High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria
High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria
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DOI：
10.4161/gmic.23571
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发表时间：
2013-01-01
期刊：
影响因子：
12.2
通讯作者：
Sadowsky, Michael J.
中科院分区：
文献类型：
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作者：
Hamilton, Matthew J.;Weingarden, Alexa R.;Sadowsky, Michael J.
粪便微生物区系移植(FMT)正成为治疗难辨梭状芽胞杆菌复发感染(CDI)的一种更为广泛的技术。虽然以前的治疗方法使用新鲜的粪便浆液作为FMT微生物群的来源，但我们最近报告了成功地使用标准化、部分纯化和冷冻的粪便微生物群来治疗CDI。在这里，我们报告高通量的16S rRNA基因测序显示，使用来自健康捐赠者的冷冻粪便细菌进行FMT后，肠道微生物区系稳定植入。从受者和供者的移植后样本中也发现了类似的细菌分类群，但相对丰度在患者和时间点之间有很大差异。FMT后患者的样本显示Firmicut和类杆菌的丰度增加，占总序列读数的75%-80%。变形杆菌和放线菌的数量比FMT前的患者少(5%)。两例患者的FMT后标本与供体标本非常相似，其中类杆菌门由类杆菌科、雷氏藻科和藻藻科的大量成员组成，主要由类杆菌属、泽泻属和副类杆菌属组成。以瘤胃球菌科、乳螺科、韦氏微生物科和未归类的梭状芽孢杆菌为代表的Firmicius门的成员和Firmicius的成员。一名患者随后因一种无关感染而接受抗生素治疗，导致肠道变形杆菌数量增加，主要是肠杆菌科细菌。我们的结果表明，来自健康供者的冷冻粪便微生物群可以有效地治疗复发的CDI，从而恢复肠道微生物区系的结构，清除艰难梭菌。
Fecal microbiota transplantation (FMT) is becoming a more widely used technology for treatment of recurrent Clostridum difficile infection (CDI). While previous treatments used fresh fecal slurries as a source of microbiota for FMT, we recently reported the successful use of standardized, partially purified and frozen fecal microbiota to treat CDI. Here we report that high-throughput 16S rRNA gene sequencing showed stable engraftment of gut microbiota following FMT using frozen fecal bacteria from a healthy donor. Similar bacterial taxa were found in post-transplantation samples obtained from the recipients and donor samples, but the relative abundance varied considerably between patients and time points. Post FMT samples from patients showed an increase in the abundance of Firmicutes and Bacteroidetes, representing 75-80% of the total sequence reads. Proteobacteria and Actinobacteria were less abundant (< 5%) than that found in patients prior to FMT. Post FMT samples from two patients were very similar to donor samples, with the Bacteroidetes phylum represented by a great abundance of members of the families Bacteroidaceae, Rikenellaceae and Porphyromonadaceae, and were largely comprised of Bacteroides, Alistipes and Parabacteroides genera. Members of the phylum Firmicutes were represented by Ruminococcaceae, Lachnospiraceae, Verrucomicrobiaceae and unclassified Clostridiales and members of the Firmicutes. One patient subsequently received antibiotics for an unrelated infection, resulting in an increase in the number of intestinal Proteobacteria, primarily Enterobacteriaceae. Our results demonstrate that frozen fecal microbiota from a healthy donor can be used to effectively treat recurrent CDI resulting in restoration of the structure of gut microbiota and clearing of Clostridum difficile.