Rijul Nanda

Background: Urinary tract infections (UTIs) are one of the most common bacterial infections around the world, affecting over 150 million people yearly with an estimated cost of UTIs being $2.8 billion¹. There is a paucity of research to discover novel strategies for UTI outside of antibiotics, especially therapies that prevent recurrent UTIs. Further, the high incidence of UTIs place undue burdens on healthcare systems due to antibiotics for UTI contributing to the spread of antibiotic-resistant bacterial pathogens. Recent research on dysbiosis of the urinary microbiome represents a path forward for novel treatments and prophylaxis of these infections, including restoring microbial diversity and preventing invasion by commensal bacteria from the gut.

Search Methods: Assessment of microbial diversity of the urinary microbiome involves different techniques, including 16S rRNA sequencing and whole genome sequencing². These techniques have been applied across several studies that have delineated dysbiosis in different organs including the gastrointestinal, urinary, and vagina tract. With this, novel treatment paradigms have been developed to address the dysbiosis and reduce the impact of antibiotic resistance on the healthcare system.

Results: Dysbiosis is frequently caused by an overabundance of E. coli, Enterococcus faecalis, and Klebsiella pneumoniae³; furthermore, some studies show that recurrences of UTIs in the same patient may be caused by varying strains of E. coli over time, for those who are primarily infected by that bacteria³. In another study, researchers found that an increased abundance of E. coli in the gut was associated with an increased risk of developing a UTI caused by E. coli⁴. Research has noted the presence of E. faecalis and E. faecium in both fecal samples and urine samples in patients with UTIs⁴, establishing a link between colonization by pathobiont bacteria in the gut with the urinary tract. Common antibiotics for UTIs have been shown modify the urinary microbiome, predisposing patients to recurrent UTIs, requiring the use of dysbiosis-associated antibiotics that further perpetuate this cycle⁵. Due to the increase in antibiotic resistance by uropathogens⁶, new treatment paradigms involving analgesics⁷, poly-bacteriophage cocktails⁸, and preparations of Lactobacillus-containing drinks and ovules⁹ have been developed.

Conclusions: Urinary microbiome dysbiosis is implicated in the pathogenesis of UTIs, and research involving dysbiosis has allowed for novel treatment discovery to address concerns of antibiotic resistance. However, there is a need to understand the extent to which analysis of dysbiosis can be adopted to predict risk for recurrence and utilize alternative therapies to mitigate this risk.

Works Cited:

1. Perez-Carrasco V, Soriano-Lerma A, Soriano M, Gutiérrez-Fernández J, Garcia-Salcedo JA. Urinary microbiome: Yin and Yang of the urinary tract. Frontiers. https://www.frontiersin.org/articles/10.3389/fcimb.2021.617002/full. Published April 29, 2021. Accessed February 20, 2023.
2. Thomas-White K, Forster SC, Kumar N, et al. Culturing of female bladder bacteria reveals an interconnected urogenital microbiota. Nature News. https://www.nature.com/articles/s41467-018-03968-5. Published April 19, 2018. Accessed February 28, 2023.
3. Chen Z, Phan M-D, Bates LJ, et al. The urinary microbiome in patients with refractory urge incontinence and recurrent urinary tract infection. International urogynecology journal. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244753/. Published June 26, 2018. Accessed February 1, 2023.
4. Magruder M, Sholi AN, Gong C, et al. Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection. Nature communications. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893017/. Published December 4, 2019. Accessed March 2, 2023.
5. Mulder M, Radjabzadeh D, Hassing RJ, et al. The effect of antimicrobial drug use on the composition of the genitourinary microbiota in an elderly population. BMC microbiology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327605/. Published January 9, 2019. Accessed March 16, 2023.
6. Thänert R, Reske KA, Hink T, et al. Comparative genomics of antibiotic-resistant uropathogens implicates three routes for recurrence of urinary tract infections. mBio. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712402/. Published August 27, 2019. Accessed March 1, 2023.
7. Palleschi G, Carbone A, Zanello PP, et al. Prospective study to compare antibiosis versus the Association of N-Acetylcysteine, D-mannose and Morinda citrifolia fruit extract in preventing urinary tract infections in patients submitted to urodynamic investigation. Archivio Italiano di Urologia e Andrologia. https://www.pagepressjournals.org/index.php/aiua/article/view/aiua.2017.1.45. Published March 31, 2017. Accessed March 20, 2023.
8. Ujmajuridze A, Chanishvili N, Goderdzishvili M, et al. Adapted bacteriophages for treating urinary tract infections. Frontiers in microbiology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090023/. Published August 7, 2018. Accessed March 1, 2023.
9. Akgül T, Karakan T. The role of probiotics in women with recurrent urinary tract infections. Turkish journal of urology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134985/. Published September 1, 2018. Accessed March 16, 2023.