To synthesize current evidence on how the gut microbiota and microbe-derived metabolites regulate immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs), and to evaluate emerging microbiome-targeted interventions.
Approach:
Literature Search: A comprehensive literature search was conducted across PubMed/MEDLINE, Web of Science Core Collection, and Embase from inception to May 1, 2026, focusing on gut microbiota, ICIs, and clinical outcomes.
Key Findings:
The gut microbiome composition influences the efficacy of ICIs, with specific taxa like Bacteroides, Bifidobacterium, and Akkermansia muciniphila playing pivotal roles.
Microbial metabolites, such as butyrate, enhance immune responses by modulating CD8+ T-cell function and promoting dendritic cell cross-presentation.
Interventions like fecal microbiota transplantation and supplementation with probiotics have shown promise in improving ICI efficacy and reducing irAEs.
Interpretation:
The interplay between the gut microbiome and the immune system is crucial for optimizing ICI therapy.
Limitations:
Heterogeneity in study cohorts and sample-processing methodologies limits the establishment of reproducible predictive models.
Current evidence is primarily from preclinical and early-phase clinical studies, necessitating larger-scale trials.
Conclusion:
Future research should focus on large-scale, multicenter studies integrating metagenomics and metabolomics to develop precise microbial interventions.
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