Microbial Metabolites in Colorectal Cancer: Basic and Clinical Implications

Abstract

Colorectal cancer (CRC) is one of the leading cancers that cause cancer-related deaths worldwide. The gut microbiota has been proved to show relevance with colorectal tumorigenesis through microbial metabolites. By decomposing various dietary residues in the intestinal tract, gut microbiota harvest energy and produce a variety of metabolites to affect the host physiology. However, some of these metabolites are oncogenic factors for CRC. With the advent of metabolomics technology, studies profiling microbiota-derived metabolites have greatly accelerated the progress in our understanding of the host-microbiota metabolism interactions in CRC. In this review, we briefly summarize the present metabolomics techniques in microbial metabolites researches and the mechanisms of microbial metabolites in CRC pathogenesis, furthermore, we discuss the potential clinical applications of microbial metabolites in cancer diagnosis and treatment.

Colorectal Cancer Stage-Specific Fecal Bacterial Community Fingerprinting of the Taiwanese Population and Underpinning of Potential Taxonomic Biomarkers

“…There are substantial reports that the general gut microbiota is associated with the initiation and progression of CRC through the production of carcinogens, cocarcinogens, or procarcinogen substances [ 29 ]. The direct interaction of gut microbes with the epithelial cells is limited due to the presence of mucosal barriers [ 31 ]. However, these microbes convert the complex chemicals provided by the host and dietary nutrients into a milieu metabolite which can be easily translocated across the mucosal barrier and play a role in tumorigenesis through multiple mechanisms, such as modifying signaling proteins [ 28 , 31 ].…”

“…The direct interaction of gut microbes with the epithelial cells is limited due to the presence of mucosal barriers [ 31 ]. However, these microbes convert the complex chemicals provided by the host and dietary nutrients into a milieu metabolite which can be easily translocated across the mucosal barrier and play a role in tumorigenesis through multiple mechanisms, such as modifying signaling proteins [ 28 , 31 ]. In previous studies, it has been demonstrated that the elevated gut microbes derived from secondary bile acids, such as deoxycholic acid, promote the development and progression of CRC [ 32 , 33 ].…”

Microbiome-Mediated Immune Signaling in Inflammatory Bowel Disease and Colorectal Cancer: Support From Meta-omics Data

“…They are present at high levels in the GI tract, where they enable rapid turnover of intestinal epithelial cells and regulate specific eukaryotic gene expression among many other functions. For many decades now, polyamines have been implicated in tumorigenesis, including CRC ( Gerner and Meyskens, 2004 ; Peng et al, 2021 ), due to their essential role in cell proliferation. Bacterial TMA production has also been linked to the consumption of red meat (a source of carnitine) and cardiovascular disease ( Koeth et al, 2014 ).…”

“…In healthy states, primary bile acids (BAs), including cholate and chenodeoxycholate, are synthesized from cholesterol in the liver and conjugated with glycine or taurine before excretion. The majority of primary BAs are reabsorbed in the ileum; however, a small proportion (approximately 5%) enter the colon where they are deconjugated and converted to secondary BAs, including deoxycholic acid and lithocholic acid, respectively, by the microbiota ( Peng et al, 2021 ). Dominant members of the healthy stool microbiome ( Human Microbiome Project Consortium, 2012 ), namely Firmicutes (including Clostridium spp., Ruminococcus gnavus and Faecalibacterium prausnitzii ) and Bacteroidetes, are potent BA deconjugators and secondary BA transformation is attributed to metabolic activity by the genera Bacteroides, Clostridium, Eubacterium, Lactobacillus , and Escherichia ( Duboc et al, 2013 ; Jia et al, 2018 ).…”

Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization

“…Advancement of analytical techniques such as nuclear magnetic resonance (NMR) has enabled the quantitative identification of a wide range of metabolites using a very small volume of sample [ 14 ]. Metabolic profiling was already applied to the study of cancer biology [ 15 , 16 , 17 , 18 ], also with the aim of identifying potential predictive disease biomarkers. A recent study already identified potential biomarkers of AK through integrated metabolomics and histopathological analysis, with the aim of investigating the effects of the field cancerization treatment [ 19 ].…”