Cervical Microbiota Associated with Higher Grade Cervical Intraepithelial Neoplasia in Women Infected with High-Risk Human Papillomaviruses

From BugSigDB
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Piyathilake CJ, Ollberding NJ, Kumar R, Macaluso M, Alvarez RD, Morrow CD
Journal
Cancer prevention research (Philadelphia, Pa.)
Year
2016
It is increasingly recognized that microbes that reside in and on human body sites play major roles in modifying the pathogenesis of several diseases, including cancer. However, specific microbes or microbial communities that can be mechanistically linked to cervical carcinogenesis remain largely unexplored. The purpose of the study was to examine the association between cervical microbiota and high-grade cervical intraepithelial neoplasia (CIN 2+) in women infected with high-risk (HR) human papillomaviruses (HPV) and to assess whether the cervical microbiota are associated with oxidative DNA damage as indicated by the presence of cervical cells positive for 8-hydroxy-2'-deoxyguanosine. The study included 340 women diagnosed with CIN 2+ (cases) and 90 diagnosed with CIN 1 (non-cases). Microbiota composition was determined by Illumina sequencing of the 16S rRNA gene amplified from DNA extracted from cervical mucus samples. Measures of alpha/beta-diversity were not associated with either CIN severity or oxidative DNA damage. However, a cervical mucosal community type (CT) dominated by L. iners and unclassified Lactobacillus spp was associated with CIN 2+ (OR = 3.48; 95% CI, 1.27-9.55). Sequence reads mapping to Lactobacillaceae, Lactobacillus, L. reuteri, and several sub-genus level Lactobacillus operational taxonomic units were also associated with CIN 2+ when examined independently (effect size >2.0; P < 0.05). Our 16S rRNA sequencing results need confirmation in independent studies using whole-genome shotgun sequencing and that would allow sharpening the suggested associations at finer taxonomic levels. Our results provide little evidence that DNA oxidative damage mediates the effect of the microbiome on the natural history of HPV infection and CIN severity. Cancer Prev Res; 9(5); 357-66. ©2016 AACR.

Experiment 1


Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
cervical glandular intraepithelial neoplasia cervical glandular intraepithelial neoplasia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
CIN1
Group 1 name Corresponds to the case (exposed) group for case-control studies
CIN2+
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients with CIN2+ confirmed by colposcopy
Group 0 sample size Number of subjects in the control (unexposed) group
90
Group 1 sample size Number of subjects in the case (exposed) group
340

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

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


Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Figure 2, supplemental table 1

Description: Linear discriminant effect size (LEfSe) analysis comparing differentially abundant taxa according to CIN status

Abundance in Group 1: increased abundance in CIN2+

NCBI Links
Lactobacillaceae
Lactobacillus
Bacteroidaceae
Bacteroides
Porphyromonadaceae
Limosilactobacillus reuteri
Parabacteroides
Coxiellaceae
Rickettsiella
Pseudomonas oleovorans
Legionellaceae
Butyricimonas
Heliobacteriaceae
Bacteroides eggerthii

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Figure 2, supplemental table 1

Description: Linear discriminant effect size (LEfSe) analysis comparing differentially abundant taxa according to CIN status

Abundance in Group 1: decreased abundance in CIN2+

NCBI Links
Oscillospiraceae
Eubacteriales

Revision editor(s): WikiWorks

Experiment 2


Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
cervical glandular intraepithelial neoplasia cervical glandular intraepithelial neoplasia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
<=38.8% 8-OHdG-positive cervical cells
Group 1 name Corresponds to the case (exposed) group for case-control studies
>38.8% 8-OHdG-positive cervical cells
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients with >38.8% of 8-OHdG-positive cervical cells

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

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


Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Supplemental Figure 2

Description: LEfSe comparing differentially abundant taxa according to 8-OH status

Abundance in Group 1: increased abundance in >38.8% 8-OHdG-positive cervical cells

NCBI Links
Betaproteobacteria
Burkholderiales
Comamonadaceae
Azotobacter group
Pseudomonas
Hyphomicrobiales
Oxalobacteraceae
Rhizobiaceae
Agrobacterium
Limnohabitans
Phenylobacterium

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Supplemental Figure 2

Description: LEfSe comparing differentially abundant taxa according to 8-OH status

Abundance in Group 1: decreased abundance in >38.8% 8-OHdG-positive cervical cells

NCBI Links
Clostridiaceae

Revision editor(s): WikiWorks

Experiment 3


Reviewed Marked as Reviewed by Fatima on 2021/07/16

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Rimsha, WikiWorks

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled (if applicable)
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
cervical glandular intraepithelial neoplasia cervical glandular intraepithelial neoplasia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
CIN1
Group 1 name Corresponds to the case (exposed) group for case-control studies
CIN2+
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
patients with CIN2+ confirmed by colposcopy
Group 0 sample size Number of subjects in the control (unexposed) group
90
Group 1 sample size Number of subjects in the case (exposed) group
340

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

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)?
Yes


Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Supplemental Table 2

Description: Log2-fold difference in sequence reads for OTUs according to CIN status

Abundance in Group 1: increased abundance in CIN2+

NCBI Links
Akkermansia muciniphila
Limosilactobacillus reuteri

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks

Source: Supplemental Table 2

Description: Log2-fold difference in sequence reads for OTUs according to CIN status

Abundance in Group 1: decreased abundance in CIN2+

NCBI Links
Prevotella copri
Blautia producta
Collinsella aerofaciens
Prevotella melaninogenica
Clostridium perfringens
Streptococcus agalactiae
Akkermansia muciniphila

Revision editor(s): WikiWorks