The Role of Gut Bacteria in Making Cancer Immunotherapy More Effective

In the treatment of non-small cell lung cancer (NSCLC), immunotherapies have brought a revolution in recent years. Yet the same treatment provides substantial benefit to some patients while remaining ineffective in others. Where might the source of this difference lie? Recent research points not to the lungs, but to the microbiome in our gut .

Study Design and Patient Group

In South Korea, Yonsei Cancer Center conducted a prospective study (September 2022 – November 2023) examining 92 patients . None of these patients had driver mutations such as EGFR, ALK, ROS1 , and none had previously received systemic treatment.

• Treatment arms:
  • (1) Single-agent pembrolizumab,
  • (2) Pembrolizumab + platinum-based chemotherapy
• PD-L1 stratification: Treatment selection was determined by PD-L1 level
• Response definition: Tumor shrinkage or stable disease for ≥6 months
• Sampling: Stool, blood and tumor tissue (before and during treatment)

🧬 Microbiome Signatures

📊 Numerical Findings: PFS and OS

Microbiome differences led to marked differences in patient survival:

Summary: High Faecalibacterium abundance was associated with an OS advantage of +10.7 months, while high Lactobacillus abundance was associated with a disadvantage of −12.9 months.

🥗 Factors Affecting the Microbiome

• Dietary fiber intake: High fiber ↔ more Faecalibacterium
• Antibiotic use: Associated with lower Faecalibacterium abundance
• Probiotic use: No significant effect detected
• Lactobacillus: No association with diet, probiotics or antibiotics

🚀 Clinical Implications and Future Perspectives

• Use as a biomarker: The microbiome profile may be used to predict response before treatment.
• Intervention pathways: Dietary changes, limiting antibiotic use, experimental approaches such as FMT
• Integrated scores: Integration of microbiome + PD-L1 + TMB + ctDNA data

Note: Randomized controlled trials are needed before these results enter clinical practice.

Conclusion

High Faecalibacterium and low Lactobacillus proportions are strongly associated with immunotherapy success in NSCLC. The gut microbiome may, in the future, serve as both a predictive biomarker and a treatment-guiding target .

📚 Source

1. Lee, J. B. (2025). Gut microbiome signatures of clinical response to pembrolizumab or pembrolizumab with chemotherapy in treatment-naïve, metastatic KHDAK. ESMO 2025.