Chronic Diabetic Wounds: Longitudinal Profiling of the Evolving Microbiome and Metabolic Landscape in Diabetic Patients
Authors: Ammons Mary Cloud Bosworth , Fuchs Amanda L , Tripet Brian P , Copie Valerie , Weaver Alan J , Braaksma Amy , Johnson Eric , Yeoman Carl 
Published: November 2023

Treatment of chronic, diabetic ulcers is a major socioeconomic burden with an estimated $58 billion annually in medical costs. Chronic, non‐healing ulcers contribute significantly to the suffering of diabetic patients with mild to severely compromised immune systems and result in nearly a quarter of diabetics enduring at least one limb amputation within their lifetime. The American Diabetes Association estimates that by 2050 there will be over 350 million diabetics in the United States correlating to nearly 80 million diabetics with at least a single limb amputation as the result of a non‐healing ulcer. While wound healing in a healthy individual proceeds through a well‐described process, in diabetic ulcers this process becomes dysregulated and stalls at the inflammatory stage. Colonizing bacteria biofilms are a major contributor to delayed healing; however how the metabolic phenotype of a colonizing biofilm influences the wound healing process remains unknown. This gap in knowledge inhibits the development of effective treatment protocols, resulting in amputation being the current standard of care. Our preliminary research indicated that specific metabolic traits (metabotypes) are associated with the microbiome in the wound environment (Ammons, et al 2015). To address the need for evidence‐based protocols, we seek to develop a statistical algorithm of diagnostic and prognostic indicators that can be incorporated into a treatment management plan executed at the bedside by nursing staff. This project utilized a longitudinal, systems biology approach to understand metabolic changes in the evolution of chronic wounds using debridement samples collected from patients at the Wound Clinic, Bozeman Deaconess Hospital. 1H NMR metabolic profiling studies revealed diagnostic changes in the metabolic landscape over time, and reflected bacterial investment in secondary metabolism. 16s rRNA sequencing was used to capture the evolving microbiome and demonstrated a clear shift in predominate species that correlated to treatment protocols. Integration of the microbiome and metabolome profiles with the metadata derived from electronic medical records lays the foundation for developing quantitative algorithms that complement symptom assessments for patient‐centered, evidence‐based treatment protocols. In addition to identifying the evolving metabolomic and microbiome biomarkers that correlate to development of chronic diabetic ulcers, these studies uncover the biochemical relationship at the root of host‐pathogen interactions within the chronic diabetic ulcers and provide knowledge that could be used in developing novel therapeutics. These studies lay the foundation for innovative treatment protocols to complement the clinical toolbox of wound care nurses facing the growing concern of chronic diabetic ulcers.Support or Funding InformationThis research was supported in part by the Office of the Vice President for Research and Economic Development, Montana State University (to M.C.B.A. and B.P.T.); NIH grant 1K01GM103821 (to M.C.B.A.); NIH grant 16‐746Q‐MSU‐PG51‐00, a sub award to CTRIN IDeA‐CTR 5U54GM104944‐03 (to M.C.B.A. and B.P.T.).