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H2020Individual fellowship2018–2020

TRIANGLE · A novel integrative strategy to prevent colorectal cancer within the diet-host-microbiota triangle: from organoids to human in vivo reality

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2018-07-01 → 2020-06-30
EU contribution
€168,277
Participants
1
Scheme
MSCA-IF-EF-ST

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Results in brief

A novel integrative strategy to prevent colorectal cancer within the diet-host-microbiota triangle: from organoids to human in vivo reality

Colorectal cancer (CRC) is the second cause of death in the EU, with one million cases of CRC seen annually worldwide, and a mortality rate of 50%. In the light of these figures, and associated costs, there is an overwhelming need to prioritize and integrate primary prevention measures in existing healthcare plans. The forecasts show that the global burden of CRC is expected to increase by 60%, to over 2.2 million new cases and 1.1 million deaths by 2030, due to an aging population and western dietary patterns. Dietary patterns, or the food we eat, are the sum of a multitude of small molecules foreign to the body. After being ingested and digested, nutrients are altered by the trillions of microorganisms that inhabit our gastrointestinal (GI) tract, shaping the chemical structures of such compounds and thus modifying the lifespan, bioavailability, and biological effects. In this context, dietary patterns modulate the gut microbiome and alter its functions by modulating the production of gut microbial metabolites (GMMs). Lastly, these GMMs are capable of regulating homeostasis and the risk of GI disease. TRIANGLE has studied the mechanisms by which GMMs may prevent CRC and promote gut health by modelling diet-microbiome-host interactions. The first objective was to establish 3D intestinal models closely recapitulating homeostasis and carcinogenesis. Secondly, diet-gut microbiota interactions were evaluated using a GI track model. Lastly, human colon organoid and tumoroids responses to GMMs deriving from flavan-3-ols were evaluated by 3D imaging techniques and multi-omics approaches.

Data: CORDIS, © European Union

Project objective

Colorectal cancer (CRC) is the second cause of death in the EU, and so far, diet has been accounted for up to 80% of the cases. In this context, dietary phytochemicals have received increasing interest due to their suspected role in the prevention of cancer. Numerous studies report the chemopreventive effects of polyphenols. However, health benefits assigned to dietary constituents are still under controversy as can be deduced from the large number of applications rejected by the EFSA (health claims). Despite the crucial role of polyphenols in many biological cases, adequate tools to decipher the relationship between diet-microbiome-host are not yet available. To unveil the mysteries in the emerging field of personalized nutrition, this proposal aims to develop a new in vitro model for the study of phytochemicals in CRC prevention.The most common approach to study the anti-proliferative activity of polyphenols against CRC involves the use of 2D cell lines. Although multiple hints on the possible anticancer effects of these compounds have been already published, these results cannot be extrapolated to human. Firstly, immortalized 2D cell lines differ metabolically from in vivo cells. Secondly, these compounds were not artificially digested and fermented. Therefore, a novel integrative strategy to deepen understanding of CRC is vital. To accomplish this, a real-life scenario is needed. In this context, colon organoids/tumoroids will be established. Afterwards, an apple will be digested/fermented in vitro using a batch culture colonic model inoculated with feces from lean/obese healthy donors. In the end, such polyphenol metabolites will be tested in colon organoids/tumoroids and the mechanisms of action will be revealed by metabolomics and organoids assays. The outcome of this proposal will significantly deepen our knowledge of polyphenols-microbiome-organoids, and, in the long term, will allow nutritional recommendations to be given for the prevention of cancer.

Original text from CORDIS.

Participants

  • UNIVERSITA DEGLI STUDI DI TRENTO · TrentoCoordinatorItaly

Links

Data: CORDIS, © European Union