Contribution of Epithelial and Gut Microbiome Inflammatory Biomarkers to the Improvement of Colorectal Cancer Patients’ Stratification

Abstract

In order to ensure that primary endpoints of clinical studies are attained, the patients’ stratification is an important aspect. Selection criteria include age, gender, and also specific biomarkers, such as inflammation scores. These criteria are not sufficient to achieve a straightforward selection, however, in case of multifactorial diseases, with unknown or partially identified mechanisms, occasionally including host factors, and the microbiome. In these cases, the efficacy of interventions is difficult to predict, and as a result, the selection of subjects is often random. Colorectal cancer (CRC) is a highly heterogeneous disease, with variable clinical features, outcomes, and response to therapy; the CRC onset and progress involves multiple sequential steps with accumulation of genetic alterations, namely, mutations, gene amplification, and epigenetic changes. The gut microbes, either eubiotic or dysbiotic, could influence the CRC evolution through a complex and versatile crosstalk with the intestinal and immune cells, permanently changing the tumor microenvironment. There have been significant advances in the development of personalized approaches for CRC screening, treatment, and potential prevention. Advances in molecular techniques bring new criteria for patients’ stratification—mutational analysis at the time of diagnosis to guide treatment, for example. Gut microbiome has emerged as the main trigger of gut mucosal homeostasis. This may impact cancer susceptibility through maintenance of the epithelial/mucus barrier and production of protective metabolites, such as short-chain fatty acids (SCFAs) via interactions with the hosts’ diet and metabolism. Microbiome dysbiosis leads to the enrichment of cancer-promoting bacterial populations, loss of protective populations or maintaining an inflammatory chronic state, all of which contribute to the development and progression of CRC. Meanwhile, variations in patient responses to anti-cancer immuno- and chemotherapies were also linked to inter-individual differences in intestine microbiomes. The authors aim to highlight the contribution of epithelial and gut microbiome inflammatory biomarkers in the improvement of CRC patients’ stratification towards a personalized approach of early diagnosis and treatment.

The connection between epigenetics and gut microbiota‐current perspective

“…Moreover, the pathogenesis of AD is associated with Proteobacteria , Bacteroidetes , Firmicutes , Escherichia coli , Actinobacteria , Verrucomicrobia , and Tenericutes . The metabolites of these microbes through inflammations such as neuroinflammation, cytokine storm syndrome, amyloid deposition, altered N ‐methyl‐ d ‐aspartate and brain‐derived neurotrophic factor play a crucial role in pathogenesis of AD 84 . The aberrant epigenetic alterations and the imbalance GM aid in the initiation of CRC 85,86 .…”

“…The metabolites of these microbes through inflammations such as neuroinflammation, cytokine storm syndrome, amyloid deposition, altered N-methyl-Daspartate and brain-derived neurotrophic factor play a crucial role in pathogenesis of AD. 84 The aberrant epigenetic alterations and the imbalance GM aid in the initiation of CRC. 85,86 The genetic expression is switched to an alternative pathway through the alteration of GM.…”

Prevention of malignant digestive system tumors should focus on the control of chronic inflammation

“…However, complex reasons behind this reflect both population ageing and global population growth, as well as changes in the prevalence and distribution of major cancer risk factors. The study found that in countries undergoing major transitions, such as Eastern Europe, Southern Europe, Central and South Asia, and South America, incidence tends to increase consistently with the human development index[ 55 ].…”