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.

微生物组是接受同种异体造血干细胞移植（allo-SCT）患者临床结果的预测因子。微生物群衍生的代谢物可以调节这些结果。目前尚不清楚细菌、真菌和病毒如何促进肠道代谢物的产生。我们将接受异基因 SCT 的患者粪便样本（n  = 78）的扩增子测序、病毒宏基因组学和靶向代谢组学结合起来，发现了Lachnospiraceae和Oscillospiraceae及其相关噬菌体的微生物组特征，与免疫调节代谢物 (IMM) 的产生相关。此外，我们还建立了 IMM 风险指数 (IMM-RI)，该指数与提高生存率和减少复发相关。在 IMM-RI 低风险患者中检测到大量的短链脂肪酸生物合成途径，特别是通过丁酰辅酶 A (CoA):乙酸 CoA 转移酶（BCoAT ，催化 EC 2.8.3.8）产生的丁酸，病毒组基因组组装鉴定出两个编码BCoAT作为辅助代谢基因的噬菌体。总之，我们的研究确定了与保护性 IMM 相关的微生物组特征，并为考虑将产生代谢物的联合体和代谢物制剂作为基于微生物组的疗法提供了理由。