Integrated microbiome and metabolomic analysis reveals associations between vaginal microbiota composition and psychological profiles

The vaginal microbiota plays a key role in women’s health and is increasingly linked to psychobiological processes, although underlying mechanisms remain poorly understood. This study investigated the relationship between vaginal community state types (CSTs), psychological dimensions, and vaginal metabolites in 105 reproductive-aged women. Vaginal microbiota composition was characterised through 16 S rRNA gene sequencing and classified into CSTs; metabolomic profiling was performed using NMR spectroscopy.

Participants completed validated questionnaires assessing trait anxiety, emotion regulation, behavioural inhibition/activation, depressive symptoms, perceived stress, and somatisation. Women with polymicrobial CST IV profiles showed significantly lower Behavioural Activation System (BAS)-Reward Responsiveness and BAS-Drive scores, whereas those with Lactobacillus iners-dominated CST III exhibited lower Behavioural Inhibition System (BIS) scores. Limited direct correlations between bacterial taxa and psychological variables emerged, but psychological dimensions strongly correlated with specific vaginal metabolites.

Exploratory mediation analyses indicated that aminobutyrate and valine partially or fully mediated the associations between CST IV and BAS dimensions, while phenylalanine partially mediated the relationship between CST IV and BIS inhibition. These findings suggest that the vaginal metabolome may represent a functional interface linking microbial community structure and psychological functioning, supporting a biopsychosocial perspective of vaginal health and the importance of integrating microbiome, metabolomic, and psychological assessments in women’s health research. The authors would like to thank all the participants who took part in the study.

The authors declare that financial support was received for the research and/or publication of this article. Paola Castellano was supported by a doctoral fellowship of the National Operation Program (PON) Research and Innovation 2014–2020 (CCI. 2014IT16M2OP005), ESF REACT-EU resources, Action IV.5 “Doctorates on Green themes.” CUP code J35F21003350006. Silvia Conti was supported by the European Union-funded grant -NextGenerationEU - Mission 4, Component 2, Investiment 1.1, 2023-PRIN-VS_001 -PRIN 2022 -CUP F53D23007190006; and by the INVAT project, CNR FOE 2022, CUP B53C22010140001.

Camilla Ceccarani’s research grant was supported by the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.4 -Call for tender No. 3138 of 16 December 2021, rectified by Decree n.3175 of 18 December 2021 of Italian Ministry of University and Research funded by the European Union -NextGenerationEU; Award Number: Project code CN_00000033, Concession Decree No. 1034 of 17 June 2022 adopted by the Italian Ministry of University and Research, CUP: B83C22002930006, Project title “National Biodiversity Future Center -NBFC”. Marielle Ezekielle Djusse was supported by the European Union-funded grant -NextGenerationEU from the National Recovery and Resilience Plan (NRRP) Mission 4, Component 1, Investment 3.4 (DM 118/2023) -Digital and Environmental Transitions -CUP: J33C23002390002. The study funders had no involvement in the design and conduct of the study, collection, management, analysis and interpretation of data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Paola Castellano, Silvia Conti and Claudio Foschi contributed equally to this work as first authors. Antonella Marangoni and Michela Mazzetti contributed equally to this work as last authors. Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, Bologna, Italy Paola Castellano, Claudio Foschi, Marielle Ezekielle Djusse, Antonella Marangoni & Michela Mazzetti Department of Psychology, Sapienza University of Rome, Via dei Marsi 78, Rome, Italy Institute of Biomedical Technologies - National Research Council, Via Fratelli Cervi 93, Segrate, Milan, 20054, Italy Silvia Conti, Tania Camboni, Camilla Ceccarani, Clarissa Consolandi, Marco Severgnini & Federica Prinelli Department of Medical Sciences, University of Ferrara, Via Luigi Borsari 46, Ferrara, 44121, Italy Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Massarenti 9, Bologna, Italy Collegio Superiore of Alma Mater Studiorum, International PhD College, University of Bologna, Bologna, Italy Human Nutrition Unit, Department of Agricultural and Food Sciences (DISTAL), University of Bologna, Cesena, Italy Centre of Foodomics, Department of Agricultural and Food Sciences (DISTAL), University of Bologna, Cesena, Italy The authors declare no competing interests.