Abstract
Metabolites detectible in human biofluids are attractive biomarkers for the diagnosis of early Lyme disease (ELD), a vector-borne infectious disease. Urine represents an easily obtained clinical sample that can be applied for diagnostic purposes. However, few studies have explored urine for biomarkers of ELD. In this study, metabolomics approaches were applied to evaluate small molecule metabolites in urine from patients with ELD (n = 14), infectious mononucleosis (n = 14) and healthy controls (n = 14). Metabolic biosignatures for ELD versus healthy controls and ELD versus infectious mononucleosis were generated using untargeted metabolomics. Pathway analyses and metabolite identification revealed the dysregulation of several metabolic processes in ELD as compared to healthy controls or mononucleosis, including metabolism of tryptophan. Linear discriminant analyses demonstrated that individual metabolic biosignatures can correctly discriminate ELD from the other patient groups with accuracies of 71 to 100%. These data provide proof-of-concept for use of urine metabolites as biomarkers for diagnostic classification of ELD.
Highlights
Lyme disease (LD) is the most commonly reported tick-borne illness in the United States, with 300,000 cases estimated to occur annually[1,2]
Comparative metabolomics analyses between early Lyme disease (ELD) and healthy controls (HC), as well as ELD and MONO resulted in metabolic biosignatures that accurately classified the patient groups used in this study
Those molecular features (MFs) with a ≥1.5-fold change between ELD and HC that met robustness and consistency criteria (Supplementary Fig. 1a) resulted in an ELD versus HC metabolic biosignature of 1,262 MFs detected in the positive-ion mode (Data File 1)
Summary
Lyme disease (LD) is the most commonly reported tick-borne illness in the United States, with 300,000 cases estimated to occur annually[1,2]. Insect-bite hypersensitivity reactions and conditions that result in an EM-like rash, including Southern Tick-Associated Rash Illness (STARI) and certain cutaneous fungal infections, can be confused with an EM skin lesion[3,8]. Infections such as infectious mononucleosis (MONO) can be clinically confused with LD. 3.4 million diagnostic tests for LD are performed annually nationwide on approximately 2.4 million specimens[1] This finding demonstrates that patients and physicians continue to seek laboratory confirmation of infection. Targeted analyses were performed to verify the identity of several MFs of altered pathways
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