Abstract
BACKGROUND: Recent research has demonstrated that microbes have a vital impact on cancer by governing immune responses, managing inflammation, and employing other methods. However, the specific relationship between the microbiome and lung cancer requires further investigation to be fully understood. METHODS: Summary data regarding lung cancer outcomes and skin bacteria were sourced from the GWAS and GWAS catalog databases, respectively. Data on gut microbiota were acquired from the MiBioGen database. Using these datasets, we performed Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) analysis to evaluate the genetic relationships and possible relationships between gut and skin microbiota and lung cancer. RESULTS: The LDSC analysis indicated that Bifidobacteria have a negative genetic correlation with lung cancer across order, family, and genus levels. Similarly, the Eubacterium Coprostanoligenes group displayed a negative genetic correlation at the genus level. Mendelian randomization analysis of gut and skin microbiome data further identified several microbiotas positively associated with lung cancer risk, including Eubacterium brachy group, Coprobacter genus, Adlercreutzia, Flavonifractor, Holdemanella, Anaerotruncus, Erysipelatoclostridium, and ASV045 [Acinetobacter]. Conversely, microbiota such as Bacteroidetes (phylum), Eubacterium rectale group, Prevotella 9, Ruminococcus1, Lachnospiraceae NK4A136 group, Gordonibacter, Eubacterium hallii group, Streptococcus genus, and ASV009 [D. nitroreducens] demonstrated a protective effect against lung cancer. Notably, the Coprobacter genus exhibited contrasting associations with lung cancer subtypes. Reverse Mendelian randomization did not reveal any potential effects of lung cancer on these microbiota abundances. Heterogeneity and pleiotropy analyses confirmed the robustness and reliability of these findings. CONCLUSION: Our Mendelian randomization analysis identified multiple microbial communities that may be associated with lung cancer risk, highlighting the complex interactions between the microbiota and lung cancer development, providing valuable insights and promising research directions for microbiota-targeted prevention and treatment strategies for lung cancer.