The Role of 418 Gut Microbiota in Small Cell Lung Cancer Progression: A Mendelian Randomisation Study.

Objective: To investigate the causal influence of gut microbiota on small cell lung cancer (SCLC) progression using Mendelian randomisation (MR), providing insights into the gut-lung axis in lung cancer pathology.

Study design: Analytical study. Place and Duration of the Study: Department of Radiotherapy, Binhai County People's Hospital, Yancheng, Jiangsu, China, and Department of Paediatrics, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China, from January to May 2024.

Methodology: The study used 18,340 single nucleotide polymorphisms (SNPs) as instrumental variables to analyse 418 gut microbiota varieties. The inverse variance weighted (IVW) and MR Egger's methods were applied to explore causal relationships. Sensitivity analyses, including leave-one-out tests and Cochrane's Q tests, ensured robust results. A uni-directional Mendelian randomisation (MR) analysis was conducted using summary statistics from genome-wide association studies (GWAS) provided by the MiBio-Gen and Finn-Gen consortia.

Results: MR identified several bacterial taxonomic groups significantly associated with SCLC risk. Protective factors included Bacteroidetes (p = 0.0154), Eubacterium ruminantium group (p = 0.0241), Barnesiella (p = 0.0015), Clostridia (p = 0.0242), Christensenellaceae (p = 0.0314), Ruminococcaceae UCG-003 (p = 0.0381), and an unknown genus in the Ruminococcaceae family (p = 0.0458). Conversely, the risk factors linked to increased SCLC risk included Firmicutes (p = 0.0456), Pasteurellaceae (p = 0.0177), Eubacterium oxidoreducens group (p = 0.0188), Pasteurellales (p = 0.0177), and Alcaligenaceae (p = 0.0423).

Conclusion: The study suggests a protective role of specific gut microbiota against SCLC and identifies others that may increase the risk. The absence of heterogeneity and pleiotropy supports the causal associations, underscoring the significance of the gut-lung axis in SCLC and the utility of MR in cancer epidemiology.

Key words: Small cell lung cancer, Gut microbiota, Mendelian randomisation, Causal inference, Cancer epidemiology.