Wang Wencai, Liu Menghao, Wang Zun, Ye Wei, Li Xianfeng
The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People's Republic of China.
Discov Oncol. 2025 Sep 26;16(1):1713. doi: 10.1007/s12672-025-02958-6.
Previous observational studies have hinted at a connection between the gut microbiota and pituitary neuroendocrine tumors, yet the causal nature of this relationship remains uncertain.
We employed a bidirectional Mendelian randomization to explore the potential impact of gut microbiota on the susceptibility to developing pituitary neuroendocrine tumors. Our analysis included weighted median estimator, simple model, weighted model, inverse variance-weighted, and the MR-Egger regression method for estimating causal effects and conducting sensitivity analyses. Additionally, reverse Mendelian randomization analysis was conducted on bacteria identified as causally linked to pituitary neuroendocrine tumors.
Causal relationships were identified between genetic predisposition in the gut microbiota and pituitary neuroendocrine tumors, involving 11 distinct bacterial families and genera. Notably, no significant causal effect was detected from pituitary neuroendocrine tumors on the gut microbiota, and there were no significant heterogeneities observed in instrumental variables or horizontal pleiotropy.
Through two-sample Mendelian randomization analysis, we pinpointed particular gut microbiota with a causal link to both the occurrence and prognosis of pituitary neuroendocrine tumors at the genetic prognostic level. These findings hold promise for serving as valuable biomarkers for early disease detection and as potential therapeutic targets for the management of pituitary neuroendocrine tumors.
以往的观察性研究已暗示肠道微生物群与垂体神经内分泌肿瘤之间存在联系，但这种关系的因果性质仍不确定。
我们采用双向孟德尔随机化方法，探讨肠道微生物群对垂体神经内分泌肿瘤发生易感性的潜在影响。我们的分析包括加权中位数估计器、简单模型、加权模型、逆方差加权法以及用于估计因果效应和进行敏感性分析的MR-Egger回归方法。此外，对被确定与垂体神经内分泌肿瘤存在因果联系的细菌进行了反向孟德尔随机化分析。
确定了肠道微生物群的遗传易感性与垂体神经内分泌肿瘤之间的因果关系，涉及11个不同的细菌科和属。值得注意的是，未检测到垂体神经内分泌肿瘤对肠道微生物群有显著因果效应，且在工具变量或水平多效性方面未观察到显著异质性。
通过两样本孟德尔随机化分析，我们在遗传预后水平上确定了与垂体神经内分泌肿瘤的发生和预后存在因果联系的特定肠道微生物群。这些发现有望作为早期疾病检测的有价值生物标志物以及垂体神经内分泌肿瘤管理的潜在治疗靶点。
