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 Drosophila 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 Acetobacter aceti. 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 A. aceti, or renal-tubule-specific suppression of IMD/NF-{kappa}B signaling, abolishes these pathological changes. Conversely, mono-association of axenic hosts with A. aceti 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.