Department of Orthopedics, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China.
Department of Pediatric Medicine, Shanxi Medical University, Taiyuan, China.
Front Immunol. 2024 Apr 19;15:1360132. doi: 10.3389/fimmu.2024.1360132. eCollection 2024.
INTRODUCTION: Considerable evidence has unveiled a potential correlation between gut microbiota and spinal degenerative diseases. However, only limited studies have reported the direct association between gut microbiota and spinal stenosis. Hence, in this study, we aimed to clarify this relationship using a two-sample mendelian randomization (MR) approach. MATERIALS AND METHODS: Data for two-sample MR studies was collected and summarized from genome-wide association studies (GWAS) of gut microbiota (MiBioGen, n = 13, 266) and spinal stenosis (FinnGen Biobank, 9, 169 cases and 164, 682 controls). The inverse variance-weighted meta-analysis (IVW), complemented with weighted median, MR-Egger, weighted mode, and simple mode, was used to elucidate the causality between gut microbiota and spinal stenosis. In addition, we employed mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and the MR-Egger intercept test to assess horizontal multiplicity. Cochran's Q test to evaluate heterogeneity, and "leave-one-out" sensitivity analysis to determine the reliability of causality. Finally, an inverse MR analysis was performed to assess the reverse causality. RESULTS: The IVW results indicated that two gut microbial taxa, the genus group and the genus , have a potential causal relationship with spinal stenosis. Moreover, eight potential associations between genetic liability of the gut microbiota and spinal stenosis were implied. No significant heterogeneity of instrumental variables or horizontal pleiotropy were detected. In addition, "leave-one-out" sensitivity analysis confirmed the reliability of causality. Finally, the reverse MR analysis revealed that no proof to substantiate the discernible causative relationship between spinal stenosis and gut microbiota. CONCLUSION: This analysis demonstrated a possible causal relationship between certain particular gut microbiota and the occurrence of spinal stenosis. Further studies focused on the mechanism of gut microbiota-mediated spinal stenosis can lay the groundwork for targeted prevention, monitoring, and treatment of spinal stenosis.
介绍：大量证据揭示了肠道微生物群与脊柱退行性疾病之间存在潜在关联。然而，仅有有限的研究报告了肠道微生物群与椎管狭窄之间的直接关联。因此，本研究采用双样本孟德尔随机化（MR）方法来阐明这种关系。
材料和方法：从肠道微生物群（MiBioGen，n=13，266）和椎管狭窄（FinnGen 生物库，9，169 例病例和 164，682 例对照）的全基因组关联研究（GWAS）中收集和总结了用于双样本 MR 研究的数据。采用逆方差加权荟萃分析（IVW），补充加权中位数、MR-Egger、加权模式和简单模式，阐明肠道微生物群与椎管狭窄之间的因果关系。此外，我们还采用孟德尔随机化多效残余和异常值（MR-PRESSO）和 MR-Egger 截距检验来评估水平多重性。采用 Cochran's Q 检验评估异质性，采用“逐个剔除”敏感性分析评估因果关系的可靠性。最后，进行了反向 MR 分析以评估反向因果关系。
结果：IVW 结果表明，两个肠道微生物属群和 属与椎管狭窄有潜在的因果关系。此外，还暗示了肠道微生物群遗传易感性与椎管狭窄之间的 8 个潜在关联。未检测到工具变量的显著异质性或水平多效性。此外，“逐个剔除”敏感性分析证实了因果关系的可靠性。最后，反向 MR 分析表明，没有证据表明椎管狭窄与肠道微生物群之间存在明显的因果关系。
结论：本分析表明，某些特定肠道微生物群与脊柱狭窄的发生之间可能存在因果关系。进一步研究集中于肠道微生物群介导的脊柱狭窄的机制，可以为脊柱狭窄的靶向预防、监测和治疗奠定基础。
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