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Higher bacterial DNAemia can affect the impact of a polyphenol-rich dietary pattern on biomarkers of intestinal permeability and cardiovascular risk in older subjects

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Abstract

Purpose

Aging can be characterized by increased systemic low-grade inflammation, altered gut microbiota composition, and increased intestinal permeability (IP). The intake of polyphenol-rich foods is proposed as a promising strategy to positively affect the gut microbiota–immune system–intestinal barrier (IB) axis. In this context, we tested the hypothesis that a PR-dietary intervention would affect the presence of bacterial factors in the bloodstream of older adults.

Methods

We collected blood samples within a randomized, controlled, crossover intervention trial in which older volunteers (n = 51) received a polyphenol-enriched and a control diet. We quantified the presence of bacterial DNA in blood by qPCR targeting the 16S rRNA gene (16S; bacterial DNAemia). Blood DNA was taxonomically profiled via 16S sequencing.

Results

Higher blood 16S levels were associated with higher BMI and markers of IP, inflammation, and dyslipidemia. PR-intervention did not significantly change bacterial DNAemia in the older population (P = 0.103). Nonetheless, the beneficial changes caused by the polyphenol-enriched diet were greatest in participants with higher bacterial DNAemia, specifically in markers related to IP, inflammation and dyslipidemia, and in fecal bacterial taxa. Finally, we found that the bacterial DNA detected in blood mostly belonged to γ-Proteobacteria, whose abundance significantly decreased after the polyphenol-rich diet in subjects with higher bacterial DNAemia at baseline.

Conclusions

This study shows that older subjects with higher bacterial DNAemia experienced a beneficial effect from a polyphenol-rich diet. Bacterial DNAemia may be a further relevant marker for the identification of target populations that could benefit more from a protective dietary treatment.

Registration

This trial was retrospectively registered at www.isrctn.org (ISRCTN10214981) on April 28, 2017.

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Data availability

Data described in the manuscript, code book, and analytic code will be made available upon request in a deidentified form pending review and approval of a formal request to the scientific coordinators of the MaPLE project (patrizia.riso@unimi.it; simone.guglielmetti@unimi.it; candres@ub.edu; paul.kroon@quadram.ac.uk).

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Acknowledgements

We sincerely thank all the volunteers for their valuable contribution and dedication to the study. We are grateful to the nursing and medical staff working at Opera Immacolata Concezione (OIC Foundation, Padua, Italy) for their coordinating activities in the nursing home and for the success of the study.

Funding

This work was completed as part of the MAPLE project (Gut and Blood Microbiomics for Studying the Effect of a Polyphenol-Rich Dietary Pattern on Intestinal Permeability in the Elderly) supported within the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI-HDHL, http://www.healthydietforhealthylife.eu/) granted by Mipaaft (Italy, D.M. 8245/7303/ 2016), MINECO (Spain, PCIN-2015-238), and BBSRC (U.K., BB/R012512/1). This work also received funding from the JPI-HDHL ERA-Net Cofund on INtesTInal MICrobiomics (ERA-HDHL INTIMIC, AC19/00096), CIBERFES funded by Instituto de Salud Carlos III and co-funded by the European Regional Development Fund "A way to make Europe"; 2017SGR1546 grant from the Generalitat de Catalunya’s Agency AGAUR, and ICREA Academia Award 2018. Additional funding was provided by the Biotechnology and Biological Sciences Research Council (UK) through an Institute Strategic Programme Grant (‘Food Innovation and Health’; Grant No. BB/R012512/1 1 and its constituent projects BBS/E/F/000PR10343 (Theme 1, Food Innovation) and BBS/E/F/000PR10346 (Theme 3, Digestion and Fermentation in the Lower GI Tract) to the Quadram Institute Bioscience. TM thanks the “Juan de la Cierva” program from MINECO (IJCI-2017-32534).

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Authors and Affiliations

  1. Division of Food Microbiology and Bioprocesses, Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Via Celoria 2, 20133, Milan, Italy

    Giorgio Gargari, Valentina Taverniti & Simone Guglielmetti

  2. Division of Human Nutrition, Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy

    Cristian Del Bo’ & Patrizia Riso

  3. Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Food Innovation Network (XIA), University of Barcelona, Barcelona, Spain

    Stefano Bernardi, Nicole Hidalgo-Liberona, Tomás Meroño & Cristina Andres-Lacueva

  4. CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Barcelona, Spain

    Stefano Bernardi, Nicole Hidalgo-Liberona, Tomás Meroño & Cristina Andres-Lacueva

  5. Quadram Institute Bioscience, Norwich Research Park, Norwich, UK

    Paul A. Kroon

  6. Geriatria, Accettazione geriatrica e Centro di Ricerca Per l’invecchiamento. IRCCS INRCA, Ancona, Italy

    Antonio Cherubini

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  1. Giorgio Gargari
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  11. Simone Guglielmetti
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Contributions

SG, Guarantor of article. PR and SG designed the trial and in collaboration with AC, CAL, and PAK optimized the study protocol including the development of the polyphenol-rich diet. SG drafted the first version of the manuscript in collaboration with GG, CDB, and PR. Laboratory work was carried out by VT, GG, NHL, and SB. GG performed bioinformatic analyses in collaboration with SG. GG and SG performed the statistical analysis in collaboration with TM. All the authors critically revised the draft and approved the final version.

Corresponding author

Correspondence to Simone Guglielmetti.

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Conflict of interest

None of the authors declares conflict of interest.

Ethical approval

The study protocol was approved by the Ethics Committee of the University of Milan (ref: 6/16/CE_15.02.16_Verbale_All-7). All participants were informed about the study protocol and signed an informed consent before the enrolment.

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Gargari, G., Taverniti, V., Del Bo’, C. et al. Higher bacterial DNAemia can affect the impact of a polyphenol-rich dietary pattern on biomarkers of intestinal permeability and cardiovascular risk in older subjects. Eur J Nutr 61, 1209–1220 (2022). https://doi.org/10.1007/s00394-021-02680-3

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