The Human Ocular Surface Microbiome and Its Associations with the Tear Proteome in Dry Eye Disease

Study information

Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-22

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

37762390

DOI Digital object identifier for electronic documents.

10.3390/ijms241814091

URI

Authors

Schlegel I, De Goüyon Matignon de Pontourade CMF, Lincke JB, Keller I, Zinkernagel MS, Zysset-Burri DC

Journal

International journal of molecular sciences

Year

2023

Keywords:

chromatography–tandem mass spectrometry, dry eye disease, ocular surface microbiome, tear proteome, whole-metagenome shotgun sequencing

Although dry eye disease (DED) is one of the most common ocular surface diseases worldwide, its pathogenesis is incompletely understood, and treatment options are limited. There is growing evidence that complex interactions between the ocular surface microbiome (OSM) and tear fluid constituents, potentially leading to inflammatory processes, are associated with ocular surface diseases such as DED. In this study, we aimed to find unique compositional and functional features of the OSM associated with human and microbial tear proteins in patients with DED. Applying whole-metagenome shotgun sequencing of forty lid and conjunctival swabs, we identified 229 taxa, with Actinobacteria and Proteobacteria being the most abundant phyla and Propionibacterium acnes the dominating species in the cohort. When DED patients were compared to controls, the species Corynebacterium tuberculostearicum was more abundant in conjunctival samples, whereas the family Propionibacteriaceae was more abundant in lid samples. Functional analysis showed that genes of L-lysine biosynthesis, tetrapyrrole biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis, and the super pathway of L-threonine biosynthesis were enriched in conjunctival samples of controls. The relative abundances of Acinetobacter johnsonii correlated with seven human tear proteins, including mucin-16. The three most abundant microbial tear proteins were the chaperone protein DnaK, the arsenical resistance protein ArsH, and helicase. Compositional and functional features of the OSM and the tear proteome are altered in patients with DED. Ultimately, this may help to design novel interventional therapeutics to target DED.

Experiment 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-22

Curated date: 2023/09/30

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Subjects

Location of subjects: Switzerland

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: Eyelid Blephara,Blepharon,Eye lid,Palpebra,Palpebrae,Eyelid,eyelid

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: 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: Dry Eye Disease diagnosis

Group 0 sample size Number of subjects in the control (unexposed) group: 10

Group 1 sample size Number of subjects in the case (exposed) group: 10

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Antibiotics within the past 3 months

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: Welch's T-Test

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

Signature 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-22

Curated date: 2023/10/01

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Source: Figure 4c

Description: Figure 4c. The distinct taxonomical and functional composition of the ocular surface microbiome between DED patients and healthy controls. The relative abundances of taxa associated with DED (Mann–Whitney test). Mean values and standard deviations are shown.

Abundance in Group 1: increased abundance in Dry Eye

NCBI	Quality Control	Links
Propionibacteriaceae

Revision editor(s): Mary Bearkland

Experiment 2

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Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-22

Curated date: 2023/10/01

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland, ChiomaBlessing

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Palpebral conjunctiva Conjunctival layer of eyelids,Eyelid conjunctiva,Tarsal conjunctiva,Tunica conjunctiva palpebrum,Palpebral conjunctiva,palpebral conjunctiva

Lab analysis

Statistical Analysis

Signature 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-22

Curated date: 2023/10/01

Curator: Mary Bearkland

Revision editor(s): Mary Bearkland

Source: Figure 4a

Description: Figure 4. The distinct taxonomical composition of the ocular surface microbiome between DED patients and healthy controls. The relative abundances of taxa (c) associated with DED (Mann–Whitney test). Mean values and standard deviations are shown.

Abundance in Group 1: increased abundance in Dry Eye

NCBI	Quality Control	Links
Corynebacterium tuberculostearicum

Revision editor(s): Mary Bearkland