Transcriptional response to a Mediterranean diet intervention exerts a modulatory effect on neuroinflammation signaling pathway

Enrique Almanza-Aguilera, Alvaro Hernáez, Dolores Corella, Daniel Muñoz Aguayo, Emilio Ros, Olga Portolés, Julieta Valussi, Ramon Estruch, Oscar Coltell, Isaac Subirana, Jordi Salas-Salvadó, Miguel Ruiz-Canela, Rafael de la Torre, Lara Nonell, Montserrat Fitó, Olga Castañer

Research output: Indexed journal article Articlepeer-review

6 Citations (Scopus)


Background: The Traditional Mediterranean Diet (TMD) is known to have beneficial effects on several chronic diseases. However, data concerning the whole transcriptome modulation of the TMD are scarce. Objective: We aimed to explore the effects of the TMD on the whole transcriptome of individuals at high cardiovascular risk. Methods: Thirty-four participants at high cardiovascular risk were randomly assigned to a TMD enriched with extra-virgin olive oil (TMD + VOO), mixed nuts (TMD + Nuts), or a control diet based on low-fat diet recommendations. A microarray analysis in circulating peripheral blood mononuclear cells of the participants was conducted before and after 3 months of the intervention. The association of changes in gene expression was modeled into canonical pathways by conducting an untargeted functional analysis with the Ingenuity Pathway Analysis® (IPA). Effects were considered significant when the absolute z-score values were ≥2.0 and the logarithm P (adjusted by the Benjamini–Hochberg procedure [BH]) values were ≥1.30. Results: According to IPA, interventions with TMD + Nuts, TMD + VOO, and control diet downregulated neuroinflammation, triggering receptor expressed on myeloid cells 1, and cholecystokinin/gastrin-mediated signaling pathways, respectively. The gene expression among these pathways included cytokines, T-cell activation receptors, nuclear factor kappa β/inflammasome components, pro-inflammatory enzymes and cell cycle regulators. Conclusion: The current findings suggest that the TMD enriched with mixed nuts or VOO downregulate transcriptomic pathways, including those related to neuroinflammation, which could influence development of neurodegenerative diseases. Our data should be corroborated in other tissue cells, such as neurons and glial cells. The PREDIMED trial was registered at (ISRCTN35739639).

Original languageEnglish
Pages (from-to)256-265
Number of pages10
JournalNutritional Neuroscience
Issue number2
Publication statusPublished - 2022


  • Mediterranean diet
  • cardiovascular risk
  • extra-virgin olive oil‌
  • functional analysis
  • ingenuity pathway analysis‌
  • microarray
  • neuroinflammation
  • nuts
  • transcriptome


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