Even doctors recoil from faecal transplants 鈥� but you might get over such squeamishness if it was your only hope of beating a killer infection
AS SOON as set eyes on the 89-year-old patient, he realised the outlook was grim. Racked with fever and delirium, the woman was convinced she was living with her long-dead parents. A sky-high white blood cell count showed her body was battling to stave off a possibly fatal infection.
A colonoscopy quickly laid bare the problem. Parts of the woman鈥檚 large intestine had become severely septic and were so tightly constricted the probe could barely pass through it. For Khoruts, a gastroenterologist at the University of Minnesota Medical School in Minneapolis, the next step was clear. He called the woman鈥檚 son 鈥� not as you might think to allow the pair a few last moments together, but to get hold of a sample of the man鈥檚 faeces.
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Khoruts is one of a handful of doctors around the world who perform what鈥檚 known as a faecal transplant. Within 24 hours of receiving an infusion of her son鈥檚 faeces into her colon, the woman鈥檚 white blood cell count had plummeted, her fever had abated and her mental composure had returned. 鈥淚t was a very dramatic change,鈥� says Khoruts.
It was not the first success story, either. Surgeons at the University of Colorado Medical School in Denver performed the first faecal transplants in 1958, on four patients whose infected colons and incessant diarrhoea had failed to respond to conventional treatment. They all recovered within 48 hours. But although some 200 sporadic case studies have since been published, the procedure has remained on the medical fringes.
Partly, that reticence is down to our taboos surrounding excreta, says , medical director of the infection prevention and control programme for the Calgary region in Alberta, Canada. 鈥淭here is a fair amount of loathing for things that are regarded as dirty. There is a huge yuck factor.鈥�
A consequence is that doctors still don鈥檛 fully appreciate what goes into making the material we defecate, says Khoruts. 鈥淔or all practical purposes, it鈥檚 just poop. We are hardly any more educated about it than an adolescent boy in middle school.鈥� Slowly, though, this attitude is changing, not least because of the relentless toll in western hospitals exacted by Clostridium difficile. This deadly superbug invades colons in which the resident microbial ecosystem has been compromised.
And a complex ecosystem it is. 鈥淧oo is a zoo,鈥� says gastroenterologist Thomas Borody of the in Five Dock, New South Wales, Australia. A menagerie of possibly 25,000 subspecies of bacteria feeds off the matter that passes through our digestive systems. Taken together, they make up a gigantic, interconnected system of cells that some biologists are coming to consider as an organ in its own right 鈥� in terms of the number of cells it contains, the largest in the human body. 鈥淚t鈥檚 the equivalent of nine human beings compacted, without the connective tissue, into the colon鈥�, says Borody.
Prolonged use of antibiotics can wreak havoc with this huge and complex ecosystem, creating niches in which C. difficile can take over. The bug is resistant to all but a few extremely powerful antibiotics, and once a course of treatment is over it will simply return to recolonise a compromised gut.
The consequences of C. difficile infection range from severe diarrhoea and colitis to sepsis and death. Khoruts鈥檚 elderly patient could easily have suffered that fate. On any given day in 2008, US hospitals contained more than 7000 in-patients with C. difficile infections, and there were 300 deaths in which the bug was implicated, according to the . Figures for C. difficile-related deaths from the UK Office for National Statistics indicate , more than twice the number caused by road-traffic accidents. Elsewhere the picture is similar. 鈥淢ost people don鈥檛 even know what hit them,鈥� says Borody. 鈥淭hey die, they get buried.鈥�
Advocates of faecal transplants insist that it needn鈥檛 be that way. By restoring the bacterial flora of the colon to something like their native state, donated faeces can stop C. difficile in its tracks, they say, either by crowding out the intruder or producing toxins that kill it.
The procedure itself is straightforward. A donor鈥檚 faeces are mixed with saline and filtered to remove large particles. How this solution, typically less than a litre, is delivered to the recipient鈥檚 colon differs from practitioner to practitioner. Some prefer a tube inserted through the nose into the stomach. Khoruts favours either a colonoscope or an enema. 鈥淚 worry that one patient one day will vomit during an infusion, and aspirate, and we鈥檒l have a problem,鈥� he says. 鈥淏esides, these bacteria belong in the colon 鈥� it feels more natural to go from below.鈥�
Siblings make the best donors: we share 80 per cent of our bacterial flora with our mothers. But in fact any poo will do, as long as the donor has a healthy bowel and has been screened for infections such as HIV and hepatitis. At his clinic, Khoruts has settled on a single donor to avoid the $1000 cost of testing each new one. 鈥淲e have one individual who has been screened, and he donates for free,鈥� he says.
Seriously scatological
Pioneering the large-scale use of this treatment has its social hazards. Borody鈥檚 clinic has now done over 1500 faecal transplants, and unsurprisingly he has been the butt of many jokes. 鈥淚 got a very bad name among my colleagues, as someone who feeds people shit,鈥� he says 鈥� despite the fact that he too favours delivery through an enema. Not that he and his colleagues are averse to some scatological fun of their own: one of their published papers bears the tongue-in-cheek title 鈥淏acteriotherapy using fecal flora: toying with human motions鈥� ().
But there鈥檚 no doubting this is serious medicine. Take the case of Coralie Muddell. In January 2005 the 50-year-old came to Borody exhausted and in severe pain, with diarrhoea that conventional treatment had failed to curb. Afraid of the pain, Muddell had stopped eating, and her weight had plunged 5 kilograms in two weeks. Recognising C. difficile at work, Borody performed a faecal transplant. 鈥淚t was totally unbelievable,鈥� says Muddell. 鈥淚 had been so unwell, but improved every single day after the treatment.鈥� She still sends Borody flowers each year.
Other doctors have similar stories. 鈥淚 have used transplants as a means of pretty much guaranteeing patients an escape from C. difficile,鈥� says Louie. Both he and Khoruts have published studies showing how faecal transplants restore populations of Bacteroides, the genus of bacteria that dominates a healthy colon. Borody and colleagues have shown that bacteria from a donor鈥檚 faeces remains in the recipient even 24 weeks after the procedure, suggesting that the repopulation of the colonic flora might be permanent (Journal of Clinical Gastroenterology, vol 44, and ).
鈥淚 have used faecal transplants to pretty much guarantee patients an escape from C. difficile鈥�
Others remain to be convinced. Peter Katelaris, a gastroenterologist at the University of Sydney, Australia, says that while there are indications that faecal transplants can be of benefit in treating tricky C. difficile infections, the procedure has yet to undergo rigorous, large-scale trials 鈥� and until it does, it remains of unproven efficacy and uncertain safety. 鈥淭he concept is appealing,鈥� he says, 鈥渂ut we mustn鈥檛 get ahead of the scientific evidence base.鈥�
That base could soon be significantly strengthened. A team led by Ed Kuijper of the Leiden University Medical Center in the Netherlands is now embarking on double-blind trials to compare the effectiveness of faecal transplants with antibiotic-led therapies. Borody hopes the results will persuade sceptical gastroenterologists to change their mind. 鈥淭hey are afraid of poo, basically,鈥� says Borody. 鈥淭hey don鈥檛 realise it鈥檚 an organ of the body. They鈥檒l transplant liver and bone marrow, but they won鈥檛 transplant stool.鈥�
For him, the bottom line is clear: faecal transplants should become the first defence against C. difficile. 鈥淲e have a therapy that is nearly 100 per cent curative. What the hell are we doing spending millions of dollars on antibiotics?鈥�
