Monday October 13 2014
Clostridium difficile infections affect the digestive system
“Capsules containing frozen faecal material may help clear up C. difficile infections,” BBC News reports.
While the prospect may sound stomach-churning, swallowing somebody else’s "poo" may help treat symptoms such as chronic diarrhoea, which can be life-threatening.
The headline is based on new research on 20 people with recurrent diarrhoea caused by C. difficile that was not cured with standard antibiotics.
C. difficile is a bacterium that is normally present harmlessly in the gut, but in people who have received courses of antibiotics, there can be an overgrowth of this bacteria, resulting in persistent, often severe, diarrhoea.
The research team gave the patients 30 capsules of frozen faecal matter containing gut bacteria from four healthy donors, in an effort to replace the illness-causing bacteria with non-harmful varieties.
No serious side effects were reported in the small group, and diarrhoea was cured in 14 of the 20 people assessed over an eight-week period. All six non-responders were retreated and four were then cured, taking the total to 18 out of 20 no longer suffering from diarrhoea. Self-reported health scores of the participants also improved.
Larger and longer clinical trials will now need to take place to prove it works, and the treatment’s safety needs to be thoroughly investigated. This treatment concept definitely falls into the “don’t try this at home” category.
The results also have a very specific application to recurrent C. difficile infection and do not relate to other causes of diarrhoea, or other digestive conditions.
Where did the story come from?
The study was carried out by researchers from Massachusetts-based hospitals and was funded by the hospital departments themselves. One of the authors declared receiving funds to conduct a clinical trial related to the treatment of C. difficile (not the current study). The study builds on previous research, published in 2012, involving mice
The study was published in the peer-reviewed medical journal JAMA and has been published on an open access basis, so is free to read online.
BBC News reported the story accurately, including warnings to tempted readers not to make their own "home brew” faecal capsules as a way of tackling diarrhoea, which could be dangerous.
The Independent’s claim that these frozen capsules are a definitive cure for C. difficile is premature, given the small size of the study.
It is important to note that these findings are specific only to people hospitalised with C. difficile-related diarrhoea. This is a specific cause of diarrhoea, which is completely different from the diarrhoea and vomiting bugs of the winter season, which are usually caused by viruses. Similarly, diarrhoea may not always be caused by infection at all. For example, inflammatory bowel diseases or bowel cancer can cause diarrhoea. As such, the study has a specific application, and does not relate to "diarrhoea treatment” in general.
What kind of research was this?
This was a feasibility study looking at whether it was possible to treat severe diarrhoea caused by a specific gut bug (C. difficile) using frozen faecal matter (poo) capsules from unrelated donors.
C. difficile is a bug that is normally present harmlessly in the gut, but in people (usually hospitalised) who have received courses of antibiotics, there can be an overgrowth of this bacteria, resulting in diarrhoea that can sometimes be severe and even life-threatening.
The rationale for faecal bacterial transplant is that the introduction of “normal” gut bacteria from a healthy donor should rebalance the system, curing the illness.
Faecal transplants have been carried out before, but using fresh donor stools and infusions. This raises a number of problems and complexities, which the researchers sought to address by developing an easy-to-take pill instead.
Feasibility studies are small studies aiming to show whether a new idea might work and to get an idea of its safety. These early studies normally involve a small number of people. If it does seem to work and appears safe, then larger, more methodologically robust studies can occur. These studies aim to establish better proof that the technique is both effective and safe. Feasibility studies on their own do not prove this; they are a stepping stone to more robust investigations.
What did the research involve?
This study recruited 20 people who had had at least three episodes of mild to moderate C. difficile infection and failed to get better with standard treatment, or who had at least two episodes of severe C. difficile infection requiring hospitalisation. Their average age (median) was 64.5 years, but ranged from 11 to 89.
Researchers created capsules containing frozen faecal matter, including bacteria, from four healthy volunteers. All 20 participants were given 15 of these capsules on two consecutive days and followed for up to six months to see if their symptoms resolved and if they had any side effects.
The main outcomes of interest were:
- resolution of the diarrhoea without recurrence up to eight weeks
- safety and side effects
Secondary outcomes included self-reported wellbeing and daily number of bowel movements.
What were the basic results?
The main results were:
- No serious side effects were reported.
- Resolution of diarrhoea (up to eight weeks without recurrence) occurred in 14 of the 20 patients (70%) after a single treatment course of the capsules.
- The remaining six participants had a second treatment round, leading to a further four resolutions. This took the total of successful treatments to 18 out of 20 (90%) with one or two treatments.
- Patients needing a second treatment to obtain resolution of symptoms had generally lower pre-treatment self-reported health scores.
- Daily number of bowel movements decreased on average from five (interquartile range [IQR] three to six) the day prior to treatment to two (IQR one to three) at day three, and one (IQR one to two) at week eight.
- Self-ranked health scores significantly improved on a scale of one to 10 from five before treatment (IQR five to seven) to eight after treatment (IQR seven to nine).
How did the researchers interpret the results?
The researchers concluded that, “This preliminary study among patients with relapsing C. difficile infection provides data on adverse events and rates of resolution of diarrhoea following administration of FMT [faecal microbiota transplantation] using frozen encapsulated inoculum from unrelated donors. Larger studies are needed to confirm these results and to evaluate long-term safety and effectiveness.”
This study showed it was possible to resolve diarrhoea symptoms in people with recurrent and treatment-resistant C. difficile diarrhoea using frozen capsules of someone else’s faeces. The pill form used is an improvement on previous methods, which require fresh stools and more complex delivery mechanisms.
The study was a small feasibility study, meaning it does not provide robust proof that the technique is yet effective or safe. It did not, for example, have a control group, so we don’t know how many people would have got better on their own. Larger, more robust, clinical trials are needed to prove its effectiveness and safety before it is known whether the experimental pill could have the potential to be developed into a new treatment.
Nonetheless, the study did show that the capsules appeared feasible, initially safe and somewhat effective, so further trials will no doubt follow to develop the technique further.
This study specifically investigated diarrhoea caused by C. difficile, so it is not currently known whether rebalancing a person’s gut bacteria using a pill containing bacteria from another person could have wider applications to other bugs and gut infections.
A final unanswered question is how many people would actually be willing to use the treatment. Given the potential severity of the condition it aims to treat, and the likely tasteless nature of the pill, uptake could be high. Nevertheless, the prospect of ingesting somebody else’s "poo" may be too hard to swallow for some.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.