The Influence of the Microbiota on the Etiology of Colorectal Cancer

Abstract

The microbiome of the gastrointestinal (GI) tract is estimated to comprise 39 trillion organisms that act in a symbiotic relationship with the surrounding tissue cells to maintain homeostasis. Constituents of the gut microbiota occupy either a planktonic niche within the fecal stream, are adherent to the gut mucosa, or are associated with the mucous layer. Alterations in the gut microbiota at any of these levels, caused by the genetics of an individual or by environmental factors, can disturb this homeostatic relationship and promote disease such as colorectal cancer (CRC). CRC is the third most common form of cancer in both men and women and the second leading cause of cancer-related death in the USA, representing a considerable disease burden. The intimate association between the microbiota and the cells of the colon sets the stage for a number of interactions that may contribute to carcinogenesis. Although only a few specific commensal species may play a direct causal role in CRC, more general shifts in the composition may promote local inflammation through the engagement of innate immune receptors encoded within the colonic tissue. Changes in gene expression within the microbiota may also be important as virulence factors are altered and metabolites are produced that may have detrimental effects on the tissue. In this chapter, we explore the theoretical bodyworks through which certain members of the microbiota are believed to cause CRC, the sensing of microbiota-associated molecular patterns by innate immune receptors known as toll-like-receptors (TLRs) and the various strategies aimed at manipulating the microbiota and targeting the TLRs, in the hope of developing new treatment approaches.