Preoperative plasma short- and branched-chain fatty acids in relation to risk of complications after colorectal cancer surgery: a prospective cohort study

BACKGROUND: Emerging evidence suggests that nutritional prehabilitation reduces risk of complications after colorectal cancer (CRC) surgery. The gut microbiota and its metabolic activity potentially link preoperative diet to postoperative outcomes. OBJECTIVE: To investigate associations between preoperative plasma levels of microbial-derived metabolites and postoperative complications in patients with CRC. METHODS: We used data from a prospective cohort study among 1220 patients with nonmetastatic CRC. The short-chain fatty acids (SCFAs) acetate, propionate, butyrate, and valerate, as well as the branched-chain fatty acids (BCFAs) isovalerate, isobutyrate, and α-methylbutyrate, were measured in plasma collected at diagnosis. Prevalence ratios (PR) were calculated using regression models adjusted for age, sex, tumor location, smoking status, and physical health status. RESULTS: Acetate levels of 40.0 μmol/L were associated with a lower risk of any postoperative complications compared with the reference of 20.0 μmol/L PR: 0.76; 95% confidence interval (CI): 0.62, 0.93. Higher levels of propionate (per 1 μmol/L) were associated with a lower risk of any complications (PR: 0.84; 95% CI: 0.73, 0.96). Similar associations were found for acetate (per 20 μmol/L) and propionate (per 1 μmol/L) in relation to surgical complications (PR: 0.75; 95% CI: 0.60, 0.93; and PR: 0.83; 95% CI: 0.69, 1.00; respectively). No associations were found for BCFAs in relation to complications. Low (below median) total SCFA levels combined with high (above median) total BCFA levels were least favorable in terms of complication risk (PR: 1.35; 95% CI: 1.02, 1.80) when compared with a low SCFA/low BCFA profile. CONCLUSIONS: Our findings suggest that microbial fermentation processes, mainly those resulting in higher SCFA levels, may be linked to postoperative recovery. These findings provide leads for future studies investigating the role of preoperative diet, especially the balance between fiber and protein intake, and microbial metabolism in relation to postoperative recovery of patients with CRC. This study was registered at clinicaltrials.gov with registration number NCT03191110.