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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Lactobacillus mucosae DPC 6426 as a bile-modifying and immunomodulatory microbe
Ryan, Paul M. ; Stolte, Ellen H. ; London, Lis E.E. ; Wells, Jerry M. ; Long, Sarah L. ; Joyce, Susan A. ; Gahan, Cormac G.M. ; Fitzgerald, Gerald F. ; Ross, R.P. ; Caplice, Noel M. ; Stanton, Catherine - \ 2019
BMC Microbiology 19 (2019)1. - ISSN 1471-2180
Bile acid - Bile salt hydrolase (BSH) - CVD - Exopolysaccharide - Hypercholesterolaemia

Background: Lactobacillus mucosae DPC 6426 has previously demonstrated potentially cardio-protective properties, in the form of dyslipidaemia and hypercholesterolemia correction in an apolipoprotein-E deficient mouse model. This study aims to characterise the manner in which this microbe may modulate host bile pool composition and immune response, in the context of cardiovascular disease. Lactobacillus mucosae DPC 6426 was assessed for bile salt hydrolase activity and specificity. The microbe was compared against several other enteric strains of the same species, as well as a confirmed bile salt hydrolase-active strain, Lactobacillus reuteri APC 2587. Results: Quantitative bile salt hydrolase assays revealed that enzymatic extracts from Lactobacillus reuteri APC 2587 and Lactobacillus mucosae DPC 6426 demonstrate the greatest activity in vitro. Bile acid profiling of porcine and murine bile following incubation with Lactobacillus mucosae DPC 6426 confirmed a preference for hydrolysis of glyco-conjugated bile acids. In addition, the purified exopolysaccharide and secretome of Lactobacillus mucosae DPC 6426 were investigated for immunomodulatory capabilities using RAW264.7 macrophages. Gene expression data revealed that both fractions stimulated increases in interleukin-6 and interleukin-10 gene transcription in the murine macrophages, while the entire secretome was necessary to increase CD206 transcription. Moreover, the exopolysaccharide elicited a dose-dependent increase in nitric oxide and interleukin-10 production from RAW264.7 macrophages, concurrent with increased tumour necrosis factor-α secretion at all doses. Conclusions: This study indicates that Lactobacillus mucosae DPC 6426 modulates both bile pool composition and immune system tone in a manner which may contribute significantly to the previously identified cardio-protective phenotype.

Prioritising areas for soil conservation measures in small agricultural catchments in Norway, using a connectivity index
Barneveld, R.J. ; Zee, S.E.A.T.M. van der; Greipsland, I. ; Kværnø, S.H. ; Stolte, J. - \ 2019
Geoderma 340 (2019). - ISSN 0016-7061 - p. 325 - 336.

Measures designed to control erosion serve two purposes: on site (reduce soil loss) and off site (reduce sediment delivery to streams and lakes). While these objectives often coincide or at least are complementary, they could result in different priority areas when spatial planning is concerned. Prioritising for soil loss reduction at the field level will single out areas with high erosion risk. When sediment flux at the catchment scale is concerned, sediment pathways need to be identified in ex ante analyses of soil conservation plans. In Norway, different subsidy schemes are in place to reduce the influx of solutes and sediments to the freshwater system. Financial support is given to agronomic measures, the most important of which is reduced autumn tillage where areas with higher erosion risk receive higher subsidies. The objectives of this study are (1) to assess the use of an index of connectivity to estimate specific sediment yields, and (2) to test whether conservation measures taken in critical source areas are more effective than those taken at where erosion risk levels are the highest. Different modelling approaches are combined to assess soil loss at catchment level from sheet and gully erosion and soil losses through the drainage system. A calibration on two parameters gave reasonable results for annual soil loss. This model calibration was then used to quantify the effectiveness of three strategies for spatial prioritisation: according to hydrological connectivity, sheet erosion risk level and estimated specific sediment yield. The latter two strategies resulted in a maximum reduction in total soil loss due to reduced autumn tillage of 10%. Both model performance and the effectiveness of the different prioritisation strategies varied between the study catchments.

Integrated, spatial distributed modelling of surface runoff and soil erosion during winter and spring
Starkloff, Torsten ; Stolte, Jannes ; Hessel, Rudi ; Ritsema, Coen ; Jetten, Victor - \ 2018
Catena 166 (2018). - ISSN 0341-8162 - p. 147 - 157.
Freezing and thawing - LISEM - Modelling - Snowmelt - Soil erosion - UEBGrid
In cold climate regions a significant fraction of annual soil erosion in agricultural land occurs during snowmelt and rain on partially frozen soils. Physically based and spatially distributed soil erosion models have proved to be good tools for understanding the processes occurring at catchment scale during rainfall erosion. However, most existing erosion models do not account for snow in a suitable way. A combination of the UEBGrid snow pack model and the LISEM erosion model was therefore used in this study. The aim was to test and validate this model combination and to assess its utility in relation to quantification and process understanding. Applying this model combination to simulate surface runoff and soil erosion showed that, in principle, it is possible to satisfactorily simulate surface runoff and observed soil erosion patterns during winter. The values for the calibration parameters were similar for the two chosen winter periods when the rainfall and snowmelt episodes occurred. However, the calibration procedure showed that the utility of this combination had several limitations. It is hoped that this study can help to improve existing models and trigger new developments in including snow pack dynamics and soil freezing and thawing in soil erosion models.
Investigating the development of shallow snowpacks on arable land, using comprehensive field observations and spatially distributed snow modelling
Starkloff, Torsten ; Stolte, Jannes ; Hessel, Rudi ; Ritsema, Coen - \ 2018
Hydrology Research 49 (2018)1. - ISSN 1998-9563 - p. 41 - 59.
Catchment scale - Snow dynamic modelling - Snow hydrology - Snow water equivalent - Spatiotemporal variability - UEBGrid
Shallow (<1 m deep) snowpacks on agricultural areas are an important hydrological component in many countries, which determines how much meltwater is potentially available for overland flow, causing soil erosion and flooding at the end of winter. Therefore, it is important to understand the development of shallow snowpacks in a spatially distributed manner. This study combined field observations with spatially distributed snow modelling using the UEBGrid model, for three consecutive winters (2013-2015) in southern Norway. Model performance was evaluated by comparing the spatially distributed snow water equivalent (SWE) measurements over time with the simulated SWE. UEBGrid replicated SWE development at catchment scale with satisfactory accuracy for the three winters. The different calibration approaches which were necessary for winters 2013 and 2015 showed the delicacy of modelling the change in shallow snowpacks. Especially the refreezing of meltwater and prevention of runoff and infiltration of meltwater by frozen soils and ice layers can make simulations of shallow snowpacks challenging.
Dietary protein sources differentially affect microbiota, mTOR activity and transcription of mTOR signaling pathways in the small intestine
Kar, Soumya K. ; Jansman, Alfons J.M. ; Benis, Nirupama ; Ramiro-Garcia, Javier ; Schokker, Dirkjan ; Kruijt, Leo ; Stolte, Ellen H. ; Taverne-Thiele, Johanna J. ; Smits, Mari A. ; Wells, Jerry M. - \ 2017
PLoS ONE 12 (2017)11. - ISSN 1932-6203
Dietary protein sources can have profound effects on host-microbe interactions in the gut that are critically important for immune resilience. However more knowledge is needed to assess the impact of different protein sources on gut and animal health. Thirty-six wildtype male C57BL/6J mice of 35 d age (n = 6/group; mean ± SEM body weight 21.9 ± 0.25 g) were randomly assigned to groups fed for four weeks with semi synthetic diets prepared with one of the following protein sources containing (300 g/kg as fed basis): soybean meal (SBM), casein, partially delactosed whey powder, spray dried plasma protein, wheat gluten meal and yellow meal worm. At the end of the experiment, mice were sacrificed to collect ileal tissue to acquire gene expression data, and mammalian (mechanistic) target of rapamycin (mTOR) activity, ileal digesta to study changes in microbiota and serum to measure cytokines and chemokines. By genome-wide transcriptome analysis, we identified fourteen high level regulatory genes that are strongly affected in SBM-fed mice compared to the other experimental groups. They mostly related to the mTOR pathway. In addition, an increased (P < 0.05) concentration of granulocyte colony-stimulating factor was observed in serum of SBM-fed mice compared to other dietary groups. Moreover, by 16S rRNA sequencing, we observed that SBM-fed mice had higher (P < 0.05) abundances of Bacteroidales family S24-7, compared to the other dietary groups. We showed that measurements of genome-wide expression and microbiota composition in the mouse ileum reveal divergent responses to diets containing different protein sources, in particular for a diet based on SBM.
Winter hydrology and soil erosion processes in an agricultural catchment in Norway
Starkloff, Torsten - \ 2017
Wageningen University. Promotor(en): Coen Ritsema, co-promotor(en): J. Stolte; Rudi Hessel. - Wageningen : Wageningen University - ISBN 9789463432207 - 154
catchment hydrology - erosion - winter - snow - norway - hydrologie van stroomgebieden - erosie - sneeuw - noorwegen

In regions with a Nordic climate, soil erosion rates in winter and early spring can exceed those occurring during other seasons of the year. In this context, this study was initiated to improve our understanding of the interaction between agricultural soils and occurring winter conditions. The main objective was to better understand how hydrological processes in a catchment are influenced by snow, ice, and freeze-thaw cycles of soils, leading to runoff and soil erosion in winter and spring conditions.

For this purpose, detailed spatially and temporally distributed measurements and observations in a small catchment in Norway were executed during three consecutive winter/spring periods. During the winter/spring periods of 2013-2014, 2014-2015 and 2015-2016, soil water content, soil temperature, and snow cover properties were measured. In addition, numerous soil samples were taken to determine the soil hydraulic characteristics of the investigated soils and to quantify the changes in their macropore networks due to freeze-thaw events, using X-ray imaging.

With the collected data and deduced process understanding, it was possible to model and quantify the spatial and temporal development of snow packs. Furthermore, the field observations revealed how the interaction of tillage, state of the soils and snow cover at a certain time can lead to none or extensive surface runoff and soil erosion.

Integrating acquired data, observations and process knowledge facilitated advances in simulating and quantifying surface runoff and soil erosion rates across the catchment under investigation. The models applied and the maps and output derived are crucial elements for presenting current state and problems in the catchment to stakeholders (such as farmers), providing a starting point for discussing ways to prevent and reduce further runoff and erosion. For model calibration and validation, including interpretation of modelling results, good knowledge of the area and availability of detailed data are essential, especially when processes such as freezing-thawing of soils and ice layer and snow-pack dynamics have to be considered also.

In order to reduce runoff and soil erosion during winter and snowmelt conditions in the future, more targeted research is required in order to address the full range of existing knowledge gaps in this field, as identified in this particular study also.

Quantifying the impact of a succession of freezing-thawing cycles on the pore network of a silty clay loam and a loamy sand topsoil using X-ray tomography
Starkloff, Torsten ; Larsbo, Mats ; Stolte, Jannes ; Hessel, Rudi ; Ritsema, Coen - \ 2017
Catena 156 (2017). - ISSN 0341-8162 - p. 365 - 374.
Freezing and thawing - Porosity analysis - Soil macropore structure - X-ray tomography

In the Nordic countries, changes in pore structure during winter can affect e.g. water transport capacity in soils after winter. A reduction in pore space can cause an increase in runoff volume due to snowmelt and rain, resulting in flooding and soil erosion. This study quantified the effect of freezing-thawing cycles (FTCs) on the macropore structure of a silt and a sandy soil. Six consecutive FTCs were applied to intact soil samples, which were scanned after 0, 1, 2, 4 and 6 FTCs with an industrial X-ray scanner. Using state-of-the-art image processing and analysis techniques, changes in soil macropore network characteristics were quantified. The results showed that freezing-thawing affected the looser sandy soil more than the silt with its more cohesive structure. However, in both soils freezing-thawing had a negative effect on properties of macropore networks (e.g. reduction in macroporosity, thickness and specific surface area of macropores). These findings can help improve understanding of how undisturbed soils react to different winter conditions, which can be beneficial in the development of models for predicting flooding and soil erosion.

Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles
Velikova, Nadya ; Mas, Nuria ; Miguel-Romero, Laura ; Polo, Lorena ; Stolte, Ellen ; Zaccaria, Edoardo ; Cao, Rui ; Taverne, Nico ; Murguía, José Ramón ; Martinez-Manez, Ramon ; Marina, Alberto ; Wells, Jerry - \ 2017
Nanomedicine: Nanotechnology, Biology, and Medicine 13 (2017)2. - ISSN 1549-9634 - p. 569 - 581.
Drug delivery - Gram negative - Multi-drug resistance - Nanotechnology - Two-component systems
Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs) into ε-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram negative (Gr−) permeability barrier for the HKAIs. The observed bactericidal activity against Gr− bacteria was shown to be due to the enhanced delivery and internalization of the HKAIs and not an inhibitory or synergistic effect of the NPs. The NPs had no adverse effects on mammalian cell viability or the immune function of macrophages in vitro and showed no signs of toxicity to zebrafish larvae in vivo. These results show that HKAIs are promising antibacterials for both Gr− and Gr + pathogens and that NPs are a safe drug delivery technology that can enhance the selectivity and efficacy of HKAIs against bacteria.
Soil threats in Europe: status, methods, drivers and effects on ecosystem services : deliverable 2.1 RECARE project
Stolte, Jannes ; Tesfai, Mehreteab ; Oygarden, Lilian ; Kvaerno, Sigrun ; Keizer, Jacob ; Verheijen, Frank ; Panagos, Pano ; Ballabio, Cristiana ; Hessel, R. - \ 2016
European Commission DG Joint Research Centre (JRC Technical reports ) - ISBN 9789279540189 - 207 p.
Solutions for ecosystem-level protection of ocean systems under climate change
Queirós, Ana M. ; Huebert, Klaus B. ; Keyl, Friedemann ; Fernandes, Jose A. ; Stolte, Willem ; Maar, Marie ; Kay, Susan ; Jones, Miranda C. ; Hamon, Katell G. ; Hendriksen, Gerrit ; Vermard, Youen ; Marchal, Paul ; Teal, Lorna R. ; Somerfield, Paul J. ; Austen, Melanie C. ; Barange, Manuel ; Sell, Anne F. ; Allen, Icarus ; Peck, Myron A. - \ 2016
Global Change Biology 22 (2016)12. - ISSN 1354-1013 - p. 3927 - 3936.
climate change - conservation - COP21 - ecosystem model - habitat - marine spatial planning - ocean - ocean acidification - species distribution - warming
The Paris Conference of Parties (COP21) agreement renewed momentum for action against climate change, creating the space for solutions for conservation of the ocean addressing two of its largest threats: climate change and ocean
acidification (CCOA). Recent arguments that ocean policies disregard a mature conservation research field and that protected areas cannot address climate change may be oversimplistic at this time when dynamic solutions for the
management of changing oceans are needed. We propose a novel approach, based on spatial meta-analysis of climate impact models, to improve the positioning of marine protected areas to limit CCOA impacts. We do this by estimating the vulnerability of ocean ecosystems to CCOA in a spatially explicit manner and then co-mapping human activities such as the placement of renewable energy developments and the distribution of marine protected areas. We test this approach in the NE Atlantic considering also how CCOA impacts the base of the food web which supports protected species, an aspect often neglected in conservation studies. We found that, in this case, current regional conservation plans protect areas with low ecosystem-level vulnerability to CCOA, but disregard how species may redistribute to new, suitable and productive habitats. Under current plans, these areas remain open to commercial
extraction and other uses. Here, and worldwide, ocean conservation strategies under CCOA must recognize the longterm importance of these habitat refuges, and studies such as this one are needed to identify them. Protecting these
areas creates adaptive, climate-ready and ecosystem-level policy options for conservation, suitable for changing oceans.
Operationalizing ecosystem services for the mitigation of soil threats : A proposed framework
Schwilch, Gudrun ; Bernet, Lea ; Fleskens, Luuk ; Giannakis, Elias ; Leventon, Julia ; Marañón, Teodoro ; Mills, Jane ; Short, Chris ; Stolte, Jannes ; Delden, Hedwig Van; Verzandvoort, Simone - \ 2016
Ecological Indicators 67 (2016). - ISSN 1470-160X - p. 568 - 597.
Decision support - Ecosystem services - Europe - Land management - Soil functions - Soil threats

Despite numerous research efforts over the last decades, integrating the concept of ecosystem services into land management decision-making continues to pose considerable challenges. Researchers have developed many different frameworks to operationalize the concept, but these are often specific to a certain issue and each has their own definitions and understandings of particular terms. Based on a comprehensive review of the current scientific debate, the EU FP7 project RECARE proposes an adapted framework for soil-related ecosystem services that is suited for practical application in the prevention and remediation of soil degradation across Europe. We have adapted existing frameworks by integrating components from soil science while attempting to introduce a consistent terminology that is understandable to a variety of stakeholders. RECARE aims to assess how soil threats and prevention and remediation measures affect ecosystem services. Changes in the natural capital's properties influence soil processes, which support the provision of ecosystem services. The benefits produced by these ecosystem services are explicitly or implicitly valued by individuals and society. This can influence decision- and policymaking at different scales, potentially leading to a societal response, such as improved land management. The proposed ecosystem services framework will be applied by the RECARE project in a transdisciplinary process. It will assist in singling out the most beneficial land management measures and in identifying trade-offs and win-win situations resulting from and impacted by European policies. The framework thus reflects the specific contributions soils make to ecosystem services and helps reveal changes in ecosystem services caused by soil management and policies impacting on soil. At the same time, the framework is simple and robust enough for practical application in assessing soil threats and their management with stakeholders at various levels.

Identification of commensal species positively correlated with early stress responses to a compromised mucus barrier
Sovran, Bruno ; Lu, Peng ; Loonen, Linda M.P. ; Hugenholtz, Floor ; Belzer, Clara ; Stolte, Ellen H. ; Boekschoten, Mark V. ; Baarlen, Peter Van; Smidt, Hauke ; Kleerebezem, Michiel ; Vos, Paul De; Renes, Ingrid B. ; Wells, Jerry M. ; Dekker, Jan - \ 2016
Inflammatory Bowel Diseases 22 (2016)4. - ISSN 1078-0998 - p. 826 - 840.
Bacteroidetes - colitis - Muc2 deficiency - stress markers

Background: Our aims were (1) to correlate changes in the microbiota to intestinal gene expression before and during the development of colitis in Muc2 -/- mice and (2) to investigate whether the heterozygote Muc2 +/- mouse would reveal host markers of gut barrier stress. Methods: Colon histology, transcriptomics, and microbiota profiling of faecal samples was performed on wild type, Muc2 +/-, and Muc2 -/- mice at 2, 4, and 8 weeks of age. Results: Muc2 -/- mice develop colitis in proximal colon after weaning, resulting in inflammatory and adaptive immune responses, and expression of genes associated with human inflammatory bowel disease. Muc2 +/- mice do not develop colitis, but produce a thinner mucus layer. The transcriptome of Muc2 +/- mice revealed differential expression of genes participating in mucosal stress responses and exacerbation of a transient inflammatory state around the time of weaning. Young wild type and Muc2 +/- mice have a more constrained group of bacteria as compared with the Muc2 -/- mice, but at 8 weeks the microbiota composition is more similar in all mice. At all ages, microbiota composition discriminated the groups of mice according to their genotype. Specific bacterial clusters correlated with altered gene expression responses to stress and bacteria, before colitis development, including colitogenic members of the genus Bacteroides. Conclusions: The abundance of Bacteroides pathobionts increased before histological signs of pathology suggesting they may play a role in triggering the development of colitis. The Muc2 +/- mouse produces a thinner mucus layer and can be used to study mucus barrier stress in the absence of colitis.

Development and application of a web-based geographical tool for WR&R technologies : Technologies for Water Recycling and Reuse in Latin American Context: Assessment, Decision Tools and Implementable Strategies under an Uncertain Future
Verzandvoort, S.J.E. ; Oertlé, Emmanuel ; Gross, T. ; Breitenmoser, L. ; Engbretsen, A. ; Stolte, J. ; Gonzalez Martin, Gerardo ; Heesmans, H.I.M. ; Heidema, A.H. ; Assinck, F.B.T. ; Elsen, H.G.M. van den; Walvoort, D.J.J. ; Beek, R. van - \ 2015
- 110 p.
Soil erosion by wind
Borrelli, Pasquale ; Panagos, P. ; Hessel, R. ; Riksen, M. ; Stolte, Jannes - \ 2015
In: Soil in Europe - threats, functions and ecosystem services / Stolte, Jannes, Tesfai, Mehreteab, Oygarden, Lillian, Bioforsk - p. 25 - 33.
Decline in organic matter in peatsoils
Akker, J.J.H. van den; Berglund, Kerstin ; Berglund, Orjan - \ 2015
In: Soil in Europe - threats, functions and ecosystems services / Stolte, Jannes, Tesfai, Mehreteab, Oygarden, Lillian, Bioforsk - p. 40 - 61.
Soil sealing
Siebelec, Gzregorz ; Prokop, Gundula ; Delden, Hedwig van; Verzandvoort, S.J.E. ; Miturski, Tomasz ; Lopatka, Artur - \ 2015
In: Soil in Europe - threats, functions and ecosystem services / Stolte, Jannes, Tesfai, Mehreteab, Oygarden, Lillian, Bioforsk - p. 94 - 108.
Kirkby, M.J. ; Hessel, R. ; Bruggeman, A. - \ 2015
In: Soil in Europe - threats, functions and ecosystem services / Stolte, Jannes, Tesfai, Mehreteab, Oygarden, Lillian, Bioforsk - p. 139 - 151.
Soil functions & ecosystem services
Schwilch, Gudrun ; Bernet, Lea ; Claringbould, Heleen ; Fleskens, L. ; Giannakis, Elias ; Leventon, Julia ; Marañón, Teodoro ; Mills, Jane ; Verzandvoort, S.J.E. - \ 2015
In: Soil in Europe - threats, functions and ecosystem services / Stolte, Jannes, Tesfai, Mehreteab, Oygarden, Lillian, Bioforsk - p. 185 - 209.
Faecalibacterium prausnitzii strain HTF-F and its extracellular polymeric matrix attenuate clinical parameters in DSS-induced colitis
Rossi, Oriana ; Khan, M.T. ; Schwarzer, Martin ; Hudcovic, Tomas ; Srutkova, Dagmar ; Duncan, Sylvia H. ; Stolte, E.H. ; Kozakova, Hana ; Flint, Harry J. ; Samsom, Janneke N. ; Harmsen, Hermie J.M. ; Wells, J.M. - \ 2015
PLoS ONE 10 (2015)4. - ISSN 1932-6203 - 17 p.

A decrease in the abundance and biodiversity of intestinal bacteria within the Firmicutes phylum has been associated with inflammatory bowel disease (IBD). In particular, the anti-inflammatory bacterium Faecalibacterium prausnitzii, member of the Firmicutes phylum and one of the most abundant species in healthy human colon, is underrepresented in the microbiota of IBD patients. The aim of this study was to investigate the immunomodulatory properties of F. prausnitzii strain A2-165, the biofilm forming strain HTF-F and the extracellular polymeric matrix (EPM) isolated from strain HTF-F. For this purpose, the immunomodulatory properties of the F. prausnitzii strains and the EPM were studied in vitro using human monocyte-derived dendritic cells. Then, the capacity of the F. prausnitzii strains and the EPM of HTF-F to suppress inflammation was assessed in vivo in the mouse dextran sodium sulphate (DSS) colitis model. The F. prausnitzii strains and the EPM had anti-inflammatory effects on the clinical parameters measured in the DSS model but with different efficacy. The immunomodulatory effects of the EPM were mediated through the TLR2-dependent modulation of IL-12 and IL-10 cytokine production in antigen presenting cells, suggesting that it contributes to the anti-inflammatory potency of F. prausnitzii HTF-F. The results show that F. prausnitzii HTF-F and its EPM may have a therapeutic use in IBD.

IL-22-STAT3 Pathway Plays a Key Role in the Maintenance of Ileal Homeostasis in Mice Lacking Secreted Mucus Barrier
Sovran, B. ; Loonen, L.M.P. ; Hugenholtz, F. ; Belzer, C. ; Kranenbarg-Stolte, H.H. ; Boekschoten, M.V. ; Baarlen, P. van; Kleerebezem, M. ; Vos, P. de; Dekker, J. ; Renes, I.B. ; Wells, J.M. - \ 2015
Inflammatory Bowel Diseases 21 (2015)3. - ISSN 1078-0998 - p. 531 - 542.
inflammatory-bowel-disease - pancreatitis-associated protein - intestinal epithelial-cells - colonic gene-expression - experimental colitis - muc2-deficient mice - mucin muc2 - microbiota - bacteria - stat3
Background: Muc2-deficient mice show no signs of ileal pathology but the mechanisms remained unknown. Methods: Wild-type (WT), Muc2+/-, and Muc2-/- mice were killed at 2, 4, and 8 weeks of age. Total RNA from ileum was used for full genome transcriptome analysis and qPCR. Microbiota composition was determined using a mouse intestinal chip (MITChip). Morphological and immunohistological studies were performed on segments of ileum. Results: The ileum was colonized by more diverse microbiota in young (week 4) WT than in Muc2-/- mice, and composition was influenced by genotype. Weaning was associated with major changes in the transcriptome of all mice, and the highest number of differentially expressed genes compared with adults, reflecting temporal changes in microbiota. Although the spatial compartmentalization of bacteria was compromised in Muc2-/- mice, gene set enrichment analysis revealed a downregulation of Toll-like receptor, immune, and chemokine signaling pathways compared to WT mice. The predicted effects of enhanced IL-22 signaling were identified in the Muc2-/- transcriptome as the upregulation of epithelial cell proliferation altered expression of mitosis and cell-cycle control pathways. This is consistent with increased villus length and number of Ki67+ epithelial cells in Muc2-/- mice. Additionally, expression of the network of IL-22 regulated defense genes, including Fut2, Reg3[beta], Reg3[gamma], Relmb, and the Defensin Defb46 were increased in Muc2-/- mice. Conclusions: These findings highlight a role for the IL-22-STAT3 pathway in maintaining ileal homeostasis when the mucus barrier is compromised and its potential as a target for novel therapeutic strategies in inflammatory bowel disease
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