'Poo transplants' explored for treating C. difficile

The BBC News informs us that "faecal transplant" is the "clue to treating the gut bug" Clostridium difficile (C. difficile).

C. difficile are bacteria that usually survive in the digestive system (gut) and do not cause any problems in healthy people. Sometimes, when people are given antibiotics to treat other illnesses, the balance of 'friendly' bacteria in the gut is disturbed. When this happens, C. difficile can multiply rapidly and produce toxins (poisons), which can cause severe diarrhoea. As C. difficile infections are usually follow antibiotic treatment, most cases happen in hospitals or care homes.

A relatively new treatment for C. difficile is termed 'faecal transplant'. This involves ingesting a sample of another person’s faeces (poo) provided by a healthy donor. The bacteria inside the faecal matter are thought to help restore the balance of good bacteria. But two drawbacks to the treatment are:

• faecal matter can introduce other harmful bacteria into the gut
• most peope are, understandably, unwilling to eat another person’s faeces (although the transplants are often done by enema)

The researchers had two main goals:

• to see if faecal transplant worked in mice (which it did)
• to identify what bacteria contained in the faecal matter had a beneficial effect

The researchers did identify six types of bacteria that seemed to be effective in suppressing the infection. But it is often difficult to interpret the results of animal research and caution should be exercised when trying to generalise the findings to humans.

Where did the story come from?

The study was carried out by researchers from the Wellcome Trust Sanger Institute, the Rowett Institute of Nutrition and Health, and the London School of Hygiene and Tropical Medicine. It was funded by the charitable foundation the Wellcome Trust and the UK Medical Research Council. The study was published in the peer-reviewed open access journal PLoS Pathogens.

The study was reported appropriately by BBC News.

What kind of research was this?

This was an animal study that investigated the effect of faecal transplantation from healthy mice to mice infected with C. difficile bacteria.

Researchers also looked at which particular bacteria species were involved in suppressing the infection. Their hope was that this research may be helpful in combating the infection known to cause epidemics in humans.

What did the research involve?

The researchers infected a group of healthy mice with C. difficile bacteria, treated them for seven days with a range of antibiotics and monitored their progress over several months. This was done in order to mimic the natural transmission of the bacteria, which is often stimulated in humans by antibiotics, which disrupt the balance of bacteria inside the digestive system (the so-called 'intestinal flora'). After treatment these mice were considered highly contagious and referred to as 'supershedders'.

Some of the mice were then treated with the antibiotic vancomycin, a strong antibiotic used as a first line of treatment in humans infected with C. difficile, and the effect on the infection was examined.

The researchers then treated some of the other infected mice (that had not been treated with vancomycin) with faecal transplantation, which is the oral administration of faeces from healthy mice to infected mice. They investigated whether this method of treatment suppressed the C. difficile infection.

Based on the results of this experiment, the researchers then further investigated the precise bacteria species that restored balance in the infected guts of the mice.

What were the basic results?

Healthy mice that were infected with C. difficile bacteria developed a chronic infection and a highly contagious state that persisted for months. Treatment with vancomycin, although initially effective, was found to lead to a relapse in disease.

The key finding of this study was that a single treatment of faeces, called faecal transplantation, from healthy mice to infected mice "rapidly suppressed C. difficile" levels within five to seven days of treatment. This suppression lasted for a period of months. The researchers found that this method was consistently associated with highly effective suppression of the 'supershedder state' in 23 out of 25 attempts. This resulted in a significant loss of contagiousness, or transmission, between mice. Faecal transplantation was also associated with a return to normal intestinal flora (bacteria levels in the gut) and a reduction in the inflammatory processes in the gut.

As part of further investigations, the researchers identified six specific bacteria species (which has been referred to in the media as a "super-six cocktail") they considered to be responsible for suppressing the infection.

How did the researchers interpret the results?

The researchers conclude that intestinal (gut) imbalances in mice caused by infection with C. difficile bacteria can be suppressed with the faeces of healthy mice leading to rapidly resolved disease, reduction in contagiousness and restoration of a healthy intestine.

As a result of the study findings, the researchers say that faecal transplantation is a promising alternative therapy for recurrent C. difficile disease in humans.

Conclusion

This was an early stage animal study that examined the effect of faecal transplantation from healthy mice to mice infected with the bacteria Clostridium difficile.

The researchers note that although faecal transplantation is a promising alternative treatment for C. difficile infection, "it is not widely used because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens" and, to put it mildly, "general patient aversion".

One of the researchers, Dr Trevor Lawley, said "antibiotics are the greatest intervention ever, but maybe we’ve overused them and C. diff is the result". He went on to add that there were differences between the bacteria growing in the guts of mice and people, so the same experiments now need to be repeated in people to find an equivalent cocktail for suppressing the infection in humans.

This is valuable research into the treatment of Clostridium difficile – a significant cause of hospital-acquired diarrhoea. It does raise the possibility that by isolating the so-called "super-six cocktail" of bacteria, and then finding a way conveniently to introduce them to the body (such as in probiotic yoghurt), it may be possible to exploit the benefits of faecal transplantation without the obvious downsides.

However, at the current time, trialling such a step in humans who are already likely to be considerably unwell seems unlikely.