TY - JOUR
T1 - Bacteria and bacteriophage consortia are associated with protective intestinal metabolites in patients receiving stem cell transplantation
AU - Thiele Orberg, Erik
AU - Meedt, Elisabeth
AU - Hiergeist, Andreas
AU - Xue, Jinling
AU - Heinrich, Paul
AU - Ru, Jinlong
AU - Ghimire, Sakhila
AU - Miltiadous, Oriana
AU - Lindner, Sarah
AU - Tiefgraber, Melanie
AU - Göldel, Sophia
AU - Eismann, Tina
AU - Schwarz, Alix
AU - Göttert, Sascha
AU - Jarosch, Sebastian
AU - Steiger, Katja
AU - Schulz, Christian
AU - Gigl, Michael
AU - Fischer, Julius C.
AU - Janssen, Klaus Peter
AU - Quante, Michael
AU - Heidegger, Simon
AU - Herhaus, Peter
AU - Verbeek, Mareike
AU - Ruland, Jürgen
AU - van den Brink, Marcel R.M.
AU - Weber, Daniela
AU - Edinger, Matthias
AU - Wolff, Daniel
AU - Busch, Dirk H.
AU - Kleigrewe, Karin
AU - Herr, Wolfgang
AU - Bassermann, Florian
AU - Gessner, André
AU - Deng, Li
AU - Holler, Ernst
AU - Poeck, Hendrik
N1 - Publisher Copyright:
© 2024, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85181245342&partnerID=8YFLogxK
U2 - 10.1038/s43018-023-00669-x
DO - 10.1038/s43018-023-00669-x
M3 - Article
AN - SCOPUS:85181245342
SN - 2662-1347
VL - 5
SP - 187
EP - 208
JO - Nature Cancer
JF - Nature Cancer
IS - 1
ER -