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Debaryomyces is enriched in Crohn's disease intestinal tissue and impairs healing in mice.

ABSTRACT: Alterations of the mycobiota composition associated with Crohn's disease (CD) are challenging to link to defining elements of pathophysiology, such as poor injury repair. Using culture-dependent and -independent methods, we discovered that Debaryomyces hansenii preferentially localized to and was abundant within incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD human subjects. D. hansenii cultures from injured mice and inflamed CD tissues impaired colonic healing when introduced into injured conventionally raised or gnotobiotic mice. We reisolated D. hansenii from injured areas of these mice, fulfilling Koch's postulates. Mechanistically, D. hansenii impaired mucosal healing through the myeloid cell-specific type 1 interferon-CCL5 axis. Taken together, we have identified a fungus that inhabits inflamed CD tissue and can lead to dysregulated mucosal healing.

SUBMITTER: Jain U

PROVIDER: S-EPMC10114606 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Debaryomyces is enriched in Crohn's disease intestinal tissue and impairs healing in mice.

Jain Umang U Ver Heul Aaron M AM Xiong Shanshan S Gregory Martin H MH Demers Elora G EG Kern Justin T JT Lai Chin-Wen CW Muegge Brian D BD Barisas Derek A G DAG Leal-Ekman J Steven JS Deepak Parakkal P Ciorba Matthew A MA Liu Ta-Chiang TC Hogan Deborah A DA Debbas Philip P Braun Jonathan J McGovern Dermot P B DPB Underhill David M DM Stappenbeck Thaddeus S TS

Science (New York, N.Y.) 20210301 6534

Alterations of the mycobiota composition associated with Crohn's disease (CD) are challenging to link to defining elements of pathophysiology, such as poor injury repair. Using culture-dependent and -independent methods, we discovered that Debaryomyces hansenii preferentially localized to and was abundant within incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD human subjects. D. hansenii cultures from injured mice and inflamed CD tissues impaired col ...[more]

PMID: 33707263

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Project description:BackgroundMucosal healing (MH) is the key aim of the treat-to-target strategy for patients with Crohn's disease (CD). The efficacy of infliximab (IFX) on MH in different ileocolonic segments is unclear. The aim of this study was to investigate endoscopic MH in different ileocolonic segments in patients with CD who received IFX treatment.MethodsA retrospective, single-center study was performed in patients with active ileocolonic CD between January 2012 and December 2018. All patients underwent IFX treatment for at least 30 weeks. The MH of five ileocolonic segments was assessed by the Simple Endoscopic Score for CD (SES-CD) at baseline, 14/22 weeks and 30/38 weeks. The SES-CD values were analyzed by a mixed-effects model after the correction for confounding factors.ResultsA total of 101 eligible patients were included. The baseline endoscopic severity was similar across segments. At 30/38 weeks, the greatest changes in the SES-CD ulcer size and ulcerated surface subscores were -94.29% and -94.32% both in the transverse colon (p < 0.0001), and the smallest changes were -67.88% and -69.67% both in the terminal ileum (p < 0.0001) compared with baseline. Stenosis mainly presented in the right colon (12/29, 41.38%). The change in the SES-CD stenosis subscore was -6.25% in the right colon at 30/38 weeks compared with -71.88% at 14/22 weeks (p = 0.0030). At 30/38 weeks, the transverse colon achieved the highest rate of complete MH (CMH) at 81.2%, and the lowest CMH rate occurred in the terminal ileum at 45.6%. Moreover, the degree of improvement in the rectum was negatively correlated with disease progression (p = 0.011).ConclusionsIleocolonic segments in CD presented different degrees of endoscopic MH during IFX treatment. The transverse colon showed the highest CMH rate, whereas the right colon with stenosis showed the poorest improvement. The differing propensities of ileocolonic segments may provide an individualized IFX treatment strategy.

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Debaryomyces is enriched in Crohn's disease intestinal tissue and impairs healing in mice.

Publications

<i>Debaryomyces</i> is enriched in Crohn's disease intestinal tissue and impairs healing in mice.

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