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

   


Authors: Thiele Orberg, E.; Meedt, E.; Hiergeist, A.; Xue, J.; Heinrich, P.; 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.
Article Title: Bacteria and bacteriophage consortia are associated with protective intestinal metabolites in patients receiving stem cell transplantation
Abstract: 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. © 2024, The Author(s), under exclusive licence to Springer Nature America, Inc.
Keywords: controlled study; gene sequence; genetics; nonhuman; follow up; prospective study; multiple reaction monitoring; mass spectrometry; metabolism; gene expression profiling; cohort analysis; hematopoietic stem cell transplantation; graft versus host reaction; allogeneic hematopoietic stem cell transplantation; immunomodulation; real time polymerase chain reaction; observational study; intestine flora; microbiology; feces; bacterium; hematologic disease; feces analysis; fatty acid synthesis; longitudinal study; butyric acid; phylogeny; lactic acid; bacteria; clinical outcome; corticosteroid therapy; microbial community; microbial diversity; bacteriophage; bacteriophages; viral metagenomics; humans; human; male; female; article; whole genome sequencing; short chain fatty acid; shotgun sequencing; lachnospiraceae; bacterial microbiome; multiomics; butyryl coenzyme a dehydrogenase; internal transcribed spacer 1; isothermal amplification; simpson index
Journal Title: Nature Cancer
Volume: 5
Issue: 1
ISSN: 2662-1347
Publisher: Nature Research  
Date Published: 2024-01-01
Start Page: 187
End Page: 208
Language: English
DOI: 10.1038/s43018-023-00669-x
PUBMED: 38172339
PROVIDER: scopus
PMCID: PMC12063274
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85181245342&doi=10.1038%2fs43018-023-00669-x&partnerID=40&md5=35cc0d76215abd2a028d327ab4386068
Notes: Article -- Source: Scopus
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MSK Authors
  1. Marcel R M Van Den Brink
    616 Van Den Brink
  2. Oriana Miltiadous
    16 Miltiadous
  3. Sarah Lindner
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