Chemistry Reference
In-Depth Information
and detoxify such compounds (Wollowski
et al., 2001). Bacteria of the
Bacteroides
and
Clostridium
genera increase the incidence and growth rate of colonic tumors
induced in animals, whereas other genera, such as
Lactobacillus
and
Bifidobacterium
prevent carcinogenesis (Pool-Zobel, 2005). Although the evidence is not conclusive,
colonic flora seems to be a major environmental factor that modulates risk of colonic
cancer in humans (Guarner and Malagelada, 2003).
Numerous
studies have shown that inulin-type fructans prevent chemically
induced preneoplastic lesions, aberrant crypt foci (ACF), and
tumors in the colon
of rats and mice (Pierre
et al., 1999, 2001; Wollowski
et al., 2001; Pool-Zobel
et al.,
2002, 2005). Contradictory studies have been shown to enhance adenoma growth in
mice (Pajari
et al., 2003; Misikangas
et al., 2005, 2008).
In humans, several trials have been carried out to examine possible effects of
prebiotics on colonic carcinogenesis. These trials used fecal butyrate concentra-
tion, fecal bile acids, and rectal crypt cell proliferation as promising surrogate
markers for the risk of colorectal carcinogenesis (Rafter, 2002). Fecal bacterial
enzymatic activities, such as
β
-glucuronidase, have been extensively studied as
they may play a role in the metabolic activation of procarcinogens and decon-
jugation processes in the colonic lumen (Goldin, 1990). Some trials have been
performed in healthy volunteers, with the aim to modify some potential marker
of colon carcinogenesis.
Fecal bacterial
β
-glucuronidase activity is increased in patients on a high meat
diet, and this enzyme could act to raise the amount of substances, such as carcinogens,
within the colonic lumen (Reddy
et al., 1998). In a previous study, we demonstrated that
sc-FOS ingestion led to a significant decrease in
β
-glucuronidase activity (Bouhnik
et
al., 1996). In a recent RCT, 15-day consumption of 10g/day sc-FOS in healthy subjects
has been shown to reduce the activity of
β
-glucuronidase in fecal samples, whereas
consumption of 15 g/day lc inulin over the same period did not change enzymatic
activities (Bouhnik
et al., 2007). Similar results were found by Kleessen et al., who did
not demonstrate changes in
β
-glucuronidase activity following lc inulin consumption
for 19 days at doses ranging from 20 to 40 g/day (Kleessen
et al., 1997).
Three interventional studies using fructans or synbiotics in patients with polyps or
cancer have been published (Boutron-Rouault
et al., 2005; Rafter
et al., 2007; Roller
et al., 2007) (Table 3.6). In one of them, the effect of a 3-month consumption of
10 g/day sc-FOS on these markers was assessed in subjects with large (>10 mm)
or small adenomas (<10 mm), or in healthy subjects (Boutron-Rouault
et al., 2005).
The butyrate concentration, which was initially significantly lower in subjects with
adenomas compared to healthy subjects, significantly increased to the level found
in healthy subjects after the 3-month sc-FOS consumption. If there is little doubt
that butyrate may exert an effect on colon cancer development, exact mechanisms by
which butyrate acts remain unclear. Variable effects could indeed be obtained accord-
ing to the
in vivo
or
in vitro
environments, the timing of butyrate administration in
relation to the stage of cancer development, the amount of butyrate administered, as
well as an interaction with dietary fat (Lupton, 2004). For example, prebiotics may be
protective against the early stages of polyp formation, but not at the stage of transition
of polyp to a carcinoma, and low amounts of butyrate may stimulate cell proliferation
