Broad Institute of MIT and Harvard, Cambridge, MA, USA; Computational and Systems Biology, MIT, Cambridge, MA, USA; The Center for Microbiome Informatics and Therapeutics, MIT, Cambridge, MA, USA.
Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Cell Host Microbe. 2018 Feb 14;23(2):229-240.e5. doi: 10.1016/j.chom.2018.01.003.
Fecal microbiota transplantation (FMT) from healthy donor to patient is a treatment for microbiome-associated diseases. Although the success of FMT requires donor bacteria to engraft in the patient's gut, the forces governing engraftment in humans are unknown. Here we use an ongoing clinical experiment, the treatment of recurrent Clostridium difficile infection, to uncover the rules of engraftment in humans. We built a statistical model that predicts which bacterial species will engraft in a given host, and developed Strain Finder, a method to infer strain genotypes and track them over time. We find that engraftment can be predicted largely from the abundance and phylogeny of bacteria in the donor and the pre-FMT patient. Furthermore, donor strains within a species engraft in an all-or-nothing manner and previously undetected strains frequently colonize patients receiving FMT. We validated these findings for metabolic syndrome, suggesting that the same principles of engraftment extend to other indications.
粪便微生物群移植（FMT）是将健康供体的粪便微生物移植到患者体内，以治疗与微生物组相关的疾病。尽管 FMT 的成功需要供体细菌在患者肠道中定植，但控制人类定植的力量尚不清楚。在这里，我们利用正在进行的临床实验，即复发性艰难梭菌感染的治疗，来揭示人类定植的规律。我们构建了一个统计模型，可以预测哪些细菌物种会在特定宿主中定植，并开发了 Strain Finder 方法，用于推断菌株基因型并随时间跟踪它们。我们发现，定植可以主要从供体和 FMT 前患者中细菌的丰度和系统发育来预测。此外，同种内的供体菌株以全有或全无的方式定植，以前未检测到的菌株经常定植于接受 FMT 的患者。我们对代谢综合征进行了这些发现的验证，表明相同的定植原则适用于其他适应症。
