Consumption of prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis has minor effects on selected immune parameters in polypectomised and colon cancer patients.

Probiotics (PRO) modulate immunity in humans, while the effect of prebiotics (PRE) and synbiotics (SYN) on the human immune system are not well studied yet. The objective of this study was to investigate whether daily intake of a SYN modulates immune functions. In a randomised double-blind, placebo-controlled trial, thirty-four colon cancer patients who had undergone 'curative resection' and forty polypectomised patients participated. Subjects of the SYN group daily received encapsulated bacteria (1 x 10(10) colony-forming units of Lactobacillus rhamnosus GG (LGG) and 1 x 10(10) colony-forming units of Bifidobacterium lactis Bb12 (Bb12)) and 10 g of inulin enriched with oligofructose. Controls received encapsulated maltodextrin and 10 g of maltodextrin. Prior to intervention (T1), and 6 (T2) and 12 weeks after the start of the intervention (T3), phagocytic and respiratory burst activity of neutrophils and monocytes, lytic activity of natural killer cells and production of interleukin (IL)-2, IL-10 and IL-12, as well as tumour necrosis factor-alpha and interferon-gamma (IFN-gamma) by activated peripheral blood mononuclear cells (PBMC) were measured. In faeces, the concentrations of transforming growth factor-beta1 and prostaglandin E2 were measured. IL-2 secretion by activated PBMC from the polyp group increased significantly between T1 or T2 and T3 (P < 0.05). In the cancer group, SYN treatment resulted in an increased capacity of PBMC to produce IFN-gamma at T3 (P < 0.05). Other immunity-related parameters were not affected by SYN treatment, neither in the cancer nor in the polyp group. In conclusion, supplementation with this SYN has minor stimulatory effects on the systemic immune system of the two study groups. Further studies in humans should aim to focus on the gut-associated immune system.

Dietary synbiotics reduce cancer risk factors in polypectomized and colon cancer patients.

BACKGROUND: Animal studies suggest that prebiotics and probiotics exert protective effects against tumor development in the colon, but human data supporting this suggestion are weak. OBJECTIVE: The objective was to verify whether the prebiotic concept (selective interaction with colonic flora of nondigested carbohydrates) as induced by a synbiotic preparation-oligofructose-enriched inulin (SYN1) + Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (BB12)-is able to reduce the risk of colon cancer in humans. DESIGN: The 12-wk randomized, double-blind, placebo-controlled trial of a synbiotic food composed of the prebiotic SYN1 and probiotics LGG and BB12 was conducted in 37 colon cancer patients and 43 polypectomized patients. Fecal and blood samples were obtained before, during, and after the intervention, and colorectal biopsy samples were obtained before and after the intervention. The effect of synbiotic consumption on a battery of intermediate bio-markers for colon cancer was examined. RESULTS: Synbiotic intervention resulted in significant changes in fecal flora: Bifidobacterium and Lactobacillus increased and Clostridium perfringens decreased. The intervention significantly reduced colorectal proliferation and the capacity of fecal water to induce necrosis in colonic cells and improve epithelial barrier function in polypectomized patients. Genotoxicity assays of colonic biopsy samples indicated a decreased exposure to genotoxins in polypectomized patients at the end of the intervention period. Synbiotic consumption prevented an increased secretion of interleukin 2 by peripheral blood mononuclear cells in the polypectomized patients and increased the production of interferon gamma in the cancer patients. CONCLUSIONS: Several colorectal cancer biomarkers can be altered favorably by synbiotic intervention.

Inulin, oligofructose and immunomodulation.

Diet is known to modulate immune functions in multiple ways and to affect host resistance to infections. Besides the essential nutrients, non-essential food constituents such as non-digestible carbohydrates may also have an impact on the immune system, especially in the area of the gut-associated lymphoid tissue (GALT). Recent data now provide first evidence that prebiotics such as inulin/oligofructose (IN/OF) modulate functions of the immune system. In animal studies IN/OF primarily activated immune cells in Peyer's patches including IL-10 production and natural killer (NK) cell cytotoxicity. Other immune functions modulated by IN/OF included the concentration of secretory IgA in ileum and caecum, splenic NK cell cytotoxicity as well as splenocyte cytokine production. In different tumour models, a lower incidence of tumours was observed, which in the case of colonic tumours was associated with enhanced NK cell cytotoxicity in the GALT. Few human studies so far have investigated the effects of IN/OF alone or in combination with other dietary supplements on immunocompetence. Supplementation of IN/OF resulted in minor changes of systemic immune functions such as decrease in phagocytic activity. No data are available on the effects of IN/OF on the GALT in man. The mechanisms of the reported effects of IN/OF on the immune system are currently investigated and include: (i) direct effects of lactic acid-producing bacteria or bacterial constituents on immune cells; (ii) the production of SCFA and binding to SCFA receptors on leucocytes. In conclusion, the current data suggest that IN/OF primarily modulate immune parameters in the GALT, but splenocytes are also activated by IN/OF. Human studies are needed to find out whether IN/OF have the potential to modulate systemic immunity in well-nourished individuals and to lower the risk of diseases such as colon cancer.

Intestinal immunity of rats with colon cancer is modulated by oligofructose-enriched inulin combined with Lactobacillus rhamnosus and Bifidobacterium lactis.

Probiotics (PRO) are known to modulate immunity in animals and human subjects and to inhibit colon carcinogenesis in experimental models, but the effects of synbiotics (SYN) are not well understood. Therefore, the effects of PRO (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12), PRE (inulin-based enriched with oligofructose, 100 g/kg) and SYN (combination of PRO and PRE) on the immune system of rats were investigated in the azoxymethane (AOM)-induced colon cancer model. After 33 weeks, rats with and without AOM treatment were killed and immune cells were isolated from spleen, mesenterial lymph nodes (MLN) and Peyer's patches (PP). AOM treatment significantly reduced natural killer (NK) cell-like cytotoxicity in control rats and in PRO- and PRE-supplemented rats. SYN supplementation prevented the AOM-induced suppression of NK cell-like cytotoxicity in PP compared with control rats (P<0.01). SYN and PRE supplementation stimulated IL-10 production in PP in these rats (P<0.01) and in MLN of rats not treated with AOM (P<0.05). Interferon-gamma production in PP was decreased by PRO supplementation (PRO and SYN groups combined; P<0.05). Proliferative responsiveness of lymphocytes (PP) from AOM-treated rats was suppressed in SYN-supplemented rats (P<0.01). Overall, SYN supplementation in carcinogen-treated rats primarily modulated immune functions in the PP, coinciding with a reduced number of colon tumours. PRE and PRO provided in combination as SYN may contribute to the suppression of colon carcinogenesis by modulating the gut-associated lymphoid tissue.

Prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis modulates intestinal immune functions in rats.

Probiotics (PRO) modulate systemic immunity in animals and humans. In contrast, the effects of prebiotics (PRE) on systemic and intestinal immunity have not been investigated. Whether the combined application of PRO and PRE [synbiotics (SYN)] has synergistic or additive effects is presently unknown. Therefore, PRO (Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12), PRE (inulin enriched with oligofructose), and SYN (combination of PRO and PRE) were fed to F344 rats for 4 wk as supplements to a high fat diet. Functions of immune cells isolated from peripheral blood mononuclear cells (PBMC), spleen, mesenterial lymph nodes and Peyer's patches (PP) were investigated. The SYN supplement increased secretory immunoglobulin A (sIgA) production in the ileum compared with controls fed the high fat diet alone (P<0.05), and decreased the oxidative burst activity of blood neutrophils (P<0.05) compared with rats fed PRO. The PRE supplement enhanced the production of interleukin-10 (P<0.05) in PP as well as the production of sIgA in the cecum (P<0.05), compared with controls. The PRO supplement modestly affected immune functions, whereas systemic immunomodulatory effects were observed in rats fed SYN. The PRE supplement primarily acted at the level of the gut-associated lymphoid tissue. The combined application of PRO and PRE has different effects from those of the individual supplements, but does not simply result in additive or synergistic effects.