Utility of DNA Next-Generation Sequencing and Expanded Quantitative Urine Culture in Diagnosis and Management of Chronic or Persistent Lower Urinary Tract Symptoms

Abstract

Many patients suffer from chronic, irritative lower urinary tract symptoms (LUTS). The evaluation and management of these patients have proven difficult with the use of standard diagnostic tools, including urinalysis and urine culture. The growing body of literature on the urinary microbiome has looked at the possible implications of the bladder microbiome and dysbiosis, or perturbations in the microbiome, in conditions associated with chronic LUTS. Disorders such as recurrent urinary tract infections (UTIs) and interstitial cystitis have been studied utilizing 16S rRNA rapid next-generation gene sequencing (NGS) and expanded quantitative urine culture (EQUC). In this article, we first present a brief review of the literature describing the current understanding of the urinary microbiome and the features and applications of NGS and EQUC. Next, we discuss the conditions most commonly associated with chronic, persistent LUTS and present the limitations of current diagnostic practices utilized in this patient population. We then review the limited data available surrounding treatment efficacy and clinical outcomes in patients who have been managed based on results provided by these two recently established diagnostic tools (DNA NGS and/or EQUC). Finally, we propose a variety of clinical scenarios in which the use of these two techniques may affect patients’ clinical outcomes.

Urinary Microbiome Characteristics in Female Patients with Acute Uncomplicated Cystitis and Recurrent Cystitis

“…Taken together, acute uncomplicated cystitis can be regarded as a temporary infection caused by a specific causative organism, but in recurrent cystitis, dysbiosis seems to play a more important role in the pathophysiology [ 41 ]. In addition, even within the same recurrent group, there is a possibility that the dysbiosis changes as the condition is prolonged.…”

A New Gold Rush: A Review of Current and Developing Diagnostic Tools for Urinary Tract Infections

“…This theory was later called into question by the initiation of the National Institutes of Health sponsored Human microbiome project which demonstrated the presence of a bladder and urinary microbiome [ 56 ]. While the data surrounding the urinary microbiome is still in its infancy, existing work has shown the primary occupants to include organisms from the genera Lactobacillus , Garderella , Streptococcus , Staphylococcus and Corynebacterium [ 58 ].…”

“…When a sample of urine is tested using NGS, the output reports bacterial presence in terms of relative sequence reads amongst species instead of absolute values [ 60 ]. To date, MicroGen DX and Aperiomics are two companies which offer NGS as a clinical application for the diagnosis of UTI’s [ 58 ].…”

“…Currently, 16S rRNA sequencing through the MicroGen Dx DNA sequencing platform is approximately 200 dollars [ 63 ]. In comparison, the cost of a urine culture can range from 60–500 dollars depending on the extent of testing for atypical species [ 58 , 61 ]. However, as previously demonstrated, standard urine culture may fail to identify some organisms even when testing for fungal or anaerobic organisms is performed.…”

The Role of Gut, Vaginal, and Urinary Microbiome in Urinary Tract Infections: From Bench to Bedside

“…Pervasive implementation of techniques designed to identify all microorganisms in the urine, most notably sequencing-based techniques (e.g., 16S rRNA sequencing or whole genome sequencing), but also cultivation-based methods of expanded quantitative urine culture [ 13 , 63 ], has shown that a wide range of bacterial species can be found in the urine of healthy, asymptomatic individuals [ 64 , 65 ]. The analysis of the urinary microbiome as a field of research is still in its infancy; hence, there is much to learn and discover regarding its role in maintaining urinary bladder and urinary tract homeostasis in different contexts.…”