Gut microbiota composition in responders vs. non-responders with hepatocellular carcinoma under ICI therapy: a systematic review and meta-analysis.

INTRODUCTION: The associations between gut microbiota and disease progression, as well as the prognostic implications of gut microbiota, remain unclear in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICIs). This study aimed to delineate gut microbiome differences among ICI-treated patients with intermediate-to-advanced HCC and assess their correlations with clinical outcomes via meta-analysis. METHODS: We searched 4 databases (PubMed, Embase, Web of Science, and the Cochrane Library) and collected related articles published before May 31, 2026. We calculated standard mean differences (SMDs) and 95% confidence intervals (CIs) using a random-effects model. Summarized hazard ratios (HRs) with 95% CIs were used to assess gut microbiome associations with overall survival (OS) and progression-free survival (PFS). Subgroup, sensitivity, and publication bias analyses were further conducted, with all statistical analyses performed using RevMan and R. RESULTS: A total of 13 eligible papers were included. (1) The meta-analysis of Alpha diversity indices between R and NR was no significant difference, but over 68% of the studies reported significant differences in beta diversity. (2) At the phylum level, Actinobacteriota were significantly enriched in the R group. At the genus level, depleted Bacteroides exhibited distinct relative abundance in the NR group. (3) Protective taxa (Collinsella, Ruminococcus.AF25_28AC, Ruminococcus.AM42_11, Erysipelotrichaceae bacterium-GAM147, Bacteroides stercoris/Parabacteroides merdae) correlated with reduced mortality risk. Risky taxa (Bacteroides.AF20_13LB, Veillonella.atypica, Veillonella.AF13_2, Veillonellaceae and s_Actinomyces_sp_ICM47) showed worse OS outcomes. (4) PFS-protective taxa (Collinsella, Bacteroidales zoogleoformans, Ruminococcus.AF25_28AC, Ru-minococcus callidus, and Erysipelotrichaceae bacterium GAM147) correlated with reduced progression risk. PFS-detrimental taxa (Prevotella 9, Bacteroides_AF20_13LB, Veillonella atypica, and Lachnoclostridium) showed worse outcomes. (5) Responders showed upregulated bile acid metabolism, fatty acid biosynthesis, methanogenesis and carbon fixation pathways associated with beneficial genera, while non-responders exhibited elevated secondary bile acid metabolism, arginine biosynthesis and carbohydrate transport pathways linked to detrimental taxa. CONCLUSIONS: HCC patients with varied treatment responses exhibit characteristic shifts in gut flora. Compositional and functional variations of intestinal microbes serve as potential indicators of disease status, promising prognostic predictors, and references for clinical therapeutic decisions. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, PROSPERO CRD420261363281.