The role of the urinary microbiome in diabetes-associated UTIs: current understanding and future directions

This review explores the interplay between type 2 diabetes mellitus (T2DM) and urinary microbiome dysbiosis, focusing on its role in urinary tract infections (UTIs). Once considered sterile, the urinary tract hosts a diverse microbiota that supports mucosal immunity and pathogen resistance. In T2DM, chronic hyperglycemia and glycosuria disrupt microbial balance, impair immune responses, and increase UTI susceptibility. Glycosuria promotes pathogenic colonization, biofilm formation, and microbial shifts, with studies reporting a threefold rise in <i>Escherichia coli</i> and a 56 % reduction in <i>Lactobacillus</i> spp. in diabetic women with recurrent UTIs. Diabetic urine shows reduced diversity, higher abundance of <i>Klebsiella</i>, <i>Pseudomonas</i>, and <i>Enterococcus</i>, and elevated IL-8. Microbiota-targeted interventions, including probiotics (<i>Lactobacillus crispatus</i>, <i>Lactobacillus rhamnosus</i> GR-1), prebiotics (astaxanthin), and phytotherapeutics (cranberry), demonstrate potential via lactic acid, hydrogen peroxide production, competitive exclusion, and NF-κB modulation. A 12-month RCT showed significant UTI recurrence reduction with probiotics. Advances in 16 S rRNA sequencing and metagenomics reveal microbial signatures associated with diabetic UTIs, though methodological heterogeneity limits comparability. A review of 1,200 publications (2000-2024) highlights the need for longitudinal studies and precision microbiota therapeutics to translate findings into clinical practice.