SUFU 2021: “Say Hello to My Little Friends”: How We Use the Microbiome in Clinical Urology

( A urinary tract infection (UTI) is defined as microbial infiltration of the normally sterile urinary tract. But there are no accepted definitions of UTI-associated symptoms, cut-offs for culture result, or definitively accepted uropathogens that can guide clinicians in the objective management of a UTI. Urine is no longer considered sterile as microbes reside within the urinary tract even in healthy immunocompromised individuals and in those without urinary symptoms. These are called urinary tract microbiomes. There has been a rapid expansion of the human microbiome –diverse, carefully balanced, well-adapted, and beneficial to the body. Dysbiosis is microbial imbalance or maladaptation on or inside the body and is implicated in many diseases.  In the genito-urinary tract, dysbiosis can cause the breakdown of epithelial barrier promoting increased vascularity, tissue infiltration of leukocytes, and if unchecked can lead to muscular, neuronal, and immune system dysfunction. Alterations in the gut, vagina, and urinary microbiota have been previously associated with a range of GU pathology (eg. Bladder cancer, BPH, IC, OAB). 

Urologist Lynn Stothers (University of British Columbia) has coined the term “UTILS (Yoo-tils)” or UTI-like symptoms, seen in patients who feel like they have a UTI but do not have the biological features of a UTI on testing and often do not respond to treatments recommended on UTI guidelines. These patients are frustrated and have led to an untested hypothesis that we are not detecting the cause of these infections due to limitations in the current testing modality. This has promoted the exploration of more sensitive testing techniques for clinical use, particularly in the diagnosis of individuals with chronic UTIs. So there are 2 categories of microbial characterization; culture-dependent where microbes grow to be detected and culture-independent in which microbial components are byproducts, instead serve as markers for the presence of specific microorganisms. Each of these categories provides useful but different information. Whereas standard clinical urine cultures have no universally accepted definition of positive, enhanced quantitative urine cultures (EQUC), pioneered at Loyola University, have longer incubations, a larger amount of urine cultured, and multiple culture conditions. EQUCs provide improved detection of urinary bacteria even in healthy individuals. But although EQUC provides better identification of uropathogens as well as, commensal bacteria, it is not yet ready for use in clinical diagnosing as it detects more bacteria in individuals without symptoms. So the standard culture remains the gold standard. But in the culture-independent method, it is not necessary that organisms grow but one is detecting either their components or their byproducts with the most common methods. The PCR, next-generation sequencing and metagenomics, isolate DNA from a biological sample and then compare the isolated sequences back to a curated database of microbial genes to determine what microorganisms are present. DNA-based detection provides the most direct assessment of which bacteria might be present and has been utilized in most technologies.  Molecular diagnostic approaches identify more bacteria in patients, identify fastidious bacteria, provide a faster assessment of antibiotic susceptibility, identify drug resistance, and recognition of community effects that affect treatment responses. The DNA next-generation sequencing (NGS) accurately identifies and provides information on resistance factors (mobile genetic elements). According to a head-to-head comparison by McDonald (2017), symptom scores were statistically significantly better for those patients whose treatment was based on DNA NGS results versus traditional C&S studies. Many companies now offering PCR urine testing, some directly to patients. But is it really better? These tests can identify bacteria in almost everybody and run the risk of overtreatment. PCR-based testing detects far higher amounts of asymptomatic colonization, up to 90% in some studies. So there is no simple way to microbiologically define a UTI versus UTILs versus asymptomatic bacteriuria. Although we are increasing our knowledge of microbial communities, we do not know how to use this information in clinical practice. Dr. Ackerman concluded by noting: bacteria is not necessarily bad as healthy GU bacteria play a role in preventing UTIs. We need to understand better which patient would benefit from intervention and what kind.

Presented by: A Lenore Ackerman, MD Ph.D., Assistant Professor of Urology and Director of Research, Division of Female Pelvic Medicine and Reconstructive Surgery, UCLA Health, Yale University

Written by: Diane K. Newman, DNP, ANP-BC, FAAN is an Adjunct Professor of Urology in Surgery, Perelman School of Medicine, University of Pennsylvania and Co-Director of the Penn Center for Continence and Pelvic Health


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