Photo Credit: TopMicrobialStock
Using an existing algorithm to track the engraftment of fecal microbiota transplants in ulcerative colitis, researchers found short-term engraftment stable.
“Microbiota transplant therapy is an emerging treatment for ulcerative colitis,” researchers note in the Journal of Crohn’s and Colitis. “One proposed mechanism for the benefit of [microbiota transplant therapy] is through engraftment of donor microbiota; however, engraftment kinetics are unknown.”
Investigators aimed to determine the mechanisms through which microbiota transplant therapy works to treat UC. To do so, they utilized SourceTracker, a tool designed to predict the source of microbial communities in a set of input samples. The study included 27 patients with UC who received either drug-encapsulated (n=13) or placebo (n=14) capsules daily for 8 weeks, followed by a 4-week washout period.
Physician’s Weekly (PW) spoke with study authors Christopher Staley, PhD, and Byron Vaughn, MD, MS, to learn more.
PW: Can you explain the context of your study?
Byron Vaughn, MD, MS: After the success of fecal microbiota transplant (FMT) in preventing recurrent Clostridioides difficile, and maybe even in treating severe fulminant Clostridioides difficile, there has been a big push to see if FMT could be beneficial for UC as well.
The results of some initial studies were a little mixed, but a few randomized controlled trials of FMT in UC have data showing a pretty reasonable response. There is a signal for response, but the mechanism of that signal is unclear. Following FMT, we aimed to take a hypothesis-driven approach to understand some of the mechanisms of donor engraftment and microbial kinetics for both donor and recipient kinetics. We realized that one of the first things we had to do before getting deeper into this was to ensure we described engraftment well. This paper was about how we assess engraftment after FMT.
Christopher Staley, PhD: We’ve been using FMT in Clostridioides difficile, and when those patients present, they’ve been completely wiped out with antibiotics. When you put the donor microbiota in, it’s straightforward. For a while, studies weren’t even really measuring donor engraftment. They were saying, “It was in the donor. Now it’s in the patient, so there’s engraftment.” I was interested in figuring out how to quantify engraftment. In conditions like UC, we do more continual dosing to ensure engraftment. But what does that look like?
What did you learn, and what is still being assessed?
Dr. Vaughn: We certainly measured clinical activity. Our primary goal was to measure engraftment and sustained engraftment up to week 12. Our original hypothesis was that engraftment is probably a marker of success. We have a manuscript being written now; we may find that engraftment was associated with success, or maybe not. There is certainly more to come from this study on the clinical side. But we realized we had a separate paper that needed to discuss engraftment before discussing the other results.
Dr. Staley: I’ll draw attention to the placebo group because this is where I get my control group. Are we still going to be able to see that donor’s signature? Is there just going to be a clinical outcome, and the microbiome doesn’t reflect that? We saw that we could still track the microbiome robustly with the Source Tracker tool we use.
What else did you learn?
Dr. Vaugn: We realized it was essential to have a robust, peer-reviewed agreement and assessment on and measurements of engraftment. There is a general trend in our thinking that engraftment of donor microbes is important. Whether or not that leads to clinically meaningful outcomes, we need to ensure that we have a good measurement of engraftment.
We also need to start thinking about what other mechanisms besides engraftment are responsible for the clinical benefit of FMT. The study showed that there does appear to be a clinical benefit. Some patients in our study had treatment success. When we pull all the data, we see a pretty impressive treatment response to FMT in UC. If that’s not engraftment, what is it?
Dr. Staley: I’ll echo Dr. Vaughn in saying that it was important that we get that agreement in the literature that Source Tracker is measuring engraftment. That’s what we found—it makes sense if there’s high community diversity.
What else is important for readers to know?
Dr. Vaughn: The engraftment seems stable, even after stopping the therapy for at least a month. At least an 8-week course of FMT engrafts for at least a month. We don’t have longer-term data at this point. Hopefully, we’ll have enough participants to make a meaningful comparison for longer-term engraftment data. However, the short-term engraftment seems stable here. That’s an important clinical finding.
