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Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status

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dc.contributor.author Mayneris Perxachs, Jordi
dc.contributor.author Arnoriaga Rodríguez, María
dc.contributor.author Luque-Córdoba, Diego
dc.contributor.author Priego-Capote, Feliciano
dc.contributor.author Pérez Brocal, Vicente
dc.contributor.author Moya, Andrés
dc.contributor.author Burokas, Aurelijus, 1982-
dc.contributor.author Maldonado, Rafael, 1961-
dc.contributor.author Fernández Real, Jose M.
dc.date.accessioned 2021-12-03T07:37:23Z
dc.date.available 2021-12-03T07:37:23Z
dc.date.issued 2020
dc.identifier.citation Mayneris-Perxachs J, Arnoriaga-Rodríguez M, Luque-Córdoba D, Priego-Capote F, Pérez-Brocal V, Moya A, et al. Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status. Microbiome. 2020 Sep 20; 8(1):136. DOI: 10.1186/s40168-020-00913-x
dc.identifier.issn 2049-2618
dc.identifier.uri http://hdl.handle.net/10230/49143
dc.description.abstract Background: Gonadal steroid hormones have been suggested as the underlying mechanism responsible for the sexual dimorphism observed in metabolic diseases. Animal studies have also evidenced a causal role of the gut microbiome and metabolic health. However, the role of sexual dimorphism in the gut microbiota and the potential role of the microbiome in influencing sex steroid hormones and shaping sexually dimorphic susceptibility to disease have been largely overlooked. Although there is some evidence of sex-specific differences in the gut microbiota diversity, composition, and functionality, the results are inconsistent. Importantly, most of these studies have not taken into account the gonadal steroid status. Therefore, we investigated the gut microbiome composition and functionality in relation to sex, menopausal status, and circulating sex steroids. Results: No significant differences were found in alpha diversity indices among pre- and post-menopausal women and men, but beta diversity differed among groups. The gut microbiota from post-menopausal women was more similar to men than to pre-menopausal women. Metagenome functional analyses revealed no significant differences between post-menopausal women and men. Gonadal steroids were specifically associated with these differences. Hence, the gut microbiota of pre-menopausal women was more enriched in genes from the steroid biosynthesis and degradation pathways, with the former having the strongest fold change among all associated pathways. Microbial steroid pathways also had significant associations with the plasma levels of testosterone and progesterone. In addition, a specific microbiome signature was able to predict the circulating testosterone levels at baseline and after 1-year follow-up. In addition, this microbiome signature could be transmitted from humans to antibiotic-induced microbiome-depleted male mice, being able to predict donor's testosterone levels 4 weeks later, implying that the microbiota profile of the recipient mouse was influenced by the donor's gender. Finally, obesity eliminated most of the differences observed among non-obese pre-menopausal women, post-menopausal women, and men in the gut microbiota composition (Bray-Curtis and weighted unifrac beta diversity), functionality, and the gonadal steroid status. Conclusions: The present findings evidence clear differences in the gut microbial composition and functionality between men and women, which is eliminated by both menopausal and obesity status. We also reveal a tight link between the gut microbiota composition and the circulating levels of gonadal steroids, particularly testosterone. Video Abstract.
dc.description.sponsorship This work was partially supported by research grants FIS (PI15/01934) from the Instituto de Salud Carlos III from Spain, SAF2015-65878-R and AEI-SAF2017-84060-R from Ministry of Economy and Competitiveness, Prometeo/2018/A/133 from Generalitat Valenciana, Spain, and also by European Commission (FP7, NeuroPain #2013-602891; #H2020-SC1-2019-2-RTD-848099 (PAINFACT)), the Catalan Government (AGAUR, #SGR2017-669, ICREA Academia Award 2015), the Spanish Instituto de Salud Carlos III (RTA, #RD16/0017/0020), the Fondo Europeo de Desarrollo Regional (FEDER) through the Programa Interreg V-A España-Francia-Andorra (POCTEFA 2014-2020), and the European Regional Development Fund (project No. 01.2.2-LMT-K-718-02-0014) under grant agreement with the Research Council of Lithuania (LMTLT). María Arnoriaga Rodríguez is funded by a predoctoral Río Hortega contract (CM19/00190, co-funded by European Social Fund “Investing in your future”) from the Instituto de Salud Carlos III, Spain. Jordi Mayneris-Perxachs is funded by the Miguel Servet Program from the Instituto de Salud Carlos III (ISCIII CP18/00009), co-funded by the European Social Fund “Investing in your future”.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.rights Copyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/s40168-020-00913-x
dc.subject.keyword Gender
dc.subject.keyword Gonadal steroids
dc.subject.keyword Microbiome
dc.subject.keyword Sex
dc.subject.keyword Sexual dimorphism
dc.subject.keyword Testosterone
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848099
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-65878-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-84060-R
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/602891
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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