Causal influence of gut microbiota on small cell lung cancer: a Mendelian randomization study

Background Previous studies have hinted at a significant link between lung cancer and the gut microbiome, yet their causal relationship remains to be elucidated. Methods GWAS data for small cell lung cancer (SCLC) was extracted from the FinnGen consortium, comprising 179 cases and 218 613 controls. Genetic variation data for 211 gut microbiota were obtained as instrumental variables from MiBioGen. Mendelian randomization (MR) was employed to determine the causal relationship between the two, with inverse variance weighting (IVW) being the primary method for causal analysis. The MR results were validated through several sensitivity analyses. Results The study identified a protective effect against SCLC for the genus Eubacterium ruminantium group (OR = 0.413, 95% CI: 0.223–0.767, p = 0.00513), genus Barnesiella (OR = 0.208, 95% CI: 0.0640–0.678, p = 0.00919), family Lachnospiraceae (OR = 0.319, 95% CI: 0.107–0.948, p = 0.03979), and genus Butyricimonas (OR = 0.376, 95% CI: 0.144–0.984, p = 0.04634). Conversely, genus Intestinibacter (OR = 3.214, 95% CI: 1.303–7.926, p = 0.01125), genus Eubacterium oxidoreducens group (OR = 3.391, 95% CI: 1.215–9.467, p = 0.01973), genus Bilophila (OR = 3.547, 95% CI: 1.106–11.371, p = 0.03315), and order Bacillales (OR = 1.860, 95% CI: 1.034–3.347, p = 0.03842) were found to potentially promote the onset of SCLC. Conclusion We identified potential causal relationships between certain gut microbiota and SCLC, offering new insights into microbiome‐mediated mechanisms of SCLC pathogenesis, resistance, mutations, and more. Mendelian randomization to investigate the causal impact of the gut microbiota on small cell lung cancer (SCLC). It begins with the careful selection of genetic instruments linked to the microbiome, utilizes robust statistical methods to address confounding elements, and arrives at meaningful conclusions. The findings are particularly significant, revealing that specific genera and families within the gut microbiota may play a role in either increasing the risk or offering protection against SCLC. This research sheds light on the intricate relationship between the gut microbiome and lung cancer, opening new avenues for understanding and potentially intervening in SCLC development.