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PreprintCC BY-NC-NDbioRxiv

Defining the Functional Consequence of the Human Ocular Microbiome

6 more authors
  1. 1University of Pittsburgh

Abstract

The ocular surface is one of the body's most environmentally exposed mucosal barriers, yet it is considered low biomass and harbors orders of magnitude fewer bacteria than microbe-rich sites like the gut. This has cast doubt on whether a functional core ocular microbiome exists at all. Having previously defined a protective gd T cell and IL-17 axis engaged by the murine commensal Corynebacterium mastitidis, we asked whether human-derived bacteria could do the same. Pairing sequencing and culturomics of healthy human conjunctiva from two geographically distinct cohorts, we define a stable core microbiome and identify Corynebacterium bovis as a consistent eye-resident commensal rather than a transient contaminant. In humans, C. bovis elicits a non-pathogenic response marked by IL-17 secretion by {gamma}{delta} T cells and circulating C. bovis-specific IgG, which suggests commensalism rather than pathology. Colonizing mice with human C. bovis strains from Pittsburgh or Miami reproduced this program and conferred protection against ocular infection with Staphylococcus aureus. Together, these findings identify C. bovis as a human-derived ocular commensal that can drive protective {gamma}{delta} T cell immunity, translating a mechanism previously defined only in mice into human relevance and a rational target against sight-threatening infection.

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BibTeX
@misc{gandhi2026defining,
  title = {{Defining the Functional Consequence of the Human Ocular Microbiome}},
  author = {J. Gandhi and B. Desai and S. Mangwani-Mordani and J. Shane and J. Bierker and A. Wessell and D. M. Rodriguez J. and S. K. Randhawa and S. Ma and C. M. Phelps and M. Meisel and A. Patel and K. Li and A. Fitch and M. Barbara and V. Jhanji and A. Galor and A. J. St. Leger},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.28.762462},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762462v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Defining the Functional Consequence of the Human Ocular Microbiome
AU  - J. Gandhi
AU  - B. Desai
AU  - S. Mangwani-Mordani
AU  - J. Shane
AU  - J. Bierker
AU  - A. Wessell
AU  - D. M. Rodriguez J.
AU  - S. K. Randhawa
AU  - S. Ma
AU  - C. M. Phelps
AU  - M. Meisel
AU  - A. Patel
AU  - K. Li
AU  - A. Fitch
AU  - M. Barbara
AU  - V. Jhanji
AU  - A. Galor
AU  - A. J. St. Leger
PY  - 2026
DA  - 2026/10/28
PB  - bioRxiv
DO  - 10.64898/2026.10.28.762462
UR  - https://www.biorxiv.org/content/10.64898/2026.10.28.762462v1
AB  - The ocular surface is one of the body's most environmentally exposed mucosal barriers, yet it is considered low biomass and harbors orders of magnitude fewer bacteria than microbe-rich sites like the gut. This has cast doubt on whether a functional core ocular microbiome exists at all. Having previously defined a protective gd T cell and IL-17 axis engaged by the murine commensal Corynebacterium mastitidis, we asked whether human-derived bacteria could do the same. Pairing sequencing and culturomics of healthy human conjunctiva from two geographically distinct cohorts, we define a stable core microbiome and identify Corynebacterium bovis as a consistent eye-resident commensal rather than a transient contaminant. In humans, C. bovis elicits a non-pathogenic response marked by IL-17 secretion by {gamma}{delta} T cells and circulating C. bovis-specific IgG, which suggests commensalism rather than pathology. Colonizing mice with human C. bovis strains from Pittsburgh or Miami reproduced this program and conferred protection against ocular infection with Staphylococcus aureus. Together, these findings identify C. bovis as a human-derived ocular commensal that can drive protective {gamma}{delta} T cell immunity, translating a mechanism previously defined only in mice into human relevance and a rational target against sight-threatening infection.
ER  -