Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial

Jesús F García-Gavilán; Alessandro Atzeni; Nancy Babio; Liming Liang; Clara Belzer; Jesús Vioque; Dolores Corella; Montserrat Fitó; Josep Vidal; Isabel Moreno-Indias; Laura Torres-Collado; Oscar Coltell; Estefanía Toledo; Clary Clish; Javier Hernando; Huan Yun; Adrián Hernández-Cacho; Sarah Jeanfavre; Courtney Dennis; Ana M Gómez-Pérez; Maria Angeles Martínez; Miguel Ruiz-Canela; Francisco J Tinahones; Frank B Hu; Jordi Salas-Salvadó

doi:10.1016/j.ajcnut.2024.02.021

Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial

Am J Clin Nutr. 2024 Feb 29:S0002-9165(24)00167-9. doi: 10.1016/j.ajcnut.2024.02.021. Online ahead of print.

Authors

Jesús F García-Gavilán¹, Alessandro Atzeni², Nancy Babio¹, Liming Liang³, Clara Belzer⁴, Jesús Vioque⁵, Dolores Corella⁶, Montserrat Fitó⁷, Josep Vidal⁸, Isabel Moreno-Indias⁹, Laura Torres-Collado⁵, Oscar Coltell¹⁰, Estefanía Toledo¹¹, Clary Clish¹², Javier Hernando⁷, Huan Yun³, Adrián Hernández-Cacho¹³, Sarah Jeanfavre¹², Courtney Dennis¹², Ana M Gómez-Pérez⁹, Maria Angeles Martínez¹, Miguel Ruiz-Canela¹¹, Francisco J Tinahones⁹, Frank B Hu¹⁴, Jordi Salas-Salvadó¹⁵

Affiliations

¹ CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Departament de Bioquímica i Biotecnologia, Alimentaciò, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Universitat Rovira i Virgili, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain.
² CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Departament de Bioquímica i Biotecnologia, Alimentaciò, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Universitat Rovira i Virgili, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain. Electronic address: alessandro.atzeni@urv.cat.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
⁴ Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
⁵ CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernández (ISABIAL-UMH), Alicante, Spain.
⁶ CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Department of Preventive Medicine, University of Valencia, Valencia, Spain.
⁷ CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Unit of Cardiovascular Risk and Nutrition, Institut Hospital del Mar de Investigaciones Médicas Municipal d'Investigació Médica (IMIM), Barcelona, Spain.
⁸ CIBER Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Endocrinology, Institut d'Investigacions Biomédiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
⁹ CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain.
¹⁰ CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Department of Computer Languages and Systems, Jaume I University, Castellón, Spain.
¹¹ CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain; Epidemiología y Salud Pública, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
¹² Metabolomics Platform, The Broad Institute of MIT and Harvard, Boston, MA, United States.
¹³ Departament de Bioquímica i Biotecnologia, Alimentaciò, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Universitat Rovira i Virgili, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain.
¹⁴ Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, United States; Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.
¹⁵ CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Departament de Bioquímica i Biotecnologia, Alimentaciò, Nutrició, Desenvolupament i Salut Mental (ANUT-DSM), Universitat Rovira i Virgili, Reus, Spain; Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus, Spain. Electronic address: jordi.salas@urv.cat.

PMID: 38428742
DOI: 10.1016/j.ajcnut.2024.02.021

Abstract

Background: The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood.

Objectives: Our goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors.

Methods: A total of 400 participants (200 from each study group), aged 55-75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota.

Results: Compared with the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular disease risk factors. We identified intervention effects on 4 stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular disease risk factors. In addition, we observed a reduction in the abundance of the genera Eubacterium hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 y of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular disease risk factors.

Conclusions: An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).

Keywords: Mediterranean diet; cardiovascular disease risk factor; fecal metabolome; fecal microbiota; lifestyle intervention; metabolic syndrome.