More than ten trillion microorganisms residing in the human body constitute the microbiome, including non-cellular, prokaryotic and eukaryotic cell microorganisms (Daniel et al., 2021). Advances in sequencing technology and refinement of analytical techniques in recent years have confirmed the existence of microbiota across various organs and regions, including the gut, lung, oral cavity and so on (Sexton et al., 2022). These microbes have garnered increasing attention for its potential influence on diverse physiological processes, including immune modulation, metabolism, and inflammation (Li et al., 2024). As the scientific community delves deeper into the intricate mechanisms of cancer biology, the role of the microbiome has emerged as a promising avenue for reshaping the landscape of cancer development and therapy.

Lung cancer remains the most prevalent and mortal malignancies (Siegel et al., 2023). The lungs, once considered sterile, are now recognized as dynamic ecosystems hosting a diverse array of microorganisms (Dong et al., 2021). Commencing with the inhalation of air-borne microbes, the respiratory tract becomes home to a unique microbial tapestry whose composition and abundance can be influenced by various factors, including environmental exposures, host genetics, and lifestyle choices (Whiteside et al., 2021). Several studies have illuminated compelling associations between alterations in the biomass, distribution, and composition of the lung microbiome and the progression of lung cancer (Mao et al., 2018, Goto, 2022, Zhao et al., 2021a). Additionally, the concept of the ‘gut-lung axis (GLA)’ serves as an intriguing dimension of microbiome research in lung cancer (Budden et al., 2017). This bidirectional communication pathway encompasses complex crosstalk between the gut microbiome and the respiratory system, influencing both local and systemic immune responses. Emerging evidence suggests that disturbances in the gut microbiome may reverberate to the lungs and vice versa (Budden et al., 2017). Understanding the dynamics of the GLA becomes pivotal in unraveling the comprehensive microbial impacts that underlies lung cancer.

Herein, besides exploring the causative role of the microbiome from the lung, gut, and oral cavity in lung cancer, this review will also navigate the uncharted territories of therapeutic possibilities and clinical implications. From harnessing the diagnostic potential of microbial biomarkers to manipulating the microbiome for therapeutic benefit, the evolving landscape of microbiome research holds promise for novel approaches in lung cancer prevention and treatment.