Abstract
Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. This review will summarize the current knowledge about the potential links between the intestinal microbiota and colorectal cancer, with a focus on the pro-carcinogenic properties of bacterial microbiota such as induction of inflammation, the biosynthesis of genotoxins that interfere with cell cycle regulation and the production of toxic metabolites. Finally, we will describe the potential therapeutic strategies based on intestinal microbiota manipulation for colorectal cancer treatment.
Highlights
Colorectal cancer (CRC) is the third most common cancer in both males and females with about 1.36 million of new cases per year and the fourth leading cause of cancer-related deaths worldwide with 700,000 deaths per year [1].CRC formation begins with the transformation of the normal epithelium mucosa into hyper-proliferative epithelium
Assessment of the tumor immune microenvironment showed that compared to the uninfected group, APCMin/+ mice infected with F. nucleatum exhibit enhanced proportion of myeloid-derived suppressor cells, which are tumor permissive myeloid cells, increased tumor-associated neutrophils, which are known to play a role in tumor progression, an enrichment of tumor-associated macrophages, which are known as promoters of carcinogenesis, and an increase in dendritic cells, which have a role in anti-tumor immunity [152]
Since gut microbiota can contribute to colorectal carcinogenesis, strategies targeting the gut microbiota have been proposed to prevent and treat CRC
Summary
Colorectal cancer (CRC) is the third most common cancer in both males and females with about 1.36 million of new cases per year and the fourth leading cause of cancer-related deaths worldwide with 700,000 deaths per year [1]. Other studies have linked the obesity-associated hormone leptin with the occurrence of CRC, as its expression is enhanced in CRC compared to normal colorectal epithelium and colorectal adenomas [25] In vitro, this adipokine is able to activate the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/AKT)/mammalian target of rapamycin (mTOR) signaling pathway and enhance proliferation and inhibit apoptosis of the human HCT116 colon cancer cells [26]. TLR2 deficiency leads to increased tumor development with higher pro-inflammatory mediators’ level in an AOM-DSS mouse model of inflammation-induced CRC [57]. Following AOM-DSS treatment, NOD1-deficient mice exhibit impaired interferon gamma (IFN-γ) production and increased inflammation-associated tumorigenesis compared to wild type mice [63] These data suggest a close link between inflammation and microbiota modulation during colorectal tumorigenesis
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