Framework for rational donor selection in fecal microbiota transplant clinical trials
Autoři:
Claire Duvallet aff001; Caroline Zellmer aff003; Pratik Panchal aff003; Shrish Budree aff003; Majdi Osman aff003; Eric J. Alm aff001
Působiště autorů:
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States of America
aff001; Center for Microbiome Informatics and Therapeutics, Cambridge, MA, United States of America
aff002; OpenBiome, Cambridge, MA, United States of America
aff003; Harvard Medical School, Boston, MA, United States of America
aff004; The Broad Institute of MIT and Harvard, Cambridge, MA, United States of America
aff005
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0222881
Souhrn
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.
Klíčová slova:
Bacteria – Clinical trials – Microbiome – Inflammatory bowel disease – Colorectal cancer – Microbial taxonomy – Metabolomics – Bile
Zdroje
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