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性别差异和睾酮通过胆汁酸信号通路干扰肠道微生物群的结构。

Sex differences and testosterone interfere with the structure of the gut microbiota through the bile acid signaling pathway.

作者信息

Duan Xueqing, Nie Yinli, Xie Xin, Zhang Qi, Zhu Chen, Zhu Han, Chen Rui, Xu Jun, Zhang Jinqiang, Yang Changfu, Yu Qi, Cai Kun, Wang Yong, Tian Weiyi

机构信息

School of Basic Medical Sciences, Guizhou University of Traditional Chinese Medicine, Gui Yang, China.

CAS-Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

出版信息

Front Microbiol. 2024 Oct 18;15:1421608. doi: 10.3389/fmicb.2024.1421608. eCollection 2024.

DOI:10.3389/fmicb.2024.1421608
PMID:39493843
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11527610/
Abstract

BACKGROUND

The gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism.

METHODS

16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues.

RESULTS

The composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically , , , and ) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway.

CONCLUSION

Sex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway.

摘要

背景

肠道微生物群对人类健康有重大影响,会导致一系列健康问题的出现和发展,包括炎症性和自身免疫性疾病、代谢紊乱、心血管问题以及精神疾病。值得注意的是,临床观察表明,这些疾病在发病率和表现上存在性别差异。本研究旨在评估肠道微生物群的组成是否与性别特异性差异相关,并阐明其机制。

方法

采用16S - rRNA测序技术、激素分析、肠道微生物群移植、性腺切除术和激素治疗来研究肠道微生物群与性别或性激素之间的相关性。同时,对肝脏和回肠组织中参与胆汁酸信号通路的基因和蛋白质进行分析。

结果

在年轻和中年的斯普拉格 - 道利(SD)大鼠中,空肠和粪便中的微生物群组成和多样性以及血清中性激素水平存在性别差异。然而,在老年大鼠中未发现类似现象。有趣的是,无论在年轻、中年还是老年大鼠中,空肠和粪便中的微生物群组成和细菌多样性都存在差异。肠道微生物群移植、性腺切除术和激素替代也表明,激素,特别是睾酮(T),会影响大鼠肠道微生物群的组成。同时,参与胆汁酸信号通路的基因(具体为 、 、 和 )的mRNA和蛋白质水平表现出性别特异性差异,T可能在介导该通路的表达中起重要作用。

结论

肠道微生物群结构的性别特异性差异由T通过胆汁酸信号通路介导,这表明性别差异和T水平可能通过胆汁酸信号通路改变肠道微生物群的组成,为疾病预防和管理技术指明了潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/a8af805b2405/fmicb-15-1421608-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/ea8837b5fb9c/fmicb-15-1421608-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/e08ed03db67c/fmicb-15-1421608-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/64d0425d6a59/fmicb-15-1421608-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/5cf0a009bc21/fmicb-15-1421608-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/3c4b0ef59b44/fmicb-15-1421608-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/8e30cb1900a8/fmicb-15-1421608-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/7616f9c31b90/fmicb-15-1421608-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/79568c4b390b/fmicb-15-1421608-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/a8af805b2405/fmicb-15-1421608-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/ea8837b5fb9c/fmicb-15-1421608-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/e08ed03db67c/fmicb-15-1421608-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/64d0425d6a59/fmicb-15-1421608-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/5cf0a009bc21/fmicb-15-1421608-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/3c4b0ef59b44/fmicb-15-1421608-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/8e30cb1900a8/fmicb-15-1421608-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/7616f9c31b90/fmicb-15-1421608-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/79568c4b390b/fmicb-15-1421608-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a96/11527610/a8af805b2405/fmicb-15-1421608-g009.jpg

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