Tumor-induced species-specific dysbiosis drives renal innate immunity and nephrogenic ascites

Ascites is a life-threatening complication of advanced malignancies, yet how tumors disrupt systemic fluid homeostasis remains poorly understood. Here, using a <i>Drosophila</i> tumor allograft model that recapitulates key features of cancer-associated ascites, we identify a tumor-microbiome-renal axis that controls host fluid balance. Tumor-bearing hosts develop severe abdominal fluid accumulation accompanied by marked expansion and systemic dissemination of the gut commensal <i>Acetobacter aceti</i> . Tumor-induced bacterial dissemination activates innate immune signaling in the Malpighian tubules, the insect renal tubules, leading to uric acid accumulation, nephrolithiasis, and progressive ascites. Selective elimination of <i>A. aceti</i> , or renal-tubule-specific suppression of IMD/NF-κB signaling, abolishes these pathological changes. Conversely, mono-association of axenic hosts with <i>A. aceti</i> is sufficient to recapitulate the ascites phenotype through IMD pathway activation. Together, these findings demonstrate that tumors can remotely induce nephrogenic pathology through species-specific microbiome-dependent immune activation, establishing a mechanistic link between cancer progression and systemic fluid imbalance.