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Thiele Orberg, E.* ; Meedt, E.* ; Hiergeist, A.* ; Xue, J. ; Heinrich, P.C.* ; Ru, J. ; Ghimire, S.* ; Miltiadous, O.* ; Lindner, S.* ; Tiefgraber, M.* ; Göldel, S.* ; Eismann, T.* ; Schwarz, A.* ; Göttert, S.* ; Jarosch, S.* ; Steiger, K.* ; Schulz, C.* ; Gigl, M.* ; Fischer, J.C.* ; Janssen, K.P.* ; Quante, M.* ; Heidegger, S.* ; Herhaus, P.* ; Verbeek, M.* ; Ruland, J.* ; van den Brink, M.R.M.* ; Weber, D.* ; Edinger, M.* ; Wolff, D.* ; Busch, D.H.* ; Kleigrewe, K.* ; Herr, W.* ; Bassermann, F.* ; Gessner, A.* ; Deng, L. ; Holler, E.* ; Poeck, H.*

Bacteria and bacteriophage consortia are associated with protective intestinal metabolites in patients receiving stem cell transplantation.

Nat. Cancer 5, 187-208 (2024)

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The microbiome is a predictor of clinical outcome in patients receiving allogeneic hematopoietic stem cell transplantation (allo-SCT). Microbiota-derived metabolites can modulate these outcomes. How bacteria, fungi and viruses contribute to the production of intestinal metabolites is still unclear. We combined amplicon sequencing, viral metagenomics and targeted metabolomics from stool samples of patients receiving allo-SCT (n = 78) and uncovered a microbiome signature of Lachnospiraceae and Oscillospiraceae and their associated bacteriophages, correlating with the production of immunomodulatory metabolites (IMMs). Moreover, we established the IMM risk index (IMM-RI), which was associated with improved survival and reduced relapse. A high abundance of short-chain fatty acid-biosynthesis pathways, specifically butyric acid via butyryl-coenzyme A (CoA):acetate CoA-transferase (BCoAT, which catalyzes EC 2.8.3.8) was detected in IMM-RI low-risk patients, and virome genome assembly identified two bacteriophages encoding BCoAT as an auxiliary metabolic gene. In conclusion, our study identifies a microbiome signature associated with protective IMMs and provides a rationale for considering metabolite-producing consortia and metabolite formulations as microbiome-based therapies.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Versus-host-disease; Gut Microbiome; Acid; Antibiotics; Diversity; Guide

ISSN (print) / ISBN 2662-1347

e-ISSN 2662-1347

Journal Nature Cancer

Quellenangaben Volume: 5, Issue: 1, Pages: 187-208

Publisher Springer

Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Virology (VIRO)

Grants Else Kroner-Fresenius-Stiftung
European Hematology Association
Bavarian Cancer Research Center
Wilhelm Sander Foundation
German Cancer Aid
Deutsche Forschungsgemeinschaft
Bavarian State Ministry of Science and Art
DKMS Foundation for Giving Life

EMBO Young Investigator Program
Deutsche Gesellschaft fur Innere Medizin
Deutsches Konsortium fur Translationale Krebsforschung
European Research Commission
German Jose Carreras Leukemia Foundation
Deutsche Forschungsgemeinschaft (German Research Foundation)