Inflammation and colorectal cancer, when microbiota-host mutualism breaks

Abstract

Structural changes in the gut microbial community have been shown to accompany the progressive development of colorectal cancer. In this review we discuss recent hypotheses on the mechanisms involved in the bacteria-mediated carcinogenesis, as well as the triggering factors favoring the shift of the gut microbiota from a mutualistic to a pro-carcinogenic configuration. The possible role of inflammation, bacterial toxins and toxic microbiota metabolites in colorectal cancer onset is specifically discussed. On the other hand, the strategic role of inflammation as the keystone factor in driving microbiota to become carcinogenic is suggested. As a common outcome of different environmental and endogenous triggers, such as diet, aging, pathogen infection or genetic predisposition, inflammation can compromise the microbiota-host mutualism, forcing the increase of pathobionts at the expense of health-promoting groups, and allowing the microbiota to acquire an overall pro-inflammatory configuration. Consolidating inflammation in the gut, and favoring the bloom of toxigenic bacterial drivers, these changes in the gut microbial ecosystem have been suggested as pivotal in promoting carcinogenesis. In this context, it will become of primary importance to implement dietary or probiotics-based interventions aimed at preserving the microbiota-host mutualism along aging, counteracting deviations that favor a pro-carcinogenic microbiota asset.

Dietary inflammatory index and inflammatory gene interactions in relation to colorectal cancer risk in the Bellvitge colorectal cancer case–control study

“…Microbiota (Candela et al 2014) and a healthy diet (Wang et al 2012) play an important role in (Shivappa et al 2014b), and therefore, their inclusion in a dietary score is crucial to properly evaluate the complex association between diet-related inflammation and CRC risk.…”

Gut microbiota trajectory in pediatric patients undergoing hematopoietic SCT

“…14 Gut microbiome dysbioses are involved in several inflammatory disorders, such as inflammatory bowel diseases, allergy and type II diabetes, 15 further highlighting the importance of the mutualistic interaction between our microbial counterpart and the immune system that, if compromised, affects inflammation at a systemic level. 5,16,17 Acute GvHD (aGvHD) is an immunological disorder that affects many organ systems, including the gastrointestinal tract, liver and skin, 18 and represents the major immuno-mediated complication of hematopoietic SCT (HSCT), limiting its success. 19,20 In the light of the gut microbiota's potential to modulate the host systemic and local immunity, 16 the hypothesis that the maintenance of a mutualistic gut microbiota layout can be a strategic driver for preventing the onset of aGvHD has been advanced.…”

“…3 Moreover, the gut microbiota has a function in host immunity, being strategic to the education and preservation of our immune homeostasis. 4,5 Several key microbiota physiological functions depend on the supply of the host with pivotal microbial metabolic products, such as short-chain fatty acids (butyrate, propionate and acetate). As the final products of the gut microbiota fermentation of complex polysaccharides in the gut, short-chain fatty acids have been demonstrated to exert a central role in our physiology.…”

Potential markers for early diagnostics of Colorectal cancer and Inflammatory bowel disease in humans : intestinal microorganisms and immune system (teammates or rivals)

“…genes coding the tumor suppressors (adenomatous polyposis coli, β-catenin and p53), IBD, high consumption of red meat, obesity, diabetes, smoking, hard drinks, etc. In the past few years, predisposition factor has been mentioned frequently due to which the qualitative and quantitative composition of intestinal microbiome has also garnered much attention [7,11].…”

“…Every year, more than one million new cases are diagnosed with more than 600,000 deaths [7][8][9]. CRC is a serious problem for public health and is a significant socioeconomic burden [7].…”