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Role of gut microbiota in epigenetic regulation of colorectal Cancer.

ABSTRACT: Colorectal cancer (CRC) remains one of the most commonly diagnosed cancers and a leading cause of cancer-related deaths worldwide. The stepwise accumulation of epigenetic alterations in the normal colorectal epithelium has been reported to act as a driving force for the initiation and promotion of tumorigenesis in CRC. From a mechanistic standpoint, emerging evidence indicates that within the colorectal epithelium, the diverse gut microbiota can interact with host cells to regulate multiple physiological processes. In fact, recent studies have found that the gut microbiota represents a potential cause of carcinogenesis, invasion, and metastasis via DNA methylation, histone modifications, and non-coding RNAs - providing an epigenetic perspective for the connection between the gut microbiota and CRC. Herein, we comprehensively review the recent research that provides a comprehensive yet succinct evidence connecting the gut microbiota to CRC at an epigenetic level, including carcinogenic mechanisms of cancer-related microbiota, and the potential for utilizing the gut microbiota as CRC biomarkers. These scientific findings highlight a promising future for manipulating the gut microbiota to improve clinical outcomes in patients suffering from CRC.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC7856101 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Role of gut microbiota in epigenetic regulation of colorectal Cancer.

Zhao Yinghui Y Wang Chuanxin C Goel Ajay A

Biochimica et biophysica acta. Reviews on cancer 20201213 1

Colorectal cancer (CRC) remains one of the most commonly diagnosed cancers and a leading cause of cancer-related deaths worldwide. The stepwise accumulation of epigenetic alterations in the normal colorectal epithelium has been reported to act as a driving force for the initiation and promotion of tumorigenesis in CRC. From a mechanistic standpoint, emerging evidence indicates that within the colorectal epithelium, the diverse gut microbiota can interact with host cells to regulate multiple phys ...[more]

PMID: 33321173

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Project description:BackgroundAging is one of the factors leading to cancer. Gut microbiota is related to aging and colorectal cancer (CRC).MethodsA total of 11 metagenomic data sets related to CRC were collected from the R package curated Metagenomic Data. After batch effect correction, healthy individuals and CRC samples were divided into three age groups. Ggplot2 and Microbiota Process packages were used for visual description of species composition and PCA in healthy individuals and CRC samples. LEfSe analysis was performed for species relative abundance data in healthy/CRC groups according to age. Spearman correlation coefficient of age-differentiated bacteria in healthy individuals and CRC samples was calculated separately. Finally, the age prediction model and CRC risk prediction model were constructed based on the age-differentiated bacteria.ResultsThe structure and composition of the gut microbiota were significantly different among the three groups. For example, the abundance of Bacteroides vulgatus in the old group was lower than that in the other two groups, the abundance of Bacteroides fragilis increased with aging. In addition, seven species of bacteria whose abundance increases with aging were screened out. Furthermore, the abundance of pathogenic bacteria (Escherichia_coli, Butyricimonas_virosa, Ruminococcus_bicirculans, Bacteroides_fragilis and Streptococcus_vestibularis) increased with aging in CRCs. The abundance of probiotics (Eubacterium_eligens) decreased with aging in CRCs. The age prediction model for healthy individuals based on the 80 age-related differential bacteria and model of CRC patients based on the 58 age-related differential bacteria performed well, with AUC of 0.79 and 0.71, respectively. The AUC of CRC risk prediction model based on 45 disease differential bacteria was 0.83. After removing the intersection between the disease-differentiated bacteria and the age-differentiated bacteria from the healthy samples, the AUC of CRC risk prediction model based on remaining 31 bacteria was 0.8. CRC risk prediction models for each of the three age groups showed no significant difference in accuracy (young: AUC=0.82, middle: AUC=0.83, old: AUC=0.85).ConclusionAge as a factor affecting microbial composition should be considered in the application of gut microbiota to predict the risk of CRC.

Dataset Information

Role of gut microbiota in epigenetic regulation of colorectal Cancer.

Publications

Role of gut microbiota in epigenetic regulation of colorectal Cancer.

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