The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5-15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host" (219), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an effect on the prevention of CRC by scavenging toxic compounds or preventing their generation in situ. Additionally, a brief consideration is given to safety evaluation and production methods in the context of probiotics efficacy.

Fig. 1.

Dietary compounds associated with either increased or decreased risk of colorectal cancer [Based on reviews or papers by Marshall (165), Butt and Sultan (43), Kim and Kwon (133), Berquin et al. (26), Pool-Zobel and Sauer (207), and Johnson and Lund (128)].

Fig. 2.

Biochemical composition of the different gastrointestinal regions [Adapted from Wang et al. (276)].

Fig. 3.

Comparison of SSU rRNA sequences isolated from colon and small intestine specimens. The phylogenetic trees depict classification of sequences isolated from non-inflammatory bowel disease (IBD) colon (left) and non-IBD small intestine (right) samples. Numbers within wedges represent the proportion of sequences within each sample set (i.e., colon or small intestine) that were assigned to a particular clade (values <2% are omitted). Wedge widths represent the taxa with the longest (top) and shortest (bottom) distances within the clade. Wedge areas represent the number of taxa in each clade. The scale bar represents base changes per site. [Reproduced with permission from Frank et al. (89)].

Fig. 4.

Pathway of induction of DNA damage and gastrointestinal cancer by bile acid (BA). COX-2, cyclooxygenase-2. [Modified from Bernstein et al. (25)].