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

Authors

• Junglyun Kim, Chungnam National University
• Joyce Stechmiller, University of Florida College of Nursing
• Michael T. Weaver, University of Florida College of Nursing
• Debra Lyon, University of Florida College of Nursing
• Timothy J. Garrett, University of Florida College of Medicine
• Fan Yi, University of Idaho
• Jungmin C. Park, University of Florida College of Nursing
• Magali R. De Carvalho, University of Florida College of Nursing
• Debra Lynch Kelly, University of Florida College of Nursing

Abstract

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.

Publication Title

Advances in Wound Care

Recommended Citation

Kim, J., Stechmiller, J., Weaver, M., Lyon, D., Garrett, T., Yi, F., Park, J., De Carvalho, M., & Kelly, D. (2024). Association of Tryptophan/Kynurenine Metabolites with Healing in Chronic Venous Leg Ulcers. Advances in Wound Care, 13 (10), 494-507. https://doi.org/10.1089/wound.2023.0137