Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, China.
Front Cell Infect Microbiol. 2023 Sep 27;13:1200299. doi: 10.3389/fcimb.2023.1200299. eCollection 2023.
The gut microbiota has been found to be associated with the risk of lung cancer. However, its causal relationship with various types of lung cancer remains unclear.
We conducted a Mendelian randomization (MR) study using the largest genome-wide association analysis of gut microbiota data to date from the MiBioGen consortium, with pooled statistics for various types of lung cancer from the Transdisciplinary Research in Cancer of the Lung, the International Lung Cancer Consortium, and FinnGen Consortium R7 release data. Inverse variance weighted, weighted model, MR-Egger regression, and weighted median were adapted to assess the causal relationship between gut microbiota and various types of lung cancer. Sensitivity analysis was used to test for the presence of pleiotropy and heterogeneity in instrumental variables. A reverse MR analysis was performed on these bacteria to determine their potential role in causing lung cancer. A reverse MR analysis was performed on these bacteria to determine their potential role in causing lung cancer. Multivariable Mendelian randomization (MVMR) was conducted to assess the direct causal impact of gut microbiota on the risk of various types of lung cancer.
Using IVW as the primary analytical method, we identified a total of 40 groups of gut microbiota with potential causal associations with various subtypes of lung cancer, of which 10 were associated with lung cancer, 10 with lung adenocarcinoma, 9 with squamous cell lung cancer, and 11 groups of bacteria associated with small cell lung cancer. After performing FDR correction, we further found that there was still a significant causal relationship between Peptococcaceae and lung adenocarcinoma. Sensitivity analyses demonstrated the robustness of these results, with no heterogeneity or pleiotropy found.
Our results confirm a causal relationship between specific gut microbiota and lung cancer, providing new insights into the role of gut microbiota in mediating the development of lung cancer.
肠道微生物群已被发现与肺癌风险相关。然而，其与各种类型肺癌的因果关系尚不清楚。
我们使用来自 MiBioGen 联盟的迄今为止最大的肠道微生物群数据全基因组关联分析的孟德尔随机化 (MR) 研究，结合来自 Transdisciplinary Research in Cancer of the Lung、International Lung Cancer Consortium 和 FinnGen 联盟 R7 发布数据的各种类型肺癌的汇总统计数据。我们采用逆方差加权、加权模型、MR-Egger 回归和加权中位数来评估肠道微生物群与各种类型肺癌之间的因果关系。敏感性分析用于检测工具变量中是否存在多效性和异质性。对这些细菌进行反向 MR 分析，以确定它们在导致肺癌中的潜在作用。进行多变量孟德尔随机化 (MVMR) 分析，以评估肠道微生物群对各种类型肺癌风险的直接因果影响。
使用 IVW 作为主要分析方法，我们总共鉴定出 40 组具有与各种肺癌亚型潜在因果关联的肠道微生物群，其中 10 组与肺癌相关，10 组与肺腺癌相关，9 组与鳞状细胞肺癌相关，11 组与小细胞肺癌相关。在进行 FDR 校正后，我们进一步发现 Peptococcaceae 与肺腺癌之间仍存在显著的因果关系。敏感性分析表明这些结果具有稳健性，未发现异质性或多效性。
我们的结果证实了特定肠道微生物群与肺癌之间存在因果关系，为肠道微生物群在介导肺癌发生中的作用提供了新的见解。
