The Gut Microbiome of Lung Cancer Patients May Affect Treatment Outcomes

A group of researchers in China investigated the uncertainty surrounding the relationship between gut flora and chemotherapy outcomes. The study included patients with locally advanced (stage 3) or advanced (stage 4) lung cancer who had received first-line chemotherapy, totaling 64 patients. The following conditions were also reported to apply to the patients:

• No clinical diagnosis of a psychiatric disorder
• No autoimmune, metabolic, or gastrointestinal disease
• No history of gastrointestinal surgery
• No history of another cancer treatment
• No acute or chronic infection within the past six months
• No antibiotic, probiotic, or steroid use within the past six months.
• No radiotherapy, targeted therapy, surgery, or immunotherapy for their cancers.

Data obtained from stool samples from these 64 patients who met the criteria and were included in the study were used. Clinical characteristics were also recorded, including age, sex, smoking/nonsmoking history, pathological tumor type, clinical stage, chemotherapy regimen, efficacy, and side effects. Tumor sizes were assessed four weeks before treatment began using computed tomography (CT) and/or magnetic resonance imaging (MRI). Microbiota composition, diversity, function, and metabolic pathway analysis were compared between patients with different clinical outcomes.

What Is Microbiota? Harmless microorganisms that may be viruses, bacteria, or fungi and live with us in our bodies are called the microbiome / microbiota / flora. They are most abundant in the gut, followed by the skin, mouth, and vagina. Gut microbiota weighs approximately 1.5 kilos and is now considered an organ because of both its function and weight. We continue to live with these beneficial microorganisms in a mutually beneficial relationship.

What Were the Study's Findings?

Of the 64 patients, 33 responded to chemotherapy and the remaining 31 did not. According to the variance analysis, Streptococus muttans and Enterococcus casseliflavus bacteria increased in responders (P < 0.05), while Leuconostoc lactis and Eubacterium siraeum were among 11 bacteria that increased in nonresponders (P < 0.05).

According to Lefse analysis, responders were associated with significantly higher Acidobacteria and Granulicella, whereas Streptococcus oligofermentans, Megasphaera micronuciformis , and Eubacterium siraeum were more abundant in nonresponders.

Streptococcus mutans and Enterococcus casseliflavus were identified as bacterial markers associated with responders using unsupervised clustering, while Leuconostoc lactis and Eubacterium siraeum were associated with nonresponders.

The pathogenic mechanism of smoking is a known risk factor for lung cancer. In patients with a long history of smoking, Streptococcus thermophilus was clearly reduced. Streptococcus thermophilus has in vitro probiotic properties along with anticancer activity. Whether smoking causes an imbalance in gut flora and thereby affects the health of the whole body is therefore a question that can be investigated.

Different cancer types appear to have their own unique gut microbial characteristics. In the study, lung cancer patients with different pathologies also showed different microbial signatures. For example, various bacteria such as Blautia obeum and Akkermansia muciniphila increase only in patients with metastatic lung cancer. Collinsella intestinalis was reduced in lung adenocarcinoma but increased in small cell lung cancer. Mitsuokella multacida and Alloscardovia omnicolens were increased in squamous cell lung carcinoma. Differences in flora between pathological types could be explored further to provide another possible diagnostic approach for patients without adequate conditions for needle biopsy.

The figure below also shows differences in flora associated with different metastatic sites identified in this study, which could form the basis of individualized treatment for patients.

Figure description: A heat map of associations between bacterial species and clinical phenotypes. Colors show correlation coefficient (r) values. Red indicates a perfectly positive correlation; purple indicates a negative correlation, and white indicates no correlation. Darker colors indicate greater relevance. Asterisks indicate the P value for correlation: a single asterisk (*) for P < 0.05; two asterisks (**) for P < 0.001; and three asterisks (***) for P < 0.001.

What Do the Findings Mean?

The gut microbiome may be a modifiable factor affecting the efficacy and toxicity of cancer treatment. This study is the first detailed report of human gut microbiome metagenomic profiling in lung cancer patients treated with first-line chemotherapy. It demonstrated correlations between gut microbiota and clinical phenotypes and identified specific candidates that may help predict chemotherapy outcomes. By providing a broader understanding of the gut microbiome's effect on chemotherapy efficacy in lung cancer patients, these findings also paved the way for further research.

Treatment outcomes in cancer patients receiving chemotherapy or chemotherapy combined with immunotherapy are positively associated with certain specific gut microbiota species, such as Bacteroides ovatus and Bacteroides xylanisolvens. However, the relationship between specific flora and chemotherapy outcomes in lung cancer patients remains unclear. The study proposed microbial biomarkers for this relationship. Streptococcus mutans and Enterococcus casseliflavus increases appear to be linked to better chemotherapy responses.

Finally, the biological mechanism by which any of the bacteria discussed in this study improves response to cancer treatment is unknown. These findings therefore need to be investigated through more in-depth experiments in a mouse model.

What Are the Study's Limitations?

The small sample size (64 patients) prevented comprehensive and systematic profiling of microbial biomarkers for chemotherapy outcomes in lung cancer patients. Further validation in larger samples and the development of a predictive model are required.

Another limitation is that, although the efficacy of the selected microbial markers was validated in the non-small cell and small cell lung cancer groups, subgroup analyses are needed for greater accuracy.

In conclusion, the study provided a description of gut microbiota in patients with different chemotherapy outcomes, an important first step toward understanding the relationship between the gut microbiome and chemotherapy efficacy in lung cancer.