A comprehensive review reveals that dysbiosis of the respiratory microbiota drives lung cancer through four integrated pathways: oncogenic signaling, epigenetic/metabolic reprogramming, and chronic immune dysregulation.
Microbial signatures in saliva, bronchoalveolar lavage fluid, and tumor tissues show promise as non-invasive biomarkers for early diagnosis, histological subtyping, staging, and prediction of immunotherapy response.
Emerging strategies including aerosolized probiotics, nanomaterial-based microbial depletion, and engineered live bacteria offer new therapeutic avenues for lung cancer.
Lung cancer remains the leading cause of cancer-related mortality, and drug resistance limits current therapies. Although gut microbiome research has dominated the field, the respiratory tract—once considered sterile—hosts a dynamic microbial community that actively influences lung cancer. A new review in Advanced Cancer Research by Huashan Hospital researchers synthesizes evidence that the respiratory microbiota is a key regulator of tumor progression and treatment outcomes.
Oral bacteria
Lung cancer patients show reduced microbial diversity and enrichment of oral bacteria like Veillonella and Streptococcus. Different subtypes have distinct microbial profiles, and certain taxa correlate with stage and metastasis. Importantly, microbial signatures can predict immunotherapy response: high Actinomyces in saliva predicts poor outcomes, while Veillonella is linked to better responses and high PD-L1.
Mechanistically, dysbiosis drives cancer through four integrated pathways: activating oncogenic signaling (ERK/PI3K), epigenetic reprogramming via metabolites like butyrate, metabolic rewiring promoting metastasis, and chronic inflammation that recruits immunosuppressive cells and exhausts CD8⁺ T cells.
Emerging therapies targeting the lung microbiota include aerosolized probiotics, nanoparticle-based pathogen elimination, and engineered live bacteria. Though preclinical, these approaches offer new hope. Future work must establish causality, standardize multi-omics, and validate biomarkers in large trials to translate these findings into clinical practice.
Key highlights include:
Respiratory dysbiosis drives lung cancer via three integrated pathways.
Respiratory microbiota signatures predict diagnosis, staging, and therapy response.
Targeting the respiratory microbiota shows preclinical promise.
Respiratory microbiota translation requires multi‑omics and clinical validation.
Next steps
The review further highlights that integrating multi-omics approaches with standardized clinical protocols will be essential to establish causal relationships and validate microbial biomarkers, ultimately accelerating the translation of microbiome-based signatures into routine diagnostic and predictive tools for lung cancer management.
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This work outlines the functional landscape of the respiratory microbiota in lung cancer, highlighting the microbial community as both an indicator and a driver of tumor progression, immune evasion, and therapeutic response. By bridging dysbiosis, immunomodulatory networks, and emerging therapeutic strategies, this review provides a roadmap for harnessing the lung microbiome toward precision oncology.
Citation: Zhao Y, Li SQ. The respiratory microbiota in lung cancer: bridging dysbiosis, immunomodulatory networks, and therapeutic opportunities. Adv. Cancer Res. 2026(1):0009, https://doi.org/10.55092/acr20260009.
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