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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    Effect of wheat bran derived prebiotic supplementation on gastrointestinal transit, gut microbiota, and metabolic health: a randomized controlled trial in healthy adults with a slow gut transit
    Müller, Mattea ; Hermes, Gerben D.A. ; Canfora, Emanuel E. ; Holst, Jens J. ; Zoetendal, Erwin G. ; Smidt, Hauke ; Troost, Freddy ; Schaap, Frank G. ; Damink, Steven Olde ; Jocken, Johan W.E. ; Lenaerts, Kaatje ; Masclee, Ad A.M. ; Blaak, Ellen E. - \ 2020
    Gut Microbes 12 (2020)1. - ISSN 1949-0976
    Arabinoxylan-Oligosaccharides - Energy metabolism - Gastrointestinal transit - Gut Hormones - Gut microbiota - Prebiotic - Stool consistency

    Acute intake of the wheat bran extract Arabinoxylan-Oligosaccharide (AXOS) modulates the gut microbiota, improves stool characteristics and postprandial glycemia in healthy humans. Yet, little is known on how long-term AXOS intake influences gastrointestinal (GI) functioning, gut microbiota, and metabolic health. In this randomized, placebo-controlled, double-blind study, we evaluated the effects of AXOS intake on GI function and metabolic health in adults with slow GI transit without constipation. Forty-eight normoglycemic adults were included with whole-gut transit time (WGTT) of >35 h receiving either 15 g/day AXOS or placebo (maltodextrin) for 12-wks. The primary outcome was WGTT, and secondary outcomes included stool parameters, gut permeability, short-chain fatty acids (SCFA), microbiota composition, energy expenditure, substrate oxidation, glucose, insulin, lipids, gut hormones, and adipose tissue (AT) function. WGTT was unchanged, but stool consistency softened after AXOS. 12-wks of AXOS intake significantly changed the microbiota by increasing Bifidobacterium and decreasing microbial alpha-diversity. With a good classification accuracy, overall microbiota composition classified responders with decreased WGTT after AXOS. The incretin hormone Glucagon-like protein 1 was reduced after AXOS compared to placebo. Energy expenditure, plasma metabolites, AT parameters, SCFA, and gut permeability were unchanged. In conclusion, intake of wheat bran extract increases fecal Bifidobacterium and softens stool consistency without major effects on energy metabolism in healthy humans with a slow GI transit. We show that overall gut microbiota classified responders with decreased WGTT after AXOS highlighting that GI transit and change thereof were associated with gut microbiota independent of Bifidobacterium. NCT02491125.

    Distal colonic transit is linked to gut microbiota diversity and microbial fermentation in humans with slow colonic transit
    Müller, Mattea ; Hermes, Gerben D.A. ; Canfora, Emanuel E. ; Smidt, Hauke ; Masclee, Ad A.M. ; Zoetendal, Erwin G. ; Blaak, Ellen E. - \ 2020
    American Journal of Physiology. Gastrointestinal and Liver Physiology 318 (2020)2. - ISSN 0193-1857 - p. G361 - G369.
    gastrointestinal transit - gut microbiota - short-chain fatty acids - stool consistency

    Longer colonic transit time and hard stools are associated with increased gut microbiota diversity. Here, we investigate to what extent quantitative measures of (segmental) colonic transit time were related to gut microbiota composition, microbial metabolites, and gut-related parameters in a human cross-sectional study. Using radiopaque markers, (segmental) colonic transit time (CTT) was measured in 48 lean/overweight participants with long colonic transit but without constipation. Fecal microbiota composition was determined using 16S rRNA gene amplicon sequencing. Associations between gastrointestinal transit (segmental CTT and stool frequency and consistency), microbiota diversity and composition, microbial metabolites [short-chain fatty acids (SCFA), branched-chain fatty acids, and breath hydrogen], habitual diet, and gut-related host parameters [lipopolysaccharide-binding protein (LBP) and fecal calprotectin] were investigated using univariate and multivariate approaches. Long descending (i.e., distal) colonic transit was associated with increased microbial α-diversity but not with stool consistency. Using unweighted and weighted UniFrac distance, microbiota variation was not related to (segmental) CTT but to demographics, diet, plasma LBP, and fecal calprotectin. Bray-Curtis dissimilarity related only to stool consistency. Rectosigmoid and descending colonic transit were negatively associated with fecal SCFA and plasma acetate, respectively. This study suggests that the distal colon transit may affect not only microbiota diversity but also microbial metabolism.NEW & NOTEWORTHY We extend previous findings showing that long distal colonic transit time influences microbial diversification and fermentation, whereas stool consistency is related to microbiota composition in humans with a long colonic transit. This study puts the importance of the (distal) colonic site in microbiota ecology forward, which should be considered in future therapeutic studies targeting, for instance, short-chain fatty acid production to improve metabolic health.

    Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome
    Weerts, Zsa Zsa R.M. ; Masclee, Ad A.M. ; Witteman, Ben J.M. ; Clemens, Cees H.M. ; Winkens, Bjorn ; Brouwers, Jacobus R.B.J. ; Frijlink, Henderik W. ; Muris, Jean W.M. ; Wit, Niek J. De; Essers, Brigitte A.B. ; Tack, Jan ; Snijkers, Johanna T.W. ; Bours, Andrea M.H. ; Ruiter-van der Ploeg, Annieke S. de; Jonkers, Daisy M.A.E. ; Keszthelyi, Daniel - \ 2020
    Gastroenterology 158 (2020)1. - ISSN 0016-5085 - p. 123 - 136.
    Functional Gastrointestinal Disorder - PERSUADE Study - RCT - Treatment

    Background & Aims: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal–release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. Methods: We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal–release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. Results: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal–release peppermint oil group had a response (46.8%, P =. 170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P =. 385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4%). We did not find differences among the groups in overall relief (9.7%, P =. 317 and 1.6%, P =. 351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P =. 016), discomfort (P =. 020), and IBS severity (P =. 020). Adverse events, although mild, were more common in both peppermint oil groups (P <. 005). Conclusions: In a randomized trial of patients with IBS, we found that neither small-intestinal–release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal–release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS., Number: NCT02716285.

    Arabinoxylan-Oligosaccharide Intake changes the microbiota and softens stool consistency without changes in gut transit and metabolic health in healthy adults
    Müller, Mattea ; Hermes, Gerben ; Canfora, Emanuel E. ; Holst, Jens J. ; Zoetendal, Erwin ; Smidt, Hauke ; Troost, Freddy ; Schaap, Frank G. ; Damink, Steven Olde ; Jocken, Johan W.E. ; Lenaerts, Kaatje ; Masclee, Ad A.M. ; Blaak, Ellen E. - \ 2019
    Wageningen University & Research
    PRJEB32919 - ERP115659 - human gut metagenome
    Prebiotic fibers may alter gastrointestinal (GI) transit time, microbiota composition and short chain fatty acid (SCFA) production, contributing to improved gut functionality and metabolic health. We investigated long-term effects of Arabinoxylan-Oligosaccharide (AXOS), a prebiotic dietary fiber on GI transit time, gut microbiota composition, and metabolic profile in adult participants.Methods: This randomized, placebo-controlled double-blind parallel study included 48 normoglycemic men and women (ages 20-55 y, body mass index (BMI) 19.8-30.5 kg/m2) with a slow whole-gut transit time (>35h) recruited during August 2015 to December 2016 in Maastricht, the Netherlands. Participants were randomly allocated to 12 weeks 15g/day AXOS or placebo (maltodextrin) intake. GI transit time, stool parameters, gut permeability, SCFA and microbiota composition were assessed before and after. Energy expenditure, substrate oxidation, glucose, insulin, lipids and incretin hormones were measured during a breakfast meal test before and after.Results: AXOS significantly changed the microbiota (p=0.05) mainly by increasing Bifidobacterium and decreased microbial alpha-diversity (P<.001) as compared to placebo. Whole-gut and upper intestinal transit were not affected, but stool consistency softened after AXOS (Bristol stool chart score 2.7 ± 0.19 to 3.3 ± 0.19, P<.01). Postprandial fat oxidation tended to increase (iAUC, P=.073) and early GLP-1 response (AUC0-90min, P=.005) was reduced after AXOS. Energy expenditure, plasma metabolites, SCFA concentrations and gut permeability were unchanged. Microbiota could classify responders in improved whole-gut transit after AXOS with an ([ROC] AUC 0.80%).Conclusion: AXOS intake, changed the microbiota, mainly increased fecal Bifidobacterium, tended to increase postprandial fat oxidation and decreased the early GLP-1 response. Whilst we did not observe changes in whole-gut transit time, overall microbiota could accurately classify responders with improved GI transit after AXOS intake.
    The impact of pectin supplementation on intestinal barrier function in healthy young adults and healthy elderly
    Wilms, Ellen ; Jonkers, Daisy M.A.E. ; Savelkoul, Huub F.J. ; Elizalde, Montserrat ; Tischmann, Lea ; Vos, Paul de; Masclee, Ad A.M. ; Troost, Freddy J. - \ 2019
    Nutrients 11 (2019)7. - ISSN 2072-6643
    Aging - Defense - Dietary fiber - Gastrointestinal - Intestinal permeability - Tight junctions - Tolerance

    Intestinal barrier function is suggested to decrease with aging and may be improved by pectin intake. The aim of this study was to investigate the e ects of four weeks pectin supplementation on gastrointestinal barrier function in vivo and ex vivo in di erent age groups. In a randomized, double-blind, placebo-controlled, parallel study, 52 healthy young adults (18–40 years) and 48 healthy elderly (65–75 years) received 15 g/day pectin or placebo for four weeks. Pre- and post-intervention, in vivo gastrointestinal permeability by a multisugar test, and defense capacity in mucosal samples were assessed. Sigmoid biopsies were collected post-intervention from subgroups for Ussing chamber experiments and gene transcription of barrier-related genes. Pectin intervention did not a ect in vivo gastroduodenal, small intestinal, colonic, and whole gut permeability in young adults nor in elderly (p ≥ 0.130). Salivary and fecal sIgA and serum IgA were not significantly di erent between pectin versus placebo in both age groups (p ≥ 0.128). In both young adults and elderly, no di erences in transepithelial electrical resistance and fluorescein flux (p ≥ 0.164) and relative expression of genes analyzed (p ≥ 0.222) were found between pectin versus placebo. In conclusion, intestinal barrier function was not a ected by four weeks pectin supplementation neither in healthy young adults nor in healthy elderly.

    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.

    Encapsulation of lipids as emulsion-alginate beads reduces food intake : a randomized placebo-controlled cross-over human trial in overweight adults
    Corstens, Meinou N. ; Troost, Freddy J. ; Alleleyn, Annick M.E. ; Klaassen, Tim ; Berton-Carabin, Claire C. ; Schroën, Karin ; Masclee, Ad A.M. - \ 2019
    Nutrition Research 63 (2019). - ISSN 0271-5317 - p. 86 - 94.
    Appetite - Encapsulated lipid - Human trial - Ileal brake - Weight management

    The objective of this study was to investigate the efficacy of lipid emulsions encapsulated in calcium-alginate beads in reducing food intake and appetite sensations. These emulsion-alginate beads were ingested in a yogurt (active) and compared to an equienergetic yogurt containing nonencapsulated nutrients with comparable sensory properties (control) in a randomized placebo-controlled trial with crossover design. Thirty-three healthy overweight volunteers (mean age: 43 years; body mass index: 27.7 kg/m2; 14 male) received the 2 treatments. Test days started with a standardized small breakfast (t = 0) followed by an active or control yogurt (t = 90 minutes). Appetite sensations and gastrointestinal symptoms were monitored prior to and after consumption of the yogurt, and food intake was measured during ad libitum pasta meal consumption (t = 210 minutes). The hypothesis for this study was that delayed release of encapsulated lipids suppresses appetite sensations and reduces food intake. Food intake was significantly reduced with 51 ± 20 kcal (213 ± 84 kJ) (P =.016) after intake of the active yogurt (770 ± 38 kcal (3222 ± 159 kJ)) compared to the control (821 ± 40 kcal (3435 ± 167 kJ)). The approach that we chose is promising to reduce food intake and could contribute to the development of an easy-to-use product for weight management.

    The effect of an encapsulated nutrient mixture on food intake and satiety : A double-blind randomized cross-over proof of concept study
    Alleleyn, Annick M.E. ; Avesaat, Mark van; Ripken, Dina ; Bleiel, Sinéad B. ; Keszthelyi, Daniel ; Wilms, Ellen ; Troost, Freddy J. ; Hendriks, Henk F.J. ; Masclee, Adrian A.M. - \ 2018
    Nutrients 10 (2018)11. - ISSN 2072-6643
    Carbohydrate - Distal release - Encapsulated nutrient mixture - Overweight - Protein - Satiety - Weight management

    Activation of the intestinal brake by infusing nutrients into the distal small intestine with catheters inhibits food intake and enhances satiety. Encapsulation of macronutrients, which protects against digestion in the proximal gastrointestinal tract, can be a non-invasive alternative to activate this brake. In this study, we investigate the effect of oral ingestion of an encapsulated casein and sucrose mixture (active) targeting the distal small intestine versus a control product designed to be released in the stomach on food intake, satiety, and plasma glucose concentrations. Fifty-nine volunteers received the active and control product on two separate test days. Food intake was determined during an ad libitum meal 90 min after ingestion of the test product. Visual analogue scale scores for satiety and blood samples for glucose analysis were collected at regular intervals. Ingestion of the active product decreased food intake compared to the control product (655 kcal compared with 699 kcal, respectively, p < 0.05). The area under the curve (AUC) for hunger was decreased (p < 0.05) and AUC for satiety was increased (p < 0.01) after ingestion of the active product compared to the control product. Ingestion of an encapsulated protein-carbohydrate mixture resulted in inhibition of food intake compared to a non-encapsulated control product.

    OP002 Assessment of disease activity patterns during the first 10 years after diagnosis in a population-based Crohn’s disease cohort shows a quiescent disease course for a substantial proportion of the population
    Wintjens, D. ; Bergey, F. ; Saccenti, E. ; Jeuring, S. ; Romberg-Camps, M. ; Oostenbrug, L. ; Masclee, A. ; Jonkers, D. ; Martins Dos Santos, V. ; Pierik, M. - \ 2018
    Journal of Crohn's and Colitis 12 (2018)supplement 1. - ISSN 1873-9946 - p. S001 - S003.
    Background Representative studies concerning the long-term prognosis and disease course in Crohn’s disease (CD) primarily describe steroid exposure, need for surgery or hospitalisations, and disease progression as characteristics of an unfavourable outcome. Real-life data on long-term disease activity are lacking. We aimed to define clusters with different disease activity patterns in the population-based IBDSL cohort. Methods All CD patients from the IBDSL cohort with at least 10 years follow-up (>18 years, diagnosed between 1991 and 2004) were included. Data on demographics, disease phenotype, medication use, hospitalisations, and surgery were available. In addition, all endoscopy and imaging reports were scrutinised. Since diagnosis, active disease was defined for each yearly quarter by (i) active disease on endoscopy or imaging, (ii) hospitalisation, (iii) surgery, or (iv) treatment adjustment for increased symptoms. Subsequently, formula-based clusters were generated based on four previously published questionnaire-based disease activity patterns,1 completed with two additional clusters (Figure 1). Prediction models were created using discriminant analysis with PLS regression based on characteristics at baseline and 6 months after diagnosis. Results In total, 432 patients were included. During 10 years follow-up after diagnosis, patients experienced 4.2 (SD 3.8) quarters of active disease on average. The distribution of patients over different clusters is shown in Figure 1. Notably, 128 patients (29.6%) were classified as quiescent and, of these, 89.8% never received immunomodulators or biologics. Ileocolonic disease location (OR 0.45; 95% CI 0.21–0.91) and smoking at diagnosis (OR 0.44; 95% CI 0.26–0.70) were negatively associated with a quiescent disease course, while surgery at diagnosis (OR 3.02; 95% CI 1.39–6.64) was positively associated. Our best prediction model for a quiescent course had an area under the ROC curve of 0.72 (p < 0.001) at baseline and 0.75 (p < 0.001) at 6 months after diagnosis.
    Age-dependent changes in GI physiology and microbiota : Time to reconsider?
    An, Ran ; Wilms, Ellen ; Masclee, Ad A.M. ; Smidt, Hauke ; Zoetendal, Erwin G. ; Jonkers, Daisy - \ 2018
    Gut 67 (2018)12. - ISSN 0017-5749 - p. 2213 - 2222.
    ageing - gastrointestinal physiology - intestinal bacteria

    Our life expectancy is increasing, leading to a rise in the ageing population. Ageing is associated with a decline in physiological function and adaptive capacity. Altered GI physiology can affect the amount and types of nutrients digested and absorbed as well as impact the intestinal microbiota. The intestinal microbiota is considered a key player in our health, and a variety of studies have reported that microbiota composition is changing during ageing. Since ageing is associated with a decline in GI function and adaptive capacity, it is crucial to obtain insights into this decline and how this is related to the intestinal microbiota in the elderly. Hence, in this review we focus on age-related changes in GI physiology and function, changes of the intestinal microbiota with ageing and frailty, how these are associated and how intestinal microbiota-targeted interventions may counteract these changes.

    Encapsulation of lipids to delay lipolysis and reduce food intake
    Corstens, Meinou N. - \ 2018
    Wageningen University. Promotor(en): C.G.P.H. Schroën; A.A.M. Masclee, co-promotor(en): C.C. Berton-Carabin; F.J. Troost. - Wageningen : Wageningen University - ISBN 9789463432382 - 200
    cum laude

    My PhD project aimed at developing an edible product for non-invasive weight management, and targeted a natural feedback mechanism to induce satiety: the ileal brake. In order to trigger the ileal brake mechanism, lipids and their non-absorbed metabolites need to be sensed in the ileum. We aimed at inducing this mechanism through targeted release of lipids after oral intake, for which we developed multi-layered emulsions and emulsion-alginate beads. We showed that emulsion-alginate beads control in vitro lipolysis as a function of bead size and alginate concentration, and confirmed these findings under dynamic in vitro gastrointestinal conditions (DIDGI). Moreover, ingestion of yoghurt with emulsion-alginate beads significantly reduced food intake by 6% in overweight volunteers compared to a control group, suggesting that activation of the ileal brake was achieved. These findings have important implications for the development of weight management strategies, and understanding satiety in general.

    Small intestinal protein infusion in humans: Evidence for a location-specific gradient in intestinal feedback on food intake and GI peptide release
    Avesaat, M. Van; Ripken, D. ; Hendriks, H.F.J. ; Masclee, A.A.M. ; Troost, F.J. - \ 2017
    International Journal of Obesity 41 (2017)2. - ISSN 0307-0565 - p. 217 - 224.

    BACKGROUND:Protein infusion in the small intestine results in intestinal brake activation: a negative feedback mechanism that may be mediated by the release of gastrointestinal peptides resulting in a reduction in food intake. It has been proposed that duodenum, jejunum and ileum may respond differently to infused proteins.OBJECTIVE:To investigate differences in ad libitum food intake, feelings of hunger and satiety and the systemic levels of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), glucose and insulin after intraduodenal, intrajejunal and intraileal protein infusion.METHODS:Fourteen subjects (four male, mean age: 23±2.1 years, mean body mass index: 21.6±1.8 kg m -2) were intubated with a naso-ileal catheter in this double-blind, randomized, placebo-controlled crossover study. Test days (four in total, executed on consecutive days) started with the ingestion of a standardized breakfast, followed by the infusion of 15 g of protein in the duodenum, jejunum or ileum over a period of 60 min. Food intake was measured by offering an ad libitum meal and Visual Analogue Scale (VAS) scores were used to assess feelings of hunger and satiety. Blood samples were drawn at regular intervals for CCK, GLP-1, PYY, glucose and insulin analyses.RESULTS:Intraileal protein infusion decreased ad libitum food intake compared with both intraduodenal and placebo infusion (ileum: 628.5±63 kcal vs duodenum: 733.6±50 kcal, P<0.01 and placebo: 712.2±53 kcal, P<0.05). GLP-1 concentrations were increased after ileal infusion compared with jejunal and placebo infusion, whereas CCK concentrations were only increased after intraileal protein infusion compared with placebo. None of the treatments affected VAS scores for hunger and satiety nor plasma concentrations of PYY and glucose.CONCLUSIONS:Protein infusion into the ileum decreases food intake during the next meal compared with intraduodenal infusion, whereas it increases systemic levels of GLP-1 compared with protein infusion into the jejunum and placebo respectively.

    Lactobacillus plantarum strains can enhance human mucosal and systemic immunity and prevent non-steroidal anti-inflammatory drug induced reduction in T regulatory Cells
    Vos, Paul de; Mujagic, Zlatan ; Haan, Bart J. de; Siezen, Roland J. ; Bron, Peter A. ; Meijerink, Marjolein ; Wells, Jerry M. ; Masclee, Ad A.M. ; Boekschoten, Mark V. ; Faas, Marijke M. ; Troost, Freddy J. - \ 2017
    Frontiers in Immunology 8 (2017). - ISSN 1664-3224 - 18 p.
    Adaptive immunity - Indomethacin - Intestinal mucosal immunity - Lactobacillus plantarum - Non-steroidal anti-inflammatory drug - Probiotics

    Orally ingested bacteria interact with intestinal mucosa and may impact immunity. However, insights in mechanisms involved are limited. In this randomized placebo-controlled cross-over trial, healthy human subjects were given Lactobacillus plantarum supplementation (strain TIFN101, CIP104448, or WCFS1) or placebo for 7 days. To determine whether L. plantarum can enhance immune response, we compared the effects of three stains on systemic and gut mucosal immunity, by among others assessing memory responses against tetanus toxoid (TT)-antigen, and mucosal gene transcription, in human volunteers during induction of mild immune stressor in the intestine, by giving a commonly used enteropathic drug, indomethacin [non-steroidal anti-inflammatory drug (NSAID)]. Systemic effects of the interventions were studies in peripheral blood samples. NSAID was found to induce a reduction in serum CD4+ /Foxp3 regulatory cells, which was prevented by L. plantarum TIFN101. T-cell polarization experiments showed L. plantarum TIFN101 to enhance responses against TT-antigen, which indicates stimulation of memory responses by this strain. Cell extracts of the specific L. plantarum strains provoked responses after WCFS1 and TIFN101 consumption, indicating stimulation of immune responses against the specific bacteria. Mucosal immunomodulatory effects were studied in duodenal biopsies. In small intestinal mucosa, TIFN101 upregulated genes associated with maintenance of T- and B-cell function and antigen presentation. Furthermore, L. plantarum TIFN101 and WCFS1 downregulated immunological pathways involved in antigen presentation and shared downregulation of snoRNAs, which may suggest cellular destabilization, but may also be an indicator of tissue repair. Full sequencing of the L. plantarum strains revealed possible gene clusters that mightbe responsible for the differential biological effects of the bacteria on host immunity. In conclusion, the impact of oral consumption L. plantarum on host immunity is strain dependent and involves responses against bacterial cell components. Some strains may enhance specific responses against pathogens by enhancing antigen presentation and leukocyte maintenance in mucosa. In future studies and clinical settings, caution should be taken in selecting beneficial bacteria as closely related strains can have different effects. Our data show that specific bacterial strains can prevent immune stress induced by commonly consumed painkillers such as NSAID and can have enhancing beneficial effects on immunity of consumers by stimulating antigen presentation and memory responses.

    Habitual diet and diet quality in Irritable Bowel Syndrome: A case-control study
    Tigchelaar, Ettje F. ; Mujagic, Zlatan ; Zhernakova, Alexandra ; Hesselink, M. ; Meijboom, S. ; Perenboom, C.W.M. ; Masclee, A.A.M. ; Wijmenga, Cisca ; Feskens, E.J.M. ; Jonkers, D. - \ 2017
    Neurogastroenterology & Motility 29 (2017)12. - ISSN 1365-2982
    Background Diet is considered to be a key factor in symptom generation in Irritable Bowel Syndrome (IBS) and patients tend to exclude food products from their diet in pursue of symptom relief, which may impair diet quality. Methods We evaluated habitual dietary intake in IBS patients with regard to nutrients and food products using an extensive food frequency questionnaire. One hundred ninety-four IBS patients were compared to 186 healthy controls using multiple logistic regression analysis. An overall diet quality score was calculated for each participant based on the criteria of the Dutch Healthy Diet (DHD) index. Key Results A lower DHD-score was found for IBS (mean [SD]: 52.9 [9.6]) vs controls (55.1 [9.2], P=.02). The diet of patients was lower in fibers (21 g vs 25 g per day, P=.002) and fructose (14 g vs 16 g, P=.033), while higher in total fat (37% vs 36% of total energy intake, P=.010) and added sugars (46 g vs 44 g, P=.029). Differences in daily intake of food products included lower consumption of apples (40 g vs 69 g, P<.001), pasta (28 vs 37 g, P=.029) and alcoholic beverages (130 g vs 193 g, P=.024) and higher consumption of processed meat (38 g vs 29 g, P<.001). Some of these findings correlated with gastrointestinal symptoms, showing differences between IBS subtypes. Conclusions and Inferences Differences in habitual diet were described, showing lower diet quality in IBS patients compared to controls, with increased consumption of fat and lower intake of fibers and fructose. Our data support the importance of personalized and professional nutritional guidance of IBS patients.
    The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; a randomized double-blind placebo controlled trial
    Mujagic, Zlatan ; Vos, Paul de; Boekschoten, Mark ; Govers, Coen ; Pieters, Harm J.H.M. ; Wit, Nicole de; Bron, Peter A. ; Masclee, Ad A.M. ; Troost, Freddy J. - \ 2017
    Wageningen University
    Homo sapiens - GSE74988 - Homo sapiens - GSE74988 - PRJNA302145
    The aim of this study was to investigate the effects of three Lactobacillus plantarum strains on in-vivo small intestinal barrier function and gene transcription in human subjects. The strains were selected for their differential effects on TLR signalling and tight junction protein rearrangement, which may lead to beneficial effects in a stressed human gut mucosa. Ten healthy volunteers participated in four different intervention periods: 7-day oral intake of either L. plantarum WCFS1, CIP48 (CIP104448), TIFN101 (CIP104450) or placebo, proceeded by a 4 weeks wash-out period. Lactulose-rhamnose ratio (an indicator of small intestinal permeability) increased after intake of indomethacin, which was given as an artificial stressor of the gut mucosal barrier (mean ratio 0.06±0.04 to 0.10±0.06, p=0.001), but was not significantly affected by the bacterial interventions. However, gene transcription pathway analysis in small intestinal biopsies, obtained by gastroduodenoscopy, demonstrated that particularly L. plantarum TIFN101 modulated cell-cell adhesion with high turnover of genes involved in tight- and adhesion junction protein synthesis and degradation (e.g. actinin alpha-4, metalloproteinase-2). These effects were less pronounced for L. plantarum WCFS1 and CIP104448. In conclusion, L. plantarum TIFN101 induced the most pronounced probiotic properties with specific effects on repair processes in the compromised intestine of healthy subjects.
    Emulsion-alginate beads designed to control in vitro intestinal lipolysis : Towards appetite control
    Corstens, Meinou N. ; Berton-Carabin, Claire C. ; Elichiry-Ortiz, Peio T. ; Hol, Karlijn ; Troost, Freddy J. ; Masclee, Ad A.M. ; Schroën, Karin - \ 2017
    Journal of Functional Foods 34 (2017). - ISSN 1756-4646 - p. 319 - 328.
    Calcium-alginate bead - Emulsion gel - Emulsion-filled hydrogel - Food - In vitro lipolysis - Satiety
    Dietary lipids and digestion products are strong inducers of satiety signals in the distal small intestine. To protect lipids against proximal absorption we encapsulate them in hydrogel beads. Physically stable beads of different sizes (0.55, 0.78 and 1.15 mm), and mesh sizes (ξ = 9.2, 6.4 and 5.4 nm) were obtained using ionotropic (Ca) gelation of alginate containing oil-in-water (O/W) emulsions (d32 ∼ 21 μm). All beads shrunk at pH 2.0, and had excellent gastric stability (2 h, pepsin, pH 3.0), while they swelled at pH 7.0, and softened under simulated intestinal conditions (2.5 h, pancreatin, bile, pH 7.0). Lipolysis could be controlled through variation of bead and mesh size, resulting in a broad range of release profiles: from 1–50% release after 1 h to 20–80% after 2.5 h. Such systems with controllable and predictable in vitro release profiles are a promising step towards ileal lipid release, where they could play a pivotal role in appetite control.
    The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; A randomized double-blind placebo controlled trial
    Mujagic, Zlatan ; Vos, Paul De; Boekschoten, Mark V. ; Govers, Coen ; Pieters, Harm J.H.M. ; Wit, Nicole J.W. De; Bron, Peter A. ; Masclee, Ad A.M. ; Troost, Freddy J. - \ 2017
    Scientific Reports 7 (2017). - ISSN 2045-2322
    The aim of this study was to investigate the effects of three Lactobacillus plantarum strains on in-vivo small intestinal barrier function and gut mucosal gene transcription in human subjects. The strains were selected for their differential effects on TLR signalling and tight junction protein rearrangement, which may lead to beneficial effects in a stressed human gut mucosa. Ten healthy volunteers participated in four different intervention periods: 7-day oral intake of either L. plantarum WCFS1, CIP104448, TIFN101 or placebo, proceeded by a 4 weeks wash-out period. Lactulose-rhamnose ratio (an indicator of small intestinal permeability) increased after intake of indomethacin, which was given as an artificial stressor of the gut mucosal barrier (mean ratio 0.06 ± 0.04 to 0.10 ± 0.06, p = 0.001), but was not significantly affected by the bacterial interventions. However, analysis in small intestinal biopsies, obtained by gastroduodenoscopy, demonstrated that particularly L. plantarum TIFN101 modulated gene transcription pathways related to cell-cell adhesion with high turnover of genes involved in tight- and adhesion junction protein synthesis and degradation (e.g. actinin alpha-4, metalloproteinase-2). These effects were less pronounced for L. plantarum WCFS1 and CIP104448. In conclusion, L. plantarum TIFN101 induced the most pronounced probiotic properties with specific gene transcriptional effects on repair processes in the compromised intestine of healthy subjects.
    Food-grade Micro-encapsulation Systems that May Induce Satiety via Delayed Lipolysis: A Review
    Corstens, M.N. ; Berton-Carabin, C.C. ; Vries, R.J. de; Troost, F.J. ; Masclee, A.A.M. ; Schroen, C.G.P.H. - \ 2017
    Critical Reviews in Food Science and Nutrition 57 (2017)10. - ISSN 1040-8398 - p. 2218 - 2244.
    In vitro digestion - Ileal brake - emulsion - Food - obesity
    The increasing prevalence of overweight and obesity requires new, effective prevention and treatment strategies. One approach to reduce energy intake is by developing novel foods with increased satiating properties, which may be accomplished by slowing down lipolysis to deliver substrates to the ileum, thereby enhancing natural gut-brain signalling pathways of satiety that are normally induced by meal intake. To develop slow release food additives, their processing in the gastrointestinal tract has to be understood; therefore, we start from a general description of the digestive system and relate that to in vitro modelling, satiety and lipolytic mechanisms. The effects of physicochemical lipid composition, encapsulation matrix and interfacial structure on lipolysis are emphasized. We give an overview of techniques and materials used, and discuss partitioning, which may be a key factor for encapsulation performance. Targeted release capsules that delay lipolysis form a real challenge because of the high efficiency of the digestive system; hardly any proof was found that intact orally ingested lipids can be released in the ileum and thereby induce satiety. We expect that this challenge could be tackled with structured o/w-emulsion-based systems that have some protection against lipase, e.g., by hindering bile salt adsorption and/or delaying lipase diffusion.
    Destabilization of multilayered interfaces in digestive conditions limits their ability to prevent lipolysis in emulsions
    Corstens, M.N. ; Berton-Carabin, C.C. ; Kester, Annemarie ; Fokkink, R.G. ; Berlo-van den Broek, J.M. van; Vries, R.J. de; Troost, F.J. ; Masclee, A.A.M. ; Schroen, C.G.P.H. - \ 2017
    Food Structure 12 (2017). - ISSN 2213-3291 - p. 54 - 63.
    Delivery of lipid fractions in the lower small intestine can induce feelings of satiety, but is only possible when lipids escape the highly efficient lipolysis and adsorption in the upper gastrointestinal (GI) tract. Our objective was to gain insight in the stability of multilayered interfaces in simulated GI conditions, and their suitability for intestinal delivery of undigested lipids. Oil-in-water emulsions (d32 ∼ 5–30 μm; one- to five-layered interfaces) were produced by sequentially adsorbing biopolymers with opposite charges at pH 3.0: whey protein isolate (WPI) (cationic), pectin (anionic), chitosan (cationic). Corresponding multilayered structures were characterized using reflectometry. Influence of layer composition and thickness on its protectiveness against lipolysis of emulsions was studied in simulated GI conditions.

    Multilayered WPI/pectin emulsions had an improved physical stability compared to WPI-stabilized emulsions, during both storage and in vitro gastric incubation, whereas chitosan-containing emulsions were physically unstable. Reflectometry and CLSM results showed that a greater number of layers increased the adsorbed amount, forming a mesoscopically heterogeneous structure. Under simulated intestinal conditions, however, outer layers instantaneously destabilized. Accordingly, similar initial lipolysis rates were recorded for all emulsions. Yet, compared to only WPI the final extent of lipolysis was lowered by addition of a second and a third layer under mild in vitro conditions. This moderate protective effect disappeared when harsher digestive conditions were applied.

    From this work, it became clear why multilayered interfaces (initially built under acidic pH) can improve gastric stability of emulsions, but are prone to disintegration under intestinal conditions. This knowledge is important for designing food systems that control release of lipolytic products in targeted locations of the GI tract; the emulsions reported here are expected to be suitable for duodenal release.
    Effect of Endoscopic Gastroplication on the Genome-Wide Transcriptome in the Upper Gastrointestinal Tract
    Wielen, Nikkie van der; Paulus, Givan ; Avesaat, Mark van; Masclee, Ad ; Meijerink, Jocelijn ; Bouvy, Nicole - \ 2017
    Obesity Surgery 27 (2017)3. - ISSN 0960-8923 - p. 740 - 748.
    Adiponectin - Duodenum - Gastric tissue - Gastroplication - Gene expression - HbA1c - Immunity - Inflammation - Transcriptome
    Background: Bariatric surgery is an effective intervention strategy in obesity, resulting in sustained weight loss and a reduction of comorbidities. Gastroplication, using the articulating circular endoscopic stapler, was recently introduced as a transoral bariatric technique. This procedure reduces gastric volume and induced 34.9 % of excess weight loss in the first year (Paulus et al. Gastrointest Endosc. 81(2):312–20, 3). The aim of the present study was to gain insight in the long-term effects and underlying mechanisms of gastroplication by investigating differences in the genome-wide gastric and duodenal transcriptome before and 1 year after intervention. Methods: Ten morbidly obese patients (BMI 39.8 ± 0.9 kg/m2 (mean ± SEM)) underwent gastroplication. Previous to the procedure and after 1 year, blood samples were taken, and mucosal biopsies were collected from the fundus, antrum and duodenum. Gene expression was measured using microarray analysis. Plasma adiponectin, HbA1c, IL-1β, IL-6, IL-7, TNF-α, IFN-γ, MCP-1, IL-8, TGF-1 and CRP levels were determined. Results: Downregulation of inflammatory genes and gene sets was observed in the fundus and duodenum 1 year after surgery. Gene expression of ghrelin and its activating enzyme GOAT were downregulated in the upper gastrointestinal tract. Patients showed a reduction in plasma HbA1c levels (from 6.17 ± 0.51 to 5.32 ± 0.14 %, p = 0.004) and an increase of plasma adiponectin (from 16.87 ± 3.67 to 27.67 ± 5.92 μg/ml, p = 0.002). Conclusions: Individuals undergoing gastroplication displayed a downregulation of inflammatory tone in the stomach and duodenum, which coincided with improved HbA1c and adiponectin levels. The reduction of inflammatory tone in the upper gastrointestinal tract may be a consequence of an improved metabolic health status or alternatively caused by the procedure itself.
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