Diet, Microbiota, and Colorectal Cancer

Abstract

The intestinal epithelium is a very dynamic tissue under a high regenerative pressure, which makes it susceptible to malignant transformation. Proper integration of various cell signaling pathways and a balanced cross talk between different cell types composing the organ are required to maintain intestinal homeostasis. Dysregulation of this balance can lead to colorectal cancer (CRC). Here, we review important insights into molecular and cellular mechanisms of CRC. We discuss how perturbation in complex regulatory networks, including the Wnt, Notch, BMP, and Hedgehog pathways; and how variations in inflammatory signaling, nutrients, and microbiota can affect intestinal homeostasis contributing to the malignant transformation of intestinal cells. INTESTINE STRUCTURE AND FUNCTION The intestine is the last part of the gastrointestinal tract, and is divided into two anatomically and functionally different sections: the small intestine and the large intestine, whose main functions are food digestion, stool compaction, and absorption of water, nutrients, and salts. Both the small and large intestines present an outer layer of smooth muscle with enteric nervous system; a middle layer composed of connective tissue, nerves, and lymphatic vessels; and an inner epithelial layer called the mucosa. The small intestine presents epithelial folds resembling finger-like protrusions called villi, which face the lumen and aim to maximize the available absorptive area. Villi are surrounded by epithelial invaginations that form the crypts of Lieberkü hn (Figure 1). In contrast, the colonic epithelium lacks villi and consists of a plane surface with multiple epithelial invaginations forming the crypts (

Sucralose Promotes Colitis-Associated Colorectal Cancer Risk in a Murine Model Along With Changes in Microbiota

“…Studies have shown that even the same species of gut bacteria may have different impacts. For instance, the enterotoxigenic strain of B. fragilis may serve as a trigger for colitis and tumorigenesis, while the non-toxigenic strain of B. fragilis may serve as an antiinflammatory probiotic and protect against colitis and CRC (11). Thus, it remains a formidable task to elucidate the association between dysbiosis of gut bacteria and diseases.…”

“…Intriguingly, inflammatory bowel disease (IBD), a devastating inflammatory disease of the gut, is also very high in developed countries (6,7), and IBD greatly increased the risk of CRC with a hazard ratio as high as 33.3 (5), suggesting a likely intimate link between CRC and IBD (8)(9)(10). Recently, dysbiosis of microbiota in the development of IBD and CRC has drawn more and more attention (11)(12)(13)(14)(15). Accumulating evidence suggests that dysbiosis of gut microbiota, gut inflammation, and CRC may have intimate interaction and connection.…”

“…Not surprisingly, diet, not only in terms of nutrients but also of dietary chemicals, may have a huge impact on gut microbiota (11,14,15). In fact, it has been long proposed that food additives such as saccharin and sucralose may have played an important causative role in IBD due to their inhibition of gut bacteria and the resultant impaired inactivation of digestive proteases by deconjugated bilirubin through the action of bacterial βglucuronidase (18,19).…”

The Impact of Diet on the Involvement of Non-Coding RNAs, Extracellular Vesicles, and Gut Microbiome-Virome in Colorectal Cancer Initiation and Progression

“…mTORC1 is a nutrient sensor that influences cell growth and proliferation in-vivo . Nutrients, stress signals such as hypoxia and glucose deprivation, growth factors (GFs) as well as cellular energy status are upstream signals that impact on mTORC1 activity ( 143 ). The activity of mTOR1 is essentially dependent on the integration of GF and nutrient signals.…”

“…The activity of mTOR1 is essentially dependent on the integration of GF and nutrient signals. The activation of mTORC1 impact on cellular processes, including nucleotide, protein, and lipid synthesis, cellular metabolism such as ATP production, and autophagy, thereby functioning to maintain balance between anabolic and catabolic processes ( 143 ). Activities such as translational machinery that promotes growth and proliferation through the phosphorylation of ribosomal protein S6 kinase (S6K) and the eukaryotic translation initiation factor 4E(elF4E)-binding protein (4EBP).…”