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

被引:9
作者
Thiele Orberg, Erik [1 ,2 ,3 ]
Meedt, Elisabeth [4 ]
Hiergeist, Andreas [5 ]
Xue, Jinling [6 ,7 ,8 ]
Heinrich, Paul [4 ,9 ]
Ru, Jinlong [6 ,7 ,8 ]
Ghimire, Sakhila [4 ]
Miltiadous, Oriana [10 ]
Lindner, Sarah [11 ]
Tiefgraber, Melanie [1 ]
Goeldel, Sophia [1 ]
Eismann, Tina [1 ]
Schwarz, Alix [1 ]
Goettert, Sascha [4 ]
Jarosch, Sebastian [12 ]
Steiger, Katja [2 ,13 ,14 ]
Schulz, Christian [15 ,16 ]
Gigl, Michael [17 ]
Fischer, Julius C. [18 ]
Janssen, Klaus-Peter [19 ]
Quante, Michael [20 ]
Heidegger, Simon [1 ,3 ]
Herhaus, Peter [1 ]
Verbeek, Mareike [1 ]
Ruland, Juergen [2 ,3 ,21 ]
van den Brink, Marcel R. M. [11 ,22 ,23 ]
Weber, Daniela [4 ]
Edinger, Matthias [4 ,9 ]
Wolff, Daniel [4 ]
Busch, Dirk H. [12 ,16 ]
Kleigrewe, Karin [17 ]
Herr, Wolfgang [4 ]
Bassermann, Florian [1 ,2 ,3 ,24 ]
Gessner, Andre [5 ]
Deng, Li [6 ,7 ,8 ]
Holler, Ernst [4 ]
Poeck, Hendrik [4 ,9 ,25 ]
机构
[1] Tech Univ Munich, Sch Med, Dept Internal Med 3, Klinikum Rechts Isar, Munich, Germany
[2] German Canc Consortium DKTK, Partner Site Munich, Munich, Germany
[3] Tech Univ Munich, Ctr Translat Canc Res TranslaTUM, Sch Med, Munich, Germany
[4] Univ Med Ctr, Dept Internal Med Hematol & Oncol 3, Regensburg, Germany
[5] Univ Med Ctr, Inst Clin Microbiol & Hyg, Regensburg, Germany
[6] Helmholtz Zentrum Munchen, Inst Virol, Munich, Germany
[7] Tech Univ Munich, Cent Inst Dis Prevent, Chair Prevent Microbial Infect Dis, Munich, Germany
[8] Tech Univ Munich, Sch Life Sci, Munich, Germany
[9] Leibniz Inst Immunotherapy, Regensburg, Germany
[10] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA
[11] Sloan Kettering Inst, Dept Immunol, New York, NY USA
[12] Tech Univ Munich, Sch Med, Inst Med Microbiol Immunol & Hyg, Munich, Germany
[13] Tech Univ Munich, Sch Med, Comparat Expt Pathol, Munich, Germany
[14] Tech Univ Munich, Inst Pathol, Sch Med, Munich, Germany
[15] Ludwig Maximilians Univ Munchen, Dept Internal Med 2, Univ Hosp, Munich, Germany
[16] German Ctr Infect Res DZ, Partner Site Munich, Munich, Germany
[17] Tech Univ Munich, Sch Life Sci, Bavarian Ctr Biomol Mass Spectrometry, Freising Weihenstephan, Germany
[18] Tech Univ Munich TUM, Sch Med, Dept Radiat Oncol, Klinikum Rechts Isar TUM, Munich, Germany
[19] Tech Univ Munich TUM, Sch Med, Dept Surg, Klinikum Rechts Isar TUM, Munich, Germany
[20] Univ Med Ctr, Dept Internal Med 2, Freiburg, Germany
[21] Tech Univ Munich, Inst Clin Chem & Pathobiochem, Sch Med, Munich, Germany
[22] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA
[23] Weill Cornell Med Coll, New York, NY USA
[24] Bavarian Canc Res Ctr BZKF, Munich, Germany
[25] Bavarian Canc Res Ctr BZKF, Regensburg, Germany
关键词
VERSUS-HOST-DISEASE; GUT MICROBIOME; ACID; ANTIBIOTICS; DIVERSITY; GUIDE;
D O I
10.1038/s43018-023-00669-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. Poeck and colleagues identify a microbiome signature in patients receiving allogenic stem cell transplantation, which is associated with protective immune-modulatory metabolites, improved survival and less transplant-related mortality.
引用
收藏
页码:224 / 225
页数:2
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