Faecal microbiota transplantation (FMT) has shown remarkable efficacy for treating recurrent C. difficile infection (CDI). In fact, the randomized controlled trial to evaluate the effectiveness of FMT for recurrent CDI versus treatment with vancomycin was terminated early because FMT was so obviously superior, with a cure rate of more than 90% (see Figure 1, below).
Figure 1: Faecal microbiota transplant for recurrent CDI. Patients with recurrent CDI randomised to FMT (n=16), vancomycin (n=12) or vancomycin + bowel lavage (n=13). Colour scheme chosen carefully.
FMT is crude in every sense. You take donor stool, put it in a blender, sieve it, and deliver it to the recipient’s gut. I had the pleasure of watching a colleague prepare a dose of FMT in our laboratory in London last week. It really is a simple preparation. The delivery of the FMT to the recipient’s gut isn’t so much tricky as it is unpleasant for the recipient, with a tube required for the procedure.
So, could you deliver FMT orally? The answer according to a recent JAMA study is yes. The team from Boston in the US developed specially formulated capsules (aka ‘crapsules’) designed to deliver the FMT to the correct part of the gut. Of the 20 patients with recurrent CDI given a short 2 day course of ‘crapsules’, 14 (70%) resolved. The 6 non-responders were given a second course and 4 of these resolved, resulting in an overall resoluation rate of 90% (18/20). The quality of life benefits are obvious, and spelled out in the reduction in number of daily bowel movements (Figure 2, below). Although this wasn’t an RCT, so the patients knew they were getting the FMT and there could have been a placebo effect, the similarity in the rate of resolution between this study and the van Nood study (Figure 1) is striking.
Figure 2: Median number of bowel movements for 20 patients suffering from recurrent CDI treated with ‘crapsules’.
Oral FMT via ‘crapsules’ takes away the unpleasantness of the delivery for the recipient (if they can get over the ‘gross’ factor). But it doesn’t solve the lingering safety concerns associated with the procedure. We simply don’t have the tools to screen donor stool for problems we don’t yet know about. The experience from delivering hepatitis C virus to haemophiliacs in the 1980s in contaminated blood products from donors is salutary, and close to my heart since one of my good friends is still suffering the consequences of this. But, this risk has to be balanced against the urgent need of patients becoming increasingly desperate with recurrent CDI. If I had recurrent CDI, I’d be joining the queue for FMT.
The real solution to this problem is synthetic FMT. Lots of people are working on this at the moment – check our some of the work by Trevor Lawley on this. I am pretty certain that a simple bacterial cocktail will not make an effective synthetic FMT. There’s huge microbial and non-microbial diversity in the gut contents which will need to be replicated somehow. Clearly, some of this will be redundant, but it will take quite some time to pick through the constituent parts to derive an effective synthetic FMT. But I’m certain it will happen, and probably over the next decade.
Until then, ‘crapsules’ offer an alternative, effective way to deliver FMT, which is remarkably effective for resolving recurrent CDI. But recurrent CDI is just the start. There’s a host of other conditions that could potentially benefit from FMT. It may even be that ‘crapsules’ become a ‘new statin’: “a crapsule a day keeps the bad bugs away”?
Article citation: Youngster I, Russell GH, Pindar C, Ziv-Baran T, Sauk J, Hohmann EL. Oral, Capsulized, Frozen Fecal Microbiota Transplantation for Relapsing Clostridium difficile Infection. JAMA 2014; in press.