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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Defining resilient pigs after a Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) challenge using activity and feeding data from accelerometers
Zande, L.E. Van Der; Dunkelberger, J.R. ; Rodenburg, Bas ; Mathur, P.K. ; Cairns, W.J. ; Keyes, M.C. ; Eggert, J.M. ; Little, E.A. ; Dee, S.A. ; Knol, E.F. - \ 2019
In: Precision Livestock Farming 2019. - Teagasc (Precision Livestock Farming 2019 - Papers Presented at the 9th European Conference on Precision Livestock Farming, ECPLF 2019 ) - ISBN 9781841706542 - p. 471 - 475.
Accelerometers - Behaviour - Pig - PRRS - Resilience - RMSE

Porcine reproductive and respiratory syndrome (PRRS) is an infectious viral disease in pigs. PRRS causes reproductive failure in sows and respiratory infections in growing pigs. To improve pig health and minimise economic losses, resilient pigs are preferred within the herd. Resilient pigs still become infected, yet are able to recover following infection, showing less variation in activity and feeding. In this study, 232 commercial crossbred pigs were equipped with individual accelerometer ear tags to monitor the number of active, feeding, and hyperactive events per individual per hour. At eight weeks of age, pigs were inoculated with PRRS virus 1-7-4. Data from accelerometers were collected 23 days prior to challenge and 42 days post-infection (dpi). Expected levels of activity, feeding, and hyperactivity were estimated by regressing behavioural traits on observed datapoints prior to challenge. This regression line was extended to 42 dpi. Then, deviations from the regression line were quantified as Root Mean Square Error (RMSE) for each individual during the following time periods: pre-challenge, 0-13 dpi, and 13-42 dpi. All traits decreased and RMSE increased post-challenge. These results are consistant with clinical signs of PRRS, including lethargy and loss of appetite. In addition, association of these traits with survival was also investigated. RMSE prior to PRRS-infection was not predictive of survival after infection. However, RMSE of feeding and activity during the peak challenge period (0-13 dpi) was predictive of survival, where pigs with less deviation in behaviour were more resilient to the PRRS challenge.

Postbiotics and Their Potential Applications in Early Life Nutrition and Beyond
Wegh, Carrie A.M. ; Geerlings, Sharon Y. ; Knol, Jan ; Roeselers, Guus ; Belzer, Clara - \ 2019
International Journal of Molecular Sciences 20 (2019)19. - ISSN 1661-6596
fermented infant formula - gut microbiota - postbiotics

Postbiotics are functional bioactive compounds, generated in a matrix during fermentation, which may be used to promote health. The term postbiotics can be regarded as an umbrella term for all synonyms and related terms of these microbial fermentation components. Therefore, postbiotics can include many different constituents including metabolites, short-chain fatty acids (SCFAs), microbial cell fractions, functional proteins, extracellular polysaccharides (EPS), cell lysates, teichoic acid, peptidoglycan-derived muropeptides and pili-type structures. Postbiotics is also a rather new term in the '-biotics' field. Where consensus exists for the definitions of pre- and probiotics, this is not yet the case for postbiotics. Here we propose a working definition and review currently known postbiotic compounds, their proposed mechanisms, clinical evidence and potential applications. Research to date indicates that postbiotics can have direct immunomodulatory and clinically relevant effects and evidence can be found for the use of postbiotics in healthy individuals to improve overall health and to relief symptoms in a range of diseases such as infant colic and in adults atopic dermatitis and different causes of diarrhea.

Genetic correlations between growth performance and carcass traits of purebred and crossbred pigs raised in tropical and temperate climates1
Godinho, Rodrigo M. ; Bergsma, Rob ; Silva, Fabyano F. ; Sevillano, Claudia A. ; Knol, Egbert F. ; Komen, Hans ; Guimarães, Simone Eliza F. ; Lopes, Marcos S. ; Bastiaansen, John W.M. - \ 2019
Journal of Animal Science 97 (2019)9. - ISSN 0021-8812 - p. 3648 - 3657.
breeding program - correlated response - crossbred pigs - genotype by environment interactions - growing-finishing pigs

In pig breeding, selection commonly takes place in purebred (PB) pigs raised mainly in temperate climates (TEMP) under optimal environmental conditions in nucleus farms. However, pork production typically makes use of crossbred (CB) animals raised in nonstandardized commercial farms, which are located not only in TEMP regions but also in tropical and subtropical regions (TROP). Besides the differences in the genetic background of PB and CB, differences in climate conditions, and differences between nucleus and commercial farms can lower the genetic correlation between the performance of PB in the TEMP (PBTEMP) and CB in the TROP (CBTROP). Genetic correlations (rg) between the performance of PB and CB growing-finishing pigs in TROP and TEMP environments have not been reported yet, due to the scarcity of data in both CB and TROP. Therefore, the present study aimed 1) to verify the presence of genotype × environment interaction (G × E) and 2) to estimate the rg for carcass and growth performance traits when PB and 3-way CB pigs are raised in 2 different climatic environments (TROP and TEMP). Phenotypic records of 217,332 PB and 195,978 CB, representing 2 climatic environments: TROP (Brazil) and TEMP (Canada, France, and the Netherlands) were available for this study. The PB population consisted of 2 sire lines, and the CB population consisted of terminal 3-way cross progeny generated by crossing sires from one of the PB sire lines with commercially available 2-way maternal sow crosses. G × E appears to be present for average daily gain, protein deposition, and muscle depth given the rg estimates between PB in both environments (0.64 to 0.79). With the presence of G × E, phenotypes should be collected in TROP when the objective is to improve the performance of CB in the TROP. Also, based on the rg estimates between PBTEMP and CBTROP (0.22 to 0.25), and on the expected responses to selection, selecting based only on the performance of PBTEMP would give limited genetic progress in the CBTROP. The rg estimates between PBTROP and CBTROP are high (0.80 to 0.99), suggesting that combined crossbred-purebred selection schemes would probably not be necessary to increase genetic progress in CBTROP. However, the calculated responses to selection show that when the objective is the improvement of CBTROP, direct selection based on the performance of CBTROP has the potential to lead to the higher genetic progress compared with indirect selection on the performance of PBTROP.

Short-term changes of intestinal microbiota composition in preterm infants after two prophylactic doses of vancomycin
d’Haens, Esther J. ; Zwittink, Romy D. ; Belzer, Clara ; Hemels, Marieke A.C. ; Lingen, Richard A. van; Renes, Ingrid B. ; Knol, Jan ; Zoeren-Grobben, Diny van - \ 2019
Acta Paediatrica : International Journal of Paediatrics 108 (2019)10. - ISSN 0803-5253 - p. 1919 - 1920.
Supplementation of diet with non-digestible oligosaccharides alters the intestinal microbiota, but not arthritis development, in IL-1 receptor antagonist deficient mice
Rogier, Rebecca ; Ederveen, Thomas H.A. ; Wopereis, Harm ; Hartog, Anita ; Boekhorst, Jos ; Hijum, Sacha A.F.T. Van; Knol, Jan ; Garssen, Johan ; Walgreen, Birgitte ; Helsen, Monique M. ; Kraan, Peter M. Van Der; Lent, Peter L.E.M. Van; De Loo, Fons A.J. Van; Abdollahi-Roodsaz, Shahla ; Koenders, Marije I. - \ 2019
PLoS ONE 14 (2019)7. - ISSN 1932-6203

The intestinal microbiome is perturbed in patients with new-onset and chronic autoimmune inflammatory arthritis. Recent studies in mouse models suggest that development and progression of autoimmune arthritis is highly affected by the intestinal microbiome. This makes modulation of the intestinal microbiota an interesting novel approach to suppress inflammatory arthritis. Prebiotics, defined as non-digestible carbohydrates that selectively stimulate the growth and activity of beneficial microorganisms, provide a relatively non-invasive approach to modulate the intestinal microbiota. The aim of this study was to assess the therapeutic potential of dietary supplementation with a prebiotic mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS) in experimental arthritis in mice. We here show that dietary supplementation with scGOS/ lcFOS has a pronounced effect on the composition of the fecal microbiota. Interestingly, the genera Enterococcus and Clostridium were markedly decreased by scGOS/lcFOS dietary supplementation. In contrast, the family Lachnospiraceae and the genus Lactobacillus, both associated with healthy microbiota, increased in mice receiving scGOS/lcFOS diet. However, the scGOS/lcFOS induced alterations of the intestinal microbiota did not induce significant effects on the intestinal and systemic T helper cell subsets and were not sufficient to reproducibly suppress arthritis in mice. As expected, we did observe a significant increase in the bone mineral density in mice upon dietary supplementation with scGOS/lcFOS for 8 weeks. Altogether, this study suggests that dietary scGOS/lcFOS supplementation is able to promote presumably healthy gut microbiota and improve bone mineral density, but not inflammation, in arthritis-prone mice.

Combining metabolomics and genomics to elucidate physiological processes related to tail damage score in pigs
Dervishi, E. ; Zande, Lisette van der; Silva Valente, T. da; Reimert, I. ; Mathur, Pramod K. ; Lopes, M.S. ; Knol, E.F. ; Plastow, G.S. - \ 2019
In: Proceedings of the 37th International Society for Animal Genetics Conference (ISAG). - - p. 147 - 147.
The purpose of this study was to identify important metabolitesrelated to tail damage (TDAM) score and to identify genomic regionsassociated with variation in the metabolites. We used 181 Tempo ×Topigs-20 animals divided over 2 batches balanced for gender and selectedfor positive (n = 81) or negative (n = 100) indirect genetic effect(IGE) for growth. Half of the pigs were housed in a barren environment,and the other half in an enriched environment. The tail scores were recordedat weaning and thereafter once a week (score 1 no visible taildamage, score 2 hair removed from the tail, score 3 bite marks and score4 clearly visible wound). Blood samples collected at 8, 9 and 22 weeksof age were used to determine metabolic profiles at The MetabolomicsInnovation Centre (University of Alberta). A total of 53 compoundswere quantified. Statistical analyses were performed in R version 3.5using a generalized mixed model with repeated measurements. A singlestep genome-wide association study (ssGWAS) was performed toidentify genomic regions associated with significant metabolites for tailbiting score. Preliminary results show that serum levels of glycerol andisopropanol were significantly associated with tail damage score. Animalswith TDAM 2 had greater glycerol concentration in blood whencompared with animals with TDAM 3 and 4 (P < 0.05). In addition,animals with TDAM 1 had lower isopropanol concentration when comparedwith animals with TDAM 2 and 3 (P < 0.05). GWAS identified2 candidate regions located on chromosome 6 associated with glyceroland isopropanol (at 45Mb, and at 149Mb respectively). The candidategenes identified in these regions were ZFP14, DOCK7, ANGPTL3,USP1 and KANK4. Angiopoietin like 3 is a secreted protein encoded byANGPTL3 that is involved in the regulation of lipid and glucose metabolism.This protein is present at high levels in the liver where it can bindto adipocytes to activate lipolysis, releasing free fatty acids and glycerol.These results suggest that animals with tail damage (propensity tobeing bitten) might have impaired lipolysis processes.
Combining metabolomics and genomics to elucidate physiological processes related to tail damage score in pigs
Dervishi, E. ; Zande, Lisette van der; Silva Valente, T. da; Reimert, I. ; Mathur, Pramod K. ; Lopes, M.S. ; Knol, E.F. ; Plastow, G.S. - \ 2019
The purpose of this study was to identify important metabolitesrelated to tail damage (TDAM) score and to identify genomic regionsassociated with variation in the metabolites. We used 181 Tempo ×Topigs-20 animals divided over 2 batches balanced for gender and selectedfor positive (n = 81) or negative (n = 100) indirect genetic effect(IGE) for growth. Half of the pigs were housed in a barren environment,and the other half in an enriched environment. The tail scores were recordedat weaning and thereafter once a week (score 1 no visible taildamage, score 2 hair removed from the tail, score 3 bite marks and score4 clearly visible wound). Blood samples collected at 8, 9 and 22 weeksof age were used to determine metabolic profiles at The MetabolomicsInnovation Centre (University of Alberta). A total of 53 compoundswere quantified. Statistical analyses were performed in R version 3.5using a generalized mixed model with repeated measurements. A singlestep genome-wide association study (ssGWAS) was performed toidentify genomic regions associated with significant metabolites for tailbiting score. Preliminary results show that serum levels of glycerol andisopropanol were significantly associated with tail damage score. Animalswith TDAM 2 had greater glycerol concentration in blood whencompared with animals with TDAM 3 and 4 (P < 0.05). In addition,animals with TDAM 1 had lower isopropanol concentration when comparedwith animals with TDAM 2 and 3 (P < 0.05). GWAS identified2 candidate regions located on chromosome 6 associated with glyceroland isopropanol (at 45Mb, and at 149Mb respectively). The candidategenes identified in these regions were ZFP14, DOCK7, ANGPTL3,USP1 and KANK4. Angiopoietin like 3 is a secreted protein encoded byANGPTL3 that is involved in the regulation of lipid and glucose metabolism.This protein is present at high levels in the liver where it can bindto adipocytes to activate lipolysis, releasing free fatty acids and glycerol.These results suggest that animals with tail damage (propensity tobeing bitten) might have impaired lipolysis processes.
The potential for pre-, pro- and synbiotics in the management of infants at risk of cow's milk allergy or with cow's milk allergy: An exploration of the rationale, available evidence and remaining questions
Fox, Adam ; Bird, J.A. ; Fiocchi, Alessandro ; Knol, Jan ; Meyer, Rosan ; Salminen, Seppo ; Sitang, Gong ; Szajewska, Hania ; Papadopoulos, Nikolaos - \ 2019
World Allergy Organization Journal 12 (2019)5. - ISSN 1939-4551
Allergy - Anaphylaxis - Bifidobacteria - Cow's milk allergy - Dysbiosis - IgE - Lactobacilli - Microbiota - Prebiotic - Probiotic - Synbiotic - World Allergy Organization

Cow's milk allergy is one of the most commonly reported childhood food allergies, with increasing incidence, persistence and severity in many countries across the world. The World Allergy Organization Special Committee on Food Allergy has identified cow's milk allergy as an area in need of a rationale-based approach in order to make progress against what it considered an onerous problem, with worldwide public health impact. There is growing interest in the potential role of the gut microbiota in the early programming and development of immune responses and allergy. This discussion paper considers the rationale and available evidence for modulation of the gut microbiota and for the use of synbiotics in the management of infants at risk of, or living with cow's milk allergy and summarizes remaining research questions that need to be answered for the development of evidence-based recommendations.

A specific synbiotic-containing amino acid-based formula restores gut microbiota in non-IgE mediated cow's milk allergic infants: A randomized controlled trial
Wopereis, Harm ; Ampting, Marleen T.J. Van; Cetinyurek-Yavuz, Aysun ; Slump, Rob ; Candy, David C.A. ; Butt, Assad M. ; Peroni, Diego G. ; Vandenplas, Yvan ; Fox, Adam T. ; Shah, Neil ; Roeselers, Guus ; Harthoorn, Lucien F. ; Michaelis, Louise J. ; Knol, Jan ; West, Christina E. - \ 2019
Clinical and Translational Allergy 9 (2019)1. - ISSN 2045-7022
Cow's milk allergy - Gut microbiota - Pediatrics - Prebiotics - Probiotics

Background: Altered gut microbiota is implicated in cow's milk allergy (CMA) and differs markedly from healthy, breastfed infants. Infants who suffer from severe CMA often rely on cow's milk protein avoidance and, when breastfeeding is not possible, on specialised infant formulas such as amino-acid based formulas (AAF). Herein, we report the effects of an AAF including specific synbiotics on oral and gastrointestinal microbiota of infants with non-IgE mediated CMA with reference to healthy, breastfed infants. Methods: In this prospective, randomized, double-blind controlled study, infants with suspected non-IgE mediated CMA received test or control formula. Test formula was AAF with synbiotics (prebiotic fructo-oligosaccharides and probiotic Bifidobacterium breve M-16V). Control formula was AAF without synbiotics. Healthy, breastfed infants were used as a separate reference group (HBR). Bacterial compositions of faecal and salivary samples were analysed by 16S rRNA-gene sequencing. Faecal analysis was complemented with the analysis of pH, short-chain fatty acids (SCFAs) and lactic acids. Results: The trial included 35 test subjects, 36 controls, and 51 HBR. The 16S rRNA-gene sequencing revealed moderate effects of test formula on oral microbiota. In contrast, the gut microbiota was substantially affected across time comparing test with control. In both groups bacterial diversity increased over time but was characterised by a more gradual increment in test compared to control. Compositionally this reflected an enhancement of Bifidobacterium spp. and Veillonella sp. in the test group. In contrast, the control-fed infants showed increased abundance of adult-like species, mainly within the Lachnospiraceae family, as well as within the Ruminococcus and Alistipes genus. The effects on Bifidobacterium spp. and Lachnospiraceae spp. were previously confirmed through enumeration by fluorescent in situ hybridization and were shown for test to approximate the proportions observed in the HBR. Additionally, microbial activity was affected as evidenced by an increase of l-lactate, a decrease of valerate, and reduced concentrations of branched-chain SCFAs in test versus control. Conclusions: The AAF including specific synbiotics effectively modulates the gut microbiota and its metabolic activity in non-IgE mediated CMA infants bringing it close to a healthy breastfed profile. Trial registration Registered on 1 May 2013 with Netherlands Trial Register Number NTR3979.

The Preterm Gut Microbiota: An Inconspicuous Challenge in Nutritional Neonatal Care
Henderickx, Jannie G.E. ; Zwittink, Romy D. ; Lingen, Richard A. van; Knol, Jan ; Belzer, Clara - \ 2019
Frontiers in Cellular and Infection Microbiology 9 (2019). - ISSN 2235-2988 - 1 p.
development - gastrointestinal tract - growth - gut microbiota - health - immune system - preterm - very low birth weight

The nutritional requirements of preterm infants are unique and challenging to meet in neonatal care, yet crucial for their growth, development and health. Normally, the gut microbiota has distinct metabolic capacities, making their role in metabolism of dietary components indispensable. In preterm infants, variation in microbiota composition is introduced while facing a unique set of environmental conditions. However, the effect of such variation on the microbiota's metabolic capacity and on the preterm infant's growth and development remains unresolved. In this review, we will provide a holistic overview on the development of the preterm gut microbiota and the unique environmental conditions contributing to this, in addition to maturation of the gastrointestinal tract and immune system in preterm infants. The role of prematurity, as well as the role of human milk, in the developmental processes is emphasized. Current research stresses the early life gut microbiota as cornerstone for simultaneous development of the gastrointestinal tract and immune system. Besides that, literature provides clues that prematurity affects growth and development. As such, this review is concluded with our hypothesis that prematurity of the gut microbiota may be an inconspicuous clinical challenge in achieving optimal feeding besides traditional challenges, such as preterm breast milk composition, high nutritional requirements and immaturity of the gastrointestinal tract and immune system. A better understanding of the metabolic capacity of the gut microbiota and its impact on gut and immune maturation in preterm infants could complement current feeding regimens in future neonatal care and thereby facilitate growth, development and health in preterm infants.

The development of early life gut microbiota in health and allergic disease
Wopereis, Harm - \ 2019
Wageningen University. Promotor(en): J. Knol; W.M. de Vos, co-promotor(en): C. Belzer. - Wageningen : Wageningen University - ISBN 9789463434157 - 184
Prebiotic oligosaccharides in early life alter gut microbiome development in male mice while supporting influenza vaccination responses
Elsen, L.W.J. van den; Tims, S. ; Jones, A.M. ; Stewart, A. ; Stahl, B. ; Garssen, J. ; Knol, J. ; Forbes-Blom, E.E. ; van’t Land, B. - \ 2019
Beneficial Microbes 10 (2019)3. - ISSN 1876-2883 - p. 279 - 291.
Antibody - Gender - HMOS - Microbiota - TIV

Beneficial modulation of the gut microbiota is an attractive therapeutic approach to improve the efficacy of vaccine-induced immunity. In this study, mice were supplemented with the prebiotic milk oligosaccharide 2’-fucosyllactose (2’FL) as well as a complex mixture of immune modulatory prebiotic short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) from different stages in early life. Adult mice were vaccinated with trivalent influenza vaccine (TIV) and both development of the gut microbiota and antibody-mediated vaccine responses were followed over time. Within the control group, female mice demonstrated a larger antibody response to TIV vaccination than male mice, which was accompanied by enhanced cytokine production by splenocytes and a higher percentage of plasma cells in skin draining lymph nodes. In addition, the prebiotic diet improved vaccine-specific antibody responses in male mice. Introduction of prebiotics into the diet modulated the gut microbiota composition and at the genus level several bacterial groups showed a significant interaction effect which potentially contributed to the immunological effects observed. This study provides insight in the effect of scGOS/lcFOS/2’FL in influenza vaccination antibody production.

Gut microbiota from infant with cow’s milk allergy promotes clinical and immune features of atopy in a murine model
Mauras, Aurélie ; Wopereis, Harm ; Yeop, Intan ; Esber, Nathalie ; Delannoy, Johanne ; Labellie, Chantal ; Reygner, Julie ; Kapel, Nathalie ; Slump, Rob ; Eijndthoven, Tiemen van; Rutten, Lieke ; Knol, Jan ; Garssen, Johan ; Harthoorn, Lucien F. ; Butel, Marie José ; Bajaj-Elliott, Mona ; Hartog, Anita ; Waligora-Dupriet, Anne Judith - \ 2019
Allergy 74 (2019)9. - ISSN 0105-4538 - p. 1790 - 1793.
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.

Supplementation of dietary non-digestible oligosaccharides from birth onwards improve social and reduce anxiety-like behaviour in male BALB/c mice
Szklany, Kirsten ; Wopereis, Harm ; Waard, Cindy de; Wageningen, Thecla van; An, Ran ; Limpt, Kees van; Knol, Jan ; Garssen, Johan ; Knippels, Leon M.J. ; Belzer, Clara ; Kraneveld, Aletta D. - \ 2019
Nutritional Neuroscience (2019). - ISSN 1028-415X
Behaviour - dietary supplementation from birth - early life - fructo-oligosaccharide - galacto-oligosaccharide - healthy mice - intestinal microbiota - prebiotics - SCFA - serotonergic system

Objective: The intestinal microbiota is acknowledged to be essential in brain development and behaviour. Their composition can be modulated by prebiotics such as short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharide (lcFOS). Several studies reported potential health benefit of prebiotics on behaviour. As the prebiotic mixture of scGOS and lcFOS is included in infant formula, we investigated the effects of dietary supplementation with this specific mixture from the day of birth onwards on behaviour and intestinal microbiota development in mice. Method: Healthy male BALB/cByJ mice received, from day of birth, a dietary supplement with or without 3% scGOS:lcFOS (9:1). Behavioural tests were performed pre-weaning, in adolescence, early adulthood and adulthood. We assessed faecal microbiota compositions over time, caecal short-chain fatty acids as well as brain mRNA expression of Htr1a, Htr1b and Tph2 and monoamine levels. Results: Compared to control fed mice, scGOS:lcFOS fed mice showed reduced anxiety-like and repetitive behaviour over time and improved social behaviour in adulthood. The serotonergic system in the prefrontal cortex (PFC) and somatosensory cortex (SSC) was affected by the scGOS:lcFOS. In the PFC, mRNA expression of brain-derived neurotrophic factor (Bdnf) was enhanced in scGOS:lcFOS fed mice. Although the bacterial diversity of the intestinal microbiota was unaffected by the scGOS:lcFOS diet, microbiota composition differed between the scGOS:lcFOS and the control fed mice over time. Moreover, an increased saccharolytic and decreased proteolytic fermentation activity were observed in caecum content. Discussion: Supplementing the diet with scGOS:lcFOS from the day of birth is associated with reduced anxiety-like and improved social behaviour during the developmental period and later in life, and modulates the composition and activity of the intestinal microbiota in healthy male BALB/c mice. These data provide further evidence of the potential impact of scGOS:lcFOS on behaviour at several developmental stages throughout life and strengthen the insights in the interplay between the developing intestine and brain.

Mice co-administrated with partially hydrolysed whey proteins and prebiotic fibre mixtures show allergen-specific tolerance and a modulated gut microbiota
Kleinjans, L. ; Veening-Griffioen, D.H. ; Wehkamp, T. ; Bergenhenegouwen, J. van; Knol, J. ; Garssen, J. ; Knippels, L.M.J. ; Belzer, C. ; Jeurink, P.V. - \ 2019
Beneficial Microbes 10 (2019)2. - ISSN 1876-2883 - p. 165 - 178.
cow’s milk allergy - microbiota - non-digestible oligosaccharides - preventive tolerance induction

Non-breastfed infants at-risk of allergy are recommended to use a hydrolysed formula before the age of 6 months. The addition of prebiotics to this formula may reduce the allergy development in these infants, but clinical evidence is still inconclusive. This study evaluates (1) whether the exposure duration to different prebiotics alongside a partially hydrolysed whey protein (pHP) influences its' effectiveness to prevent allergy development and (2) whether the gut microbiota plays a role in this process. Mice orally sensitised with whey and/or cholera toxin were orally treated for six days before sensitization with phosphate buffered saline, whey or pHP to potentially induce tolerance. Two groups received an oligosaccharide diet only from day -7 until -2 (GFshort and GFAshort) whereas two other groups received their diets from day -15 until 37 (GFlong and GFAlong). On day 35, mice underwent an intradermal whey challenge, and the acute allergic skin response, shock score, and body temperatures were measured. At day 37, mice received whey orally and serum mouse mast cell protease-1, SLPI and whey-specific antibodies were assessed. Faecal samples were taken at day -15, -8 and 34. Feeding mice pHP alone during tolerance induction did not reduce ear swelling. The tolerance inducing mechanisms seem to vary according to the oligosaccharide-composition. GFshort, GFlong, and GFAlong reduced the allergic skin response, whereas GFAshort was not potent enough. However, in the treatment groups, the dominant Lactobacillus species decreased, being replaced by Bacteroidales family S24-7 members. In addition, the relative abundance of Prevotella was significantly higher in the GFlong, GFAshort and GFAlong groups. Co-administration of oligosaccharides and pHP can induce immunological tolerance in mice, although tolerance induction was strongest in the animals that were fed oligosaccharides during the entire protocol. Some microbial changes coincided with tolerance induction, however, a specific mechanism could not be determined based on these data.

Defining resilient pigs after a PRRS challenge using activity and feeding data from accelerometers
Zande, Lisette van der; Dunkelberger, Jenelle R. ; Rodenburg, T.B. ; Mathur, Pramod K. ; Cairns, W.J. ; Keyes, Michael C. ; Knol, E.F. ; Dee, Scott A. ; Little, Erin A. - \ 2019
In: Trade-offs in science – keeping the balance. - Wageningen University & Research - p. 48 - 48.
Selecting for changes in average “parity curve” pattern of litter size in Large White pigs
Sell-Kubiak, Ewa ; Knol, Egbert Frank ; Mulder, Herman Arend - \ 2019
Journal of Animal Breeding and Genetics 136 (2019)2. - ISSN 0931-2668 - p. 134 - 148.
random regression - reproduction traits - sows - total number born - within-sow variation

This study aimed to analyse genetic background of variation in reproductive performance between parities of a sow and to investigate selection strategies to change the “parity curve”. Total number born (TNB) recorded in Large White sows was provided by Topigs Norsvin. Analysis with basic (BM) and random regression (RRM) models was done in ASReml 4.1. The BM included only a fixed “parity curve”, while RRM included 3rd order polynomials for additive genetic and permanent sow effects. Parameters from RRM were used in simulations in SelAction 2.1. Based on Akaike information criterion, RRM was a better model for TNB data. Genetic variance and heritability estimates of TNB from BM and RRM were increasing with parity from parity 2. Genetically, parity 1 is the most different from parities 7 to 10, whereas most similar to parities 2 and 3. This indicates presence of genetic variation to change the “parity curve”. Based on simulations, the selection to increase litter size in parity 1 only increases TNB in all parities, but does not change the observed shape of “parity curve”, whereas selection for increased TNB in parity 1 and reduced TNB in parity 5 decreases differences between parities, but also reduces overall TNB in all parities. Changing the “parity curve” will be difficult as the genetic and phenotypic relationships between the parities are hard to overcome even when selecting for one parity.

A specific synbiotic-containing amino acid-based formula in dietary management of cow's milk allergy : A randomized controlled trial
Fox, Adam T. ; Wopereis, Harm ; Ampting, Marleen T.J. van; Oude Nijhuis, Manon M. ; Butt, Assad M. ; Peroni, Diego G. ; Vandenplas, Yvan ; Candy, David C.A. ; Shah, Neil ; West, Christina E. ; Garssen, Johan ; Harthoorn, Lucien F. ; Knol, Jan ; Michaelis, Louise J. - \ 2019
Clinical and Translational Allergy 9 (2019)1. - ISSN 2045-7022
Bifidobacterium breve M-16V - Cow's milk allergy - Gut microbiota - Prebiotic - Probiotic - Symptoms

Background: Here we report follow-up data from a double-blind, randomized, controlled multicenter trial, which investigated fecal microbiota changes with a new amino acid-based formula (AAF) including synbiotics in infants with non-immunoglobulin E (IgE)-mediated cow's milk allergy (CMA). Methods: Subjects were randomized to receive test product (AAF including fructo-oligosaccharides and Bifidobacterium breve M-16V) or control product (AAF) for 8 weeks, after which infants could continue study product until 26 weeks. Fecal percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) were assessed at 0, 8, 12, and 26 weeks. Additional endpoints included stool markers of gut immune status, clinical symptoms, and safety assessments including adverse events and medication use. Results: The trial included 35 test subjects, 36 controls, and 51 in the healthy reference group. Study product was continued by 86% and 92% of test and control subjects between week 8-12, and by 71% and 80%, respectively until week 26. At week 26 median percentages of bifidobacteria were significantly higher in test than control [47.0% vs. 11.8% (p < 0.001)], whereas percentages of ER/CC were significantly lower [(13.7% vs. 23.6% (p = 0.003)]. Safety parameters were similar between groups. Interestingly use of dermatological medication and reported ear infections were lower in test versus control, p = 0.019 and 0.011, respectively. Baseline clinical symptoms and stool markers were mild (but persistent) and low, respectively. Symptoms reduced towards lowest score in both groups. Conclusion: Beneficial effects of this AAF including specific synbiotics on microbiota composition were observed over 26 weeks, and shown suitable for dietary management of infants with non-IgE-mediated CMA.

Follicular development of sows at weaning in relation to estimated breeding value for within-litter variation in piglet birth weight
Costermans, N.G.J. ; Teerds, K.J. ; Keijer, J. ; Knol, E.F. ; Koopmanschap, R.E. ; Kemp, B. ; Soede, N.M. - \ 2019
Animal 13 (2019)3. - ISSN 1751-7311 - p. 554 - 563.
lactation - litter uniformity - metabolism - reproduction - sows

In this study we aimed to identify possible causes of within-litter variation in piglet birth weight (birth weight variation) by studying follicular development of sows at weaning in relation to their estimated breeding value (EBV) for birth weight variation. In total, 29 multiparous sows (parity 3 to 5) were selected on their EBV for birth weight variation (SD in grams; High-EBV: 15.8±1.6, N=14 and Low-EBV: −24.7±1.5, N=15). The two groups of sows had similar litter sizes (15.7 v. 16.9). Within 24 h after parturition, piglets were cross-fostered to ensure 13 suckling piglets per sow. Sows weaned 12.8±1.0 and 12.7±1.0 piglets, respectively, at days 26.1±0.2 of lactation. Blood and ovaries were collected within 2 h after weaning. The right ovary was immediately frozen to assess average follicle size and percentage healthy follicles of the 15 largest follicles. The left ovary was used to assess the percentage morphologically healthy cumulus-oocyte complexes (COCs) of the 15 largest follicles. To assess the metabolic state of the sows, body condition and the circulating metabolic markers insulin, IGF1, non-esterified fatty acid, creatinine, leptin, urea and fibroblast growth factor 21 were analysed at weaning. No significant differences were found in any of the measured follicular or metabolic parameters between High-EBV and Low-EBV. A higher weight loss during lactation was related to a lower percentage healthy COCs (β= −0.65, P=0.02). Serum creatinine, a marker for protein breakdown, was negatively related to average follicle size (β= −0.60, P=0.05). Backfat loss during lactation was related to a higher backfat thickness at parturition and to a higher average follicle size (β=0.36, P<0.001) at weaning. In conclusion, we hypothesise that modern hybrid sows with more backfat at the start of lactation are able to mobilise more energy from backfat during lactation and could thereby spare protein reserves to support follicular development.

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