Cervicovaginal microbiome and natural history of Chlamydia trachomatis in adolescents and young women

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Usyk M, Carlson L, Schlecht NF, Sollecito CC, Grassi E, Wiek F, Viswanathan S, Strickler HD, Nucci-Sack A, Diaz A, Burk RD
Journal
Cell
Year
2025
Keywords:
Chlamydia trachomatis, adolescent and young women, bacterial vaginosis, cervicovaginal, longitudinal cohort analysis, microbial network and CT infection, microbial risk score, microbiome, miscarriage, molBV algorithm, molecular Nugent score, pelvic inflammatory disease, post-treatment CVM changes, prospective cohort study, reinfection and clinical sequelae, risk factors for CT acquisition
This study investigated the cervicovaginal microbiome's (CVM's) impact on Chlamydia trachomatis (CT) infection among Black and Hispanic adolescent and young adult women. A total of 187 women with incident CT were matched to 373 controls, and the CVM was characterized before, during, and after CT infection. The findings highlight that a specific subtype of bacterial vaginosis (BV), identified from 16S rRNA gene reads using the molBV algorithm and community state type (CST) clustering, is a significant risk factor for CT acquisition. A microbial risk score (MRS) further identified a network of bacterial genera associated with increased CT risk. Post treatment, the CVM associated with CT acquisition re-emerged in a different subset of cases leading to reinfection. Additionally, the analysis showed a connection between post-treatment CVM and the development of pelvic inflammatory disease (PID) and miscarriage, further underscoring the CVM's contributing role to incident CT natural history and highlighting its consideration as a therapeutic target.

Experiment 1


Needs review

Curated date: 2025/03/06

Curator: MyleeeA

Revision editor(s): MyleeeA

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
Uterine cervix Canalis cervicis uteri,Caudal segment of uterus,Cervical canal,Cervical canal of uterus,Cervix,Cervix of uterus,Cervix uteri,Neck of uterus,Uterine cervix,uterine cervix
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Bacterial vaginosis BACT VAGINITIDES,BACT VAGINITIS,BACT VAGINOSES,BACT VAGINOSIS,Bacterial Vaginitides,Bacterial Vaginitis,Bacterial Vaginoses,bacterial vaginosis,BV,Nonspecific Vaginitis,VAGINITIDES BACT,Vaginitides, Bacterial,VAGINITIS BACT,Vaginitis, Bacterial,Vaginitis, Nonspecific,VAGINOSES BACT,Vaginoses, Bacterial,VAGINOSIS BACT,Vaginosis, Bacterial,Bacterial vaginosis
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Chlamydia trichomonas Controls (t0)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Chlamydia trichomonas Cases (t0)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Cervicovaginal samples were collected approximately at time of the incident detection of CT infection.
Group 0 sample size Number of subjects in the control (unexposed) group
187
Group 1 sample size Number of subjects in the case (exposed) group
373

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4
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).
centered log-ratio
Statistical test
ANCOM
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
Matched on Factors on which subjects have been matched on in a case-control study
age, ethnic group, Matched on: "year of enrollment" 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.year of enrollment, Matched on: "past 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.past history, Matched on: "duration of illness" 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.duration of illness

Alpha Diversity

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

Signature 1

Needs review

Curated date: 2025/03/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 4E

Description: Results of ANCOM analysis of differentially abundant genera associated with Chlamydia trichomonas Cases (t0) vs Chlamydia trichomonas Controls (t0).

Abundance in Group 1: increased abundance in Chlamydia trichomonas Cases (t0)

NCBI Quality ControlLinks
Actinomyces
Anaerococcus
Arcanobacterium
Atopobium
Chlamydia
Gardnerella
Gemella
Mobiluncus
Mycoplasma
Parvimonas
Prevotella
Sneathia

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2025/03/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 4E

Description: Results of ANCOM analysis of differentially abundant genera associated with Chlamydia trichomonas Cases (t0) vs Chlamydia trichomonas Controls (t0).

Abundance in Group 1: decreased abundance in Chlamydia trichomonas Cases (t0)

NCBI Quality ControlLinks
Streptococcus
Lactobacillus

Revision editor(s): MyleeeA

Experiment 2


Needs review

Curated date: 2025/03/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Chlamydia trichomonas Cases (t-1)
Group 0 sample size Number of subjects in the control (unexposed) group
373

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
age, ethnic group, time from diagnosis, Matched on: "year of enrollment" 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.year of enrollment, Matched on: "past 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.past history


Signature 1

Needs review

Curated date: 2025/03/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 4G

Description: Results of ANCOM analysis of differentially abundant genera associated with Chlamydia trichomonas Cases (t0) vs Chlamydia trichomonas Cases (t-1).

Abundance in Group 1: increased abundance in Chlamydia trichomonas Cases (t0)

NCBI Quality ControlLinks
Chlamydia
Atopobium
Parvimonas
Clostridium

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2025/03/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 4G

Description: Results of ANCOM analysis of differentially abundant genera associated with Chlamydia trichomonas Cases (t0) vs Chlamydia trichomonas Cases (t-1).

Abundance in Group 1: decreased abundance in Chlamydia trichomonas Cases (t0)

NCBI Quality ControlLinks
Lactobacillus
Ureaplasma

Revision editor(s): MyleeeA

Experiment 3


Needs review

Curated date: 2025/03/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Risk factor Factor, Risk,Factors, Risk,Risk Factors,Risk factor,risk factor
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Molecular Bacterial vaginosis (mBV B)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Molecular Bacterial vaginosis (mBV A)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Cervicovaginal microbiome community state types (CSTs) were generated using VALENCIA.30 To incorporate CST definitions into our mBV analysis we dichotomized mBV-positive (i.e., molBV 7-10 increased risk for CT infection) participants into mBV-A subtype if they concurrently had CST-IVA and molBV 7-10.
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified


Signature 1

Needs review

Curated date: 2025/03/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 3

Description: Results of ANCOM analysis of differentially abundant genera associated with mBV-A and mBV-B groups.

Abundance in Group 1: increased abundance in Molecular Bacterial vaginosis (mBV A)

NCBI Quality ControlLinks
Megasphaera
Moryella
Actinomyces
Porphyromonas
Ca. Lachnocurva vaginaeCa. Lachnocurva vaginae
Lachnospiraceae G-7Lachnospiraceae G-7
Campylobacter
Adlercreutzia
Flavobacterium

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2025/03/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 3

Description: Results of ANCOM analysis of differentially abundant genera associated with mBV-A and mBV-B groups.

Abundance in Group 1: decreased abundance in Molecular Bacterial vaginosis (mBV A)

NCBI Quality ControlLinks
Gemella
Atopobium
Anaerococcus
Aerococcus
Gardnerella

Revision editor(s): MyleeeA