Su Mengchan, Tang Yidan, Kong Weishuang, Zhang Shuangyi, Zhu Tao
Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.
Front Microbiol. 2023 Apr 14;14:1157451. doi: 10.3389/fmicb.2023.1157451. eCollection 2023.
BACKGROUND: Previous studies have implicated a vital association between gut microbiota/gut microbial metabolites and low back pain (LBP), but their causal relationship is still unclear. Therefore, we aim to comprehensively investigate their causal relationship and identify the effect of gut microbiota/gut microbial metabolites on risk of LBP using a two-sample Mendelian randomization (MR) study. METHODS: Summary data from genome-wide association studies (GWAS) of gut microbiota (18,340 participants), gut microbial metabolites (2,076 participants) and LBP (FinnGen biobank) were separately obtained. The inverse variance-weighted (IVW) method was used as the main MR analysis. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were conducted to evaluate the horizontal pleiotropy and to eliminate outlier single-nucleotide polymorphisms (SNPs). Cochran's -test was applied for heterogeneity detection. Besides, leave-one-out analysis was conducted to determine whether the causal association signals were driven by any single SNP. Finally, a reverse MR was performed to evaluate the possibility of reverse causation. RESULTS: We discovered that 20 gut microbial taxa and 2 gut microbial metabolites were causally related to LBP ( < 0.05). Among them, the lower level of family (OR: 0.771, 95% CI: 0.652-0.913, FDR-corrected = 0.045) and (OR: 0.875, 95% CI: 0.801-0.955, FDR-corrected = 0.045) retained a strong causal relationship with higher risk of LBP after the Benjamini-Hochberg Corrected test. The Cochrane's test revealed no Heterogeneity ( > 0.05). Besides, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy ( > 0.05). Furthermore, leave-one-out analysis confirmed the robustness of MR results. After adding BMI to the multivariate MR analysis, the 17 gut microbial taxa exposure-outcome effect were significantly attenuated and tended to be null. CONCLUSION: Our findings confirm the the potential causal effect of specific gut microbiota and gut microbial metabolites on LBP, which offers new insights into the gut microbiota-mediated mechanism of LBP and provides the theoretical basis for further explorations of targeted prevention strategies.
背景：先前的研究表明肠道微生物群/肠道微生物代谢产物与腰痛（LBP）之间存在重要关联，但其因果关系仍不清楚。因此，我们旨在通过两样本孟德尔随机化（MR）研究全面调查它们之间的因果关系，并确定肠道微生物群/肠道微生物代谢产物对LBP风险的影响。 方法：分别获取了来自肠道微生物群全基因组关联研究（GWAS）（18340名参与者）、肠道微生物代谢产物（2076名参与者）和LBP（芬兰基因生物银行）的汇总数据。采用逆方差加权（IVW）方法作为主要的MR分析。进行孟德尔随机化多效性残差和异常值（MR-PRESSO）以及MR-Egger回归，以评估水平多效性并消除异常单核苷酸多态性（SNP）。应用Cochran's Q检验进行异质性检测。此外，进行留一法分析以确定因果关联信号是否由任何单个SNP驱动。最后，进行反向MR以评估反向因果关系的可能性。 结果：我们发现20种肠道微生物分类群和2种肠道微生物代谢产物与LBP存在因果关系（P<0.05）。其中，在Benjamini-Hochberg校正检验后，[具体分类群1]家族水平较低（OR：0.771，95%CI：0.652-0.913，FDR校正P=0.045）和[具体分类群2]（OR：0.875，95%CI：0.801-0.955，FDR校正P=0.045）与较高的LBP风险保持着强烈的因果关系。Cochrane's Q检验显示无异质性（P>0.05）。此外，MR-Egger和MR-PRESSO检验显示无显著的水平多效性（P>0.05）。此外，留一法分析证实了MR结果的稳健性。在多变量MR分析中加入BMI后，17种肠道微生物分类群的暴露-结局效应显著减弱并趋于无效。 结论：我们的研究结果证实了特定肠道微生物群和肠道微生物代谢产物对LBP的潜在因果效应，这为LBP的肠道微生物群介导机制提供了新的见解，并为进一步探索靶向预防策略提供了理论依据。
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