It will take years to accumulate the data necessary to fully understand FMT and all its implications, Dr. Kelly said. In the interim, the IND requirement will likely shrink the already-small pool of gastroenterologists performing FMTs. "Some will be motivated to get an IND, but the average person in practice won’t," she predicted. "You need to put hours and hours of work into it, and then you’re still under FDA’s oversight because this is not an approved therapy. So that means you have to submit adverse events reports, keep records, and report annually on your program. And at any time, without any warning, [the FDA] can come and inspect your facility."
Dr. Brandt agreed. "It’s a huge amount of paperwork documentation, record-keeping, and follow-up that the average practitioner is simply not going to do." The requirement for an IND means there are simply going to be fewer and fewer physicians who do them, he said.
Admittedly, though, the risks of no regulation can endanger patients, Dr. Kelly said. "If things go on completely unregulated, stupid things will happen," including the spread of infectious diseases like hepatitis C and parasitic infestations.
Indeed, Dr. Alexander Khoruts of the University of Minnesota, Minneapolis, who spoke at the workshop, described the case of an FMT "do-it-yourselfer" who called for some advice on improving her outcomes. Specifically, she had mixed stool from a neighbor and her son’s mother-in-law and administered it to herself without results. "She wanted to know if maybe the chlorine in the water killed off everything. ... Six months later she called me back and said her C. diff was gone, but now she had parasites."
"There are already predatory practices out there [performing FMTs]," Dr. Khoruts said. "I got an e-mail from someone who couldn’t make the drive up to see me, but she found someone near her who would do it for $10,000."
Courtesy of Dr. Colleen Kelly
With current regulations on stool transplants, preparation, filtration, and even method of delivery vary between procedures.
Well-designed and well-executed studies would not only address these immediate safety questions, but would also examine the more nebulous concerns about the long-term effects of tampering with an individual’s unique ecosystem of gut microbes. In recent years, research has begun to document how the balance and proportion of microbial species in the gut can either protect from – or predispose to – metabolic syndrome, obesity, diabetes, cardiovascular disease, arthritis, and even cognitive disorders.
An engrafting microbial transplant could predispose the recipient to develop illnesses that would otherwise never have been destined to occur, Dr. Slater said. "All of the evidence we have suggests that manipulating the gut microbiome is a powerful act that may have long-reaching and subtle effects."
The move toward a standardized FMT product and process is inevitable, Dr. Brandt said. "We’re not going to be doing fecal transplants much longer. This is a temporary situation. We’re already developing compounds that will do the same thing."
Researchers at the University of Guelph, Ontario, have developed a machine that distills and cultures microbes from human feces, producing a kind of super-probiotic that can be used in place of fresh stool.
Also, the Canadian biotech company Rebiotix is working on a similar product, which it intends to test in a phase II randomized controlled trial.
But until those machine-made products are available, physicians and patients with have to stay with the man-made version. "We have access to a substance that is free and has a virtually unlimited supply," Dr. Kelly said. "We cannot deny this effective therapy to these patients who’ve failed all other available treatments."
None of the sources quoted in this article had any financial declarations.
