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

From BugSigDB
Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22
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


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22

Curated date: 2023/10/09

Curator: Tolulopeo

Revision editor(s): Tolulopeo, ChiomaBlessing

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 UTI History
Group 1 name Corresponds to the case (exposed) group for case-control studies
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(−))
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
25
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 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
Sanger

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Negative Binomial Regression
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

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
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo, ChiomaBlessing

Source: Fig 3D + 3E

Description: Differentially abundant taxa in the rUTI History, UTI(−) group compared to the No UTI History group

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

NCBI Quality ControlLinks
Aerococcus
Anaerococcus lactolyticus
Anaerococcus vaginalis
Lactobacillus
Lactobacillus crispatus
Limosilactobacillus vaginalis
Aerococcus urinae

Revision editor(s): Tolulopeo, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Chloe, ChiomaBlessing, Tolulopeo, Chinelsy

Source: Fig 3D + 3E

Description: Differentially abundant taxa in the rUTI History, UTI(−) group compared to the No UTI History group

Abundance in Group 1: increased abundance in 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
Gleimia europaea
Hoylesella timonensis
Klebsiella
Peptoniphilus lacrimalis
Schaalia turicensis
Staphylococcus epidermidis
Staphylococcus hominis
Streptococcus
Ureaplasma
Ureaplasma parvum

Revision editor(s): Chloe, ChiomaBlessing, Tolulopeo, Chinelsy

Experiment 2


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Hormone replacement therapy HORMONE REPLACE THER,Hormone Replacement Therapies,Hormone Replacement Therapy,REPLACE THER HORMONE,Replacement Therapies, Hormone,Replacement Therapy, Hormone,THER HORMONE REPLACE,Therapies, Hormone Replacement,Therapy, Hormone Replacement,Hormone replacement therapy,hormone replacement therapy
Group 0 name Corresponds to the control (unexposed) group for case-control studies
EHT- Group (Premenopausal women in the 'No UTI History and rUTI History( UTI(−) cohorts' who did not use estrogen hormone therapy (EHT))
Group 1 name Corresponds to the case (exposed) group for case-control studies
EHT+ Group (Premenopausal women in the 'No UTI History and rUTI History( UTI(−) cohorts' who used estrogen hormone therapy (EHT))
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Premenopausal women in the 'No UTI History and rUTI History( UTI(−) cohorts' 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

Statistical test
LEfSe
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

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
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo, Chinelsy, ChiomaBlessing

Source: Fig 4C + 4H

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

Abundance in Group 1: increased abundance in EHT+ Group (Premenopausal women in the 'No UTI History and rUTI History( UTI(−) cohorts' who used estrogen hormone therapy (EHT))

NCBI Quality ControlLinks
Lactobacillus
Lactobacillus crispatus
Limosilactobacillus vaginalis

Revision editor(s): Tolulopeo, Chinelsy, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22

Curated date: 2023/10/25

Curator: Tolulopeo

Revision editor(s): Tolulopeo, OdigiriGreat, ChiomaBlessing

Source: Fig 4H

Description: Urogenital microbiomes of EHT(+) women compared to those of EHT(-) women

Abundance in Group 1: increased abundance in EHT+ Group (Premenopausal women in the 'No UTI History and rUTI History( UTI(−) cohorts' who used estrogen hormone therapy (EHT))

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

Revision editor(s): Tolulopeo, OdigiriGreat, ChiomaBlessing

Experiment 3


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-22

Curated date: 2024/02/22

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing

Differences from previous experiment shown

Subjects

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 UTI History
Group 1 name Corresponds to the case (exposed) group for case-control studies
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) and an active, symptomatic UTI at the time of urine donation
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
25

Lab analysis

Statistical Analysis

Statistical test
Negative Binomial Regression
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
Not specified

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
Richness Number of species
unchanged