- Bacterial metabolites and colorectal cancer.
| Bacterial metabolites | Examples | Effect on CRC |
|---|---|---|
| SCFAs | Butyrate, propionate, and acetate | - Immunomodulation via regulation of AhR - Rebalance gut microbiota diversity and composition - Inhibit NF-kB and activate apoptosis - Antitumor effect via modulation of Tc17 cells and CTLs - Inhibit ERK1/2, causing tumor growth disruption - Induce ROS activity and decrease glucose oxidation - Induce HDAC |
| Bile acid | Primary and secondary bile acids | - Bind to FXR as CRC inhibitor - Promote cancer initiation by upregulating IL-8, ERK1/2, and inhibiting STAT3 phosphorylation - Activate MAPK pathway via upregulation of uPAR and calcium signaling |
| Lactate | - Creates an acidification environment - Stimulates angiogenic response to oxygen transfer, glucose delivery and nutrition delivery that promote CRC invasion, proliferation, and migration | |
| Succinate | - Inhibits CRC proliferation and induces CRC metastasis via SUCNR1 signaling | |
| Protein-derived metabolites | HO-PAA, PAA, phenol (produced from tyrosine), acetaldehyde, H2S, and NOCs | - Hydrogen sulfide inhibits the anti-inflammatory outcome in CRC cell lines by activating NF-kB pathway signaling - NOCs contribute to K-ras mutation, which drives CRC proliferation |
SCFAs: short-chain fatty acids, HO-PAA: 4-hydroxyphenylacetic acid, PAA: phenylacetic acid, H2S: hydrogen sulfide, NOCs: N-nitroso compounds, AhR: aryl hydrocarbon receptor, NF-kB: nuclear factor kappa B, Tc17: IL-17-secreting CD8 T cells), CTLs: cytotoxic T lymphocytes, ERK1/2: protein kinases 1 and 2, ROS: reactive oxygen species, HDAC: histone deacetylases, FXR: farnesoid X receptor, CRC: colorectal cancer, IL: interleukin, STAT3: Signal Transducer and Activator of Transcription 3, MAPK: mitogen-activated protein kinase, uPAR: urokinase plasminogen activator, SUCNR1: succinate receptor 1, K-ras: Kirsten rat sarcoma viral oncogene homolog