激素替代疗法可逆转卵巢早衰引起的肠道微生物组和血清代谢组的改变。
Hormone Replacement Therapy Reverses Gut Microbiome and Serum Metabolome Alterations in Premature Ovarian Insufficiency.
机构信息
Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Hangzhou, China.
出版信息
Front Endocrinol (Lausanne). 2021 Dec 23;12:794496. doi: 10.3389/fendo.2021.794496. eCollection 2021.
OBJECTIVE
We explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI.
METHODS
Fecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman's rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between and ovarian fibrosis, the mice were inoculated with () through oral gavage.
RESULTS
The abundance of genus significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-β1 levels; this increase was reversed by HRT. The abundance of was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-β1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by in mice.
CONCLUSIONS
The interactions between the gut microbiota, serum metabolites, and serum TGF-β1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-β1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.
目的
本研究旨在探索卵巢早衰（POI）患者的肠道微生物组和血清代谢组变化，以及激素替代疗法（HRT）的影响，以期揭示 POI 的病理机制。
方法
分别采用 16S rRNA 基因测序和非靶向代谢组学分析，对健康女性（HC，n=10）和接受 HRT 治疗（n=10）或未接受 HRT 治疗（n=10）的 POI 患者的粪便和血清样本进行分析。采集外周血样本检测血清激素和细胞因子水平。采用 Spearman 秩相关分析评估性激素和细胞因子之间以及肠道微生物群和血清代谢物之间的相关性。为进一步证实 与卵巢纤维化的相关性，通过口服灌胃将 （）接种到小鼠中。
结果
与 HC 样本相比，POI 患者粪便样本中属 的丰度显著增加，而接受 HRT 治疗的 POI 患者该丰度则降低。POI 患者的血清代谢特征明显改变，血清 TGF-β1 水平升高；HRT 治疗可逆转这一变化。的丰度与代谢特征的改变呈正相关，而代谢特征又与所有受试者的血清 TGF-β1 水平呈正相关。雌激素可改善 诱导的小鼠卵巢纤维化。
结论
POI 患者肠道微生物群、血清代谢物和 TGF-β1 之间的相互作用可能在 POI 的发生发展中起关键作用。HRT 不仅在 POI 患者中模拟了正常卵巢激素的产生，而且还减轻了肠道微生物群失调和血清代谢物及 TGF-β1 水平失衡，这些变化据称与纤维化有关。本研究结果可能为 POI 患者的预防和治疗策略的发展铺平道路。
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