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Cleaning up an Image: The Crusade to Rename Fecal Microbiota Transplant
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The intrigue surrounding the use of fecal microbiota transplantation to treat various gastrointestinal disorders and infections has intensified over the last several years.
As research continues to ramp up in the area of FMT, more and more people are becoming interested in the use of fecal microbiota as a remedy for Clostridioides difficile infection as well as inflammatory bowel disease.
Recently however, the FDA issued a safety alert regarding the use of FMT after two adults with weakened immune systems developed invasive infections caused by extended-spectrum beta-lactamase-producing Escherichia coli after receiving investigational FMT.
One patient subsequently died as a result of their infection.
As more attention is directed toward FMT, there too has been an uptick in misrepresentations of the treatment that has notably increased people’s misconceptions.
As Alexander Khoruts, MD, medical director of the University of Minnesota Microbiota Therapeutics Program, notes, part of the problem lies with the language used to describe this treatment. People, including physicians and scientists, commonly forgo the word “microbiota” when talking about it and simply refer to it as “fecal transplant.”
Khoruts spoke with Healio Gastroenterology and Liver Disease about this increased misrepresentation of FMT, as well as an effort he and Lawrence J. Brandt, MD, of Montefiore Medical Center, are spearheading to change the name of fecal microbiota transplantation to something a little more accurate. – by Ryan McDonald
Healio: What has the history been surrounding the naming conventions of what now is referred to as fecal microbiota transplantation?
Khoruts: This treatment has gone through many permutations in how it has been named.
The term ‘fecal microbiota transplant’ emerged in 2010. Prior to that, the most common term was fecal bacteriotherapy. But that was not the only term in existence. For example, one prominent researcher referred to it as ‘human probiotic infusion.’ But, in 2010 a group of physicians gathered together from across the U.S. and published the first recommendations, or a consensus statement, on how to perform this treatment.
At the time, Dr. Brandt raised the question as to how it should actually be named since the term ‘bacteriotherapy’ implied that we were only using bacteria. But the human microbiota is far more complex and also includes archaea, fungi, protists, and viruses. It’s not just the bacteria.
So, what was the proper term to really describe the entire microbial community? The two terms that people typically use is either ‘microbiome’ or ‘microbiota.’ ‘Microbiome’ technically refers only to the DNA or genomic content of a microbial community, which is how we generally study and characterize it. ‘Microbiota’ refers to live microbial communities, which is why we chose this term.
The use of the word ‘transplant’ had several reasons, one of which was at the time recent demonstration of sustained engraftment of donor bacteria in the recipient. That suggested a transplant-like phenomenon. Additionally, we were not sure how the treatment would be regulated by the FDA, as well as other regulators, and the consensus among that group was that the tissue transplant regulatory paradigm offered the best fit.
Then we debated about the proper adjective to describe the microbiota. Several terms were thrown around, but the majority of physicians insisted on using the word ‘fecal’ to describe its source. There was a minority that didn’t like the term even then.
Healio: What has happened since that consensus of deeming it ‘fecal microbiota transplantation’?
Khoruts: In practice, the term ‘microbiota’ has proven to be burdensome for most people, and the majority, including scientists, have excised it and just refer to the treatment as ‘fecal transplant.’ However, while this sounds interesting and provocative, it’s total nonsense.
Feces is a very complex substance. It is impossible to actually transplant feces. The only part that may engraft is the microbiota. The term ‘fecal transplant,’ or ‘stool transplant,’ was annoying, but everyone has been using it. If you look in PubMed, the term ‘fecal transplant’ is more common than ‘fecal microbiota transplant.’ Recently, there has been an additional irritant. While the industry is developing products based on fecal microbiota, it is carefully avoiding the word ‘fecal’ for their own products. In fact, I have noticed in some of their presentations the term being used derisively. For example, some show pictures of melting stool, and tell the audience, ‘you see, this is why we need formulations that are more aesthetic.’ The audience is generally very receptive, even though it does not realize that the aesthetic problems associated with fecal microbiota preparations have largely been solved.
Healio: How have you reacted to the misrepresentation of fecal microbiota transplantation?
Khoruts: Dr. Brandt and I have decided to rethink the terminology and we recently went through a bunch of terms. In the end we agreed that the only necessary change is elimination of the word ‘fecal’ and its replacement with ‘intestinal.’ ‘Fecal’ was never meant to be used in a nominative sense; it was supposed to be merely a descriptor of the microbiota source. However, ‘intestinal’ is just as good a descriptor and it would not allow excision of ‘microbiota,’ which is the material that is actually being transplanted.
We were not concerned with regulatory implications since the FDA has already determined that microbiota is classified as a drug. However, we wanted to retain ‘transplant’ as it accurately describes a treatment where something is taken from one individual and engrafted into another. There is this human donor-recipient pair, which is central to the ‘transplant’ paradigm. That is different from, say an ‘implant.’ Implants generally refer to artificial devices. I think cultured bacteria used as a therapeutic would be more appropriately called an ‘implant.’ But as long as there is a live individual donor, and that material is taken from one and placed into a recipient – that is a transplant. Some people have used the term ‘transfer’ instead of ‘transplant.’
That also does not acknowledge the human donor and also does not acknowledge engraftment, which has been amply documented. Of course, we are also retaining the term ‘microbiota,’ which is the term that describes the donor microbial communities in their full complexity. The adjusted terminology – intestinal microbiota transplant – merely shifts the focus from the donor to the recipient. The patients are getting an intestinal microbiota transplant because their own intestinal microbiota requires repair. We’re certainly not trying to fix someone’s feces.
Healio: How has this confusion in naming convention impacted your practice?
Khoruts: In practice, I have found that the term fecal is confusing to both patients and health care providers. For example, medical students used to ask if they could see this ‘mysterious procedure.’ I would see in their eyes, their wheels turning, imagining FMT to be a procedure where we suture a turd into an intestine. Then I would show them our capsules and that the patient was simply going to swallow them. That’s the end of the procedure. They would snicker at their own prior vision.
My greatest surprise since we have changed the terminology in my institution has been the patients’ reception. Most patients I see in my practice have recurrent C. difficile infections; they have dealt with violent diarrhea for on average about 8 to 9 months, and they are not put off anymore by anything that is related to feces. Their physician referral typically states that they’re sent in to be evaluated for a ‘fecal’ or ‘stool’ transplant. When I mention to the patients that the treatment is actually called ‘intestinal microbiota transplant’, there is often sigh of relief, with patients saying, ‘oh, that sounds so much better.’ Of course, I explain to them how the transplant material is obtained and processed.
The published literature suggests that patients suffering with GI problems don’t care what we call things. However, I have found that many do. Further, it makes total sense given what we know about cognitive linguistics – language has a powerful influence on our thinking. Importantly, now that all our nursing staff has been educated on the use of the term ‘IMT,’ the cringeworthy improvised terminology used by them in the past is gone, and some of the prior smirking from less experienced personnel is gone as well.
Many people still like to use the word ‘fecal’ because it’s provocative. However, although we initiated the change in terminology for academic reasons in order to improve the descriptive accuracy, it is the patient reactions that convinced me of the importance of this change.
Healio: What are some of the ways that you can try to influence the changing of the nomenclature?
Khoruts: It’s part of the crusade. I publish a number of papers on various aspects of this treatment every year. I have pledged to not use the ‘FMT’ term in my own publications, and when I collaborate with other investigators, I insist on the same. At the minimum I try to acknowledge the ‘intestinal microbiota transplant’ term. I do the same in my talks. I have approached OpenBiome about it, and they are mulling it over.
However, I think the momentum will pick up once people start to experience its effects in their practice. Frankly, I would be perfectly fine if the term ‘microbiota’ continued to be used as originally intended. At least that would maintain accuracy. However, ‘fecal transplant’ is wrong and irritating, and most importantly it is potentially embarrassing, unpleasant, and offensive to patients.
Healio: Do you think more physicians will begin to implement the change?
Khoruts: This remains to be seen. Ultimately, language is determined by consensus. When I interact with referring physicians, I correct them, and they have the same reaction as patients – it does sound better. I'm now seeing a change at my institution, and we take every opportunity to explain the reasons for our updated terminology. I do see a rapid adaptation in parts of our academic center; for example, the nursing and endoscopy staff have made a very quick transition, and they also educate their own colleagues and other health care providers. The obligatory inclusion of the term ‘microbiota’ is also a great educational tool about the role of intestinal microbes in health and disease.
Disclosures: Khoruts reports no relevant financial disclosures.
Perspective
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Richard Kellermayer, MD, PhD
We congratulate Khoruts for his work in the field of microbial therapeutics and would like to note that it is was our group at Texas Children’s Hospital, Baylor College of Medicine, who coined the acronym of IMT to better describe FMT in 2013. Our proposed terminology is “intestinal microbiome therapy” instead of “intestinal microbiota transplantation” since it is currently of debate if the microbiota (ie, only the live microorganisms within the microbiome [live microorganisms, dead microorganisms, their products and surrounding microenvironment]) itself is sufficient or is the critical element to carry the beneficial effects of IMT. Additionally, this treatment cannot be designated as transplantation in the traditional sense, since only part of the donor material engrafts the recipient, while recipient-specific, shared donor-recipient and previously undetected new species/strains of bacteria are the result of IMT in the recipient.
The volume and extent of donor-specific bacterial species/strain engraftment can only be determined currently by single nucleotide variant based metagenome analysis. Such studies have rarely been done and only on a few FMT recipients with a follow-up time of 4 or less months, making the engraftment/transplantation nature of IMT difficult to determine. Therefore, at the current state of the art, and with the perceived future of microbial therapeutics, intestinal microbiome therapy (IMT) as the new terminology for FMT seems more appropriate than intestinal microbiota transplantation.
A feasible and widely accepted term to designate human feces originated microbial therapeutics is rather important in respect to research, regulation and policy surrounding IMT, where safety is a critical consideration. I strongly share the opinion of European colleagues who are promoting for regulating, screening and disseminating feces under the national blood bank systems. Such policy could ensure the safe and widely accessible use of the most effective microbial therapeutic to date. An appropriate terminology for IMT could facilitate this process worldwide.
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