BackgroundRecent　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.MethodsSummary　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.ResultsThe　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.ConclusionOur　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.