Gut microbiota alterations in patients with non-small-cell lung cancer undergoing chemoradiotherapy.

Abstract

Growing evidence suggests that gut microbial features may predict-and potentially modulate-responses to cancer therapy, particularly immunotherapy. However, the impact of concurrent chemoradiotherapy (CRT) on the gut microbiota remains less well-understood. This knowledge gap is especially relevant in locally advanced non-small-cell lung cancer (NSCLC), where CRT typically precedes immunotherapy. We therefore investigated whether CRT alters gut microbial composition and whether such changes are associated with survival outcomes. Fecal samples were collected at three time points: prior to CRT (baseline), at completion of CRT, and immediately before initiation of consolidation immunotherapy, from 62 patients with locally advanced NSCLC. Microbiota profiling was performed using a qPCR-based panel (PMP™) targeting 108 prevalent microbial taxa. Within-sample (alpha) and between-sample (beta) bacterial diversity were assessed across time points and clinical subgroups defined by antibiotic exposure and survival outcomes. Alpha diversity remained stable from baseline to completion of CRT (all P > 0.60). Patients who received broad-spectrum antibiotics during CRT had significantly lower alpha diversity compared with those who did not receive antibiotics (P = 0.017), reflecting a transient between-group difference. Beta diversity differed modestly but significantly at baseline between survival groups (progression-free survival ≥ 18 vs < 18 months; PERMANOVA R² = 0.028, P = 0.045). The gut microbiota appears largely stable during CRT for locally advanced NSCLC but is susceptible to disruption by antibiotic use. Baseline beta diversity differences between survival groups may signal a potential role for gut microbial composition as a future preliminary biomarker and warrant further investigation.