Ni Tianyi, Shen Ziyu, Shi Hekai, Han Zhao
Department of Otorhinolaryngology Head & Neck Surgery, Huadong Hospital Affiliated Fudan University, Shanghai, China.
Department of Algology, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
Medicine (Baltimore). 2025 Jun 6;104(23):e42590. doi: 10.1097/MD.0000000000042590.
Previous studies have revealed the association between gut microbiota (GM) and temporomandibular joint inflammation, which leads to temporomandibular joint disorders (TMD). However, the causality of the associations remains unknown. This Mendelian randomization (MR) study aims to clarify the causal relationships between GM and TMD. We employed a two-sample MR approach to analyze GM data from the MiBioGen consortium, including 18,340 participants and 211 taxa, and TMD data from the FinnGen consortium R10 release, including 6314 cases and 222,498 controls. Various MR methods, including inverse-variance weighted (IVW), MR-Egger, and weighted median analyses, alongside comprehensive sensitivity analyses, were used to assess causality. After comprehensive sensitivity analyses, the study found causal links between 6 certain GM at the genus level and TMD, including Eubacterium fissicatena group (IVW's odds ratio [OR] = 1.18; 95% confidence interval [CI]: 1.02-1.37; P = .027), Catenibacterium (IVW's OR = 1.33; 95% CI: 1.11-1.59; P = .002), Oxalobacter (IVW's OR = 0.85; 95% CI: 0.75-0.97; P = .013), Ruminococcaceae NK4A214 (IVW's OR = 0.80; 95% CI: 0.66-0.99; P = .036), and Senegalimassilia (IVW's OR = 0.75; 95% CI: 0.59-0.96; P = .024). Following replication verification analysis, Catenibacterium (FDR = .04) at the genus level were positively correlated to the risk of TMD. The reverse MR analysis revealed that TMD had no significant effect on the 6 GMs. The findings of this MR study support a strong and negative causal association between genus Catenibacterium and TMD, highlighting potential targets for the prevention and treatment of TMD.
先前的研究揭示了肠道微生物群（GM）与颞下颌关节炎症之间的关联，这种炎症会导致颞下颌关节紊乱（TMD）。然而，这些关联的因果关系仍然未知。这项孟德尔随机化（MR）研究旨在阐明GM与TMD之间的因果关系。我们采用两样本MR方法来分析来自MiBioGen联盟的GM数据，包括18340名参与者和211个分类群，以及来自FinnGen联盟R10版本的TMD数据，包括6314例病例和222498名对照。使用了各种MR方法，包括逆方差加权（IVW）、MR-Egger和加权中位数分析，以及全面的敏感性分析，来评估因果关系。经过全面的敏感性分析后，该研究发现属水平上6种特定的GM与TMD之间存在因果联系，包括裂齿真杆菌群（IVW的优势比[OR]=1.18；95%置信区间[CI]：1.02-1.37；P=.027）、链状杆菌属（IVW的OR=1.33；95%CI：1.11-1.59；P=.002）、草酸杆菌属（IVW的OR=0.85；95%CI：0.75-0.97；P=.013）、瘤胃球菌科NK4A214（IVW的OR=0.80；95%CI：0.66-0.99；P=.036）和塞内加尔马西拉菌属（IVW的OR=0.75；95%CI：0.59-0.96；P=.024）。经过重复验证分析后发现，属水平上的链状杆菌属（FDR=.04）与TMD风险呈正相关。反向MR分析表明，TMD对这6种GM没有显著影响。这项MR研究的结果支持了链状杆菌属与TMD之间存在强烈的负因果关联，突出了TMD预防和治疗的潜在靶点。
