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

Objective: 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 with regard to wound healing. The study applied metabolomics to elucidate the TRP-l-KYN pathway associated with wound healing in chronic venous leg ulcers (CVLUs). Approach: 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 (nonhealed wounds). Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to analyze targeted metabolites. A Bayesian approach was used to examine robust correlations between changes in metabolite values and linear healing slope and to compare by group. Results: The mean age was 71.13 (±9.46 years). Half of the sample were female and the minority (17%) were Black. The mean values of evaluated metabolites for the nonhealed 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, credibility intervals [CrI] = -0.62, -0.04; probability of direction [PD] = 98%). Results suggest that KYN and TRP may be markers for healing in individuals with CVLUs. Innovation and Conclusion: 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.