TY - JOUR
T1 - Substantial overlap between symptomatic and asymptomatic genitourinary microbiota states
AU - Adu-Oppong, Boahemaa
AU - Thänert, Robert
AU - Wallace, Meghan A.
AU - Burnham, Carey Ann D.
AU - Dantas, Gautam
N1 - Funding Information:
This work was supported in part by awards to G.D. and C.A.B. from The Foundation for Barnes-Jewish Hospital ICTS Pilot Award (8037-88), and to G.D. from the NIH Director’s New Innovator Award, the National Institute of Diabetes and Digestive and Kidney Diseases (DP2DK098089) and the National Institute of General Medical Sciences (R01GM099538). B.A.-O. was supported by a National Science Foundation graduate research fellowship (DGE-1143945). R.T. was supported by the Deutsche Forschungsgemeinschaft, the German Research Foundation (402733540). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: 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. 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. Results: The 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. Conclusion: Here, 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. [MediaObject not available: see fulltext.]
AB - Background: 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. 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. Results: The 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. Conclusion: Here, 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. [MediaObject not available: see fulltext.]
KW - Clinical diagnostics
KW - Dysbiosis
KW - Genitourinary microbiome
KW - Urinary tract infections
UR - http://www.scopus.com/inward/record.url?scp=85123095309&partnerID=8YFLogxK
U2 - 10.1186/s40168-021-01204-9
DO - 10.1186/s40168-021-01204-9
M3 - Article
C2 - 35039079
AN - SCOPUS:85123095309
VL - 10
JO - Microbiome
JF - Microbiome
IS - 1
M1 - 6
ER -