肠道菌群通过肠道-性腺轴影响生殖功能的机制
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1)浙江理工大学生命科学与医药学院,杭州 310018;2)浙大宁波理工学院生物与化学工程学院,宁波 315100;3)浙江大学明州医院,宁波 315000

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国家重点研发计划(2022YFD1300301),宁波市重大科技计划项目(2021Z112,2024Z180),宁波市科技特派员项目(2022S225)和宁波市自然科学基金(2022J151,2023J270)资助。


Mechanisms of Gut Microbiota Influencing Reproductive Function via The Gut-Gonadal Axis
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1)College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China;2)School of Biological and Chemical Engineering, NingboTech University, Ningbo 315100, China;3)Zhejiang University Mingzhou Hospital, Ningbo 315000, China

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This work was supported by grants from National Key R&D Program (2022YFD1300301), Ningbo Major Science and Technology Research Project(2021Z112, 2024Z180), Ningbo Science and Technology Special Commissioner Project (2022S225), and Ningbo Natural Science Foundation(2022J151, 2023J270).

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    摘要:

    生殖系统疾病是导致社会生育率下降、老龄化加剧的原因之一,严重危害人们的身心健康和生活质量。近年来的研究揭示,肠道菌群(GM)在改善生殖系统疾病方面表现出巨大的潜力。健康状况下,GM处于动态平衡,而失衡会引起免疫炎症反应、代谢紊乱等,进而诱发生殖系统疾病。肠道菌群组成与男女生殖系统具有密切的因果关系,短链脂肪酸、胆汁酸等典型GM代谢产物通过调控免疫反应、内分泌系统、维生素代谢以及下丘脑-垂体-性腺轴等多种机制影响生殖系统。微生态制剂、粪便微生物群移植以及药物通过调控GM及肠道免疫功能,发挥治疗生殖疾病的作用。本综述主要概括了GM变化与生殖系统疾病的相关性,GM通过肠道-性腺轴影响机体繁殖能力的内在机制及其在生殖疾病治疗领域的研究进展。

    Abstract:

    Reproductive system diseases are among the primary contributors to the decline in social fertility rates and the intensification of aging, posing significant threats to both physical and mental health, as well as quality of life. Recent research has revealed the substantial potential of the gut microbiota in improving reproductive system diseases. Under healthy conditions, the gut microbiota maintains a dynamic balance, whereas dysfunction can trigger immune-inflammatory responses, metabolic disorders, and other issues, subsequently leading to reproductive system diseases through the gut-gonadal axis. Reproductive diseases, in turn, can exacerbate gut microbiota imbalance. This article reviews the impact of the gut microbiota and its metabolites on both male and female reproductive systems, analyzing changes in typical gut microorganisms and their metabolites related to reproductive function. The composition, diversity, and metabolites of gut bacteria, such as Bacteroides, Prevotella, and Firmicutes, including short-chain fatty acids, 5-hydroxytryptamine, γ-aminobutyric acid, and bile acids, are closely linked to reproductive function. As reproductive diseases develop, intestinal immune function typically undergoes changes, and the expression levels of immune-related factors, such as Toll-like receptors and inflammatory cytokines (including IL-6, TNF-α, and TGF-β), also vary. The gut microbiota and its metabolites influence reproductive hormones such as estrogen, luteinizing hormone, and testosterone, thereby affecting folliculogenesis and spermatogenesis. Additionally, the metabolism and absorption of vitamins can also impact spermatogenesis through the gut-testis axis. As the relationship between the gut microbiota and reproductive diseases becomes clearer, targeted regulation of the gut microbiota can be employed to address reproductive system issues in both humans and animals. This article discusses the regulation of the gut microbiota and intestinal immune function through microecological preparations, fecal microbiota transplantation, and drug therapy to treat reproductive diseases. Microbial preparations and drug therapy can help maintain the intestinal barrier and reduce chronic inflammation. Fecal microbiota transplantation involves transferring feces from healthy individuals into the recipient’s intestine, enhancing mucosal integrity and increasing microbial diversity. This article also delves into the underlying mechanisms by which the gut microbiota influences reproductive capacity through the gut-gonadal axis and explores the latest research in diagnosing and treating reproductive diseases using gut microbiota. The goal is to restore reproductive capacity by targeting the regulation of the gut microbiota. While the gut microbiota holds promise as a therapeutic target for reproductive diseases, several challenges remain. First, research on the association between gut microbiota and reproductive diseases is insufficient to establish a clear causal relationship, which is essential for proposing effective therapeutic methods targeting the gut microbiota. Second, although gut microbiota metabolites can influence lipid, glucose, and hormone synthesis and metabolism via various signaling pathways—thereby indirectly affecting ovarian and testicular function—more in-depth research is required to understand the direct effects of these metabolites on germ cells or granulosa cells. Lastly, the specific efficacy of gut microbiota in treating reproductive diseases is influenced by multiple factors, necessitating further mechanistic research and clinical studies to validate and optimize treatment regimens.

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赵亚琪,齐莉莉,王进波,胡徐琦,王梦婷,毛海光,孙秋珍.肠道菌群通过肠道-性腺轴影响生殖功能的机制[J].生物化学与生物物理进展,,():

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  • 收稿日期:2024-11-06
  • 最后修改日期:2025-03-18
  • 接受日期:2025-02-27
  • 在线发布日期: 2025-02-28
  • 出版日期: