Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients

Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients
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DOI:
10.1371/journal.pone.0182585
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发表时间:
2017-08-21
期刊:
影响因子:
3.7
通讯作者:
Bhatt, Ami S.
Bhatt, Ami S.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Moss, Eli L.;Falconer, Shannon B.;Bhatt, Ami S.

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免疫功能低下的个体患艰难梭菌相关疾病(CDAD)的风险很高。粪便微生物群移植 (FMT) 是治疗难治性或复发性 CDAD 的一种高效疗法,尽管存在安全问题,但最近已被提供给免疫功能低下的患者。我们对免疫功能低下患者进行 FMT 后细菌组成的基因组学进行了一年多的研究。对两名受 CDAD 影响的造血干细胞 (HCT) 接受者 FMT 后的宏基因组、菌株和基因水平细菌动力学进行了表征。我们发现了基因内容的改变,包括毒力和抗生素抗性基因的丧失。这些变化伴随着物种和菌株水平上的长期细菌分化。我们的研究结果表明,FMT 引入的特定细菌群的持久性有限,并表明微生物组功能潜力的改变比单独通过分类信息推断的更为复杂。我们观察到,单独使用 FMT 不能诱导 HCT 受者微生物群的长期供体样改变,这表明 FMT 不能无限期地取代塑造细菌组成的环境和/或宿主因素。
Immunocompromised individuals are at high risk of developing Clostridium difficile-associated disease (CDAD). Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory or recurrent CDAD and, despite safety concerns, has recently been offered to immunocompromised patients. We investigated the genomics of bacterial composition following FMT in immunocompromised patients over a 1-year period. Metagenomic, strain and gene-level bacterial dynamics were characterized in two CDAD-affected hematopoietic stem cell (HCT) recipients following FMT. We found alterations in gene content, including loss of virulence and antibiotic resistance genes. These alterations were accompanied by long-term bacterial divergence at the species and strain levels. Our findings suggest limited durability of the specific bacterial consortium introduced with FMT and indicate that alterations of the functional potential of the microbiome are more complex than can be inferred by taxonomic information alone. Our observation that FMT alone cannot induce long-term donor-like alterations of the microbiota of HCT recipients suggests that FMT cannot indefinitely supersede environmental and/or host factors in shaping bacterial composition.