Gut microbiome composition correlates with chemotherapy response in advanced lung cancer

The gut microbiome is already known to modulate immunotherapy response. However, the role of the gut microbiome is less clear in patients treated with chemotherapy. An analysis of 64 advanced lung cancer patients receiving chemotherapy was presented at WCLC 2020, finding that specific microbiota species were associated with chemotherapy response, as well as phenotypic presentations of disease.

Introduction

Accumulating evidence suggests the gut microbiome modulates the efficacy of immunotherapy in advanced lung cancer. However, whether a similar relationship exists with respect to chemotherapy is less clear. In a study presented at WCLC 2020, the association between gut microbiome and response to chemotherapy was evaluated in a cohort of patients with locally advanced, or metastatic lung cancer. In total, 64 chemotherapy treated NSCLC patients were included in this analysis. Baseline stool samples were collected and sequenced using metagenomics. In a second step, the diversity, composition, function and metabolic pathways of gut microbiota were compared between responding and non-responding patients.

Patients enriched with 5 bacterial species had a longer progression-free survival

At time of data cut-off, 33 of the enrolled 64 patients were considered chemotherapy responders, with the remaining 31 being non-responders. The median progression-free survival (PFS) among the 64 patients was 7.0 months. Interestingly, both Streptococcus mutans (p= 0.026) and Enterococcus casseliflavus (p= 0.049) were significantly enriched in the gut microbiome of responder. Conversely, non-responders were enriched for 11 other bacteria, including Leuconostoc lactis (p= 0.002), Butyrivibrio crossotus (p= 0.009), Turicibacter sanguinis (p= 0.036) and Streptococcus oligofermentans (p= 0.036). Differences in relative abundance of microbiome species were also observed when patients were stratified by PFS duration. Responders with a PFS over 7 months were enriched with 5 species, including Haemophilus haemolyticus (p=0.008) and Fusobacterium periodonticum (p= 0.008). Interestingly, higher levels of Turicibacter sanguinis were found to be correlated with a PFS of more than 7 months (p= 0.008), while 7 other bacteria, including Streptococcus anginosus were associated with a PFS below 7 months (p= 0.013) (HR[95%CI]: 0.189[0.092-0.387], p< 0.0001). Subsequent analyses of metabolic pathways found the L-glutamate degradation VIII pathway to be enriched in responders (p= 0.014) while 3 pathways, including the C4 photosynthetic carbon assimilation cycle, were enriched in non-responders (p< 0.05). Finally, 4 metabolic pathways, including purine nucleobases degradation I, were enriched in responders with a PFS over 7 months (p< 0.05).

Statistically significant associations were also found between the presence of certain species and the clinical lung cancer presentation. In fact, Rothia aeria, Rothia dentocariosa, Aggregatibacter aphrophilus, Enterococcus gallinarum, Campylobacter concisus (all P< 0.001), Solobacterium moorei, Bacteroides coprophilus, Aggregatibacter segnis and mitsuokella multacida (all p< 0.01) were associated with pleural metastases, whilst Campylobacter hominis, Pseudomonas mandelii, Prevotella buccae, Streptococcus lutetiensis and Collinsella intestinalis (all p< 0.001) were associated with hepatic metastases.

Conclusion

In this analysis, varying gut microbiome compositions and certain microbiotic metabolic pathways were shown to be associated with the clinical outcomes of chemotherapy in locally advanced or metastatic lung cancer. Furthermore, certain microbiome species were associated with specific phenotypic presentations of lung cancer. Although these results need to be validated in a larger cohort, these microbiotic associations could potentially be used as prognostic biomarkers for chemotherapy in lung cancer.

Reference

Zhao Z et al., The Role of Gut Microbiome in the Efficacy of Chemotherapy in Patients With Locally Advanced and Advanced Lung Cancer. Presented at WCLC 2020; Abstract MA01.03