biostudies-literatureQiao TGuangdong Basic and Applied Basic Research FoundationGuangzhou Basic and Applied Basic Research Project2595https://www.ebi.ac.uk/biostudies/studies/S-EPMC12654497biostudies-literatureUnknown13(11)An increasing number of studies have confirmed that the gut microbiota, especially bacteria, is closely related to the efficacy of immune checkpoint inhibitor (ICI) therapy. However, the effectiveness of multi-kingdom microbiota and their interactions in predicting the therapeutic effect of ICI therapy remains uncertain. We integrated extensive gut metagenomic databases, including 1712 samples of 10 cohorts from 7 countries worldwide, to conduct rigorous differential analysis and co-occurrence network analysis targeting multi-kingdom microbiota (bacteria, fungi, archaea, and virus). We ultimately identified two subtypes (C1 and C2) by employing a weighted similarity network fusion (WSNF) method. Subtype C2 exhibited higher microbial diversity, better treatment response, and improved prognoMicroorganismsMulti-Kingdom Gut Microbiome Interaction Characteristics Predict Immune Checkpoint Inhibitor Efficacy Across Pan-Cancer Cohorts.PMC126544972025A04J52642023A1515010744Zhu ZQiao TfalseMulti-Kingdom Gut Microbiome Interaction Characteristics Predict Immune Checkpoint Inhibitor Efficacy Across Pan-Cancer Cohorts.An increasing number of studies have confirmed that the gut microbiota, especially bacteria, is closely related to the efficacy of immune checkpoint inhibitor (ICI) therapy. However, the effectiveness of multi-kingdom microbiota and their interactions in predicting the therapeutic effect of ICI therapy remains uncertain. We integrated extensive gut metagenomic databases, including 1712 samples of 10 cohorts from 7 countries worldwide, to conduct rigorous differential analysis and co-occurrence network analysis targeting multi-kingdom microbiota (bacteria, fungi, archaea, and virus). We ultimately identified two subtypes (C1 and C2) by employing a weighted similarity network fusion (WSNF) method. Subtype C2 exhibited higher microbial diversity, better treatment response, and improved progno2025-01-01T00:00:00Z2025 Nov2026-07-05T03:09:37.308Z2026-07-05T03:08:15.843ZS-EPMC126544974130427810.3390/microorganisms13112595