Alterations of ocular surface microbiome in glaucoma and its association with dry eye

From BugSigDB
Reviewed Marked as Reviewed by KateRasheed on 2025-8-28
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Kamdougha H, Taminiau B, Fall PA, Ben Amor S, Trigui A, Daube G, Mnif B
Journal
Journal of medical microbiology
Year
2025
Keywords:
conjunctiva, dry eye disease, dysbiosis, glaucoma, microbiome, preservatives
Introduction. Alterations in ocular surface microbiota (OSM) have been noted in both dry eye disease (DED) and glaucoma. However, the combined effects of these conditions on OSM have not been explored.Hypothesis. We hypothesized that patients with both glaucoma and dry eye would exhibit distinct changes in OSM composition and diversity compared to those with only glaucoma, only dry eye or healthy individuals.Aim. We employed amplicon sequencing to investigate OSM profiles in patients with glaucoma and/or dry eye disease.Methods. Swab samples from the conjunctiva of both eyes were collected from 28 glaucomatous patients [13 without dry eye syndrome (G-only) and 15 with dry eye syndrome (G-DED)], 13 DED patients without glaucoma (DED-only) and 31 age-matched healthy controls (HCs). After V3-V4 16S rRNA sequencing, MOTHUR tools and R language were used to elucidate and compare OSM composition and diversity between groups.Results. Our data revealed very diverse bacterial communities with 28 phyla and 785 genera. All the groups shared the three most abundant phyla, Actinobacteria (67.47%), Firmicutes (17.14%) and Proteobacteria (13.73%). Corynebacterium (54.75%), Staphylococcus (10.71%), Cutibacterium (8.77%) and Streptococcus (3.20%) were the most abundant genera. Only the G-DED group showed higher alpha diversity than the HC group (P<0.05). However, significant differences in beta diversity were observed between all three patient groups and the HC group. The Differential Expression for Sequencing 2 (DESeq2) analysis unveiled an increased presence of opportunistic bacteria across all pathological groups, with the G-DED group demonstrating the most pronounced alterations.Conclusions. Our findings confirm the predominance of Gram-positive bacteria in normal OSM and the rise of opportunistic Gram-negative bacteria in glaucoma and dry eye disease. This is the first study to characterize OSM in glaucoma patients with DED.

Experiment 1


Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/20

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Subjects

Location of subjects
Tunisia
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
Conjunctiva Conjunctiva,conjunctiva,Conjunctivae,Conjunctivas,Tunica conjunctiva,Wall of conjunctival sac
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Glaucoma glaucoma,glaucoma (disease),Glaucoma (disorder),Glaucoma associated with other ocular disorders,Glaucoma associated with other ocular disorders (disorder),Glaucoma associated with other ocular disorders NOS,Glaucoma associated with other ocular disorders NOS (disorder),GLAUCOMA NEC,Glaucoma NOS,Glaucoma NOS (disorder),Glaucoma, NOS,Glaucomas,Other specified forms of glaucoma,Other specified forms of glaucoma (disorder),Other specified glaucoma,Other specified glaucoma NOS,Other specified glaucoma NOS (disorder),Unspecified glaucoma,Glaucoma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
HC (Healthy Controls)
Group 1 name Corresponds to the case (exposed) group for case-control studies
G-­only (Glaucomatous patients without dry eye syndrome)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Glaucomatous patients without dry eye syndrome
Group 0 sample size Number of subjects in the control (unexposed) group
60
Group 1 sample size Number of subjects in the case (exposed) group
24
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
1 month

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

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 2A, Supplementary table 2

Description: Most differentially abundant genera and phyla between groups, identified by DESeq2.

Abundance in Group 1: increased abundance in G-only (Glaucomatous patients without dry eye syndrome)

NCBI Quality ControlLinks
Actinomyces
Bradyrhizobium
Cutibacterium
Enterobacter
Fusobacterium
Gemella
Granulicatella
Proteus
Pseudomonadota
Pseudomonas
Streptococcus
Veillonella
Escherichia/Shigella sp.
Neisseria
Corynebacterium

Revision editor(s): Anne-mariesharp

Experiment 2


Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
G-­DED (Glaucomatous patients with dry eye syndrome)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Glaucomatous patients with dry eye syndrome
Group 1 sample size Number of subjects in the case (exposed) group
30

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 2A, Supplementary table 2

Description: Most differentially abundant genera and phyla between groups, identified by DESeq2.

Abundance in Group 1: increased abundance in G-DED (Glaucomatous patients with dry eye syndrome)

NCBI Quality ControlLinks
Acinetobacter
Bacillota
Bacteroidota
Burkholderia
Corynebacterium
Cutibacterium
Escherichia/Shigella sp.
Exiguobacterium
Granulicatella
Haemophilus
Kocuria
Leptotrichia
Massilia
Neisseria
Paracoccus
Porphyromonas
Prevotella
Pseudomonadota
Pseudomonas
Rhodobacter
Serratia
Staphylococcus
Streptococcus
Veillonella
Prevotella_7Prevotella_7

Revision editor(s): Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Supplementary table 2

Description: Most differentially abundant genera between groups, identified by DESeq2.

Abundance in Group 1: decreased abundance in G-DED (Glaucomatous patients with dry eye syndrome)

NCBI Quality ControlLinks
Enterobacter

Revision editor(s): Anne-mariesharp

Experiment 3


Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

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 1 name Corresponds to the case (exposed) group for case-control studies
DED-­only (Dry eye syndrome patients without glaucoma)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Dry eye syndrome (DED) patients without glaucoma
Group 1 sample size Number of subjects in the case (exposed) group
25

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/25

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Supplementary table 2

Description: Most differentially abundant genera between groups, identified by DESeq2.

Abundance in Group 1: increased abundance in DED-only (Dry eye syndrome patients without glaucoma)

NCBI Quality ControlLinks
Acinetobacter
Bradyrhizobium
Corynebacterium
Cutibacterium
Enterobacter
Haemophilus
Pseudomonas
Staphylococcus
Streptococcus
Veillonella
Escherichia/Shigella sp.

Revision editor(s): Anne-mariesharp

Experiment 4


Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/26

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
G-only (Glaucomatous patients without dry eye syndrome)
Group 1 name Corresponds to the case (exposed) group for case-control studies
G-DED (Glaucomatous patients with dry eye syndrome)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Glaucomatous patients with dry eye syndrome
Group 0 sample size Number of subjects in the control (unexposed) group
24
Group 1 sample size Number of subjects in the case (exposed) group
30

Lab analysis

Statistical Analysis

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

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/26

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 2A, Supplementary table 2

Description: Most differentially abundant genera and phyla between groups, identified by DESeq2.

Abundance in Group 1: increased abundance in G-DED (Glaucomatous patients with dry eye syndrome)

NCBI Quality ControlLinks
Acinetobacter
Bacillota
Haemophilus
Kocuria
Micrococcus
Paracoccus
Pseudomonadota
Rhodobacter
Staphylococcus

Revision editor(s): Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/26

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Supplementary table 2

Description: Most differentially abundant genera between groups, identified by DESeq2.

Abundance in Group 1: decreased abundance in G-DED (Glaucomatous patients with dry eye syndrome)

NCBI Quality ControlLinks
Enterobacter
Proteus

Revision editor(s): Anne-mariesharp

Experiment 5


Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/26

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Glaucoma glaucoma,glaucoma (disease),Glaucoma (disorder),Glaucoma associated with other ocular disorders,Glaucoma associated with other ocular disorders (disorder),Glaucoma associated with other ocular disorders NOS,Glaucoma associated with other ocular disorders NOS (disorder),GLAUCOMA NEC,Glaucoma NOS,Glaucoma NOS (disorder),Glaucoma, NOS,Glaucomas,Other specified forms of glaucoma,Other specified forms of glaucoma (disorder),Other specified glaucoma,Other specified glaucoma NOS,Other specified glaucoma NOS (disorder),Unspecified glaucoma,Glaucoma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
DED-­only (Dry eye syndrome patients without glaucoma)
Group 1 name Corresponds to the case (exposed) group for case-control studies
G-only (Glaucomatous patients without dry eye syndrome)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Glaucomatous patients without dry eye syndrome
Group 0 sample size Number of subjects in the control (unexposed) group
25
Group 1 sample size Number of subjects in the case (exposed) group
24

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/26

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 2A, Supplementary table 2

Description: Most differentially abundant genera and phyla between groups, identified by DESeq2.

Abundance in Group 1: increased abundance in G-only (Glaucomatous patients without dry eye syndrome)

NCBI Quality ControlLinks
Enterobacter
Pseudomonadota

Revision editor(s): Anne-mariesharp

Experiment 6


Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/27

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
G-DED (Glaucomatous patients with dry eye syndrome)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Glaucomatous patients with dry eye syndrome
Group 1 sample size Number of subjects in the case (exposed) group
30

Lab analysis

Statistical Analysis

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-8-28

Curated date: 2025/08/27

Curator: Anne-mariesharp

Revision editor(s): Anne-mariesharp

Source: Figure 2A

Description: Most differentially abundant phyla between groups, identified by DESeq2.

Abundance in Group 1: increased abundance in G-DED (Glaucomatous patients with dry eye syndrome)

NCBI Quality ControlLinks
Bacillota
Pseudomonadota
Bacteroidota

Revision editor(s): Anne-mariesharp