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

微生物群 毛螺菌科 移植 代谢组学 生物 造血干细胞移植 代谢物 基因组 干细胞 细菌 微生物学 生物信息学 基因 医学 内科学 遗传学 生物化学 厚壁菌 16S核糖体RNA
作者
Erik Thiele Orberg,Elisabeth Meedt,Andreas Hiergeist,Jinling Xue,Paul Heinrich,Jinlong Ru,Sakhila Ghimire,Oriana Miltiadous,Sarah Lindner,Melanie Tiefgraber,Sophia Göldel,Tina Eismann,Alix Schwarz,Sascha Göttert,Sebastian Jarosch,Katja Steiger,Christian Schulz,Michael Gigl,Julius Fischer,Klaus‐Peter Janssen
出处
期刊:Nature cancer [Nature Portfolio]
卷期号:5 (1): 187-208 被引量:16
标识
DOI:10.1038/s43018-023-00669-x
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.
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