Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.
Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.
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DOI：
10.1038/s41564-021-00966-0
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发表时间：
2021-10
影响因子：
28.3
通讯作者：
Faith J
中科院分区：
文献类型：
--
作者：
Aggarwala V;Mogno I;Li Z;Yang C;Britton GJ;Chen-Liaw A;Mitcham J;Bongers G;Gevers D;Clemente JC;Colombel JF;Grinspan A;Faith J
粪便微生物群移植（FMT）已成功应用于治疗人类复发性艰难梭菌感染，但缺乏一种精确的方法来测量哪些细菌菌株稳定植入受体并评估其与临床结局的相关性。我们收集了从22名FMT供体和受体的粪便样本中培养的> 1，000种不同的细菌菌株。使用我们的菌株集合结合来自相同样品的宏基因组测序数据，我们开发了一种名为Strainer的统计方法，用于从宏基因组测序数据中检测和跟踪细菌菌株。我们应用Strainer评估了13个FMT纵向临床干预的队列，并检测到FMT后5年内接受者中71%的供体微生物群菌株的稳定植入。我们发现，FMT前80%的受体肠道细菌菌株被FMT消除，FMT后存在的菌株与环境获得的菌株一起持续长达5年。接受者中供体细菌菌株植入的定量独立地解释了初始和重复FMT后的临床结果（复发或成功）（精确度100%，召回率95%）。我们报告了一个细菌物种和菌株的纲要，这些物种和菌株随着时间的推移一直在接受者体内移植，可以用于定义的活生物制品中作为FMT的替代品。我们的分析框架和Strainer可以应用于系统地评估FMT或定义的活细菌治疗研究，通过量化受体中的菌株植入。使用Strainer算法对粪便微生物组移植后的肠道细菌菌株进行定量描述了长期稳定的植入，这解释了患者的结局。
Fecal microbiota transplantation (FMT) has been successfully applied to treat recurrent Clostridium difficile infection in humans, but a precise method to measure which bacterial strains stably engraft in recipients and evaluate their association with clinical outcomes is lacking. We assembled a collection of >1,000 different bacterial strains that were cultured from the fecal samples of 22 FMT donors and recipients. Using our strain collection combined with metagenomic sequencing data from the same samples, we developed a statistical approach named Strainer for the detection and tracking of bacterial strains from metagenomic sequencing data. We applied Strainer to evaluate a cohort of 13 FMT longitudinal clinical interventions and detected stable engraftment of 71% of donor microbiota strains in recipients up to 5 years post-FMT. We found that 80% of recipient gut bacterial strains pre-FMT were eliminated by FMT and that post-FMT the strains present persisted up to 5 years later, together with environmentally acquired strains. Quantification of donor bacterial strain engraftment in recipients independently explained (precision 100%, recall 95%) the clinical outcomes (relapse or success) after initial and repeat FMT. We report a compendium of bacterial species and strains that consistently engraft in recipients over time that could be used in defined live biotherapeutic products as an alternative to FMT. Our analytical framework and Strainer can be applied to systematically evaluate either FMT or defined live bacterial therapeutic studies by quantification of strain engraftment in recipients. Quantification of gut bacterial strains after fecal microbiome transplantation using the Strainer algorithm delineates long-term stable engraftment that explains patient outcomes.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
5.8
作者：
Kokot, Marek;Dlugosz, Maciej;Deorowicz, Sebastian
通讯作者：
Deorowicz, Sebastian
DOI：
10.1038/nrmicro2259
发表时间：
2010-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
39.2
作者：
Kelly CR;Khoruts A;Staley C;Sadowsky MJ;Abd M;Alani M;Bakow B;Curran P;McKenney J;Tisch A;Reinert SE;Machan JT;Brandt LJ
通讯作者：
Brandt LJ
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.