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Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status.
Microbiome ( IF 15.5 ) Pub Date : 2020-09-20 , DOI: 10.1186/s40168-020-00913-x
Jordi Mayneris-Perxachs 1, 2 , María Arnoriaga-Rodríguez 1, 2 , Diego Luque-Córdoba 3, 4 , Feliciano Priego-Capote 3, 4 , Vicente Pérez-Brocal 5, 6 , Andrés Moya 5, 6, 7 , Aurelijus Burokas 8, 9 , Rafael Maldonado 8, 10 , José-Manuel Fernández-Real 1, 2
Affiliation  

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. 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. 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.

中文翻译:

肠道菌群类固醇性二态及其对性腺类固醇的影响:肥胖和更年期状态的影响。

有人建议将性腺甾体激素作为在代谢性疾病中观察到的性二态性的潜在机制。动物研究还证明了肠道微生物组与代谢健康之间的因果关系。但是,在肠道菌群中性二态性的作用以及微生物组在影响性类固醇激素和形成对疾病的性二态易感性方面的潜在作用已被大大忽略。尽管有一些证据表明肠道菌群的多样性,组成和功能存在性别特异性差异,但结果不一致。重要的是,这些研究大多数都没有考虑到性腺类固醇的状态。因此,我们研究了与性别,绝经状态和循环性类固醇有关的肠道微生物组组成和功能。绝经前后男女之间的α多样性指数均无显着差异,但各组之间的β多样性不同。绝经后女性的肠道菌群与男性相似,而不是绝经前女性。元基因组功能分析显示,绝经后男女之间无显着差异。性腺类固醇与这些差异特别相关。因此,绝经前妇女的肠道菌群富含类固醇生物合成和降解途径的基因,前者在所有相关途径中的折叠变化最强。微生物类固醇途径也与睾丸激素和孕激素的血浆水平显着相关。此外,特定的微生物组特征能够预测基线和1年随访后的循环睾丸激素水平。此外,这种微生物组特征可以从人身上传播到抗生素诱导的微生物组枯竭的雄性小鼠中,从而能够在4周后预测供体的睾丸激素水平,这暗示着受体小鼠的微生物群分布受到了供体性别的影响。最后,肥胖消除了非肥胖的绝经前妇女,绝经后妇女和男性在肠道菌群组成(Bray-Curtis和加权unifracβ多样性),功能和性腺类固醇状态方面观察到的大多数差异。本研究结果表明,男女肠道微生物组成和功能的差异明显,而绝经和肥胖状态均可消除。
更新日期:2020-09-21
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