When treating antibiotic-resistant infections, injecting patients with other people’s excrement - a fecal transplant - can be highly effective. Could it be the answer to dementia, anorexia and obesity too?
The man and woman are wearing blue hospital gowns and clear face shields. Dr James Sones and Dr Indu Srinivasan are in a room in the Division of Digestive Diseases at the University of Mississippi Medical Center in Jackson. They are about to create something that has spread through medicine like, well, a shitstorm.
Sones takes a brown gloopy material and spoons it into what looks like a regular kitchen blender. The camera zooms in to a label on it: faecal blender. The brown gloopy stuff is, depending on your profession and level of politeness, faecal matter, stool, excrement or poo. It has been donated by a generous volunteer and it is almost certainly going to transform the life of the person who is going to receive it.
Once blended and mixed with saline, the brown stuff is poured into large syringes and infused into a willing patient by colonoscopy. (Nasogastric tubes and enemas are other delivery methods.) In the UK, this treatment is available for patients suffering from repeated infections of Clostridium difficile or C diff.
These bacteria can live harmlessly inside us. But in patients who are given strong antibiotics, C diff can survive, overwhelm a gut wiped of its microbiome, then secrete a toxin that causes severe pain, awful diarrhoea and vomiting. In the worst cases, it can be fatal. Even when vanquished by antibiotics, it can return except if the patient receives an infusion of poo, a procedure known as a faecal microbiota transplant (FMT).
Human waste is a misnomer. What we excrete contains nutrients and bacteria, and it can be a useful fertiliser or fuel. That the bacteria it contains can also cure ailing guts was known by ancient Chinese writers, who wrote of “yellow soup” (assumed to have been liquidised excrement), which was used to treat food poisoning and bad diarrhoea.
In 2013, Dutch researchers halted a randomised control trial – the gold standard of medical trials – because FMT was so much more effective than vancomycin. By 2014, the procedure was accepted enough that the UK National Institute for Health and Care Excellence issued guidelines allowing faecal transplants to be used in clinical practice, but only for C diff.
Even so, says Prof Tariq Iqbal of the Microbiome Treatment Centre (MTC) at the University of Birmingham,“it was very poorly taken up. Only about 30 hospitals [in the UK] had ever done a faecal transplant. Only four had done 10 or more.”
Partly, there was a supply problem: where was the poo to come from? In the early years of FMT, patients were often infused with faecal material donated by a close relative or friend. Slowly, though, the concept of a stool donor emerged. Now, MTC is one of only two licensed stool banks in the UK, and in its first year of operation sent out 150 samples, at a cost of £650 for each 50ml.
Donors are recruited by poster and word of mouth. Iqbal says they need to drop off their stools for 10 days in a row before 11am (so they have to be regular in more ways than one). Although MTC is next to Queen Elizabeth hospital, healthcare workers are excluded because they are exposed to too many bugs.
Screening is rigorous: it has to be, when each sample can be different. More than 90% of volunteers are turned away. For safety reasons, each sample is kept for three months before being used, in case a donor is incubating something. A sample will be kept indefinitely, too. The screening tests are as severe as the donor questionnaires: all samples are tested for a wide range of pathogens.
What does a finished FMT sample look like? Does it smell? Iqbal looks at my coffee cup. “It’s the colour of latte.” And yes, of course it smells. “It’s shit.” Patients, he says, have no problem accepting the procedure. They won’t smell it, for a start, in a nasogastric tube or colonoscopy. And you can’t afford an ick factor when you are desperately ill.
He had an enema of FMT once a week for eight weeks. “After six weeks, there was a drastic improvement. After the course I was 90% to 95% well.” He remembers clearly that it was during the World Cup two years ago, because when he went in for a final assessment by an internal camera, “the room went up in applause. I remember comparing it to watching England playing the night before and these people were cheering at my colon.”
Because it is so simple and widely available and seems so miraculous, the use of FMT has long since departed from sterile medical establishments into home bathrooms and YouTube. If it transforms the microbiome so well for C diff, why shouldn’t it do it for other conditions? If the microbiome plays a part in all sorts of body functions from mood to metabolism, as research seems to show, why shouldn’t a dose of healthy poo sort out other problems, too?
There are more than 300 clinical trials listed on clinicaltrials.gov that are using FMT to treat a range of conditions including autism, dementia, anorexia, and obesity. The most recent wants to explore FMT as a treatment for faecal incontinence (the inability to control bowel movements) in women.
But Mark Wilcox, professor of medical microbiology at the University of Leeds, is circumspect. “The thing that’s common about FMT is that, wherever you are, there are particular enthusiasts, and in the US in particular. It’s a major fee-earning opportunity in the US. But it is, like it or not, an experimental procedure.”
Animal trials have shown that conditions and pre-conditions can be transmitted with the faecal material. “There are data that gut bacteria play a role in gut cancers, blood pressure, diabetes, obesity. You can turn fat mice thin and thin mice fat by transplanting their gut bacteria. Because we don’t know the full roles of the gut microbiome, you are potentially transferring someone’s bacteria that have something to do with cancer, diabetes, obesity and so on.”
Last year, two people participating in trials in the US contracted E Coli from faecal transplants – one died – because samples had not been tested for that pathogen. But even this news does not stop people who can’t get FMT on the NHS or can’t afford it in the US (where it can cost $1,000) from doing their own thing. Adrienne Grierson, an Australian film-maker based in London, describes herself as “an antibiotic child”. Since then she has suffered “terrible stomach troubles” including “cramps, doubling over, vomiting, diarrhoea, boiling hot flush, sweating, agony”.
In 2015, stuck in bed, she turned to Google and discovered faecal transplants and the microbiome. “I thought, my God, I’ve been playing here with half a deck of cards. There’s only so much I can do with what I’ve destroyed.” She paid for 10 FMTs from a private clinic and “by the third day, it was like somebody had switched my brain on, like the antibiotics used to do. And that was a shock. I hadn’t thought that far ahead. I just wanted my guts to not fall out.”
Since then, Grierson has had faecal transplants every three months or so, although now she does it DIY, at home. When we spoke, she had had a faecal infusion two days earlier, thanks to a friend. “She poops in a bag and I plop it on a sieve, a couple of scoops. Then I pour saline and I mash it through so I don’t get all the big particles. Then I suck it up through a syringe and pretend I’m at a clinic.”
Grierson paid for her friend to be comprehensively screened when she first started donating. Now, she trusts her to be healthy. “If you do pick up other people’s characters and personalities, I really hope I get hers because she’s really lovely. I have zero history of cancer in my family. I don’t come from sickly people. The concerns are, what if I can get all of that from somebody? You have to decide: do you want to take a risk and live really well or do you want to keep on living like that?”
Iqbal has a clinician’s reaction to DIY faecal transplants. “I think doing it yourself really needs to be a thing of the past. Because we don’t know what we’re doing, really.” Although metagenomic tests to analyse bacteria are now far more affordable, there are countless unknowns about FMT and the microbiome. “When you do metagenomics on stool samples,” says Iqbal, “you still find a whole bunch of stuff that is not in the databases. It’s very early days.”
FMT has even made its way into popular culture with a mention in an episode of South Park. But it is exciting enough for serious money to be invested in improving upon it. Vedanta Biosciences, a large pharmaceutical company, is one of several working on developing a “rationally defined consortia of human microbiome-derived bacteria”. In other words, distilling the useful stuff from poo into a safe, commercial product that probably won’t be the colour of latte or mixed in a blender.
Iqbal is convinced this will happen sooner rather than later. “FMT is too empirical,” he says. “We need to understand the mechanisms. I hope in five years’ time we won’t be doing FMT any more.”