Pan Yongdong, Su Jingyi, Liu Shengnan, Li Yueyan, Xu Guofeng
Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Heliyon. 2024 Feb 14;10(4):e25704. doi: 10.1016/j.heliyon.2024.e25704. eCollection 2024 Feb 29.
Recent studies increasingly suggest notable changes in both the quantity and types of gut microbiota among individuals suffering from urinary tract stones. However, the causal relationship between GMB and urinary tract stone formation remains elusive, which we aim to further investigate in this research through Mendelian Randomization (MR) analysis.
Single nucleotide polymorphisms (SNPs) associated with the human GMB were selected from MiBioGen International Consortium GWAS dataset. Data on urinary tract stone-related traits and associated SNPs were sourced from the IEU Open GWAS database. To investigate the causal relationships between gut microbiota and urinary tract stones, Mendelian Randomization (MR) was applied using genetic variants as instrumental variables, utilizing a bidirectional two-sample MR framework. This analysis incorporated various statistical techniques such as inverse variance weighting, weighted median analysis, MR-Egger, and the maximum likelihood method. To ensure the reliability of the findings, a range of sensitivity tests were conducted, including Cochran's Q test, the MR-Egger intercept, leave-one-out cross-validation, and examination of funnel plots.
The results revealed the causal relationship between the increase in the abundance of 10 microbial taxa, including Genus-Barnesiella (IVW OR = 0.73, 95%CI 0.73-0.89, P = 2.29 × 10-3) and Genus-Flavonifractor (IVW OR = 0.69, 95%CI 0.53-0.91, P = 8.57 × 10-3), and the decreased risk of urinary tract stone formation. Conversely, the development of urinary tract stones was observed to potentially instigate alterations in the abundance of 13 microbial taxa, among which Genus-Ruminococcus torques group was notably affected (IVW OR = 1.07, 95%CI 0.64-0.98, P = 1.86 × 10-3). In this context, Genus-Clostridium sensustricto1 exhibited a bidirectional causal relationship with urinary tract stones, while the remaining significant microbial taxa demonstrated unidirectional causal effects in the two-sample MR analysis. Sensitivity analyses did not identify significant estimates of heterogeneity or pleiotropy.
To summarize, the results of this study suggest a likely causative link between gut microbiota and the incidence of urinary tract stones. This insight opens up potential pathways for discovering biomarkers and therapeutic targets in the management and prevention of urolithiasis. However, further in-depth research is warranted to investigate these associations.
近期研究越来越多地表明，患有尿路结石的个体肠道微生物群的数量和种类都发生了显著变化。然而，肠道微生物群与尿路结石形成之间的因果关系仍不明确，我们旨在通过孟德尔随机化（MR）分析在本研究中进一步探究。
从MiBioGen国际联盟全基因组关联研究（GWAS）数据集中选择与人类肠道微生物群相关的单核苷酸多态性（SNP）。尿路结石相关性状和相关SNP的数据来自IEU开放GWAS数据库。为了研究肠道微生物群与尿路结石之间的因果关系，采用遗传变异作为工具变量，运用双向双样本MR框架进行孟德尔随机化分析。该分析纳入了多种统计技术，如逆方差加权、加权中位数分析、MR-Egger和最大似然法。为确保研究结果的可靠性，进行了一系列敏感性测试，包括Cochran's Q检验、MR-Egger截距、留一法交叉验证以及漏斗图检查。
结果显示，包括Barnesiella属（逆方差加权比值比[IVW OR]=0.73，95%置信区间[CI]0.73 - 0.89，P = 2.29×10⁻³）和Flavonifractor属（IVW OR = 0.69，95%CI 0.53 - 0.91，P = 8.57×10⁻³）在内的10种微生物类群丰度增加与尿路结石形成风险降低之间存在因果关系。相反，观察到尿路结石的发生可能会促使13种微生物类群的丰度发生改变，其中torques组瘤胃球菌属受到显著影响（IVW OR = 1.07，95%CI 0.64 - 0.98，P = 1.86×10⁻³）。在此背景下，狭义梭菌属与尿路结石呈现双向因果关系，而其余显著的微生物类群在双样本MR分析中表现出单向因果效应。敏感性分析未发现显著的异质性或多效性估计。
总之，本研究结果表明肠道微生物群与尿路结石发病率之间可能存在因果联系。这一见解为发现尿路结石管理和预防中的生物标志物及治疗靶点开辟了潜在途径。然而，仍需进一步深入研究以探究这些关联。
