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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    Enduring Behavioral Effects Induced by Birth by Caesarean Section in the Mouse
    Morais, Livia H. ; Golubeva, Anna V. ; Moloney, Gerard M. ; Moya-Pérez, Angela ; Ventura-Silva, Ana Paula ; Arboleya, Silvia ; Bastiaanssen, Thomaz F.S. ; O'Sullivan, Orla ; Rea, Kieran ; Borre, Yuliya ; Scott, Karen A. ; Patterson, Elaine ; Cherry, Paul ; Stilling, Roman ; Hoban, Alan E. ; Aidy, Sahar El; Sequeira, Ana M. ; Beers, Sasja ; Moloney, Rachel D. ; Renes, Ingrid B. ; Wang, Shugui ; Knol, Jan ; Ross, R.P. ; O'Toole, Paul W. ; Cotter, Paul D. ; Stanton, Catherine ; Dinan, Timothy G. ; Cryan, John F. - \ 2020
    Current Biology 30 (2020)19. - ISSN 0960-9822 - p. 3761 - 3774.e6.
    behavior - Caesarean section - co-housing - gut-brain axis - microbiota - microbiota gut-brain axis - prebiotics - probiotics

    Birth by Caesarean (C)-section impacts early gut microbiota colonization and is associated with an increased risk of developing immune and metabolic disorders. Moreover, alterations of the microbiome have been shown to affect neurodevelopmental trajectories. However, the long-term effects of C-section on neurobehavioral processes remain unknown. Here, we demonstrated that birth by C-section results in marked but transient changes in microbiome composition in the mouse, in particular, the abundance of Bifidobacterium spp. was depleted in early life. Mice born by C-section had enduring social, cognitive, and anxiety deficits in early life and adulthood. Interestingly, we found that these specific behavioral alterations induced by the mode of birth were also partially corrected by co-housing with vaginally born mice. Finally, we showed that supplementation from birth with a Bifidobacterium breve strain, or with a dietary prebiotic mixture that stimulates the growth of bifidobacteria, reverses selective behavioral alterations in C-section mice. Taken together, our data link the gut microbiota to behavioral alterations in C-section-born mice and suggest the possibility of developing adjunctive microbiota-targeted therapies that may help to avert long-term negative consequences on behavior associated with C-section birth mode.

    Intestinal Microbiota and Immune Modulation in Zebrafish by Fucoidan From Okinawa Mozuku (Cladosiphon okamuranus)
    Ikeda-Ohtsubo, Wakako ; López Nadal, Adrià ; Zaccaria, Edoardo ; Iha, Masahiko ; Kitazawa, Haruki ; Kleerebezem, Michiel ; Brugman, Sylvia - \ 2020
    Frontiers in Nutrition 7 (2020). - ISSN 2296-861X
    fucoidan - immunomodulation - microbiota - seaweed polysaccharides - zebrafish

    Fucoidan represents fucose-rich sulfated polysaccharides derived from brown seaweeds, which exerts various biological activities applicable for functional foods and therapeutic agents. The objective of the present study was to investigate in vivo effects of fucoidan extracted from Okinawa mozuku (Cladosiphon okamuranus), common edible seaweed in Japan, on immune responses and microbiota composition in zebrafish. We treated larvae and adult zebrafish with Okinawa mozuku (OM) fucoidan by immersion (100 and 500 μg/mL, 3 days) and by feeding (3 weeks), respectively. The effect of OM fucoidan on immune responses in zebrafish larvae was evaluated by live imaging of neutrophils and macrophages as well as quantitative polymerase chain reaction of pro- and anti-inflammatory cytokine genes. Whole microbiota of zebrafish larvae and intestinal microbiota of adult zebrafish treated with OM fucoidan were analyzed by Illumina MiSeq pair-end sequencing of the V3–V4 region of 16S rRNA genes. Fucoidan treatment only slightly affected the composition of the larvae microbiota and the number of neutrophils and macrophages, while pro- and anti-inflammatory cytokine gene expression levels were upregulated in the larvae treated with 500 μg/mL OM fucoidan. In contrast, feeding of OM fucoidan clearly altered the intestinal microbiota composition of adult zebrafish, which was characterized by the emergence and predominance of multiple bacterial operational taxonomic units (OTUs) affiliated with Rhizobiaceae and Comamonadaceae at the expense of E. coli-related Enterobacteriaceae, the dominant OTUs throughout the studied samples. These changes were accompanied by decreased expression levels of pro-inflammatory cytokine il1b in the intestines of the adult zebrafish. Our current study provides the first insights into in vivo modulatory effects of fucoidan on microbiota and immune responses of unchallenged zebrafish, which underscores the potential of fucoidan to play a modulatory role in the diet–microbiota–host interplay.

    The effect of maternal antibiotic use in sows on intestinal development in offspring
    Greeff, Astrid de; Schokker, Dirkjan ; Roubos-van den Hil, Petra ; Ramaekers, Peter ; Vastenhouw, Stephanie A. ; Harders, Frank ; Bossers, Alex ; Smits, Mari A. ; Rebel, Johanna M.J. - \ 2020
    Journal of Animal Science 98 (2020)6. - ISSN 0021-8812
    antibiotic - gut development - immune response - microbiota - piglets - transgenerational

    The objective of this study is to investigate the effect of a maternal antibiotic administration during the last week of gestation on the early life intestinal development in neonatal piglets. Colonization of the gut with bacteria starts during birth and plays a major role in the intestinal and immunological development of the intestine. We demonstrate that maternal interventions induced changes in the sows (n = 6 to 8 per treatment) fecal microbiota diversity around birth (P < 0.001, day 1). Whole-genome microarray analysis in small intestinal samples of 1-d old piglets (n = 6 to 8 per treatment) showed significantly expressed genes (Padj < 0.05) which were involved in processes of tight junction formation and immunoglobulin production. Furthermore, when performing morphometry analysis, the number of goblet cells in jejunum was significantly (P < 0.001) lower in piglets from amoxicillin administered sows compared with the respective control piglets. Both significantly expressed genes (Padj < 0.05) and significant morphometry data (jejunum P < 0.05 and ileum P < 0.01) indicate that the crypts of piglets from amoxicillin administered sows deepen around weaning (day 26) as an effect of the amoxicillin administration in sows. The latter might imply that the intestinal development of piglets was delayed by maternal antibiotic administration. Taken together, these results show that maternally oral antibiotic administration changes in early life can affect intestinal development of the offspring piglets for a period of at least 5 wk after the maternal antibiotic administration was finished. These results show that modulation of the neonatal intestine is possible by maternal interventions.

    Microbiota of sows and their offspring
    Schokker, Dirkjan ; Bossers, Alex ; Greeff, Astrid de - \ 2020
    Zenodo
    microbiota - piglets - antibiotic - gut development - immune response - transgenerational
    Microbiota composition was determined of sow feces, sow vaginal swabs and piglet jejunal digesta. Samples were frozen on dry-ice and stored at -80°C. To isolate DNA, samples were mixed in a 1:1 ratio with phosphate buffered saline (PBS) and centrifuged for 5 min at 4°C at 300xg. Supernatant was collected and centrifuged for 10 min at 4°C at 9000xg. DNA was extracted from the pellet using the “QIAamp DNA stool minikit” (Qiagen, Valencia, CA, USA) according to manufacturers’ instructions, after mechanical shearing of the bacteria in Lysing Matrix B tubes using the FastPrep-24 (MP Biomedicals, Solon, OH, USA). Quality and quantity of DNA were checked using the NANOdrop (Agilent Technologies, Santa Clara, CA, USA). PCR was used to amplify (20 cycles) the 16S rRNA gene V3 fragment using forward primer V3_F (CCTACGGGAGGCAGCAG) and reverse primer V3_R (ATTACCGCGGCTGCTGG). PCR efficiency was checked on agarose gel. Amplicons were sequenced using paired-end, excluding one sample that did not pass the quality control, 150bp technology on a MiSeq sequencer (Illumina, San Diego, CA, USA) at a sequencing depth in the range of 196K-1.2M read-pairs per sample (median 670,647 read-pairs per sample).
    Fermentation of Chicory Fructo-Oligosaccharides and Native Inulin by Infant Fecal Microbiota Attenuates Pro-Inflammatory Responses in Immature Dendritic Cells in an Infant-Age-Dependent and Fructan-Specific Way
    Logtenberg, Madelon J. ; Akkerman, Renate ; An, Ran ; Hermes, Gerben D.A. ; Haan, Bart J. de; Faas, Marijke M. ; Zoetendal, Erwin G. ; Schols, Henk A. ; Vos, Paul de - \ 2020
    Molecular Nutrition & Food Research 64 (2020)13. - ISSN 1613-4125
    dendritic cells - in vitro fermentation - infant formula - inulin-type fructans - microbiota

    Scope: Inulin-type fructans are commonly applied in infant formula to support development of gut microbiota and immunity. These inulin-type fructans are considered to be fermented by gut microbiota, but it is unknown how fermentation impacts immune modulating capacity and whether the process of fermentation is dependent on the infant's age. Methods and results: The in vitro fermentation of chicory fructo-oligosaccharides (FOS) and native inulin are investigated using pooled fecal inocula of two- and eight-week-old infants. Both inocula primarily utilize the trisaccharides in FOS, while they almost completely utilize native inulin with degree of polymerization (DP) 3–8. Fecal microbiota of eight-week-old infants degrades longer chains of native inulin up to DP 16. This correlates with a higher abundance of Bifidobacterium and higher production of acetate and lactate after 26 h of fermentation. Fermented FOS and native inulin attenuate pro-inflammatory cytokines produced by immature dendritic cells (DCs), but profiles and magnitude of attenuation are stronger with native inulin than with FOS. Conclusion: The findings demonstrate that fermentation of FOS and native inulin is dependent on the infant's age and fructan structure. Fermentation enhances attenuating effects of pro-inflammatory responses in DCs, which depend mainly on microbial metabolites formed during fermentation.

    Long-Term β-galacto-oligosaccharides Supplementation Decreases the Development of Obesity and Insulin Resistance in Mice Fed a Western-Type Diet
    Mistry, Rima H. ; Liu, Fan ; Borewicz, Klaudyna ; Lohuis, Mirjam A.M. ; Smidt, Hauke ; Verkade, Henkjan J. ; Tietge, Uwe J.F. - \ 2020
    Molecular Nutrition & Food Research 64 (2020)12. - ISSN 1613-4125
    adipose tissue - galactooligosaccharides - lipid absorption - microbiota - prebiotics

    Scope: The gut microbiota might critically modify metabolic disease development. Dietary fibers such as galacto-oligosaccharides (GOS) presumably stimulate bacteria beneficial for metabolic health. This study assesses the impact of GOS on obesity, glucose, and lipid metabolism. Methods and results: Following Western-type diet feeding (C57BL/6 mice) with or without β-GOS (7% w/w, 15 weeks), body composition, glucose and insulin tolerance, lipid profiles, fat kinetics and microbiota composition are analyzed. GOS reduces body weight gain (p < 0.01), accumulation of epididymal (p < 0.05), perirenal (p < 0.01) fat, and insulin resistance (p < 0.01). GOS-fed mice have lower plasma cholesterol (p < 0.05), mainly within low-density lipoproteins, lower intestinal fat absorption (p < 0.01), more fecal neutral sterol excretion (p < 0.05) and higher intestinal GLP-1 expression (p < 0.01). Fecal bile acid excretion is lower (p < 0.01) in GOS-fed mice with significant compositional differences, namely decreased cholic, α-muricholic, and deoxycholic acid excretion, whereas hyodeoxycholic acid increased. Substantial changes in microbiota composition, conceivably beneficial for metabolic health, occurred upon GOS feeding. Conclusion: GOS supplementation to a Western-type diet improves body weight gain, dyslipidemia, and insulin sensitivity, supporting a therapeutic potential of GOS for individuals at risk of developing metabolic syndrome.

    Dietary Isomalto/Malto-Polysaccharides Increase Fecal Bulk and Microbial Fermentation in Mice
    Mistry, Rima H. ; Borewicz, Klaudyna ; Gu, Fangjie ; Verkade, Henkjan J. ; Schols, Henk A. ; Smidt, Hauke ; Tietge, Uwe J.F. - \ 2020
    Molecular Nutrition & Food Research 64 (2020)12. - ISSN 1613-4125
    bile acids - cholesterol - IMMP - microbiota - polysaccharides - prebiotics - short-chain fatty acids

    Scope: The prevalence of metabolic-syndrome-related disease has strongly increased. Nutritional intervention strategies appear attractive, particularly with novel prebiotics. Isomalto/malto-polysaccharides (IMMPs) represent promising novel prebiotics that promote proliferation of beneficial bacteria in vitro. The present study investigates for the first time the in vivo effects of IMMP in mice. Methods and results: C57BL/6 wild-type mice received control or IMMP-containing (10%, w/w) diets for 3 weeks. IMMP leads to significantly more fecal bulk (+26%, p < 0.05), higher plasma non-esterified fatty acids (colorimetric assay, +10%, p < 0.05), and lower fecal dihydrocholesterol excretion (mass spectrometry, −50%, p < 0.05). Plasma and hepatic lipid levels (colorimetric assays following lipid extraction) are not influenced by dietary IMMP, as are other parameters of sterol metabolism, including bile acids (gas chromatography/mass spectrometry). IMMP is mainly fermented in the cecum and large intestine (high-performance anion exchange chromatography). Next-generation sequencing demonstrates higher relative abundance of Bacteroides and butyrate producers (Lachnospiraceae, Roseburia Odoribacter) in the IMMP group. Conclusion: The combined results demonstrate that IMMP administration to mice increases fecal bulk and induces potentially beneficial changes in the intestinal microbiota. Further studies are required in disease models to substantiate potential health benefits.

    Effect of fructans, prebiotics and fibres on the human gut microbiome assessed by 16S rRNA-based approaches : a review
    Swanson, K.S. ; Vos, W.M. de; Martens, E.C. ; Gilbert, J.A. ; Menon, R.S. ; Soto-Vaca, A. ; Hautvast, J. ; Meyer, P.D. ; Borewicz, K. ; Vaughan, E.E. ; Slavin, J.L. - \ 2020
    Beneficial Microbes 11 (2020)2. - ISSN 1876-2883 - p. 101 - 129.
    health - intestine - inulin - microbiota - nutrition

    The inherent and diverse capacity of dietary fibres, nondigestible oligosaccharides (NDOs) and prebiotics to modify the gut microbiota and markedly influence health status of the host has attracted rising interest. Research and collective initiatives to determine the composition and diversity of the human gut microbiota have increased over the past decade due to great advances in high-throughput technologies, particularly the 16S ribosomal RNA (rRNA) sequencing. Here we reviewed the application of 16S rRNA-based molecular technologies, both community wide (sequencing and phylogenetic microarrays) and targeted methodologies (quantitative PCR, fluorescent in situ hybridisation) to study the effect of chicory inulin-type fructans, NDOs and specific added fibres, such as resistant starches, on the human intestinal microbiota. Overall, such technologies facilitated the monitoring of microbiota shifts due to prebiotic/fibre consumption, though there are limited community-wide sequencing studies so far. Molecular studies confirmed the selective bifidogenic effect of fructans and galactooligosaccharides (GOS) in human intervention studies. Fructans only occasionally decreased relative abundance of Bacteroidetes or stimulated other groups. The sequencing studies for various resistant starches, polydextrose and beta-glucan showed broader effects with more and different types of gut microbial species being enhanced, often including phylotypes of Ruminococcaceae. There was substantial variation in terms of magnitude of response and in individual responses to a specific fibre or NDO which may be due to numerous factors, such as initial presence and relative abundance of a microbial type, diet, genetics of the host, and intervention parameters, such as intervention duration and fibre dose. The field will clearly benefit from a more systematic approach that will support defining the impact of prebiotics and fibres on the gut microbiome, identify biomarkers that link gut microbes to health, and address the personalised response of an individual's microbiota to prebiotics and dietary fibres.

    Feed, Microbiota, and Gut Immunity: Using the Zebrafish Model to Understand Fish Health
    López Nadal, Adrià ; Ikeda-Ohtsubo, Wakako ; Sipkema, Detmer ; Peggs, David ; McGurk, Charles ; Forlenza, Maria ; Wiegertjes, Geert F. ; Brugman, Sylvia - \ 2020
    Frontiers in Immunology 11 (2020). - ISSN 1664-3224
    gut - immunity - intestine - microbiota - prebiotics - probiotics - zebrafish

    Aquafeed companies aim to provide solutions to the various challenges related to nutrition and health in aquaculture. Solutions to promote feed efficiency and growth, as well as improving the fish health or protect the fish gut from inflammation may include dietary additives such as prebiotics and probiotics. The general assumption is that feed additives can alter the fish microbiota which, in turn, interacts with the host immune system. However, the exact mechanisms by which feed influences host-microbe-immune interactions in fish still remain largely unexplored. Zebrafish rapidly have become a well-recognized animal model to study host-microbe-immune interactions because of the diverse set of research tools available for these small cyprinids. Genome editing technologies can create specific gene-deficient zebrafish that may contribute to our understanding of immune functions. Zebrafish larvae are optically transparent, which allows for in vivo imaging of specific (immune) cell populations in whole transgenic organisms. Germ-free individuals can be reared to study host-microbe interactions. Altogether, these unique zebrafish features may help shed light on the mechanisms by which feed influences host-microbe-immune interactions and ultimately fish health. In this review, we first describe the anatomy and function of the zebrafish gut: the main surface where feed influences host-microbe-immune interactions. Then, we further describe what is currently known about the molecular pathways that underlie this interaction in the zebrafish gut. Finally, we summarize and critically review most of the recent research on prebiotics and probiotics in relation to alterations of zebrafish microbiota and immune responses. We discuss the advantages and disadvantages of the zebrafish as an animal model for other fish species to study feed effects on host-microbe-immune interactions.

    The Use of Proton Pump Inhibitors May Increase Symptoms of Muscle Function Loss in Patients with Chronic Illnesses
    Vinke, Paulien ; Wesselink, Evertine ; Orten-Luiten, Wout van; Norren, Klaske van - \ 2020
    International Journal of Molecular Sciences 21 (2020)1. - ISSN 1661-6596
    cachexia - cancer - COPD - heart failure - inflammation - magnesium - microbiota - proton pump inhibitors - sarcopenic obesity - vitamin D

    Long-term use of proton pump inhibitors (PPIs) is common in patients with muscle wasting-related chronic diseases. We explored the hypothesis that the use of PPIs may contribute to a reduction in muscle mass and function in these patients. Literature indicates that a PPI-induced reduction in acidity of the gastrointestinal tract can decrease the absorption of, amongst others, magnesium. Low levels of magnesium are associated with impaired muscle function. This unwanted side-effect of PPIs on muscle function has been described in different disease backgrounds. Furthermore, magnesium is necessary for activation of vitamin D. Low vitamin D and magnesium levels together can lead to increased inflammation involved in muscle wasting. In addition, PPI use has been described to alter the microbiota's composition in the gut, which might lead to increased inflammation. However, PPIs are often provided together with nonsteroidal anti-inflammatory drugs (NSAIDs), which are anti-inflammatory. In the presence of obesity, additional mechanisms could further contribute to muscle alterations. In conclusion, use of PPIs has been reported to contribute to muscle function loss. Whether this will add to the risk factor for development of muscle function loss in patients with chronic disease needs further investigation.

    Prediction of nutrient digestibility in grower-finisher pigs based on faecal microbiota composition
    Verschuren, Lisanne M.G. ; Schokker, Dirkjan ; Bergsma, Rob ; Jansman, Alfons J.M. ; Molist, Francesc ; Calus, Mario P.L. - \ 2020
    Journal of Animal Breeding and Genetics 137 (2020)1. - ISSN 0931-2668 - p. 23 - 35.
    digestion - metagenomics - microbiota - pig

    Microbiota play an important role in total tract nutrient digestion, especially when fibrous diets are fed to pigs. This study aimed to use metagenomics to predict faecal nutrient digestibility in grower-finisher pigs. The study design consisted of 160 three-way crossbreed grower-finisher pigs (80 female and 80 male) which were either fed a diet based on corn/soybean meal or a more fibrous diet based on wheat/barley/by-products. On the day before slaughter, faecal samples were collected and used to determine faecal digestibility of dry matter, ash, organic matter, crude protein, crude fat, crude fibre and non-starch polysaccharides. The faecal samples were also sequenced for the 16S hypervariable region of bacteria (V3/V4) to profile the faecal microbiome. With these data, we calculated the between-animal variation in faecal nutrient digestibility associated with variation in the faecal microbiome, that is the “microbiability”. The microbiability values were significantly greater than zero for dry matter, organic matter, crude protein, crude fibre and non-starch polysaccharides, ranging from 0.58 to 0.93, as well as for crude fat with a value of 0.37, but not significantly different from zero for ash. Using leave-one-out cross-validation, we estimated the accuracy of predicting digestibility values of individual pigs based on their faecal microbiota composition. The accuracies of prediction for crude fat and ash digestibility were virtually 0, and for the other nutrients, the accuracies ranged from 0.42 to 0.63. In conclusion, the faecal microbiota composition gave high microbiability values for faecal digestibility of dry matter, organic matter, crude protein, crude fibre and non-starch polysaccharides. The accuracies of prediction are relatively low if the interest is in precisely predicting faecal nutrient digestibility of individual pigs, but are promising from the perspective of ranking animals in a genetic selection context.

    Gut microbial composition of C57BL/6J mice and levels of betaines in related samples
    Koistinen, Ville M. ; Kärkkäinen, Olli ; Borewicz, Klaudyna ; Zarei, Iman ; Jokkala, Jenna ; Micard, Valérie ; Rosa-Sibakov, Natalia ; Auriola, Seppo ; Aura, Anna Marja ; Smidt, Hauke ; Hanhineva, Kati - \ 2019
    University of Eastern Finland
    microbiota - betaine - metabolomics
    1) The gut microbial composition of C57BL/6J mice fed with diets enriched with rye bran and wheat aleurone, analyzed with 16S rRNA sequencing. 2) Betaine levels in the colon contents of C57BL/6J mice fed with diets enriched with rye bran and wheat aleurone; 3) betaine levels in the caecal tissue of C57BL/6J mice fed with diets enriched with rye bran and wheat aleurone; 4) betaine levels in tissues of murine pathogen free (MPF) and germ-free (GF) C57BL/6NTac mice on a basal diet; 5) betaine levels in the in vitro model of the human gut; 6) betaine levels in cereal samples; all betaine levels analyzed with UPLC–QTOF-MS
    Biomarker Research in ADHD: The Impact of Nutrition (BRAIN) - Study protocol of an open-label trial to investigate the mechanisms underlying the effects of a few-foods diet on ADHD symptoms in children
    Stobernack, Tim ; Vries, Stefan P.W. De; Rodrigues Pereira, Rob ; Pelsser, Lidy M. ; Braak, Cajo J.F. Ter; Aarts, Esther ; Baarlen, Peter Van; Kleerebezem, Michiel ; Frankena, Klaas ; Hontelez, Saartje - \ 2019
    BMJ Open 9 (2019)11. - ISSN 2044-6055
    ADHD - biomarker - brain activity - few-foods diet - fMRI - microbiota

    Introduction Attention deficit hyperactivity disorder (ADHD) is the most common childhood behavioural disorder, causing significant impediment to a child's development. It is a complex disorder with numerous contributing (epi)genetic and environmental factors. Currently, treatment consists of behavioural and pharmacological therapy. However, ADHD medication is associated with several side effects, and concerns about long-term effects and efficacy exist. Therefore, there is considerable interest in the development of alternative treatment options. Double-blind research investigating the effects of a few-foods diet (FFD) has demonstrated a significant decrease in ADHD symptoms following an FFD. However, an FFD requires a considerable effort of both child and parents, limiting its applicability as a general ADHD treatment. To make FFD intervention less challenging or potentially obsolete, we need to understand how, and in which children, an FFD affects ADHD behaviour and, consequently, the child's well-being. We hypothesise that an FFD affects brain function, and that the nutritional impact on ADHD is effectuated by a complex interplay between the microbiota, gut and brain, that is, the microbiota-gut-brain axis. Methods and analysis The Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) study is an open-label trial with researchers blinded to changes in ADHD symptoms during sample processing and initial data analyses. Ethics and dissemination The Medical Research and Ethics Committee of Wageningen University has approved this study (NL63851.081.17, application 17/24). Results will be disseminated through peer-reviewed journal publications, conference presentations, (social) media and the BRAIN study website. A summary of the findings will be provided to the participants. Trial registration number NCT03440346. Study dates Collection of primary outcome data started in March 2018 and will be ongoing until 100 children have participated in the study. Sample data analysis will start after all samples have been collected.

    Allogenic Faecal Microbiota Transfer Induces Immune-Related Gene Sets in the Colon Mucosa of Patients with Irritable Bowel Syndrome
    Holster, Savanne ; Hooiveld, Guido J. ; Repsilber, Dirk ; Vos, Willem M. de; Brummer, Robert J. ; König, Julia - \ 2019
    Biomolecules 9 (2019)10. - ISSN 2218-273X
    faecal microbiota transplantation - gene expression - host-microbe interaction - irritable bowel syndrome - microbiota

    Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.

    Sugar Beet Pectin Supplementation Did Not Alter Profiles of Fecal Microbiota and Exhaled Breath in Healthy Young Adults and Healthy Elderly
    An, Ran ; Wilms, Ellen ; Smolinska, Agnieszka ; Hermes, Gerben D.A. ; Masclee, Ad A.M. ; Vos, Paul de; Schols, Henk A. ; Schooten, Frederik J. van; Smidt, Hauke ; Jonkers, Daisy M.A.E. ; Zoetendal, Erwin G. ; Troost, Freddy J. - \ 2019
    Nutrients 11 (2019)9. - ISSN 2072-6643
    aging - dietary fiber - elderly - exhaled air - microbiota - pectin - young adults

    Aging is accompanied with increased frailty and comorbidities, which is potentially associated with microbiome perturbations. Dietary fibers could contribute to healthy aging by beneficially impacting gut microbiota and metabolite profiles. We aimed to compare young adults with elderly and investigate the effect of pectin supplementation on fecal microbiota composition, short chain fatty acids (SCFAs), and exhaled volatile organic compounds (VOCs) while using a randomized, double-blind, placebo-controlled parallel design. Fifty-two young adults and 48 elderly consumed 15 g/day sugar beet pectin or maltodextrin for four weeks. Fecal and exhaled breath samples were collected before and after the intervention period. Fecal samples were used for microbiota profiling by 16S rRNA gene amplicon sequencing, and for analysis of SCFAs by gas chromatography (GC). Breath was used for VOC analysis by GC-tof-MS. Young adults and elderly showed similar fecal SCFA and exhaled VOC profiles. Additionally, fecal microbiota profiles were similar, with five genera significantly different in relative abundance. Pectin supplementation did not significantly alter fecal microbiota, SCFA or exhaled VOC profiles in elderly or young adults. In conclusion, aside from some minor differences in microbial composition, healthy elderly and young adults showed comparable fecal microbiota composition and activity, which were not altered by pectin supplementation.

    Microbial communities in a dynamic in vitro model for the human ileum resemble the human ileal microbiota
    Stolaki, Maria ; Minekus, Mans ; Venema, Koen ; Lahti, Leo ; Smid, Eddy J. ; Kleerebezem, Michiel ; Zoetendal, Erwin G. - \ 2019
    FEMS microbiology ecology 95 (2019)8. - ISSN 0168-6496
    in vitro model - gut health - ileum - microbial diversity - microbiota - short chain fatty acids

    The important role for the human small intestinal microbiota in health and disease has been widely acknowledged. However, the difficulties encountered in accessing the small intestine in a non-invasive way in healthy subjects have limited the possibilities to study its microbiota. In this study, a dynamic in vitro model that simulates the human ileum was developed, including its microbiota. Ileostomy effluent and fecal inocula were employed to cultivate microbial communities within the in vitro model. Microbial stability was repetitively achieved after 10 days of model operation with bacterial concentrations reaching on average 107 to 108 16S rRNA copy numbers/ml. High diversities similar to those observed in in vivo ileum samples were achieved at steady state using both fecal and ileostomy effluent inocula. Functional stability based on Short Chain Fatty Acid concentrations was reached after 10 days of operation using fecal inocula, but was not reached with ileostomy effluent as inoculum. Principal Components and cluster analysis of the phylogenetic profiles revealed that in vitro samples at steady state clustered closest to two samples obtained from the terminal ileum of healthy individuals, independent of the inoculum used, demonstrating that the in vitro microbiota at steady state resembles that of the human ileum.

    Anaerobic Degradation of N-ϵ-Carboxymethyllysine, a Major Glycation End-Product, by Human Intestinal Bacteria
    Bui, Thi Phuong Nam ; Troise, Antonio Dario ; Fogliano, Vincenzo ; Vos, Willem M. De - \ 2019
    Journal of Agricultural and Food Chemistry 67 (2019)23. - ISSN 0021-8561 - p. 6594 - 6602.
    dietary advanced glycation end-products - intestinal metabolism - Maillard reaction - microbiota - N-ϵ-carboxymethyllysine

    Modifications of lysine contribute to the amount of dietary advanced glycation end-products reaching the colon. However, little is known about the ability of intestinal bacteria to metabolize dietary N-ϵ-carboxymethyllysine (CML). Successive transfers of fecal microbiota in growth media containing CML were used to identify and isolate species able to metabolize CML under anaerobic conditions. From our study, only donors exposed to processed foods degraded CML, and anaerobic bacteria enrichments from two of them used 77 and 100% of CML. Oscillibacter and Cloacibacillus evryensis increased in the two donors after the second transfer, highlighting that the bacteria from these taxa could be candidates for anaerobic CML degradation. A tentative identification of CML metabolites produced by a pure culture of Cloacibacillus evryensis was performed by mass spectrometry: carboxymethylated biogenic amines and carboxylic acids were identified as CML degradation products. The study confirmed the ability of intestinal bacteria to metabolize CML under anoxic conditions.

    Corrigendum: Sialyllactose and Galactooligosaccharides Promote Epithelial Barrier Functioning and Distinctly Modulate Microbiota Composition and Short Chain Fatty Acid Production In Vitro
    Perdijk, Olaf ; Baarlen, Peter van; Fernandez-Gutierrez, Marcela M. ; Brink, Erik van den; Schuren, Frank H.J. ; Brugman, Sylvia ; Savelkoul, Huub F.J. ; Kleerebezem, Michiel ; Neerven, R.J.J. van - \ 2019
    Frontiers in Immunology 10 (2019). - ISSN 1664-3224 - 1 p.
    epithelium - galactooligosaccharides - microbiota - short chain fatty acids - sialyllactose

    [This corrects the article DOI: 10.3389/fimmu.2019.00094.].

    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.

    Polyphenols and Tryptophan Metabolites Activate the Aryl Hydrocarbon Receptor in an in vitro Model of Colonic Fermentation
    Koper, Jonna E.B. ; Loonen, Linda M.P. ; Wells, Jerry M. ; Troise, Antonio Dario ; Capuano, Edoardo ; Fogliano, Vincenzo - \ 2019
    Molecular Nutrition & Food Research 63 (2019)3. - ISSN 1613-4125
    aryl hydrocarbon receptor - luteolin - microbiota - SHIME - tryptophan

    Scope: Many dietary phytochemicals have been reported to promote gut health. Specific dietary phytochemicals, such as luteolin, as well as specific microbial metabolites of tryptophan are ligands of the aryl hydrocarbon receptor (AhR), which plays a role in immunity and homeostasis of the gut barrier. Here, the fate of luteolin during colonic fermentation and the contribution of tryptophan metabolites to AhR activity in different parts of the colon are investigated. Methods and results: Several polyphenols are screened for AhR activation and oregano, containing the ligand luteolin, is added to batch cultures of human microbiota from the distal colon. Luteolin is rapidly metabolized, with no measurable increase in AhR activity. In the second experiment, using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME), not all luteolin is metabolized in the ascending colon, but disappear rapidly in the transverse colon. The greatest AhR activity is due to microbiota-derived metabolites of tryptophan, particularly in the descending colon. Conclusions: Luteolin in food is rapidly metabolized in the transverse colon. Tryptophan metabolism by the microbiota in the colon contributes substantially to the pool of lumen metabolites that can activate the AhR.

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