Recurrent urinary tract infection and estrogen shape the taxonomic ecology and function of the postmenopausal urogenital microbiome

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Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Neugent ML, Kumar A, Hulyalkar NV, Lutz KC, Nguyen VH, Fuentes JL, Zhang C, Nguyen A, Sharon BM, Kuprasertkul A, Arute AP, Ebrahimzadeh T, Natesan N, Xing C, Shulaev V, Li Q, Zimmern PE, Palmer KL, De Nisco NJ
Journal
Cell reports. Medicine
Year
2022
Keywords:
Escherichia coli, Lactobacillus crispatus, antibiotic resistance, bladder, dysbiosis, estrogen, metagenomics, postmenopausal women, urinary tract infection, urogenital microbiome
Postmenopausal women are severely affected by recurrent urinary tract infection (rUTI). The urogenital microbiome is a key component of the urinary environment. However, changes in the urogenital microbiome underlying rUTI susceptibility are unknown. Here, we perform shotgun metagenomics and advanced culture on urine from a controlled cohort of postmenopausal women to identify urogenital microbiome compositional and function changes linked to rUTI susceptibility. We identify candidate taxonomic biomarkers of rUTI susceptibility in postmenopausal women and an enrichment of lactobacilli in postmenopausal women taking estrogen hormone therapy. We find robust correlations between Bifidobacterium and Lactobacillus and urinary estrogens in women without urinary tract infection (UTI) history. Functional analyses reveal distinct metabolic and antimicrobial resistance gene (ARG) signatures associated with rUTI. Importantly, we find that ARGs are enriched in the urogenital microbiomes of women with rUTI history independent of current UTI status. Our data suggest that rUTI and estrogen shape the urogenital microbiome in postmenopausal women.

Experiment 1


Needs review

Curated date: 2023/10/09

Curator: Tolulopeo

Revision editor(s): Tolulopeo

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
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)
Group 0 name Corresponds to the control (unexposed) group for case-control studies
No UTI History
Group 1 name Corresponds to the case (exposed) group for case-control studies
rUTI History, UTI (-), rUTI History, UTI(+)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Consists of post menopausal (PM) women with a recent history of recurring urinary tract infection ( rUTI) but no active UTI at the time of urine donation (rUTI History, UTI(−)), and(rUTI History, UTI(+))consisted of PM women with a history of rUTI and an active, symptomatic UTI at the time of urine donation respectively
Group 0 sample size Number of subjects in the control (unexposed) group
25
Group 1 sample size Number of subjects in the case (exposed) group
50

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
Sanger

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)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2
Matched on Factors on which subjects have been matched on in a case-control study
age, body mass index, Matched on: "Urine pH" 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.Urine pH, Matched on: "Urinary Creatinine concentration" 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.Urinary Creatinine concentration, Matched on: "smoking history" 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.smoking history
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "sample size" 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.sample size, Confounders controlled for: "Uncomplicated UTI" 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.Uncomplicated UTI, Confounders controlled for: "UTI History" 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.UTI History

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Needs review

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo

Source: Fig 3B

Description: Differentially abundant taxa between the No UTI History and rUTI History, UTI(−) groups using BMDA .

Abundance in Group 1: increased abundance in rUTI History, UTI (-), rUTI History, UTI(+)

NCBI Quality ControlLinks
Aerococcus
Lactobacillus

Revision editor(s): Tolulopeo

Signature 2

Needs review

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Chinelsy, Chloe

Source: Fig 3E

Description: Comparison of differentially abundant taxa between the rUTI History, UTI(−) group the No UTI History

Abundance in Group 1: increased abundance in rUTI History, UTI (-), rUTI History, UTI(+)

NCBI Quality ControlLinks
Anaerococcus hydrogenalis
Anaerococcus prevotii
Bacteroides
Bacteroides uniformis
Brevibacterium ravenspurgense
Clostridiales Family XIII bacterium
Corynebacterium pseudogenitalium
Eggerthella
Enterococcus faecalis
Escherichia
Facklamia hominis
Finegoldia magna
Gemella
Hoylesella timonensis
Klebsiella
Peptoniphilus lacrimalis
Schaalia turicensis
Staphylococcus epidermidis
Staphylococcus hominis
Streptococcus
Ureaplasma
Ureaplasma parvum
Gleimia europaea

Revision editor(s): Tolulopeo, Chinelsy, Chloe

Experiment 2


Needs review

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Premenopausal women with no UTI History and rUTI History( UTI(−) groups) without estrogen hormone therapy (EHT)
Group 1 name Corresponds to the case (exposed) group for case-control studies
EHT+ Premenopausal women with no UTI History and rUTI History( UTI(−) groups) with estrogen hormone therapy (EHT)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Premenopausal women with no UTI History and rUTI History( UTI(−) groups) with systemic and vaginal estrogen hormone therapy (EHT) who did not have UTI at the time of urine donation.
Group 0 sample size Number of subjects in the control (unexposed) group
21
Group 1 sample size Number of subjects in the case (exposed) group
29

Lab analysis

Statistical Analysis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.0032
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
4.5
Matched on Factors on which subjects have been matched on in a case-control study
Not specified
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
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased

Signature 1

Needs review

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Chinelsy

Source: Fig 4H

Description: Urogenital microbiomes of EHT(+) (aggregated systemic and vaginal) women compared to those of EHT(−) women using BMDA model

Abundance in Group 1: increased abundance in EHT+ Premenopausal women with no UTI History and rUTI History( UTI(−) groups) with estrogen hormone therapy (EHT)

NCBI Quality ControlLinks
Lactobacillus
Lactobacillus crispatus
Limosilactobacillus vaginalis

Revision editor(s): Tolulopeo, Chinelsy

Signature 2

Needs review

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo, OdigiriGreat

Source: Fig 4H

Description: Urogenital microbiomes of EHT(−) women compared to those of EHT(+) (aggregated systemic and vaginal) women using the BMDA model.

Abundance in Group 1: increased abundance in EHT+ Premenopausal women with no UTI History and rUTI History( UTI(−) groups) with estrogen hormone therapy (EHT)

NCBI Quality ControlLinks
Streptococcus infantis
Streptococcus mitis
Streptococcus oralis
Streptococcus pneumoniae
Fannyhessea vaginae

Revision editor(s): Tolulopeo, OdigiriGreat

Signature 3

Needs review

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo

Source: Fig 4G

Description: Urogenital microbiomes of EHT(+) (aggregated systemic and vaginal) women compared to those of EHT(−) women using LEfSe model

Abundance in Group 1: increased abundance in EHT+ Premenopausal women with no UTI History and rUTI History( UTI(−) groups) with estrogen hormone therapy (EHT)

NCBI Quality ControlLinks
Lactobacillus

Revision editor(s): Tolulopeo

Signature 4

Needs review

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo

Source: Fig 4H

Description: Urogenital microbiomes of EHT(−) women compared to those of EHT(+) (aggregated systemic and vaginal) women using LEfSe model

Abundance in Group 1: increased abundance in EHT+ Premenopausal women with no UTI History and rUTI History( UTI(−) groups) with estrogen hormone therapy (EHT)

NCBI Quality ControlLinks
Streptococcus

Revision editor(s): Tolulopeo

Signature 5

Needs review

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo

Source: Fig 4A

Description: Relative abundance of the top 22 bacterial genera among EHT(−) (n = 21) and EHT(+) (n = 29) women in the No UTI History and rUTI History, UTI(−) groups.

Abundance in Group 1:
NCBI Quality ControlLinks
Lactobacillus
Aerococcus
Klebsiella
Escherichia
Enterococcus
Bifidobacterium
Streptococcus
Gardnerella
Staphylococcus
Actinobaculum
Finegoldia
Corynebacterium
Propionibacterium
Facklamia
Anaerococcus
Prevotella
Peptoniphilus
Alloscardovia
Varibaculum
Actinomyces
Atopobium
Ruminococcus

Revision editor(s): Tolulopeo

Signature 6

Needs review

Curated date: 2023/10/28

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Chinelsy

Source: Fig 4B

Description: Species-level taxonomic profiles of the relative abundance of the top 22 bacterial genera among EHT(−) (n = 21) and EHT(+) (n = 29) women in the No UTI History and rUTI History, UTI(−) groups.

Abundance in Group 1:
NCBI Quality ControlLinks
Actinotignum schaalii
Alloscardovia omnicolens
Anaerococcus lactolyticus
Anaerococcus prevotii
Bifidobacterium breve
Bifidobacterium dentium
Bifidobacterium longum
Corynebacterium aurimucosum
Corynebacterium pyruviciproducens
Corynebacterium striatum
Enterococcus faecalis
Escherichia coli
Facklamia hominis
Fannyhessea vaginae
Finegoldia magna
Gardnerella vaginalis
Hoylesella timonensis
Klebsiella pneumoniae
Lactobacillus crispatus
Lactobacillus delbrueckii
Lactobacillus gasseri
Lactobacillus iners
Peptoniphilus harei
Prevotella bivia
Propionimicrobium lymphophilum
Staphylococcus haemolyticus
Streptococcus agalactiae
Streptococcus anginosus
Streptococcus parasanguinis
Varibaculum cambriense
Winkia neuii
Falseniella ignava

Revision editor(s): Tolulopeo, Chinelsy