A mixture of trans-galactooligosaccharides reduces markers of metabolic syndrome and modulates the fecal microbiota and immune function of overweight adults

Metabolic syndrome is a set of disorders that increases the risk of developing cardiovascular disease. The gut microbiota is altered toward a less beneficial composition in overweight adults and this change can be accompanied by inflammation. Prebiotics such as galactooligosaccharides can positively modify the gut microbiota and immune system; some may also reduce blood lipids. We assessed the effect of a galactooligosaccharide mixture [Bi2 muno (B-GOS)] on markers of metabolic syndrome, gut microbiota, and immune function in 45 overweight adults with $3 risk factors associated with metabolic syndrome in a double-blind, randomized, placebo (maltodextrin)-controlled, crossover study (with a 4-wk wash-out period between interventions). Whole blood, saliva, feces, and anthropometric measurements were taken at the beginning, wk 6, and end of each 12-wk intervention period. Predominant groups of fecal bacteria were quantified and full blood count, markers of inflammation and lipid metabolism, insulin, and glucose were measured. B-GOS increased the number of fecal bifidobacteria at the expense of less desirable groups of bacteria. Increases in fecal secretory IgA and decreases in fecal calprotectin, plasma C-reactive protein, insulin, total cholesterol (TC), TG, and the TC:HDL cholesterol ratio were also observed. Administration of B-GOS to overweight adults resulted in positive effects on the composition of the gut microbiota, the immune response, and insulin, TC, and TG concentrations. B-GOSmay be a useful candidate for the enhancement of gastrointestinal health, immune function, and the reduction of metabolic syndrome risk factors in overweight adults.

Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D concentrations on metabolic and cardiovascular disease outcomes

AIM: 25-hydroxyvitamin D (25OHD) concentrations have been shown to be associated with major clinical outcomes, with a suggestion that individual risk may vary according to common genetic differences in the vitamin D receptor (VDR) gene. Hence, we tested for the interactions between two previously studied VDR polymorphisms and 25OHD on metabolic and cardiovascular disease-related outcomes in a large population-based study. METHODS: Interactions between two previously studied VDR polymorphisms (rs7968585 and rs2239179) and 25OHD concentrations on metabolic and cardiovascular disease-related outcomes such as obesity- (body mass index, waist circumference, waist-hip ratio (WHR)), cardiovascular- (systolic and diastolic blood pressure), lipid- (high- and low-density lipoprotein, triglycerides, total cholesterol), inflammatory- (C-reactive protein, fibrinogen, insulin growth factor-1, tissue plasminogen activator) and diabetes- (glycated haemoglobin) related markers were examined in the 1958 British Birth cohort (n up to 5160). Interactions between each SNP and 25OHD concentrations were assessed using linear regression and the likelihood ratio test. RESULTS: After Bonferroni correction, none of the interactions reached statistical significance except for the interaction between the VDR SNP rs2239179 and 25OHD concentrations on waist-hip ratio (WHR) (P=0.03). For every 1nmol/L higher 25OHD concentrations, the association with WHR was stronger among those with two major alleles (-4.0%, P=6.26e-24) compared to those with either one or no major alleles (-2.3%, P≤8.201e-07, for both) of the VDR SNP rs2239179. CONCLUSION: We found no evidence for VDR polymorphisms acting as major modifiers of the association between 25OHD concentrations and cardio-metabolic risk. Interaction between VDR SNP rs2239179 and 25OHD on WHR warrants further confirmation.

Flavonoid-rich fruits and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease – FLAVURS: a randomized controlled trial

BACKGROUND: Observed associations between increased fruit and vegetable (F&V) consumption, particularly those F&Vs that are rich in flavonoids, and vascular health improvements require confirmation in adequately powered randomized controlled trials. OBJECTIVE: This study was designed to measure the dose-response relation between high-flavonoid (HF), low-flavonoid (LF), and habitual F&V intakes and vascular function and other cardiovascular disease (CVD) risk indicators. DESIGN: A single-blind, dose-dependent, parallel randomized controlled dietary intervention study was conducted. Male and female low-F&V consumers who had a ≥1.5-fold increased risk of CVD (n = 174) were randomly assigned to receive an HF F&V, an LF F&V, or a habitual diet, with HF and LF F&V amounts sequentially increasing by 2, 4, and 6 (+2, +4, and +6) portions/d every 6 wk over habitual intakes. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness [pulse wave velocity, pulse wave analysis (PWA)], 24-h ambulatory blood pressure, and biomarkers of nitric oxide (NO), vascular function, and inflammation were determined at baseline and at 6, 12, and 18 wk. RESULTS: In men, the HF F&V diet increased endothelium-dependent microvascular reactivity (P = 0.017) with +2 portions/d (at 6 wk) and reduced C-reactive protein (P = 0.001), E-selectin (P = 0.0005), and vascular cell adhesion molecule (P = 0.0468) with +4 portions/d (at 12 wk). HF F&Vs increased plasma NO (P = 0.0243) with +4 portions/d (at 12 wk) in the group as a whole. An increase in F&Vs, regardless of flavonoid content in the groups as a whole, mitigated increases in vascular stiffness measured by PWA (P = 0.0065) and reductions in NO (P = 0.0299) in the control group. CONCLUSION: These data support recommendations to increase F&V intake to ≥6 portions daily, with additional benefit from F&Vs that are rich in flavonoids, particularly in men with an increased risk of CVD. This trial was registered at www.controlled-trials.com as ISRCTN47748735.

Effects of increased wholegrain consumption on immune and inflammatory markers in healthy low habitual wholegrain consumers

Purpose Wholegrain (WG) consumption is associated with reduced risk of cardiovascular disease, but clinical data on inflammation and immune function is either conflicting or limited. The objective of this study was to assess the impact of increasing WG consumption to at least 80 g/d on markers of inflammation and glucose metabolism and on phenotypic and functional aspects of the immune system, in healthy, middle-aged adults with low habitual WG intake. Methods Subjects consumed a diet high in WG (> 80 g/d) or low in WG (< 16 g/d, refined grain diet) in a crossover study, with 6-week intervention periods, separated by a 4-week washout. Adherence to the dietary regimes was achieved by dietary advice and provision of a range of food products, with compliance verified through analysis of plasma alkylresorcinols (ARs). Results On the WG intervention, WG consumption reached 168 g/d (P < 0.001), accompanied by an increase in plasma ARs (P < 0.001) and fibre intake (P < 0.001), without affecting other aspects of dietary intake. On the WG arm there were trends for lower ex vivo activation of CD4+ T cells and circulating concentrations of IL-10, C-reactive protein, C-peptide, insulin and plasminogen activator inhibitor-1. The percentage of CD4+ central memory T cells and circulating levels of adipsin tended to increase during the WG intervention. Conclusions Despite the dramatic increase in WG consumption, there were no effects on phenotypic or functional immune parameters, markers of inflammation or metabolic markers.

Bacillus coagulans GBI-30, 6086 modulates Faecalibacterium prausnitzii in older men and women

Abstract Background: Advancing age is linked to a decrease in beneficial bacteria such as Bifidobacterium spp. and reduced aspects of innate immune function. Objectives: We investigated whether daily consumption of a probiotic [Bacillus coagulans GBI-30, 6086 (BC30); GanedenBC30] could improve immune function and gut function in men and women aged 65–80 y, using a double-blind, placebo-controlled crossover design. Method: Thirty-six volunteers were recruited and randomly assigned to receive either a placebo (microcrystalline cellulose) or the probiotic BC30 (1 3 109 colony-forming units/capsule). Volunteers consumed 1 treatment capsule per day for 28 d, followed by a 21-d washout period before switching to the other treatment. Blood and fecal samples were collected at the beginning and end of each treatment period. Fecal samples were used to enumerate bacterial groups and concentrations of calprotectin. Peripheral blood mononuclear cells (PBMCs) were extracted from whole blood to assess natural killer cell activity and lipopolysaccharide (LPS)-stimulated cytokine production. C-reactive protein concentrations were measured in plasma. Results: Consumption of BC30 significantly increased populations of Faecalibacterium prausnitzii by 0.1 log10 cells/mL more than during consumption of the placebo (P = 0.03), whereas populations of Bacillus spp. increased significantly by 0.5 log10 cells/mL from baseline in volunteers who consumed BC30 (P = 0.007). LPS-stimulated PBMCs showed a 0.2 ng/mL increase in the anti-inflammatory cytokine IL-10 28 d after consumption of BC30 (P < 0.05), whereas the placebo did not affect IL-10, and no overall difference was found in the effect of the treatments. Conclusions: Daily consumption of BC30 by adults aged 65–80 y can increase beneficial groups of bacteria in the human gut and potentially increase production of anti-inflammatory cytokines. This study shows the potential benefits of a probiotic to improve dysbiosis via modulation of the microbiota in older persons. J Nutr doi: 10.3945/jn.114.199802.

Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly persons

It is recognised that ageing induces various changes to the human colonic microbiota. Most relevant is a reduction in bifidobacteria, which is a health-positive genus. Prebiotics, such as galacto-oligosaccharides (GOS), are dietary ingredients that selectively fortify beneficial gut microbial groups. Therefore, they have the potential to reverse the age-related decline in bifidobacteria and modulate associated health parameters. We assessed the effect of GOS mixture (Bimuno (B-GOS)) on gut microbiota, markers of immune function and metabolites in forty elderly (age 65-80 years) volunteers in a randomised, double-blind, placebo (maltodextrin)-controlled, cross-over study. The intervention periods consisted of 10 weeks with daily doses of 5·5 g/d with a 4-week washout period in between. Blood and faecal samples were collected for the analyses of faecal bacterial populations and immune and metabolic biomarkers. B-GOS consumption led to significant increases in bacteroides and bifidobacteria, the latter correlating with increased lactic acid in faecal waters. Higher IL-10, IL-8, natural killer cell activity and C-reactive protein and lower IL-1β were also observed. Administration of B-GOS to elderly volunteers may be useful in positively affecting the microbiota and some markers of immune function associated with ageing.

New insights into the impact of Lactobacillus population on host-bacteria metabolic interplay

We aimed at evaluating the association between intestinal Lactobacillus sp. composition and their metabolic activity with the host metabolism in adult and elderly individuals. Faecal and plasma metabolites were measured and correlated to the Lactobacillus species distribution in healthy Estonian cohorts of adult (n=16; <48 y) and elderly (n=33; >65 y). Total cholesterol, LDL, C-reactive protein and glycated hemoglobin were statistically higher in elderly, while platelets, white blood cells and urinary creatinine were higher in adults. Aging was associated with the presence of L. paracasei and L. plantarum and the absence of L. salivarius and L. helveticus. High levels of intestinal Lactobacillus sp. were positively associated with increased concentrations of faecal short chain fatty acids, lactate and essential amino acids. In adults, high red blood cell distribution width was positively associated with presence of L. helveticus and absence of L. ruminis. L. helveticus was correlated to lactate and butyrate in faecal waters. This indicates a strong relationship between the composition of the gut Lactobacillus sp. and host metabolism. Our results confirm that aging is associated with modulations of blood biomarkers and intestinal Lactobacillus species composition. We identified specific Lactobacillus contributions to gut metabolic environment and related those to blood biomarkers. Such associations may prove useful to decipher the biological mechanisms underlying host-gut microbial metabolic interactions in an ageing population.

Does reactive surface area depend on grain size? Results from pH 3, 25 circle C far-from-equilibrium flow-through dissolution experiments on anorthite and biotite

Laboratory determined mineral weathering rates need to be normalised to allow their extrapolation to natural systems. The principle normalisation terms used in the literature are mass, and geometric- and BET specific surface area (SSA). The purpose of this study was to determine how dissolution rates normalised to these terms vary with grain size. Different size fractions of anorthite and biotite ranging from 180-150 to 20-10 mu m were dissolved in pH 3, HCl at 25 degrees C in flow through reactors under far from equilibrium conditions. Steady state dissolution rates after 5376 h (anorthite) and 4992 h (biotite) were calculated from Si concentrations and were normalised to initial- and final- mass and geometric-, geometric edge- (biotite), and BET SSA. For anorthite, rates normalised to initial- and final-BET SSA ranged from 0.33 to 2.77 X 10(-10) mol(feldspar) m(-2) s(-1), rates normalised to initial- and final-geometric SSA ranged from 5.74 to 8.88 X 10(-10) mol(feldspar) m(-2) s(-1) and rates normalised to initial- and final-mass ranged from 0.11 to 1.65 mol(feldspar) g(-1) s(-1). For biotite, rates normalised to initial- and final-BET SSA ranged from 1.02 to 2.03 X 10(-12) mol(biotite) m(-2) s(-1), rates normalised to initial- and final-geometric SSA ranged from 3.26 to 16.21 X 10(-12) mol(biotite) m(-2) s(-1), rates normalised to initial- and final-geometric edge SSA ranged from 59.46 to 111.32 x 10(-12) mol(biotite) m(-2) s(-1) and rates normalised to initial- and final-mass ranged from 0.81 to 6.93 X 10(-12) mol(biotite) g(-1) s(-1). For all normalising terms rates varied significantly (p <= 0.05) with grain size. The normalising terms which gave least variation in dissolution rate between grain sizes for anorthite were initial BET SSA and initial- and final-geometric SSA. This is consistent with: (1) dissolution being dominated by the slower dissolving but area dominant non-etched surfaces of the grains and, (2) the walls of etch pits and other dissolution features being relatively unreactive. These steady state normalised dissolution rates are likely to be constant with time. Normalisation to final BET SSA did not give constant ratios across grain size due to a non-uniform distribution of dissolution features. After dissolution coarser grains had a greater density of dissolution features with BET-measurable but unreactive wall surface area than the finer grains. The normalising term which gave the least variation in dissolution rates between grain sizes for biotite was initial BET SSA. Initial- and final-geometric edge SSA and final BET SSA gave the next least varied rates. The basal surfaces dissolved sufficiently rapidly to influence bulk dissolution rate and prevent geometric edge SSA normalised dissolution rates showing the least variation. Simple modelling indicated that biotite grain edges dissolved 71-132 times faster than basal surfaces. In this experiment, initial BET SSA best integrated the different areas and reactivities of the edge and basal surfaces of biotite. Steady state dissolution rates are likely to vary with time as dissolution alters the ratio of edge to basal surface area. Therefore they would be more properly termed pseudo-steady state rates, only appearing constant because the time period over which they were measured (1512 h) was less than the time period over wich they would change significantly. (c) 2006 Elsevier Inc. All rights reserved.

c-Jun N-terminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins for JNK signalling in mitochondrion-dependent apoptosis

The molecular mechanisms underlying the initiation and control of the release of cytochrome c during mitochondrion-dependent apoptosis are thought to involve the phosphorylation of mitochondrial Bcl-2 and Bcl-x(L). Although the c-Jun N-terminal kinase (JNK) has been proposed to mediate the phosphorylation of Bcl-2/Bcl-x(L) the mechanisms linking the modification of these proteins and the release of cytochrome c remain to be elucidated. This study was aimed at establishing interdependency between JNK signalling and mitochondrial apoptosis. Using an experimental model consisting of isolated, bioenergetically competent rat brain mitochondria, these studies show that (i) JNK catalysed the phosphorylation of Bcl-2 and Bcl-x(L) as well as other mitochondrial proteins, as shown by two-dimensional isoelectric focusing/SDS/PAGE; (ii) JNK-induced cytochrome c release, in a process independent of the permeability transition of the inner mitochondrial membrane (imPT) and insensitive to cyclosporin A; (iii) JNK mediated a partial collapse of the mitochondrial inner-membrane potential (Deltapsim) in an imPT- and cyclosporin A-independent manner; and (iv) JNK was unable to induce imPT/swelling and did not act as a co-inducer, but as an inhibitor of Ca-induced imPT. The results are discussed with regard to the functional link between the Deltapsim and factors influencing the permeability transition of the inner and outer mitochondrial membranes. Taken together, JNK-dependent phosphorylation of mitochondrial proteins including, but not limited to, Bcl-2/Bcl-x(L) may represent a potential of the modulation of mitochondrial function during apoptosis.