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

• DOI: 10.1186/s12866-020-01762-2
• Publication Date: 2020-04-22T23:05:02Z
• Authors: Qing Wang; Jianzhong Ye; Daiqiong Fang; Longxian Lv; Wenrui Wu; Ding Shi; Yating Li; Liya Yang; Xiaoyuan Bian; Jingjing Wu; Xianwan Jiang; Kaicen Wang; Qiangqiang Wang; Mark P. Hodson; Loïc M. Thibaut; Joshua W. K. Ho; Eleni Giannoulatou; Lanjuan Li
• Keywords: 0301 basic medicine; 570; Colon; Microbiology; 2726 Microbiology (medical); Epigenesis, Genetic; Mucosal microbiome; 03 medical and health sciences; Humans; Intestinal Mucosa; DNA methylation; Bacteria; Research; 2404 Microbiology; Butyrate; DNA Methylation; Colorectal cancer; QR1-502; Gastrointestinal Microbiome; 3. Good health; Gene Expression Regulation, Neoplastic; Butyrates; Reelin Protein; Metabolome; Colorectal Neoplasms; Transcriptome

AbstractBackgroundThe 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.ResultsWe 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 genusFusobacteriumabundance 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 familyHalomonadaceaewas correlated with the decreased expression of reelin (RELN). The decreased abundance of genusPaeniclostridiumand genusEnterococcuswere 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.ConclusionsOur 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.