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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    Metaproteomic and 16S rRNA Gene Sequencing Analysis of the Infant Fecal Microbiome
    Cortes, Laetitia ; Wopereis, Harm ; Tartiere, Aude ; Piquenot, Julie ; Gouw, Joost W. ; Tims, Sebastian ; Knol, Jan ; Chelsky, Daniel - \ 2019
    International Journal of Molecular Sciences 20 (2019)6. - ISSN 1661-6596
    fecal - infants - intestinal - mass spectrometry - metabolism - metacluster - microbiome

    A metaproteomic analysis was conducted on the fecal microbiome of eight infants to characterize global protein and pathway expression. Although mass spectrometry-based proteomics is now a routine tool, analysis of the microbiome presents specific technical challenges, including the complexity and dynamic range of member taxa, the need for well-annotated metagenomic databases, and high inter-protein sequence redundancy and similarity. In this study, an approach was developed for assessment of biological phenotype and metabolic status, as a functional complement to DNA sequence analysis. Fecal samples were prepared and analysed by tandem mass spectrometry and a homology-based meta-clustering strategy was used to combine peptides from multiple species into representative proteins. In total, 15,250 unique peptides were sequenced and assigned to 2154 metaclusters, which were then assigned to pathways and functional groups. Differences were noted in several pathways, consistent with the dominant genera observed in different subjects. Although this study was not powered to draw conclusions from the comparisons, the results obtained demonstrate the applicability of this approach and provide the methods needed for performing semi-quantitative comparisons of human fecal microbiome composition, physiology and metabolism, as well as a more detailed assessment of microbial composition in comparison to 16S rRNA gene sequencing.

    Ecophysiology of novel intestinal butyrate-producing bacteria
    Bui, Thi Phuong Nam - \ 2016
    Wageningen University. Promotor(en): Willem de Vos, co-promotor(en): Caroline Plugge. - Wageningen : Wageningen University - ISBN 9789462577015 - 202
    butyrates - butyric acid bacteria - intestines - microbial interactions - faecal examination - mice - man - infants - genomics - intestinal physiology - microbial physiology - biochemical pathways - lysine - sugar - butyraten - boterzuurbacteriën - darmen - microbiële interacties - fecesonderzoek - muizen - mens - zuigelingen - genomica - darmfysiologie - microbiële fysiologie - biochemische omzettingen - lysine - suiker

    The human intestinal tract harbours a trillion on microbial cells, predominantly anaerobes. The activity and physiology of these anaerobes is strongly associated with health and disease. This association has been investigated for a long time.However, this has not been fully understood. One of the reasons is the limited availability of cultured representatives. It is estimated that there may be more than 3000 species colonised in the gut of healthy individuals, however, only a bit over 1000 species have been isolated and characterised. Among the intestinal microbes, butyrate-producing bacteria are of special interest as the butyrate produced, is crucial to maintain a healthy gut. In addition, butyrate-producing bacteria have shown a reverse correlation with several intestinal diseases. In Chapter 2 we described a novel species Anaerostipes rhamnosivorans 1y2T isolated from an infant stool. This strain belonged to genus Anaerostipes within Clostridium cluster XIVa. A. rhamnosivorans had a capability of converting rhamnose into butyrate that is unique within intestinal butyrate-producing bacteria. The genomic analysis also revealed the entire rhamnose fermentation pathway as well as the acetyl-CoA pathway for butyrate production. This bacterium is able to produce butyrate from a wide range of sugars as well as lactate plus acetate. In Chapter 3, we described the microbial interactions between A. rhamnosivorans and Bacteriodes thetaiotaomicron in dietary pectins; Blautia hydrogenotrophica in lactate and small amount of acetate; Methanobrevibacter smithii in glucose. We observed that A. rhamnosivorans was able to benefit from its partners in all cocultures for butyrate production. This is likely due to its high metabolic flexibility. While the interaction between A. rhamnosivorans and B. thetaiotaomicron appeared as syntrophy, the interaction between A. rhamnosivorans and hydrogenotrohic microbes were cross-feeding type where hydrogen was transferred between two species. The latter resulted in an increase in butyrate level. In Chapter 4 we described a novel species Intestinimonas butyriciproducens SRB521T representing a novel genus Intestinimonas from a mouse caecum within Clostridium cluster IV. This bacterium produced butyrate and acetate as end products from Wilkins-Chalgren-Anaerobe broth.

    Butyrate production is assumed to derive from carbohydrate employing acetyl-CoA pathway. No gut bacterium is known to convert proteins or amino acids to butyrate although butyrogenic pathways from amino acid degradation have been detected in the human gut using metagenomic approach. In Chapter 5 we discovered a novel butyrate synthesis pathway from the amino acid lysine and the Amadori product fructoselysine in Intestinimonas butyriciproducens AF211 that was isolated from human stool. This strain appeared to grow much better in lysine as compared to sugars although lysine and acetyl-CoA pathways were both detected in its complete genome. Moreover, the strain AF211 was able to metabolise efficiently fructoselysine into butyrate, and acetate was found to affect the fructoselysine fermentation, representing the impact of the environmental conditions where acetate is abundant in the gut. While the lysine pathway was found in the gut of many individuals, the fructoselysine pathway was present in only half of those samples. The finding that strain I. butyriciproducens AF211 is capable of the butyrogenic conversion of amino acid lysine and fructoselysine, an Amadori product formed in heated foods via the Maillard reaction, indicated a missing link that coupling protein metabolism and butyrate formation. As this Amadori product has been implicated to play a role in aging process, the use of strain AF211 as fructoselysine clearance in the gut needs further investigation. In Chapter 6 we performed genomic and physiological comparison between the I. butyriciproducens strain AF211 (human isolate) and SRB521T (mouse isolate). I. butyriciproducens was the most abundant species within the Intestinimonas genus and highly prevalent in humans based on metadata analysis on 16S amplicons. We confirmed that the butyrogenesis from lysine was a shared characteristic between the two I. butyriciproducens strains. We also observed the host specific features including tolerance to bile, cellular fatty acid composition, more efficient capability of converting sugars into butyrate, especially galactose and arabinose, in the human strain AF211. In addition, genomic rearrangements as well as variations in bacteriophages differed among strains.

    'Mum, can I have Brussels sprouts again?’ : development of vegetable preferences during the first 2 years of life
    Barends, C. - \ 2015
    Wageningen University. Promotor(en): Kees de Graaf, co-promotor(en): Jeanne de Vries; Jos Mojet. - Wageningen : Wageningen University - ISBN 9789462573505 - 187
    voedselvoorkeuren - voedselopname - zuigelingen - spenen - eten - smaakgevoeligheid - groenten - food preferences - food intake - infants - weaning - eating - taste sensitivity - vegetables


    Background and aim

    Most children do not eat the recommended amount of vegetables. Their low vegetable intake may be attributed to their low preference for vegetables. Since the first years of life is a sensitive period in the development of taste preferences, and since taste preferences track over time, we started a longitudinal intervention study to investigate the effect of starting weaning with repeated exposure to vegetable purées on vegetable intake and liking during the first 2 years of life. The primary aim of this thesis was to investigate whether starting weaning with vegetables compared to weaning with fruit had an effect on the intake and liking of vegetables on the short and on the long term. The secondary aim was to investigate whether starting weaning with vegetables compared to weaning with fruit, influenced the preferences for sweet taste and daily intake of sugar.


    First, we conducted an intervention study (n = 101) that investigated the effects of repeated exposure to either vegetable purées (vegetable groups) or fruit purées (fruit groups) on infants’ acceptance of vegetable or fruit purées during the first 18 days of weaning. Intake of the purées and mothers’ rated liking were measured in the lab. From a subsample (n = 60), we also measured liking by analysing the infants’ facial expressions and behaviour after consuming green beans purée in the lab. In two follow-up studies, when the infants were 12 (n = 84) and 23 months of age (n = 81), the long-term effect of the intervention was measured on intake and mothers’ rated liking of the purées in the lab. Additionally, infants’ daily vegetable intake was assessed with 3-day food records at both follow-ups. At the second follow-up, also the influence of starting with vegetables or fruits on children’s preferences for sweet and salty tastes (n = 81), were measured with sweetened and salted water solution and by calculating their daily mono- and disaccharides intake from the 3-day food records. Additionally, a systematic review investigated the current status of knowledge about effective strategies to increase vegetable intake in children younger than 3 y.


    The studies showed that the group of children who were repeatedly exposed to vegetables increased their vegetable intake from 24 ± 28 g to 45 ± 44g (p < 0.001), while the children who were repeatedly exposed to fruit increased their fruit intake from 46 ± 40 g to 66 ± 42 g (p < 0.05) . Interestingly, the first vegetable intake in the fruit group, which was directly after the 18 days of exposure to fruit purées, was as low as the first vegetable intake of the children in the vegetable group at day 1. This indicates that the repeated exposure to fruit did not influence the children’s vegetable intake. These results were confirmed by the results of the facial expressions, showing a decrease in negative facial expressions after repeated exposure to green beans.

    At the follow-ups, when the infants were 12 and 23 months of age, no differences between the vegetable and fruit groups in green beans or apple purée were found in the lab. Daily intake of vegetables at 12 months of age, was 38% higher (p = 0.02) in the vegetable group (75 ± 43 g) than in the fruit group (54 ± 29 g). At 23 months of age, no significant difference in daily vegetable intake was found between the groups. Also the 23 month olds’ preference for sweet water solutions and their daily mono- and disaccharides intake did not differ between groups.

    Finally, the systematic review of literature showed that counselling of the parents on healthy eating and nutrition did have a positive long-term effect on their children’s’ vegetable intake, although the effect was relatively small. The review further showed that repeated exposure was the most studied and also the most effective strategy, since all studies reported an increase in intake after repeated exposure to a vegetable. Also exposure to a variety of vegetables showed to have a positive effect on the intake of a new vegetable.


    Weaning with repeated exposure to vegetables has a positive influence on vegetable intake until at least 12 months of age.

    Endogenous human milk Peptide release is greater after preterm birth than term birth
    Dallas, D.C. ; Smink, C.J. ; Robinson, R.C. ; Tian, T. ; Guerrero, A. ; Parker, E.A. ; Smilowitz, J.T. ; Hettinga, K.A. ; Underwood, M.A. ; Lebrilla, C.B. ; German, J.B. ; Barile, D. - \ 2015
    The Journal of Nutrition 145 (2015)3. - ISSN 0022-3166 - p. 425 - 433.
    breast-milk - bioactive peptides - plasmin activity - early lactation - casein - enzyme - proteins - infants - trypsin - carboxypeptidase
    Background: Hundreds of naturally occurring milk peptides are present in term human milk. Preterm milk is produced before complete maturation of the mammary gland, which could change milk synthesis and secretion processes within the mammary gland, leading to differences in protein expression and enzymatic activity, thereby resulting in an altered peptide profile. Objective: This study examined differences in peptides present between milk from women delivering at term and women delivering prematurely.
    Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria
    Nylund, L. ; Nermes, M. ; Isolauri, E. ; Salminen, S. ; Vos, W.M. de; Satokari, R. - \ 2015
    Allergy 70 (2015)2. - ISSN 0105-4538 - p. 241 - 244.
    gut microbiota - dermatitis - infants
    The reports on atopic diseases and microbiota in early childhood remain contradictory and both decreased and increased microbiota diversity have been associated with atopic eczema. In this study, the intestinal microbiota signatures associated with the severity of eczema in 6-month-old infants were characterized. Further, the changes in intestinal microbiota composition related to the improvement of this disease 3 months later were assessed. The severity of eczema correlated inversely with microbiota diversity (r=-0.54, P=0.002) and with the abundance of butyrate-producing bacteria (r= -0.52, P=0.005). During the 3 months follow-up, microbiota diversity increased (P
    Efficacy of repeated exposure and flavour-flavour learning as mechanisms to increase preschooler's vegetable intake and acceptance
    Wild, V.W.T. de; Graaf, C. de; Jager, G. - \ 2015
    Pediatric Obesity 10 (2015)3. - ISSN 2047-6310 - p. 205 - 212.
    childrens food preferences - mere exposure - fruit - consumption - childhood - variety - life - perspective - infants - obesity
    Background - Dutch children's diets, like the diets of many children in Europe and the US are not balanced, do not contain enough vegetables and have been associated with a high prevalence of childhood obesity. Promoting children's vegetable intake is challenging. Objective - We investigated the relative effectiveness of repeated exposure and flavour–flavour learning in increasing vegetable intake and acceptance in preschoolers. Methods - During an intervention period of 7 weeks, 39 toddlers (aged 1.5 to 4¿years) consumed red beet and parsnip crisps at day-care centres in Wageningen, the Netherlands. Half of the group received red beet crisps with a dip of tomato ketchup (Conditioned [C]) and parsnip with a neutral white sauce (Unconditioned, [UC]), whereas for the other half the order was reversed (red beet [UC], parsnip [C]). Preference and ad libitum consumption of vegetable crisps were measured once before and three times after the intervention over the course of a 6-month follow-up period to assess longer-term effects. Results - Intake increased significantly after the intervention for both vegetables (on average with 8¿g; an increase of approximately 300%), and this effect was persistent even 6 months afterwards. The increase was irrespective of crisps being offered with C or UC dip sauce. Conclusions These results suggest a robust and persistent effect of repeated exposure but no effect of flavour–flavour learning. Offering pure vegetable tastes repeatedly is sufficient to increase intake.
    Specificity and effector functions of human RSV-specific IgG from bovine milk
    Hartog, C.G. den; Jacobino, S. ; Bont, L. ; Cox, L. ; Ulfman, L.H. ; Leusen, J.H.W. ; Neerven, R.J.J. van - \ 2014
    PLoS ONE 9 (2014)11. - ISSN 1932-6203 - 8 p.
    respiratory syncytial virus - acute otitis-media - childhood asthma - immune-response - inverse association - influenza-virus - infection - antibody - infants - protection
    Background Respiratory syncytial virus (RSV) infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins. Objective To investigate whether IgG purified from bovine milk (bIgG) can modulate immune responses against human RSV. Methods ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fc¿ receptors (Fc¿R) or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated. Results bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to Fc¿RII on neutrophils, monocytes and macrophages, but not to Fc¿RI and Fc¿RIII, and could bind simultaneously to hRSV and human Fc¿RII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV. Conclusions The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human Fc¿RII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV.
    Consequences of the Trans-Atlantic slave trade on medicinal plant selection: plant use for cultural boud syndromes affecting children in Suriname and Western Africa.
    Vossen, T. ; Towns, A.M. ; Ruysschaert, S. ; Quiroz Villarreal, D.K. ; Andel, T. van - \ 2014
    PLoS ONE 9 (2014)11. - ISSN 1932-6203
    sexual abstinence - bulging fontanel - rural ghana - health - care - infants - deficiency - diarrhea - illness - symptom
    Folk perceptions of health and illness include cultural bound syndromes (CBS), ailments generally confined to certain cultural groups or geographic regions and often treated with medicinal plants. Our aim was to compare definitions and plant use for CBS regarding child health in the context of the largest migration in recent human history: the trans-Atlantic slave trade. We compared definitions of four CBS (walk early, evil eye, atita and fontanels) and associated plant use among three Afro-Surinamese populations and their African ancestor groups in Ghana, Bénin and Gabon. We expected plant use to be similar on species level, and assumed the majority to be weedy or domesticated species, as these occur on both continents and were probably recognized by enslaved Africans. Data were obtained by identifying plants mentioned during interviews with local women from the six different populations. To analyse differences and similarities in plant use we used Detrended Component Analysis (DCA) and a Wald Chi-square test. Definitions of the four cultural bound syndromes were roughly the same on both continents. In total, 324 plant species were used. There was little overlap between Suriname and Africa: 15 species were used on two continents, of which seven species were used for the same CBS. Correspondence on family level was much higher. Surinamese populations used significantly more weedy species than Africans, but equal percentages of domesticated plants. Our data indicate that Afro-Surinamers have searched for similar plants to treat their CBS as they remembered from Africa. In some cases, they have found the same species, but they had to reinvent the largest part of their herbal pharmacopeia to treat their CBS using known plant families or trying out new species. Ideas on health and illness appear to be more resilient than the use of plants to treat them.
    Effect of starting weaning exclusively with vegetables on vegetable intake at the age of 12 and 23 months
    Barends, C. ; Vries, J.H.M. de; Mojet, J. ; Graaf, C. de - \ 2014
    Appetite 81 (2014). - ISSN 0195-6663 - p. 193 - 199.
    taste preferences - repeated exposure - food preferences - acceptance - children - fruit - infants - variety - consumption - adolescents
    Background: The low vegetable intake in children may be attributed to their low preference for vegetables. During the first year of life, first taste preferences are formed, which may track over time. In a previous study to increase infants' vegetable intake and liking, we found that at the start of weaning, infants had a higher vegetable intake in the lab after repeated exposure to vegetable purées than to fruit purées. The current study is a follow-up of these infants at the age of 12 and 23¿months, and examined whether the group that started weaning with vegetables continued eating more vegetables than the group that started weaning with fruits. Methods: At 12 (n¿=¿86) and 23 (n¿=¿81) months of age the children's daily vegetable consumption was reported by their parents using a 3-day food diary. The intake of green beans and apple purée was measured in the laboratory. Results: Reported daily intake of vegetables at 12¿months of age was 38 % higher (P¿=¿0.02) in the vegetable group (75¿±¿43¿g) than in the fruit group (54¿±¿29¿g), but was similar for both groups at 23¿months of age (49¿±¿43, 57¿±¿35¿g, respectively; NS). Both at 12 and 23¿months of age, apple and green beans intake in the lab did not differ significantly between the groups. Conclusion: These findings suggest that weaning exclusively with vegetables results in a higher daily vegetable consumption until at least 12¿months of age. More research is needed to investigate how to maintain this effect.
    Effectiveness of flavour nutrient learning and mere exposure as mechanisms to increase toddler's intake and preference for green vegetables
    Wild, V.W.T. de; Graaf, C. de; Jager, G. - \ 2013
    Appetite 64 (2013). - ISSN 0195-6663 - p. 89 - 96.
    childrens food preferences - high dietary-fat - european countries - young-children - pro children - acceptance - fruit - infants - rats - intervention
    Children’s consumption of vegetables is still below recommendations. Since preference is the most important predictor of children’s intake and most children dislike vegetables, new strategies are needed to increase their preferences for vegetables. Flavour nutrient learning (FNL) could be an effective mechanism to change preferences. Forty healthy toddlers were included in a randomized intervention study. During an intervention period of 7 weeks, they consumed vegetable soups (endive and spinach) twice per week. Half of the group received a high-energy variant of one soup (e.g. HE spinach) and a low energy variant of the other (LE endive), whereas for the other half the order was reversed (HE endive, LE spinach). Primary outcome measures were preference and ad libitum consumption (with a maximum of 200 g) of both vegetable products (LE), measured before, shortly after the intervention period, and 2 and 6 months following conditioning to assess longer-term effects. After completion of the intervention period, 28 children (14 girls and 14 boys, age 35 months; SD ± 8.3) met criteria for FNL to occur, and were included in further data analysis. Results showed a significant increase (~58 g) in ad libitum intake for both vegetable soups (stable over time), but irrespective of the energy content. This indicates a robust effect of mere exposure on intake, but no FNL. For preference, however, results showed a significant shift in liking for the vegetable soup consistently paired with high energy, supporting FNL.
    Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation
    Fekete, K. ; Berti, C. ; Trovato, M. ; Lohner, S. ; Dullemeijer, C. ; Souverein, O.W. ; Cetin, I. ; Decsi, T. - \ 2012
    Nutrition Journal 11 (2012). - ISSN 1475-2891
    folic-acid supplementation - neural-tube defects - serum folate - growth-retardation - orofacial clefts - fetal-growth - infants - risk - vitamin - mothers
    The beneficial effect of folic acid supplementation before and shortly after conception is well recognized, whereas the effect of supplementation during the second and third trimesters is controversial and poorly documented. Our aims were to systematically review randomized controlled trials (RCTs) investigating the effect of folate supplementation on birth weight, placental weight and length of gestation and to assess the dose–response relationship between folate intake (folic acid plus dietary folate) and health outcomes. The MEDLINE, EMBASE and Cochrane Library CENTRAL databases were searched from inception to February 2010 for RCTs in which folate intake and health outcomes in pregnancy were investigated. We calculated the overall intake-health regression coefficient ( ß ˆ ) by using random-effects meta-analysis on a loge-loge scale. Data of 10 studies from 8 RCTs were analyzed. We found significant dose–response relationship between folate intake and birth weight (P=0.001), the overall ß ˆ was 0.03 (95% confidence interval (CI): 0.01, 0.05). This relationship indicated 2% increase in birth weight for every two-fold increase in folate intake. In contrast, we did not find any beneficial effect of folate supplementation on placental weight or on length of gestation. There is a paucity of well-conducted RCTs investigating the effect of folate supplementation on health outcomes in pregnancy. The dose–response methodology outlined in the present systematic review may be useful for designing clinical studies on folate supplementation and for developing recommendations for pregnant women.
    Insecticide-treated plastic sheeting for emergency malaria prevention and shelter among displaced populations: an observational cohort study in a refugee setting in Sierra Leone
    Burns, M.R. ; Rowland, M. ; N'Guessan, R. ; Carneiro, I. ; Beeche, A. ; Sesler Ruiz, S. ; Kamara, S. ; Takken, W. ; Carnevale, P. ; Allan, R. - \ 2012
    American Journal of Tropical Medicine and Hygiene 87 (2012)2. - ISSN 0002-9637 - p. 242 - 250.
    anopheles-gambiae - rural area - children - vectors - camps - transmission - nets - resistance - exposure - infants
    A double-blind phase III malaria prevention trial was conducted in two refugee camps using pre-manufactured insecticide-treated plastic sheeting (ITPS) or untreated polyethylene sheeting (UPS) randomly deployed to defined sectors of each camp. In Largo camp the ITPS or UPS was attached to inner walls and ceilings of shelters, whereas in Tobanda the ITPS or UPS was used to line only the ceiling and roof. In Largo the Plasmodium falciparum incidence rate in children up to 3 years of age who were cleared of parasites and monitored for 8 months was 163/100 person-years under UPS and 63 under ITPS (adjusted odds ratio [AOR] = 0.40, 95% confidence interval [CI] = 0.33–0.47). In Tobanda incidence was 157/100 person-years under UPS and 134 under ITPS (AOR = 0.85, 95% CI = 0.75–0.95). Protective efficacy was 61% under fully lined ITPS and 15% under roof lined ITPS. Anemia rates improved under ITPS in both camps. This novel tool proved to be a convenient, safe, and long-lasting method of malaria control when used as a full shelter lining in an emergency setting.
    Rapid recognition at 10 months as a predictor of language development
    Junge, C. ; Kooijman, V.M. ; Hagoort, P. ; Cutler, A. - \ 2012
    Developmental Science 15 (2012)4. - ISSN 1363-755X - p. 463 - 473.
    event-related potentials - word segmentation - continuous speech - phonotactic knowledge - sound patterns - infants - brain - acquisition - nonsense - memory
    Infants' ability to recognize words in continuous speech is vital for building a vocabulary. We here examined the amount and type of exposure needed for 10-month-olds to recognize words. Infants first heard a word, either embedded within an utterance or in isolation, then recognition was assessed by comparing event-related potentials to this word versus a word that they had not heard directly before. Although all 10-month-olds showed recognition responses to words first heard in isolation, not all infants showed such responses to words they had first heard within an utterance. Those that did succeed in the latter, harder, task, however, understood more words and utterances when re-tested at 12 months, and understood more words and produced more words at 24 months, compared with those who had shown no such recognition response at 10 months. The ability to rapidly recognize the words in continuous utterances is clearly linked to future language development.
    Control of iron deficiency in the first 1000 days in life: prevention of impaired child development
    Chang, S. - \ 2012
    Wageningen University. Promotor(en): Frans Kok, co-promotor(en): Inge Brouwer; J. Chen; -- Guansheng Ma. - S.l. : s.n. - ISBN 9789461733825 - 125
    ijzergebrekanemie - peuters en kleuters - zuigelingen - kindervoedering - aanvullende voedingsprogramma's - bijvoeding - voedselsupplementen - fortificatie - china - kinderontwikkeling - cognitieve ontwikkeling - iron deficiency anaemia - preschool children - infants - child feeding - supplemental feeding programs - supplementary feeding - food supplements - fortification - china - child development - cognitive development

    Evidence indicates that the first 1000 days of life (the period from the woman’s pregnancy continuing into the child’s second year) is the most critical period. This is where nutritional deficiencies have a significant and often irreversible adverse impact on child survival and growth affecting their ability to learn in school and productivity in later life. Sufficient iron supply and intake during pregnancy and in children under two years of age are an important component for nutrition interventions during these critical 1000 days. A causal relationship between iron deficiency and poorer brain function has not been demonstrated yet. In addition, there is ample evidence that the high frequency of iron deficiency anemia (IDA) in the developing world has substantial health and economic costs. It is therefore of public health significance to explore effective and optimal approaches for iron supplementation and iron fortification among high risk populations (i.e., pregnant women, infants and young children).

    This thesis addresses some of the above outstanding areas, aiming at i) exploring the long-term effect of IDA in pregnancy and IDA in children under 2 years on cognitive and psychomotor function and social emotional behaviour, ii) understanding the impact of prenatal multiple micronutrient supplementation on health outcomes of newborns, and iii) investigating iron absorption from a complementary food fortified with a mixture of FeSO4 and NaFeEDTA.

    The human brain is vulnerable during critical periods of development, including the last trimester of fetal life and the first 2 years of childhood - a period of rapid brain growth termed the “brain growth spurt”. We found that iron deficiency anemia in the third trimester of pregnancy is associated with impaired mental development of the child before 24 months of age. The children whose mothers had iron deficiency anemia showed a significantly lower Mental Development Index (MDI) at 12, 18 and 24 months of age. The adjusted mean difference was 5.8 (95% Confidence interval [CI] 1.1 to 10.5), 5.1 (95% CI 1.2 to 9.0) and 5.3 (95% CI 0.9 to 9.7) respectively. Further analysis showed MDI in the prenatal IDA and non-prenatal IDA groups were similar with supplementation of iron-folic acid (60 mg iron), but significantly lower in the prenatal IDA group with supplementation of folic acid or multiple micronutrients. Prenatal iron supplementation with sufficient iron protects child development even when women’s IDA was not properly corrected during pregnancy (chapter 2).

    In a second study, we compared social emotional affect and behavior of three groups of non-anemic 4-year-old children: children with IDA in infancy whose anemia was not corrected before 24 months (chronic IDA, n=27); children with IDA in infancy whose anemia was corrected before 24 months (corrected IDA, n=70), and children who were non-IDA in infancy and at 24 months (n=64). Children’s social referencing, wariness, frustration tolerance behavior and affect were observed in a laboratory setting. The whole procedure was videotaped. Child affective and behavioral display was coded using a time-sampling (5-second segments) coding scheme. Preschool aged children whohad chronic IDA in the first 2 years of life showed affected social emotional behavior. In contrast, children whose anemia was corrected before 24 months were comparable to children who were non-iron deficient and anemic throughout the first 2 years of life in terms of behavior and affect (chapter 3).

    Overall, our results indicate that adverse effects can be reduced and/or prevented with iron supplementation during critical periods of brain development.WHO recommends universal distribution of iron-folic acid supplements to pregnant women in developing countries to prevent and treat iron deficiency anemia. However, pregnant women are often deficient in several other nutrients concurrently, all of which can negatively affect their own health as well as their infants’ health, growth and development across the life course. Multiple micronutrient supplements containing iron and other micronutrients should be more efficient to help to reduce anemia, because other nutrients often lacking in the diets of pregnant women in poor populations, including vitamin A, riboflavin and vitamin B6 and B12, are also needed for hemoglobin synthesis. Improving maternal status of multiple micronutrients could also benefit pregnancy outcome, infant micronutrient stores at birth and breast milk content of micronutrients.

    In a randomized double blind controlled trial described in chapter 4, we examined the impact of prenatal supplementation with multiple micronutrients or iron-folic acid compared to folic acid alone on birth weight, duration of gestation and maternal hemoglobin concentration in the third trimester. In total 5828 pregnant women were involved. The results suggest multiple micronutrients are as effective as iron folic acid in increasing maternal hemoglobin concentration, birth weight and mean duration of gestation. Our study also shows good adherence can be achieved with multiple micronutrients during pregnancy.

    Using 2000 and 2005 Food and Nutrition Surveillance data, we found that complementary feeding practices are suboptimal in both rural and poor rural areas in China, although significant improvements in practices have been made from year 2000 to year 2005. The percentage of consuming meat/eggs more than 4 times a week among 6-9 months children was only 30%, for other age groups only around 50% or less. The high energy and nutrient requirements relative to body size, the capacity to only consume small amounts of foods indicate that nutrient-dense foods must be provided from 6 months until the second and third year of life. Inclusion of animal products can meet the energy and nutrients gap in some cases, but this increases costs and may not be feasible for the lowest-income groups. Furthermore, the amount of animal products that can feasibly be included are generally not sufficient for iron, calcium and sometimes zinc. Thus strategies to optimize nutrient intake from locally available foods may need to be combined with other approaches such as complementary food fortification in order to fully address the problems of micronutrient malnutrition (chapter 6).

    In-home fortification of complementary food is an effective approach to provide additional iron and other nutrients to infants and young children in developing countries. To determine whether iron absorption is enhanced with a mixture of FeSO4 and NaFeEDTA, we conducted an iron absorption study with a crossover design in two groups with children aged 24 to 31 months. A complementary food consisting of millet porridge with cabbage, tofu, and pork-filled wheat flour dumplings was fortified with 2 mg iron as either FeSO4 or NaFeEDTA (study 1) or 4 mg iron as FeSO4 or a mixture of 2 mg each of FeSO4 and NaFeEDTA (study 2). Iron absorption was determined based on erythrocyte incorporation of stable iron isotopes. In study 1, the geometric mean iron absorption(±SD) was 8.0% (3.1, 20.8) and 9.2% (3.1, 27.0) from food fortified with FeSO4 and NaFeEDTA, respectively. In study 2, iron absorption was significantly higher from food fortified with 4 mg iron as 1:1 mixture of FeSO4/NaFeEDTA than from food fortified with FeSO4 only; the geometric mean iron absorption was 6.4% (3.0, 13.5) and 4.1% (1.9, 8.9), respectively. We concluded that the equal mixture of FeSO4 and NaFeEDTA significantly enhanced iron absorption and can be a strategy to ensure adequate iron absorption from phytate-containing complementary foods (Chapter 5).

    The studies in this thesis provide further evidence on the association between IDA during the first critical 1000 days of live and the long-term impact on child development. Our research results and the meta-analysis of 12 randomized controlled trials (including our trial in China) suggest that the daily provision of multiple micronutrients is an optimal approach for pregnant women in developing countries including China in terms of the health outcome of newborns. The benefits of giving at least 30 mg iron daily to pregnant women shown in our study as well as by others can provide guidance to policy makers on the development of a prenatal nutrient supplementation standard in China. Moreover, enhanced iron absorption from a mixture of FeSO4 and NaFeEDTA as a fortificant supports China’s current practice on the use of NaFeEDTA for in-home fortification of complementary food.Considering our study findings and research by others, the following research is proposed for the near future. 1) Continuing research into the causal relationship of iron deficiency and child behaviour; 2) Developing of better measurement tools to assess child development; 3) Exploring the causality of anemia in the region.

    Rapid control of Chinese star anise fruits and teas for neurotoxic anisatin by Direct Analysis in Real Time (DART) high resolution mass spectrometry
    Shen, Y. ; Beek, T.A. van; Claassen, F.W. ; Zuilhof, H. ; Chen, B. ; Nielen, M.W.F. - \ 2012
    Journal of Chromatography. A, Including electrophoresis and other separation methods 1259 (2012). - ISSN 0021-9673 - p. 179 - 186.
    illicium-anisatum - gas-chromatography - ambient conditions - verum - identification - consumption - infants - intoxication - adulterant - desorption
    After ingestion, products containing Chinese star anise (Illicium verum) contaminated or adulterated with Japanese star anise (Illicium anisatum) or other Illicium species, can cause epilepsy, hallucinations, and nausea due to the rare neurotoxic sesquiterpene dilactone anisatin that is present in Japanese star anise. Thus a rapid, simple and unambiguous method for distinguishing between the morphologically similar Chinese star anise and toxic Japanese star anise is important for food safety issues. Direct Analysis in Real Time (DART) ambient ionisation coupled with orbitrap high resolution mass spectrometry allowed the recording of mass spectra of anisatin in solid star anise fruits in seconds without any prior sample pretreatment. Spectra could be obtained in both positive ([M+NH4]+ at m/z 346.1496, C15H24NO8) and negative mode ([M-H]- at m/z 327.1074, C15H19O8) and gave the same outcome provided a mass resolution of at least 27,000 is available. The anisatin signal was typically >1000 times larger in Japanese star anise than in Chinese star anise thus allowing an unequivocal qualitative determination. Herbal teas containing star anise fragments too small to be visually recognised, could be analysed by preparing a tea in 6 min and subsequently sampling ~2 µL of tea on a glass rod. None of the 8 investigated retail teas contained significant quantities of anisatin. Spiking a complex herbal tea containing Chinese star anise with an equally concentrated tea prepared from Japanese star anise provided a linear calibration curve (R2 = 0.995) after normalising on a native constituent of Chinese star anise (standard addition method). This showed that adulteration down to 1% (w/w) is still measurable. Compared with existing PCR, TLC, GC–MS and HPLC–ESI-MS/MS procedures, the proposed DART–HRMS procedure is faster and simpler and moreover measures the actual biotoxin
    Fortification Iron as Ferrous Sulfate Plus Ascorbic Acid Is More Rapidly Absorbed Than as Sodium Iron EDTA but Neither Increases Serum Nontransferrin-Bound Iron in Women
    Troesch, B. ; Egli, I. ; Zeder, C. ; Hurrell, R.F. ; Zimmermann, M.B. - \ 2011
    The Journal of Nutrition 141 (2011)5. - ISSN 0022-3166 - p. 822 - 827.
    double stable-isotope - ethylenediaminetetraacetic acid - revised recommendations - breakfast meal - healthy women - absorption - plasma - transferrin - infants - quantification
    The absorption profile of iron fortificants may be a determinant of their ability to generate nontransferrin-bound iron (NTBI) and, thus, their potential safety. Ferrous iron may be absorbed more rapidly than chelated ferric iron, but differences at the fortification level cannot be distinguished with nonisotopically labeled serum iron curves. Using stable isotope appearance curves (SIAC) in serum, we measured iron absorption profiles from FeSO(4) with ascorbic acid (AA) and from NaFeEDTA, as well as the serum hepcidin and NTBI response following the meals. Healthy women (n = 16) were given 6 mg oral iron as labeled FeSO(4) and NaFeEDTA with a maize porridge using a crossover design. SIAC, NTBI, and serum hepcidin were measured over 8 h after the meal. Iron from FeSO(4) plus AA was more rapidly absorbed, resulting in a 35% greater relative AUC during the first 2 h than for NaFeEDTA (P <0.001). Median (95% CI) fractional iron absorption from the FeSO(4)- and NaFeEDTA-fortified meals was 15.2% (11.0-19.5) and 6.0% (5.0-9.2), respectively (P <0.001). In response to the FeSO(4)-fortified meal, here was an similar to 60% increase in median serum hepcidin (P <0.05) but no significant change in NTBI. There was no significant change in serum hepcidin or NTBI after the NaFeEDTA-fortified meal. SIAC are a useful new tool to compare iron absorption profiles from different iron compounds in fortified foods. Even with the use of a very well absorbed ferrous iron compound, iron fortification in this population does not increase NTBI, suggesting a low risk for adverse health consequences. J. Nutr. 141: 822-827, 2011.
    Gastrointestinal-active oligosaccharides from human milk and functional foods
    Albrecht, S.A. - \ 2011
    Wageningen University. Promotor(en): Harry Gruppen; Fons Voragen, co-promotor(en): Henk Schols. - [S.l.] : S.n. - ISBN 9789085859871 - 200
    oligosacchariden - moedermelk - spijsverteringskanaal - zuigelingen - borstvoeding - koolhydraatmetabolisme - oligosaccharides - human milk - digestive tract - infants - breast feeding - carbohydrate metabolism

    Keywords: human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), konjac glucomannan (KGM), breast milk, baby feces, gastrointestinal metabolization, blood-group specific conjugates, CE-LIF-MSn

    Oligosaccharides, as present in human milk or supplemented to food, are renowned for their biological activity in the gastrointestinal tract. So far, little is known about the implication of oligosaccharide structures on their gastrointestinal fate. The influence of diet-related oligosaccharides on the postnatal gastrointestinal development and on the establishment of a balanced microflora is of special interest. Therefore, the present research aimed at an advanced understanding of the gastrointestinal metabolization of diet-related oligosaccharides, focusing on infant nutrition.

    Capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) was introduced as a sensitive, qualitative and quantitative method for the analysis of individual galactooligosaccharides (GOS) from complex food matrices. The method also showed to be useful for the monitoring and characterization of complex konjac glucomannan (KGM) oligosaccharides, resulting from enzymatic digestion of the KGM polysaccharide andin vitro fermentation with human gut flora. The analysis and identification of human milk oligosaccharides (HMOs) in breast milk and the characterization of oligosaccharides as present in the feces of breast-, formula- and mixed-fed babies was performed by CE-LIF coupled to a mass spectrometer (CE-LIF-MSn). The type of feeding determines the presence of diet-related oligosaccharides in baby feces. For breast-fed babies a gradual change in fecal oligosaccharide profile was found during the first six months postpartum. Three continuous stages of fecal oligosaccharide profiles were defined, comprising the presence of the genetically determined HMO-profile of the breast milk consumed (stage 1), the presence of HMO-units conjugated to blood group determinants from gastrointestinal mucins (stage 2) and predominantly oligosaccharides characteristic for follow-up feeding when solid food is introduced (stage 3). In total, sixteen fecal oligosaccharides, which pointed to the degradation and gastrointestinal metabolization of diet-related oligosaccharides and which were not present in human milk or infant formula, were identified in this research.

    Monitoring the gastrointestinal fate of diet-related oligosaccharides pointed to an individual-dependent gastrointestinal adaptation to enteral food during the postnatal period.

    Teff (Eragrostis tef) production constraints on Vertisols in Ethiopia: farmers' perceptions and evaluation of low soil zinc as yield-limiting factor.
    Haileselassie, B. ; Stomph, T.J. ; Hoffland, E. - \ 2011
    Soil Science and Plant Nutrition 57 (2011)4. - ISSN 0038-0768 - p. 587 - 596.
    iron - supplementation - manganese - infants - copper - trial
    Teff (Eragrostis tef (Zucc.) Trotter) is a major food crop in Ethiopia and Eritrea. It is well adapted to Vertisols. Yields are low (around 1000¿kg ha-1) despite fertilization with urea and diammonium phosphate. The objectives of this study were to understand farmers’ perception on teff production constraints and to evaluate on-farm yield response of teff to zinc (Zn) fertilization. We conducted a farm survey and a participatory fertilization experiment in three teff-based sites (peasant associations) on Vertisols in the mid highland and lowland agroecological zones in Ethiopia. Per site 10 farmers participated in the survey and on-farm experiment. Poor soil fertility in the mid highland and moisture deficit in the lowland agroecological zones were mentioned by farmers as major teff production constraints, respectively. On-farm application of Zn fertilizer at a rate of 8¿kg Zn ha-1 increased teff grain and straw yields by 14% and 15% on average, respectively, which could be economically profitable. Not all plots showed a positive response, however, indicating the necessity for enhanced insight in indicators for soil Zn bioavailability as a yield-limiting factor. Our study indicates the importance of Zn in teff production on Vertisols. We propose further research on management options to prepare for effective interventions based on the farm survey and on-farm experiment.
    The Genome of Akkermansia muciniphila, a Dedicated Intestinal Mucin Degrader, and Its Use in Exploring Intestinal Metagenomes
    Passel, M.W.J. van; Kant, R. ; Zoetendal, E.G. ; Plugge, C.M. ; Derrien, M.M.N. ; Malfatti, S.A. ; Palva, A. ; Vos, W.M. de; Smidt, H. - \ 2011
    PLoS ONE 6 (2011)3. - ISSN 1932-6203 - 8 p.
    gut microbiota - diversity - bacteria - tool - prokaryotes - resistance - selection - sequence - infants - tract
    Background: The human gastrointestinal tract contains a complex community of microbes, fulfilling important health-promoting functions. However, this vast complexity of species hampers the assignment of responsible organisms to these functions. Recently, Akkermansia muciniphila, a new species from the deeply branched phylum Verrucomicrobia, was isolated from the human intestinal tract based on its capacity to efficiently use mucus as a carbon and nitrogen source. This anaerobic resident is associated with the protective mucus lining of the intestines. Methodology/Principal Findings: In order to uncover the functional potential of A. muciniphila, its genome was sequenced and annotated. It was found to contain numerous candidate mucinase-encoding genes, but lacking genes encoding canonical mucus-binding domains. Numerous phage-associated sequences found throughout the genome indicate that viruses have played an important part in the evolution of this species. Furthermore, we mined 37 GI tract metagenomes for the presence, and genetic diversity of Akkermansia sequences. Out of 37, eleven contained 16S ribosomal RNA gene sequences that are >95% identical to that of A. muciniphila. In addition, these libraries were found to contain large amounts of Akkermansia DNA based on average nucleotide identity scores, which indicated in one subject co-colonization by different Akkermansia phylotypes. An additional 12 libraries also contained Akkermansia sequences, making a total of ~16 Mbp of new Akkermansia pangenomic DNA. The relative abundance of Akkermansia DNA varied between
    Incidental learning and memory for food varied in sweet taste in children
    Laureati, M. ; Pagliarini, E. ; Mojet, J. ; Köster, E.P. - \ 2011
    Food Quality and Preference 22 (2011)3. - ISSN 0950-3293 - p. 264 - 270.
    recognition memory - flavor memory - odor memory - age - recollection - experience - texture - infants - novelty - young
    This experiment investigated incidental learning and memory in children (age 7–10 years) for three different foods (fruit juice, fruit purée and biscuit), varied in sweetness. Children (N = 286) were exposed to three target foods and 24 h later their incidental learning was tested for one of the foods by asking them to recognize the target among distractors varying in sweetness. Children were also asked to rate their liking for the products. Overall, the children showed incidental learning for the food eaten the previous day, but recognition was not equal for all stimuli: a memory effect was found for fruit purée but not for biscuit and fruit juice. Memory was based on the correct rejection of the distractors rather than on target recognition. Hedonic scores were high, but lowest for fruit purée. Memory was not related to liking, but it is likely that other factors like novelty and familiarity may have been influential.
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