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Bacteria Cocktail Wipes Out Superbug C. Diff In Mice

Clostridium difficile (C. diff) is a highly infectious "superbug" associated with many deaths in hospital. Now scientists in the UK have identified a "cocktail" of bacteria that successfully wipes out the deadly bacterium in mice. They suggest their findings will have a significant impact on the control and treatment of such infections in humans.

First author Trevor Lawley, from the Wellcome Trust Sanger Institute, near Cambridge, and colleagues, write about their work in a study published online on 25 October in PLoS Pathogens.

C. diff lives naturally in the gut of some people, where normally, competition from other bacteria prevents it spreading. But treatment with broad-spectrum antibiotics such as clindamycin can alter that balance, allowing the gut to be overrun with C. diff, which can cause bloating, abdominal pain, and diarrhoea.

People in hospital, nursing homes, and other care facilities can accidentally ingest the spores of C. diff from infected patients. In 2011, the pathogen contributed to over 2,000 deaths in the UK.

For their study, Lawley and colleagues investigated a strain of C. diff known as O27, which has been responsible for epidemics in Europe, North America and Australia. Supershedding C. diff Hard to Treat They found the O27 strain of C. diff establishes a prolonged, persistent contagious period known as "supershedding" that is hard to treat with antibiotics, during which the bacterium releases spores that are highly resistant, can survive for long periods, and are difficult to eradicate from the environment.

But using mice, they found six naturally occurring bacteria that eliminate this highly contagious strain of C. diff. Three of the bacteria have not been described before.

In a statement, Lawley relates how as a first step, they tried treating the mice with a range of antibiotics but they "consistently relapsed to a high level of shedding or contagiousness". Fecal Transplants Then the researchers treated the infected mice with fecal transplants from a healthy mouse and found this "quickly and effectively supressed the disease and supershedding state with no reoccurrence in the vast majority of cases".

This is a similar approach to that of another study reported recently, where researchers transplanted donated human stool into patients infected with C. diff and cured 90% of them.

But Lawley and colleagues wanted to take this further: they wanted to find and isolate the bacteria that suppressed C. diff and restored balance in the gut flora. Cocktail of Six Bacteria Suppressed Supershedder State With painstaking effort they cultured and tested large numbers of bacteria that are present naturally in the gut of mice, in various combinations, until they isolated a cocktail of six that were most effective in suppressing the C. diff infection.

Co-senior author professor Harry Flint, from the University of Aberdeen, says:

"The mixture of six bacterial species effectively and reproducibly suppressed the C. difficile supershedder state in mice, restoring the healthy bacterial diversity of the gut."

To identify the six bacteria precisely, the team sequenced their genomes and compared their genetic family trees. This is how they found three of them were already known, but the other three were novel species. They say the mix of six is genetically diverse and includes species from all four main groups of bacteria found in mammals.

Discovery Paves the Way for New Approaches and Treatments Co-senior author professor Gordon Dougan, also of the Wellcome Trust Sanger Institute, says:

"Our results open the way to reduce the over-use of antibiotic treatment and harness the potential of naturally occurring microbial communities to treat C. difficile infection and transmission, and potentially other diseases associated with microbial imbalances."

He says their approach offers a better option for patients than stool transplants, which patients find disgusting, and besides, can also introduce harmful pathogens.

"This model encapsulates some of the features of faecal therapy and acts as a basis to develop standardized treatment mixture," says Dougan.

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