Write a PREreview

Background: Accumulating evidence suggests that gut microbiome composition influences response to immune checkpoint inhibitor (ICI) therapy in cancer patients. Dietary interventions represent a modifiable approach to optimize microbiome profiles for improved immunotherapy outcomes. This systematic review and meta-analysis quantifies the association between dietary interventions targeting gut microbiome modulation and clinical outcomes in cancer immunotherapy. Methods: We conducted a systematic search of PubMed, Embase, Web of Science, Cochrane CENTRAL, and Scopus databases from January 2010 to August 2025, following a prospectively registered protocol (PROSPERO: CRD42025395817). We included clinical studies evaluating dietary interventions (≥7 days duration) with quantitative microbiome assessment and immunotherapy outcomes. Two reviewers independently performed study selection, data extraction, and quality assessment using Risk of Bias 2 (RoB-2) and Newcastle-Ottawa Scale tools. Meta-analysis was performed using random-effects models with the metafor package in R. Evidence certainty was assessed using GRADE methodology. Results: Eight studies encompassing 1,247 cancer patients met inclusion criteria. Dietary interventions included high-fiber diets (n=4 studies), Mediterranean diet patterns (n=2), prebiotic supplementation (n=1), and combined probiotic-prebiotic approaches (n=1). Meta-analysis revealed that dietary interventions were associated with significantly improved objective response rates to ICI therapy compared to standard care (pooled odds ratio [OR] 2.27, 95% confidence interval [CI] 1.48-3.46, p=0.0002). Statistical heterogeneity was moderate (I²=65%). Leave-one-out sensitivity analysis confirmed robust findings (OR range: 2.01-2.67). A post-hoc subgroup analysis suggested consistent effects across cancer types. Publication bias assessment revealed minimal evidence of small-study effects (Egger/Begg tests are underpowered with <10 studies; non-significant p values do not prove absence of bias.). Conclusions: Dietary interventions targeting gut microbiome modulation are associated with improved objective response rates to immune checkpoint inhibitor therapy, with moderate certainty evidence. These findings are promising and may inform clinical trials and pilot implementation; however, routine clinical adoption is premature without confirmatory randomized trials.