Research project
36 | monthsENDOPHENOL

Investigation of in vivo endogenous and/or exogenous production of phenolic metabolites using (un)targeted metabolomics

Related toSpoke 04

Principal investigators
Pedro Mena,Daniele Del Rio,Marco Ventura

Other partecipantsLetizia Bresciani, Laila Guimaraes Zeraik Cardoso, Claudia Favari, Nicola Luigi Bragazzi
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Task involved

Task 4.3.2.

Identification of nutrient and non-nutrient food components (and their metabolic products) potentially involved in the promotion of consumer health, and evaluation of their bio accessibility, bioavailability, and effect on the gut microbiota, using in silico, in vitro, ex vivo and in vivo approaches on humans/animals to confirm the actual absorption and bioactivity of non-nutrient components also considering specific dietary patterns and target groups.

Project deliverables


Systematic reviews of specific nutrients and non-nutrients bioavailability and putative health effects (M20)


Evaluation of the bioavailability and bioactivity of at least two components of foods proven to directly impact human health (M36)

State of the art

Dietary (poly)phenols ingested with plant-based foods and beverages are not fully absorbed in the upper gastrointestinal tract, passing from the small intestine to colon. The catabolism of these non-nutrients phytochemicals leads to the formation of low molecular weight compounds, namely phenolic acids. However, many of these catabolites can also be present in sizable amounts after a well-controlled (poly)phenol-free diet, being not derived exclusively from dietary (poly)phenols (Di Pede et al, Mol Aspects Med. 2022). Due to the possible health promoting characteristics proposed for these small phenolic acids (Carregosa et al., Compr Rev Food Sci Food Saf 2022), it is of paramount importance to investigate the microbiota-mediated catabolism of dietary phenolics to distinguish between genuine (poly)phenol catabolites and background phenolics derived from other sources.

Operation plan

An intervention study with human volunteers will be designed and submitted to the Ethics Committee for its approval. A (poly)phenol-free diet well controlled for energy and macronutrient intake, and a known source of dietary (poly)phenols will be administered to healthy volunteers in a randomized cross-over trial. Urine samples will be collected at different established time points for (un)targeted LC-MS metabolomics analyses. The targeted approach will be applied to check for the expected metabolites, based on published literature data, as well as on the research unit experience in the field. Untargeted metabolomics will allow to check for new phenolic endogenous and/or exogenous bioactive metabolites. The gut microbiota and genetic profile will also be considered. The endogenous/exogenous ratio of common low molecular weight colonic catabolites will be investigated.

Expected results

Low molecular weight phenolics have been associated with possible health promoting effects in humans. However, the same phenolics could derived from endogenous human metabolism, confounding the role of non-nutrient-derived metabolites in health promotion. With this study, we expect to apply a metabolomics approach to shed lights on:

  • The prevalence of exogenous phenolic metabolites, strictly related to (poly)phenols, in comparison to their endogenous production.
  • The endogenous/exogenous ratio of common low molecular weight catabolites generally obtained in the framework of a varied and balanced diet.
  • The ability of specific nutrients (carbohydrates, proteins and lipids) and non-nutrient compounds ((poly)phenols) to influence the endo/exo phenolic ratio, considering also differences in the gut microbiota profile.