Nathalie Vergnolle, director of research
at Inserm, and her team at the Centre for Physiopathology at
Toulouse Purpan (CPTP Inserm / Université Toulouse III – Paul
Sabatier /CNRS), with Philippe Langella director of research at INRA
and his team at the Institut Micalis (Institut MICrobiologie de
l’ALImentation au Service dela Santé Humaine - INRA/AgroParisTech -
in Jouy-en-Josas), in collaboration with the Institut Pasteur, have
recently succeeded in producing “beneficial bacteria” capable of
protecting the body against intestinal inflammation. This protection
is provided by a human protein, Elafin, which is artificially
introduced into dairy produce bacteria (Lactococcus lactis and
Lactobacillus casei). In time, this discovery could be useful for
individuals suffering from chronic inflammatory diseases such as
Crohn’s disease or ulcerative colitis. The results of this research
were published in the Science Translational Medicine review on 31
October 2012.
In France, nearly 200,000 individuals
suffer from chronic inflammatory bowel disease, known as IBD,
(specifically Crohn’s disease and ulcerative colitis). The
occurrence rate of this type of disease continues to rise (8,000 new
cases diagnosed per year). During inflammatory outbreaks, IBDs are
chiefly characterised by abdominal pain, frequent diarrhoea
(sometimes with bleeding) or even disorders in the anal area
(fissure, abscesses). These symptoms mean that taboos are associated
with these diseases.
Different avenues are being explored to
explain the origin of IBDs, including the role of genetic or
environmental factors. The intestinal flora seems to play an
important role in the outbreak of inflammation, although little is
known about it. Identifying an effective treatment is also at the
heart of the investigations.
Researchers are focussing on a human
protein, known for its anti-inflammatory proprieties: Elafin.
Although this protein is found naturally in the intestine to protect
it against attacks, it disappears in patients suffering from IBDs.
Their hypothesis? Administering Elafin
directly into the intestine could protect against inflammatory
attacks and restore intestinal equilibrium and its functions.
Using non-pathogenic bacteria found
naturally in the intestine and food, scientists from Inserm and Inra
have designed modified bacteria to produce Elafin. To this end, the
human Elafin gene, isolated in collaboration with a team from the
Institut Pasteau, was introduced in Lactococcus lactis and
Lactobacillus casei, two food-grade bacteria found in dairy
products.
When administered orally to mice, the
human Elafin-producing bacteria are found a few hours later on the
surface of the intestine where they deliver the anti-inflammatory
protein. In different mice models of chronic or acute intestinal
inflammation, oral treatment using these Elafin-producing bacteria
provided significant protection of the intestine and decreased
inflammatory symptoms.
Elafin expressed by these bacteria also
protects cultured human intestinal cell lines from inflammatory
outbreaks similar to those observed in chronic inflammatory bowel
diseases. Elafin produced in this way restores the equilibrium of
intestinal mucus by reducing inflammation and accelerating cell
healing processes.
These results may result in a clinical
application where Elafin would be administered to patients suffering
from IBDs using beneficial bacteria (probiotic), which are already
commonly found in food (yoghurt, cheese), thus protecting the
patients from inflammatory symptoms. According to the researchers
“This kind of secure treatment could even be used over the
long-term, to treat inflammatory diseases”.
This research is protected by a patent
and an exclusive licence assigned to an industrial partner, managed
by Inserm Transfert.
For more information
http://www.inserm.fr/
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