Non-digestible polysaccharides for gut and immune health

Food fibres are good for our health. Some fibres have clearly demonstrated lowering or maintaining normal blood cholesterol levels, have shown to regulate glucose levels and can contribute to a good stool (increase in faecal bulk). EFSA has recognised these health effects by approving claims for some specific fibres for which enough proof was available for substantiation of such a claim. We have to make clear here that not all fibres are of the same origin, have undergone identical isolation procedures or processing methods, in addition to which food matrix effects will possibly also contribute to the final biological effects when consuming these fibres.

Most people see fibres as possible prebiotic compounds, benefitting the positive microbes in our gut and by that favouring the ‘good’ over the possible ‘harmful’ bacteria. The oligo – saccharides developed for this goal are expected to function in this way. However, showing that a food compound can change the microbiota composition in the gut is currently not enough as no conclusive evidence can be referred to linking these changes to an improved immune system and by that to an improved maintenance of health. For sub – stantiation of an EFSA claim, it will be important to link the changes in gut microbiota compo – sition to biological relevant immune effects and health parameters such as reduction of common cold symptoms.

Few people realise that sugar moieties are an extremely variable chemical class of compounds and that the immune system is using the uniqueness of these sugar groups for their recognition system, leading to activation of the innate and adaptive immune system. The recognition of bacteria and yeast by immune cells is often based on specific sugar groups and spacing of the groups in the molecule which can lead to clustering of receptors on immune cells and by that, activate the defence response. Could it therefore be the case that some of these fibres, like those within the group of non-digestible poly – saccharides (NPS), trigger broad spectrum defence responses in humans which improve the whole immune system?

Earlier this year, the EU invested six million Euros to support the food industry and food research community by granting a project on non-digestible polysaccharides to study the effect on gut and immune health. NPS represent a class of food fibres which have a chain of sugars (more than 10 sugar moieties). NPS can have a complex composition of different type of sugars linked by binding on different positions and can have different degrees of side branches. Polysaccharides that are easily digested in the upper gastric track (like starch) are excluded from this group as effects will be less based on the complex structure of the sugar groups. The group of NPS contains many intriguing compounds like ß-glucans, pectins, arabino – galactans, resistant starch, arabinoxylan, exopolysaccharides and many more. The EU project, named FibeBiotics, has its focus on improving the understanding of the effects these compounds can have on human health by developing systematic strategies, common practices and standardised protocols, setting up methods for biochemical analysis, validating biomarkers and designing formats for clinical trials to increase coherency in the analyses of biochemical and biological effects of this compound category.

Questions to address are why do some NPS activate immune effects and others not, what immune biomarkers should be used to sub – stantiate relevant health effects, what can we learn from in vitro (lab scale responses of compounds when exposed to human cells lines) effects to improve extrapolation to what happens at in vivo level (effects after a food intervention using human volunteers) and how biochemical analyses can support product development etc.

To address all these questions, the FibeBiotics consortium is enlisting four universities, five research institutes and eight companies (either active as compound providers or as providing services to support analysis of health effects). The FibeBiotics consortium works in a team to perform the analyses, define validated biomarkers and clinical endpoints, and to conduct clinical trials for NPS. The consortium is coordinated by Food & Biobased Research, an institute that is part of Wageningen University & Research Centre, Wageningen, The Netherlands. The NPS compounds which will receive attention within the FibeBiotics project are: a yeast ß-glucan, an oat ß-glucan, a fungal (shiitake) ß-glucan, arabinoxylan from wheat, specific pectin fractions from apple and exo-polysaccharides from fermented milk.

A challenging part of the FibeBiotics project is the identification of biomarkers that can support the evidence for immune effects. Blood cholesterol levels can be easily measured and is accepted as risk factor for vascular diseases. Sugar regulation is also an easy biomarker for development of insulin resistance and also stool can be easily measured by standardised protocols. But what about immune biomarkers? Changes in pro or anti-inflammatory cytokines and chemokines after a food intervention cannot be seen as full understanding of health effects, because, depending on individual immune status, these changes can be desirable or not. So it all depends on how these effects are balanced and regulated, which makes it a challenge to study them. Potential interesting biomarkers will be analysed within FibeBiotics to increase our understanding and will be linked to other immune markers like antibody titers after a standard influenza vaccination. Especially the antibody titers that are formed in the first weeks after the vaccination have been recognised by the EFSA as sound scientific support to demonstrate effects towards the immune system, which very likely can be extrapolated to general immune supportive effects for the healthy population. After pilot trials the most important biomarkers will be linked in a final human trial with clinical endpoints which will be planned with only a very limited number of ‘elite’ compounds.

The FibeBiotics project is structured in eight work packages (WPs). These reflect the different aspects, which we consider as an organisational requirement to achieve a better overall understanding and positioning of the health related research on NPS. WP2 is dedicated to perform biochemical analyses to study compounds, the effect of processing on bioavailability and to support the development of products with sustained bioactivity. WP3 will focus on the development of standardised in vitro screening methods both for direct immune effects on immune cells and those taking place indirectly via the microbiota including fermentation studies with the an in vitro model. Mechanistic studies on how these compounds mediate their effect on the gut and innate immune system will be studied in WP4. Pilot and pivotal intervention studies based on elderly subjects, having a main focus on innate and adaptive immune responses as well as endpoint health parameter will be performed in WP5. As a pile of data will be generated which should be studied in coherence and should lead to improved systematic food development in the future, a data warehouse system, together with analyses and correlative mathematical tools will be needed which will be developed in WP6. In parallel to the health effect analysis, also the interest of the industry and consumers regarding these ingredients and products will be addressed. When bio logically relevant effects are found these will also be communicated for which WP7 also will develop educational methods to inform the public. The final WP is for dissemination and exploitation of the developed expertise, research tools and products.

The consortium has planned to do much of its exploitation via an Industrial Platform (InP). The FibeBiotics InP is open to enterprises from the food, feed and beverage industry and related sectors. This can range from breeders, growers and producers of polysaccharide compounds, industry involved in processing and the industry that applies or is interested in applying polysaccharides in their products to potentially increase health impact of the product. In particular, companies that would like to use the built-up knowledge from the consortium to have other polysaccharides studied or have products designed using strategies developed within FibeBiotics are invited to join the Industrial Platform. InP members will regularly receive project infor – mation via newsletters, will receive access to a special InP login section at the FibeBiotics website, will be invited to the Industrial Platform meetings at which results and strategies will be presented (first meeting held on 4 October 2012) and will be invited to workshops at which new technologies or strategies will be demonstrated. Interested stakeholders can find more info at the FibeBiotics website and can download the InP company sheet and the InP Support Letter from there.

The EU recognised the project as highly important for the food industry and a prototype of how ingredients should be studied when aiming at supporting health effects. It takes into account the EFSA guidelines, builds upon SMEs that are owner of compounds for which health effects are studied, includes also research oriented SMEs that can support the industry by dedicated technologies and provides both new insights in fundamental questions and answers on applied questions. An example of the latter is, for instance how to develop a product via a complex production process while retaining the potential health effects. Especially this translation from pure ingredients to the fate of ingredient when placed into a food application is very important for the consumer. Since food matrices and food processing may affect bioactivity of ingredients, investigations on how active ingredients are thereafter exposed to immune cells and taken up in the blood are warranted. Such research is needed to substantiate the effects that an ingredient may have in realistic human delivery systems (i.e. functional foods).

The overriding benefit of FibeBiotics is as much its sole benefit to the involved ß-glucans and arabinoxylans as it is the goal to develop crossovers to other potential ingredients that might boost gut health and the immune system. These can range from fresh products like mushrooms and fermented products to probiotics and immunomodulating proteins. Some of the tools and technologies employed in the project can be used for studying these and other ingredients. Moreover it should provide tools that can support product development in such a way that relative costly clinical trials will have a higher success rate, because only those products will be tested with the highest potential for biological relevant effects. These trials can then also be performed more effectively, only analysing those bio – markers that are relevant and using a population size not exceeding the strictly needed size, thus reducing costs needed for substantiation of claims.

While the main scope of FibeBiotics is to focus on NPS, many parallels can be drawn with the potential outcomes for research on probiotics. Moreover, it is likely that NPS and probiotics can work synergistically. Possibly, NPS aid probiotic strains to better survive gastric passage and to more effectively colonise the gut, in addition to improving the immune response to the probiotics. As such, the NPS can act complementarily or enhance each other and by that broaden the immune effect even further. The expected FibeBiotics deliverables constitute a benchmark for better under – standing of immune health biomarkers on the whole, but the program that is initiated also offers a look at how other ingredient sectors might want to consider approaching scientific data collection to back up health claims. When resulting data support this, the aim of FibeBiotics is to support the submission of an EFSA claim for one or several of the NPS that are studied.

About the author

FibeBiotics is coordinated by Dr. Jurriaan J. Mes, senior scientist at Food & BioBased Research-WUR, The Netherlands. His background is molecular biology in the area of plant pathogen interaction and agronomical important plant and fruit quality traits. He is currently leading the Food Quality & Analysis Group which focuses on the quality (e.g. texture, shelf life) and health effects of food products, ranging from fresh to processed products, using a combination of biochemical, molecular and cell based analysis. The group mainly focuses on the effects of food on the mouth, gut and immune system. It includes a molecular approach on aspects like taste (e.g. perception of sweetness), safety (allergens, gut integrity) as well as positive effects (digestibility, bioavailability, bioactivity).