La COPROLOGIE sur le Web
DIGESTIVE ECOSYSTEM, MUCUS AND C. DIFFICILE
INFECTIONS: FROM RESEARCH LAB TO BEDSIDE
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Mucus is as much a partner of the digestive ecosystem
as the flora, luminal contents (physico-chemical conditions, nutrients,
metabolites, secretions) and intestinal motility. The intestinal ecologist
needs an overall view and an integrated approach to disturbances in the
ecosystem and how to prevent or correct them. All the more so since any
change to one of its components, be it physiological, due to disease or
to treatment, will have an effect on the others.
The paper by Boureau and Trevino summarises their valuable work
on the interrelations between Clostridium difficile and the colonic
ecosystem.
C. difficile is a micro-organism doctors know well because of the
pathogenic strains that secrete toxins (A and B). The anatomical and clinical
expression of C. difficile is polymorphic, and ranges from the asymptomatic
healthy carrier (1 to 3% of the general population and 20% of subjects recently
on antibiotics) to pseudomembranous colitis, through colitis of greater
or lesser severity and colitis-free diarrhoea situations.
Research is in progress to understand the relationships between
C. difficile and the colonic ecosystem, and to develop ecological
treatments to eradicate or prevent C. difficile-related diseases
in man. Reasons for the research include :
- the frequency of C. difficile transmission in hospitals (considered
by some to be the main micro-organism responsible for nosocomial infections,
- the seriousness of pseudomembranous colitis,
- the frequency of relapse on ceasing antibiotic treatment (20% on the
first occasion, and 40% in patients having already relapsed once or more),
- the failure of antibiotics to eradicate C. difficile in healthy
carriers.
Research teams are trying to pinpoint the role of the endogenous
flora, and to influence the ecosystem by introducing new micro-organisms.
The aim is to try and treat by stool washouts (not authorised by the French
pharmacopoeia) and, above all, to use transiting micro-organisms such as
Saccharomyces boulardii or Lactobacillus strains. Other
teams, including the authors', are trying to understand the precise role
of mucus.
The two approaches are not distinct; often, they are complementary
and integrated. For example "probiotic" candidates may be selected
for their innocuousness to the digestive mucus. Similarly, products
such as diosmectite which act on the mucus (mucostabilisation, mucosecretion)
could function by anti-adherence mechanisms during bacterial cytoaggression.
Thus, other than the work reported by Boureau and Trevino, two further
series have recently added to our knowledge of the interrelations between
C. difficile and the digestive mucus. Borriello et al. have shown
that mucus has a specific chemotactic effect on C. difficile and
that it contains micro-organism receptors different to those on the epithelium1.
Laboisse et al. observed on the clone 16E model of HT29 cells (cells secreting
mucus) that C. difficile inhibited the secretion of mucus induced
by stimulation.
This fundamental research confirms that mucus is a partner in the colon
ecosystem able to modulate C. difficile infections. The practical
therapeutic consequences are still unknown but do have a rational footing.
It is perfectly reasonable to think that a drug which could limit mucus
degradation or stimulate its secretion would protect the enterocyte from
the Clostridium's harmful effects. The road from research lab to
patient's bed is still not ended.
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