Framework for rational donor selection in fecal microbiota transplant clinical trials
Framework for rational donor selection in fecal microbiota transplant clinical trials
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DOI：
10.1371/journal.pone.0222881
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发表时间：
2019-10-10
期刊：
影响因子：
3.7
通讯作者：
Alm, Eric J.
中科院分区：
文献类型：
--
作者：
Duvallet, Claire;Zellmer, Caroline;Alm, Eric J.
早期的临床成功正在推动对粪便微生物群移植（FMT）的热情，通过整个粪便转移健康的肠道细菌，因为新兴的研究将微生物群与许多不同的疾病联系起来。然而，初步试验产生了混合的结果，并表明供体粪便的异质性可能在患者反应中起作用。因此，临床试验失败可能是因为选择了无效的供体，而不是因为FMT不适合该适应症。在这里，我们描述了一个概念框架，以指导合理的供体选择，以增加FMT临床试验成功的可能性。我们认为，假设微生物组与给定适应症相关的机制应该告知如何选择健康供体进行FMT试验，将这些机制分为四种疾病模型，并提出相关的供体选择策略。接下来，我们将介绍基于先前发表的FMT试验和正在进行的调查的例子，以说明供体选择在实践中可能发生的情况。最后，我们表明，典型的FMT试验是没有权力发现个人分类介导的患者反应，这表明临床医生应该制定有针对性的假设，回顾性分析和设计相应的临床试验。展望未来，开发和应用新的临床试验设计方法，如合理的供体选择，将是必要的，以确保FMT成功地转化为临床影响。
Early clinical successes are driving enthusiasm for fecal microbiota transplantation (FMT), the transfer of healthy gut bacteria through whole stool, as emerging research is linking the microbiome to many different diseases. However, preliminary trials have yielded mixed results and suggest that heterogeneity in donor stool may play a role in patient response. Thus, clinical trials may fail because an ineffective donor was chosen rather than because FMT is not appropriate for the indication. Here, we describe a conceptual framework to guide rational donor selection to increase the likelihood that FMT clinical trials will succeed. We argue that the mechanism by which the microbiome is hypothesized to be associated with a given indication should inform how healthy donors are selected for FMT trials, categorizing these mechanisms into four disease models and presenting associated donor selection strategies. We next walk through examples based on previously published FMT trials and ongoing investigations to illustrate how donor selection might occur in practice. Finally, we show that typical FMT trials are not powered to discover individual taxa mediating patient responses, suggesting that clinicians should develop targeted hypotheses for retrospective analyses and design their clinical trials accordingly. Moving forward, developing and applying novel clinical trial design methodologies like rational donor selection will be necessary to ensure that FMT successfully translates into clinical impact.