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β2-1 Fructans are carbohydrate molecules with prebiotic properties. Through resistance to digestion in the upper gastrointestinal tract, they reach the colon intact, where they selectively stimulate the growth and/or activity of beneficial members of the gut microbiota. Through this modification of the intestinal microbiota, and by additional mechanisms, β2-1 fructans may have beneficial effects upon immune function, ability to combat infection, and inflammatory processes and conditions. In this paper, we have collated, summarised and evaluated studies investigating these areas. Twenty-one studies in laboratory animals suggest that some aspects of innate and adaptive immunity of the gut and the systemic immune systems are modified by β2-1 fructans. In man, two studies in children and nine studies in adults indicate that the adaptive immune system may be modified by β2-1 fructans. Thirteen studies in animal models of intestinal infections conclude a beneficial effect of β2-1 fructans. Ten trials involving infants and children have mostly reported benefits on infectious outcomes; in fifteen adult trials, little effect was generally seen, although in specific situations, certain β2-1 fructans may be beneficial. Ten studies in animal models show benefit of β2-1 fructans with regard to intestinal inflammation. Human studies report some benefits regarding inflammatory bowel disease (four positive studies) and atopic dermatitis (one positive study), but findings in irritable bowel syndrome are inconsistent. Therefore, overall the results indicate that β2-1 fructans are able to modulate some aspects of immune function, to improve the host's ability to respond successfully to certain intestinal infections, and to modify some inflammatory conditions.

β2-1 fructans are prebiotics and, as such, may modulate some aspects of immune function. Improved immune function could enhance the host's ability to respond to infections. There is limited information on the effects of β2-1 fructans on immune responses in humans. The objective of the study was to determine the effect of a specific combination of long-chain inulin and oligofructose (Orafti(®) Synergy1) on immune function in middle-aged humans, with the primary outcome being response to seasonal influenza vaccination. Healthy middle-aged humans (45-63 years of age) were randomly allocated to consume β2-1 fructans in the form of Orafti(®) Synergy1 (8 g/day; n = 22) or maltodextrin as control (8 g/day; n = 21) for 8 weeks. After 4 weeks, participants received the 2008/2009 seasonal influenza vaccine. Blood and saliva samples were collected prior to vaccination and 2 and 4 weeks after vaccination. They were used to measure various immune parameters. The primary outcome was the serum concentration of anti-vaccine antibodies. Serum antibody titers against the vaccine and vaccine-specific immunoglobulin concentrations increased post-vaccination. Antibodies to the H3N2-like hemagglutinin type 3, neuraminidase type 2-like strain were higher in the Synergy1 group (P = 0.020 for overall effect of treatment group), as was serum vaccine-specific IgG1 2 weeks post-vaccination (P = 0.028 versus control). There were no other differences between groups in antibody titers or anti-vaccine immunoglobulin concentrations, in blood immune cell phenotypes, or in a range of immune parameters. It is concluded that Orafti(®) Synergy1, a combination of β2-1 fructans, can enhance some aspects of the immune response in healthy middle-aged adults, but that this is not a global effect.

The main objective was to investigate the potential immunomodulatory effects of β-hydroxy-β-methylbutyrate (HMB) in human cells. Peripheral blood mononuclear cells were isolated from the blood of eight volunteers and assayed for proliferation, cell cycle progression, surface expression of CD25, intracellular expression of pERK1/2, and cytokine production after in vitro exposure to a range of HMB concentrations (0.1 to 10 mM). Above 1 mM, HMB decreased the extent of proliferation normally observed after stimulation by concanavalin A. The decrease was evident at 10 mM HMB, when the proliferation index was 50% reduced when compared with the absence of HMB. Cell cycle analysis demonstrated an increase in the proportion of cells at the G0-G1 phase at 10 mM HMB. CD25 and pERK1/2 expression were not related to the observed effect on proliferation. HMB affected the concentrations of all five cytokines measured following stimulation. Tumor necrosis factor-α concentration in the culture medium was reduced by ∼35% at all HMB concentrations. Th1/Th2 cytokine production was modified toward a Th2 profile when HMB was at 1 or 10 mM. Thus, HMB at 10 mM impairs lymphocyte proliferation and progression through the cell cycle. The lowest concentration used here (0.1 mM) exerted some actions on cytokine production, including decreasing TNF-α production, but not on proliferation and cell cycle progression. HMB may be a useful agent to consider for modulation of immune function in specific situations.

β2-1 fructans are considered to be prebiotics. Current literature indicates that β2-1 fructans may modulate some aspects of immune function, improve the host's ability to respond to certain intestinal infections, and modify some inflammatory outcomes in human subjects. However, there is a need to find out more about the modulation of immune markers by β2-1 fructans in humans. Healthy human subjects aged 45–65 years were randomly allocated to β2-1 fructans (Orafti® Synergy1; 8 g/d; n 22) or the digestible carbohydrate maltodextrin as placebo (n 21) for 4 weeks. Blood, saliva and faecal samples were collected at study entry and after 4 weeks. Immune parameters were measured using the blood and saliva samples and bifidobacteria were measured in the faecal samples. Faecal bifidobacteria numbers increased in the Orafti® Synergy1 group (P < 0·001) and were different at 4 weeks from numbers in the placebo group (P = 0·001). There was no significant effect of Orafti® Synergy1 on any of the immune parameters measured (blood immune cell subsets, total serum Ig, salivary IgA, neutrophil and monocyte phagocytosis of Escherichia coli and respiratory burst in response to E. coli or phorbol ester, natural killer cell activity, T cell activation and proliferation, production of six cytokines by T cells). It is concluded that, compared with maltodextrin, Orafti® Synergy1 has a bifidogenic effect in healthy middle-aged human subjects but does not alter immune responses examined in the absence of an in vivo immune challenge.

[beta]2-1 fructans are considered to be prebiotics. Current literature indicates that [beta]2-1 fructans may modulate some aspects of immune function, improve the host's ability to respond to certain intestinal infections, and modify some inflammatory outcomes in human subjects. However, there is a need to find out more about the modulation of immune markers by [beta]2-1 fructans in humans. Healthy human subjects aged 45-65 years were randomly allocated to [beta]2-1 fructans (Orafti® Synergy1; 8 g/d; n 22) or the digestible carbohydrate maltodextrin as placebo (n 21) for 4 weeks. Blood, saliva and faecal samples were collected at study entry and after 4 weeks. Immune parameters were measured using the blood and saliva samples and bifidobacteria were measured in the faecal samples. Faecal bifidobacteria numbers increased in the Orafti® Synergy1 group (P < 0·001) and were different at 4 weeks from numbers in the placebo group (P = 0·001). There was no significant effect of Orafti® Synergy1 on any of the immune parameters measured (blood immune cell subsets, total serum Ig, salivary IgA, neutrophil and monocyte phagocytosis of Escherichia coli and respiratory burst in response to E. coli or phorbol ester, natural killer cell activity, T cell activation and proliferation, production of six cytokines by T cells). It is concluded that, compared with maltodextrin, Orafti® Synergy1 has a bifidogenic effect in healthy middle-aged human subjects but does not alter immune responses examined in the absence of an in vivo immune challenge. [PUBLICATION ABSTRACT]

The main objective was to investigate the potential immunomodulatory effects of β-hydroxy-β-methylbutyrate (HMB) in human cells. Peripheral blood mononuclear cells were isolated from the blood of eight volunteers and assayed for proliferation, cell cycle progression, surface expression of CD25, intracellular expression of pERK1/2, and cytokine production after in vitro exposure to a range of HMB concentrations (0.1 to 10 mM). Above 1 mM, HMB decreased the extent of proliferation normally observed after stimulation by concanavalin A. The decrease was evident at 10 mM HMB, when the proliferation index was 50% reduced when compared with the absence of HMB. Cell cycle analysis demonstrated an increase in the proportion of cells at the G0-G1 phase at 10 mM HMB. CD25 and pERK1/2 expression were not related to the observed effect on proliferation. HMB affected the concentrations of all five cytokines measured following stimulation. Tumor necrosis factor-α concentration in the culture medium was reduced by ∼35% at all HMB concentrations. Th1/Th2 cytokine production was modified toward a Th2 profile when HMB was at 1 or 10 mM. Thus, HMB at 10 mM impairs lymphocyte proliferation and progression through the cell cycle. The lowest concentration used here (0.1 mM) exerted some actions on cytokine production, including decreasing TNF-α production, but not on proliferation and cell cycle progression. HMB may be a useful agent to consider for modulation of immune function in specific situations.

Prebiotics are defined as \"non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth, and/or activity, of one or a limited number of beneficial bacteria in the colon and thus improve host health\". Prebiotics include the β2-1 fructans, molecules which contain fructosyl-fructose linkages. A review of studies conducted in laboratory animals and in humans indicated that β2-1 fructans may modulate some aspects of immune function, improve the host's ability to respond to certain intestinal infections, and to modify some inflammatory outcomes. Studies looking at these same outcomes in humans supplemented with probiotics were also reviewed, and overall, the picture that emerges from these studies is mixed and there appear to be large species and strain differences in effects seen. This thesis describes a study that investigated the effect of Orafti* Synergy 1 on the functioning of the immune system in healthy human middle-aged adults, an age group that is underrepresented in the literature. A pilot study was conducted initially in order to develop a vaccination protocol, as response to vaccination has been identified as the most meaningful measure of the immune response. This protocol was then used in an intervention study to investigate the effect of β2-1 fructans on human immune responses. Healthy adults aged 45-65 years (n = 22 in test group, n = 21 in placebo group) were supplemented with Orafti' Synergyl (8 g/d for eight weeks) or maltodextrin, and vaccinated with the 2008/2009 seasonal influenza vaccination after four weeks. Fasting blood samples were taken at baseline (week zero) and weeks four, six and eight for analysis of various systemic immune parameters; anti-vaccine antibodies (the primary outcome), total antibody concentrations, immune cell phenotypes, neutrophil and monocyte phagocytosis and oxidative burst, ex vivo lymphocyte responsiveness (activation, proliferation and cytokine production) to the mitogen concanavalin A (ConA) and the vaccine. Faecal bifidobacteria were measured at weeks zero and four. Supplementation with Orafti* Synergyl (8 g/d) for four weeks had a bifidogengic effect. However, no effect of the supplement was seen on immune function measured in the absence of vaccination. Furthermore, few differences were seen between groups in most immune outcomes measured post-vaccination. However, two important and novel observations were made. First, the prebiotic supplement enhanced the antibody response to the HAH3_UR strain of the vaccine (p = 0.0019), and enhanced the IgCl-specific antibody response to the vaccine (p = 0.0019). Therefore, it can be concluded that Orafti* Synergyl is able to alter some aspects of immune function in healthy middle-aged adults.