Multi-omic profiling reveals associations between the gut mucosal microbiome, the metabolome, and host DNA methylation associated gene expression in patients with colorectal cancer

BMC Microbiology

article

Wang, Qing¹  Wu, Jingjing¹  Jiang, Xianwan¹  Wang, Kaicen¹  Wang, Qiangqiang¹  Hodson, Mark P.⁴  Thibaut, Loïc M.³  Ho, Joshua W. K.⁷  Giannoulatou, Eleni³  Li, Lanjuan¹  Ye, Jianzhong¹  Fang, Daiqiong¹  Lv, Longxian¹  Wu, Wenrui¹  Shi, Ding¹  Li, Yating¹  Yang, Liya¹  Bian, Xiaoyuan¹ 

[1]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University

[2]Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases

[3]Computational Genomics Laboratory, Victor Chang Cardiac Research Institute

[4]Freedman Foundation Metabolomics Facility, Victor Chang Innovation Centre, Victor Chang Cardiac Research Institute

[5]School of Pharmacy, University of Queensland

[6]School of Mathematics and Statistics

[7]Bioinformatics and Systems Medicine Laboratory, Victor Chang Cardiac Research Institute

[8]School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong

[9]St Vincent’s Clinical School

关键词: Colorectal cancer;    Mucosal microbiome;    Metabolome;    Transcriptome;    DNA methylation;    Butyrate;   

DOI  :  10.1186/s12866-020-01762-2

学科分类：放射科、核医学、医学影像

来源: BioMed Central

【 摘 要 】

The human gut microbiome plays a critical role in the carcinogenesis of colorectal cancer (CRC). However, a comprehensive analysis of the interaction between the host and microbiome is still lacking. We found correlations between the change in abundance of microbial taxa, butyrate-related colonic metabolites, and methylation-associated host gene expression in colonic tumour mucosa tissues compared with the adjacent normal mucosa tissues. The increase of genus Fusobacterium abundance was correlated with a decrease in the level of 4-hydroxybutyric acid (4-HB) and expression of immune-related peptidase inhibitor 16 (PI16), Fc Receptor Like A (FCRLA) and Lymphocyte Specific Protein 1 (LSP1). The decrease in the abundance of another potentially 4-HB-associated genus, Prevotella 2, was also found to be correlated with the down-regulated expression of metallothionein 1 M (MT1M). Additionally, the increase of glutamic acid-related family Halomonadaceae was correlated with the decreased expression of reelin (RELN). The decreased abundance of genus Paeniclostridium and genus Enterococcus were correlated with increased lactic acid level, and were also linked to the expression change of Phospholipase C Beta 1 (PLCB1) and Immunoglobulin Superfamily Member 9 (IGSF9) respectively. Interestingly, 4-HB, glutamic acid and lactic acid are all butyrate precursors, which may modify gene expression by epigenetic regulation such as DNA methylation. Our study identified associations between previously reported CRC-related microbial taxa, butyrate-related metabolites and DNA methylation-associated gene expression in tumour and normal colonic mucosa tissues from CRC patients, which uncovered a possible mechanism of the role of microbiome in the carcinogenesis of CRC. In addition, these findings offer insight into potential new biomarkers, therapeutic and/or prevention strategies for CRC.

【 授权许可】

CC BY|CC0