Long- and short-term effects of fecal microbiota transplantation on antibiotic resistance genes: results from a randomized placebo-controlled trial

ABSTRACT

In small series, third-party fecal microbiota transplantation (FMT) has been successful in decolonizing the gut from clinically relevant antibiotic resistance genes (ARGs). Less is known about the short- and long-term effects of FMT on larger panels of ARGs. We analyzed 226 pre- and post-treatment stool samples from a randomized placebo-controlled trial of FMT in 100 patients undergoing allogeneic hematopoietic cell transplantation or receiving anti-leukemia induction chemotherapy for 47 ARGs. These patients have heavy antibiotic exposure and a high incidence of colonization with multidrug-resistant organisms. Samples from each patient spanned a period of up to 9 months, allowing us to describe both short- and long-term effects of FMT on ARGs, while the randomized design allowed us to distinguish between spontaneous changes vs. FMT effect. We find an overall bimodal pattern. In the first phase (days to weeks after FMT), low-level transfer of ARGs largely associated with commensal healthy donor microbiota occurs. This phase is followed by long-term resistance to new ARGs as stable communities with colonization resistance are formed after FMT. The clinical implications of these findings are likely context-dependent and require further research. In the setting of cancer and intensive therapy, long-term ARG decolonization could translate into fewer downstream infections.

KEYWORDS:

• Acute myeloid leukemia
• antibiotic resistance gene
• fecal microbiota transplantation
• hematopoietic cell transplantation

Disclosure statement

No potential conflict of interest was reported by the author(s). AR receives consulting fees from Seres Therapeutics, Ltd and serves as a member of an Emmes DSMC.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2327442

Additional information

Funding

National Institutes of Health grant KL2TR002492. National Institutes of Health grant UL1TR002494. National Cancer Institute grant P30CA07759. University of Minnesota Chainbreaker grant.Funds from Achieving Cures Together. The content is solely the responsibility of the authors and does not represent the official views of the listed organizations. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and final responsibility for the decision to submit for publication.