisation. However, the increase was much stronger in the inulin mix group as indicated by the significantly higher specific blood Salmonella immunoglobulin G and faecal immunoglobulin A responses (P=0.01 and P=0.04 vs. control, respectively). The specific anti-LPS faecal IgA and anti-flagellin serum IgG in mice are illustrated in Figures 1 and 2. The phagocytic activity of peritoneal cells (1 week post-immunisation) was higher in the inulin mix group (52.5 ± 0.7%) than in the control group (38.1 ± 3.3 %, P=0.02). After 4 weeks, however, the level returned to the level in the control group. No detectable effects were observed on the percentage of lymphoid cell subsets in the spleen.
However, the production of cytokines, interferon-γ(IF-γ), interleukin-12 (IL-12), and tumour necrosis factor α (TNF-α) was numerically increased in spleen cultures (after mitogen stimulation) in the inulin mix fed mice, 1 and 4 weeks post-immunisation. Also, IL-12 levels were significantly higher in splenocytes after stimulation with concanavalin (T-cell stimulant) (64 ± 2 ng/l for the inulin mix and 42 ± 2 ng/l for the controls, P<0.05) and poke-weed mitogen (B-cell stimulant) (27 ± 9 for the inulin mix and 12 ± 5 ng/l for the controls, P<0.05) at 4 weeks post-immunisation. IF-γ was significantly enhanced in splenocytes after stimulation with (S.typhimurium) LPS (monocyte and B-cell stimulant) at 1 week (935 ± 207 ng/ l for the inulin mix and 404 ± 166 ng/l for the controls, P<0.05) and 4 weeks post-immunisation (210 ± 55 ng/l and 40 ± 19 ng/l, P<0.05). Salmonella translocation to lymphoid organs was not affected by feeding the inulin mix.
In study 2, three weeks following Salmonella infection, the survival rate in the groups receiving the control diet and the diet with inulin mix (without vaccination) was not different (e.g. 10% survival). However, vaccination of mice led to a 40% protection in the control group. This protection rate improved to 73% upon the inulin mix feeding (P=0.05 vs. non-vaccinated mice and vaccinated mice fed the control diet).
In conclusion, the results of this study show that the addition of an inulin and oligofructose mixture is able to improve the immune response to a Salmonella vaccine which contributes to increased vaccine efficacy. This is concomitant with an increase in the survival rate upon challenge with a virulent Salmonella strain. These data support the hypothesis that a diet enriched with a mixture of inulin and oligofructose is able to trigger and stimulate the gut mucosal immune system and to enhance oral vaccine efficacy.
Benyacoub J, Rochat F, Saudan K-Y, Rochat I, Antille N, Cherbut C, von der Weid T, Schiffrin EJ, Blum S (2008) Feeding a diet containing a fructooligosaccharide mix can enhance Salmonella vaccine efficacy in mice. J. Nutr. 138: 123-129.
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