Gut Microbiota Interventions to Enhance Immune Checkpoint Inhibitor Therapy Clinical Applications Challenges and Future Perspectives

Abstract

Immune checkpoint inhibitors (ICIs) have emerged as a critical component of cancer immunotherapy, yet the limited response rates and immune-related adverse events (irAEs) continue to restrict their efficacy and safety. The gut microbiota, increasingly recognized as an important regulator of host immunity, has demonstrated its potential in shaping systemic antitumor responses and influencing sensitivity to immune checkpoint blockade. This paper focuses on gut microbiota-targeted interventions as a strategy to enhance ICI efficacy, with particular emphasis on fecal microbiota transplantation (FMT) and probiotics. Recent studies from both experimental models and early clinical trials suggest that such interventions are associated with improved immunotherapy responses and enhanced clinical outcomes in combination with ICIs. Although different in form, FMT and probiotic-based strategies converge on the concept that reshaping the intestinal microbial environment may help overcome suboptimal responses to ICIs. At the same time, the clinical applicability of these approaches is still under active investigation. Overall, this paper summarizes current progress in gut microbiota modulation for cancer immunotherapy, discusses existing limitations, and outlines key challenges for future research. A clearer understanding of how microbiota-targeted interventions interact with ICI therapy is of great importance for their rational integration into clinical practice.