Gut`s natural defence that fights off C.difficile found

London: For the first time, scientists have discovered how cells in the gut fight off toxins produced by a hospital bug, a finding they say could lead to effective treatments for the bacteria that cause inflammation and severe diarrhoea.

Researchers at the Case Western Reserve University in the US found that a chemical, called GSNO, deactivates the toxin from Clostridium difficile, a bacterium which generally spread in hospitals, the BBC reported.

C. difficile is one of many bacteria which can live in the human gut without causing health problems. A course of antibiotics, which wipes out other bacteria in the gut, can
allow C. difficile to multiply and run rampant in the bowels.

They produce large numbers of toxins that enter the cells lining the bowel. This damages the cells causing inflammation, cramps, fever, diarrhoea and blood-stained stools.

According to the scientists, who detailed their study in the journal Nature Medicine, the whole toxin is unable to penetrate cells so it needs to cleave off a smaller chunk.

But the chemical GSNO (S-nitrosoglutathione), produced by the bowels in response to inflammation, can bind to the toxin, preventing cleavage, so the toxin cannot enter cells, the researchers said.

"Understanding how this mechanism deactivates toxins provides a basis for developing new therapies that can target toxins directly and thereby keep bacterial infections, like C.
diff, from spreading," said Dr Jonathan Stamler, one of the study authors.

Inspired by this natural mechanism, the team developed a treatment that mimics this process, preventing the toxin from damaging the cell.

In experiments on mice, they found giving the chemical orally increased survival. The researchers now want to begin clinical trials.

Lead author Professor Tor Savidge, from the University of Texas, said the technique could be used on other infections.

"Along with its potential to provide a much-needed new approach to treating Clostridium difficile infection, the discovery could be applied to developing new treatments for other forms of diarrhoea, as well as non-diarrheal diseases caused by bacteria," he said.

Prof Nigel Minton of the University of Nottingham called the discovery exciting and said: "Anything that can add to our scant arsenal of available treatments for combating this devastating disease is an important step forward.

"Having said that, one imagines that an actual therapeutic based on this discovery is some way off, either from being developed, and more importantly, from entering the clinic."


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