Identification of Immunophenotypes as a Mediator of Gut Microbiota-Driven Female Anovulation-Induced Infertility: A Mediation Mendelian Randomization Study

IF 2.4 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology Pub Date : 2025-08-11 DOI:10.1111/aji.70135

Xiyin Wang, Jing Zhang, Xianyuan Yi, Duozhen Chen

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Abstract

Background

The mediatory roles of immune cells in the gut microbiota and anovulation-induced infertility remain unclear. This study aimed to investigate the correlations among gut microbiota, immunophenotypes, and anovulation-induced female infertility using a mediation Mendelian randomization (MR) study.

Methods

An MR design investigates the causal links among gut microbiota (n = 14 306, 195 bacterial taxa), 731 immunophenotypes, and anovulation-induced female infertility (5667 anovulation-induced infertile women and 117 098 controls). The causal effects were evaluated by MR Egger, weighted median, inverse variance weighted (IVW), simple mode method, and weighted mode.

Results

Two phylum members (Cyanobacteria and Bacteroidetes), an order member (Burkholderiales), a family member (Defluviitaleaceae), and seven genus members were causally correlated with the anovulation-induced infertility. Among the seven genera, Subdoligranulum, Clostridium innocuum group, and Escherichia.Shigella were the risk factors, and Prevotella9, Ruminococcus torques group, Eubacterium ventriosum group, and Eubacterium fissicatena group were the protective factors in anovulation-induced infertility. Next, 35 immunophenotypes were identified to be also causally correlated with the anovulation-induced infertility. Among them, 15 immunophenotypes were significantly driven by the seven-microbiota genus and might be the internal mediating mechanism of the influence of gut microbiota on anovulation-induced female infertility. In the mediated MR analysis, four (Clostridium innocuum group, Eubacterium fissicatena group, Eubacterium ventriosum group, and Prevotella9) of the microbiota were directly influenced by six immunophenotypes (T cell, B cell, and dendritic cell panels) and then affected the anovulation-induced infertility.

Conclusion

The mediation MR study provides evidence supporting immunophenotypes as mediators of gut microbiota-influenced female infertility, especially anovulation-induced infertility.

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鉴定免疫表型作为肠道微生物群驱动的女性无排卵诱导不孕的中介：一项中介孟德尔随机研究

背景免疫细胞在肠道菌群和无排卵性不孕中的调节作用尚不清楚。本研究旨在通过孟德尔随机化（MR）研究，探讨肠道微生物群、免疫表型和无排卵诱导的女性不孕症之间的相关性。方法采用磁共振设计研究肠道微生物群（n = 14 306, 195个细菌分类群）、731种免疫表型与无排卵性不孕女性（5667例无排卵性不孕女性和117 098例对照组）之间的因果关系。因果效应评价采用MR Egger、加权中位数、方差加权逆（IVW）、简单模式法和加权模式。结果2门（蓝藻门和拟杆菌门）、1目（布氏菌门）、1科（赤潮菌科）、7属与无排卵性不孕存在因果关系。在这7个属中，有低穗芽孢杆菌属、无芽梭菌属和埃希氏菌属。志贺氏菌是无排卵性不孕的危险因素，普雷沃菌、鲁米诺球菌组、室状真杆菌组和裂裂真杆菌组是无排卵性不孕的保护因素。接下来，确定了35种免疫表型也与无排卵性不孕有因果关系。其中15种免疫表型受7个菌群属的显著驱动，可能是肠道菌群影响无排卵性女性不育的内在中介机制。在介导的MR分析中，4种微生物群（无芽梭菌组、裂丝真杆菌组、室状真杆菌组和普雷沃菌9）直接受到6种免疫表型（T细胞、B细胞和树突状细胞组）的影响，进而影响无排卵性不孕。结论介导的MR研究提供了证据，支持免疫表型作为肠道微生物群影响的女性不育的介质，特别是无排卵性不孕。

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来源期刊

American Journal of Reproductive Immunology 医学-免疫学

CiteScore

6.20

自引率

5.60%

发文量

314

审稿时长

2 months

期刊介绍： The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.