There is considerable evidence linking colorectal cancer (CRC) progression with shifts in the metabolic output of the gut microbiome. To quantify these changes, Sun and colleagues performed in-depth analysis of fecal and plasma metabolites from 111 healthy individuals, 119 CRC patients, and 143 individuals with premalignant colorectal adenoma. This revealed key metabolites that are specifically enriched (e.g., oleic acid) or depleted (e.g., allocholic acid) in CRC. Experiments with cultured cells, patient-derived organoids and murine models demonstrated that those metabolites bind to tumor cell receptors to modulate downstream oncogenic pathways. The authors also developed a panel of 17 serum metabolites that accurately discriminated patients with different stages of CRC. This panel was validated in three other cohorts totaling 878 healthy individuals and CRC or adenoma patients, which has potential for earlier intervention through minimally-invasive testing.
Sun Y,...