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

ABSTRACT

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 https://www.controlled-trials.com (ISRCTN35739639).

KEYWORDS:

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

Acknowledgments

We thank to Stephanie Lonsdale for her help in editing the English text. EAA thanks to CONACYT (Mexico) for the postdoctoral fellowship (2018-000022-01EXTV-00459). JSS gratefully acknowledges the financial support by ICREA under the ICREA Academia programme. CIBERFES, CIBEROBN, and CIBERESP are initiatives of the Instituto de Salud Carlos III (ISCIII), Madrid, Spain. The authors’ contributions were as follows: EAA, OC, and MF designed the research; AH, DC, ER, RE, JSS, MRC, and RdlT participated in the design of research and data collection; AH, DC, DMA, OP, JV, OCo, LN, MF and OC conducted the research; IS provided methodologic and statistical assistance; EAA analyzed data and wrote the paper; AH, DC, MF, OCo and OC interpreted data and revised manuscript for important intellectual content. OC had primary responsibility for final content. All authors have read and approved the final manuscript.

Disclosure statement

Dr. Ros reports grants, personal fees, non-financial support and other from California Walnut Commission, outside the submitted work. Dr. Estruch reports grants and personal fees from Fundación Cerveza y Salud, Spain; personal fees from FIVIN, Spain; and personal fees from Wine and Culinary International International Forum, outside the submitted work. Dr. Salas-Salvadó reports personal fees from Instituto Danone, personal fees from Danone SA, personal fees from Aguas Font Vella Lanjarón, grants from Eroski Distributors, grants, non-financial support and other from Nut and Dried Fruit Foundation, non-financial support from Nuts for Life, outside the submitted work.

Additional information

Funding

This work was supported by the Agència de Gestió d’Ajuts Universitaris i de Recerca [grant number 2017 SGR 222]; Fundació La Marató de TV3 [grant number 201512.31]; and the Instituto de Salud Carlos III [grant numbers JR17/00022 and PI15/00047].

Notes on contributors

Enrique Almanza-Aguilera

Enrique Almanza-Aguilera is a junior postdoctoral researcher at the Cardiovascular Risk and Nutrition research group of the Hospital del Mar Research Institute.

Alvaro Hernáez

Alvaro Hernáez is a junior postdoctoral researcher at the Cardiovascular Risk, Nutrition and Aging Research Unit of the August Pi i Sunyer Biomedical Research Institute.

Dolores Corella

Dolores Corella is professor at the department of internal medicine of the University of Valencia, and member of the steering committee of PREDIMED study.

Daniel Muñoz Aguayo

Daniel Muñoz Aguayo is a laboratory technician at the Cardiovascular Risk and Nutrition research group of the Hospital del Mar Research Institute.

Emilio Ros

Emilio Ros is professor at the department of internal medicine of University of Barcelona, and member of the steering committee of PREDIMED study.

Olga Portolés

Olga Portolés is professor at the department of internal medicine of the University of Valencia.

Julieta Valussi

Julieta Valussi is a master student at the Cardiovascular Risk and Nutrition research group of the Hospital del Mar Research Institute.

Ramon Estruch

Ramon Estruch is professor of the department of internal medicine of University of Barcelona, and member of the steering committee of PREDIMED study.

Oscar Coltell

Oscar Coltell is professor at the department of computer science and languages of the University Jaume I.

Isaac Subirana

Isaac Subirana is statistician at the Cardiovascular Epidemiology and Genetics Research group of the Hospital del Mar Research Institute.

Jordi Salas-Salvadó

Jordi Salas-Salvadó is professor at the Hospital Rovira i Virgili University, and member of the steering committee of PREDIMED study.

Miguel Ruiz-Canela

Miguel Ruiz-Canela is professor at the department of preventive medicine and public health of the University of Navarra.

Rafael de la Torre

Rafael de la Torre is head of the integrative pharmacology and systems neuroscience research group of the Hospital del Mar Research Institute.

Lara Nonell

Lara Nonell is head of the Microarrays analysis service of the Hospital del Mar Research Institute.

Montserrat Fitó

Montserrat Fitó is head of the Cardiovascular Risk and Nutrition research group of the Hospital del Mar Research Institute, and member of the steering committee of PREDIMED study.

Olga Castañer

Olga Castañer is a senior postdoctoral researcher at the Cardiovascular Risk and Nutrition research group of the Hospital del Mar Research Institute.