Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Center of Excellence for Gastrointestinal Inflammation and Immunity Research, Edmonton, AB, Canada.
Gut Microbes. 2019;10(6):676-687. doi: 10.1080/19490976.2019.1586037. Epub 2019 Mar 13.
: Fecal microbial transplantation (FMT) is used in the treatment of relapsing infection (rCDI). Failure rate for FMT is as high as 10% but the mechanisms contributing to a failed FMT are not understood. We utilized metagenomic data to identify the role of bacteria and bacteriophages on FMT success.: Subjects with rCDI (n = 19) received FMT from volunteer donors (n = 7) via colonoscopy. Twelve patients fully recovered after a single FMT, while seven patients required a subsequent FMT. DNA was extracted from patient and donor stool samples for shotgun metagenomic analysis. Metagenomics libraries were analyzed focusing on bacterial taxonomy and bacteriophage sequences. Gammaproteobacteria were dominant in rCDI patients prior to FMT largely due to elevated levels of and . A successful FMT led to increased levels of Clostridia and Bacteroidia and a reduction in Gammaproteobacteria. In contrast, a failed FMT led to no significant changes in bacterial composition. Bacteriophages were classified during whole metagenomic analysis of each sample and were markedly different between rCDI patients, donors, and a healthy control cohort (n = 96). Bacteriophage sequence reads were increased in CDI patients compared with donors and healthy controls. Successful FMT donors had higher bacteriophage α-diversity and lower relative abundance compared to the donors of a failed initial FMT.: In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.
粪便微生物移植(FMT)用于治疗复发性感染(rCDI)。FMT 的失败率高达 10%,但导致 FMT 失败的机制尚不清楚。我们利用宏基因组数据来确定细菌和噬菌体在 FMT 成功中的作用。
rCDI 患者(n=19)通过结肠镜接受志愿者供体(n=7)的 FMT。12 名患者在单次 FMT 后完全康复,而 7 名患者需要进行后续 FMT。从患者和供体粪便样本中提取 DNA 进行鸟枪法宏基因组分析。重点分析宏基因组文库中的细菌分类和噬菌体序列。rCDI 患者在 FMT 前的γ变形菌门占主导地位,主要是由于 和 的水平升高。成功的 FMT 导致厚壁菌门和拟杆菌门水平升高,而γ变形菌门减少。相比之下,FMT 失败导致细菌组成没有明显变化。噬菌体在每个样本的全宏基因组分析中进行分类,在 rCDI 患者、供体和健康对照组(n=96)之间有显著差异。与供体和健康对照组相比,CDI 患者的噬菌体序列读数增加。与首次 FMT 失败的供体相比,FMT 成功的供体具有更高的噬菌体α多样性和更低的相对丰度。
在这项回顾性分析中,噬菌体α多样性增加的 FMT 更有可能成功治疗 rCDI。此外,导致 FMT 成功的供体中噬菌体的相对数量较低。这些结果表明,噬菌体丰度可能在确定 FMT 的相对成功率方面发挥作用。