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In-Depth Information
is not due to detoxification of the carcinogen, as nonviable heat and acid-treated
LBGG and LC-705 still demonstrated carcinogen-binding properties (El-Nezami et
al., 1998). It is believed that this binding involves bacterial cell surface carbohy-
drates. Further, new noncovalent or hydrophobic interactions were also found to be
significant in the treated cells, as was demonstrated with the binding of the dietary
mutagenic pyrolyzate, 3-amino-1,4-dimethyl-5-H-pyrido [4,3-b]indole (Trp-P-1) to a
Lactococcus
strain. Of minor significance is the electrostatic interactions produced
by the presence of metal cations, especially with divalent cations, which are che-
lated by AFB1 and bound by bacterial cell walls to lessen bacterial AFB1 binding
(Haskard et al., 2000).
Perhaps more germane to the current discussion is whether carcinogen binding
demonstrated
in vitro
can be extrapolated to an
in vivo
situation. Bolognani et al.
(1997) showed that while certain lactic acid bacteria are indeed able to effectively
bind a range of dietary carcinogens
in vitro
, with differing species and carcinogen
specificities, no reduction in
in vivo
mutagenicity was detected in animal studies.
Thus, they concluded that binding of carcinogens to the fecal microbiota does not
exert a significant influence on intestinal absorption, metabolic transformation, and
distribution. They have offered explanations pertaining to the rise in pH between the
stomach and the small intestine or changes in other relevant conditions that could
have reversed binding
in vivo
. In addition, varying nutritional states prior to treat-
ment may have contributed to disagreement among studies (Bolognani et al., 1997).
14.3.3 Modulation of Immune response
The immune system consists of a complex series of interlinked mechanisms,
which function in protection against infections (Perdigon et al., 1995) and uncon-
trollably growing tumor cells (Wollowski et al., 2001). The intrinsic properties of
lactobacilli to modulate the immune system make them attractive for health applica-
tions. The mechanisms by which probiotics may inhibit colon cancer are not yet fully
characterized; however, one mechanism by which this may occur is via modulation
of the mucosal and systemic immune responses and by reduction in the inflamma-
tory response to host flora.
Modulation of the immune system can occur through intrinsic adjuvance and
cytokine-inducing properties of lactobacilli. Administration of lactobacilli can
affect cytokine expression in specific and nonspecific manners. The ability to
perform phagocytosis and kill microbes including bacterial pathogens is a major
effector function of macrophages. Different strains of lactobacilli are able to acti-
vate macrophages and induce production of tumor necrosis factor-alpha (TNF-α),
interleukins (IL), specifically viz. IL-1, IL-6, IL-12, IL-18 (Maassen, 2000), which
increase the process of phagocytosis. The natural killer (NK) cells play a key role in
protection against viral infections and tumor development.
Studies describing a probiotic-mediated increase in antitumor immunity via
mechanisms including cytokine production and modification of T-cell function
have been reviewed previously (Hirayama and Rafter, 2000; Rafter 2003). Recently,
it has been demonstrated that lactic acid bacteria, particularly the cytoplasmic
