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Auto-FMT successful in patients undergoing stem cell transplantation

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October 10, 2018

Autologous fecal microbiota transplantation, or auto-FMT, re-established intestinal microbiota composition and increased microbial diversity among patients who underwent allogeneic hematopoietic stem cell transplantation and was found to be well-tolerated, according to study findings published in Science Translational Medicine.

“Antibiotic treatment damages the microbiota and increases risk of intestinal infection. Although this effect has been recognized for more than 60 years, remediation of the antibiotic-depleted gut microbiota has yet to become standard clinical practice,” Ying Taur, MD, MPH, infectious disease specialist at Memorial Sloan Kettering Cancer Center, and colleagues wrote. “In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotics are routinely given to treat or reduce the risk of serious infection. Prospective studies of allo-HSCT patients demonstrated that the intestinal microbiota is markedly altered during treatment.”

“Antibiotics must remain as a vital and necessary component of allo-HSCT treatment, given that patients experience many infections over the course of transplantation,” they wrote. “However, the unintended consequences of antibiotic treatment, which were long surmised, are now more apparent than ever before.”

Taur and colleagues conducted a single-center, open-label, randomized, controlled phase 2 clinical trial investigating the feasibility, safety and efficacy of auto-FMT for the reconstitution of gut microbiota in patients undergoing allo-HSCT. They collected fecal samples from study participants, which were frozen and stored before the initiation of allo-HSCT and screened for intestinal pathogens. Patients provided an additional fecal sample and were re-evaluated 1 to 5 weeks later, upon hematopoietic cell engraftment. Any patient with insufficient healthy bacteria belonging to the Bacteroidetes phylum continued to auto-FMT randomization.

Taur and colleagues evaluated patients who provided stool samples before and within 14 days of randomization. A total of 31 patients were randomly assigned — 16 to the treatment arm and 15 to control — but only 25 were evaluable. Of these, 14 were randomly assigned to treatment and 11 to control.

Taur and colleagues analyzed the intestinal microbiota profiles via collected stool samples over a year-long follow-up period. They observed a significant increase in microbiota diversity associated with auto-FMT (P < .0001). In the control group, the baseline inverse Simpson (IS) index — a measure of diversity — increased 38.7% (95% CI, 17.9%-59.6%). However, the IS index for auto-FMT patients increased by an additional average of 63.8% (95% CI, 36.6%-91.2%).

Taur and colleagues also observed improved recovery in patients who underwent auto-FMT, which they said indicates that the procedure “restored not only diversity but also the patient’s personal gut microbiota components” (P <.0001).

The results “demonstrate the potential for fecal sample banking and post-treatment remediation of a patient’s gut microbiota after microbiota-depleting antibiotic treatment,” Taur and colleagues wrote. They are still monitoring patients to determine if there are measurable improvements in clinical outcomes associated with auto-FMT.

“For now, we can conclude that the auto-FMT procedure was well-tolerated and effectively re-established commensal bacterial populations at the critical early immune reconstitution stage after allo-HSCT,” Taur and colleagues wrote. “We have demonstrated the potential of auto-FMT as a clinical intervention to restore intestinal microbiota diversity to levels deemed safe in patients, thereby reversing the disruptive effects of broad-spectrum antibiotic treatment for patients undergoing allo-HSCT transplant.” – by Marley Ghizzone

Disclosures: Taur reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

itj+ Perspective

Colleen Kraft
Perspective

I have been looking forward to the release of this study for a long time. This is a very elegantly designed randomized controlled trial of individuals who have dysbiotic intestinal microbiota after undergoing a hematopoietic stem cell transplant. The main two things that are compelling about this is the medically vulnerable population and that they were able to improve patient gut microbiota diversity after their receipt of a stem cell transplants.

The clinical implications about whether or not this leads to better graft uptake after the stem cell transplant and whether this has any impact on the clinical outcomes, such as mortality and morbidity after stem cell transplants, will undoubtedly be addressed in future articles.

We know that antibiotics disrupt our gut microbiota, and these give rise to infections that have the potential to cause a lot of morbidity and mortality in these patients. The idea that we could restore their gut microbiota after we have decimated it with the antibiotics and chemotherapeutics is an innovative approach to health and infectious disease treatment.

There are many implications about what to do with this information going forward. It may be that, since this is safe and able to be performed in this high-risk population, this is something we can and should consider doing in all patients after antibiotics, whether it be in the form of an auto-FMT — which could be logistically complicated — or a microbiome-restoring pill. Whether it is in a truly efficacious probiotic or some sort of stool derivative — that remains to be seen. Looking for surrogate microbiome restoration therapy could be an answer for every person who is prescribed and taking an antibiotic. We are aware from many different studies that whenever a person takes an antibiotic, it disrupts their microbiota. Even in healthy individuals we know that it can take them up to 6 months to restore their gut diversity after they’ve just had one course of antibiotics.

From this study of individuals who had banked their stool for this study, we have seen that there is improved gut microbiota diversity even if they have already had antibiotics and chemotherapy. In this very high-risk population of stem-cell recipients, the authors demonstrated that they could reconstitute their gut microbiota with an auto-FMT.

In future publications we will know if it helps patient morbidity or mortality after the stem cell transplant. Safety will always need to be continually monitored.

Further research is needed using healthy donors in this high-risk population. Research is also ongoing in figuring out a way that we can standardize this restoration or reconstitution of the gut microbiota with either a really efficacious probiotic, a bacterial mix or some sort of stool derivative that could be FDA approved.

Colleen S. Kraft, MD, MSc

Associate professor, pathology and laboratory medicine
Emory University School of Medicine
Medical director, microbiology laboratory
Emory University Hospital

Disclosure: Kraft reports serving on an advisory board for Bio-Rad Laboratories Scientific regarding a diagnostic for dysbiosis.