Evidence suggests that probiotic bacteria modulate both innate and adaptive immunity in the host, and in some situations can result in reduced severity of common illnesses, such as acute rotavirus infection and respiratory infections. Responses to vaccination are increasingly being used to provide high quality information on the immunomodulatory effects of dietary components in humans. The present review focuses on the effect of probiotic administration upon vaccination response. The majority of studies investigating the impact of probiotics on responses to vaccination have been conducted in healthy adults, and at best they show modest effects of probiotics on serum or salivary IgA titres. Studies in infants and in elderly subjects are very limited, and it is too early to draw any firm conclusions regarding the potential for probiotics to act as adjuvants in vaccination. Although some studies are comparable in terms of duration of the intervention, age and characteristics of the subjects, most differ in terms of the probiotic selected. Further well designed, randomized, placebo-controlled studies are needed to understand fully the immunomodulatory properties of probiotics, whether the effects exerted are strain-dependent and age-dependent and their clinical relevance in enhancing immune protection following vaccination.
COCs containing 150 μg DSG or 3 mg DR significantly increase endothelium-dependent vasodilation in both large vessels and peripheral microvasculature. These effects may be due to the progestins exhibiting differential effects on eNOS expression.
Bifidobacterium longum bv. infantis CCUG 52486 has immunomodulatory properties, which are strongly influenced by ageing (1) . The PRIMAGE (Probiotics, Immunity and AGEing) study examined the influence of this probiotic in combination with a commercial prebiotic (BioEcolians; glucooligosaccharide) on the immune response to influenza vaccination in young and older subjects; effects of the B cell response are reported here.58 young (18-35 y) and 54 older (60-85 y) subjects were treated with Bifidobacterium longum bv. infantis CCUG 52486 (5 × 10 8 CFU/day) and glucooligosaccharide (8 g/d) combined as a powder, or with placebo (maltodextrin) (9 g/day) for 8 weeks in total, with the seasonal (2010-2011 northern hemisphere) influenza vaccination being given at 4 weeks. Blood samples were taken at weeks 0, 4, 6 and 8 and peripheral blood mononuclear cells (PBMCs) were isolated and cryopreserved for analysis. B cell phenotype and expression of immunoglobulin (Ig) A and G were analysed by multi-parameter flow cytometry.The absolute numbers of memory and plasma B-cells at baseline were significantly lower in old subjects compared to young subjects and there was also a significantly lower number of class switched IgA + and IgG + memory and total IgA + and IgG + B-cells in older subjects. Seroconversion to all three vaccine subunits was significantly lower in the older subjects (data not shown) and successful seroconversion associated with a significantly greater increase in IgG + memory (P < 0.05) and total IgG + B-cells (P < 0.05) 2 weeks after vaccination. In the older subjects, treatment with the pre-and probiotic increased the number of IgG + memory B-cells and total IgG + B-cells compared with the placebo group 4 weeks after vaccination (P < 0.02 and P < 0.05 respectively) (Data not shown).In conclusion, ageing was associated with lower numbers of class switched B cells. The pre-and probiotic enhanced the production of IgG + memory and total B-cells following vaccination in old subjects. IgG expression is associated with successful seroconversion, but in older subjects, the increase in IgG was not sufficient to enable comparable seroconversion to the young subjects.
Changes in endothelial function have been shown to correlate with risk of CVD (1) . Studies investigating endothelial function in premenopausal women must be carefully designed to account for cyclic changes in estrogen, a potent vasoactive hormone (2) . A small number of studies have used flow mediated dilatation (FMD) to investigate the effect of menstrual cycle phase on endothelial function in premenopausal women; both free-cycling (3) , and those taking two different formulations of oral contraceptives (OC) (4,5) . These studies confirmed the oestrogen-correlated variation in FMD response in free-cycling women, but have also indicated that the response in women taking OC depends on the type of progestin. The current study aimed to compare three types of OC on endothelial function using a range of endothelial function measurements.Twenty-nine healthy young women who had been taking OC for at least 3 months were recruited. All were non-smokers, with normal BMI and blood pressure. The women were taking OC containing 150 mg levonorgestrel (Microgynon, n 10), 150 mg desogestrel (Marvelon, n 10) or 3 mg drospirenone (Yasmin, n 9). All OC regimes involved no pills during days 1-7 (corresponding to the menstrual phase) then active pills during days 8-28 (progestin plus 30 mg ethinylestradiol). Subjects had four visits, one during days 5-7 (pill-free phase) and one during days 26-28 (active-pill phase) for two consecutive menstrual cycles.FMD response was significantly higher during the active-pill than pill-free phases in women receiving desogestrel and drospirenone (both P < 0.001), but not in those receiving levonorgestrel. This was also seen using endothelium-dependent vasodilation as measured by laser Doppler iontophoresis (LDI-ACh) (both P < 0.02). No significant differences between phases were observed in any group using other techniques (pulse wave analysis, pulse wave velocity, digital volume pulse or endothelial-independent vasodilation measured using LDI). Women receiving drospirenone had larger changes in FMD between the pill phases than women on desogestrel (P < 0.001), and women taking levonorgestrel had lower LDI-ACh values during their active-pill phase than women on the other OC (P < 0.02).These results confirm the previous report of a negative effect of levonorgestrel on endothelial function, indicating an antagonism of the effect of estrogen. Neither desogestrel nor drospirenone appear to have this effect. FMD and LDI measures also confirmed these differences between pill phases, but other techniques are either lacking in adequate sensitivity or else are measuring aspects of vascular reactivity that do not change during between pill phases. This information may help researchers understand the variation in different endothelial function measurements that occur in premenopausal women taking different OC. This may begin to provide researchers with more confidence regarding the inclusion of premenopausal women in their cohorts, and address the lack of research into vascular function in this subject group.
Conditions associated with impairments in insulin sensitivity (SI), such as obesity and type-II diabetes (T2D), often present with elevated NEFA. While lipid infusion studies have shown that increasing NEFA can impair glucose metabolism (1) , there are relatively few studies investigating the effect of NEFA elevation following fat loads of differing composition.Sixty healthy volunteers participated in a single-blind crossover trial. Subjects were randomly assigned to either 0.75 g/kg bodyweight (bw) of palm stearin (SFA) or 0.65 g/kg bw of palm stearin and 0.1 g/kg bw of DHA-rich fish oil (n-3 PUFA) on separate occasions; study visits for females were conducted at 4-week intervals to control for the menstrual cycle. The oils were emulsified into chocolate drinks and given as a bolus at baseline (0 min), followed by smaller drinks every 30 min. At 60 min, an infusion of heparin (500 IU bolus + 0.4 IU/ kg bw/min) was administered to activate lipoprotein lipase (2) . At 240 min, a hyperinsulinaemic (HI)-euglycaemic clamp (1 mU/kg/min) was initiated. SI was calculated as the mean glucose infusion rate for the last 30 min of the 150 min clamp, either adjusted for bw or fat-free mass (ffm). Plasma NEFA increased with the heparin infusion and subsequently declined during the HI clamp (Fig. 1); NEFA did not differ between the two study days. Insulin sensitivity was significantly greater during the consumption of n-3 PUFA than SFA for males but not females (Table).Our data suggest that the substitution of a relatively small amount of SFA for n-3 PUFA during oral fat feeding with heparin infusion acutely increases SI in males. The reasons for the gender-specific effect are unclear, but there is some evidence to indicate that men may be more sensitive to the effects of lipid-induced impairments in SI (3,4) . Long-term trials are needed to investigate whether these acute study results could infer any benefit of dietary fish oil supplementation in improving SI in males.
The potential health benefits of both pre-and probiotics have expanded in recent years from maintaining bowel regularity and a balance of gut microflora to improving micronutrient status and immune function. There is particular interest in the positive influences of pre-and probiotics in older people, who are subject to alteration in gut microbiota composition and also to immunosenescence (deterioration and dysregulation of the immune system). The PRIMAGE study is a randomised, double-blind, placebo-controlled, parallel study investigating the influence of Bifidobacterium longum bv. Infantis CCUG 52486 (5 • 10 8 CFU/d) combined with gluco-oligosaccharide (8 g/d) on the immune response to influenza vaccination among healthy young (18-35 y, n = 58) and older (60-85 y, n = 54) volunteers. Volunteers consumed either a placebo (9 g/d maltodextrin) or treatment for a total of 8 weeks, and a trivalent influenza vaccination (2010/2011 northern hemisphere) was administered after 4 wks of treatment. Blood and faecal samples were collected at baseline, week 4 and after vaccination. Older volunteers were asked to complete a self-reported illness form for six months post-vaccination. 43 healthy older volunteers were vaccinated in October/November 2010 in accordance with UK NHS vaccination schedules, and 41 returned a six-month self-reported illness form. Treatment did not significantly alter the incidence of cold or flu-like symptoms. Three participants within the treatment group reported a sudden onset of flu like illness, resulting in a significantly higher duration of this symptom among volunteers on treatment in the six months post-vaccination (p = 0.0047). Volunteers receiving treatment had significantly lower cumulative duration of fatigue, runny nose, headache and sore throat symptoms during the six months post-vaccination compared to placebo (p < 0.0001). Cumulative symptom duration (days)
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