Recurrent Urinary Tract Infections: Unraveling the Complicated Environment of Uncomplicated rUTIs

Abstract

Urinary tract infections (UTIs) are frequent in humans, affecting the upper and lower urinary tract. Present diagnosis relies on the positive culture of uropathogenic bacteria from urine and clinical markers of inflammation of the urinary tract. The bladder is constantly challenged by adverse environmental stimuli which influence urinary tract physiology, contributing to a dysbiotic environment. Simultaneously, pathogens are primed by environmental stressors such as antibiotics, favoring recurrent UTIs (rUTIs), resulting in chronic illness. Due to different confounders for UTI onset, a greater understanding of the fundamental environmental mechanisms and microbial ecology of the human urinary tract is required. Such advancements could promote the tandem translation of bench and computational studies for precision treatments and clinical management of UTIs. Therefore, there is an urgent need to understand the ecological interactions of the human urogenital microbial communities which precede rUTIs. This review aims to outline the mechanistic aspects of rUTI ecology underlying dysbiosis between both the human microbiome and host physiology which predisposes humans to rUTIs. By assessing the applications of next generation and systems level methods, we also recommend novel approaches to elucidate the systemic consequences of rUTIs which requires an integrated approach for successful treatment. To this end, we will provide an outlook towards the so-called ‘uncomplicated environment of UTIs’, a holistic and systems view that applies ecological principles to define patient-specific UTIs. This perspective illustrates the need to withdraw from traditional reductionist perspectives in infection biology and instead, a move towards a systems-view revolving around patient-specific pathophysiology during UTIs.