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Marzorati M.,Ghent University | Vanhoecke B.,Ghent University | De Ryck T.,Ghent University | Sadaghian Sadabad M.,University of Groningen | And 10 more authors.
BMC Microbiology | Year: 2014

Background: Recent scientific developments have shed more light on the importance of the host-microbe interaction, particularly in the gut. However, the mechanistic study of the host-microbe interplay is complicated by the intrinsic limitations in reaching the different areas of the gastrointestinal tract (GIT) in vivo. In this paper, we present the technical validation of a new device - the Host-Microbiota Interaction (HMI) module - and the evidence that it can be used in combination with a gut dynamic simulator to evaluate the effect of a specific treatment at the level of the luminal microbial community and of the host surface colonization and signaling. Results: The HMI module recreates conditions that are physiologically relevant for the GIT: i) a mucosal area to which bacteria can adhere under relevant shear stress (3 dynes cm -2); ii) the bilateral transport of low molecular weight metabolites (4 to 150 kDa) with permeation coefficients ranging from 2.4 × 10 -6 to 7.1 × 10-9 cm sec-1; and iii) microaerophilic conditions at the bottom of the growing biofilm (PmO2 = 2.5 × 10-4 cm sec-1). In a long-term study, the host's cells in the HMI module were still viable after a 48-hour exposure to a complex microbial community. The dominant mucus-associated microbiota differed from the luminal one and its composition was influenced by the treatment with a dried product derived from yeast fermentation. The latter - with known anti-inflammatory properties - induced a decrease of pro-inflammatory IL-8 production between 24 and 48 h. Conclusions: The study of the in vivo functionality of adhering bacterial communities in the human GIT and of the localized effect on the host is frequently hindered by the complexity of reaching particular areas of the GIT. The HMI module offers the possibility of co-culturing a gut representative microbial community with enterocyte-like cells up to 48 h and may therefore contribute to the mechanistic understanding of host-microbiome interactions. © 2014 Marzorati et al.; licensee BioMed Central Ltd.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2011.2.2-01 | Award Amount: 7.85M | Year: 2012

The project goal is to support the development of functional food ingredients and products that are beneficial for the human gut & immune system and therefore of crucial importance for quality of life. The project will study the effects of specific non-digestible polysaccharides which have shown health potential in this field. The health effects of NPS will be focused around enhancing immune defence against pathogens, the reduction of infectious diseases like common cold and influenza of elderly and will make use of EFSA supported biomarkers that enable immune function claims and underpin the mechanism involved. The studied mechanisms are the innate and adaptive immune system and the possible involvement of the microbiota and microbiota-mediated products. To achieve this goal new and existing NPS will be studied for their health effects in a systematic way by developing a toolbox of dedicated assays and models that can be used by industry and authorities to study and approve food ingredients with a similar health focus. The project will: 1) perform biochemical analyses to study compounds, effect of processing and bioavailability, 2) develop standardized in vitro screening methods to be able to predict in vivo effects, 3) use dedicated in vivo and ex vivo analyses to study mechanisms of action and to validate biomarkers and 4) use and validate this knowledge in an intervention study. By combining the knowledge that will be gained from molecular, cellular and whole-organism studies, the goal will be to understand the bioactive mechanisms of these NPS and use this knowledge to design functional food products. SMEs make a very large contribution to the project, both as beneficiary of the products and as a technology service provider related to health research. This proposed project should provide the scientific basis for international nutritional organisations to recommend an immune-related functional health claim for some of the NPS studied.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2013.2.6-01 | Award Amount: 2.57M | Year: 2013

CARODEL aims to valorise the results from the previous FP7 COLORSPORE project, in which initial isolation and characterization work was performed on Bacillus strains producing gastric-stable carotenoids. As the stability in the gastrointestinal tract (GIT), antioxidant activity and bioavailability of particular Bacillus carotenoids was shown to be higher than those of common dietary carotenoids, the conclusions from COLORSPORE provided strong and compelling reasons to support further development and commercialisation of these bacteria-derived carotenoids. CARODEL will therefore focus on the development of an efficient oral delivery strategy of such highly active carotenoids, in combination with evaluation of potential direct health-beneficial (probiotic) activity of the Bacillus delivery vehicle, with the ultimate aim to improve biomarkers associated with (the prevention of) cardiovascular disease (CVD). The relevance of using carotenoids for CVD prevention was recently shown by a positive EFSA opinion on the use of tomato lycopene for maintenance of a healthy blood flow. In practice, effective delivery of the carotenoids to the human body will be compared upon administration as i) vegetative Bacillus cells, ii) Bacillus spores or iii) extracted carotenoids. In parallel, the ability of the Bacillus strain to exert bona fide effects (i.e., effects on the host microbiota, metabolism and immunity) will be investigated using in vitro gut models and in vivo rat studies. Based on this, the best delivery strategy will be selected and validated in a human study, in which carotenoid bioavailability will be validated as well as endpoints related to CVD biomarkers and potential probiotic activity. In combination with a full safety assessment, a proof-of-concept production strategy and development of a business plan, the scientific evidence compiled in this project will provide a framework for efficient further commercialisation of a well-documented Bacillus carotenoid product


Grant
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.2.2-01 | Award Amount: 7.65M | Year: 2012

The main objective of the BACCHUS project is to develop tools and resources that will facilitate the generation of robust and exploitable scientific evidence that can be used to support claims of a cause and effect relationship between consumption of bioactive peptides and polyphenols, and beneficial physiological effects related to cardiovascular health in humans. To achieve this, the BACCHUS consortium has assembled 12 leading Research & Technological centres and 16 SMEs (with ca 30% of the EC requested contribution allocated to the SMEs). BACCHUS thus contains SMEs directly involved in developing food products and pursuing health claims, experts in health claims legislation and the EFSA review process, and academic and industry partners who provide high quality food and health research that can underpin health claims. Existing SME-developed products that have clear potential for obtaining favourable opinions for health claims have been selected as test cases for study. These have been aligned with a series of work-packages each of which addresses key aspects of the EFSA health claim evaluation process (legislation and dossiers; product/bioactive characterisation; habitual intakes; bioavailability; mechanisms and biomarkers; clinical trials evidence of health benefit) that will deliver tools, processes and high quality original science. Scientific results and best practice guidelines will be made publically available and thus support future claims for industry. The scope and completeness of the existing bioactive database (eBASIS) that includes both compositional and biological effects data will be extended and developed as a sustainable tool with various training materials. All outcomes will be disseminated broadly by direct engagement with SMEs via an existing European SME association, with stakeholders via seminars, newsletters and press releases, as well as through traditional scientific routes (high quality publications, and conference presentations).


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.77M | Year: 2014

The BIopolymer BAsed FOOd Delivery Systems (BIBAFOODS) network will train young researchers for the advancement of food science and technology, by providing them with the complementary skills necessary to develop the future sustainable food industry and entrepreneurial skills crucial for creating biotechnological food oriented start-up companies. This collaborative training network will combine the complementary training capabilities of each individual partner institution to improve the trainees chances for employment and promote health and welfare in the EC by providing the capability to develop novel functional foods. The scientific focus of the research training is on colloidal delivery systems to protect and deliver active components via foods, resulting in novel functional foods. The development of these systems is to be based on only food-grade ingredients and upon economical feasible processes. The hypothesis is that the materials and coatings can be made responsive to the external chemical conditions and therefore suitable for controlled releases targeted at a desired stage during food processing or at a specific point during digestion of the food, e.g. in the intestinal tract. This will involve probiotic bacteria and enzymes that are liberated and allowed to be active in a controllable way. The ultimate successful materials ensure stability of the active component during long term storage prior to food production, during food production or during digestion, but at the same time liberating the active component at the right point. The behaviour and interaction of the delivery systems will be studied by simulation of gastric and intestinal conditions and by implementation in food production and formulation into probiotic products. To summarize, through the training in BIBAFOODS, 14 young researchers will achieve superior qualifications that will make them highly competitive and attractive for the European food and bio-tech industry.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-TP | Phase: KBBE.2011.2.3-04 | Award Amount: 8.03M | Year: 2012

The SATIN project has been devised to develop food products produced by novel food processing that control satiety through modification of food structure. To achieve this the SATIN project will: 1. Integrate advanced technologies to screen novel food structures through in vitro models to isolate and refine products according to their satiating potential. 2. Develop novel food processing technologies that combine active ingredients and change food structure to produce a range of novel satiety enhancing ingredients. 3. Produce finished foods products that pass through safety analysis, early sensory evaluation and consumer testing. 4. Demonstrate the effects of prototype products on biomarkers of satiety and on nutrient bioavailability using in vivo studies and validating new in vivo approaches. 5. Demonstrate the effects of final foods products on within-meal satiation, post-meal satiety and / or reduced appetite and biomarkers of satiety. 6. Demonstrate the enduring effects of individual food products on satiety and their potential to induce weight loss. 7. Demonstrate the long-term consumer and health benefits of adhering to a diet containing satiety enhancing products. 8. Validate health claim endpoints and commercialise technologies and products. The SATIN consortium consists of 7 SMEs and 4 commercial partners ensuring that advanced technologies developed to process and screen novel food products are applied to the food industry and improve European economic competitiveness. The safety and efficacy of products developed will be rigorously examined by 7 leading international academic research teams ensuring consumers will have new high quality processed foods to help them achieve a balanced diet.


Marzorati M.,Ghent University | Verhelst A.,ProDigest | Luta G.,Mannatech Inc | Sinnott R.,Mannatech Inc | And 3 more authors.
International Journal of Food Microbiology | Year: 2010

The use of prebiotics is a possible strategy to manage and steer the complex gut microbial community towards a health-promoting composition (Gastrointestinal Resource Management). In this study, the Simulator of the Human Intestinal Microbial Ecosystem was used to investigate the effects of two commercially-available plant polysaccharide supplements on the structure, composition and metabolism of an in vitro cultured colon microbial community.Microbial analyses showed both a bifidogenic (up to +. 1.3. log cfu/mL) and a lactobacillogenic (up to +. 0.9 log. cfu/mL) effect during treatment with the dietary supplements. Quantitative PCR confirmed that the increase of Bifidobacteria spp. was statistically significant (P<0.05) in all of the colon compartments and showed a significant increase of the bacteroides-prevotella group concentration (+. 0.6. log cells/ml) in the compartment simulating the proximal colon. Denaturant gradient gel electrophoresis analyses and a relative ecological interpretation, in combination with sugar and short-chain fatty acids quantification, provided evidence of a positive effect of both the tested products. Overall, the treatment period was associated with (i) good and selective fermentability of the polysaccharide supplements along the entire colon; (ii) positive and selective bifidogenic effect; (iii) the possibility of enhancing species belonging to Bacteroidetes, a phylum recently associated with body weight management. © 2010 Elsevier B.V.


Marzorati M.,Ghent University | Possemiers S.,Ghent University | Verhelst A.,ProDigest | Cade D.,Capsugel | And 2 more authors.
LWT - Food Science and Technology | Year: 2015

The delivery of acid sensitive actives in the gastrointestinal tract (GIT) requires specific formulation technology that can act as protection against harsh physiological conditions. Recently, vegetarian capsules based on hypromellose have become commercially available (for example, Vcaps®, Vcaps® plus and DRcaps™). Among them, DRcaps™ shows a dissolution profile that is resistant at low pH (1.2). The objective of this study is to assess the efficacy the DRcaps™ in protecting and delivering pure probiotic and enzymatic activities under gastrointestinal relevant conditions such as fasted and fed status, using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) technology platform. When compared with other formulations, DRcaps™ show - especially under fasted conditions - an increased ability to protect both probiotic microorganisms (at least an increase of 1 Log) and acid-sensitive enzymes, i.e. lipase and amylase (at least an activity increase of 1.5 times over the other formulations) during gastrointestinal digestion. Additional trials with DRcaps™ also show a 100% residual viability for probiotic bacteria in a 24-month shelf-life test (temperature of 25°C and 30°C/13.8 and 18.2g/m3 relative humidity, respectively). Finally, customers perceive that this new type of capsule has a superior organoleptic performance, assessed by the reduction or absence of an aftertaste, when compared with compressed tablets. © 2014 Elsevier Ltd.


Marzorati M.,Ghent University | Maignien L.,Ghent University | Verhelst A.,ProDigest | Luta G.,Mannatech Inc | And 5 more authors.
Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology | Year: 2013

The combination of a Simulator of the Human Intestinal Microbial Ecosystem with ad hoc molecular techniques (i.e. pyrosequencing, denaturing gradient gel electrophoresis and quantitative PCR) allowed an evaluation of the extent to which two plant polysaccharide supplements could modify a complex gut microbial community. The presence of Aloe vera gel powder and algae extract in product B as compared to the standard blend (product A) improved its fermentation along the entire simulated colon. The potential extended effect of product B in the simulated distal colon, as compared to product A, was confirmed by: (i) the separate clustering of the samples before and after the treatment in the phylogenetic-based dendrogram and OTU-based PCoA plot only for product B; (ii) a higher richness estimator (+33 vs. -36 % of product A); and (iii) a higher dynamic parameter (21 vs. 13 %). These data show that the combination of well designed in vitro simulators with barcoded pyrosequencing is a powerful tool for characterizing changes occurring in the gut microbiota following a treatment. However, for the quantification of low-abundance species - of interest because of their relationship to potential positive health effects (i.e. bifidobacteria or lactobacilli) - conventional molecular ecological approaches, such as PCR-DGGE and qPCR, still remain a very useful complementary tool. © 2012 Springer Science+Business Media Dordrecht.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: NMBP-10-2016 | Award Amount: 6.00M | Year: 2017

Inflammatory bowel diseases (IBD) are the second most common immune-mediated disorders in Europe, affecting more particularly young people. The current therapies, including antibodies, show three main drawbacks: efficacy, tolerability and convenience. NEW DEAL solution will offer radical therapeutic progress for all IBD patients, thanks to the improved efficacy and increased safety of the specific JAK3 inhibition, which has been proven in clinics to be a target of great interest, the better tolerability of siRNA in term of immunogenicity and the good convenience with oral administration. To achieve this challenge, we will address three objectives: i) Specifically inhibit JAK 3 in a highly selective and safer manner by the mean of siRNA carefully designed and validated, ii) Deliver the siRNA therapeutic locally to the inflamed gut, by combining innovative nanostructured lipid carriers enabling their transport across the mucus, the intestinal barrier and the plasma membrane of the target cells, with polymeric capsules for protecting siRNA nanotherapeutics during their transit along the GI tract, thus allowing an oral administration, and iii) Promote the clinical translation and the future industrial transfer of this new clinical product, by addressing manufacturing, safety and efficacy evaluation at the late preclinical stage, to generate a Regulatory Submission Package and a Clinical Development Plan. The NEW DEAL project brings together clinical experts on IBD, leading scientists in nanomedicine, RNAi biology and immunology, innovative SMEs with a strong background in nanosafety, design of capsules and regulatory issues and an established pharma company with historic expertise on gastroenterology medicinal products. If successful, NEW DEAL will open new avenues for siRNA-based therapy in IBD with oral administration.

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