https://orcid.org/0000-0002-7580-3639
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ABSTRACT
Trillions of microbes are indigenous to the human gastrointestinal tract, together forming an ecological community known as the gut microbiota. The gut microbiota is involved in dietary digestion to produce various metabolites. In healthy condition, microbial metabolites have unneglectable roles in regulating host physiology and intestinal homeostasis. However, increasing studies have reported the correlation between metabolites and the development of colorectal cancer (CRC), with the identification of oncometabolites. Meanwhile, metabolites can also influence the efficacy of cancer treatments. In this review, metabolites derived from microbes-mediated metabolism of dietary carbohydrates, proteins, and cholesterol, are introduced. The roles of pro-tumorigenic (secondary bile acids and polyamines) and anti-tumorigenic (short-chain fatty acids and indole derivatives) metabolites in CRC development are then discussed. The impacts of metabolites on chemotherapy and immunotherapy are further elucidated. Collectively, given the importance of microbial metabolites in CRC, therapeutic approaches that target metabolites may be promising to improve patient outcome.
Disclosure statement
No potential conflict of interest was reported by the authors.
Abbreviations
| AhR | = | Aryl hydrocarbon receptor |
| AUC | = | Area under the curve |
| CRC | = | Colorectal cancer |
| DCA | = | Deoxycholic acid |
| FFAR2 | = | Free fatty acid receptor 2 |
| 5-FU | = | 5-Fluorouracil |
| ICIs | = | Immune checkpoint inhibitors |
| IFN | = | Interferon |
| IL | = | Interleukin |
| isoDCA | = | 3β-Hydroxydeoxycholic acid |
| NK | = | Natural killer |
| Th | = | Helper T cells |
| Treg | = | Regulatory T cells |
| SBAs | = | Secondary bile acids |
| SCFAs | = | Short-chain fatty acids |
| TMAO | = | Trimethylamine N-oxide |
| TME | = | Tumor microenvironment |
Author contributions
YL researched data for the article, designed the figures, and wrote the manuscript. HCHL revised the figures and manuscript. JY supervised the study and revised the figures and manuscript.
Data availability statement
Data is available within the article or its supplementary materials.