Broad-spectrum Antibiotics Associated Gut Microbiome Disturbance Impairs T Cell Immunity and Promotes Lung Cancer Metastasis: a Retrospective Study

Background: Gut microbiome has been linked to a regulatory role in cancer progression. However, whether broad-spectrum antibiotics (ATB) associated gut microbiome dysbiosis contributes to an impaired T cell immune function, and ultimately promotes lung cancer metastasis is not well known.

Methods: In this study, a retrospective analysis was performed in a cohort of 263 patients initially diagnosed with non-small cell lung cancer (NSCLC) patients, including the ATB group (patients with broad-spectrum antibiotics treatment) (n = 124), and non-ATB group (n = 139) as control. ATB patients were prescribed ATB for over 5 days within 30 days prior to the collection of blood and fecal specimens and followed surgical treatment or first-line therapy. T cell immune function and metastasis-free survival (MFS) were evaluated between the two groups. Gut microbiota was evaluated by 16S rDNA sequencing. The predictive value of T cell immunity for MFS was evaluated by ROC analysis and Cox regression analysis.

Results: Our results suggest that broad-spectrum antibiotics (ATB) impair T cell immune function in patients with either early-stage or advanced NSCLC, which likely contribute to the promotion of lung cancer metastasis. Results of the survival analysis show that metastasis-free survival (MFS) is significantly shorter in the ATB patients than that in the non-ATB patients with stage III NSCLC. The 16S rDNA sequencing shows that ATB administration contributes to a significant dysbiosis of the composition and diversity of gut microbiota. Moreover, ROC analysis results of CD4 (AUC 0.642, p = 0.011), CD8 (AUC was 0.729, p < 0.001), CD16 + 56 + (AUC 0.643, p = 0.003), and the combination of CD4, CD8 and CD16 + 56+ (AUC 0.810, p < 0.001), or Cox regression analysis results of CD4 (HR 0.206, p < 0.001), CD8 (HR 0.555, p = 0.009), which is likely regulated by ATB administration, have significantly predictive values for MFS.

Conclusion: These results provide evidence of gut microbiome disturbance due to ATB administration is involved in the regulation of T cell immunity, and their predictive value for the tumor metastasis in lung cancer patients. Thus, gut microbiota may serve as a therapeutic target for lung cancer. Consequently, caution should be exercised before the long-term administration of broad-spectrum antibiotics in cancer patients.