Imagine receiving a “faecal microbiota transplant”: an infusion of someone else’s stool microbes into your gut. “It doesn’t sound like something you might want at first glance,” admits Carolyn Edelstein, director of global partnerships at OpenBiome, who will talk in Ireland this week about the practicalities of running a “stool bank” to provide screened, donated material for such a procedure.
Why would anyone want such a thing? Faecal microbiota transplantation, or FMT, is not a new idea, but there is a resurgence of interest in it as a treatment for recurrent bowel infection with Clostridium difficile ["C. diff"], explains Edelstein.
“C. diff is a terrible gut bug. It causes pretty awful diarrhoea, patients usually have to go to the bathroom 10 to 20 times a day, and it causes pretty bad stomach cramping, poor digestion and loss of appetite and energy,” she says.
If the infection keeps coming back, introducing someone else’s gut microbes through FMT might offer some help. “The mechanism isn’t quite understood but it seems like the healthy community of bacteria from the donor outcompetes the C. diff infection,” says Edelstein.
Down to business
For FMT, a donor provides a stool sample, which is typically processed to a liquid infusion and introduced to the patient’s bowel through a colonoscopy or enema, or into the upper intestine through an upper endoscopy or a tube that passes through the nose.
It sounds reasonably straightforward, but in order to ensure that the donated matter doesn’t seed more problems than it solves, donors need to be carefully screened, and that is where OpenBiome looks to make things easier with its stool bank in the US.
The inspiration came from a relative of Edelstein’s who had recurring C. diff infections and found it difficult to get a clinician to carry out the FMT procedure.
“It’s such a pain for a clinician to have to find and screen donors and get them tested for the barrage of tests they should be screened for, then when you do find a donor who does pass, setting up the administrative permissions to deal with stool onsite is also not necessarily straightforward,” she explains.
“The donor then has to come in and deliver on command, which is not easy, and then the procedure happens. It’s messy and long and involved for the clinician.”
Banking on stools
To smooth the path for donations, OpenBiome has set up a repository of frozen samples from screened donors, and ships the samples to clinicians for FMT.
Donors are paid, but not everyone can deposit for the stool bank: applicants are screened for potential issues.
“There has been a lot of interesting research in the past few years associating the [gut] microbiome [the trillions of microbes that live in our guts, some of which are passed out in faeces] with a number of conditions in human health,” says Edelstein. “We don’t really know yet how those relationships work and what is causative, so we tend to be extremely conservative and anything that could potentially be linked to the microbiome we tend to use as an exclusion criterion.”
Only about 3 per cent of applicants make it through the full battery of screening tests, and when they do they are encouraged to donate frequently, so OpenBiome typically works with donors who live close to the Massachusetts facility.
To date the bank has provided samples for more than 5,000 transplants, mostly in the US, and OpenBiome has sequenced genetic material from samples to gather scientific information. The organisation also follows up with recipients of the banked samples over the course of a year, says Edelstein. “The focus is to get some sense of longitudinal impact that it has on their microbiome and to look out for any long-term safety impact.”
New landscapes
OpenBiome now plans to expand its network in Ireland and the UK, but the regulatory environment for FMT in Europe is different to the US, where the FDA views faecal microbiota as an investigational new drug (IND), but issued guidance in 2013 that said it “intends to exercise enforcement discretion regarding the IND requirements for the use of FMT to treat
C
. difficile
infection not responding to standard therapies”.
"Normally in the US an investigational drug is made available through clinical trials, but in this case the FDA guidance enables physicians to use FMT outside of clinical trials for for C. difficile patients, when antibiotics aren't working," explains Edelstein.
In Europe, the regulation of FMT is currently at the discretion of the EU member states, according to the Health Products Regulatory Authority, formerly known as the Irish Medicines Board, which has the matter under consideration. “The HPRA has reviewed a study using FMT as a treatment and did not consider that the study required approval under clinical trials legislation for medicines; the study did require ethical approval. It is noted that FMT encompasses a number of different techniques and products and their respective regulation may differ,” it states.
“This is a new area of developing medical interest and the HPRA will continue to review how best to regulate such practices, in conjunction with clinicians, in the best interest of their patients.”
It’s a landscape that Openbiome needs to navigate, says Edelstein, but she sees advantages in going the repository route. “In addition to being selective about the stool that we use, we can monitor the use of stool and follow up with patients a lot more systematically on a much broader scale,” she says. “Also, we can source donors and use them over multiple treatments, so we can spread the cost of finding donors.”
Research
Edelstein will speak this week at a symposium on Microbes and Modern Diseases at the APC Microbiome Institute in Cork, which carries out research on gut microbes, including research relating to FMT, as the institute’s director, Prof Fergus Shanahan explains.
“FMT is a centuries-old procedure but we are trying to study it in the modern era with new technology to make it safer, and will scientifically assess it to determine mechanisms of action and to clarify which patients should and should not receive it,” he says.
“APC, and in particular Paul O’Toole’s lab in University College Cork, is working with OpenBiome to achieve standardisation of the process, which will greatly help with assessing comparative results in different clinical trials.”
