Faecal transplants; the future therapy for Clostridium difficile?

Clostridium difficile from a stool sample (CDC/Lois S. Wiggs, 2004)

Clostridium difficile, commonly known as C. diff, is a species of bacteria generally found in soil where it can remain dormant and survive the worst excesses of the elements. In this non-growing state it is shielded by a thick, protective spore which forms around the bacterium. It is not unusual for the bacteria to live in the gut of healthy people without causing any problems. They dwell in the intestines of people who are oblivious to the messy mayhem their minute bacterial squatters could cause. Infection by C. diff, under certain circumstances, can have painful and sometimes fatal consequences.

A highly distasteful therapy has been devised that could herald the development of a useful weapon against this pervasive and potentially deadly bacteria. The treatment is faecal transplantation; taking a morsel of matter from a healthy gut, liquidising it and pumping it into an infected gut.

C diff infection (CDI) is associated with people who spend time in hospital, receive antibiotic treatment or somehow have a compromised immune system. It is most commonly found in over-65s, a group of the population more likely to be admitted to hospital and receive antibiotics because their immune system, as a result of ageing, is not as substantial as it once was. CDI is more a problem in developed than developing countries because the fruits of economic and social advance mean the populations of Europe, North America and Japan are aging. Their hospitals are filled with the decrepit and wrinkly consequence of industrialisation: lives artificially prolonged by medical science beyond any point prior generations could have thought possible

CDI’s association with hospitals and antibiotic treatment is intrinsically linked to the microorganisms’ biology and the contents of a human’s gut. CDIs are not often picked up outside the hospital walls because a healthy person has a vibrant community of bacteria living in their guts. This is the gut micro-flora and these non-harmful bacteria are called commensal bacteria.

The micro-flora of a healthy gut is a complicated ecosystem in itself, with limited space and limited food. This results in intense competition between the microorganisms that live there. Therefore any invading organism must somehow dominate this established population before it can cause the human host any harm.

C. diff is resistant to a number of antibiotics and when cocooned in its spore many cleaning products and detergents cannot kill it. As a result C. diff can spread around hospitals and nursing homes, carried by the hands of a patient, a visitor, or the staff from the loo to a light switch or door handle and then to the patients. The alcohol-based hand gel that you see all over medical centres are about as effective as a sandbag full of sugar – the alcohol gel selectively kills pretty much everything on your hands except C. diff.

Once established C. diff produces toxins which cause serious inflammation of the gut wall. White blood cells rush to the thin layer of cells that coat the inside of the gut, called the epithelium, to defend against the effects of the toxins. This can lead to the epithelium breaking in tiny ruptures and the white blood cells and the contents of the bursting epithelial cells flood into the central passage through the intestines called the lumen. This causes the characteristics symptoms of C. diff infection; protracted and painful diarrhoea sometimes described as “green and foul-smelling”.

The diarrhoea can develop into a much more serious condition called toxic megacolon, where the gut lumen swells and bloats even though it is not blocked. This can lead to peritonitis, where the gut lining bursts causing the contents of the intestines to spill out into the body cavity. Without immediate treatment peritonitis leads to massive infections throughout the body and a painful death.

Currently CDIs are treated with antibiotics however this is not guaranteed to clear all the C. diff from the gut. It does kill off much of the surviving gut microflora which only serves to reduce the C. diff bacteria’s competition. This can make the situation worse, enabling the infection to return after a few months hiatus. This happens in roughly one third of cases.

Faecal transplant involves taking 30 grams (1oz) of faeces from a close relative or cohabitant so that, because of similar diet and living environment, the donor and recipient share gut-flora characteristics. This modest contribution is diluted to produce a “faecal fluid”; 30 millilitres, a little more than two tablespoons, of which is then pumped down a tube inserted, via the patient’s nose, into the large intestine.

Dr Alisdair McConnachie of Gartnavel General Hospital in Glasgow has produced a 75 per cent success rate for treatment of recurrent C. diff infection. Others have reported more than 90 per cent success. There are full clinical trials recruiting patients in Canada and the Netherlands. The Dutch study is accepting CDI sufferers from across Europe – apparently even the supposedly scatological Lowlanders are a bit iffy about the idea of this transplant.

Professor Ian Poxton of the University of Edinburgh explains where faecal transplants could lead us: “It proves without doubt that you can give people a bacterial cocktail that will prevent relapse” he said. “Now we need to identify the components [of the gut-microflora] that does the protecting.” The faecal transplants have proven the principle that replenishing the gut microflora is an effective treatment. This could be translated into a probiotic that actually cures recurring CDI.

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