Hormonal contraception alters vaginal microbiota and cytokines in South African adolescents in a randomized trial

Study information

EditHistoryDelete

Mark reviewed

Your review change was submittedAdd a new Experiment

• Quality control
  • Retracted paper
  • Contamination issues suspected
  • Batch effect issues suspected
  • Uncontrolled confounding suspected
  • Results are suspect (various reasons)
  • Apply tags

    Tags applied

Needs review

study design

randomized controlled trial

Citation

PMID PubMed identifier for scientific articles.

33149114

DOI Digital object identifier for electronic documents.

10.1038/s41467-020-19382-9

URI

Authors

Balle C, Konstantinus IN, Jaumdally SZ, Havyarimana E, Lennard K, Esra R, Barnabas SL, Happel AU, Moodie Z, Gill K, Pidwell T, Karaoz U, Brodie E, Maseko V, Gamieldien H, Bosinger SE, Myer L, Bekker LG, Passmore JS, Jaspan HB

Journal

Nature communications

Year

2020

Young women in sub-Saharan Africa are disproportionally affected by HIV infection and unintended pregnancies. However, hormonal contraceptive (HC) use may influence HIV risk through changes in genital tract microbiota and inflammatory cytokines. To investigate this, 130 HIV negative adolescent females aged 15-19 years were enrolled into a substudy of UChoose, an open-label randomized crossover study (NCT02404038), comparing acceptability and contraceptive product preference as a proxy for HIV prevention delivery methods. Participants were randomized to injectable norethisterone enanthate (Net-En), combined oral contraceptives (COC) or etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR) for 16 weeks, then crossed over to another HC for 16 weeks. Cervicovaginal samples were collected at baseline, crossover and exit for characterization of the microbiota and measurement of cytokine levels; primary endpoints were cervical T cell activation, vaginal microbial diversity and cytokine concentrations. Adolescents randomized to COCs had lower vaginal microbial diversity and relative abundance of HIV risk-associated taxa compared to Net-En or CCVR. Cervicovaginal inflammatory cytokine concentrations were significantly higher in adolescents randomized to CCVR compared to COC and Net-En. This suggests that COC use may induce an optimal vaginal ecosystem by decreasing bacterial diversity and inflammatory taxa, while CCVR use is associated with genital inflammation.

Experiment 1

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

Needs review

Curated date: 2024/11/14

Curator: Tosin

Revision editor(s): Tosin

Subjects

Location of subjects

South Africa

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

Vagina Vagina,vagina,Distal oviductal region,Distal portion of oviduct,Vaginae

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Vaginal microbiome measurement vaginal flora measurement,vaginal microbiota measurement,Vaginal microbiome measurement,vaginal microbiome measurement

Group 0 name Corresponds to the control (unexposed) group for case-control studies

NET-En (norethisterone enanthate ) arm

Group 1 name Corresponds to the case (exposed) group for case-control studies

COC (combined oral contraceptives) arm

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Participants (adolescents) who were randomized to combined oral contraceptives.

Group 0 sample size Number of subjects in the control (unexposed) group

28

Group 1 sample size Number of subjects in the case (exposed) group

35

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)

Past 3 months

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).

raw counts

Statistical test

DESeq2

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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment

antibiotic exposure

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

decreased

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/11/14

Curator: Tosin

Revision editor(s): Tosin

Source: Table 3

Description: DESeq2 analysis of taxa differentially abundant between randomized study arms at crossover [COC (combined oral contraceptives) vs Net EN (norethisterone enanthate) arm].

Abundance in Group 1: increased abundance in COC (combined oral contraceptives) arm

NCBI	Quality Control	Links
Lactobacillus iners
Lactobacillus jensenii
Veillonella montpellierensis
Lactobacillus johnsonii
Lactobacillus gasseri
Lactobacillus taiwanensis

Revision editor(s): Tosin

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/11/15

Curator: Tosin

Revision editor(s): Tosin

Source: Table 3

Description: DESeq2 analysis of taxa differentially abundant between randomized study arms at crossover COC (combined oral contraceptives) vs Net EN (norethisterone enanthate ) arm].

Abundance in Group 1: decreased abundance in COC (combined oral contraceptives) arm

NCBI	Quality Control	Links
Hoylesella shahii
Lachnoanaerobaculum saburreum
Prevotella amnii
Prevotella denticola
Segatella baroniae
Segatella oulorum
Tannerella
Treponema vincentii
Weeksellaceae
Clostridium BVAB3_M_indolicusClostridium BVAB3_M_indolicus
Olsenella

Revision editor(s): Tosin

Experiment 2

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

Needs review

Curated date: 2024/11/14

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

CCVR (combined contraceptive vaginal ring) arm

Group 0 sample size Number of subjects in the control (unexposed) group

32

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

unchanged

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/11/15

Curator: Tosin

Revision editor(s): Tosin

Source: Table 3

Description: DESeq2 analysis of taxa differentially abundant between randomized study arms at crossover [COC (combined oral contraceptives) vs CCVR (combined contraceptive vaginal ring) arm].

Abundance in Group 1: increased abundance in COC (combined oral contraceptives) arm

NCBI	Quality Control	Links
Prevotella melaninogenica
Lactobacillus johnsonii
Lactobacillus gasseri
Lactobacillus taiwanensis

Revision editor(s): Tosin

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/11/15

Curator: Tosin

Revision editor(s): Tosin

Source: Table 3

Description: DESeq2 analysis of taxa differentially abundant between randomized study arms at crossover [COC (combined oral contraceptives) vs CCVR (combined contraceptive vaginal ring) arm].

Abundance in Group 1: decreased abundance in COC (combined oral contraceptives) arm

NCBI	Quality Control	Links
Enterobacteriaceae
Prevotella amnii

Revision editor(s): Tosin

Experiment 3

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

Needs review

Curated date: 2024/11/14

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

Net-En (norethisterone enanthate) arm

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Participants (adolescents) who were randomized to injectable norethisterone enanthate.

Group 1 sample size Number of subjects in the case (exposed) group

28

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

unchanged

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/11/15

Curator: Tosin

Revision editor(s): Tosin

Source: Table 3

Description: DESeq2 analysis of taxa differentially abundant between randomized study arms at crossover [Net-En (norethisterone enanthate) vs CCVR (combined contraceptive vaginal ring) arm].

Abundance in Group 1: increased abundance in Net-En (norethisterone enanthate) arm

NCBI	Quality Control	Links
Actinomyces
Bergeyella
Lachnoanaerobaculum saburreum
Prevotella nigrescens
Segatella baroniae
Segatella oulorum
Selenomonas infelix
Tannerella
Treponema
Treponema socranskii
Treponema vincentii
Weeksellaceae

Revision editor(s): Tosin

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/11/15

Curator: Tosin

Revision editor(s): Tosin

Source: Table 3

Description: DESeq2 analysis of taxa differentially abundant between randomized study arms at crossover [Net-En (norethisterone enanthate) vs CCVR (combined contraceptive vaginal ring) arm].

Abundance in Group 1: decreased abundance in Net-En (norethisterone enanthate) arm

NCBI	Quality Control	Links
Gardnerella
Gemelliphila asaccharolytica
Lactobacillus jensenii
Metamycoplasma hominis
Prevotella disiens

Revision editor(s): Tosin

Experiment 4

EditHistoryDelete

Mark reviewed

Your review change was submittedDuplicate this ExperimentAdd a new Signature

Needs review

Curated date: 2024/11/14

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Net-En (norethisterone enanthate) arm

Group 1 name Corresponds to the case (exposed) group for case-control studies

COC (combined oral contraceptives) arm

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Participants (adolescents) who were randomized to combined oral contraceptives.

Group 1 sample size Number of subjects in the case (exposed) group

34

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

decreased

Signature 2

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/11/15

Curator: Tosin

Revision editor(s): Tosin

Source: Table 3

Description: DESeq2 analysis of taxa differentially abundant between randomized study arms at crossover [COC (combined oral contraceptives) vs Net EN (norethisterone enanthate) arm ].

Abundance in Group 1: increased abundance in COC (combined oral contraceptives) arm

NCBI	Quality Control	Links
Lactobacillus iners

Revision editor(s): Tosin

Signature 3

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/11/15

Curator: Tosin

Revision editor(s): Tosin

Source: Table 3

Description: DESeq2 analysis of taxa differentially abundant between randomized study arms at crossover [COC (combined oral contraceptives) vs Net EN (norethisterone enanthate) arm ].

Abundance in Group 1: decreased abundance in COC (combined oral contraceptives) arm

NCBI	Quality Control	Links
Campylobacter
Clostridium moniliforme
Clostridium perfringens
Metamycoplasma hominis
Prevotella disiens

Revision editor(s): Tosin