Bottom Line: A randomized clinical trial at Memorial Sloan Kettering Cancer Center (MSK) has shown that fecal microbiota transplants (FMTs) can reestablish the health-promoting bacteria that are often damaged by intense antibiotic treatment in people who have stem cell or bone marrow transplants for blood cancer.
Background: In allogeneic hematopoietic cell transplantation (allo-HCT), a person’s stem cells are replaced with healthy new stem cells. Unfortunately, the same antibiotics that are essential for healing the body after the transplant also significantly disrupt the diversity of intestinal microbiota, leading to the loss of many beneficial microbes and an increased risk of intestinal infection. Earlier work from MSK physician-scientists Eric Pamer, MD, and Marcel van den Brink, MD, PhD, has shown that out-of-balance intestinal microbes can contribute to serious side effects that can affect outcomes after stem cell transplants.
In order to counteract these unintended consequences of antibiotic treatments, researchers are looking to FMTs (also known as stool transplants). In this clinical trial, a team of MSK researchers led by MSK infectious diseases specialist Ying Taur, MD, MPH, explored whether the microbiota could be restored through the use of autologously derived FMTs (meaning the sample comes from the individual undergoing treatment). The researchers hypothesized that auto-FMTs would minimize the risk of exposure to potentially pathogenic microorganisms not previously encountered by the person.
Findings and Method: MSK researchers initiated the randomized controlled trial of auto-FMTs versus no intervention and analyzed the intestinal microbiota profiles of 25 allo-HCT individuals (14 treatment and 11 control). The goal of this clinical trial was to determine the feasibility, safety, and efficacy of the procedure for the reconstitution of the microbiota.
Participants’ own fecal material was collected before beginning the stem cell transplant process. The collected sample was processed and frozen to preserve the healthy microbe balance and thawed shortly before reintroduction after the stem cell transplant.
The 14 individuals who received auto-FMTs consistently regained pre-allo-HCT microbiota diversity and composition, despite dramatic shifts after allo-HCT. In contrast, the 11 individuals who did not receive auto-FMTs had reduced recovery of microbial composition to pre-allo-HCT levels. In addition, the post-allo-HCT compositional similarity in people receiving auto-FMTs also recovered better, indicating that the auto-FMT not only restored diversity but also the patient’s personal microbiota components.
The investigators observed successful restoration of bacteria from beneficial groups, including Lachnospiraceae, Ruminococcaceae, and Bacteriodetes. These groups have each correlated significantly with host benefit in prior studies and are important members of a healthy gut microbiota.
To confirm the results, a statistical analysis using a mixed effects model was conducted, concluding that auto-FMT improves microbiota diversity and restores a microbiota composition.
The study continues to accrue participants.
Author Comment: “While antibiotics remain a vital component of allo-HCT treatment, the unintended consequences of antibiotic treatment are now more apparent than ever before,” explained Dr. Pamer. “This study demonstrates that FMTs can restore the natural balance of the intestinal microbiota that is damaged by intense antibiotic treatment, thereby reversing the disruptive effects of broad-spectrum antibiotic treatment and minimizing transplant-related risks.”
Journal: “Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant” was published in Science Translational Medicine on September 26, 2018. Dr. Pamer and Joao Xavier, PhD, served as corresponding authors.
Funding: This research is supported by the Lucille Castori Center for Microbes, Inflammation, and Cancer at MSK and funds from the Tow Foundation and Cycle for Survival. Sequencing of fecal samples for microbiota determination was supported by the National Institute of Allergy and Infectious Diseases of the NIH under award no. U01 AI12427, the Lymphoma Foundation, the Susan and Peter Solomon Divisional Genomics Program, NIH grant no. P30 CA008748 Memorial Sloan Kettering Cancer Center Support Grant/Core Grant, and the Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center.