Last month, a familiar package arrived on the doorstep of Sydney gastroenterologist, Professor Tom Borody.
And just like every other time for the past 20 years, he took delivery of the single long stemmed rose and paused for a moment to reflect. The flower always comes with a message, and of all the notes he has received, this one is his favourite – “to the world you may be one person, but to me you are the world”.
The much-appreciated gift has come from a grateful patient who came to him desperate to try and find a cure for the chronic diarrhoea that was crippling her.
“She would need to go (to the toilet) 15 to 30 times in one day and had tried everything, even not eating,” he remembers.
Professor Borody found a cure for his patient, and even after two decades she is symptom-free and enjoying a happy, healthy, and active life. And it’s all because someone donated her some healthy poo which was then transplanted into her own body via her colon.
“The reversal of symptoms happened overnight,” he said. “It’s interesting to think that poo did that,” he tells the limbic.
While his patient hasn’t looked back and many more have undergone the sometimes controversial procedure with outstanding success, Professor Borody has had to endure significant stigma and even revulsion for a procedure that basically involves taking healthy faeces from a donor or multiple donors.
The donor faeces is then filtered to remove larger particles and blended with a saline solution to liquefy it before it is administered to the patient, usually through the colon or via a nasogastric tube.
It’s a good thing that Professor Borody has a sense of humour. He is also unafraid to get his hands dirty in the name of medicine – even if it means getting up close and personal with human poo.
As if that’s not bad enough, he has also had to deal with widespread scepticism in his own profession, and even been called a ‘charlatan’ by a high-profile colleague. Another suggested he was mentally ill.
Professor Borody has spent almost three decades unapologetically pioneering the use of faecal microbiota transplantation (FMT) to treat a range of debilitating and often fatal gut diseases, including antibiotic-resistant C.difficile colitis and Crohn’s cases.
“I’ve got thick skin, and I don’t worry about it anymore,” he said. “I was in deep shit when I started doing this and that’s where I’ve stayed, but it’s made a lot of people much better and that’s what’s important.”
Not quite mainstream
While the procedure is yet to gain widespread mainstream national support, a handful of Australian doctors now offer it and Professor Borody’s Centre for Digestive Diseases has a huge waiting list, while in the US FMT is now recognised as a first line treatment for C.difficile.
And the release of study in The Lancet last month, co-authored by Professor Borody, could signal change is on the horizon.
The randomised placebo-controlled trial was conducted at three hospitals in Australia between 2013 and 2015. Patients with active ulcerative colitis (Mayo score 4-10) were treated either with FMT or placebo colonoscopic infusion, followed by enemas five days per week for eight weeks.
The primary outcome was steroid-free clinical remission with endoscopic remission or response at week eight. This was achieved in 11 (27%) of 41 patients allocated FMT, compared to just three (8%) of the 40 patients who were assigned placebo.
Adverse events were reported by 32 (78%) of patients allocated FMT and 33 (83%) of those who were assigned the placebo. Most were “self-limiting gastrointestinal complaints, with no significant difference in number or type of adverse events between treatment groups”.
“Intensive-dosing, multi-donor, faecal microbiota transplantation induces clinical remission and endoscopic improvement in active ulcerative colitis and is associated with distinct microbial changes that relate to outcome,” the authors concluded.
“Faecal microbiota transplantation is, thus, a promising new therapeutic option for ulcerative colitis. Future work should focus on precisely defining the optimum treatment intensity and the role of donor-recipient matching based on microbial profiles.” (see our story here).
FMT will become a gold standard treatment
Professor Borody is used to controversy and headlines and remembers only too well the scepticism he encountered when he was working on the development of the now well-accepted triple therapy (bismuth, metronidazole and tetracycline) for infection with Helicobacter pylori bacteria.
The triple therapy, pioneered in 1984, has become the gold standard for treating peptic ulcer disease caused by Helicobacter pylori infection, and Professor Borody believes FMT will follow the same route.
“The criticism was unbelievable when we were working on use of antibiotic therapy for the Helicobacter ulcer disease, and it came from a good category of scientists and gastroenterologists,” he said. “It turned out they were wrong.”
So what really drives him to persevere in the face of opposition? Yes he believes in the procedure, but it’s the hope that he can offer his patients that gets him up every morning.
Many people living with colitis, Crohn’s or another gut disease spend their days housebound because they are too afraid to leave the safety of a nearby bathroom, unable to exercise because they are overcome with cramps and pain, and have to suffer the embarrassment of excess gas and even faecal incontinence. It’s a lonely and painful disease, says Professor Borody.
So it’s not too hard to see how desperate they would become that they would be prepared to ingest faecal matter from another person.
He remembers his very first FMT patient, a woman called Josie who came to him suffering terribly from indeterminate colitis after a trip to Fiji.
“She was at suicide level,” he remembers.
Professor Borody remembered reading somewhere about FMT and in his research found a 1958 paper which detailed the use of faecal transplant to treat C.difficile. He suggested it to Josie and she agreed to try it.
She had three infusions and then left for a work conference.
“Where she went there was no way to contact her and I couldn’t sleep wondering how it had gone,” he said.
“When I did speak to her she said ‘I’m great, I’m terrific, I haven’t been so great, I’ve got all my energy back.”
Professor Borody believes this was the first time FMT had been used successfully to treat colitis.
And he now thinks it may have even greater potential in the treatment of other auto-immune and neurological diseases and conditions. Including rheumatoid arthritis, Parkinson’s and autism.
The Gastroenterological Society of Australia (GESA) is more cautious about this.
Its 2015 Position Statement on FMT does support its use as “currently the most efficacious treatment for recurrent or refractory C. difficile infection (rCDI)”. The statement goes on to say FMT “is an important medical advance in this setting as the rate of first relapse following antibiotic therapy for CDI is 25-30%”.
“GESA therefore recommends that FMT should be made available as a treatment option for all patients in the Australian healthcare system with recurrent or refractory CDI,” the statement reads.
However, as part of the same position statement, GESA recommends that, “at this time, FMT for indications other than for CDI should be carried out only in the clinical trial setting and with careful evaluation and transparent reporting of efficacy and safety.”
Professor Borody is philosophical about this, largely because he is convinced that the gut is a gateway that allows disease-causing toxins to enter the body, and has seen positive outcomes in patients with rheumatoid arthritis and Parkinson’s, as well as good gains in the treatment of colitis.
“We’ve got 30 patients cured of colitis now, and these are small numbers (about eight in 100) when you consider the cure rate for C. difficile is 95%,” he said.
“There is still a way to go, but I think we will get there.”
The use of FMT beyond C. difficile
Other researchers and clinicians agree. In a paper published late last year in the Nature Reviews, Gastroenterology and Hepatology journal, co-author and US-based clinical gastroenterologist Dr Alexander Khoruts wrote that the general principles of FMT might be instructive for future research beyond the treatment of C. difficile.
“The increased recognition of gut microbiota as a true organ, contained within the intestine and integral to human physiology, has suggested that FMT can be applied to many diseases, including many problems pertaining to the digestive tract such as IBD and IBS,” he and his colleagues wrote.
“This recognition has also generated speculation that FMT might be beneficial as a treatment for problems with metabolism, autoimmunity and nervous system development.
“However, many challenges remain before we learn whether this approach can offer any benefit in these indications. In some respects, the issues often revolve around questions of cause versus effect.
Even if dysbiotic gut microbiota are causally linked to pathophysiology of some of these problems, it is not known whether ‘normalizing’ the gut microbial community structure will result in clinical improvement once the clinical disorder is established.
“Possibly, certain immunological and metabolic consequences are set during a critical developmental time window in microbiota– host interaction, and cannot be reversed.”
These authors believe the next major applications of FMT will probably continue to be related to complications of antibiotic treatments and emergence of increasingly more virulent, multidrug-resistant pathogens.
“Many of these pathogens form reservoirs within the gastrointestinal tract under antibiotic pressure that is routinely applied in the context of intense medical care,” they wrote.
“FMT has the potential to restore the normal microbial gut ecology and might contribute to the range of innovative therapeutic approaches to cure infectious diseases that does not drive antibiotic resistance and might actually decrease it.”
Meanwhile, one of the next big frontiers for Professor Borody and his like-minded colleagues is the development of a laboratory-grown, synthetic ‘poo’ that can be taken in a capsule form. He believes this will make the treatment far more palatable, less invasive and more cost effective.
“The capsules will make a big difference because they are synthetic and there is no actual poo in them,” he tells the limbic. “The capsules are where the future is.”