Host Metabolic Response in Early Lyme Disease

Lyme
disease is a tick-borne bacterial illness that occurs in areas
of North America, Europe, and Asia. Early infection typically presents
as generalized symptoms with an erythema migrans (EM) skin lesion.
Dissemination of the pathogen Borrelia burgdorferi can result in multiple EM skin lesions or in extracutaneous manifestations
such as Lyme neuroborreliosis. Metabolic biosignatures of patients
with early Lyme disease can potentially provide diagnostic targets
as well as highlight metabolic pathways that contribute to pathogenesis.
Sera from well-characterized patients diagnosed with either early
localized Lyme disease (ELL) or early disseminated Lyme disease (EDL),
plus healthy controls (HC), from the United States were analyzed by
liquid chromatography–mass spectrometry (LC–MS). Comparative
analyses were performed between ELL, or EDL, or ELL combined with
EDL, and the HC to develop biosignatures present in early Lyme disease.
A direct comparison between ELL and EDL was also performed to develop
a biosignature for stages of early Lyme disease. Metabolic pathway
analysis and chemical identification of metabolites with LC-tandem
mass spectrometry (LC–MS/MS) demonstrated alterations of eicosanoid,
bile acid, sphingolipid, glycerophospholipid, and acylcarnitine metabolic
pathways during early Lyme disease. These metabolic alterations were
confirmed using a separate set of serum samples for validation. The
findings demonstrated that infection of humans with B. burgdorferi alters defined metabolic pathways
that are associated with inflammatory responses, liver function, lipid
metabolism, and mitochondrial function. Additionally, the data provide
evidence that metabolic pathways can be used to mark the progression
of early Lyme disease.