Published in Nature Communications, the study reveals that DAT, a metabolite produced by gut bacteria from dietary flavonoids found in foods such as kale, berries, and grapes — can protect patients from graft-versus-host disease (GvHD), a severe and often life-threatening complication following a stem cell transplantation from a donor. The discovery offers a promising new approach to improving survival outcomes for transplant patients.
In mouse models, treatment with synthetic DAT prevented intestinal damage, promoted regeneration of intestinal stem cells, and preserved the beneficial graft-versus-leukemia effect — the immune response that destroys residual cancer cells. Importantly, these protective effects remained even after antibiotic treatment that disrupts the microbiome.
The researchers found that DAT activates two key signaling pathways — known as mTORC1 and STING — in intestinal stem cells, promoting regeneration and protecting tissue from inflammation and radiation damage.
“Desaminotyrosine represents a remarkable link between the microbiome and our body’s ability to regenerate tissue after injury, and enhance antitumor immunity” said Dr. Erik Orberg, physician scientist at UKR and co-first author of the study.
The study also suggests that administering DAT-producing bacteria, such as Flavonifractor plautii, could serve as a precision microbiome therapy to improve transplant outcomes.
“This work opens up exciting possibilities for precision microbiome-based therapies,” adds Sascha Göttert, PhD Candidate and first author of the study. “We envision DAT—or DAT-producing bacteria—being developed as novel interventions to improve transplant outcomes and minimize immune-related side effects”, explains Prof. Poeck, managing senior physician of the clinic and research group leader at UKR and LIT.
These results pave the way for new treatments that harness microbial metabolites to repair tissues, control inflammation, and enhance the efficacy and safety of cellular immunotherapies.
Publication:
Göttert, S. et al. “The microbial metabolite desaminotyrosine protects against graft-versus-host disease via mTORC1 and STING-dependent intestinal regeneration.”
Nature Communications (2025). DOI: 10.1038/s41467-025-65180-6
https://www.nature.com/articles/s41467-025-65180-6
Within the Collaborative Research Centre/Transregio (CRC/TRR) 221 innovative immune modulation strategies will be investigated to separate GvHD from GvL effects in order to enhance the safety and efficacy of allo-HSCT in the future.
