Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease.
Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease.
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DOI：
10.1016/j.bbmt.2014.01.030
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发表时间：
2014-05
期刊：
影响因子：
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通讯作者：
Oefner PJ
中科院分区：
文献类型：
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作者：
Holler E;Butzhammer P;Schmid K;Hundsrucker C;Koestler J;Peter K;Zhu W;Sporrer D;Hehlgans T;Kreutz M;Holler B;Wolff D;Edinger M;Andreesen R;Levine JE;Ferrara JL;Gessner A;Spang R;Oefner PJ
对31例接受同种异体干细胞移植（SCT）患者的粪便标本中分离的16s rRNA基因高变V3区进行了新一代测序，以阐明同种异体干细胞移植过程中肠道微生物组组成的变化。宏基因组分析辅以菌株特异性肠球菌PCR和尿吲哚酚硫酸盐的液相色谱-串联质谱间接评估细菌负荷。入院时，患者以共生菌为主。移植后，观察到肠球菌的相对转移，在抗生素预防和治疗中性粒细胞减少感染时更为明显。这种转变在随后发生或患有活动性胃肠道（GI）移植物抗宿主病（GVHD）的患者中尤为突出。移植后粪便标本中肠球菌的平均比例在未发生GI GVHD的患者中为21%，而在随后发生GI GVHD的患者中为46%，在GVHD活动性时为74%。肠球菌PCR证实在这些标本中以粪肠球菌或粪肠球菌和粪肠球菌均占优势。由于细菌多样性的丧失，所有移植后样本的尿吲哚酚硫酸盐平均水平从42.5±11µmol/L降至11.8±2.8µmol/L，活动性GVHD患者样本的尿吲哚酚硫酸盐平均水平降至3.5±3µmol/L。我们的研究揭示了异基因SCT过程中主要的微生物组变化发生在抗生素治疗期间，但与GI GVHD的关系更为突出。我们的数据表明，在同种异体SCT的情况下，早期微生物组的变化和肠道微生物组多样性的丧失可能会影响肠道炎症。
Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42.5 ± 11 µmol/L to 11.8 ± 2.8 µmol/L in all post-transplant samples and to 3.5 ± 3 µmol/L in samples from patients with active GVHD. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT.