Göttert, Sascha and Thiele Orberg, Erik and Fan, Kaiji and Heinrich, Paul and Matthe, Diana M. and Khalid, Omer and Klostermeier, Lena and Suriano, Chiara and Strieder, Nicholas and Gebhard, Claudia and Vonbrunn, Eva and Mamilos, Andreas and Hirsch, Daniela and Meedt, Elisabeth and Kleigrewe, Karin and Hiergeist, Andreas and Schwarz, Alix and Gläsner, Joachim and Ghimire, Sakhila and Joachim, Laura and Voll, Florian and Neuhaus, Klaus and Janssen, Klaus-Peter and Perl, Markus and Pielmeier, Franziska and Ruland, Jürgen and Kreutz, Marina and Weber, Daniela and Schmidl, Christian and Köhler, Natalie and Tschurtschenthaler, Markus and Hoffmann, Petra and Edinger, Matthias and Wolff, Daniel and Bassermann, Florian and Rehli, Michael and Haller, Dirk and Evert, Matthias and Hildner, Kai and Büttner-Herold, Maike and Herr, Wolfgang and Gessner, Andre and Heidegger, Simon and Holler, Ernst and Poeck, Hendrik (2025) The microbial metabolite desaminotyrosine protects against graft-versus-host disease via mTORC1 and STING-dependent intestinal regeneration. NATURE COMMUNICATIONS, 16 (1): 9282. ISSN 2041-1723
Full text not available from this repository. (Request a copy)Abstract
Changes in the intestinal microbiome and microbiota-derived metabolites predict clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we report that desaminotyrosine (DAT), a product of bacterial flavonoid metabolism, correlates with improved overall survival and reduced relapse rates in patients receiving allo-HSCT. In preclinical mouse models, treatment with synthetic DAT prevents graft-versus-host disease by protecting the intestinal barrier and promoting intestinal regeneration and contributes to graft-vs.-leukemia responses. DAT<acute accent>s beneficial effects on intestinal regeneration remain effective despite broad-spectrum antibiotics-induced dysbiosis, also when administered by fecal microbiota transfer with flavonoid-degrading F. plautii. Mechanistically, DAT promotes mTORC1-dependent activation and proliferation of intestinal stem cells, with concomitant engagement of the innate immune receptor STING required to mitigate metabolic stress and maintain an undifferentiated stem cell state independently of type-I interferon responses. Additionally, DAT can skew T cells towards an effector phenotype to modulate graft-versus-leukemia responses. Our data uncover DAT's dual, tissue- and immune-modulating properties and underscore its potential in precision microbiome-based therapies to improve tissue regeneration and minimize immune-mediated side effects.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHAIN FATTY-ACIDS; GUT MICROBIOTA; STEM-CELLS; RISK; DIFFERENTIATION; TRANSPLANTATION; IDENTIFICATION; ANTIBIOTICS; ACTIVATION; EPITHELIUM |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jul 2026 07:01 |
| Last Modified: | 28 Jul 2026 07:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/66981 |
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