The Hospital Affiliated to Medical School of Yangzhou University (Taizhou People's Hospital), Taizhou, Jiangsu, China.
Department of Physiology, Human Biology Building, School of Medicine, National University of Ireland (NUI), Galway, Ireland.
Front Immunol. 2024 Jun 4;15:1362753. doi: 10.3389/fimmu.2024.1362753. eCollection 2024.
Investigating the relationship between gut microbiota and Rheumatic Valve Disease (RVD) is crucial for understanding the disease's etiology and developing effective interventions. Our study adopts a novel approach to examine the potential causal connections between these factors.
Utilizing a two-sample Mendelian Randomization (MR) framework, we incorporated a multi-variable MR (MVMR) strategy to assess the mediatory mechanisms involved. This approach involved analyzing data from the MiBioGen consortium for gut microbiota and the FinnGen for RVD, among other sources. Instrumental variables (IVs) were carefully selected based on rigorous MR principles, and statistical analysis was conducted using bidirectional two-sample MR, such as inverse variance-weighted (IVW), weighted median, MR-Egger regression and MR Steiger Test methods. The MR-PRESSO strategy was employed for outlier detection, and MVMR was used to untangle the complex relationships between multiple microbiota and RVD.
Our analysis highlighted several gut microbiota classes and families with potential protective effects against RVD, including , and . In contrast, certain genera, such as and , were identified as potential risk factors. The MVMR analysis revealed significant mediation effects of various immune cell traits and biomarkers, such as CD4CD8 T cells, CD3 on Terminally Differentiated CD8+ T cell and Pentraxin-related protein PTX, elucidating the complex pathways linking gut microbiota to RVD.
This study underscores the intricate and potentially causal relationship between gut microbiota and RVD, mediated through a range of immune and hormonal factors. The use of MVMR in our methodological approach provides a more comprehensive understanding of these interactions, highlighting the gut microbiota's potential as therapeutic targets in RVD management. Our findings pave the way for further research to explore these complex relationships and develop targeted interventions for RVD.
研究肠道微生物群与风湿性瓣膜病（RVD）之间的关系对于了解该疾病的病因和开发有效的干预措施至关重要。我们的研究采用了一种新方法来研究这些因素之间潜在的因果关系。
利用两样本孟德尔随机化（MR）框架，我们采用多变量 MR（MVMR）策略来评估所涉及的中介机制。这种方法涉及分析 MiBioGen 联盟的肠道微生物群数据和 FinnGen 的 RVD 数据，以及其他来源的数据。根据严格的 MR 原则仔细选择工具变量（IVs），并使用双向两样本 MR 进行统计分析，例如反向方差加权（IVW）、加权中位数、MR-Egger 回归和 MR Steiger 检验方法。使用 MR-PRESSO 策略进行异常值检测，并使用 MVMR 来梳理多种微生物群和 RVD 之间的复杂关系。
我们的分析突出了几种具有潜在保护作用的肠道微生物群类和家族，可以预防 RVD，包括、和。相比之下，某些属，如和，被确定为潜在的风险因素。MVMR 分析显示，各种免疫细胞特征和生物标志物，如 CD4+CD8+ T 细胞、CD3 对终末分化的 CD8+ T 细胞和 Pentraxin 相关蛋白 PTX，具有显著的中介作用，阐明了肠道微生物群与 RVD 之间复杂的联系途径。
这项研究强调了肠道微生物群与 RVD 之间复杂且潜在的因果关系，这些关系通过一系列免疫和激素因素介导。我们在方法学方法中使用 MVMR 提供了对这些相互作用的更全面理解，突出了肠道微生物群作为 RVD 管理中治疗靶点的潜力。我们的研究结果为进一步研究这些复杂关系并开发针对 RVD 的靶向干预措施铺平了道路。
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