The conjunctival microbiome in health and trachomatous disease: a case control study
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Zhou Y, Holland MJ, Makalo P, Joof H, Roberts CH, Mabey DC, Bailey RL, Burton MJ, Weinstock GM, Burr SE
Journal
Genome medicine
Year
2014
BACKGROUND: Trachoma, caused by Chlamydia trachomatis, remains the world's leading infectious cause of blindness. Repeated ocular infection during childhood leads to scarring of the conjunctiva, in-turning of the eyelashes (trichiasis) and corneal opacity in later life. There is a growing body of evidence to suggest non-chlamydial bacteria are associated with clinical signs of trachoma, independent of C. trachomatis infection. METHODS: We used deep sequencing of the V1-V3 region of the bacterial 16S rRNA gene to characterize the microbiome of the conjunctiva of 220 residents of The Gambia, 105 with healthy conjunctivae and 115 with clinical signs of trachoma in the absence of detectable C. trachomatis infection. Deep sequencing was carried out using the Roche-454 platform. Sequence data were processed and analyzed through a pipeline developed by the Human Microbiome Project. RESULTS: The microbiome of healthy participants was influenced by age and season of sample collection with increased richness and diversity seen in younger participants and in samples collected during the dry season. Decreased diversity and an increased abundance of Corynebacterium and Streptococcus were seen in participants with conjunctival scarring compared to normal controls. Abundance of Corynebacterium was higher still in adults with scarring and trichiasis compared to adults with scarring only. CONCLUSIONS: Our results indicate that changes in the conjunctival microbiome occur in trachomatous disease; whether these are a cause or a consequence is yet unknown.
Experiment 1
Subjects
- Location of subjects
- Gambia
- 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
- Conjunctiva Conjunctivae,Conjunctivas,Tunica conjunctiva,Wall of conjunctival sac,Conjunctiva
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Chlamydia trachomatis Chlamydozoon trachomatis,Rickettsia trachomae,Rickettsia trachomatis,Chlamydia trachomatis
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Controls aged <= 10 years
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Controls aged > 10 years
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Control individuals with normal conjunctiva (F0P0C0 - 1981 WHO trachoma grading system) and age > 10 years old.
- 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
- 84
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- not mentioned
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V1-V3
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Roche454
Statistical Analysis
- Statistical test
- Metastats
- 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
- Matched on Factors on which subjects have been matched on in a case-control study
- age, ethnic group, geographic area, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Richness Number of species
- decreased
Signature 1
Source: Table 2
Description: Changes in taxa abundance between control individuals aged <= 10 years and > 10 years
Abundance in Group 1: increased abundance in Controls aged > 10 years
| NCBI | Quality Control | Links |
|---|---|---|
| Corynebacterium | ||
| Paracoccus | ||
| Propionibacterium | ||
| Myceligenerans | ||
| Promicromonosporaceae | ||
| Actinomycetales |
Revision editor(s): Andre
Signature 2
Source: Table 2
Description: Changes in taxa abundance between control individuals aged <= 10 years and > 10 years
Abundance in Group 1: decreased abundance in Controls aged > 10 years
| NCBI | Quality Control | Links |
|---|---|---|
| Streptococcus | ||
| Kocuria | ||
| Staphylococcus | ||
| Micrococcus | ||
| Brachybacterium |
Revision editor(s): Andre
Experiment 2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Controls aged > 10 years with samples collected in the wet season
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Controls aged > 10 years with samples collected in the dry season
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Control individuals with normal conjunctiva (F0P0C0 - 1981 WHO trachoma grading system) and age > 10 years old with samples collected during the dry season. Of note, all samples from participants <= 10 years old were collected during the wet season, therefore, were not included in the analysis of the seasonal effect on the conjunctival microbiome.
- Group 1 sample size Number of subjects in the case (exposed) group
- 63
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- ethnic group, geographic area, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Richness Number of species
- increased
Signature 1
Source: Table 2
Description: Difference in taxa abundance between normal conjunctiva in wet season and normal conjunctiva in dry season
Abundance in Group 1: increased abundance in Controls aged > 10 years with samples collected in the dry season
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillus | ||
| Tumebacillus |
Revision editor(s): Andre
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Controls aged <= 10 years
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cases aged <= 10 years
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Children (age <= 10 years old) with follicles (F>0) or papillae (1 case of F0P3C0). Of note, all samples in children were collected in the wet season.
- Group 1 sample size Number of subjects in the case (exposed) group
- 29
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Not mentioned
Lab analysis
Statistical Analysis
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Not specified
- Matched on Factors on which subjects have been matched on in a case-control study
- geographic area, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Experiment 4
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Controls aged > 10 years with samples collected during the dry season
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cases aged > 10 years with samples collected during the dry season
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants aged > 10 years with clinical signs of conjunctival scarring (Cicatricae > 0 with or without trachomatous trichiasis (TT))
- 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
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Source: Table 2
Description: Changes in taxa abundance between groups
Abundance in Group 1: increased abundance in Cases aged > 10 years with samples collected during the dry season
| NCBI | Quality Control | Links |
|---|---|---|
| Corynebacterium | ||
| Streptococcus |
Revision editor(s): Andre
Signature 2
Source: Table 2
Description: Changes in taxa abundance between groups
Abundance in Group 1: decreased abundance in Cases aged > 10 years with samples collected during the dry season
| NCBI | Quality Control | Links |
|---|---|---|
| Globicatella |
Revision editor(s): Andre
Experiment 5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Controls aged > 10 years with samples collected during the wet season
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cases aged > 10 years with samples collected during the wet season
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
Experiment 6
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Cases with conjunctival scarring (C>0) alone, with samples collected in the dry season
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cases with conjunctival scarring (C>0) and trachomatous trichiasis (TT),with samples collected in the dry season
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants aged >10 years with clinical signs of conjunctival scarring (Cicatricae > 0) and with trachomatous trichiasis (TT))
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Richness Number of species
- unchanged
Signature 1
Source: Table 2
Description: Changes in taxa abundance between groups
Abundance in Group 1: increased abundance in Cases with conjunctival scarring (C>0) and trachomatous trichiasis (TT),with samples collected in the dry season
| NCBI | Quality Control | Links |
|---|---|---|
| Corynebacterium | ||
| Kocuria |
Revision editor(s): Andre
Signature 2
Source: Table 2
Description: Changes in taxa abundance between groups
Abundance in Group 1: decreased abundance in Cases with conjunctival scarring (C>0) and trachomatous trichiasis (TT),with samples collected in the dry season
| NCBI | Quality Control | Links |
|---|---|---|
| Myceligenerans | ||
| Promicromonosporaceae | ||
| Actinomycetales | ||
| Paracoccus |
Revision editor(s): Andre
Experiment 7
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Cases with conjunctival scarring (C>0) alone, with samples collected in the wet season
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Cases with conjunctival scarring (C>0) and trachomatous trichiasis (TT),with samples collected in the wet season
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
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