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The authors thank all PREDIMED-Plus participants and investigators. CIBEROBN, CIBERESP, and CIBERDEM are initiative of the Instituto de Salud Carlos III (ISCIII), Madrid, Spain. The authors also thank the PREDIMED-Plus Biobank Network as a part of the National Biobank Platform of the ISCIII for storing and managing the PREDIMED-Plus biological samples. This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS), which is co-funded by the European Regional Development Fund (six coordinated FIS projects lead by J.S.-S. and J.Vi., including the following projects: PI13/00233, PI13/00728, PI13/00462, PI14/01206, PI14/ 00696, PI16/00533, PI16/00366, PI16/00501, PI17/01441, PI17/00855, PI19/00017, PI19/00781, PI19/00576, PI20/00557, PI21/0046; the Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant to J.S.-S.; the Recercaixa (number 2013ACUP00194) grant to J.S.-S.; grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/ 2017/017 and PROMETEO/2021/21 grants from the Conselleria de Innovacion, Universidades, Ciencia y Sociedad Digital from the Generalitat Valenciana; and by NIH grant R01DK127601. This research was also partially funded by the Eat2beNICE/H2020-SFS-2016-2 EU- H2020 European grant, and the Horizon 2020 PRIME study (Prevention and Remediation of Insulin Multimorbidity in Europe; grant agreement #847879). J.S.-S., the senior author of this paper, was partially supported by ICREA under the ICREA Academia programme. A.H.-C. is supported by a predoctoral grant from Marti Franques- INVESTIGO research fellowship funded and supported by NextGenerationEU, Servicio Publico de Empleo Estatal and Universitat Rovira i Virgili (2022PMF-INV-01). I.M.-I. was supported by a Miguel Servet type II grant from Instituto de Salud Carlos III, Madrid, Spain (CPII21/00013). J.N. is supported by a predoctoral grant from Ministerio de Ciencia, Innovacion y Universidades (FPU 20/00385). None of the funding sources took part in the design, collection, analysis, interpretation of the data, writing the report, or in the decision to submit the manuscript for publication.

Analysis of institutional authors

Munné Cuevas, José CarlosAuthorGarcia-Gavilan, Jesus FCorresponding AuthorAtzeni, AlessandroAuthorBabio, NancyAuthorSalas-Salvado, JordiCorresponding Author

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May 10, 2025
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Article

Multi-omics approach identifies gut microbiota variations associated with depression

Publicated to:Npj Biofilms And Microbiomes. 11 (1): 68- - 2025-04-28 11(1), DOI: 10.1038/s41522-025-00707-9

Authors: Hernandez-Cacho, Adrian; Garcia-Gavilan, Jesus F; Atzeni, Alessandro; Konstanti, Prokopis; Belzer, Clara; Vioque, Jesus; Corella, Dolores; Fito, Montserrat; Vidal, Josep; Mela, Virginia; Liang, Liming; Torres-Collado, Laura; Coltell, Oscar; Babio, Nancy; Clish, Clary; Hernando-Redondo, Javier; Martinez-Gonzalez, Miguel A; Wang, Fenglei; Moreno-Indias, Isabel; Ni, Jiaqi; Dennis, Courtney; Ruiz-Canela, Miguel; Tinahones, Francisco J; Hu, Frank B; Salas-Salvado, Jordi

Affiliations

Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA USA - Author
Broad Inst Harvard & MIT, Boston, MA USA - Author
Harvard Med Sch, Boston, MA USA - Author
Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA - Author
Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA - Author
Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA - Author
Hosp Univ Virgen de la Victoria, Dept Endocrinol & Nutr, Inst Invest Biomed Malaga, Malaga, Spain - Author
Inst Hosp del Mar Invest Med Municipal Invest Med, Unit Cardiovasc Risk & Nutr, Barcelona, Spain - Author
Inst Invest Sanitaria Pere Virgili IISPV, Reus, Spain - Author
Inst Salud Carlos III ISCIII, CIBER Diabet & Enfermedades Metab CIBERDEM, Madrid, Spain - Author
Inst Salud Carlos III, CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain - Author
Inst Salud Carlos III, CIBER Fisiopatol Obes & Nutr, Madrid, Spain - Author
Jaume I Univ, Dept Comp Languages & Syst, Castellon De La Plana, Castellon, Spain - Author
Navarra Inst Hlth Res, IdiSNA, Pamplona, Spain - Author
Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi Sunyer IDIBAPS, Dept Endocrinol, Barcelona, Spain - Author
Univ Miguel Hernandez ISABIAL UMH, Inst Invest Sanitaria & Biomed Alicante, Alicante, Spain - Author
Univ Navarra, Dept Prevent Med & Publ Hlth, Pamplona, Spain - Author
Univ Rovira i Virgili, Dept Bioquim & Biotecnol Alimentacio Nutr, Reus, Spain - Author
Univ Valencia, Dept Prevent Med, Valencia, Spain - Author
Wageningen Univ, Lab Microbiol, Wageningen, Netherlands - Author
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Abstract

The gut microbiota plays a potential role in the pathophysiology of depression through the gut-brain axis. This cross-sectional study in 400 participants from the PREDIMED-Plus study investigates the interplay between gut microbiota and depression using a multi-omics approach. Depression was defined as antidepressant use or high Beck Depression Inventory-II scores. Gut microbiota was characterized by 16S rRNA sequencing, and faecal metabolites were analysed via liquid chromatography-tandem mass spectrometry. Participants with depression exhibited significant differences in gut microbial composition and metabolic profiles. Differentially abundant taxa included Acidaminococcus, Christensenellaceae R-7 group, and Megasphaera, among others. Metabolomic analysis revealed 15 significantly altered metabolites, primarily lipids, organic acids, and benzenoids, some of which correlated with gut microbial features. This study highlights the interplay between the gut microbiota and depression, paving the way for future research to determine whether gut microbiota influences depression pathophysiology or reflects changes associated with depression.

Keywords

AgedBacteriaCross-sectional studiesDepressionFecesFemaleGastrointestinal microbiomeGeneHumansInflammationLifMaleMediterranean dietMetabolismMetabolomeMetabolomicsMiddle agedMultiomicsPopulationRna, ribosomal, 16sSymptom severityTandem mass spectrometryTryptophanValidity

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Npj Biofilms And Microbiomes due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 11/177, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biotechnology & Applied Microbiology. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-10-02:

  • WoS: 2
  • Scopus: 2

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-10-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 18.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 18 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 23.35.
  • The number of mentions on the social network X (formerly Twitter): 4 (Altmetric).
  • The number of mentions in news outlets: 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/20.500.11797/imarina9452919

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Netherlands; United States of America.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Hernandez-Cacho, Adrian) and Last Author (Salas Salvadó, Jorge).

the authors responsible for correspondence tasks have been García Gavilán, Jesús Francisco and Salas Salvadó, Jorge.