Article Text

Original research
Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake
  1. Victoria Meslier1,
  2. Manolo Laiola2,
  3. Henrik Munch Roager3,
  4. Francesca De Filippis2,4,
  5. Hugo Roume1,
  6. Benoit Quinquis1,
  7. Rosalba Giacco5,
  8. Ilario Mennella2,
  9. Rosalia Ferracane2,
  10. Nicolas Pons1,
  11. Edoardo Pasolli2,4,
  12. Angela Rivellese4,6,
  13. Lars Ove Dragsted3,
  14. Paola Vitaglione2,4,
  15. Stanislav Dusko Ehrlich1,
  16. Danilo Ercolini2,4
  1. 1 Université Paris-Saclay, INRAE, MGP, Jouy-en-Josas, France
  2. 2 Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy
  3. 3 Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark
  4. 4 Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy
  5. 5 Institute of Food Science of CNR, Avellino, Italy
  6. 6 Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
  1. Correspondence to Professor Danilo Ercolini, Department of Agricultural Sciences, University of Naples Federico II, Portici 80055, Italy; ercolini{at}; Professor Stanislav Dusko Ehrlich, Metagenopolis, INRAE, 78350 Jouy en Josas, France; stanislav.ehrlich{at}; Dr Paola Vitaglione, Department of Agricultural Sciences, University of Naples Federico II, Portici 80055, Italy; paola.vitaglione{at}


Objectives This study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease.

Design Eighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period.

Results Increased MD adherence in the MedD group successfully reprogrammed subjects’ intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading Faecalibacterium prausnitzii and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa.

Conclusion Switching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health.

  • intestinal microbiology
  • diet
  • nutrition

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Supplementary materials


  • Twitter @hroager, @hroager, @DaniloErcolini

  • VM, ML and HMR contributed equally.

  • Contributors The principal investigators (DE, DSE and LOD) and the other coapplicants (PV) designed the study and obtained funding. The nutritional intervention was carried out at the University of Naples Federico II by AAR, RG, IM and PV. HMR, RF, LOD and PV generated and analysed the metabolomics data. HR and BQ generated the metagenomics data, and ML, VM, FDF, EP and NP analysed the microbiome data and performed the statistical analyses. All authors participated in the data interpretation; DE wrote the paper with contributions by ML, HMR, PV and VM. All authors read, edited and approved the final version of the manuscript.The corresponding authors attest that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding The study was conducted within the Diet-Induced Arrangement of the gut Microbiome for the Improvement of Cardiometabolic health (DINAMIC) project funded within the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL) – Joint Action “Intestinal Microbiomics”. The DINAMIC national funding organization are (i) the Italian Ministry of Education, University and Research (prot.0000426); (ii) the Innovation Fund Denmark (grant # 5195‐00001B) and (iii) the French National Research agency (ANR-15-HDIM-0002-04). The study was also partially supported by a Semper Ardens grant to Lars Ove Dragsted and the Metagenopolis grant ANR-11-DPBS-0001.A full list of the DINAMIC consortium and their affiliations appears in the online supplementary material.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The trial was conducted at the University of Naples Federico II and was approved by the related Ethics Committee (Protocol number: 108/16)

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

  • Data availability statement Data are available in a public, open access repository. Metagenomic reads generated in this study are available (without conditions of reuse) under the accession number PRJEB33500 at the European Nucleotide Archive (ENA) in EBI (

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