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Y.F. van Lier et al.
Table 2. Outstanding questions and potential investigational approaches. Key questions
Bacterial composition-focused
Which ‘protective’ taxa from associative studies are truly
beneficial as therapeutics?
What is the best way to collect additional data to support that change
in bacterial composition is indeed the mechanism of clinical improvement?
What is the optimal diet for the patient to produce the optimal microbiome?
Metabolite-focused
Which are most important (SCFA, bile acids etc.)? Where do they need to act for maximum benefit?
Which patient-intrinsic factors influence therapy efficacy (e.g. baseline diversity, presence of specific taxa, level of epithelial damage,
genetic factors)?
What is the optimal timing and interval for intervention?
Potential investigational approach
Transfer defined bacterial consortia in HCT patients + trials with more
invasive sampling especially at time of GvHD diagnosis.
Add important secondary endpoints to initial studies as well as clinical responses (e.g., fecal engraftment of specific taxa, bacterial diversity, active metabolic pathways, serum and fecal SCFA concentrations).
Start with observational diet studies, move toward interventional randomized trials.
Mouse studies + trials of ‘post-biotic’ compounds.
Large (interventional) randomized studies of the microbiome-targeting intervention of interest.
Small interventional studies + trials with long-term follow-up.
HCT: hematopoietic cell transplantation; GvHD: graft-versus-host disease; SCFA: short-chain fatty acids.
ting with regard to how we may target the microbiome for maximal benefit for patients.
Disclosures
MRMvdB has received research support from Seres Therapeutics; has consulted for, received honorarium from or par- ticipated in advisory boards for Seres Therapeutics, WindMIL therapeutics, Rheos, Frazier Healthcare Partners, Nektar Therapeutics, Notch Therapeutics, Forty Seven inc., Priothera,
Ceramedix, Lygenesis, Pluto Immunotherapeutics, Magenta Therapeutics, Merck & Co, Inc., and DKMS Medical Council (Board); has IP Licensing with Seres Therapeutics, Juno Therapeutics, and stock options from Seres and Notch Therapeutics. None of the other authors has anything to disclose.
Contributions
YvL and KAM wrote the manuscript. MRMvdB and MDH provided critical feedback and edited the manuscript.
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