Alterations in the Gut Microbiota and Their Metabolites in Colorectal Cancer: Recent Progress and Future Prospects

Abstract

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. The etiology and pathogenesis of CRC remain unclear. A growing body of evidence suggests dysbiosis of gut bacteria can contribute to the occurrence and development of CRC by generating harmful metabolites and changing host physiological processes. Metabolomics, a systems biology method, will systematically study the changes in metabolites in the physiological processes of the body, eventually playing a significant role in the detection of metabolic biomarkers and improving disease diagnosis and treatment. Metabolomics, in particular, has been highly beneficial in tracking microbially derived metabolites, which has substantially advanced our comprehension of host-microbiota metabolic interactions in CRC. This paper has briefly compiled recent research progress of the alterations of intestinal flora and its metabolites associated with CRC and the application of association analysis of metabolomics and gut microbiome in the diagnosis, prevention, and treatment of CRC; furthermore, we discuss the prospects for the problems and development direction of this association analysis in the study of CRC. Gut microbiota and their metabolites influence the progression and causation of CRC, and the association analysis of metabolomics and gut microbiome will provide novel strategies for the prevention, diagnosis, and therapy of CRC.

New Insights into Bile Acids Related Signaling Pathways in the Onset of Colorectal Cancer

“…Studies back to the 1970s have highlighted that the risk for developing CRC was much higher among Japanese people who switched from a low-fiber to a high-fat ‘Western’ diet after immigration to the United States [ 86 , 87 ]. Since then, the prevalence of unhealthy dietary lifestyles has been linked to a dysregulation of gut microbiota [ 88 ], raising the incidence of CRC worldwide [ 89 ]. Specifically, both the dysbiosis of the resident gut microbiota (rather than simply certain pathogens), as well as the reduction in several helpful gut microbiota metabolites, such as short-chain fatty acids (SCFAs), have been shown to significantly alter the cancer risk or progression by causing immune response abnormalities [ 88 ].…”

“…This model incorporates a novel aggregate environmental risk score (ERS) and a recently expanded polygenic risk score (PRS) and allows for identifying individuals at differential relative and absolute risk for early onset CRC [ 90 ]. Indeed, CRC may be related to several factors: immunity, environment, dietary habits, and more general lifestyle, all involved in the microbiota composition [ 91 ]; recently it has been proposed that CRC is essentially a genetic disease, as well as a microbiological disease [ 88 ].…”

Molecular Underpinnings and Environmental Drivers of Spontaneous Loss of Heterozygosity in Drosophila Intestinal Stem Cells

“…It is possible that roles in translation or subtle differences in stem cell viability may preclude detections of changes in LOH frequency in Pe conditions. In humans, inflammatory bowel disease and colorectal cancer have been linked to alteration of the microbiome [76][77][78]. In particular, the NC101 strain of Escherichia coli causes DNA damage [79], and creates a specific mutational signature [80].…”

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

“…Bacteria, fungi, and viruses constitute the microbiota residing within the gastrointestinal tract. However, the gut microbiota and their metabolites can be altered in the TME and directly influence CRC progression[ 93 , 94 ]. Various bacteria have been implicated in these processes by modulating the β-catenin pathway.…”