**2.5.2 IGF regulation**

220 Cancer Prevention – From Mechanisms to Translational Benefits

foods and nutrition. Recently, the focus has been on the prebiotic and probiotic effects,

Feeding specific food products with a prebiotic effect have been reported to reduce the incidence of tumors and cancers (Roberfroid et al., 2010). There are 100 trillion microbial organisms, called the microbiota, in human adult gut (Davis & Milner, 2009). Carbohydrate and proteolytic fermentation are the two main types of anaerobic fermentation in the

Prebiotics are non-digestible food ingredients which stimulate beneficial gut microbiota (Lim et al., 2005), e.g. inulin and other oligosaccharides, lactulose and resistant starch, such as fructooligosaccharides, inulin, lactulose and galactooligosaccharides (Tuohy et al., 2005). Probiotics are live bacteria found in processed foods or in dietary supplements, e.g. yogurt, cheese, fermented milks, juices, smoothies, cereal, and nutrition bars (Penner et al., 2005; Davis & Milner, 2009). Synbiotics are a combination of a probiotic with a prebiotic. A

Prebiotics must survive acidic conditions in the stomach and resist digestion in the small intestine. Then they need to be selectively fermented, and stimulate beneficial bacteria, usually bifidobacteria or lactobacilli, in the colon (Tuohy et al., 2005). In the randomized, double-blind, placebo-controlled trial for 12 weeks, dietary synbiotics reduced colon cancer risk, through increasing *Bifidobacterium* and *Lactobacillus*, and decreasing *Clostridium* 

A 4-year supplementation regime employing *Lactobacillus casei* decreased the recurrence of

Several animal studies and human trials showed that prebiotics, probiotics and synbiotics reduced toxic metabolite production, like caecal β-glucuronidase, nitrate reductase activities and caecal pH, in the gut, resulting in the prevention of colorectal cancer. On the other hand,

An increased number of bifidobacteria and/or lactobacilli may also play an important role in DNA protective modification and chemically-induced DNA damage (Tuohy et al., 2005). An increased number of biofidobacteria and/or lactobacilli in the gut may suppress the number or activity of putative enteropathogens such as *Escherichia coli* and *Clostridium perfingens* (Reddy, 1999). Prebiotics may also stimulate protective enzyme activities within the intestinal mucosa or reduce the immune inflammatory response (Burns & Rowland,

Since prebiotics are mostly oligosaccharides, it is considered that they reduce blood glucose. Increasing glycosylated hemogloin (HbA1c), which is a biomarker of glucose control for diabetes, was associated with an increased risk of colorectal cancer in women (Chan & Giovannucci, 2010). However, the consumption of short-chain fructooligosaccharides did

Transplantation of the gut microflora from normal mice into germ-free recipients resulted in increasing their body fat without increasing food consumption (Bajzer & Seeley, 2006). A 1-

some human studies denied the beneficial effects of prebiotics (Tuohy et al., 2005).

not have a significant affect on the glucose level in blood (Luo et al., 2000).

gastrointestinal tract (Davis & Milner, 2009, as cited in (McIntosh et al., 1999).

prebiotic can support the activity of a probiotic (Gibson & Roberfroid, 1995).

insulin-like growth factor (IGF) regulation, and calorie restriction.

**2.5.1 Prebiotic and probiotic effects** 

*perfringens* (Rafter et al., 2007).

2000).

atypical colonic polyps (Ishikawa et al., 2005).

IGF play important roles in proliferation, differentiation and transfomation in a variety of cell types, and thus it has been suggested that dysregulation of the IGF is an important cancer risk factor (Park, 2008).

A study on colon adenocarcinoma showed that n-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), increased IGFBP-6 in human colon adenocarcinoma Caco-2 cells, and the authors proposed that low IGF-II/IGFBP-6 ratios have resulted in less free IGF-II and a resulting slower proliferation of Caco-2 cells (Roynette et al., 2004). All-trans retinoic acid (tRA) showed an anti-proliferative effect in Caos-2 cells, and it was considered that this was due to a partly increased IGFBP-6 expression (Kim et al., 2002).

A low-calcemic vitamin D analogus decreased the secretion of IGF-II and suppressed HT-29 cell proliferation (Oh et al., 2001).
