Substantial overlap between symptomatic and asymptomatic genitourinary microbiota states
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Adu-Oppong B, Thänert R, Wallace MA, Burnham CD, Dantas G
Journal
Microbiome
Year
2022
Keywords:
Clinical diagnostics, Dysbiosis, Genitourinary microbiome, Urinary tract infections
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. Video Abstract.
Experiment 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Urine Urine,urine
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Urinary tract infection INFECTION, URINARY TRACT,TRACT, INFECTION OF URINARY,urinary tract infection,urinary tract infection (disease),Urinary tract infection
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- No Growth
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Culture Positive
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with urine specimen with significant growth of 1–2 uropathogenic species at ≥10^5 colony forming units (CFU)/mL
- Group 0 sample size Number of subjects in the control (unexposed) group
- 51
- Group 1 sample size Number of subjects in the case (exposed) group
- 48
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 2 Weeks
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Confounders controlled for: "medication" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.medication
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Source: Fig 3 and Result Text (under "Diagnostic categories reflect different states of urobiome health, paragraph 2")
Description: Significantly enriched microbiota in suspected Urinary Tract Infection specimens from different clinical categories.
Abundance in Group 1: increased abundance in Culture Positive
| NCBI | Quality Control | Links |
|---|---|---|
| Escherichia coli | ||
| Klebsiella oxytoca | ||
| Klebsiella pneumoniae |
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Source: Fig 3 and Result Text (under "Diagnostic categories reflect different states of urobiome health, paragraph 2")
Description: Significantly enriched microbiota in suspected Urinary Tract Infection specimens from different clinical categories.
Abundance in Group 1: decreased abundance in Culture Positive
| NCBI | Quality Control | Links |
|---|---|---|
| Ascomycota | ||
| Cutibacterium acnes |
Experiment 2
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Insignificant Samples
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Culture Positive Samples
- Group 0 sample size Number of subjects in the control (unexposed) group
- 17
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Source: Fig 3 and Result Text (under "Diagnostic categories reflect different states of urobiome health, paragraph 2")
Description: Significantly enriched microbiota in suspected Urinary Tract Infection specimens from different clinical categories.
Abundance in Group 1: increased abundance in Culture Positive Samples
| NCBI | Quality Control | Links |
|---|---|---|
| Klebsiella pneumoniae |
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Source: Fig 3 and Result Text (under "Diagnostic categories reflect different states of urobiome health, paragraph 2")
Description: Significantly enriched microbiota in suspected Urinary Tract Infection specimens from different clinical categories.
Abundance in Group 1: decreased abundance in Culture Positive Samples
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides ovatus | ||
| [Ruminococcus] torques |
Experiment 3
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Asymptomatic
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Insignificant Samples
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with specimen with bacterial growth <10^5 CFU/mL present during culturing but below the threshold for significance
- Group 0 sample size Number of subjects in the control (unexposed) group
- 10
- Group 1 sample size Number of subjects in the case (exposed) group
- 17
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Source: Fig 3
Description: Significantly enriched microbiota in suspected Urinary Tract Infections specimens from different clinical categories.
Abundance in Group 1: decreased abundance in Insignificant Samples
| NCBI | Quality Control | Links |
|---|---|---|
| Staphylococcus aureus |
Revision editor(s): MyleeeA
Experiment 4
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- No Growth
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with urine samples with no visible Microorganism growth (Bacterial/Fungal)
- Group 1 sample size Number of subjects in the case (exposed) group
- 51
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Source: Fig 3 and Table S3
Description: LefSe enrichment results; Significantly enriched microbiota in suspected Urinary Tract Infection specimens from different clinical categories.
Abundance in Group 1: increased abundance in No Growth
| NCBI | Quality Control | Links |
|---|---|---|
| Cutibacterium acnes |
Revision editor(s): MyleeeA
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-3-13
Source: Fig 3 and Table S3
Description: LefSe enrichment results; Significantly enriched microbiota in suspected Urinary Tract Infection specimens from different clinical categories.
Abundance in Group 1: decreased abundance in No Growth
| NCBI | Quality Control | Links |
|---|---|---|
| Subdoligranulum sp. |
Revision editor(s): MyleeeA
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