BACKGROUND & AIMS: Short chain fatty acid (SCFAs) are bacterially derived metabolites suggested to have protective roles against colorectal cancer (CRC) development. However, there is sparse evidence from epidemiological studies in this context. Here, we assessed whether circulating SCFA concentrations varied in patients with colorectal adenomas (CRA) and CRC. METHODS: Levels of seven SCFAs were extracted from plasma samples and determined by gas chromatography for 213 individuals from Ireland and the Czech Republic (CRC, n = 84; CRA, n = 66; controls, n = 63). RESULTS: In the Irish CRA/CRC cohort, only levels of 2-MethylButyric acid were significantly higher in cancers compared to the adenoma and control groups (p-values = 0.016 and 0.043). Using regression analysis, we observed that levels of Acetic and Propionic acid were associated with an increased CRC risk in the Czech cohort (Odd Ratio (OR): 1.02; 95% Confidence interval (CI): 1.00-1.03; OR: 1.29; 95% CI: 1.05-1.59, respectively), while i-Valeric and Valeric acid levels were associated with a decreased cancer risk (OR: 0.92; 95% CI: 0.86-0.99; OR: 0.67; 95% CI: 0.44-1.00). In the Irish cohort, levels of SCFAs were not associated with CRC risk. CONCLUSIONS: The association with colorectal neoplasia varied between the studied SCFAs. Future studies need to confirm these findings and address the mechanism of how these acids may promote or prevent colorectal carcinogenesis.
