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

Microbiome

Jordi Mayneris-Perxachs¹  José-Manuel Fernández-Real¹  María Arnoriaga-Rodríguez¹  Vicente Pérez-Brocal²  Andrés Moya³  Rafael Maldonado⁴  Aurelijus Burokas⁵  Feliciano Priego-Capote⁶  Diego Luque-Córdoba⁶ 

[1] Department of Endocrinology, Diabetes and Nutrition, Departament de Ciències Mèdiques, Hospital of Girona “Dr JosepTrueta”, Girona Biomedical Research Institute (IdibGi), University of Girona, Carretera de França s/n, 17007, Girona, Spain;CIBERobn Pathophysiology of Obesity and Nutrition, Instituto de Salud Carlos III, Madrid, Spain;Department of Genomics and Health, Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO-Public Health), Valencia, Spain;CIBER in Epidemiology and Public Health (CIBEResp), Madrid, Spain;Department of Genomics and Health, Foundation for the Promotion of Health and Biomedical Research of Valencia Region (FISABIO-Public Health), Valencia, Spain;CIBER in Epidemiology and Public Health (CIBEResp), Madrid, Spain;Institute for Integrative Systems Biology (I2SysBio), The University of Valencia and The Spanish National Research Council (CSIC-UVEG), Valencia, Spain;Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain;Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain;Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain;Present address: Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania;Maimónides Institute of Biomedical Research (IMIBIC), Reina Sofía University Hospital, University of Cordoba, Cordoba, Spain;CIBERfes Frailty and Healthy Aging, Instituto de Salud Carlos III, Madrid, Spain;

关键词: Sex;    Gender;    Gonadal steroids;    Testosterone;    Progesterone;    Microbiome;    Sexual dimorphism;   

DOI  :  10.1186/s40168-020-00913-x

来源: Springer

【 摘 要 】

BackgroundGonadal 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.ResultsNo 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.ConclusionsThe 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.2iXSzDgpNvVgxYPgDJLmSKVideo Abstract

【 授权许可】

CC BY