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Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes

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Abstract

Purpose

There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated.

Methods

Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites.

Results

(Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids.

Conclusions

The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet.

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Acknowledgements

We thank the volunteers who participated in the study, Polly Page for her key role in study steering and management oversight, and the Volunteer Studies and Clinical Services and Sample Management Teams at MRC EWL for their assistance in the conduction of the study. We acknowledge Prof. Alan Crozier (University of California, Davis, USA) for his help with manuscript revision and data discussion. We are also grateful to Gary Williamson (University of Leeds, UK), Denis Barron (Nestle Research Center, Lausanne, Switzerland), and Takao Yokota (Teikyo University, Japan) for the generous gift of a number of phase II metabolites. Dr. Les Bluck, joint senior author for this work, played a fundamental role in the design of the original study; it is with much sadness that his death prevented him from seeing the research come to fruition.

Funding

This work was partially funded by MRC core funding (Physiological Modelling of Metabolic Risk, MC_UP_A090_1005, and Nutrition, Surveys and Studies, MC_U105960384) and University of Parma core funding (FIL 2014-2017). P.M. was partially funded by a Grant of the Postdoctoral Fellowship Program from Fundación Séneca (Murcia Region, Spain). I.A.L. was supported by a postdoctoral fellowship funded by the Spanish Ministry of Economy and Competitiveness (IJCI-2014-20689).

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Author notes

  1. Pedro Mena, Iziar A. Ludwig and Virginia B. Tomatis contributed equally as first author.

  2. Les J. Bluck and Daniele Del Rio contributed equally as last author.

Authors and Affiliations

  1. Human Nutrition Unit, Department of Food and Drugs, University of Parma, Medical School Building C, Via Volturno, 39, 43125, Parma, Italy

    Pedro Mena, Iziar A. Ludwig, Luca Calani, Alice Rosi, Furio Brighenti & Daniele Del Rio

  2. Food Technology Department, Universitat de Lleida-Agrotecnio Center, Lleida, Spain

    Iziar A. Ludwig

  3. UK Medical Research Council Elsie Widdowson Laboratory (formerly MRC Human Nutrition Research), Cambridge, UK

    Virginia B. Tomatis, Animesh Acharjee, Sumantra Ray, Julian L. Griffin & Les J. Bluck

  4. Department of Biochemistry, University of Cambridge, Cambridge, UK

    Virginia B. Tomatis, Animesh Acharjee & Julian L. Griffin

  5. Institute of Cancer and Genomic Sciences, Centre for Computational Biology, University of Birmingham, Birmingham, UK

    Animesh Acharjee

  6. Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

    Animesh Acharjee

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  1. Pedro Mena
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  2. Iziar A. Ludwig
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Contributions

PM and IL designed and conducted research, analyzed data, performed statistical analysis, and wrote the paper; VT designed and conducted research, analyzed data, and performed statistical analysis; AA performed statistical analysis; LC conducted research; AR, FB, and JLG provided critical review of the manuscript; SR designed and conducted research, and provided critical review; LJB designed research; DDR designed research and had primary responsibility for final content. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Pedro Mena or Daniele Del Rio.

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Authors declare no conflict of interest.

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Les J. Bluck is deceased.

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Mena, P., Ludwig, I.A., Tomatis, V.B. et al. Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes. Eur J Nutr 58, 1529–1543 (2019). https://doi.org/10.1007/s00394-018-1683-4

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