Metagenomic Analysis Reveals the Heterogeneity of Conjunctival Microbiota Dysbiosis in Dry Eye Disease
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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.
URI
Authors
Liang Q, Li J, Zou Y, Hu X, Deng X, Zou B, Liu Y, Wei L, Liang L, Wen X
Journal
Frontiers in cell and developmental biology
Year
2021
Keywords:
aqueous tear deficiency, conjunctival microbiota, dry eye disease, meibomian gland dysfunction, metagenomic shotgun sequencing
Background: Dry eye disease (DED) is a multifactorial inflammatory disease of the ocular surface. It is hypothesized that dysbiosis of the conjunctival microbiota contributes to the development of DED. However, species-level compositions of the conjunctival microbiota in DED and the potential dysbiosis involving microorganisms other than bacteria remain largely uncharacterized. Methods: We collected conjunctival impression samples from a cohort of 95 individuals, including 47 patients with DED and 48 healthy subjects. We examined the conjunctival microbiota of these samples using shotgun metagenomic sequencing and analyzed microbial dysbiosis in DED at the species level. Results: The conjunctival microbiota in DED exhibited a decreased α-diversity and an increased inter-individual variation. The α-diversity of female patients with DED was higher than that of male patients. Despite a decreased prevalence in DED, 23 microbial species were identified to show abnormally high abundance in DED samples positive for the species. Among these species, a fungal species Malassezia globosa was enriched female patients. In addition, distinct patterns of associations with disease status were observed for different species of the same genus. For DED subtypes, Staphylococcus aureus and S. capitis were associated with meibomian gland dysfunction (MGD), whereas S. hominis was enriched in patients solely with aqueous tear deficiency (ATD). The microbiota of patients with a mixed type of diagnosis was more similar to MGD patients than ATD patients. Conclusion: We demonstrated that the conjunctival microbiota dysbiosis in DED is characterized by significant heterogeneity. Microbial signatures may offer novel insights into the complicated etiology of DED and potentially promote the development of personalized treatment for DED in the future.
Experiment 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Subjects
- Location of subjects
- China
- 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
- Bulbar conjunctiva Ocular conjunctiva,Bulbar conjunctiva,bulbar conjunctiva
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Biological sex Biological sex,biological sex
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- female patients with dry eye disease
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- male patients with dry eye disease
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- male patients with dry eye disease
- Group 0 sample size Number of subjects in the control (unexposed) group
- 22
- Group 1 sample size Number of subjects in the case (exposed) group
- 25
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 90 days prior to enrollment
Lab analysis
- Sequencing type
- WMS
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- 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
- Linear Regression
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 2
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Source: Supp fig 2c and 2d
Description: Sex-related differences of the conjunctival microbiota in patients with dry eye.
Abundance in Group 1: decreased abundance in male patients with dry eye disease
| NCBI | Quality Control | Links |
|---|---|---|
| Deinococcus sp. NW-56 | ||
| Pseudomonas aeruginosa |
Revision editor(s): Mary Bearkland, ChiomaBlessing
Experiment 2
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy female
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Healthy male
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Healthy male without dry eye disease
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Source: Supp fig 2c and 2d, Figure 3D
Description: Sex-related differences of the conjunctival microbiota in healthy individuals.
Abundance in Group 1: increased abundance in Healthy male
| NCBI | Quality Control | Links |
|---|---|---|
| Pseudomonas aeruginosa | ||
| Malassezia globosa |
Revision editor(s): Mary Bearkland, ChiomaBlessing
Experiment 3
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Dry eye syndrome dry eye,Dry Eye Syndrome,dry eye syndrome,Dry Eye Syndromes,dry eye(s),eye(s), dry,KCS,Keraconjunctivitis sicca,Keratoconjunctivitis Sicca,Keratoconjunctivitis sicca,keratoconjunctivitis sicca,Keratoconjunctivitis sicca (disorder),sicca, keratoconjunctivitis,Tear film insufficiency,tear film insufficiency,Dry eye syndrome
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Aqueous tear deficient (ATD) DED
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Meibomian Gland Dysfunction (MGD) DED
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with MGD DED
- Group 0 sample size Number of subjects in the control (unexposed) group
- 14
- Group 1 sample size Number of subjects in the case (exposed) group
- 19
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 90 days prior to study enrollment
Lab analysis
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.15
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Source: Supp. fig 5
Description: Differentially abundant Staphylococcus species between patients with aqueous tear deficiency (ATD) and meibomian gland dysfunction (MGD)
Abundance in Group 1: increased abundance in Meibomian Gland Dysfunction (MGD) DED
| NCBI | Quality Control | Links |
|---|---|---|
| Staphylococcus aureus | ||
| Staphylococcus capitis |
Revision editor(s): Mary Bearkland, ChiomaBlessing
Signature 2
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Source: Supp. fig 5
Description: Differentially abundant Staphylococcus species between patients with aqueous tear deficiency (ATD) and meibomian gland dysfunction (MGD)
Abundance in Group 1: decreased abundance in Meibomian Gland Dysfunction (MGD) DED
| NCBI | Quality Control | Links |
|---|---|---|
| Staphylococcus hominis |
Revision editor(s): Mary Bearkland, ChiomaBlessing
Experiment 4
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Mixed DED
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with mixed type diagnosis of DED (more closely related to MGD than ATD)
- Group 1 sample size Number of subjects in the case (exposed) group
- 35
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Source: Supp fig 5
Description: Differentially abundant Staphylococcus species between patients with aqueous tear deficiency (ATD) and mixed dry eye
Abundance in Group 1: increased abundance in Mixed DED
| NCBI | Quality Control | Links |
|---|---|---|
| Staphylococcus aureus | ||
| Staphylococcus capitis | ||
| Staphylococcus cohnii |
Revision editor(s): Mary Bearkland, ChiomaBlessing
Experiment 5
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Meibomian Gland Dysfunction (MGD) DED
- Group 0 sample size Number of subjects in the control (unexposed) group
- 19
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Experiment 6
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Dry Eye
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Dry eye disease
- Group 0 sample size Number of subjects in the control (unexposed) group
- 48
- Group 1 sample size Number of subjects in the case (exposed) group
- 47
Lab analysis
Statistical Analysis
- Statistical test
- MaAsLin2
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-23
Source: Supp table 4
Description: Comparison between dry eye group and healthy group showing species with polarized abundance (decreased abundance) in dry eye samples
Abundance in Group 1: increased abundance in Dry Eye
Revision editor(s): Mary Bearkland, ChiomaBlessing
Experiment 7
Reviewed Marked as Reviewed by Folakunmi on 2024-2-23
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Dry Eye -nonATD
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Dry Eye- ATD
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Dry eye disease characterized as aqueous tear deficient
- Group 0 sample size Number of subjects in the control (unexposed) group
- 54
- Group 1 sample size Number of subjects in the case (exposed) group
- 14
Lab analysis
Statistical Analysis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.1
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-2-23
Source: Figure 4b
Description: B) Model coefficients of top-ranked species associated with either ATD or non-ATD dry eye (p < 0.1, coefficient >0.2)
Abundance in Group 1: increased abundance in Dry Eye- ATD
| NCBI | Quality Control | Links |
|---|---|---|
| Janibacter melonis |
Revision editor(s): Mary Bearkland
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-2-23
Source: Figure 4b
Description: Figure 4b) Model coefficients of top-ranked species associated with either ATD or non-ATD dry eye (p < 0.1, coefficient >0.2) (
Abundance in Group 1: decreased abundance in Dry Eye- ATD
| NCBI | Quality Control | Links |
|---|---|---|
| Capnocytophaga gingivalis |
Revision editor(s): Mary Bearkland
Experiment 8
Reviewed Marked as Reviewed by Folakunmi on 2024-2-23
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Dry Eye -nonMGD
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Dry Eye- MGD
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Dry eye disease characterized as meibomian gland disorder
- Group 0 sample size Number of subjects in the control (unexposed) group
- 49
- Group 1 sample size Number of subjects in the case (exposed) group
- 19
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-2-23
Source: Figure 4c
Description: Model coefficients of top-ranked species associated with either MGD or non-MGD dry eye (p < 0.1, coefficient >0.2)
Abundance in Group 1: increased abundance in Dry Eye- MGD
| NCBI | Quality Control | Links |
|---|---|---|
| Acinetobacter sp. WCHA45 | ||
| Deinococcus sp. NW-56 | ||
| Staphylococcus aureus | ||
| Staphylococcus capitis | ||
| Staphylococcus cohnii |
Revision editor(s): Mary Bearkland
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-2-23
Source: Figure 4c
Description: Model coefficients of top-ranked species associated with either MGD or non-MGD dry eye (p < 0.1, coefficient >0.2)
Abundance in Group 1: decreased abundance in Dry Eye- MGD
| NCBI | Quality Control | Links |
|---|---|---|
| Collinsella aerofaciens |
Revision editor(s): Mary Bearkland
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