Systemic defense against oxidative stress - The role of iron imbalance revealed by multiomics mechanisms leading to urosepsis.

Urinary Tract Infections (UTIs) and urosepsis represent significant challenges in clinical medicine, necessitating a deeper understanding of the molecular intricacies underlying these conditions. In this study, we employed a multi-omics approach to elucidate the molecular landscape associated with UTIs and urosepsis, with a specific focus on ferroptosis and oxidative stress. Through integrative analysis of metabolomic, proteomic, and genetic data, we identified potential bacterial and human biomarkers linked to iron sequestration, oxidative damage, and dysregulated pathways associated with the progression and severity of UTIs and urosepsis. Elevated levels of glutathione, iron-handling proteins, and pro-inflammatory cytokines: Interleukin-6, Interleukin-8 suggest a mechanistic link between oxidative stress and ferroptosis in urosepsis. Importantly, our study highlights the role of oxidative damage in exacerbating tissue injury and systemic dysfunction during the progression of sepsis. We also identified 5,6-Dihydroxyindole-2-carboxylic acid as a novel biomarker for urosepsis, indicating that oxidative stress and iron metabolism dysregulation may extend beyond standard organs to influence broader systemic responses. This metabolite may serve as an early indicator for detecting and differenting of urosepsis from uncomplicated UTIs, providing a valuable tool to improve diagnostic precision and patient outcomes.