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cytokines IL-1β, TNF-α, and interferon (IFN)-γ, reduced protein levels of colonic
I L-1β and IL-6, and reduced the bacterial degradation activities of chondroitin sul-
fate and hyaluronic acid. Similarly, Osman and colleagues described a reduction in
disease activity, MPO activity, and bacterial translocation following L. plantarum
administration in the DSS model of colitis, 55 while Schultz and colleagues reported
efficacy of L. plantarum in the IL-10-deficient (IL-10 -/- ) model of colitis as indicated
by decreased IL-12 and IFN-γ production. 37 Furthermore, Bujalance and colleagues
demonstrated the ability of L. plantarum to improve immune function in immuno-
compromised hosts. 56 The various beneficial mechanisms of L. plantarum highlight
its therapeutic potential in GI disorders, such as IBD.
Peran and colleagues demonstrated the preventative effects of L. reuteri and L.
fermentum in the rat TNBS colitis model. 45 Oral administration of these probiotics
reduced colonic inflammation scores, MPO activity, colonic TNF-α expression, and
inducible NO synthase expression when compared to untreated rats. Interestingly,
only L. fermentum treatment lowered colonic cyclo-oxygenase-2 expression and
increased SCFA production in the colonic contents, indicating a greater efficacy of
L. fermentum in the treatment of experimental colitis. These findings are supported
by Zoumpopoulou and colleagues who also reported efficacy of L. fermentum in a
mouse model of TNBS-induced colitis. 42 In a separate study, Peran and colleagues
demonstrated the ability of L. acidophilus , L. casei, and B. lactis to reduce intes-
tinal inflammation in the TNBS model. 38 Interestingly, each probiotic displayed a
unique antiinflammatory profile: L. acidophilus reduced MPO activity and leuko-
triene B 4 production; B. lactis reduced colonic TNF-α production edema; and L.
casei decreased cyclooxygenase-α expression in the colon. These findings further
highlight the different mechanisms by which probiotics can exert their beneficial
effects.
I L-10 -/- mice spontaneously develop colitis following colonization with conven-
tional flora, and have been frequently used to screen probiotics for therapeutic poten-
tial. Neonatal IL-10 -/- mice typically possess low levels of colonic lactobacilli, and
Madsen and colleagues reported normalization of lactobacilli levels following rectal
administration of L. reuteri . 57 Furthermore, L. reuteri treatment reduced levels of
colonic mucosal adherent and translocated bacteria and prevented the development
of colitis. Administration of L. gasseri (10 9 cfu/mL), a strain that produces high lev-
els of manganese superoxide dismutase (MnSOD, an antioxidant), reduced intes-
tinal inflammation compared to untreated animals in the IL-10 -/- model. 58 When
compared to wild-type L. gasseri , treatment with the MnSOD-producing strain led
to significantly lower histological inflammation scores and provides an example of
how probiotics can be used as vehicles to deliver therapeutic compounds as well
as exerting their own beneficial effects. Both L. salivarius UCC118 and B. infantis
were shown to attenuate the development of colitis in IL-10 -/- mice. 28 The authors
concluded that this was a result of reduced Th1-type cytokine production, as well as
maintenance of transforming growth factor (TGF)-β levels.
Gnotobiotic mice have been used to elucidate the effects of probiotics on the
host immune response. Menard and colleagues tested a number of Bifidobacterium
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