Revealing a causal relationship between gut microbiota and lung cancer: a Mendelian randomization study

Yingchen Li; Ke Wang; Yuchong Zhang; Jitao Yang; Ying Wu; Mingfang Zhao

doi:10.3389/fcimb.2023.1200299

Revealing a causal relationship between gut microbiota and lung cancer: a Mendelian randomization study

Front Cell Infect Microbiol. 2023 Sep 27:13:1200299. doi: 10.3389/fcimb.2023.1200299. eCollection 2023.

Authors

Yingchen Li¹, Ke Wang², Yuchong Zhang¹, Jitao Yang², Ying Wu³, Mingfang Zhao¹

Affiliations

¹ Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
² Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, China.
³ Phase I Clinical Trails Center, The First Hospital of China Medical University, Shenyang, China.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Mendelian randomization; causal inference; genome-wide association study; gut microbiota; lung cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma of Lung*
Gastrointestinal Microbiome*
Genome-Wide Association Study
Humans
Lung Neoplasms* / genetics
Mendelian Randomization Analysis

Grants and funding

This work received support from the following funding sources: Scientific Research Foundation of Education Department in Liaoning Province (Grant LJKZ0739), Science and Technology Plan Project of Shenyang (Grant 21-173-9-30), Educational funding of Liaoning Province (Grant No: LJKZ0739), Social Scientific planning funding (Grant No: L21BGL059), the planned projects of Liaoning provincial central government guiding local science and technology development funding (Grant No: 2022010127-JH6/1001), and Scientific Research Funding Project of Education Department of Liaoning Province (Grant No. JCZR2020010).