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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    Faecal microbiota transplantation halts progression of human new-onset type 1 diabetes in a randomised controlled trial
    Groot, Pieter De; Nicolic, Tanja ; Pellegrini, Silvia ; Sordi, Valeria ; Imangaliyev, Sultan ; Rampanelli, Elena ; Hanssen, Nordin ; Attaye, Ilias ; Bakker, Guido ; Duinkerken, Gaby ; Joosten, Annemarie ; Prodan, Andrei ; Levin, Evgeni ; Levels, Han ; Potter Van Loon, Bartjan ; Bon, Arianne Van; Brouwer, Catherina ; Dam, Sytze Van; Simsek, Suat ; Raalte, Daniel Van; Stam, Frank ; Gerdes, Victor ; Hoogma, Roel ; Diekman, Martin ; Gerding, Martin ; Rustemeijer, Cees ; Bakker, Bernadette De; Hoekstra, Joost ; Zwinderman, Aeilko ; Bergman, Jacques ; Holleman, Frits ; Piemonti, Lorenzo ; Vos, Willem De; Roep, Bart ; Nieuwdorp, Max - \ 2020
    Gut (2020). - ISSN 0017-5749
    diabetes mellitus

    Objective: Type 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota-immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT). Design: Patients with recent-onset (<6 weeks) T1D (18-30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition. Results: Stimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal Prevotella was inversely related to residual beta cell function (r=-0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal Desulfovibrio piger and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics. Conclusion: FMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D. Trial registration number: NTR3697.

    Determinants of adherence to micronutrient powder use among young children in Ethiopia
    Samuel, Aregash ; Brouwer, Inge D. ; Pamungkas, Nindya P. ; Terra, Tosca ; Lelisa, Azeb ; Kebede, Amha ; Osendarp, Saskia J.M. - \ 2020
    Maternal and Child Nutrition (2020). - ISSN 1740-8695
    In Ethiopia, home fortification of complementary foods with micronutrient powders (MNPs) was introduced in 2015 as a new approach to improve micronutrient intakes. The objective of this study was to assess factors associated with intake adherence and drivers for correct MNP use over time to inform scale‐up of MNP interventions. Mixed methods including questionnaires, interviews and focus group discussions were used. Participants, 1,185 children (6–11 months), received bimonthly 30 MNP sachets for 8 months, with instruction to consume 15 sachets/month, that is, a sachet every other day and maximum of one sachet per day. Adherence to distribution (if child receives ≥14 sachets/month) and adherence to instruction (if child receives exactly 15[±1] sachets/month) were assessed monthly by counting used sachets. Factors associated with adherence were examined using generalized estimating equations. Adherence fluctuated over time, an average of 58% adherence to distribution and 28% for adherence to instruction. Average MNP consumption was 79% out of the total sachets provided. Factors positively associated with adherence included ease of use (instruction), child liking MNP and support from community (distribution and instruction) and mother's age >25 years (distribution). Distance to health post, knowledge of correct use (OR = 0.74, 95% CI = 0.66–0.81), perceived negative effects (OR = 0.73, 95% CI = 0.54–0.99) and living in Southern Nations, Nationalities and People Region (OR = 0.59, 95% CI = 0.52–0.67) were inversely associated with adherence to distribution. Free MNP provision, trust in the government and field staff played a role in successful implementation. MNP is promising to be scaled‐up, by taking into account factors that positively and negatively determine adherence.
    Youngest children get more snacks
    Brouwer-Damen, Femke - \ 2020
    Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case–Control Study
    Haak, Bastiaan W. ; Westendorp, Willeke F. ; Engelen, Tjitske S.R. van; Brands, Xanthe ; Brouwer, Matthijs C. ; Vermeij, Jan Dirk ; Hugenholtz, Floor ; Verhoeven, Aswin ; Derks, Rico J. ; Giera, Martin ; Nederkoorn, Paul J. ; Vos, Willem M. de; Beek, Diederik van de; Wiersinga, W.J. - \ 2020
    Translational Stroke Research (2020). - ISSN 1868-4483
    Butyrate - Microbiome - Stroke - Trimethylamine-N-oxide

    In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case–control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67–75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62–80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 μM, Wilcoxon p < 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77, p = 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections.

    Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans
    Oude Munnink, Bas B. ; Sikkema, Reina S. ; Nieuwenhuijse, David F. ; Molenaar, Robert Jan ; Munger, Emmanuelle ; Molenkamp, Richard ; Spek, Arco Van Der; Tolsma, Paulien ; Rietveld, Ariene ; Brouwer, Miranda ; Bouwmeester-vincken, Noortje ; Harders, Frank ; Hakze-van Der Honing, Renate ; Wegdam-blans, Marjolein C.A. ; Bouwstra, Ruth J. ; Geurts van Kessel, Corine ; Eijk, Annemiek A. Van Der; Velkers, Francisca C. ; Smit, Lidwien A.M. ; Stegeman, Arjan ; Poel, Wim H.M. Van Der; Koopmans, Marion P.G. - \ 2020
    Science (2020). - ISSN 0036-8075
    Animal experiments have shown that non-human primates, cats, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2. In addition, SARS-CoV-2 RNA has been detected in felids, mink and dogs in the field. Here, we describe an in-depth investigation using whole genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced from humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period several weeks prior to detection. Despite enhanced biosecurity, early warning surveillance and immediate culling of infected farms, transmission occurred between mink farms in three big transmission clusters with unknown modes of transmission. Sixty-eight percent (68%) of the tested mink farm residents, employees and/or contacts had evidence of SARS-CoV-2 infection. Where whole genomes were available, these persons were infected with strains with an animal sequence signature, providing evidence of animal to human transmission of SARS-CoV-2 within mink farms.
    Macroinvertebrate taxonomic and trait-based responses to large-wood reintroduction in lowland streams
    Brouwer, Jan H.F. de; Verdonschot, Piet F.M. ; Eekhout, Joris P.C. ; Verdonschot, Ralf C.M. - \ 2020
    Freshwater Science (2020). - ISSN 2161-9549
    Benthic invertebrates - Colonization - Habitat heterogeneity - Stream restoration - Traits

    In hydromorphologically-degraded lowland streams, large-wood reintroductions are often used to reestablish instream physical structure, which might also increase biodiversity. However, the success rate of this approach varies in terms of positive macroinvertebrate assemblage responses. To obtain better insight into macroinvertebrate–wood relationships, we studied macroinvertebrate assemblage composition and its associated ecological and functional traits in 3 lowland streams in The Netherlands where wood was reintroduced. We used a before–after control–impact design in which we studied stream sections in 3 y: 1 y before and 2 y after large wood was added to some stream sections but not others. We recorded changes in physical structure expressed as substrate diversity, complexity, patchiness, and stability and then compared these parameters within and among the control and treated sections in each stream. We also sampled macroinvertebrates to determine whether the assemblage composition changed because of the wood addition. Finally, we assessed whether changes in macroinvertebrate assemblage could be related to taxa preferences for substrate type and flow and to their functional traits related to mode of locomotion and feeding type. Habitat heterogeneity increased after the wood additions and was relatively stable between years. Macroinvertebrate assemblages changed relative to the control sections in the 2 y after introduction, with 50 to 58% of the taxa increasing or decreasing significantly in abundance. Despite the changes in substrate composition and habitat heterogeneity, most of the functional relationships we expected between macroinvertebrates and large wood were either not apparent or site specific. The only characteristic shared by the macroinvertebrates that consistently increased in response to wood additions was a high affinity for hard substrates. In 1 stream we also observed an increase in taxa with a preference for high-flow velocity and a grazer–scraper feeding mode. These findings suggest that an increase in the surface area of stable, hard substrate was the main underlying ecological effect of reintroducing large wood to the stream channel of sand-bed lowland streams, at least in the short term, and that this change only affected a specific part of the macroinvertebrate assemblage. Changes in assemblage composition occurred primarily during the 1st y after the wood additions and decreased between the 1st and 2nd y, so colonization in this early successional stage seems to be limited to the species pool present in the immediate surroundings.

    Malnutrition, hypertension risk, and correlates : An analysis of the 2014 ghana demographic and health survey data for 15–19 years adolescent boys and girls
    Azupogo, Fusta ; Abizari, Abdul Razak ; Aurino, Elisabetta ; Gelli, Aulo ; Osendarp, Saskia J.M. ; Bras, Hilde ; Feskens, Edith J.M. ; Brouwer, Inge D. - \ 2020
    Nutrients 12 (2020)9. - ISSN 2072-6643 - p. 1 - 23.
    Adolescents - Ghana - Overweight - Pre-hypertension/hypertension - Stunting - Underweight

    The sex differences in malnutrition and hypertension during adolescence is largely inconclusive. There is also a paucity of data on the sex-specific correlates of malnutrition and hypertension for adolescents. Hence, this study aimed to assess the association between malnutrition, pre-hypertension/hypertension (PHH) and sex among adolescents. The study also aimed to determine and contrast the factors associated with these risks in Ghana. We analysed data of non-pregnant adolescent girls (n = 857) and adolescent boys (n = 870) aged 15–19 years from the 2014 Ghana Demographic and Health Survey (DHS). We modelled the prevalence risk ratio (PRR) of malnutrition and PHH using Cox proportional hazard models. Compared to adolescent girls, boys were more than twice likely to be stunted (PRR = 2.58, 95% C.I (1.77, 3.76)) and underweight (PRR = 2.67, 95% C.I (1.41, 5.09)) but less likely to be overweight/obese (PRR = 0.85, 95% C.I (0.08, 0.29)). Boys were also about twice likely to have PHH (PRR = 1.96, 95% C.I (1.47, 2.59)) compared to their female peers. Girls were more at risk of the detrimental effects of poor education on stunting and PHH. Empowerment index while protective of stunting for girls (PRR = 0.82, 95% C.I (0.67, 0.99)) also increased their risk of overweight/obesity (PRR = 1.31, 95% C.I (1.02, 1.68)). A higher household wealth index (HWI) increased the risk of overweight/obesity for adolescent girls but was protective of stunting and PHH for adolescent boys. Improvement in household water, hygiene, and sanitation (WASH) reduced the risk of stunting by 15% for adolescent boys. Overall, our findings suggest a double-burden of malnutrition with an up-coming non-communicable disease burden for adolescents in Ghana. Our indings may also be highlighting the need to target adolescent boys alongside girls in nutrition and health intervention programmes.

    Linked data platform for solanaceae species
    Singh, Gurnoor ; Kuzniar, Arnold ; Brouwer, Matthijs ; Martinez-Ortiz, Carlos ; Bachem, Christian W.B. ; Tikunov, Yury M. ; Bovy, Arnaud G. ; Visser, Richard G.F. ; Finkers, Richard - \ 2020
    Applied Sciences 10 (2020)19. - ISSN 2076-3417
    Linked data - Plant breeding - Prioritization of candidate genes - QTLs - Semantic web - Solanaceae

    Genetics research is increasingly focusing on mining fully sequenced genomes and their annotations to identify the causal genes associated with traits (phenotypes) of interest. However, a complex trait is typically associated with multiple quantitative trait loci (QTLs), each comprising many genes, that can positively or negatively affect the trait of interest. To help breeders in ranking candidate genes, we developed an analytical platform called pbg-ld that provides semantically integrated geno- and phenotypic data on Solanaceae species. This platform combines both unstructured data from scientific literature and structured data from publicly available biological databases using the Linked Data approach. In particular, QTLs were extracted from tables of full-text articles from the Europe PubMed Central (PMC) repository using QTLTableMiner++ (QTM), while the genomic annotations were obtained from the Sol Genomics Network (SGN), UniProt and Ensembl Plants databases. These datasets were transformed into Linked Data graphs, which include cross-references to many other relevant databases such as Gramene, Plant Reactome, InterPro and KEGG Orthology (KO). Users can query and analyze the integrated data through a web interface or programmatically via the SPARQL and RESTful services (APIs). We illustrate the usability of pbg-ld by querying genome annotations, by comparing genome graphs, and by two biological use cases in Jupyter Notebooks. In the first use case, we performed a comparative genomics study using pbg-ld to compare the difference in the genetic mechanism underlying tomato fruit shape and potato tuber shape. In the second use case, we developed a seamlessly integrated workflow that uses genomic data from pbg-ld knowledge graphs and prioritization pipelines to predict candidate genes within QTL regions for metabolic traits of tomato.

    Sequential fusion of information from two portable spectrometers for improved prediction of moisture and soluble solids content in pear fruit
    Mishra, Puneet ; Marini, Federico ; Brouwer, Bastiaan ; Roger, Jean Michel ; Biancolillo, Alessandra ; Woltering, Ernst ; Hogeveen van Echtelt, Esther - \ 2020
    Talanta 223 (2020)Part 2. - ISSN 0039-9140
    Chemometrics - Miniature near infrared (NIR) spectrometers - Multi-block data analysis - Multivariate analysis - Pear (Pyrus communis L.) - Sequential data fusion

    Near infrared (NIR) spectroscopy allows rapid estimation of quality traits in fresh fruit. Several portable spectrometers are available in the market as a low-cost solution to perform NIR spectroscopy. However, portable spectrometers, being lower in cost than a benchtop counterpart, do not cover the complete near infrared (NIR) spectral range. Often portable sensors either use silicon-based visible and NIR detector to cover 400–1000 nm, or InGaAs-based short wave infrared (SWIR) detector covering the 900–1700 nm. However, these two spectral regions carry complementary information, since the 400–1000 nm interval captures the color and 3rd overtones of most functional group vibrations, while the 1st and the 2nd overtones of the same transitions fall in the 1000–1700 nm range. To exploit such complementarity, sequential data fusion strategies were used to fuse the data from two portable spectrometers, i.e., Felix F750 (~400–1000 nm) and the DLP NIR Scan Nano (~900–1700 nm). In particular, two different sequential fusion approaches were used, namely sequential orthogonalized partial-least squares (SO-PLS) regression and sequential orthogonalized covariate selection (SO-CovSel). SO-PLS improved the prediction of moisture content (MC) and soluble solids content (SSC) in pear fruit, leading to an accuracy which was not obtainable with models built on any of the two spectral data set individually. Instead, SO-CovSel was used to select the key wavelengths from both the spectral ranges mostly correlated to quality parameters of pear fruit. Sequential fusion of the data from the two portable spectrometers led to an improved model prediction (higher R2 and lower RMSEP) of MC and SSC in pear fruit: compared to the models built with the DLP NIR Scan Nano (the worst individual block) where SO-PLS showed an increase in R2p up to 56% and a corresponding 47% decrease in RMSEP. Differences were less pronounced to the use of Felix data alone, but still the R2p was increased by 2.5% and the RMSEP was reduced by 6.5%. Sequential data fusion is not limited to NIR data but it can be considered as a general tool for integrating information from multiple sensors.

    Exploring the Influence of Alcohol Industry Funding in Observational Studies on Moderate Alcohol Consumption and Health
    Vos, Moniek ; Soest, Annick P.M. van; Wingerden, Tim Van; Janse, Marion L. ; Dijk, Rick M. ; Brouwer, Rutger J. ; Koning, Iris De; Feskens, Edith J.M. ; Sierksma, Aafje - \ 2020
    Advances in Nutrition 11 (2020)5. - ISSN 2161-8313 - p. 1384 - 1391.
    alcohol industry funding - all-cause mortality - cancer - cardiovascular disease - sponsorship bias - type 2 diabetes

    Funding of research by industry in general can lead to sponsorship bias. The aim of the current study was to conduct an initial exploration of the impact of sponsorship bias in observational alcohol research by focusing on a broad spectrum of health outcomes. The purpose was to determine whether the outcome depended on funding source. We focused on moderate alcohol consumption and used meta-analyses that are the basis of several international alcohol guidelines. These meta-analyses included observational studies that investigated the association of alcohol consumption with 14 different health outcomes, including all-cause mortality, several cardiovascular diseases and cancers, dementia, and type 2 diabetes. Subgroup analyses and metaregressions were conducted to investigate the association between moderate alcohol consumption and the risk of different health outcomes, comparing findings of studies funded by the alcohol industry, ones not funded by the alcohol industry, and studies with an unknown funding source. A total of 386 observational studies were included. Twenty-one studies (5.4%) were funded by the alcohol industry, 309 studies (80.1%) were not funded by the alcohol industry, and for the remaining 56 studies (14.5%) the funding source was unknown. Subgroup analyses and metaregressions did not show an effect of funding source on the association between moderate alcohol intake and different health outcomes. In conclusion, only a small proportion of observational studies in meta-analyses, referred to by several international alcohol guidelines, are funded by the alcohol industry. Based on this selection of observational studies the association between moderate alcohol consumption and different health outcomes does not seem to be related to funding source.

    "Dit is echt een uithangbord"
    Wolf, Pieter de - \ 2020

    Interview met Pieter de Wolf over Boerderij van de Toekomst

    Azolla ferns testify: seed plants and ferns share a common ancestor for leucoanthocyanidin reductase enzymes
    Güngör, Erbil ; Brouwer, Paul ; Dijkhuizen, Laura W. ; Chaerul Shaffar, Dally ; Nierop, Klaas G.J. ; Vos, C.H. de; Toraño, Javier Sastre ; Meer, Ingrid M. van der; Schluepmann, Henriette - \ 2020
    New Phytologist (2020). - ISSN 0028-646X
    Questions about in vivo substrates for proanthocyanidin (PA) biosynthesis and condensation have not been resolved and wide gaps in the understanding of transport and biogenesis in ‘tannosomes’ persist. Here we examined the evolution of PA biosynthesis in ferns not previously reported, asking what PAs are synthesised and how.
    Chemical and gene‐expression analyses were combined to characterise PA biosynthesis, leveraging genome annotation from the floating fern Azolla filiculoides. In vitro assay and phylogenomics of PIP‐dehydrogenases served to infer the evolution of leucoanthocyanidin reductase (LAR).
    Sporophyte‐synthesised (epi)catechin polymers, averaging only seven subunits, accumulated to 5.3% in A. filiculoides, and 8% in A. pinnata biomass dry weight. Consistently, a LAR active in vitro was highly expressed in A. filiculoides. LAR, and paralogous fern WLAR‐enzymes with differing substrate binding sites, represent an evolutionary innovation of the common ancestor of fern and seed plants.
    The specific ecological niche of Azolla ferns, a floating plant–microbe mat massively fixing CO2 and N2, shaped their metabolism in which PA biosynthesis predominates and employs novel fern LAR enzymes. Characterisation of in vivo substrates of these LAR, will help to shed light on the recently assigned and surprising dual catalysis of LAR from seed plants.
    Improving moisture and soluble solids content prediction in pear fruit using near-infrared spectroscopy with variable selection and model updating approach
    Mishra, Puneet ; Woltering, Ernst ; Brouwer, Bastiaan ; Hogeveen-van Echtelt, Esther - \ 2020
    Postharvest Biology and Technology 171 (2020). - ISSN 0925-5214
    Chemometric - Covariate selection - Fruit-quality - Interval partial least-squares regression - Non-destructive

    To obtain robust near-infrared (NIR) spectroscopy data calibration models, variable selection and model updating with recalibration approaches were used for predicting quality parameters in pear fruit. For variables selection, interval partial least-squares regression and covariate selection approaches were used and compared. Model updating with recalibration was performed by incorporating a few new samples in the calibration set of existing batch data. The interaction of variable selection and model updating was also explored. The results showed that with variable selection, the model performance when tested on a new independent batch of fruit was greatly improved. Further, the model updating with only a few new samples resulted in a reduction of the bias when tested on the new batch. In the case of MC prediction, the variable selection reduced the bias from 1.31 % to 0.19 % and the RMSEP from 1.44 % to 0.58 %, compared to the standard partial least-squares regression (PLS2R). In the case of SSC prediction, the variable selection reduced the bias from -0.62 % to 0.07 % and the RMSEP from 0.90 % to 0.63 %, compared to the standard PLS2R. With a combination of variable selection and model updating the bias and RMSEP were further reduced. The interval-based method performed better compared to the filter-based method. As few as only 10 samples from the new batch already lead to a significant improvement in model performance. In the case of MC, spectral regions of 749-759 nm and 879-939 nm were identified as the most important region. In the case of the SSC, 709-759 nm and 789-999 nm were found to be important spectral regions. Robust models made on selected variables combined with model updating strategy can support to make NIR spectroscopy a preferred choice for non-destructive assessment of quality features of fresh fruit.

    Linear growth failure of Ethiopian children : The role of protein, zinc and mycotoxin intake
    Anegago, Masresha Tessema - \ 2020
    Wageningen University. Promotor(en): E.J.M. Feskens, co-promotor(en): I.D. Brouwer; N.S. Gunaratna. - Wageningen : Wageningen University - ISBN 9789463953498 - 238

    Linear growth failure manifested as stunting is a major public health problem in developing countries. Stunting is often considered as an important marker of an adverse quality of population’s life and child development. Over 90% of stunted children live in 10 developing countries, in Asia and Africa. Ethiopia is the country with the high burden of linear growth failure. In 2016, it was estimated that about 5 million children suffered from poor linear growth or stunting in Ethiopia. The prevalence of stunting in Ethiopia has been reduced from 52% in 2000 to 37% in 2019, however, the number of stunted children has increased by about 1 million in the same period. There is a high level of commitment to reducing stunting globally and nationally. Although the government of Ethiopia formulated ambitious goals to reduce stunting, the progress to reduce stunting in Ethiopia remains too slow partly due to the fact that the aetiology of linear growth failure is still poorly understood. Stunting or poor linear growth is caused by a diverse and complex interaction of household, environmental, socioeconomic and cultural influences, related to, amongst others, poor nutrition, infectious diseases, unfavorable prenatal conditions and genetic disorders. The aim of this thesis was to contribute to the understanding of the aetiology of poor linear growth and stunting in rural Ethiopia by studying the effect of household-level quality protein maize (QPM) promotion and consumption, and the role of protein, zinc, and mycotoxins intake on linear growth of Ethiopian children. The first chapter provides background information on the role of QPM, protein, and zinc (in soil and serum) in linear growth of children. Furthermore, the research questions were described in detail.

    Chapter 2 describes a randomized controlled trial conducted in real practice in which households make their own decisions whether to adopt QPM, how much to adopt and cultivate, and whether and how to incorporate QPM into children’s diets. The intervention had two components: a) nutrition-focused adoption encouragement and provision of free QPM seed (AE), and b) a consumption encouragement (CE) primarily targeting female caregivers and encouraging earmarking and integration of QPM into diets for infants and young children. Eligible children (n=873) aged 6-35 months at baseline were randomly assigned to 3 groups: a first intervention group receiving AE only; a second intervention group receiving both AE and CE; and a control group. We hypothesized that promotion and consumption of QPM could improve the protein and amino acids status, which could, in turn, improve linear growth of children. Children consumed QPM based foods on average 4 days per week, while non-QPM based foods were consumed mostly. In addition, the quantitative intake of QPM was low (27 gram per day) contributing to only 5% of their total protein, 12% of lysine and 15% of tryptophan intakes, compared with conventional maize (80 gram per day) contributing to 16%, 9%, 13% of protein, lysine and tryptophan intakes respectively. Encouragement to adopt and feed QPM to infants and young children in a real-life setting had no effect on children’s protein biomarkers (p=0.19) or linear growth (p=0.17). Further evaluation of multi-year interventions is needed to understand how biofortified crops promoted at scale could change behavior and increase intakes at the household level which in turn improve biomarkers and outcomes in target populations.

    In chapter 3, we performed a cross-sectional analysis using baseline data of the QPM intervention study conducted in chapter 2. We investigated the association between protein intake, and protein and amino acids status with linear growth of children. The results indicated that protein intake (b=0.01, p=0.01) and protein status (b=2.58, p=0.04) as well as tryptophan intake/status (p<0.05) were positively associated with linear growth of children. Furthermore, most children had low energy intake (76%) coupled with high intestinal parasites (48%) and inflammation (35%). Also, protein and amino acids status were negatively correlated with inflammation, which suggests that the current requirement of protein and amino acids may not be adequate for children with low food intake or low energy intake and infection in Ethiopia. Linear growth failure in Ethiopian children is likely associated with low-quality protein intake and inadequate energy intake. Nutrition programs that emphasize improved protein quantity and quality and energy intake may enhance linear growth of young children.

    In chapter 4, we assessed exposure to aflatoxins and fumonisins measured in serum in two seasons, post-harvest and pre-harvest, and we also assessed mechanisms through which linear growth of children was affected. Children (n=873) 6-35 months old were enrolled in an intervention trial on quality protein maize consumption in rural Ethiopia as described in chapter 2. These children were stratified by baseline stunting status, and 102 children (50 stunted and 52 non-stunted) were randomly selected for this sub-study. Blood samples were collected during pre-harvest (August-September 2015) and post-harvest (February 2016) season. In the pre-harvest season, the proportions of children exposed to AFG1 (8%), AFG2 (33%) and AFM1 (7%) were higher than in the post-harvest season (4%, 28% and 4%, respectively). Likewise, the proportion of children exposed to any aflatoxin was higher in the pre-harvest than in the post-harvest season (51% vs. 41%). Exposure to fumonisins ranged from 0-11%, depending on the type of fumonisins. Exposure to any aflatoxin was not associated with inflammation (p>0.05), serum transthyretin (p >0.05) or serum IGF-1 (p >0.05), nor with linear growth (p >0.05) after adjusting for potential confounders. Our study revealed that exposure to most aflatoxins was high in pre-harvest season. Good practices in both post-harvest (to reduce accumulation of aflatoxins) and pre-harvest (to reduce aflatoxin levels) are needed for preventing contamination of aflatoxin. The mechanism in which aflatoxin affects linear growth of children is not clear. Aflatoxins are carcinogenic properties and the current exposure is a major public health problem that warrants intervention. Future studies on mechanisms between aflatoxin exposure and linear growth and sources of exposure with large sample size needed. In addition, future research is also needed on the complex and interacting pathophysiology of multiple mycotoxins and exposure management.

    In chapter 5, we use data from the cross-sectional, nationally representative Ethiopian National Micronutrient Survey (n=1776), which provided anthropometric and serum zinc (n=1171) data on children aged 6–59 months. Data on soil zinc levels were extracted for each child from the Africa Soil Information Service. With these data, we assessed the geographic distribution of poor soil zinc, poor zinc status and growth faltering at the national level. Zinc deficiency in soil was prevalent (20%) at the national level, with a higher prevalence in low land of Ethiopia (87%). Nationally, one in four children was zinc deficient, as measured by serum zinc level. High zinc in agricultural soils was positively associated with zinc status (b=0.9, p=0.02), however, linear growth of children was not associated with soil zinc or serum zinc. The findings from our study suggest that agricultural biofortification of zinc could be an alternative strategy for reducing zinc deficiency in developing countries. In Ethiopia most households consume food that comes from own production, however, crop production on zinc-deficient soils and its effect on human health has not yet been studied. Therefore, a future longitudinal experimental study on the effects of soil zinc application on crop zinc content and human serum zinc levels will help to elucidate this relationship. The phytate content of foods may affect zinc bioavailability. Future research is also needed on the effect of phytate on zinc bioavailability of crops grown on zinc-deficient soils.

    Finally, chapter 6 discusses the main findings, and the internal and external validity of the studies addressed in this thesis. Furthermore, the public health perspective including recommendations for possible future research is presented. Overall, we can conclude that low protein (of low quality) intake, high prevalence of zinc deficiency and high exposure to multiple aflatoxins are public health problems in Ethiopia. Linear growth of children is positively associated with protein intake, energy intake, as well as protein status, but not with zinc soil levels, zinc status or multiple aflatoxin exposure. Our study has demonstrated that the implementation of QPM in real life had no effect on the protein and amino acids status nor on linear growth of children. Therefore, in our study and also in other nutrition intervention programs, measuring intermediate indicators as outcomes of improved linear growth may be a more feasible approach than measuring linear growth or stunting.

    Diet quality and colorectal tumor risk in persons with Lynch syndrome
    Eijkelboom, Anouk H. ; Brouwer, Jesca G.M. ; Vasen, Hans F.A. ; Bisseling, Tanya M. ; Koornstra, Jan J. ; Kampman, Ellen ; Duijnhoven, Fränzel J.B. van - \ 2020
    Cancer Epidemiology 69 (2020). - ISSN 1877-7821
    colorectal cancer - colorectal tumors - diet - healthy diet - hereditary non-polyposis colorectal cancer - Lynch syndrome - risk factors

    Background: Persons with Lynch syndrome (LS) have an increased risk of developing colorectal tumors (CRTs). Adherence to diet quality indices associated with colorectal cancer (CRC) risk in the general population has not been studied before in LS. Methods: Dietary habits of 490 participants with LS from a prospective cohort study was collected using a food frequency questionnaire. The Dutch Healthy Diet index 2015 (DHD15-index) and Dietary Approaches to Stop Hypertension (DASH) were used to score food-based diet quality. Diet quality scores were divided into tertiles where a higher tertile reflects a higher diet quality. Multivariable Cox proportional hazard regression models were used to estimate the association between the DHD15-index, DASH score and CRT risk. Results: During a median follow-up time of 53.4 months, 210 participants (42.9%) developed CRTs. The DHD-index and DASH score were not associated with CRT risk; hazard ratios for highest vs. lowest tertile were 1.00 (95% Confidence Interval (CI): 0.67-1.48) and 1.11 (95% CI: 0.74-1.69), respectively. No linear trends across the DHD-index and DASH score tertiles were observed (P-trend = 0.97 and 0.83 respectively). Conclusion: In contrast to observations in the general population, no evidence for an association between the food-based DHD15-index or DASH score and CRT risk was observed in persons with LS. Further studies are needed investigating the association between diet quality and mechanisms leading to the development of LS-associated tumors.

    Mobile colistin resistance gene mcr-1 is detected on an Incl1 plasmid in E.coli from meat
    Brouwer, Mike ; Goodman, Richard N. ; Kant, A. ; Mevius, D.J. ; Newire, Enas ; Roberts, Adam P. ; Veldman, K.T. - \ 2020
    Journal of Global Antimicrobial Resistance 23 (2020). - ISSN 2213-7165 - p. 145 - 148.
    Objectives: Mobile colistin resistance (mcr) genes encoded on conjugative plasmids, although described only relatively recently, have been reported globally both in humans and livestock. The genes are often associated with the insertion sequence ISApl1 that can transpose the genes to novel genetic locations. Since its first report, multiple variants of mcr have been discovered in a variety of genetic locations in Escherichia coli, in plasmids and integrated into the chromosome.
    Methods: Using hybrid assembly of short-read and long-read whole-genome sequencing data, the presence ofmcr-1 was confirmed on an IncI1 plasmid in E. coli. In vitro conjugation assays were performed to determine the potential to transfer between strains. Genetic comparison with previously reported IncI1 plasmids was performed.
    Results: The genomic sequence identified thatmcr-1 is present on a complete IncI1 plasmid. Comparison with previously reported extended-spectrum β-lactamase (ESBL)-encoding plasmids from E. coli in the Netherlands from the same time period indicated a distinct lineage for this plasmid.
    Conclusions: The observation ofmcr-1 on an IncI1 plasmid confirms that the genetic region of this gene is actively transposed between genetic locations. This active transposition has consequences for the study of the epidemiology of mcr in populations.
    Metrics to analyze and improve diets through food Systems in low and Middle Income Countries
    Melesse, Mequanint B. ; Berg, Marrit van den; Béné, Christophe ; Brauw, Alan de; Brouwer, Inge D. - \ 2020
    Food Security 12 (2020). - ISSN 1876-4517 - p. 1085 - 1105.
    Food systems - Indicators - Metrics - SDGs

    Taking a food systems approach is a promising strategy for improving diets. Implementing such an approach would require the use of a comprehensive set of metrics to characterize food systems, set meaningful goals, track food system performance, and evaluate the impacts of food system interventions. Food system metrics are also useful to structure debates and communicate to policy makers and the general public. This paper provides an updated analytical framework of food systems and uses this to identify systematically relevant metrics and indicators based on data availability in low and middle income countries. We conclude that public data are relatively well available for food system drivers and outcomes, but not for all of the food system activities. With only minor additional investments, existing surveys could be extended to cover a large part of the required additional data. For some indicators, however, targeted data collection efforts are needed. As the list of indicators partly overlaps with the indicators for the Sustainable Development Goals (SGDs), part of the collected data could serve not only to describe and monitor food systems, but also to track progress towards attaining the SDGs.

    Food systems everywhere: Improving relevance in practice
    Brouwer, Inge D. ; McDermott, John ; Ruben, Ruerd - \ 2020
    Global Food Security 26 (2020). - ISSN 2211-9124
    Environment - Food system transformation - Governance - Nutrition - Systems analysis

    Food systems approaches are increasingly used to better understand transitions in diets, sustainable resource use and social inclusion. Moreover, food systems frameworks are also widely used in many recent policy and foresight studies. We assess 32 highly-cited international studies, identifying and comparing differences in the frameworks used for food systems analysis, and discrepancies in the procedures to identify strategies for and performances of food system transformation. We show that the relevance of existing food systems analysis for identifying critical trade-offs and understanding relevant policies and practices for achieving synergies remains limited. While many studies are largely descriptive, some offer more practical insights into and evidence of entry points for food system transformation as well as opportunities for improving multiple food system outcomes (i.e. nutrition and health, environmental sustainability and resilience, social inclusion). We distinguish four different pathways for food system transformation and outline their analytical underpinnings, their views on multi-stakeholder governance, and how they deal with critical trade-offs between multiple food system objectives. We conclude that food systems approaches must be useful to decision makers and performance can only be improved if decision makers have a better understanding of these underlying interactions and dynamics of food systems change.

    Tumour development in Lynch syndrome : genes load the gun, lifestyle pulls the trigger?
    Brouwer, Jesca G.M. - \ 2020
    Wageningen University. Promotor(en): E. Kampman; H.F.A.. Vasen, co-promotor(en): F.J.B. van Duijnhoven. - Wageningen : Wageningen University - ISBN 9789463952965 - 169

    Lynch syndrome (LS) is caused by a dominantly inherited pathogenic variant in one of the DNA mismatch repair genes. Persons with LS are predisposed to early onset cancer, mainly colorectal and endometrial cancer, and colorectal adenomas which are precursor lesions of colorectal cancer. Cancer risk estimates are variable within and between families with the same mutated gene which suggests that, similar to cancer in the general population, lifestyle-related factors may be involved in cancer development. A limited number of studies on the influence of lifestyle-related factors on cancer risk exist for persons with LS. This thesis aimed at evaluating the association between the inflammatory potential of the diet and the risk of colorectal tumours (i.e. colorectal adenomas and carcinomas), between height and the risk of both colorectal and endometrial cancer, and between body mass index (BMI) at young adulthood and the risk of cancer at all sites and cancer outside the colorectum and/or outside the endometrium for persons with LS. It was also explored whether a colorectal tumour diagnosis was associated with a change in lifestyle habits. For the research aims, data of persons with LS residing in the Netherlands and participating in the GEOLynch study has been used separately or has been  used after harmonization with data of persons with LS residing in Australia, New Zealand, Canada and the USA from the Colon Cancer Family Registry (CCFR).

    In chapter 2, dietary intake of 457 participants of the GEOLynch study was determined with a food frequency questionnaire (FFQ) and used to calculate the adapted dietary inflammatory index (ADII). A higher ADII score reflects a higher inflammatory potential of an individual’s diet. After a median follow-up time of 59 months, 200 (43.8%) participants developed a colorectal adenoma or carcinoma (CRT). A higher inflammatory potential of the diet was not associated with the risk of CRTs for persons with LS.

    Harmonized data of both the GEOLynch study and CCFR has been used to evaluate the association between height and colorectal cancer risk for men and women separately and between height and endometrial cancer risk for women in chapter 3. Self-reported height of 1155 men and 1553 women was used and cancer diagnoses were obtained from or confirmed, where possible, in medical records and/or pathology reports. After 28 279 and 37 090 person years for men and women respectively, colorectal cancer was diagnosed in 511 (44.2%) men and 436 (28.1%) women. For endometrial cancer, 1544 women were included of whom 171 (11.1%) were diagnosed with endometrial cancer after 39 227 person years. No evidence for an association was observed between height and colorectal cancer for men and women, and between height and endometrial cancer for women with LS.

    In chapter 4, the association between body fatness, as reflected by BMI, at young adulthood and cancer risk for persons with LS was evaluated. Harmonized data of 1044 men and 1446 women with LS from the GEOLynch and CCFR studies was used. BMI at young adulthood  was calculated with self-reported height and recalled weight at the age of 18 or 20 years. Where possible, medical records and/or pathology reports were used to  identify  cancer diagnoses. A  5 kg/m2 increment in BMI at young adulthood was associated with an increased risk of cancer  at all sites for women, but not for men. No association was observed between BMI at young adulthood and cancer outside the colon for men and women with LS, and for cancers outside both the colorectum and endometrium for women with LS.

    Data of the GEOLynch study was used to explore if a colorectal tumour diagnosis was associated with a change in lifestyle habits for persons with LS in chapter 5. A FFQ and a general questionnaire about lifestyle habits were completed by 324 participants at both baseline and after a median follow-up of 82.0 [interquartile range, 71.4-86.3] months. A CRT was diagnosed in 146 (45.1%) persons between baseline and follow-up. Apart from a potentially higher likelihood of smoking cessation for those with a CRT diagnosis compared to those without a CRT diagnosis, no evidence was observed for a difference in change in intake of energy, alcohol, red meat, processed meat, dairy, fruit, vegetables and dietary fibre, and in adult BMI, physical activity level and non-steroidal anti-inflammatory drugs use for persons with LS.

    No previous research has been published in which the association between the inflammatory potential of the diet and colorectal tumour risk has been evaluated for persons with LS. Nor does another publication exist in which the association between a colorectal tumour diagnosis and a change in lifestyle habits has been investigated. For height and BMI at young adulthood, inconsistent results for the association between height and colorectal tumours were observed in previous research for persons with LS whereas a higher BMI at young adulthood was associated with an increased risk of colorectal cancer, but not for endometrial cancer. For the general population, a more pro-inflammatory potential of the diet seems to be associated with an increased risk of colorectal tumours, being taller or having a higher BMI at young adulthood increases the risk of colorectal and endometrial cancer, and inconsistent results are reported for an association between a cancer diagnosis and a change in lifestyle habits. The observed contradiction in associations between lifestyle-related factors and tumour risk for persons with LS compared with the general population may be explained by differences in tumour development for persons with LS versus the general population. Moreover, the discovery of LS-associated colorectal cancer development without adenoma or polyp formation, may  explain why associations between lifestyle-related factors and colorectal adenoma risk do not agree with studies in which LS-associated colorectal cancer was used as endpoint. Methodological issues that resulted from combining data of the GEOLynch study and CCFR, and consequences of the applied data analyses did not introduce biases to such an extent that they can explain the observed results of this thesis.

    Overall, results of this thesis suggest that the inflammatory potential of the diet and height are not associated with tumour development for persons with LS. For BMI at young adulthood, a positive association with cancer at all sites is observed for women, but not for men. A colorectal tumour diagnosis does not seem to trigger a change in lifestyle factors. Current cancer prevention recommendations for the general population do not seem to be harmful for the cancer burden in persons with LS and hence, the cancer prevention recommendation to eat a healthy diet and maintain a healthy body weight – also at young adulthood - may be suggested for persons with LS as well. Future studies to lifestyle-related factors and tumour risk for persons with LS may focus on evaluating whether a change in lifestyle-related factors influences subsequent tumour risk. Preferably, such studies should consider molecular characteristics of the developed tumours and/or present results by LS-causing mutated gene. The question mark that ends the subtitle of this thesis, i.e. Genes load the gun, lifestyle pulls the trigger?, will currently remain and cannot be replaced by a period (yet).

    Understanding the psychological and social environmental determinants driving infant and young child feeding practices among Rwandan households: a salutogenic approach
    Ahishakiye, Jeanine - \ 2020
    Wageningen University. Promotor(en): M.A. Koelen; H.W. Vaandrager, co-promotor(en): I.D. Brouwer. - Wageningen : Wageningen University - ISBN 9789463954563 - 166

    Although adequate nutrition and good health are children’s rights, they are often violated, especially in developing countries where undernutrition is one of the leading causes of mortality among children under the age of five. The problem is more pertinent in Sub-Saharan Africa (SSA), that still suffers from the highest under-five mortality rates in the world. Rwanda does not escape from this sad trend because despite continuous policy efforts, chronic malnutrition (stunting) among under-five remains a key public health concern. The 2014/15 Rwanda Demographic and Health Survey (RDHS) shows that 38% of under-five years old children were stunted in 2015. Hence, the Government of Rwanda has implemented numerous strategies to tackle the problem of chronic malnutrition. However, to date, much of our understanding on child chronic (mal) nutrition has been primarily based on research conducted on the nutritional physiological determinants of stunting such as the timing, composition and frequency of infant and young child feeding (IYCF). This view, however, has lacked a holistic orientation, ignoring the contextual and social determinants of IYCF practices. Moreover, the approach to tackle child undernutrition has been predominantly disease and risk-oriented, looking at the factors underlying stunting (pathogenic orientation). From this perspective, IYCF practices have been researched in relation to their contribution to stunting and the determinants of inadequate IYCF practices. Very little is known on factors contributing to good nutritional status, with a particular focus on factors facilitating mothers’ appropriate IYCF in the context of their everyday lives. The overall aim of this thesis is to identify factors that enable healthy IYCF practices in Rwandan households in order to contribute to the development of solution-oriented strategies for reducing child malnutrition. This dissertation is guided by the the salutogenic model of health that, in contrary to pathogenesis (that searches for causes of diseases), focuses on the search for the origins of health.

    The study was carried out in the catchment areas of Rutobwe and Buramba health centres located in a rural part of the district of Muhanga, in the southern province of Rwanda. The study adopted both cross-sectional and longitudinal designs. Four qualitative studies have been carried out. The first study was conducted among key informants ( mothers and fathers of infant aged 0–23 months, grandmothers and community health workers, n=144), focussed on a general understanding of IYCF practices, the challenges and the responses towards appropriate IYCF practices in the context in which mothers must live their lives (Chapter 2). Next, an in-depth study has been carried out on factors that impede or facilitate appropriate IYCF practices from the perspective of mothers themselves (n=39), specifically during the first 6 months of a child’s life (Chapter 3). The third study focused on coping strategies and facilitating factors among mothers who managed to follow the recommended IYCF practices during the first year of a child’s life (n=17; Chapter 4). Finally, the fourth study focused on unravelling how those mothers managed to do well by exploring the life course learning experiences that play a role in shaping healthy IYCF practices during the first year of a child’s life (n=14; Chapter 5).

    Based on the studies carried out, this thesis concludes that appropriate IYCF practices reflect not only food related practices to support the physical health but also the social and emotional needs of the mother and the child. In everyday life, mothers face challenges when they try to pursue the recommended IYCF practices. The results from this thesis reveal that mothers experienced an interplay of barriers and facilitators for appropriate IYCF practices, ranging from individual to group and societal levels. The perceived challenges consisted mainly of poverty, food insecurity, heavy workload and the influence of significant others. The results of this thesis also show that in a sea of those challenges, mothers’ sense of agency which refers to the feeling of being in control of one’s own actions play an important role in combatting and overcoming food and non-food related IYCF challenges. This sense of agency results from the combination of intrapersonal factors and the capacity of mothers to develop diverse coping strategies. Intrapersonal factors that facilitated coping with IYCF challenges included mothers’ confidence in the ability to breastfeed, self-efficacy, a sense of responsibility over their children’s health, and religious belief. Coping strategies consisted of balancing work and child feeding, prioritizing childcare, preparing child’s food in advance, active uptake of the recommendations and persistence in overcoming barriers. Furthermore, the findings indicate that appropriate IYCF practices result from the interaction of mothers with their social environment (interpersonal factors) exposed to not only during motherhood but also during earlier life course stages, for instance during childhood.  In view of these findings, policy makers and health professionals that aim to improve IYCF practices and thus reducing child malnutrition have to create optimal preconditions for appropriate IYCFpractices in which mothers’ sense of agency and capacities as well as optimal social conditions are highlighted, enabled and supported.

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