Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study
Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study
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DOI：
10.1093/ofid/ofz173
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发表时间：
2019-05-01
影响因子：
4.2
通讯作者：
Okhuysen, Pablo C.
中科院分区：
文献类型：
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作者：
Galloway-Pena, Jessica R.;Peterson, Christine B.;Okhuysen, Pablo C.
背景越来越多的证据表明，肠道微生物组可能会显着影响造血干细胞移植（HSCT）受者的结果。在临床可行的时间范围内提供基于16S核糖体RNA的微生物组表征目前是有问题的。因此，确定微生物代谢物作为微生物组组成的替代物可以提供实用的生物标志物。收集44例患者HSCT前至移植后100天的纵向粪便标本（n = 451），以及健康志愿者（n = 18）的1次样本作为对照。使用16S核糖体RNA V4测序确定微生物群组成。采用液相色谱串联质谱法测定粪便吲哚和丁酸水平。在HSCT受者中，粪便吲哚和丁酸水平与Shannon多样性指数在基线时（分别为P = .02和P = .002）和移植后（分别为P = .006和P < .001）相关。具有高丁酸水平的样品富集梭菌目，而含有高吲哚的样品也富集拟杆菌目。在移植时较低的Shannon多样性指数与急性肠移植物抗宿主病（iGVHD）（P = .02）和移植相关死亡（P = .03）的发生率增加相关。尽管粪便代谢产物与急性iGVHD或总生存率无关，但移植后30天内感染血流的患者粪便丁酸盐水平显著降低（P = 0.03）。HSCT后粪便微生物组和代谢物的纵向分析确定丁酸盐和吲哚为微生物多样性和特定分类群的潜在替代标记物。粪便代谢产物是否可作为HSCT后急性iGVHD或菌血症的生物标志物，还需要进一步研究。
Background. Accumulating evidence suggests that the intestinal microbiome may dramatically affect the outcomes of hematopoietic stem cell transplant (HSCT) recipients. Providing 16S ribosomal RNA based microbiome characterization in a clinically actionable time frame is currently problematic. Thus, determination of microbial metabolites as surrogates for microbiome composition could offer practical biomarkers.Methods. Longitudinal fecal specimens (n = 451) were collected from 44 patients before HSCT through 100 days after transplantation, as well as 1-time samples from healthy volunteers (n = 18) as controls. Microbiota composition was determined using 16S ribosomal RNA V4 sequencing. Fecal indole and butyrate levels were determined using liquid chromatography tandem mass spectrometry.Results. Among HSCT recipients, both fecal indole and butyrate levels correlated with the Shannon diversity index at baseline (P = .02 and P = .002, respectively) and directly after transplantation (P = .006 and P < .001, respectively). Samples with high butyrate levels were enriched for Clostridiales, whereas samples containing high indole were also enriched for Bacteroidales. A lower Shannon diversity index at the time of engraftment was associated with increased incidence of acute intestinal graft-vs-host disease (iGVHD) (P = .02) and transplant-related deaths (P = .03). Although fecal metabolites were not associated with acute iGVHD or overall survival, patients contracting bloodstream infections within 30 days after transplantation had significantly lower levels of fecal butyrate (P = .03).Conclusions. Longitudinal analysis of fecal microbiome and metabolites after HSCT identified butyrate and indole as potential surrogate markers for microbial diversity and specific taxa. Further studies are needed to ascertain whether fecal metabolites can be used as biomarkers of acute iGVHD or bacteremia after HSCT.