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  1. Philip J Smith
  1. Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
  1. Correspondence to Dr Philip J Smith, Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, L7 8XP, UK; Philip.Smith{at}liverpoolft.nhs.uk

https://doi.org/10.1136/gutjnl-2021-324971

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    Debaryomyces hansenii impairs wound healing in Crohn’s disease

    Jain U, Ver Heul A, Xiong S, et al. Debaryomyces is enriched in Crohn’s disease intestinal tissue and impairs healing in mice. Science 2021; 3716534,: 1154–1159.

    Impaired wound healing is a hallmark of Crohn’s disease (CD) and is associated with alterations in bacterial and fungal populations. Despite the association of specific microbes, no single organism has been conclusively linked to pathophysiological aspects of CD such as impaired healing. Using a murine biopsy injury model, Jain et al established a central role for the fungus Debaryomyces hansenii (also known as Candida famata) in CD-associated defective tissue repair. Using culture-dependent and independent methods, the authors demonstrated that D. hansenii was abundant in mucosal wounds. Administration of D. hansenii to wild-type (WT) mice was sufficient to impair wound healing. D. hansenii also impaired wound healing in dextran sodium sulfate treated gnotobiotic mice illustrating that bacterial factors were not required for D. hansenii to mediate tissue repair. Using cytokine expression profiling, D. hansenii was shown to induce macrophage production of chemokine ligand 5 (CCL5). Indeed, in a CCL5 knockout model, despite similar colonisation as WT mice, D. hansenii gavage did not impair healing. Finally, using ileal biopsies as well as resection specimens from patients with CD, D. hansenii was shown to be (1) ubiquitously present in patients with CD compared with healthy controls and (2) highly enriched in inflamed tissue. They also demonstrated serum IgA antibodies against D. hansenii in patients with CD. Furthermore, clinical isolates of D. hansenii caused impaired healing when WT mice were gavaged with a pure isolate. In summary, D. hansenii appears to play a crucial role in CD pathogenesis and is a novel therapeutic target.

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    Footnotes

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Commissioned; internally peer reviewed.