Manipulating the activity of the gut microbiota with fermentable carbohydrates to maximise the bioavailability of bioactive phenolic acids for health

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci


It is now widely recognised that much of the metabolism of the major polyphenol classes occurs in the large intestine, under the control of the resident microbiota. The microbiota degrades parent polyphenolics to a range of intermediates and end-products such as phenolic acids. Evidence is emerging for the health benefits of these intermediates and end-products and given their high bioavailability in comparison to the parent compounds, they may explain in a large part many of the biological effects of polyphenolics.

The main substrates driving metabolic activity of the microbiota in the large intestine are fermentable carbohydrates derived largely from dietary fibre. Our preliminary evidence suggests that there is an interaction between carbohydrate fermentation and polyphenol metabolism in the large intestine. However, a greater understanding of this interaction is necessary in order to predict and manipulate the way polyphenols are metabolised by the gut microbiota.

Manipulating the microbiota with fermentable carbohydrates will mimic the whole-food scenario under normal dietary conditions when polyphenols are released from foods alongside fermentable carbohydrate. The fermentable carbohydrate component will influence the activity of the microbiota and therefore the bioavailability of polyphenolic intermediates and end-products. In addition, the polyphenols may also act with prebiotic and antimicrobial properties, which together with fermentable carbohydrate may promote a more health associated microbiome.

This project will provide new insights into the relationship between fermentable carbohydrates and polyphenols and the role the gut microbiota plays in mediating the health benefits of polyphenol rich foods. Importantly it will also inform Industry about compositions which maximise the bioavailability of phenolic acids and the role these play in mediating the protective effects of polyphenols in health. With increasing pressure, particularly in the beverage market, to reduce sugar intake, replacement of sugar with alternative carbohydrates may be an important avenue to optimising polyphenol intake and polyphenol bioefficacy.

Technical Summary

Our aim is to develop a systematic evidence base describing the impact of fermentable carbohydrates on the metabolism of polyphenols by the gut microbiota. It is now recognised that a substantial part of polyphenol metabolism occurs in the large intestine and fermentable carbohydrates are major dietary factors driving gut microbial metabolism.

This project aims to use a combination of in vitro and in vivo studies to examine the interactions between fermentable carbohydrate and polyphenol metabolism by the gut microbiota. The project aims to determine whether adding fermentable carbohydrate alters the bioavailability and bioefficacy of polyphenols whilst also providing evidence regarding the mechanisms of action for such effects.

Beginning with in vitro model gut screening studies, we will examine the interactions between different fermentable carbohydrate types and polyphenol types. Using this evidence, we will undertake a bioavailability study in human volunteers. Using stable isotope labelling, we will characterise the impact of fermentable carbohydrates on the bioavailability of a parent polyphenol and phenolic acid products of microbial metabolism.

Finally, in a longer term feeding study, we will examine the effects of fermentable carbohydrate and polyphenols on a range or health outcomes to examine the role of fermentation in the health benefits of polyphenols.

Planned Impact

This project has significant potential for long term impact on a wide range of stakeholders from consumers through to policy makers. In addition to the academic beneficiaries listed, the outputs of the research will impact on the following stakeholder groups:

Food Industry: The outputs from this project will enable the food industry to develop optimised food and beverage preparations that maximise the bioefficacy of ingested polyphenols. Polyphenol rich foods represent a multibillion pound industry, with UK fruit juices sales estimated at up to £2bn, with more than 7000 employees (IBIS World March 20124). However, establishing credible evidence for the health benefits of consuming polyphenol-rich foods is limited by our knowledge of the bioactivity of key metabolites from a range of products. Interactions with food industry will enable exchange of ideas and results to inform decision making in the project and enhance the impact of outcomes. Further research will allow these concepts to be incorporated into a wide range of food and beverages with current levels or perhaps enhanced consumer acceptance. Food with high nutritional impact is a growing sector for the food industry and increasingly requires robust scientific evidence of supporting health benefits. This project and future projects will support health claims and further growth and give the UK food industry a competitive advantage.

Consumers: Individual consumers will have new knowledge regarding the health benefits of polyphenol containing foods and will have information on optimum consumption patterns. For example, if fermentable carbohydrate enhances polyphenol health benefits, then consumer can be advised to consume foods rich in polyphenols with particular fibre containing foods. There is also the potential to present the consumer with new or enhanced products which have the optimum combination of fermentable carbohydrates and polyphenols.

Public Health: There is an increased awareness that optium nutrition and gut health both have a role to play in maintaining health and preventing disease. We rarely eat a single compound or compound class in isolation in a mixed diet. Thus, an increased understanding about how food components interact to elicit their health effects has long term implications for disease prevention. If we understand how to deliver the right mix of nutrients to the right site in the gut at the right time to maximise the health benefits, a range of options can be presented to the consumer that maximises the health benefits across the population. Food industry has a key role in delivering a range of options to the consumer which requires a strong evidence base with which to guide product development. The data produced will also help inform policy and guideline writers and health professionals.

Staff and students: training in specialist scientific skills, shared access to specialist equipment and opportunities to interact directly with the media (dissemination) and the public, hence gaining further transferable skills. The applicants have strong link with the agrofood industry and knowledge transfer networks, and this will facilitate the interactions of the staff with industrial and governmental stakeholders.

To maximise impact, we will assemble an Advisory Panel composed of various stakeholders including academic beneficiaries and industry. The panel will meet four times during the project to review progress and advise on future directions and potential for exploitation.


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Description Polyphenols are small compounds in fruits and vegetables, considered to be beneficial for health. Average daily intake is approximately 1g/day. Specific polyphenolics, the flavonoids (a small but significant component) are recognised as bioactive, but are poorly absorbed, and therefore reach the large intestine where they are broken down by the resident bacteria.
We are studying specific flavonoids: rutin, cyanidin-O-glucoside, catechin, kaempferol and strawberry ellagitannins. These are present in the diet in significant quantities and have been tested in human cells in both in vitro and in vivo studies. The in vitro biological activities of their breakdown products (after action of gut bacteria) can be superior to that of their parent products in relation to processes related to oxidative stress and inflammation, for example. These breakdown products can be absorbed and released into the bloodstream and are speculated to be responsible for health effects previously attributed to the parent compounds. Our research has shown that the presence of dietary fibres which are fermented by the gut bacteria can affect the way (in terms of quality and quantity) these flavonoids are broken down in a model of the gut.
We have investigated the effect of increasing the dose of different fibres on the metabolism of rutin, and the range of breakdown products released in in vitro "fermentation" models using faecal bacteria, mimicking the human colon. We have also established the effects of these compounds on the main products from carbohydrate fermentation - short chain fatty acids (SCFA).
The presence of fibre alone in the fermentation model modified the amount key flavonoid breakdown products. We showed that some fibres are rich sources of polyphenolics, which are trapped within the fibre itself until it reaches the colon.
The doses of fibre and flavonoids we used are comparable to what can be achieved through diet only - making our studies "physiologically relevant ".
We have shown that fibres such as plant-derived components are excellent sources of breakdown products which are likely to be important for health. Combination of fibres and additional sources of polyphenolics, from fruit and vegetable juices for example, may lead to an improved formation and absorption of these breakdown products. The next stage of our research is to test selected fibre/polyphenolic mixtures in humans in short and longer term trials.
Exploitation Route The results will be of interest for those designing diets and making dietary recommendations and for those designing food products to increase production of bacterial bioactive molecules.
Sectors Agriculture, Food and Drink,Healthcare

Title stable isotope tracer studies 
Description Using stable isotope tracers to follow pathways of metabolism of individual polyphenols by microbiota and host 
Type Of Material Physiological assessment or outcome measure 
Provided To Others? No  
Impact provides an alternative to animal experiments as we can study indirectly in humans 
Description DRINC meetings 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact BBSRC DRINC meeting with industry participation
Year(s) Of Engagement Activity 2016,2017
Description Rodin discussion group 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Sharing the research area and likely impacts with group of mixed professionals ( including non science)
Year(s) Of Engagement Activity 2017