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In-Depth Information
for its use as a therapeutic for cytokine-mediated GI diseases. All of the mechanisms
responsible were not identified, however; an earlier study also reported that soluble
products of LGG were able to activate MAP-kinases and induce cryoprotective heat
shock proteins in intestinal epithelial cells, further mechanisms that could contribute
to the beneficial clinical effects of LGG.
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The production of multiple bioactive compounds by probiotic bacteria has pre-
viously been reported in
L. johnsonii
NCC 533.
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The supernatant was shown to
contain products capable of catalyzing the synthesis of the antimicrobial compound,
hydrogen peroxide, in addition to the previously identified lactic acid and other bac-
teriocins. Production of hydrogen peroxide was also observed in eight other
L. john-
sonii
strains, suggesting a degree of species, rather than strain, specificity.
12.5.3 Efficacy of Probiotics, Prebiotics, and synbiotics
Probiotic, prebiotic, and synbiotic treatments have the potential to decrease the
severity of IBD. A number of potential mechanisms have been identified, includ-
ing increased SCFA production, reduction of proinflammatory cytokine secretion
and gene expression, strengthening of the intestinal epithelial wall and improvement
of barrier function, improvement of the Th1/Th2 balance, and the elimination of
pathogenic bacteria, among others. As a result of their variable successes, concerns
remain related to the use of probiotics as therapeutics for IBD. Although some exert
beneficial effects, many strains have been reported to be ineffective while some have
been shown to exacerbate disease severity. A critical step to improve the effective-
ness of these therapies is to gain a better understanding of the intestinal microbiota
and its relationship with disease development. This information would facilitate the
identification of specific targets for manipulation and allow for strategic selection of
the most beneficial probiotics for a given disease. Furthermore, a greater mechanistic
understanding of probiotics, prebiotics, and synbiotics would facilitate the selection
of the strains and combinations most suited to each gut disorder. Finally, it is essen-
tial that the manner in which the probiotic treatments interact with the commensal
bacteria be determined. The microenvironment differs between individuals and it
is feasible to predict that treatments may be selected to suit the individual based on
their own unique bacterial profile.
The risk of sepsis associated with the administration of live probiotic bacteria
is low, but nevertheless worthy of consideration. Probiotic-related cases of sepsis
are rare and usually observed in immunocompromised patients with impaired bar-
rier function. In addition, the difficulties associated with maintaining a high degree
of quality control is another problem hindering the development of probiotic-based
therapeutics.
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Both of these issues can be addressed through the use of either inac-
tivated probiotic bacteria or the supernatant products of probiotics. Inactivated bac-
teria and supernatants have been tested
in vivo
and
in vitro
and have demonstrated
efficacy in the setting of intestinal inflammation. They could potentially allow the
same beneficial effects of probiotics to be exerted, without the risk of sepsis or harm-
ful interactions with the host microbiota. Furthermore, once the sources of beneficial
effects associated with probiotics have been identified, whether it be the microbial
