Oral–Gut Microbiome Coalescence and Ecosystem Fragility Drive Carbapenem-Resistant Organism Colonization and Infection in Relapsed/Refractory Acute Leukemia

The microbiome actively determines infection outcomes in immunocompromised hosts. Here we reveal that oral–gut microbiome coalescence marks a fragile microbial ecosystem that predisposes relapsed/refractory acute leukemia (R/R AL) patients to carbapenem-resistant organism (CRO) colonization and infection. A longitudinal cohort (n = 18, 144 samples) and a cross-sectional validation cohort (n = 23, 47 samples) demonstrated microbial instability and increased oral–gut convergence dominated by Enterococcus and Klebsiella in R/R AL patients. In vitro assays confirmed a fourfold reduction in colonization resistance in R/R-derived microbiota (44.0 vs 11.2 CFU, p = 0.023). A clinical cohort (n = 1,821) validated R/R status as an independent risk factor for CRO infection (OR = 1.57, p = 0.038) and 30-day mortality (OR = 3.35, p < 0.001), partially mediated by colonization (22.8%). Our study integrates microbial ecology, functional validation, and clinical causality, defining oral–gut community coalescence as both a biomarker and a mechanism of infection vulnerability in R/R AL patients.