THE average adult human is weighed down by about 1–1.5 kg of stool, which contains an enormously diverse array of microbial species.
Collectively, this is called the faecal microbiota (or alternatively, the “microbiome” when referring to the collective genome of these many organisms).
Most of the bacterial species cannot easily be cultured in the laboratory but our knowledge of their role in health and disease is growing as rapid DNA sequencing techniques become cheaper and more widely available.
There is one disease that we know is due to the disruption to the normal faecal microbiota — Clostridium difficile-associated disease (CDAD).
In recent years, CDAD has become more common, more severe and more difficult to treat. This has been particularly bad in some parts of the world where hypervirulent strains, possibly associated with greater use of the fluoroquinolone class of antibiotics, have caused higher than usual numbers of very severe and potentially life-threatening CDAD.
Traditionally, treatment of CDAD has been with 10–14 days of either metronidazole or oral vancomycin. A recent addition to this has been fidaxomicin, although comparisons of this agent with vancomycin don’t suggest any major advantage.
With all these therapies, there is a relatively high rate of post-treatment relapse, which gets higher with each subsequent round of treatment.
In earlier attempts to normalise the faecal microbiota, clinicians have attempted therapy with probiotics, generally with only one or a few bacterial species. These have been met with disappointing results, most likely due to the inadequate bacterial diversity in these probiotics.
Enter — or should I say re-enter — faecal microbiota transplant (FMT). This involves the delivery of stool from a healthy donor to a person with CDAD, a therapy that has been tried as far back as the 1950s.
It can be given either from the top end (via duodenoscopy or nasojejunal tube), or from the bottom end (via colonoscopy, rectal tube or enema). The donor is generally a healthy household contact or relative, who must first be screened for various enteric and blood-borne pathogens.
There is also interest in developing healthy stool banks that could be called upon more quickly so that donor identification and screening need not delay FMT.
FMT has been attempted in both recurrent and refractory CDAD. Most of the available evidence is for recurrent disease, where success rates have been generally in the range of 80%–100%, compared with about 30% for drug treatment of multiply relapsed CDAD.
For refractory disease, there is less evidence but case reports have shown some promise where the alternative would have been total colectomy (or even death).
FMT obviously can have potential problems, not least of which is the “gross out” factor. There have been rare reports of vomiting and aspiration of the infused fluid, perforations by endoscopes, bacteraemias due to enteric flora, and even the development of obesity following use of stool from an overweight donor.
There is also the task of preparing the liquefied stool solution — a task which cannot be described as pleasant.
Despite these potential negatives, the high success rate of FMT means that interest in this procedure is growing.
We still need more data on how much stool needs to be infused, which mode of delivery is superior, whether frozen stool from stool banks will be as good as freshly donated samples, and what other long-term risks may occur.
However, as long as we continue to see a rising incidence of CDAD and frequent failures with standard drug therapy, this therapy is likely to be used more and more often.
Associate Professor Patrick Charles is a physician in Infectious Diseases and General Medicine at Austin Health, Melbourne