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

Author

Thiele Orberg, Erik, primary, Meedt, Elisabeth, additional, Hiergeist, Andreas, additional, Xue, Jinling, additional, Heinrich, Paul, additional, Ru, Jinlong, additional, Ghimire, Sakhila, additional, Miltiadous, Oriana, additional, Lindner, Sarah, additional, Tiefgraber, Melanie, additional, Göldel, Sophia, additional, Eismann, Tina, additional, Schwarz, Alix, additional, Göttert, Sascha, additional, Jarosch, Sebastian, additional, Steiger, Katja, additional, Schulz, Christian, additional, Gigl, Michael, additional, Fischer, Julius C., additional, Janssen, Klaus-Peter, additional, Quante, Michael, additional, Heidegger, Simon, additional, Herhaus, Peter, additional, Verbeek, Mareike, additional, Ruland, Jürgen, additional, van den Brink, Marcel R. M., additional, Weber, Daniela, additional, Edinger, Matthias, additional, Wolff, Daniel, additional, Busch, Dirk H., additional, Kleigrewe, Karin, additional, Herr, Wolfgang, additional, Bassermann, Florian, additional, Gessner, André, additional, Deng, Li, additional, Holler, Ernst, additional, and Poeck, Hendrik, additional

Published
2024
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2. Bacteriophage-modulated Production of Intestinal Immuno-modulatory Metabolites is Associated with Protection in Allogeneic Stem Cell Transplantation Patients

Author

Orberg, Erik Thiele, Meedt, Elisabeth, Hiergeist, Andreas, Jinling Xue, Heinrich, Paul, Sakhila Ghimire, Tiefgraber, Melanie, Göldel, Sophia, Eismann, Tina, Schwarz, Alix, Göttert, Sascha, Jarosch, Sebastian, Steiger, Katja, Schulz, Christian, Gigl, Michael, Fischer, Julius, Klaus-Peter Janssen, Quante, Michael, Heidegger, Simon, Herhaus, Peter, Verbeek, Mareike, Ruland, Jürgen, Weber, Daniela, Wolff, Daniel, Edinger, Matthias, Busch, Dirk, Kleigrewe, Karin, Herr, Wolfgang, Bassermann, Florian, Gessner, André, Deng, Li, Holler, Ernst, and Poeck, Hendrik

Abstract

The human microbiome directly affects clinical outcome in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). Besides bacteria, fungal and viral kingdoms as well as microbiota-derived metabolites play a role. Previous research has focused on their systemic effects, but increasingly their local, tissue-specific role e.g., in regulating intestinal homeostasis, is appreciated. Yet, it is still unclear how dynamic shifts in the three kingdoms contribute to the production of intestinal metabolites, how these metabolites are altered by microbiome modulation and whether they are associated with clinical outcome. Here, we performed a prospective, longitudinal study that combined three-kingdom (bacteria, fungi, viruses) analysis of intestinal microbial communities with targeted metabolomics in allo-SCT patients (n=78) at two different transplantation centers. We uncovered a functional microbiome signature of bacteria from the Lachnospiraceae and Oscillospiraceae families and their associated bacteriophages, which correlated with the production of immuno-modulatory metabolites including short-chain fatty acids (SCFAs), branched-chain fatty acids (BCFA), metabolites associated with induction of type-I IFN signaling (IIMs) and immuno-modulatory secondary bile acids. We established an Immuno-modulatory Metabolite Risk Index consisting of five index immuno-modulatory metabolites (IMMs), which was associated with improved survival and reduced relapse rate. Microbiome modulation, either inadvertently by onset of GI-GvHD or exposure to antibiotics, or as proof-of-concept via fecal microbiome transplantation (FMT) significantly impacted intestinal levels of protective IMMs. Via metagenomic sequencing, we observed that in IMM-RI low-risk patients, sustained production of protective IMMs was associated with a high abundance of SCFA biosynthesis pathways, specifically butyric acid via butyryl-CoA:acetate CoA-transferase (BCoAT). By viral metagenomic sequencing from isolated viral particles, we detected BCoAT contained within two unique temperate bacteriophages, suggesting they may augment bacterial metabolite biosynthesis. Our study demonstrates that bacteriophage-modulated bacterial consortia are associated with protective IMMs and provides a rationale for the development of engineered metabolite-producing consortia and defined metabolite combination drugs as novel microbiome-based therapies

Published
2023
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3. Identification of Bacterial and Viral Consortia for the Production of Intestinal Microbiota-Derived Metabolites Associated with Protection in Allogeneic Stem Cell Transplantation Patients

Author

Thiele Orberg, Erik, primary, Meedt, Elisabeth, additional, Hiergeist, Andreas, additional, Xue, Jinling, additional, Heinrich, Paul, additional, Ghimire, Sakhila, additional, Tiefgraber, Melanie, additional, Göldel, Sophia, additional, Eismann, Tina, additional, Schwarz, Alix, additional, Jarosch, Sebastian, additional, Steiger, Katja, additional, Kleigrewe, Karin, additional, Fischer, Julius Clemens, additional, Janssen, Klaus-Peter, additional, Quante, Michael, additional, Heidegger, Simon, additional, Herhaus, Peter, additional, Verbeek, Mareike, additional, Ruland, Jürgen, additional, Schulz, Christian, additional, Weber, Daniela, additional, Edinger, Matthias, additional, Wolff, Daniel, additional, Busch, Dirk, additional, Herr, Wolfgang, additional, Bassermann, Florian, additional, Deng, Li, additional, Gessner, Andre, additional, Holler, Ernst, additional, and Poeck, Hendrik, additional

Published
2022
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4. Identification of Protective, Metabolite-producing Bacterial and Viral Consortia in Allogeneic Stem Cell Transplantation Patients

Author

Orberg, Erik Thiele, primary, Meedt, Elisabeth, additional, Hiergeist, Andreas, additional, Xue, Jinling, additional, Ghimire, Sakhila, additional, Tiefgraber, Melanie, additional, Göldel, Sophia, additional, Eismann, Tina, additional, Schwarz, Alix, additional, Jarosch, Sebastian, additional, Steiger, Katja, additional, Gigl, Michael, additional, Kleigrewe, Karin, additional, Fischer, Julius, additional, Janssen, Klaus-Peter, additional, Quante, Michael, additional, Heidegger, Simon, additional, Herhaus, Peter, additional, Verbeek, Mareike, additional, Ruland, Jürgen, additional, Weber, Daniela, additional, Wolff, Daniel, additional, Edinger, Matthias, additional, Busch, Dirk, additional, Herr, Wolfgang, additional, Bassermann, Florian, additional, Gessner, André, additional, Deng, Li, additional, Holler, Ernst, additional, and Poeck, Hendrik, additional

Published
2022
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5. Longitudinal Analysis of Gut Bacteriome, Mycobiome, Virome and Metabolome in Allogeneic Stem Cell Transplantation Reveals Susceptibility for Acute Graft-Versus-Host Disease

Author

Thiele Orberg, Erik, primary, Meedt, Elisabeth, additional, Hiergeist, Andreas, additional, Xue, Jinling, additional, Ghimire, Sakhila, additional, Tiefgraber, Melanie, additional, Eismann, Tina, additional, Göldel, Sophia, additional, Herhaus, Peter, additional, Verbeek, Mareike, additional, Bassermann, Florian, additional, Quante, Michael, additional, Weber, Daniela, additional, Edinger, Matthias, additional, Wolff, Daniel, additional, Herr, Wolfgang, additional, Deng, Li, additional, Gessner, André, additional, Holler, Ernst, additional, and Poeck, Hendrik, additional

Published
2021
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