■新的证据表明,甲状腺结节(TNs)发展后,肠道微生物群(GM)组成发生了变化,但因果关系尚不清楚.利用孟德尔随机化(MR),本研究旨在阐明GM和TNs之间的因果动力学.
■使用来自MiBioGen联盟(n=18,340)和FinnGen联盟的汇总统计数据(1,634个TNs案例,263,704个控件),我们进行了单变量和多变量MR分析,以探讨GM-TNs相关性.包括逆方差加权的技术,MR-Egger回归,加权中位数,和MR-PRESSO用于因果推断。通过Cochran的Q统计量和留一分析评估工具变量的异质性。反向MR应用于显示显着的正向MR关联的分类单元,对混杂因素进行多变量调整。
■我们的研究结果表明,某些微生物群,鉴定为Ruminocycaceae_NK4A214_组(OR,1.89;95CI,0.47-7.64;p=0.040),塞内加尔(或,1.72;95CI,1.03-2.87;p=0.037),落叶松科(或,0.64;95CI,0.41-0.99;p=0.045),对TNs的发展表现出保护性影响,由负因果关联表示。相比之下,分类为脱硫弧菌的微生物群(或,0.63;95CI,0.41-0.95;p=0.028),Prevotella_7(或,0.79;95CI,0.63-1.00;p=0.049),粪杆菌(OR,0.66;95CI,0.44-1.00;p=0.050),脱硫弧菌科(或,0.55;95CI,0.35-0.86;p=0.008),Deltaproteobacteria(OR,0.65;95CI,0.43-0.97;p=0.036)与TNs呈正相关,这表明它们可能是危险因素。反向MR分析没有建立显著的因果关系。在对混杂因素进行全面调整后,脱硫弧菌类群(订单),脱硫弧菌科(科),Deltaproteobacteria(Class)仍然是TNs风险的潜在贡献者。
■这项研究证实了GM成分与TNs发育之间的显著因果联系,强调甲状腺-肠轴的相关性。调查结果倡导将转基因概况纳入转基因疫苗的预防和管理,为该领域的未来研究奠定了基础。
UNASSIGNED: Emerging evidence suggests alterations in gut microbiota (GM) composition following thyroid nodules (TNs) development, yet the causal relationship remains unclear. Utilizing Mendelian Randomization (MR), this
study aims to elucidate the causal dynamics between GM and TNs.
UNASSIGNED: Employing summary statistics from the MiBioGen consortium (n=18,340) and FinnGen consortium (1,634 TNs cases, 263,704 controls), we conducted univariable and multivariable MR analyses to explore the GM-TNs association. Techniques including inverse variance weighted, MR-Egger regression, weighted median, and MR-PRESSO were utilized for causal inference. Instrumental variable heterogeneity was assessed through Cochran\'s Q statistic and leave-one-out analysis. Reverse MR was applied for taxa showing significant forward MR associations, with multivariate adjustments for confounders.
UNASSIGNED: Our findings suggest that certain microbiota, identified as Ruminococcaceae_NK4A214_group (OR, 1.89; 95%CI, 0.47-7.64; p = 0.040), Senegalimassilia (OR, 1.72; 95%CI, 1.03-2.87; p =0.037), Lachnospiraceae (OR,0.64; 95%CI,0.41-0.99; p =0.045), exhibit a protective influence against TNs\' development, indicated by negative causal associations. In contrast, microbiota categorized as Desulfovibrionales (OR, 0.63; 95%CI, 0.41-0.95; p =0.028), Prevotella_7 (OR, 0.79; 95%CI, 0.63-1.00; p =0.049), Faecalibacterium (OR, 0.66; 95%CI, 0.44-1.00; p =0.050), Desulfovibrionaceae (OR, 0.55; 95%CI, 0.35-0.86; p =0.008), Deltaproteobacteria (OR, 0.65; 95%CI, 0.43-0.97; p =0.036) are have a positive correlation with with TNs, suggesting they may serve as risk factors. Reverse MR analyses did not establish significant causal links. After comprehensive adjustment for confounders, taxa Desulfovibrionales (Order), Desulfovibrionaceae (Family), Deltaproteobacteria (Class) remain implicated as potential contributors to TNs\' risk.
UNASSIGNED: This
study substantiates a significant causal link between GM composition and TNs development, underscoring the thyroid-gut axis\'s relevance. The findings advocate for the integration of GM profiles in TNs\' prevention and management, offering a foundation for future research in this domain.