Association of Tryptophan: Kynurenine Metabolites with Healing in Chronic Venous Leg Ulcers.

Abstract

Chronic wound healing is a complex process that is still not well understood. The tryptophan (TRP)-L-Kynurenine (KYN) pathway has recently been under increased scrutiny in regards to wound healing. The study applied metabolomics to elucidate the TRP-L- KYN pathway associated with wound healing in chronic venous leg ulcers (CVLUs). This study used a longitudinal comparative design of 60 serum samples collected from 30 older adult patients with CVLUs, receiving weekly sharp debridement at a wound clinic. The serum samples were collected at baseline and week 4 (healed wounds) or week 8 (non-healed wounds). Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to analyze targeted metabolites. A Bayesian approach was employed to examine robust correlations between changes in metabolite values and linear healing slope and to compare by group. The mean age was 71.13 (±9.46). Half of the sample were female and the minority (17%) were Black. The mean values of evaluated metabolites for the non-healed group were consistently lower than those for the healed group. The healed group (n=12) had higher KYN values; Those on a healing trajectory (n=23) had lower KYN levels and higher TRP levels at baseline and over time. There was moderate support (Bayes Factor = 3.70) for a negative association between change in Kynurenic Acid and linear healing slope (r = -0.35, CrI = -0.62, -0.04, PD= 98%). Results suggest KYN and TRP may be markers for healing in individuals with CVLUs. Gaining a better understanding of the associations between the TRP-L- KYN pathway and the healing of CVLUs may help to clarify the links of inflammation with the rate and success of wound healing. Biomarker development focused on the TRP-L- KYN pathway could be pursued, if the associations are further supported by focused research studies.