Immunomodulatory mechanisms of gut microbiota-derived metabolites in non-small cell lung cancer: a gut–lung axis perspective
Abstract
Immunotherapy has emerged as a crucial component in the treatment of non-small cell lung cancer (NSCLC). Nevertheless, interindividual variability in efficacy, along with both primary and acquired resistance, as well as immune-related adverse events, continue to limit the benefits for patients. The gut microbiota and its associated metabolites are believed to play a significant role in pulmonary immune regulation via the gut–lung axis, with alterations in this system being associated with NSCLC development and progression, as well as the outcomes of immunotherapy. This review summarizes the key features of gut microbial and metabolic profiles in patients with NSCLC, focusing particularly on the mechanisms by which short-chain fatty acids, bile acids, gut microbiota-associated Trp metabolites, and other microbial metabolites may influence the tumor immune microenvironment and responses to immunotherapy. Furthermore, we consider their potential value in supporting NSCLC diagnosis, prognostic assessment, and treatment-response prediction. Therapies aimed at targeting metabolic pathways, fecal microbiota transplantation, dietary interventions, and microbiome-based preparations present additional avenues for enhancing the efficacy of NSCLC immunotherapy and managing treatment-related toxicity. However, current evidence primarily stems from small clinical studies and animal models, while methodological discrepancies and limited causal evidence impede clinical translation. Future research that integrates longitudinal multi-omics analyses, metabolic tracing, and controlled clinical trials is essential to elucidate the clinical significance of the gut microbiota-metabolite axis in NSCLC immunotherapy and precision medicine.
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BibTeX
@article{ye2026immunomodulatory,
title = {{Immunomodulatory mechanisms of gut microbiota-derived metabolites in non-small cell lung cancer: a gut–lung axis perspective}},
author = {Shumin Ye and Tian Tian and Junkang Huangfu and Huimin Liu and Peiyan Liu and Jun Zhou},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1999117},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1999117},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immunomodulatory mechanisms of gut microbiota-derived metabolites in non-small cell lung cancer: a gut–lung axis perspective
AU - Shumin Ye
AU - Tian Tian
AU - Junkang Huangfu
AU - Huimin Liu
AU - Peiyan Liu
AU - Jun Zhou
PY - 2026
DA - 2026/10/30
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1999117
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1999117
AB - Immunotherapy has emerged as a crucial component in the treatment of non-small cell lung cancer (NSCLC). Nevertheless, interindividual variability in efficacy, along with both primary and acquired resistance, as well as immune-related adverse events, continue to limit the benefits for patients. The gut microbiota and its associated metabolites are believed to play a significant role in pulmonary immune regulation via the gut–lung axis, with alterations in this system being associated with NSCLC development and progression, as well as the outcomes of immunotherapy. This review summarizes the key features of gut microbial and metabolic profiles in patients with NSCLC, focusing particularly on the mechanisms by which short-chain fatty acids, bile acids, gut microbiota-associated Trp metabolites, and other microbial metabolites may influence the tumor immune microenvironment and responses to immunotherapy. Furthermore, we consider their potential value in supporting NSCLC diagnosis, prognostic assessment, and treatment-response prediction. Therapies aimed at targeting metabolic pathways, fecal microbiota transplantation, dietary interventions, and microbiome-based preparations present additional avenues for enhancing the efficacy of NSCLC immunotherapy and managing treatment-related toxicity. However, current evidence primarily stems from small clinical studies and animal models, while methodological discrepancies and limited causal evidence impede clinical translation. Future research that integrates longitudinal multi-omics analyses, metabolic tracing, and controlled clinical trials is essential to elucidate the clinical significance of the gut microbiota-metabolite axis in NSCLC immunotherapy and precision medicine.
SN - 1664-3224
ER -