Urinary Glycosaminoglycans Are Associated with Recurrent UTI and Urobiome Ecology in Postmenopausal Women

Abstract

Glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides composed of repeating disaccharide units of uronic acid and amino sugars. The luminal surface of the bladder epithelium is coated with a GAG layer. These urothelial GAGs are thought to provide a protective barrier and serve as a potential interaction site with the urinary microbiome (urobiome). Previous studies have profiled urinary GAG composition in mixed cohorts, but the urinary GAG composition in postmenopausal women remains undefined. To investigate the relationship between GAGs and recurrent urinary tract infection (rUTI), we profiled urinary GAGs in a controlled cohort of postmenopausal women. We found that chondroitin sulfate (CS) is the major urinary GAG in postmenopausal women and that urinary CS was elevated in women with active rUTI. We also associated urinary GAGs with urobiome composition and identified bacterial species that significantly associated with urinary GAG concentration. Corynebacterium amycolatum, Porphyromonas somerae, and Staphylococcus pasteuri were positively associated with heparin sulfate or hyaluronic acid, and bacterial species associated with vaginal dysbiosis were negatively correlated with urinary CS. Altogether, this work defines changes in urinary GAG composition associated with rUTI and identifies new associations between urinary GAGs and the urobiome that may play a role in rUTI pathobiology.

Lower Urinary Tract Inflammation and Infection: Key Microbiological and Immunological Aspects

“…Consisting of several layers of urothelium and an overlaying glycosaminoglycan (GAG) layer, this membrane is the most impermeable in the body, providing a barrier against the external environment and urine [1]. The GAG layer plays a key role in immune responsiveness, with altered layer composition being associated with recurrent UTIs in a cohort of post-menopausal women [2]. While mechanical and physiological barriers provide good protection against pathogen exposure, additional mechanisms are required to provide a secondary layer of defense.…”

Synthesis of current pediatric urinary microbiome research

“…To date, there are no other female-only studies, and there are no studies at all that examine the healthy urobiome of exclusively females across any age range. While the importance of understanding urobiome development for recurrent UTI studies in female participants is clearly shown ( 54 ), no studies have yet addressed this issue carefully in female children.…”