Substantial overlap between symptomatic and asymptomatic genitourinary microbiota states

Boahemaa Adu-Oppong,Gautam Dantas,Meghan A Wallace,Carey-Ann D Burnham,Robert Thänert

doi:10.1186/s40168-021-01204-9

Boahemaa Adu-Oppong, Gautam Dantas + Show 3 more

Open Access

https://doi.org/10.1186/s40168-021-01204-9

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Journal: Microbiome	Publication Date: Jan 17, 2022
Citations: 4	License type: open-access

Affiliation: Washington University in St. Louis

Abstract

BackgroundThe lack of a definition of urinary microbiome health convolutes diagnosis of urinary tract infections (UTIs), especially when non-traditional uropathogens or paucity of bacteria are recovered from symptomatic patients in routine standard-of-care urine tests. Here, we used shotgun metagenomic sequencing to characterize the microbial composition of asymptomatic volunteers in a set of 30 longitudinally collected urine specimens. Using permutation tests, we established a range of asymptomatic microbiota states, and use these to contextualize the microbiota of 122 urine specimens collected from patients with suspected UTIs diagnostically categorized by standard-of-care urinalysis within that range. Finally, we used a standard-of-care culture protocol to evaluate the efficiency of culture-based recovery of the urinary microbiota.ResultsThe majority of genitourinary microbiota in individals suspected to have UTI overlapped with the spectrum of asymptomatic microbiota states. Longitudinal characterization of the genitourinary microbiome in urine specimens collected from asymptomatic volunteers revealed fluctuations of microbial functions and taxonomy over time. White blood cell counts from urinalysis suggested that urine specimens categorized as ‘insignificant’, ‘contaminated’, or ‘no-growth’ by conventional culture methods frequently showed signs of urinary tract inflammation, but this inflammation is not associated with genitourinary microbiota dysbiosis. Comparison of directly sequenced urine specimens with standard-of-care culturing confirmed that culture-based diagnosis biases genitourinary microbiota recovery towards the traditional uropathogens Escherichia coli and Klebsiella pneumoniae.ConclusionHere, we utilize shotgun metagenomic sequencing to establish a baseline of asymptomatic genitourinary microbiota states. Using this baseline we establish substantial overlap between symptomatic and asymptomatic genitourinary microbiota states. Our results establish that bacterial presence alone does not explain the onset of clinical symptoms.EDHjECaP7CBMthS1cSEo_nVideo

Highlights

The lack of a definition of urinary microbiome health convolutes diagnosis of urinary tract infections (UTIs), especially when non-traditional uropathogens or paucity of bacteria are recovered from symptomatic patients in routine standard-of-care urine tests
Suspect urine specimens were classified into one of four categories based on standard-of-care clinical procedures: (1) ‘culture-positive’, if the specimen had significant growth of one or two uropathogens (n = 48), (2) ‘contaminated’, 3 or more bacterial species growing in concentrations above threshold in standard-of-care clinical culture (105) (n = 6), (3) ‘insignificant’, < 105 colony forming unites/mL present during culturing (n = 17) and (4) ‘no growth’, specimen had no visible signs of microorganism growth during culturing (n = 51)
Specimens were categorized via standard-of-care clinical urine culture as: (1) ‘culture-positive’, growth of 1–2 uropathogenic species at ≥105 colony forming units (CFU)/mL (n = 48), (2) ‘contaminated’, growth of ≥ 3 bacterial species at ≥ 105 CFU/mL (n = 6), (3) ‘insignificant’, bacterial growth < 105 CFU/mL (n = 17), and (4) no growth, no bacterial or fungal growth (n = 51)

Summary

Introduction

The lack of a definition of urinary microbiome health convolutes diagnosis of urinary tract infections (UTIs), especially when non-traditional uropathogens or paucity of bacteria are recovered from symptomatic patients in routine standard-of-care urine tests. Using permuta‐ tion tests, we established a range of asymptomatic microbiota states, and use these to contextualize the microbiota of 122 urine specimens collected from patients with suspected UTIs diagnostically categorized by standard-of-care urinalysis within that range. Inconclusive or incorrect microbiological diagnosis can select for antimicrobial resistance through the initiation of inappropriate or ineffective antibiotic therapies. Even with increased specificity, diagnostic cultures often remain negative or inconclusive and reports of clinical overtreatment of urinary disorders are frequent [14,15,16,17]

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