A. Vriesema

Energy Research Centre of the Netherlands, Heerhugowaard, North Holland, Netherlands

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Publications (12)26.94 Total impact

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    ABSTRACT: Background. The immunomodulatory nutritional product NR100157 has been developed for human immunodeficiency virus (HIV) - infected individuals. We hypothesised that targeting the compromised gastrointestinal tract of HIV-infected subjects would result in systemic immunological benefits. Methods. In a multicentre, randomised controlled double-blind trial (ISRCTN81868024 - BITE), 340 HIV-1 positive adults not on antiretroviral therapy, with CD4(+) T-cell counts <800/l were given either NR100157, or an isocaloric and isonitrogenous control for 52 weeks. Primary outcome was CD4(+) T-cell count. Secondary outcomes included plasma viral load (pVL), safety, and tolerability. In a pilot study (n=20), levels of CD4(+)CD25(+) and CD8(+)CD38(+) activation were measured (n=20). The trial is registered at the Dutch Trial Register (NTR886) and ISRCTN81868024. Results. At 52 weeks, CD4(+) T-cell decline showed a 40 cell/l difference (p=0·03) in the ITT population in favour of the immunomodulatory NR100157 (control vs active, -68±15 vs -28±16 cells/l/year). The change in pVL from baseline was similar between groups (p=0·81). In the pilot study, %CD4(+)CD25(+) was lower in the active group (p<0·05) and correlated with changes in CD4(+) T-cell count (r=-0·55, p<0·05). %CD8(+)CD38(+) levels were unaffected. Conclusions. The specific immunonutrition NR100157 significantly reduces CD4(+) decline in HIV-1 infected individuals and this is associated with decreased levels of CD4(+)CD25(+). (This nutritional intervention is likely to affect locally gut integrity and gut-associated lymphoid tissue homeostasis, which in turn translates positively to systemic effects.).
    Clinical Infectious Diseases 03/2013; · 9.37 Impact Factor
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    ABSTRACT: To provide insight in the molecular basis for intestinal host-microbe interactions, we determined the genome-wide transcriptional response of human intestinal epithelial cells following exposure to cells of Bifidobacterium breve. To select an appropriate test system reflecting inflammatory conditions, the responsiveness to TNF-α was compared in T84, Caco-2 and HT-29 cells. The highest TNF-α response was observed in HT-29 cells and this cell line was selected for exposure to the B. breve strains M-16V, NR246 and UCC2003. After one hour of bacterial pre-incubation followed by two hours of additional TNF-α stimulation, B. breve M-16V (86%), but to a much lesser extent strains NR246 (50%) or UCC2003 (32%), showed a strain-specific reduction of the HT-29 transcriptional response to the inflammatory treatment. The most important functional groups of genes that were transcriptionally suppressed by the presence of B. breve M-16V, were found to be involved in immune regulation and apoptotic processes. About 54% of the TNF-α induced genes were solely suppressed by the presence of B. breve M-16V. These included apoptosis-related cysteine protease caspase 7 (CASP7), interferon regulatory factor 3 (IRF3), amyloid beta (A4) precursor proteinbinding family A member 1 (APBA1), NADPH oxidase (NOX5), and leukemia inhibitory factor receptor (LIFR). The extracellular IL-8 concentration was determined by an immunological assay but did not change significantly, indicating that B. breve M-16V only partially modulates the TNF-α pathway. In conclusion, this study shows that B. breve strains modulate gene expression in HT-29 cells under inflammatory conditions in a strain-specific way.
    Beneficial Microbes 06/2011; 2(2):115-28. · 1.47 Impact Factor
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    ABSTRACT: Intestinal mucosal immune system is an early target for human immunodeficiency virus type 1 (HIV-1) infection, resulting in CD4(+) T-cell depletion, deterioration of gut lining, and fecal microbiota composition. We evaluated the effects of a prebiotic oligosaccharide mixture in highly active antiretroviral therapy (HAART)-naive HIV-1-infected adults. In a pilot double-blind, randomized, placebo-controlled study, 57 HAART-naive HIV-1-infected patients received a unique oligosaccharide mixture (15 or 30 g short chain galactooligosaccharides/long chain fructooligosaccharides/pectin hydrolysate-derived acidic oligosaccharides (scGOS/lcFOS/pAOS) daily) or a placebo for 12 weeks. Microbiota composition improved significantly with increased bifidobacteria, decreased Clostridium coccoides/Eubacterium rectale cluster, and decreased pathogenic Clostridium lituseburense/Clostridium histolyticum group levels upon prebiotic supplementation. In addition, a reduction of soluble CD14 (sCD14), activated CD4(+)/CD25(+) T cells, and significantly increased natural killer (NK) cell activity when compared with control group were seen in the treatment group. The results of this pilot trial highly significantly show that dietary supplementation with a prebiotic oligosaccharide mixture results in improvement of the gut microbiota composition, reduction of sCD14, CD4(+) T-cell activation (CD25), and improved NK cell activity in HAART-naive HIV-infected individuals.
    Mucosal Immunology 04/2011; 4(5):554-63. · 7.54 Impact Factor
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    ABSTRACT: Bifidobacteria are a predominant group present among adult human intestinal microbiota and are considered to be beneficial to host health. Both the dynamics and functional activity of bifidobacteria from the intestinal tract of four adults, following ingestion of a mix consisting of short chain galactooligosaccharides, long chain fructooligosaccharides and acidic oligosaccharides from pectin hydrolysate (GFP), was investigated. The percentage of total bifidobacteria, monitored by quantitative real time PCR, was not significantly altered but marked species-specific changes occurred in all individuals over time, indicating a dynamic bifidobacterial community. Insight into the functional activity of the bifidobacteria was acquired using a clone library-based microarray comprising the genomes of various bifidobacteria to reveal the bifidobacterial transcriptome within the fecal community. Total RNA from the fecal microbial community was hybridized to the microarray and 310 clones were selected for sequencing which revealed genes belonging to a wide range of functional groups demonstrating substantial metabolic activity. While the intake of GFP did not have a significant effect on the overall change in gene expression, 82 genes showed a significant change. Most of the predicted genes were involved in metabolism of carbohydrates of plant origin, house keeping functions such as DNA replication and transcription, followed by membrane transport of a wide variety of substrates including sugars and metals and amino acid metabolism. Other genes were involved in transport, nucleotide metabolism, amino acid metabolism, environmental information processing and cellular processes and signalling. A smaller number of genes were involved in general metabolism, glycan metabolism, energy metabolism, lipid metabolism and cell surface. These results support the notion that bifidobacteria utilize mainly indigestible polysaccharides as their main source of energy and biosynthesis of cellular components.
    Gut Microbes 01/2011; 2(4):217-26.
  • Beneficial Microbes. 01/2011; 2(2):115-128.
  • Clinical Nutrition Supplements 01/2009; 4(2):139-140.
  • Clinical Nutrition Supplements 01/2009; 4(2):140-140.
  • Clinical Nutrition Supplements 01/2008; 3:119-119.
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  • Allergy 01/2008; 63:557-557. · 5.88 Impact Factor
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    C van Limpt, A Crienen, A Vriesema, J Knol
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    ABSTRACT: Background: It has been demonstrated that the addition of a specific prebiotic mixture of galacto- and fructo-oligosaccharides to an infant formula can change the intestinal flora of formula-fed infants. The microbial composition, the metabolic end products and the pH of the feces shift in the direction of values typical for breast-fed infants. To test the relevance of the observed changes, the effect of the different short chain fatty acids, lactate and pH on the growth of opportunistic pathogens and gut commensals was tested in vitro.Methods: Representative concentrations of D- and L-lactate and SCFA's (acetate, propionate and butyrate), either individually or in combinations, were tested in Tryptic Soy Broth in a pH-range of 5 to 7.5. Inhibition of several opportunistic pathogens (Salmonella typhimurium, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Klebseilla pneumoniae) and some gut commensals (Lactobacillus rhamnosus, Lactobacillus plantarum and Bifidobacterium breve) by these metabolic end products was tested by comparing the individual growth curves as determined by turbidity measurements (OD600).Results: The different SCFA's, and especially acetate, gave a concentration dependent inhibition of the different pathogens. The growth inhibition was most pronounced at lower pH values. The combination of lactate (12.5 mM), SCFA's (Acetate 25 mM, Butyrate 2.5 mM, Propionate 5 mM) and a low pH (5.5) as found in the feces of breast- and prebiotic-fed infants, almost completely inhibited all tested pathogens. The tested commensal bacteria were only slightly affected by these combinations, and in these cases sometimes even a stimulation of growth was observed.Conclusion: Acetate, an end product of bifidobacteria in the gut of breast-fed and prebiotic-fed infants, is an efficient growth inhibitor of many common pathogens. Especially at lower pH values the growth in vitro is strongly reduced. The other SCFA's and lactate have an additive effect on the inhibition of the pathogens tested. Growth of commensals, like bifidobacteria and lactobacilli, is hardly affected under these conditions. The physiological changes induced by a mixture of galacto- and fructo-oligosaccharides can therefor be considered as an important mechanism for the inhibition of pathogens in the gut.
    Pediatric Research 08/2004; 56(3):487-487. · 2.67 Impact Factor