Relationship between the Cervical Microbiome, HIV Status, and Precancerous Lesions

From BugSigDB
Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Klein C, Gonzalez D, Samwel K, Kahesa C, Mwaiselage J, Aluthge N, Fernando S, West JT, Wood C, Angeletti PC
Journal
mBio
Year
2019
Keywords:
16S RNA, cervical cancer, deep sequencing, human immunodeficiency virus, human papillomavirus, microbiome
Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with high-grade squamous intraepithelial lesions (HSIL) (P = 0.13) than those without lesions. The most abundant OTUs associated with high-grade squamous intraepithelial lesions were Mycoplasmatales, Pseudomonadales, and Staphylococcus We suggest that a chronic mycoplasma infection of the cervix may contribute to HPV-dependent dysplasia by sustained inflammatory signals.IMPORTANCE HPV is known to be the causal agent in the majority of cervical cancers. However, the role of the cervical bacterial microbiome in cervical cancer is not clear. To investigate that possibility, we collected cervical cytobrush samples from 144 Tanzanian women and performed deep sequencing of bacterial 16S rRNA genes. We found that HIV-positive patients had greater bacterial richness (P = 0.01) than HIV-negative patients. We also observed that women with high-grade squamous intraepithelial lesions (HSIL) had greater cervical bacterial diversity than women with cytologically normal cervices. Data from our precise sampling of cervical lesions leads us to propose that Mycoplasma contributes to a cervical microbiome status that promotes HPV-related cervical lesions. These results suggest a greater influence of the bacterial microbiota on the outcome of HPV infection than previously thought.

Experiment 1


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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Peace Sandy

Subjects

Location of subjects
United Republic of Tanzania
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
Human papilloma virus infection HPV,Human Papilloma Virus Infection,Human papilloma Virus infection,human papilloma virus infection,Human papillomavirus caused disease or disorder,Human papillomavirus disease or disorder,Human Papillomavirus Infection,Human Papillomavirus infection,Human papillomavirus infectious disease,Human papilloma virus infection
Group 0 name Corresponds to the control (unexposed) group for case-control studies
negative for intraepithelial lesion or malignancy
Group 1 name Corresponds to the case (exposed) group for case-control studies
high-grade squamous intraepithelial lesions
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
high-grade squamous intraepithelial lesions (HSIL) comfirmed by Pap smear
Group 0 sample size Number of subjects in the control (unexposed) group
23
Group 1 sample size Number of subjects in the case (exposed) group
45

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).
relative abundances
Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.1
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes

Alpha Diversity

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 6a

Description: LEfSe linear discriminant analysis (LDA) scores between unmatched high-grade squamous intraepithelial lesions (HSIL) and negative for intraepithelial lesion (NILM)

Abundance in Group 1: increased abundance in high-grade squamous intraepithelial lesions

NCBI Quality ControlLinks
Azotobacter group
Staphylococcus
Pseudomonadales
Mycoplasmatota
Mycoplasmatales
Staphylococcaceae

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 6a

Description: LEfSe linear discriminant analysis (LDA) scores between unmatched high-grade squamous intraepithelial lesions (HSIL) and negative for intraepithelial lesion (NILM)

Abundance in Group 1: decreased abundance in high-grade squamous intraepithelial lesions

NCBI Quality ControlLinks
Gammaproteobacteria
Finegoldia

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, Victoria

Differences from previous experiment shown

Subjects

Group 0 sample size Number of subjects in the control (unexposed) group
4
Group 1 sample size Number of subjects in the case (exposed) group
4

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
age

Alpha Diversity

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 6b

Description: LEfSe linear discriminant analysis (LDA) scores between matched high-grade squamous intraepithelial lesions (HSIL) and negative for intraepithelial lesion (NILM)

Abundance in Group 1: increased abundance in high-grade squamous intraepithelial lesions

NCBI Quality ControlLinks
Streptococcus
Parvimonas
Mycoplasmatota
Mollicutes
Mycoplasmatales

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 6b

Description: LEfSe linear discriminant analysis (LDA) scores between matched high-grade squamous intraepithelial lesions (HSIL) and negative for intraepithelial lesion (NILM)

Abundance in Group 1: decreased abundance in high-grade squamous intraepithelial lesions

NCBI Quality ControlLinks
Lactobacillaceae
Lactobacillus iners
Bacilli
Lactobacillales
Finegoldia

Revision editor(s): WikiWorks

Experiment 3


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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV infection [X]Human immunodeficiency virus disease,[X]Human immunodeficiency virus disease (disorder),[X]Unspecified human immunodeficiency virus [HIV] disease,[X]Unspecified human immunodeficiency virus [HIV] disease (disorder),HIV - Human immunodeficiency virus infection,HIV INFECT,HIV Infection,HIV infection,HIV Infections,HIV infectious disease,HTLV III INFECT,HTLV III Infections,HTLV III LAV INFECT,HTLV III LAV Infections,HTLV WIII INFECTIONS,HTLV WIII LAV INFECTIONS,HTLV-III Infection,HTLV-III Infections,HTLV-III-LAV Infection,HTLV-III-LAV Infections,HUMAN IMMUNO VIRUS DIS,human immunodeficiency virus,Human immunodeficiency virus [HIV] disease,HUMAN IMMUNOdeficiency VIRUS [HIV] INFECTION,Human immunodeficiency virus caused disease or disorder,Human immunodeficiency virus disease,Human immunodeficiency virus disease (disorder),Human immunodeficiency virus disease or disorder,Human immunodeficiency virus infection,Human immunodeficiency virus infection (disorder),Human immunodeficiency virus infection, NOS,Human immunodeficiency virus infectious disease,human immunodeficiency virus infectious disease,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,LYMPHOTROPIC VIRUS TYPE III INFECTIONS HUMAN T,T LYMPHOTROPIC VIRUS TYPE III INFECT HUMAN,T Lymphotropic Virus Type III Infections, Human,T-Lymphotropic Virus Type III Infections, Human,Unspecified human immunodeficiency virus [HIV] disease (disorder),hIV infection
Group 0 name Corresponds to the control (unexposed) group for case-control studies
HIV-
Group 1 name Corresponds to the case (exposed) group for case-control studies
HIV+
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
HIV+ comfirmed by Standard Diagnostics HIV-1/2 3.0 detection kit
Group 0 sample size Number of subjects in the control (unexposed) group
95
Group 1 sample size Number of subjects in the case (exposed) group
39

Lab analysis

Statistical Analysis

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

Alpha Diversity

Chao1 Abundance-based estimator of species richness
increased

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, Merit

Source: figure 6c

Description: LEfSe linear discriminant analysis (LDA) scores.

Abundance in Group 1: increased abundance in HIV+

NCBI Quality ControlLinks
Actinomycetaceae
Actinomycetales
Aerococcus
Alphaproteobacteria
Bacillota
Bifidobacteriaceae
Carnobacteriaceae
Clostridia
Gemella
Granulicatella
Haemophilus influenzae
Mollicutes
Moryella
Mycoplasmataceae
Mycoplasmatales
Mycoplasmatota
Peptostreptococcaceae
Peptostreptococcus
Peptostreptococcus anaerobius
Rhizobiaceae
Staphylococcus
Streptococcus
Streptococcus anginosus

Revision editor(s): WikiWorks, Merit

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 6c

Description: LEfSe linear discriminant analysis (LDA) scores.

Abundance in Group 1: decreased abundance in HIV+

NCBI Quality ControlLinks
Arcanobacterium
Ureaplasma
Limosilactobacillus reuteri
Actinomycetes
Bifidobacteriales
Bifidobacterium

Revision editor(s): WikiWorks