# A Silent Saboteur of Immunotherapy: Antibiotic Use and Its Impact on Immune Checkpoint Inhibitors Efficacy, a Systematic Review and Meta-Analysis of Recent Studies

## TL;DR

Taking antibiotics while undergoing immunotherapy may reduce treatment effectiveness by disrupting gut bacteria, according to a review of recent studies.

## Contribution

This study is the first systematic review and meta-analysis to show a consistent link between antibiotic use and reduced efficacy of immune checkpoint inhibitors in solid tumors.

## Key findings

- Antibiotic exposure was associated with worse overall survival in patients receiving immune checkpoint inhibitors.
- A sensitivity analysis in non-small cell lung cancer confirmed the link between antibiotics and poorer treatment outcomes.
- The findings suggest gut microbiota disruption by antibiotics may impair immunotherapy effectiveness.

## Abstract

Immune checkpoint inhibitors (ICIs) have improved outcomes in many solid tumors, but durable responses occur in only a minority of patients. Given the role of the gut microbiota in shaping antitumor immunity, systemic antibiotic therapy (ABT) may impair the effectiveness of immune checkpoint inhibitors (ICIs) by inducing gut dysbiosis. This PRISMA 2020-compliant systematic review and meta-analysis searched PubMed, Scopus, and EMBASE for studies published from 2018 to 2025 that evaluated ABT exposure (with clearly defined timing windows) and survival outcomes in ICI-treated solid tumors. Fifteen studies including 52,489 patients were analyzed primarily using random-effects models. ABT exposure was associated with worse overall survival (HR 1.16, 95% CI 1.03–1.29) and a trend toward worse progression-free survival (HR 1.11, 95% CI 0.95–1.27). In a sensitivity analysis of non-small cell lung cancer, ABT was consistently linked to inferior outcomes, supporting the association. These findings argue for careful antibiotic stewardship during ICI therapy and for prospective studies incorporating microbiome profiling.

Background: Immune checkpoint inhibitors (ICIs) have transformed the management of solid tumors, yet only a subset of patients achieve durable benefit. The gut microbiota is a key modulator of antitumor immunity, and systemic antibiotic therapy (ABT), frequently prescribed—and sometimes overused—in oncology, can profoundly disrupt microbial homeostasis. Observational studies suggest that ABT may impair ICI efficacy, but results remain heterogeneous, warranting an updated synthesis. Methods: We conducted a systematic review and meta-analysis in accordance with the PRISMA 2020 guidelines. PubMed, Scopus, and EMBASE were searched for studies published between 2018 and 2025 evaluating the association between ABT exposure and time-to-event outcomes in patients with solid tumors treated with ICIs. Studies were required to report explicit definition of the ABT exposure window. Random-effects models were considered primary. A sensitivity analysis was performed in non-small cell lung cancer (NSCLC). Results: Fifteen studies encompassing 52,489 patients were included. ABT exposure was associated with significantly worse OS (random-effects HR 1.16, 95% CI 1.03–1.29) and PFS (random-effects HR 1.11, 95% CI 0.95–1.27), indicating an increased risk of death and disease progression compared with no ABT exposure. In the NSCLC sensitivity analysis, ABT was consistently associated with inferior PFS and, when accounting for heterogeneity, with significantly reduced OS, supporting the robustness of the association. Conclusions: ABT administered in temporal proximity to ICIs is associated with clinically meaningful worsening of survival outcomes across solid tumors, consistent with microbiome-mediated impairment of immunotherapy efficacy. These findings support cautious ABT stewardship in patients receiving ICIs and highlight the need for prospective studies integrating microbiome profiling and standardized ABT exposure assessment.