Navigating the gut–metabolite–immune axis: enhancing efficacy and mitigating toxicity of immune checkpoint inhibitors

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Immune checkpoint inhibitors (ICIs) target PD-1, PD-L1, and CTLA-4, transforming cancer treatment and becoming first-line therapies for various malignancies.
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Interpatient variability in ICI efficacy is linked to gut microbiome composition, influencing immune response and treatment outcomes.
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Microbial metabolites, such as butyrate, enhance CD8+ T-cell function and improve responses to ICI therapy by modulating the tumor microenvironment.
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Fecal microbiota transplantation and probiotics have shown potential in enhancing ICI efficacy and reducing immune-related adverse events in early studies.
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Future research must focus on large-scale studies to develop predictive models integrating microbiome data to optimize ICI treatment.

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