Framework for rational donor selection in fecal microbiota transplant clinical trials
Name
journal.pone.0222881.pdf
Description
Published version
Size
1.23 MB
Format
Adobe PDF
Checksum (MD5)
feab47311470b859cee6dc06408426b6
Author(s)
Duvallet, Claire
Panchal, Pratik
Budree, Shrish
Osman, Majdi
Alm, Eric J
Date Issued
October 10, 2019
Journal
PloS one
Publisher
Public Library of Science (PLoS)
Citation
Duvalle, Claire et al. "Framework for rational donor selection in fecal microbiota transplant clinical trials." PloS one 14(2019): e022288 © 2019 The Author(s)
Version
Final published version
Abstract
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.
Subjects
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences
General Medicine
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Civil and Environmental Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/journal.pone.0222881
