Article Text

Original research
Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries
  1. Tarini Shankar Ghosh1,2,
  2. Simone Rampelli3,
  3. Ian B Jeffery1,2,
  4. Aurelia Santoro4,5,
  5. Marta Neto1,2,
  6. Miriam Capri3,
  7. Enrico Giampieri4,
  8. Amy Jennings6,
  9. Marco Candela3,
  10. Silvia Turroni3,
  11. Erwin G Zoetendal7,
  12. Gerben D A Hermes7,
  13. Caumon Elodie8,
  14. Nathalie Meunier8,
  15. Corinne Malpuech Brugere9,
  16. Estelle Pujos-Guillot10,
  17. Agnes M Berendsen11,
  18. Lisette C P G M De Groot11,
  19. Edith J M Feskins11,
  20. Joanna Kaluza12,
  21. Barbara Pietruszka12,
  22. Marta Jeruszka Bielak12,
  23. Blandine Comte10,
  24. Monica Maijo-Ferre13,
  25. Claudio Nicoletti13,14,
  26. Willem M De Vos7,15,
  27. Susan Fairweather-Tait16,
  28. Aedin Cassidy17,
  29. Patrizia Brigidi18,
  30. Claudio Franceschi19,20,
  31. Paul W O'Toole1,2
  1. 1 School of Microbiology, University College Cork, Cork, Ireland
  2. 2 APC Microbiome Ireland, University College Cork, Cork, Ireland
  3. 3 Unit of Microbial Ecology of Health, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
  4. 4 Department of Experimental, Diagnostic and Speciality Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy
  5. 5 CIG Interdepartmental Centre “L Galvani”, Alma Mater Studiorum, University of Bologna, Bologna, Italy
  6. 6 Norwich Medical School, University of East Anglia Faculty of Medicine and Health Sciences, Norwich, Norfolk, UK
  7. 7 Laboratory of Microbiology, Wageningen University and Research, Wageningen, Netherlands
  8. 8 CRNH Auvergne, F-63000 Clermont-Ferrand, CHU Clermont-Ferrand, Clermont-Ferrand, France
  9. 9 Unité de Nutrition Humaine, Université Clermont Auvergne, Clermont-Ferrand, Auvergne, France
  10. 10 Plateforme d’Exploration du Métabolisme, MetaboHUB Clermont, Clermont-Ferrand, Université Clermont Auvergne, Clermont-Ferrand, Auvergne, France
  11. 11 Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, Netherlands
  12. 12 Department of Human Nutrition, Warsaw University of Life Sciences, Warszawa, Poland
  13. 13 Gut Health Institute Strategic Programme, Quadram Institute Bioscience, Norwich, Norfolk, UK
  14. 14 Department of Experimental and Clinical Medicine, Section of Anatomy, University of Florence, Firenze, Toscana, Italy
  15. 15 Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
  16. 16 Department of Nutrition and Preventive Medicine, Norwich Medical School, University of East Anglia, Norwich, Norfolk, UK
  17. 17 The Institute of Global Food Security, Queen's University Belfast, Belfast, UK
  18. 18 Unit of Microbial Ecology of Health, Department of Pharmacy and Biotechnology, University of Bologna, Bolognas, Italy
  19. 19 Department of Experimental, Diagnostic and Speciality Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Emilia-Romagna, Italy
  20. 20 Department of Applied Mathematics, Institute of Information Technology, Mathematics and Mechanics (ITMM), Lobachevsky State University of Nizhny Novgorod-National Research University (UNN), Nizhny Novgorod, Russian Federation
  1. Correspondence to Dr Paul W O'Toole, School of Microbiology, University College Cork APC Microbiome Institute, Cork T12 YN60, Ireland; pwotoole{at}


Objective Ageing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty.

Design We profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet).

Results Adherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks.

Conclusion Collectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.

  • diet
  • enteric bacterial microflora
  • ageing
  • inflammation
  • intestinal bacteria

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Supplementary materials


  • TSG, SR, IBJ and AS contributed equally.

  • Contributors TSG, IBJ, POT, CF and AS conceived and designed the analysis. MN, AS, MC, EG, AJ, MC, ST, EGZ, GDAH, CE, NM, CMB, EP-G, AM, JK, BP, BC, MN, MM-F and others collected and/or contributed data. TSG, IBJ and SR performed the analysis. TSG, IBJ and POT wrote the paper assisted by SR, AS, PB, EGZ and WMDeV. WMDeV, SF-T, AC, PB, CF, POT and others reviewed the analysis and the manuscript.

  • Funding The authors are funded in part by Science Foundation Ireland (APC/SFI/12/RC/2273) in the form of a research centre, APC Microbiome Ireland. IBJ was supported by a Science Foundation Ireland grant (13/SIRG/2128). The NU-AGE project is supported by the European Union’s Seventh Framework Programme under grant agreement no. 266 486 (‘NU-AGE: New dietary strategies addressing the specific needs of the elderly population for healthy ageing in Europe’).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. The majority of results corresponding to the current study are included in the article or uploaded as supplementary information. Other data are available on request from the authors.

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