Chemistry Reference
In-Depth Information
were likely to be important for the inhibition of bacterial pathogens; and that future
studies should focus on isolating and testing these compounds.
Schlee and colleagues
40
investigated the mechanism via which the antimicro-
bial human beta defensin-2 (hBD-2) gene (which is important for the maintenance
of intestinal barrier function) was induced by the probiotic strains:
L. fermentum
PZ-1138,
L. acidophilus
PZ1138,
E. coli
Nissle 1917, and VSL#3 (a combination
of eight bacterial strains).
40
It was determined that hBD-2 induction by probiotic
bacteria was both time and dose dependent, and that deletion of the NF-κB and
activator protein-1 binding sites on the hBD-2 promoter completely inhibited
the probiotic effect. Furthermore, inhibition of mitogen-activated protein kinase
(MAPK) also impeded hBD-2 induction. Schlee and colleagues demonstrated that
selected lactobacilli and VSL#3 were able to strengthen intestinal barrier function
via the upregulation of hBD-2 through the induction of MAPKs and the proinflam-
matory NF-κB and AP-1 pathways.
40
In addition to improving barrier function,
further studies using
L. fermentum
highlight other potentially beneficial effects.
Lactobacillus fermentum
ACA-DC 179
displayed antimicrobial immunomodula-
tory activity as it reduced
Salmonella enterica
viability and increased IL-10 levels
in vitro
.
42
In support of the findings of Schlee and colleagues,
E. coli
Nissle 1917 was
also demonstrated to improve intestinal barrier function, although this effect was
detected in an
in vitro
model of intestinal inflammation induced by an
E. coli
chal-
lenge.
43
Following DNA micro-array analysis, Nissle 1917 has been shown to alter
both the distribution and expression of zonula occludin (ZO)-2 proteins and a number
of protein kinase C isotypes; both of which are involved in the maintenance of tight
junctions within the epithelial barrier. Although it is possible these changes occurred
in conjunction with the effect on hBD-2 observed by Schlee and colleagues, the
findings of this study are potentially of greater relevance to IBD treatment (assum-
ing that microbial pathogens are involved in the disorder) as they occur following
pathogen-induced damage to the cell monolayer. In addition to the maintenance of
barrier function, Nissle 1917 has also been shown to have an antiinflammatory effect
on human epithelial cells
in vitro
.
33
Following the addition of TNF-α, treatment
with Nissle 1917 reduced the production of proinflammatory IL-8 without altering
transactivation pathways, such as NF-κB activation, nuclear translocation, or nuclear
binding. The ability of
E. coli
Nissle 1917 to increase both intestinal barrier function
and antiinflammatory cytokine production makes it a promising therapeutic option
for IBD. Indeed, clinical trials have been performed and are discussed here.
In addition to reducing pathogen adhesion, Candela and colleagues reported that
Bifidobacterium longum
Ba r33 a nd
L. acidophilus
Ba r13 were able to re duce t he pro -
duction of proinflammatory IL-8.
34
Interestingly, the experiments were performed
on two different cell lines, with pathogen competition observed in Caco-2 cells,
and immunomodulation reported in the HT-29 cell line. Probiotic activity can be
influenced by the environment; therefore, further studies should investigate whether
these effects are repeatable in multiple cell lines, and whether they are observed
in vivo.
Similarly, Jankowska and colleagues reported that
L. paracasei
IBB2588
reduced adhesion of harmful
S. enterica
to Caco-2 cells,
32
finding that displacement
