Chemistry Reference
In-Depth Information
probiotics, prebiotics as they are indigestible have been associated with reduced risk
of colon cancer mainly by production of short-chain fatty acids, such as butyrate.
The possible mechanism by which both probiotics and prebiotics mediate their effect
in preventing colon cancer is discussed in the following sections.
14.3.1 Changes in Colon ph
pH in gut plays a very important role as an innate immune barrier. Lactic acid
bacteria have the potential to produce various free fatty acids, organic acids, and
other metabolites, which lead to decreased pH in the gut. Decrease in colon pH
is considered as one of the potent properties of probiotic bacteria in reducing the
incidence of colon cancer. Reddy et al. (1997) observed that a stimulated growth
of bifidobacteria in the colon could lead to the inhibition of azoxymethane-induced
colon carcinogenesis. This inhibition in ACF and its multiplicity was attributed to
the pH-lowering effect of bifidobacteria in the colon, which subsequently inhibited
the growth of
Escherichia coli
and clostridia. The decrease in growth of patho-
genic microorganisms may also produce modulation of such bacterial enzymes
as β-glucuronidase that can convert procarcinogens to carcinogens (Kulkarni and
Reddy, 1994). Moreover, a prebiotic-induced decrease in luminal colonic pH may
function to improve mineral solubility and uptake, namely, calcium, magnesium, and
iron. In particular, enhanced bacterial fermentation has also been shown to have this
effect on calcium ions, through the fermentation of such substances as phytate (myo-
inositol hexaphosphate), which binds to divalent cations, such as calcium. Improved
calcium absorption would provide adequate calcium for various physiological pro-
cesses (Roberfroid et al., 1995; Younes et al., 2001). Additionally, calcium is sug-
gested to be beneficial toward colorectal cancer, with increasing evidence that it
inhibits proliferation and enhances differentiation and apoptosis of mucosal cells
(Lamprecht and Lipkins, 2003). Further, an acidic luminal environment may reduce
procarcinogenic enzyme activity, such as that of 7a-hydroxylase and nitroreductase
(Ballongue et al., 1997).
14.3.2 Altering xenobiotic Metabolism in gut system
Various chemical substances are responsible for the induction of colon cancer.
These substances appear either to come with food or to be produced by gut com-
mensal flora. A xenobiotic is “a chemical found in organisms, but not expected to
be produced or present in them,” and many, if not most, human carcinogens are
xenobiotics. A range of enzymes (xenobiotic metabolizing enzymes, or XME) are
classed as either phase 1 or phase 2, which function to convert these exogenous
compounds into reactive metabolites or carry out conjugation reactions in order to
detoxify reactive compounds for excretion, respectively (Lhoste et al., 2001). Phase
1 enzymes include the cytochrome P450s (CYP) and phase 2 enzymes include glu-
tathione-
S
-transferase (GST) and NAD(P), quinine reductase (quinone reductase),
UDP-glucuronosyltransferase (UGT), sulfotransferases, and
N
-acetyl transferase
(NATs) (Hashimoto and Degawa, 1995; Joseph and Jaiswal,1994; Lin et al., 1994).
