2. Academic Validation
  3. The Microbiome Modulates Corneal Wound Healing via the Induction of Cholesterol Sulfotransferase Pathway

The Microbiome Modulates Corneal Wound Healing via the Induction of Cholesterol Sulfotransferase Pathway

  • FASEB J. 2026 Jan 31;40(2):e71429. doi: 10.1096/fj.202503669R.
Mamoru Ogawa 1 2 3 4,  Yosuke Isobe 1 5 6,  Haruki Uchino 1,  Masatoshi Hirayama 2 7,  Tamotsu Kato 8 9,  Kazuno Negishi 2,  Makoto Arita 1 5 6 10
Affiliations

Affiliations

  • 1 Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan.
  • 2 Department of Ophthalmology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
  • 3 Cornea Cell Biology (CCB), Keio University School of Medicine, Shinjuku, Tokyo, Japan.
  • 4 Department of Ophthalmology, Keiyu Hospital, Yokohama, Kanagawa, Japan.
  • 5 Division of Physiological Chemistry and Metabolism, Keio University Faculty of Pharmacy, Minato, Tokyo, Japan.
  • 6 Molecular and Cellular Epigenetics Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa, Japan.
  • 7 Department of Ophthalmology, Faculty of Medicine, Fukuoka University, Fukuoka, Fukuoka, Japan.
  • 8 Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan.
  • 9 Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa, Japan.
  • 10 Human Biology Microbiome Quantum Research Center (WPI-Bio2Q), Keio University, Shinjuku, Tokyo, Japan.
PMID: 41524110 DOI: 10.1096/fj.202503669R
Abstract

The ocular surface is in direct contact with the external environment and is susceptible to injury from dust, dryness, or Other foreign objects. Once corneal injury occurs, a local inflammatory response is triggered, followed by effective repair of the epithelial layer. In this study, we demonstrated that Antibiotic treatment delayed corneal wound healing in mice. LC-MS/MS-based untargeted lipidomics and qPCR analyses revealed that the levels of Cholesterol sulfate (CS) and the CS-synthesizing enzyme SULT2B1 were significantly upregulated by Antibiotic treatment, and SULT2B1 knockout mice exhibited accelerated corneal wound healing along with increased recruitment of neutrophils and eosinophils. Topical application of CS delayed corneal wound healing. In vitro scratch assays revealed that CS delayed the wound healing of human corneal epithelial cells, potentially by inhibiting the DOCK2-Rac pathway. These results highlight the role of commensal bacteria in controlling corneal wound healing via the cholesterol-sulfotransferase pathway.

Keywords

cholesterol sulfate; commensal bacteria; corneal wound healing; lipid mediators; lipidomics; metabolomics; microbiota; ocular surface; sulfotransferase (SULT); sulfuryltransferase.

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