Baseline Gut Microbiota Composition Links Immune–nutritional Status to Clinical Outcomes in Non-small Cell Lung Cancer Treated With Atezolizumab-based Immunotherapy: A Multicenter Prospective Study

Background/Aim: Immune–nutritional status and gut microbiota composition have been proposed as biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). However, their interrelationship and longitudinal dynamics during immunotherapy remain unclear. Patients and Methods: In this multicenter prospective study, patients with advanced or recurrent NSCLC treated with atezolizumab-based immunotherapy were enrolled. Serial fecal samples were analyzed using 16S rRNA gene sequencing. Immune–nutritional status was evaluated using the prognostic nutritional index (PNI). Associations between baseline PNI, gut microbiota composition, treatment response, immune-related adverse events (irAEs), and longitudinal microbiota changes were assessed. Results: Sixty-five patients were included (27 responders and 38 non-responders). Pretreatment PNI was significantly associated with treatment response (p=0.0048) and improved progression-free and overall survival. During follow-up, 12 patients (18.5%) developed irAEs. Lachnospiraceae UCG-008 was enriched in patients with high PNI and in those without irAEs. Longitudinal analysis showed stable abundance of this taxon during treatment with no significant temporal changes. Conclusion: Pretreatment gut microbiota composition was associated with immune–nutritional status and clinical outcomes in patients with NSCLC receiving atezolizumab-based immunotherapy. Lachnospiraceae UCG-008 was linked to favorable host status and lower irAE risk, remaining stable during treatment. These findings suggest that baseline gut microbiota may serve as a clinically relevant biomarker for both the efficacy and safety of immunotherapy.