Metabolic Biosignatures of Lyme Disease in Human Urine
Abstract
Metabolomics has emerged as a powerful tool to study biochemical differences between specific diseases and healthy populations, and as a method to identify diagnostic or prognostic biomarkers for individual diseases. We have demonstrated that this is a viable approach for a novel non-antibody based laboratory diagnostic of early Lyme disease. The proposed research will capitalize on our previous findings to produce diagnostic metabolic biosignatures of early Lyme disease. This effort will be directed at urine as the clinical diagnostic sample for Lyme disease. Additionally, the metabolic pathways and metabolites that differ between multiple presentations of early Lyme disease will be elucidated. Thus, the proposed research directly addresses two of the FY17 TBDRP focus areas: (1) Diagnosis - biomarkers of diagnosis, prognosis, and cure; and (2) Pathogenesis - new research tools to support studies of pathogenesis. It is estimated that over 3 million diagnostic tests for Lyme disease occur each year. However, current laboratory diagnostics have major limitations for the early diagnosis of Lyme disease. Thus, there is a significant need for novel early diagnostic tests that facilitate rapid therapeutic intervention. The design of experiments to identify and apply a urine-based metabolic signature for the diagnosis of Lyme disease takes into account the heterogeneity of the LD patient population and non-Lyme disease patients that present to a clinic with symptoms similar to those of Lyme disease. We will target a diversity of early Lyme disease presentations that include erythema migrans positive and negative patients, and two-tier serology positive and negative patients. Additionally, we will study pediatric as well as adult Lyme disease patients. The direct impact of the proposed research will be the development of a novel diagnostic assay for Lyme disease that uses a noninvasive clinical sample and exploits instrumentation and approaches already applied in clinical diagnostic laboratories. We anticipate that by the end of the research period, a functional assay that uses urine as the clinical sample will be ready for testing and validation in a larger multi-center clinical study. The outcomes of this research will ultimately impact the treatment of Lyme disease patients by providing a novel and more accurate laboratory diagnostic test. Additionally, the research will provide understanding of the biology and biochemistry of Lyme disease that allow for metabolic profiling to be applied as an effective diagnostic tool. Large data collection technologies are rapidly transforming the approaches and resources available for health care. The application of metabolomics for the diagnosis of infectious diseases has only recently emerged but has proven to offer insights and tools that complement those of genomics, proteomics, and transcriptomics. Thus, the development of metabolomics-based approaches for the study and diagnosis of vector-borne infectious disease is expected to expand. This is directly pertinent to the U.S. military, since existing vector-borne diseases and the emergence of new diseases are a concern for troop readiness and deployment in areas endemic for vector-borne diseases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810458
Entities
People
- John T Belisle
Organizations
- Colorado State University
- United States Army