Xu Ran, Li Si, Zhang Ying, Pu Yue, Luo Guangcheng, Wang Xinjun
Department of Urology, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Department of Pediatric Surgery, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen, China.
Front Microbiol. 2024 May 28;15:1342172. doi: 10.3389/fmicb.2024.1342172. eCollection 2024.
Osteomyelitis is characterized by an inflammatory process initiated by microorganisms, leading to infection and subsequent degradation of bone tissue. Several studies have indicated a potential link between gut microbiota and the occurrence of osteomyelitis. Utilizing the benefits of Mendelian randomization, which mitigates issues of confounding and reverse causation, we employed this approach to ascertain the presence of a causal connection between gut microbiota and osteomyelitis. Additionally, we aimed to pinpoint gut microbiota that could potentially exert substantial influence.
We performed a rigorous screening of single nucleotide polymorphisms in GWAS summary statistics for gut microbiota and osteomyelitis. The 2,542 instrumental variables obtained after screening were subjected to MR analyses, including inverse variance weighting, weighted median, weighted mode, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier test. We then validated the reliability of the results by performing sensitivity analyses on the MR of 196 well-defined gut microbiota.
We established a causal relationship between gut microbiota and osteomyelitis through MR analysis. Additionally, we identified a taxon of significant importance and six taxons with nominal significance. Specifically, the family Bacteroidales S24.7 group exhibited an association with a diminished risk of osteomyelitis development. Conversely, the class Bacilli, class Bacteroidia, order Bacteroidales, order Lactobacillales, family Streptococcaceae, and genus Coprococcus3 displayed an increased risk of developing osteomyelitis. The MR outcomes for these seven taxa remained stable throughout a series of sensitivity analyses.
This study demonstrated a causal relationship between gut microbiota and osteomyelitis by Mendelian randomization. We hope that this study will provide a new direction for the treatment of osteomyelitis, which has a paucity of therapeutic options.
骨髓炎的特征是由微生物引发的炎症过程，导致骨组织感染及随后的降解。多项研究表明肠道微生物群与骨髓炎的发生之间存在潜在联系。利用孟德尔随机化的优势，其可减轻混杂和反向因果关系问题，我们采用这种方法来确定肠道微生物群与骨髓炎之间是否存在因果关系。此外，我们旨在找出可能产生重大影响的肠道微生物群。
我们对肠道微生物群和骨髓炎的全基因组关联研究（GWAS）汇总统计中的单核苷酸多态性进行了严格筛选。筛选后获得的2542个工具变量进行了孟德尔随机化分析，包括逆方差加权、加权中位数、加权模式、孟德尔随机化Egger回归以及孟德尔随机化多效性残差和离群值检验。然后，我们通过对196种明确的肠道微生物群的孟德尔随机化进行敏感性分析，验证了结果的可靠性。
通过孟德尔随机化分析，我们确定了肠道微生物群与骨髓炎之间的因果关系。此外，我们确定了一个具有重要意义的分类群和六个具有名义意义的分类群。具体而言，拟杆菌目S24.7组与骨髓炎发病风险降低有关。相反，芽孢杆菌纲、拟杆菌纲、拟杆菌目、乳杆菌目、链球菌科和粪球菌属3显示出患骨髓炎的风险增加。在一系列敏感性分析中，这七个分类群的孟德尔随机化结果保持稳定。
本研究通过孟德尔随机化证明了肠道微生物群与骨髓炎之间的因果关系。我们希望这项研究将为治疗选择匮乏的骨髓炎提供新的方向。
