Metabolic Response in Patients With Post-treatment Lyme Disease Symptoms/Syndrome
Clinical Infectious Diseases
Fitzgerald BL, Graham B, Delorey MJ, Pegalajar-Jurado A, Islam MN, Wormser GP, Aucott JN, Rebman AW, Soloski MJ, Belisle JT, Molins CR
Background: Post-treatment Lyme disease symptoms/syndrome (PTLDS) occurs in approximately 10% of Lyme disease patients following antibiotic treatment. Biomarkers or specific clinical symptoms to identify PTLDS patients do not currently exist and the PTLDS classification is based on the report of persistent, subjective symptoms for ? 6 months following antibiotic treatment for Lyme disease.
Methods: Untargeted liquid chromatography-mass spectrometry metabolomics was used to determine longitudinal metabolic responses and biosignatures in PTLDS and clinically cured non-PTLDS Lyme patients. Evaluation of biosignatures included: 1) defining altered classes of metabolites; 2) elastic net regularization to define metabolites that most strongly defined PTLDS and non-PTLDS patients at different timepoints; 3) changes in the longitudinal abundance of metabolites; 4) linear discriminant analysis to evaluate robustness in a second patient cohort.
Results: This study determined that observable metabolic differences exist between PTLDS and non-PTLDS patients at multiple timepoints. The metabolites with differential abundance included those from glycerophospholipid, bile acid and acylcarnitine metabolism. Distinct longitudinal patterns of metabolite abundance indicated a greater metabolic variability in PTLDS vs non-PTLDS patients. Small numbers of metabolites (6-40) could be used to define PTLDS vs. non-PTLDS patients at defined time points, and the findings were validated in a second cohort of PTLDS and non-PTLDS patients.
Conclusions: These data provide evidence that an objective metabolite-based measurement can distinguish patients with PTLDS and help understand the underlying biochemistry of PTLDS.