**1. Introduction**

216 Lactic Acid Bacteria – R & D for Food, Health and Livestock Purposes

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Pathways. Gastroenterology Research and Practice Volume 111: 1-16.

Colon cancer (CC) is one of the commonest causes of death among all types of cancers [1]. The development of cancer is a multifactorial process influenced by genetic, physiological, and environmental factors [2,3]. Regarding environmental factors, the lifestyle, particularly dietary intake, may affect the risk of CC developing [1,4]. Western diet, rich in animal fat and poor in fiber, is generally associated with an increased risk of colon cancer [5,6,7]. Thus, it has been hypothesized that the connection between the diet and CC, may be the influence that the diet has on the colon microbiota and bacterial metabolism, making both relevant factors in the etiology of the disease [8,9]. Additionally, it has been clearly demonstrated that the gut microbiota may be modulated by many factors including diet [10].

Several studies have indicated that the intestinal microbiota is an important determinant for general health of the human body [1]. Therefore, a beneficial modulation of the composition and metabolic activity of the gut microbiota might represent an interesting approach to improve health, reducing the risk of CC development. This modulation may be though about probiotic consumption.

Probiotics are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host [11]. Among the best known probiotic microorganisms are strains belonging to the *Lactobacillus* and *Bifidobacterium* genera. However, other microorganisms, such as *Enterococcus* spp., *Streptococcus* spp., *Escherichia coli* Nissle 1917, some bacilli, and *Saccharomyces cerevisiae* subsp. *boulardii* have also been considered for use as probiotics [12].

Even though the mechanisms by which probiotics may inhibit colon cancer are not fully elucidated, certain potential mechanisms have been disclosed, such as the alteration of the

© 2013 Sivieri et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

composition and the metabolic activities of the intestinal microbiota, the changing physicochemical conditions in the colon, the binding of dietary carcinogens, the production of short chain fatty acids (SCFA), the protection of the colonic mucosa and enhancement the immune system [1,3].

Probiotics and Intestinal Microbiota: Implications in Colon Cancer Prevention 219

This neoplasia is considered to have a good prognosis when diagnosed in the early stages. Colon cancer like others forms of cancer develops as a result of interaction between endogenous and environmental factors. Among the factors that may affect the risk of developing this disease are age, eating habits, physical activity, alcohol consumption, smoking, nutritional status, presence of polyps, cancer history of self and family, cases of

Most cases of CC occur sporadically, being the most common type of adenocarcinoma, which develops from glandular cells that cover the wall of the intestine [17]. Adenocarcinomas grow from normal epithelium through an accumulation of mutations that

Genomic instability is fundamental to this process and is related to the rearrangement of genes, or loss of DNA fragments, aneuploidy and loss of heterozygosis [19]. In addition, inactivation of tumor suppressor genes, such as APC, DCC, DPC4 and p53, along with the activation of oncogenes, of which the family of *ras* genes are the best well described, play

Generally, the colon tumor is detected for the first time as a polyp (mass of cells growing out of the wall of the colon), although nowadays it is possible to detect small lesions affecting the crypts, called aberrant crypts foci (ACF) [18]. ACF are not only morphologically but also genetically distinct lesions and are precursors of adenoma and cancer. Tumors can appear anywhere in the colon, although most sporadic rectal colon cancers are located on the left

Epidemiological studies have pointed to the high consumption of red meat, fat and low fiber intake, typical of the Western diet as risk factors in the etiology of this type of cancer [20].

One of the possible effects of a Western diet on colon cancer is related to increased excretion of bile acids [21]. In addition, the increased ammonia production in rats consuming a diet rich in protein has also been linked to an increased risk of cancer [22]. However, high consumption of fruits, cereals, fish and calcium may reduce the risk of developing colon

The effect of diet on carcinogenesis can be modulated by changes in metabolic activity and composition of the intestinal microbiota [23]. Several studies have trial to establish relationships between bacteria and colon cancer. We know that various bacterial metabolites are carcinogenic, examples being, the nitrosamines, phenol, indole, ammonia and amines

There is multiple evidence that bacteria play a key role in the emergence of chronic inflammatory bowel diseases. Experimental studies demonstrate the impossibility of developing this inflammation in the absence of bacteria and researches have tried for many years trying to identify a possible causative agent of inflammatory bowel diseases. Studies suggest that chronic inflammatory intestinal activity seems, paradoxically to be triggered by bacteria belonging to the normal commensal which take on microbiota in situations as yet

unknown, a pathological role that can activate the local immune apparatus [24].

ulcerative enterocolitis and chronic constipation [15,16].

important parts in the appearance of malignancy [17].

side of the distal colon (including the rectum and sigmoid colon) [19].

result in malignant transformation [19].

cancer [23].

[13].

The anticarcinogenic effects of probiotic microorganisms *in vitro* and in animal studies are well documented [3]. In clinical trials, the probiotics are thought to play a protective role in the initial process of carcinogenesis. Nevertheless, it is important to determine whether the long-term administration of these microorganisms might result in changes in the incidence of CC in humans [13]. Additionally, there are several challenges for the development of probiotics, including the selection of the appropriate microorganisms, control of dietary intake, time and frequency of probiotic dosing and the use of accepted biomarkers for raised cancer risk that might be monitored during clinical trials [4,13]. Further experimental models are needed to understand the exact mechanisms involved in the influence of probiotics on colon cancer development.

Therefore, this chapter will discuss the effects of probiotics in colon cancer prevention and the possible mechanisms of action these microorganisms. Additionally, this chapter will also show the results of original work, carried out by our research group, about the effects of probiotic *Enterococcus faecium* CRL 183 (strain isolated from Tafí cheese, a homemade traditional highlands cheese the province of Tucumán, Argentina) on intestinal microbiota and colon cancer prevention.
