How Advanced Is Our Understanding of the Role of Intestinal Barrier Dysfunction in the Pathogenesis of Recurrent Urinary Tract Infections

Abstract

A comprehensive understanding of urinary tract infections (UTIs), one of the most common human infections, is required as they are complex and poorly understood diseases. Periurethral and vaginal colonization by rectal flora, with the constant presence of pathogens in the urethra, is the initial step of the recurrent UTIs pathway. Current scientific data describe the genetic, etiological, biological, and behavioral risk factors for recurring UTIs, but they do not include the effect of intestinal barrier function on the disease. Although gut microbiota has been proposed as the main source for UTIs, the cross-talk between intestinal barrier dysfunction and the recurrence of UTIs has not yet been supported by scientific data. In this opinion review, based on published data and the results of our clinical studies, I aimed to outline the possible contribution of intestinal barrier dysfunction to the pathogenesis of recurrent UTIs. I believe that the unanswered questions raised by this review can guide further experimental and controlled studies to clarify the mechanisms underlying the role of intestinal barrier dysfunction in the pathogenesis of recurrent UTIs.

The Gut-Peritoneum Axis in Peritoneal Dialysis and Peritoneal Fibrosis

“… 33 , 34 , 35 The disruption of the intestinal barrier by dysbiosis facilitates the circulation of LPSs, metabolites, and toxins to the organs and initiates the inflammatory cascade, contributing to the progression and adverse outcomes of CKD. 30 , 36 , 37 , 38 …”

Cranberry Polyphenols and Prevention against Urinary Tract Infections: New Findings Related to the Integrity and Functionality of Intestinal and Urinary Barriers

“…Preservation of the integrity and functionality of the intestinal barrier is dependent on the intactness of the apical plasma membrane on the epithelial cells as well as the intercellular tight junctions (TJ) . Moreover, TJ disruption can cause increased intestinal permeability, leading to “leakiness” in the way that pathogens (i.e., extraintestinal pathogenic Escherichia coli [ExPEC]) can cross the gut epithelium via paracellular permeation, facilitating their translocation to the urinary tract . In the case of the bladder, it has been reported that the urothelium permeability increases as the expression of TJ proteins decreases, allowing the entry/passage of bacteria as well as the passage of ions through the blood-urinary barrier .…”

“…8 Moreover, TJ disruption can cause increased intestinal permeability, leading to "leakiness" in the way that pathogens (i.e., extraintestinal pathogenic Escherichia coli [ExPEC]) can cross the gut epithelium via paracellular permeation, facilitating their translocation to the urinary tract. 7 In the case of the bladder, it has been reported that the urothelium permeability increases as the expression of TJ proteins decreases, allowing the entry/passage of bacteria as well as the passage of ions through the bloodurinary barrier. 9 In addition, it has been found that UPEC infection disrupts the tight binding barrier with decreased expression of TJ proteins.…”

“…5 Urothelium dysfunctions have been closely associated with UTI pathogenesis and/or its recurrence, 6 whereas the cross talk between intestinal barrier dysfunction and UTI has not been extensively studied. 7 Both the intestinal and urinary tracts are lined with layers of epithelial cells that provide permeability to allow a rapid exchange of solutes and nutrients, and these layers also maintain a physical and functional barrier to harmful microorganisms and their products. Preservation of the integrity and functionality of the intestinal barrier is dependent on the intactness of the apical plasma membrane on the epithelial cells as well as the intercellular tight junctions (TJ).…”

A review on pilus assembly mechanisms in Gram-positive and Gram-negative bacteria

“…Pili acts as an initiator of host-pathogen interaction ( Zhou et al, 2021 ). In particular, pilin subunits proteins (both major and minor) play a significant role in aiding the bacterial attachment and colonization to the host cells and other conditioned surfaces found on implants such as catheters ( Flores-Mireles et al, 2015 , Govindarajan et al, 2020 , Jacobsen et al, 2008 , Nallapareddy et al, 2011 , Stepanova, 2022 ). Interaction of pili with host cells takes place in a sequential manner which requires proper subcellular secretion of pilin subunits in the cytoplasmic membrane and translocation to the surface of the bacterial cell to complete the assembly of pilus fiber ( Flores-Mireles et al, 2015 , Kline et al, 2010 , Proft and Baker, 2009 ).…”