Plasma concentrations of gut microbial tryptophan metabolites and risk of complications after colorectal cancer surgery

Abstract Background The gut microbiota has been linked to complications after colorectal cancer (CRC) surgery. The essential amino acid tryptophan is metabolized by the gut microbiota, resulting in the production of indole metabolites. Some of these microbial tryptophan metabolites have been shown to benefit gut health and hence may support recovery after CRC surgery; however, clinical studies confirming this hypothesis are lacking. Here, we investigate whether preoperative plasma concentrations of indole metabolites are associated with risk of postoperative complications and length of hospital stay in patients with CRC. Methods Data are used from a prospective cohort study among 1222 patients with non-metastatic CRC. Plasma concentrations of 3-indoxyl sulfate (3IS), indole-3-acetamide (IAM), indole-3-acetate (IAA), indole-3-lactate (ILA), indole-3-aldehyde (IAld), and indole-3-propionate (IPA) were measured at diagnosis. Multivariable-adjusted regression models were assessed for indole metabolites in relation to postoperative complications and length of hospital stay. Results Higher concentrations of IAM and IPA are associated with a lower risk of complications (RR per2nmol/L 0.89; 95%CI 0.82, 0.97; and RR per1μmol/L 0.88; 95%CI 0.78, 0.98; respectively). Higher concentrations of IPA are also associated with a shorter hospital stay (beta per1μmol/L −0.6; 95%CI −1.4, 0.1), while higher 3IS concentrations are associated with a longer hospital stay (beta 14.1versus3.7μmol/L 2.2; 95%CI 0.1, 4.4). Higher preoperative intake of dietary fiber is associated with higher concentrations of IAM and IPA, while higher intake of protein is associated with lower concentrations of IPA. Conclusions Our findings provide potential leads for further studies aiming at modulation of gut microbial tryptophan metabolism to support postoperative recovery after CRC surgery.