Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants
Candy, David C.A. ; Ampting, Marleen T.J. Van; Oude Nijhuis, Manon M. ; Wopereis, Harm ; Butt, Assad M. ; Peroni, Diego G. ; Vandenplas, Yvan ; Fox, Adam T. ; Shah, Neil ; West, Christina E. ; Garssen, Johan ; Harthoorn, Lucien F. ; Knol, Jan ; Michaelis, Louise J. - \ 2018
Pediatric Research 83 (2018)3. - ISSN 0031-3998 - p. 677 - 686.
BackgroundPrebiotics and probiotics (synbiotics) can modify gut microbiota and have potential in allergy management when combined with amino-acid-based formula (AAF) for infants with cow's milk allergy (CMA).MethodsThis multicenter, double-blind, randomized controlled trial investigated the effects of an AAF-including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) in feces from infants with suspected non-IgE-mediated CMA. Feces from age-matched healthy breastfed infants were used as reference (healthy breastfed reference (HBR)) for primary outcomes. The CMA subjects were randomized and received test or control formula for 8 weeks. Test formula was a hypoallergenic, nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V. Control formula was AAF without synbiotics.ResultsA total of 35 (test) and 36 (control) subjects were randomized; HBR included 51 infants. At week 8, the median percentage of bifidobacteria was higher in the test group than in the control group (35.4% vs. 9.7%, respectively; P<0.001), whereas ER/CC was lower (9.5% vs. 24.2%, respectively; P<0.001). HBR levels of bifidobacteria and ER/CC were 55% and 6.5%, respectively.ConclusionAAF including specific synbiotics, which results in levels of bifidobacteria and ER/CC approximating levels in the HBR group, improves the fecal microbiota of infants with suspected non-IgE-mediated CMA.
Intestinal microbiota in infants at high risk for allergy : Effects of prebiotics and role in eczema development
Wopereis, Harm ; Sim, Kathleen ; Shaw, Alexander ; Warner, John O. ; Knol, Jan ; Kroll, J.S. - \ 2018
Journal of Allergy and Clinical Immunology 141 (2018)4. - ISSN 0091-6749 - p. 1334 - 1342.e5.
Allergy - Butyrate - Eczema - Gastrointestinal - Infants - Lactate - Microbiome - Microbiota - Prebiotics - Short-chain fatty acids
Background: Development of the gut microbiota in infancy is important in maturation of the immune system. Deviations in colonization patterns have been associated with allergic manifestations such as eczema, but exact microbiome dysfunctions underlying allergies remain unclear. We studied the gut microbiota of 138 infants at increased risk of allergy, participating in a clinical trial investigating the effectiveness of a partially hydrolyzed protein formula supplemented with nondigestible oligosaccharides on the prevention of eczema. Objective: The effects of interventions and breast-feeding on fecal microbiota were investigated. Additionally, we aimed to identify microbial patterns associated with the onset of eczema. Methods: Bacterial taxonomic compositions in the first 26 weeks of life were analyzed by using 16S rRNA gene sequencing. Additionally, fecal pH and microbial metabolite levels were measured. Results: Fecal microbial composition, metabolites, and pH of infants receiving partially hydrolyzed protein formula supplemented with nondigestible oligosaccharides was closer to that of breast-fed infants than that of infants receiving standard cow's milk formula. Infants with eczema by 18 months showed temporal differences that were marked by decreased relative abundances of Parabacteroides and Enterobacteriaceae at 4 weeks and decreased relative abundances of lactate-utilizing bacteria producing butyrate at 26 weeks, namely Eubacterium and Anaerostipes species, supported by increased lactate and decreased butyrate levels. Conclusions: We showed that a partially hydrolyzed protein infant formula with specific prebiotics modulated the gut microbiota closer to that of breast-fed infants. Additionally, we identified a potential link between microbial activity and onset of eczema, which might reflect a suboptimal implementation of gut microbiota at specific developmental stages in infants at high risk for allergy.
Aberrant intestinal microbiota due to IL-1 receptor antagonist deficiency promotes IL-17- and TLR4-dependent arthritis
Rogier, Rebecca ; Ederveen, Thomas H.A. ; Boekhorst, Jos ; Wopereis, Harm ; Scher, Jose U. ; Manasson, Julia ; Frambach, Sanne J.C.M. ; Knol, Jan ; Garssen, Johan ; Kraan, Peter M. van der; Koenders, Marije I. ; Berg, Wim B. van den; Hijum, Sacha A.F.T. van; Abdollahi-Roodsaz, Shahla - \ 2017
Microbiome 5 (2017)1. - ISSN 2049-2618 - p. 63 - 63.
Autoimmune arthritis - IL-1 receptor antagonist - Microbiota - T helper 17 cells - Toll-like receptors
BACKGROUND: Perturbation of commensal intestinal microbiota has been associated with several autoimmune diseases. Mice deficient in interleukin-1 receptor antagonist (Il1rn -/- mice) spontaneously develop autoimmune arthritis and are susceptible to other autoimmune diseases such as psoriasis, diabetes, and encephalomyelitis; however, the mechanisms of increased susceptibility to these autoimmune phenotypes are poorly understood. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) in regulation of commensal intestinal microbiota, and assessed the involvement of microbiota subsets and innate and adaptive mucosal immune responses that underlie the development of spontaneous arthritis in Il1rn -/- mice.RESULTS: Using high-throughput 16S rRNA gene sequencing, we show that IL-1Ra critically maintains the diversity and regulates the composition of intestinal microbiota in mice. IL-1Ra deficiency reduced the intestinal microbial diversity and richness, and caused specific taxonomic alterations characterized by overrepresented Helicobacter and underrepresented Ruminococcus and Prevotella. Notably, the aberrant intestinal microbiota in IL1rn -/- mice specifically potentiated IL-17 production by intestinal lamina propria (LP) lymphocytes and skewed the LP T cell balance in favor of T helper 17 (Th17) cells, an effect transferable to WT mice by fecal microbiota. Importantly, LP Th17 cell expansion and the development of spontaneous autoimmune arthritis in IL1rn -/- mice were attenuated under germ-free condition. Selective antibiotic treatment revealed that tobramycin-induced alterations of commensal intestinal microbiota, i.e., reduced Helicobacter, Flexispira, Clostridium, and Dehalobacterium, suppressed arthritis in IL1rn -/- mice. The arthritis phenotype in IL1rn -/- mice was previously shown to depend on Toll-like receptor 4 (TLR4). Using the ablation of both IL-1Ra and TLR4, we here show that the aberrations in the IL1rn -/- microbiota are partly TLR4-dependent. We further identify a role for TLR4 activation in the intestinal lamina propria production of IL-17 and cytokines involved in Th17 differentiation preceding the onset of arthritis.CONCLUSIONS: These findings identify a critical role for IL1Ra in maintaining the natural diversity and composition of intestinal microbiota, and suggest a role for TLR4 in mucosal Th17 cell induction associated with the development of autoimmune disease in mice.
Synbiotics-supplemented amino acid-based formula supports adequate growth in cow's milk allergic infants
Burks, A.W. ; Harthoorn, L.F. ; Ampting, M.T.J. Van; Oude Nijhuis, M.M. ; Langford, J.E. ; Wopereis, Harm ; Goldberg, S.B. ; Ong, P.Y. ; Essink, B.J. ; Scott, R.B. ; Harvey, B.M. - \ 2015
Pediatric Allergy and Immunology 26 (2015)4. - ISSN 0905-6157 - p. 316 - 322.
Amino acid-based formula - Cow's milk allergy - Growth - Infant - Prebiotics - Probiotics - Randomized double-blind controlled trial - Safety

Background: Children with cow's milk allergy (CMA) are at risk for inadequate nutritional intake and growth. Dietary management of CMA, therefore, requires diets that are not only hypoallergenic but also support adequate growth in this population. This study assessed growth of CMA infants when using a new amino acid-based formula (AAF) with prebiotics and probiotics (synbiotics) and evaluated its safety in the intended population. Methods: In a prospective, randomized, double-blind controlled study, full-term infants with diagnosed CMA received either an AAF (control; n = 56) or AAF with synbiotics (oligofructose, long-chain inulin, acidic oligosaccharides, Bifidobacterium breve M-16V) (test; n = 54) for 16 wk. Primary outcome was growth, measured as weight, length and head circumference. Secondary outcomes included allergic symptoms and stool characteristics. Results: Average age (±SD) of infants at inclusion was 4.5 ± 2.4 months. Both formulas equally supported growth according to WHO 2006 growth charts and resulted in similar increases of weight, length and head circumference. At week 16, differences (90% CI) in Z-scores (test-control) were as follows: weight 0.147 (-0.10; 0.39, p = 0.32), length -0.299 (-0.69; 0.09, p = 0.21) and head circumference 0.152 (-0.15; 0.45, p = 0.40). Weight-for-age and length-for-age Z-scores were not significantly different between the test and control groups. Both formulas were well tolerated and reduced allergic symptoms; the number of adverse events was not different between the groups. Conclusions: This is the first study that shows that an AAF with a specific synbiotic blend, suitable for CMA infants, supports normal growth and growth similar to the AAF without synbiotics. This clinical trial is registered as NCT00664768.

Assessment of rice self-sufficiency in 2025 in eight African countries
Oort, P.A.J. van; Saito, K. ; Tanaka, A. ; Amovin-Assagaba, E. ; Bussel, L.G.J. van; Wart, J. van; Groot, H.L.E. de; Ittersum, M.K. van; Cassman, K.G. ; Wopereis, M.C.S. - \ 2015
Global Food Security 5 (2015). - ISSN 2211-9124 - p. 39 - 49.
Most African countries are far from self-sufficient in meeting their rice consumption; in eight countries the production: consumption ratio, ranged from 0.16 to 1.18 in 2012. We show that for the year 2025, with population growth, diet change and yield increase on existing land (intensification), countries cannot become fully self-sufficient in rice. This implies that for the future, a mixture of area expansion and imports will be needed on top of yield gap closure. Further research is needed for identification of most suitable new land for rice area expansion and areas that should be protected.
Analyzing metabolomics-based challenge tests
Vis, D.J. ; Westerhuis, J.A. ; Jacobs, D.M. ; Duynhoven, J.P.M. van; Wopereis, S. ; Ommen, B. van; Hendriks, M.M.W.B. ; Smilde, A.K. - \ 2015
Metabolomics 11 (2015)1. - ISSN 1573-3882 - p. 50 - 63.
glucose-tolerance test - insulin sensitivity - mathematical-models - component analysis - plasma metabolome - health - asca - reconstruction - phenotype - discovery
Challenge tests are used to assess the resilience of human beings to perturbations by analyzing responses to detect functional abnormalities. Well known examples are allergy tests and glucose tolerance tests. Increasingly, metabolomics analysis of blood or serum samples is used to analyze the biological response of the individual to these challenges. The information content of such metabolomics challenge test data involves both the disturbance and restoration of homeostasis on a metabolic level and is thus inherently different from the analysis of steady state data. It opens doors to study the variation of resilience between individuals beyond the classical biomarkers; preferably in terms of underlying biological processes. We review challenge tests in which metabolomics was used to analyze the biological response. Specifically, we describe strategies to perform statistical analyses on the responses and we will show some examples of these strategies applied to a postprandial challenge that was used to study a diet with anti-inflammatory properties. Finally we discuss open issues and give recommendation for further research.
Aberrant intestinal microbiota due to IL-1 receptor antagonist deficiency promotes IL-17- and TLR4-dependent arthritis
Rogier, Rebecca ; Ederveen, Thomas H.A. ; Boekhorst, Jos ; Wopereis, H.J. ; Scher, Jose U. ; Manasson, Julia ; Knol, J. ; Garssen, Johan ; Kraan, Peter M. van der; Koenders, Marije I. ; Berg, Wim B. van den; Hijum, Sacha A.F.T. van; Abdollahi-Roodsaz, Shahla - \ 2014
PRJEB7447 - ERP007176
The aim of this study was to investigate the role of IL-1 receptor signalling and the involvement of Toll-like receptor (TLR) 2 and TLR4 in defining the intestinal microbiota and the associated mucosal and systemic immune response. Multiplex 454 pyrosequencing of V5 and V6 hyper-variable regions of fecal bacterial 16S rRNA was used to define intestinal microbial communities in BALB/c wild type (WT), IL-1Ra-/- and IL-1Ra/TLR double knock-out (DKO) mice.
The first thousand days – intestinal microbiology of early life: establishing a symbiosis
Wopereis, H. ; Oozeer, R. ; Knipping, K. ; Belzer, C. ; Knol, J. - \ 2014
Pediatric Allergy and Immunology 25 (2014)5. - ISSN 0905-6157 - p. 428 - 438.
gradient gel-electrophoresis - infant gut microbiota - fecal microbiota - atopic-dermatitis - allergic diseases - immune-system - galacto-oligosaccharides - fructo-oligosaccharides - reduced diversity - human-milk
The development of the intestinal microbiota in the first years of life is a dynamic process significantly influenced by early-life nutrition. Pioneer bacteria colonizing the infant intestinal tract and the gradual diversification to a stable climax ecosystem plays a crucial role in establishing host–microbe interactions essential for optimal symbiosis. This colonization process and establishment of symbiosis may profoundly influence health throughout life. Recent developments in microbiologic cultivation-independent methods allow a detailed view of the key players and factors involved in this process and may further elucidate their roles in a healthy gut and immune maturation. Aberrant patterns may lead to identifying key microbial signatures involved in developing immunologic diseases into adulthood, such as asthma and atopic diseases. The central role of early-life nutrition in the developmental human microbiota, immunity, and metabolism offers promising strategies for prevention and treatment of such diseases. This review provides an overview of the development of the intestinal microbiota, its bidirectional relationship with the immune system, and its role in impacting health and disease, with emphasis on allergy, in early life.
Altered gut microbiota and activity in a murine model of autism spectrum disorders
Theije, C.G. de; Wopereis, H.J. ; Ramadan, M. ; Eijndthoven, T. van; Lambert, J. ; Knol, J. ; Garssen, J. ; Kraneveld, A.D. ; Oozeer, R. - \ 2014
Brain, Behavior, and Immunity 37 (2014). - ISSN 0889-1591 - p. 197 - 206.
valproic acid - intestinal microbiota - maternal separation - host interactions - propionic-acid - onset autism - children - brain - microflora - exposure
Autism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders with evidence of genetic predisposition. Intestinal disturbances are reported in ASD patients and compositional changes in gut microbiota are described. However, the role of microbiota in brain disorders is poorly documented. Here, we used a murine model of ASD to investigate the relation between gut microbiota and autism-like behaviour. Using next generation sequencing technology, microbiota composition was investigated in mice in utero exposed to valproic acid (VPA). Moreover, levels of short chain fatty acids (SCFA) and lactic acid in caecal content were determined. Our data demonstrate a transgenerational impact of in utero VPA exposure on gut microbiota in the offspring. Prenatal VPA exposure affected operational taxonomic units (OTUs) assigned to genera within the main phyla of Bacteroidetes and Firmicutes and the order of Desulfovibrionales, corroborating human ASD studies. In addition, OTUs assigned to genera of Alistipes, Enterorhabdus, Mollicutes and Erysipelotrichalis were especially associated with male VPA-exposed offspring. The microbial differences of VPA in utero-exposed males deviated from those observed in females and was (i) positively associated with increased levels of caecal butyrate as well as ileal neutrophil infiltration and (ii) inversely associated with intestinal levels of serotonin and social behaviour scores. These findings show that autism-like behaviour and its intestinal phenotype is associated with altered microbial colonization and activity in a murine model for ASD, with preponderance in male offspring. These results open new avenues in the scientific trajectory of managing neurodevelopmental disorders by gut microbiome modulation
Assessment of inflammatory resilience in healthy subjects using dietary lipid and glucose challenges
Wopereis, S. ; Wolvers, D. ; Erk, M. van; Gribnau, M. ; Kremer, B. ; Dorsten, F.A. van; Boelsma, E. ; Garczarek, U. ; Cnubben, N. ; Frenken, L. ; Logt, P. van der; Hendriks, H.F.J. ; Albers, R. ; Duynhoven, J.P.M. van; Ommen, B. van; Jacobs, D.M. - \ 2013
BMC Medical Genomics 6 (2013). - ISSN 1755-8794 - 16 p.
type-2 diabetic-patients - necrosis-factor-alpha - oxidative stress - endothelial dysfunction - cytokine concentrations - postprandial variations - fatty-acids - obese men - fish-oil - markers
Background Resilience or the ability of our body to cope with daily-life challenges has been proposed as a new definition of health, with restoration of homeostasis as target resultant of various physiological stress responses. Challenge models may thus be a sensitive measure to study the body’s health. The objective of this study was to select a dietary challenge model for the assessment of inflammatory resilience. Meals are a challenge to metabolic homeostasis and are suggested to affect inflammatory pathways, yet data in literature are limited and inconsistent. Method The kinetic responses of three different dietary challenges and a water control challenge were assessed on various metabolic and inflammatory markers in 14 healthy males and females using a full cross-over study design. The dietary challenges included glucose (75 g glucose in 300 ml water), lipids (200 ml whipping cream) and a mix of glucose and lipids (same amounts as above), respectively. Blood samples were collected at baseline and at 0.5, 1, 2, 4, 6, 8 and 10 h after consumption of the treatment products. Inflammation (IFN¿, IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF-a CRP, ICAM-1, VCAM-1, SAA, E-selectin, P-selectin, thrombomodulin, leukocytes, neutrophils, lymphocytes) and clinical (e.g. glucose, insulin, triglycerides) markers as well as gene expression in blood cells and plasma oxylipin profiles were measured. Results All three dietary challenges induced changes related to metabolic control such as increases in glucose and insulin after the glucose challenge and increases in triglycerides after the lipid challenge. In addition, differences between the challenges were observed for precursor oxylipins and some downstream metabolites including DiHETrE’s and HODE’s. However, none of the dietary challenges induced an acute inflammatory response, except for a modest increase in circulating leukocyte numbers after the glucose and mix challenges. Furthermore, subtle, yet statistically significant increases in vascular inflammatory markers (sICAM-1 and sVCAM-1) were found after the mix challenge, when compared to the water control challenge. Conclusions This study shows that dietary glucose and lipid challenges did not induce a strong acute inflammatory response in healthy subjects, as quantified by an accurate and broad panel of parameters.
Towards a new approach for understanding interactions of technology with environment and society in small-scale rice farming
Nuijten, H.A.C.P. ; Temudo, M.P. ; Richards, P. ; Okry, F. ; Teeken, B.W.E. ; Mokuwa, G.A. ; Struik, P.C. - \ 2013
In: Realizing Africa's rice promise / Wopereis, M.C.S., Johnson, D.E., Ahmadi, N., Tollens, E., Jalloh, A., Oxfordshire : CABI - ISBN 9781845938123 - p. 355 - 366.
Gene flow in African rice farmers' fields
Nuijten, H.A.C.P. ; Richards, P. - \ 2013
In: Realizing Africa's rice promise / Wopereis, M.C.S., Johnson, D.E., Ahmadi, N., Tollens, E., Jalloh, A., Oxfordshire : CABI - ISBN 9781845938123 - p. 108 - 129.
Influence of fermented milk products, prebiotics and probiotics on microbiota composition and health
Ceapa, C.D. ; Wopereis, H.J. ; Rezaïki, L. ; Kleerebezem, M. ; Knol, J. ; Oozeer, R. - \ 2013
Best Practice & Research: Clinical Gastroenterology 27 (2013)1. - ISSN 1521-6918 - p. 139 - 155.
irritable-bowel-syndrome - 1st 6 months - human lactobacillus strain - formula-fed infants - germ-free mice - gut microbiota - intestinal microbiota - atopic-dermatitis - double-blind - human feces
The gut microbiota is a highly diverse and relative stabile ecosystem increasingly recognized for its impact on human health. The homeostasis of microbes and the host is also referred to as eubiosis. In contrast, deviation from the normal composition, defined as dysbiosis, is often associated with localized diseases such as inflammatory bowel disease or colonic cancer, but also with systemic diseases like metabolic syndrome and allergic diseases. Modulating a gut microbiota dysbiosis with nutritional concepts may contribute to improving health status, reducing diseases or disease symptoms or supporting already established treatments. The gut microbiota can be modulated by different nutritional concepts, varying from specific food ingredients to complex diets or by the ingestion of particular live microorganisms. To underpin the importance of bacteria in the gut, we describe molecular mechanisms involved in the crosstalk between gut bacteria and the human host, and review the impact of different nutritional concepts such as pre-, pro- and synbiotics on the gastrointestinal ecosystem and their potential health benefits. The aim of this review is to provide examples of potential nutritional concepts that target the gut microbiota to support human physiology and potentially health outcomes.
Lipidomics reveals multiple pathway effects of a multi components preparation on lipd biochemistry in ApoeE*3Leiden.CETP mice
Wei, H. ; Hu, C. ; Wang, M. ; Hoek, A.M. van den; Reijmers, T.H. ; Wopereis, S. ; Bouwman, J. ; Ramaker, R. ; Korthout, H.A.A.J. ; Vennik, M. ; Hankemeier, T. ; Havekes, L.M. ; Witkamp, R.F. ; Verheij, E.R. ; Xu, G. ; Greef, J. de - \ 2012
PLoS One 7 (2012)1. - ISSN 1932-6203
cholesteryl ester transfer - systems biology - apoe-asterisk-3-leiden.cetp mice - aggravates atherosclerosis - overweight patients - chinese medicine - weight-reduction - transfer protein - hdl-cholesterol - transgenic mice
Background: Causes and consequences of the complex changes in lipids occurring in the metabolic syndrome are only partly understood. Several interconnected processes are deteriorating, which implies that multi-target approaches might be more successful than strategies based on a limited number of surrogate markers. Preparations from Chinese Medicine (CM) systems have been handed down with documented clinical features similar as metabolic syndrome, which might help developing new intervention for metabolic syndrome. The progress in systems biology and specific animal models created possibilities to assess the effects of such preparations. Here we report the plasma and liver lipidomics results of the intervention effects of a preparation SUB885C in apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE*3Leiden.CETP) mice. SUB885C was developed according to the principles of CM for treatment of metabolic syndrome. The cannabinoid receptor type 1 blocker rimonabant was included as a general control for the evaluation of weight and metabolic responses. Methodology/Principal Findings: ApoE*3Leiden.CETP mice with mild hypercholesterolemia were divided into SUB885C-, rimonabant- and non-treated control groups. SUB885C caused no weight loss, but significantly reduced plasma cholesterol (-49%, p <0.001), CETP levels (-31%, p
Enhanced catch-up growth after a challenge in animals on organic feed
Huber, M. ; Coulier, L. ; Wopereis, S. ; Savelkoul, H.F.J. ; Nierop, D. ; Hoogenboom, L.A.P. - \ 2012
biologische landbouw - diergezondheid - pluimveehouderij - pluimveevoeding - kippen - kuikens - organic farming - animal health - poultry farming - poultry feeding - fowls - chicks
A feeding experiment was performed in two generations of three groups of chickens with different immune responsiveness. All groups were fed identically composed feeds from either organic or conventional production. In the young animals of the second generation an immune challenge was imposed. The chickens fed conventional feed showed overall a higher weight gain, whereas feed intake of the groups was similar. The animals on organic feed showed an enhanced immune reactivity, a stronger reaction to the immune challenge, as well as an enhanced ’catch-up-growth’ after the challenge.
Comparative transcriptomics and metabolomic analysis of fenofibrate and fish oil treatments in mice
Lu Yingchang (Kevin), Y. ; Boekschoten, Mark ; Wopereis, Suzan ; Muller, Michael ; Kersten, Sander - \ 2011
Mus musculus - GSE32706 - PRJNA147003
Elevated circulating triglycerides, which are considered a risk factor for cardiovascular disease, can be targeted by treatment with fenofibrate or fish oil. To gain insight into underlying mechanisms, we carried out a comparative transcriptomics and metabolomics analysis of the effect of 2 week treatment withfenofibrate and fish oil in mice. Plasma triglycerides were significantly decreased byfenofibrate (-49.1%) and fish oil (-21.8%), whereas plasma cholesterol was increased by fenofibrate (+29.9%) and decreased by fish oil (-32.8%). Levels of various phospholipid species were specifically decreased by fish oil, while levels of Krebs cycle intermediates were increased specifically by fenofibrate. Plasma levels of many amino acids were altered by fenofibrate and to a lesser extent by fish oil. Both fenofibrate and fish oil upregulated genes involved in fatty acid metabolism, and downregulated genes involved in blood coagulation and fibrinolysis. Significant overlap in gene regulation by fenofibrate and fish oil was observed, reflecting their property as high or low affinity agonist for PPARα, respectively. Fenofibrate specifically downregulated genes involved in complement cascade and inflammatory response. Fish oil specifically downregulated genes involved in cholesterol and fatty acid biosynthesis, and upregulated genes involved in amino acid and arachidonic acid metabolism. Taken together, the data indicate that despite being similarly potent towards modulating plasma free fatty acids, cholesterol and triglyceride levels, fish oil causes modest changes in gene expression likely via activation of multiple mechanistic pathways, whereas fenofibrate causes pronounced gene expression changes via a single pathway, reflecting the key difference between nutritional and pharmacological intervention.
Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil treatments in mice
Lu, Y. ; Boekschoten, M.V. ; Wopereis, S. ; Muller, M.R. ; Kersten, A.H. - \ 2011
Physiological genomics 43 (2011)23. - ISSN 1094-8341 - p. 1307 - 1318.
activated-receptor-alpha - polyunsaturated fatty-acids - coronary-heart-disease - ppar-alpha - gene-expression - eicosapentaenoic acid - vitamin-k - lipoprotein metabolism - adiponectin secretion - protein expression
Elevated circulating triglycerides, which are considered a risk factor for cardiovascular disease, can be targeted by treatment with fenofibrate or fish oil. To gain insight into underlying mechanisms, we carried out a comparative transcriptomics and metabolomics analysis of the effect of 2 wk treatment with fenofibrate and fish oil in mice. Plasma triglycerides were significantly decreased by fenofibrate (-49.1%) and fish oil (-21.8%), whereas plasma cholesterol was increased by fenofibrate (+29.9%) and decreased by fish oil (-32.8%). Levels of various phospholipid species were specifically decreased by fish oil, while levels of Krebs cycle intermediates were increased specifically by fenofibrate. Plasma levels of many amino acids were altered by fenofibrate and to a lesser extent by fish oil. Both fenofibrate and fish oil upregulated genes involved in fatty acid metabolism and downregulated genes involved in blood coagulation and fibrinolysis. Significant overlap in gene regulation by fenofibrate and fish oil was observed, reflecting their property as high or low affinity agonist for peroxisome proliferator-activated receptor-a, respectively. Fenofibrate specifically downregulated genes involved in complement cascade and inflammatory response. Fish oil specifically downregulated genes involved in cholesterol and fatty acid biosynthesis and upregulated genes involved in amino acid and arachidonic acid metabolism. Taken together, the data indicate that despite being similarly potent toward modulating plasma free fatty acids, cholesterol, and triglyceride levels, fish oil causes modest changes in gene expression likely via activation of multiple mechanistic pathways, whereas fenofibrate causes pronounced gene expression changes via a single pathway, reflecting the key difference between nutritional and pharmacological intervention.
Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies
Ommen, B. van; Bouwman, J.H. ; Dragsted, L.O. ; Drevon, C.A. ; Elliott, R. ; Groot, P.J. de; Kaput, J. ; Mathers, J.C. ; Müller, M.R. ; Pepping, F. ; Saito, J. ; Scalbert, A. ; Radonjic, M. ; Rocca-Serra, P. ; Travis, A. ; Wopereis, S. ; Evelo, C. - \ 2010
Genes & Nutrition 5 (2010)3. - ISSN 1555-8932 - p. 189 - 203.
gene-expression - metabolic phenotypes - association - framework - services - network - complex - health - diet
The challenge of modern nutrition and health research is to identify food-based strategies promoting life-long optimal health and well-being. This research is complex because it exploits a multitude of bioactive compounds acting on an extensive network of interacting processes. Whereas nutrition research can profit enormously from the revolution in ‘omics’ technologies, it has discipline-specific requirements for analytical and bioinformatic procedures. In addition to measurements of the parameters of interest (measures of health), extensive description of the subjects of study and foods or diets consumed is central for describing the nutritional phenotype. We propose and pursue an infrastructural activity of constructing the “Nutritional Phenotype database” (dbNP). When fully developed, dbNP will be a research and collaboration tool and a publicly available data and knowledge repository. Creation and implementation of the dbNP will maximize benefits to the research community by enabling integration and interrogation of data from multiple studies, from different research groups, different countries and different-omics levels. The dbNP is designed to facilitate storage of biologically relevant, pre-processed-omics data, as well as study descriptive and study participant phenotype data. It is also important to enable the combination of this information at different levels (e.g. to facilitate linkage of data describing participant phenotype, genotype and food intake with information on study design and-omics measurements, and to combine all of this with existing knowledge). The biological information stored in the database (i.e. genetics, transcriptomics, proteomics, biomarkers, metabolomics, functional assays, food intake and food composition) is tailored to nutrition research and embedded in an environment of standard procedures and protocols, annotations, modular data-basing, networking and integrated bioinformatics. The dbNP is an evolving enterprise, which is only sustainable if it is accepted and adopted by the wider nutrition and health research community as an open source, pre-competitive and publicly available resource where many partners both can contribute and profit from its developments. We introduce the Nutrigenomics Organisation (NuGO, http://www.nugo.org) as a membership association responsible for establishing and curating the dbNP. Within NuGO, all efforts related to dbNP (i.e. usage, coordination, integration, facilitation and maintenance) will be directed towards a sustainable and federated infrastructure
Effects of organically and conventionally produced feed on biomarkers of health in a chicken model
Huber, M. ; Vijver, L.P.L. van de; Parmentier, H.K. ; Savelkoul, H.F.J. ; Coulier, L. ; Wopereis, S. ; Verheij, E. ; Greef, J. de; Nierop, D. ; Hoogenboom, R.A.P. - \ 2010
British Journal of Nutrition 103 (2010)5. - ISSN 0007-1145 - p. 663 - 676.
red-blood-cells - catch-up growth - antibody-responses - natural antibodies - immune-responses - lines - foods - metabolomics - systems - consequences
Consumers expect organic products to be healthier. However, limited research has been performed to study the effect of organic food on health. The present study aimed to identify biomarkers of health to enable future studies in human subjects. A feeding experiment was performed in two generations of three groups of chickens differing in immune responsiveness, which were fed identically composed feeds from either organic or conventional produce. The animals of the second generation were exposed to an immune challenge and sacrificed at 13 weeks of age. Feed and ingredients were analysed on macro- and micronutrients, i.e. vitamins, minerals, trace elements, heavy metals and microbes. The chickens were studied by general health and immune parameters, metabolomics, genomics and post-mortem evaluation. The organic and conventional feeds were comparable with respect to metabolisable energy. On average, the conventionally produced feeds had a 10 % higher protein content and some differences in micronutrients were observed. Although animals on both feeds were healthy, differences between the groups were found. The random control group of chickens fed conventional feed showed overall a higher weight gain during life span than the group on organic feed, although feed intake was mostly comparable. The animals on organic feed showed an enhanced immune reactivity, a stronger reaction to the immune challenge as well as a slightly stronger ‘catch-up growth’ after the challenge. Biomarkers for future research were identified in the parameters feed intake, body weight and growth rate, and in immunological, physiological and metabolic parameters, several of these differing most pronounced after the challenge
Long-term effects of mineral and organic fertilization on soil organic matter fractions and sorghum yield under Sudano-Sahelian conditions
Mando, A. ; Bonzi, M. ; Wopereis, M.C.S. ; Lompo, F. ; Stroosnijder, L. - \ 2005
Soil Use and Management 21 (2005)1. - ISSN 0266-0032 - p. 396 - 401.
land-use - management - dynamics - tillage - carbon - residues - systems
Knowledge of changes in soil organic matter (SOM) fractions resulting from agricultural practice is important for decision-making at farm level because of the contrasting effects of different SOM fractions on soils. A long-term trial sited under Sudano-Sahelian conditions was used to assess the effect of organic and inorganic fertilization on SOM fractions and sorghum performance. Sorghum straw and kraal manure were applied annually at 10 t ha(-1), with and without urea at 60 kg N ha(-1). The other treatments included fallowing, a control (no fertilization), and inorganic fertilization only (urea, 60 kg N ha(-1)). Fallowing gave significantly larger soil organic carbon and nitrogen (N) levels than any other treatment. Total soil SOM and N concentrations increased in the following order: urea only <straw <control <straw+urea <manure with or without urea <fallow. Farming had an adverse effect on SOM and N status; however, this mostly affected the fraction of SOM > 0.053 mm (particulate organic matter, POM). The POM concentrations in the control, straw and urea-only treatments were about one-half of the POM concentrations in the fallow treatment. POM concentrations increased in the following order: urea only <control <straw with or without urea <manure with or without urea <fallow. The fraction of SOM <0.053 mm (fine organic matter, FOM) was greater than POM in all plots except in fallow and manure+urea plots. Total N concentration followed the same trend as SOM, but cultivation led to a decline in both POM-N and FOM-N. Crop yield was greatest in the manure plots and lowest in the straw, control and urea-only plots. Results indicate that under Sudano-Sahelian conditions, SOM, POM and FOM fractions and crop performance were better maintained using organic materials with a low C/N ratio (manure) than with organic material with a high C/N ratio (straw). Urea improved the effect of straw on crop yield and SOM concentration.
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