Changes in the Composition of the Human Fecal Microbiome After Bacteriotherapy for Recurrent Clostridium difficile-associated Diarrhea

Changes in the Composition of the Human Fecal Microbiome After Bacteriotherapy for Recurrent Clostridium difficile-associated Diarrhea
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DOI:
10.1097/mcg.0b013e3181c87e02
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发表时间:
2010-05-01
影响因子:
2.9
通讯作者:
Sadowsky, Michael J.
Sadowsky, Michael J.
中科院分区:
医学3区
文献类型:
--
作者:
Khoruts, Alexander;Dicksved, Johan;Sadowsky, Michael J.

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艰难梭菌相关疾病(CDAD)是腹泻和结肠炎的主要已知原因,并且该疾病被认为是由肠道微生物群的持续破坏引起的。通过粪便移植的细菌疗法可用于治疗复发性CDAD,这被认为是重建正常的结肠微生物群。然而,传统的微生物技术的局限性,直到最近,排除了这个想法的测试。在这项研究中,我们使用末端限制性片段长度多态性和16 S rRNA基因测序方法来表征结肠菌群的细菌组成的患者患有复发性CDAD之前和之后的治疗粪便移植从健康供体。虽然患者的残余结肠微生物群在治疗之前缺乏细菌部门-厚壁菌门和拟杆菌门的成员,但移植对患者肠道微生物群的组成产生了巨大影响。到移植后14天,受体的粪便细菌组成与供体的粪便细菌组成高度相似,并且以拟杆菌属(Bacteroides spp.)菌株和未表征的丁酸生产细菌。细菌组成的变化伴随着患者症状的缓解。在细菌疗法之后,受体和供体的肠道微生物群的惊人相似性表明供体的细菌迅速占据了它们所需的小生境,导致存在的微生物群落的结构和功能的恢复。
Clostridium difficile-associated disease (CDAD) is the major known cause of antibiotic-induced diarrhea and colitis, and the disease is thought to result from persistent disruption of commensal gut microbiota. Bacteriotherapy by way of fecal transplantation can be used to treat recurrent CDAD, which is thought to reestablish the normal colonic microflora. However, limitations of conventional microbiologic techniques have, until recently, precluded testing of this idea. In this study, we used terminal-restriction fragment length polymorphism and 16S rRNA gene sequencing approaches to characterize the bacterial composition of the colonic microflora in a patient suffering from recurrent CDAD before and after treatment by fecal transplantation from a healthy donor. Although the patient's residual colonic microbiota, prior to therapy was deficient in members of the bacterial divisions-Firmicutes and Bacteriodetes, transplantation had a dramatic impact on the composition of the patient's gut microbiota. By 14 days posttransplantation, the fecal bacterial composition of the recipient was highly similar to that of the donor and was dominated by Bacteroides spp. strains and an uncharacterized butyrate producing bacterium. The change in bacterial composition was accompanied by resolution of the patient's symptoms. The striking similarity of the recipient's and donor's intestinal microbiota following after bacteriotherapy suggests that the donor's bacteria quickly occupied their requisite niches resulting in restoration of both the structure and function of the microbial communities present.