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Multi-cohort analysis identifying core ocular surface microbiome and bacterial alterations in eye diseases

Eye volume 39, pages 1276–1285 (2025)Cite this article

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Abstract

Purpose

Inconsistency exists among reported studies on the composition of human ocular surface microbiome (OSM). The roles of OSM in ocular diseases remain uncertain. In this study, we aimed to determine the composition of OSM and to evaluate its potential roles and functions from multiple cohorts.

Methods

Raw 16 s sequencing data were obtainable from publicly available repositories, sourced from 17 published studies. Employing a standardized method, we processed the data and conducted a cross-cohort analysis. Through bioinformatics pipelines QIIME2 and PICRUSt2, we processed a total of 1875 ocular surface samples. Core microbiome analyses, genera comparisons, and MetaCyc pathway analyses were performed within each cohort independently. The results were then combined to identify shared patterns across different datasets.

Results

The core OSM comprised seven genera: Corynebacterium, Staphylococcus, Acinetobacter, Streptococcus, Pseudomonas, Cutibacterium and Bacillus. Corynebacterium and Staphylococcus are the most abundant genera on ocular surface. Most ocular diseases showed OSM alterations and eight genera demonstrated a non-specific, shared response among two or more ocular diseases. Moreover, changes in various metabolic pathways were predicted following OSM alteration, indicating potential roles of OSM in biological processes.

Conclusion

We refined the core OSM candidates combining multiple cohorts. The common pattern shared by different cohorts is worth further investigation. Changes in metabolic pathways based on bioinformatic analysis indicated a role of OSM on ocular diseases. Our results help extend the knowledge and encourage further investigations on the associations between OSM and ocular diseases.

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Fig. 1: Diversity of microbiome composition in healthy participants.
Fig. 2: Core microbiome identified across 17 cohorts.
Fig. 3: Microbial response to ocular diseases.
Fig. 4: Metabolic pathway prediction of OSM by PICRUSt2.

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Data availability

Raw sequencing data for each study is accessible as described in Supplementary Table 1. Our re-analysed OTU/ASV tables are available at: https://github.com/ficion1/meta-analysis-of-OSM. Our study can be reproduced using these files. Supplementary files include tables showing the prevalence rates of core microbiomes and the q-values of univariate comparisons for each dataset. All other relevant data supporting the study findings are available in this article and its supplementary files, as well as from the corresponding author upon request.

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Acknowledgements

We thank all the authors who made their data available as well as those who provided data through personal communications.

Funding

The authors have no proprietary or commercial interest in any materials disclosed in this article. This study was supported in part by National Natural Science Foundation of China (82171089 [JCY]); the General Research Fund (GRF), Research Grants Council, Hong Kong (14111515 and 14103419 [JCY]); Collaborative Research Fund (C7149-20G [JCY]); Health and Medical Research Fund (HMRF), Hong Kong (5160836 [LJC], 07180826 [XJZ] and 21220251 [PCP]),), and the Direct Grants of the Chinese University of Hong Kong, (4054193 [LJC] and 4054121 & 4054199 [JCY] and 178662514 and 4054634 [XJZ] and 2015.1.056); the Innovation and Technology Fund (7010590 [JCY]), the UBS Optimus Foundation Grant 8984 (JCY); the Centaline Myopia Fund [JCY]; the CUHK Jockey Club Children’s Eye Care Programme, and the CUHK Jockey Club Myopia Prevention Programme.

Author information

Author notes

  1. These authors contributed equally: Xiangtian Ling, Xiu Juan Zhang.

Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China

    Xiangtian Ling, Xiu Juan Zhang, Christine H. T. Bui, Hei Nga Chan, Fang Yao Tang, Ka Wai Kam, Alvin L. Young, Clement C. Tham, Chi Pui Pang, Li Jia Chen & Jason C. Yam

  2. Department of Paediatrics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China

    Jennifer Wing Ki Yau & Kam Lun Hon

  3. Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong SAR, China

    Ka Wai Kam, Alvin L. Young, Clement C. Tham, Li Jia Chen & Jason C. Yam

  4. Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Patrick Ip

  5. Hong Kong Eye Hospital, Kowloon, Hong Kong SAR, China

    Clement C. Tham & Jason C. Yam

  6. Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China

    Clement C. Tham, Chi Pui Pang, Li Jia Chen & Jason C. Yam

  7. Department of Ophthalmology, Hong Kong Children Hospital, Hong Kong SAR, China

    Jason C. Yam

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  1. Xiangtian Ling
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Contributions

XL, XZ, HNC, and JCY conceived of the research. XL and XZ identified and downloaded the datasets. XL and JWY processed the data. CHTB and XL interpreted the results and prepared the manuscript. LJC and JCY supervised the work. All authors discussed and revised the manuscript.

Corresponding authors

Correspondence to Li Jia Chen or Jason C. Yam.

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The authors declare no competing interests. Alvin Young is a member of the Eye editorial board.

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Ling, X., Zhang, X.J., Bui, C.H.T. et al. Multi-cohort analysis identifying core ocular surface microbiome and bacterial alterations in eye diseases. Eye 39, 1276–1285 (2025). https://doi.org/10.1038/s41433-024-03589-x

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