Abstract

Borrelia burgdorferi (Bb) is the spirochete that causes Lyme disease (LD). Transmission to humans occurs via bites of infected Ixodes spp. ticks. Doxycycline is often used to treat LD patients, which is sometimes delayed due to current diagnostic challenges. Recently, several lines of evidence show dysbiosis of the gut microbiome in LD patients, which may be a host factor contributing to pathogenesis and symp tomology but is still an understudied area in the field. To address this knowledge gap, we longitudinally compared the immune response and gut microbial composi tion of Japanese macaques after intradermal infection with Bb strain 297 with or without doxycycline treatment. Immunological and microbial changes were monitored longitudinally using enzyme-linked immunosorbent assay, flow cytometry, single-cell genomics, and 16S amplicon sequencing assays. All Bb-inoculated animals serocon verted to produce Bb-specific antibodies. Borrelial DNA was undetected by real-time quantitative PCR in the skin, blood, and cerebrospinal fluid. Levels of CXCL13, a B cell chemoattractant, increased following infection but reached a nadir after treatment. The frequency of circulating immune cells remained constant over the course of the study, but gene expression analysis showed downregulation of antimicrobial genes in monocytes, dendritic cells, and B cells until late in infection, regardless of treat ment. Infection and antibiotic treatment led to a loss of gut commensals important for maintaining gut integrity. Finally, untreated infected animals showed mononuclear myocarditis along with sporadic detection of borrelial DNA. Data from this study suggest aberrant B cell activity, myocarditis, and loss of important commensal microbes as factors contributing to symptoms of untreated Lyme disease.

Document Type

Article

Publication Date

2025

Notes/Citation Information

© 2025 Napier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Digital Object Identifier (DOI)

https://doi.org/10.1128/mbio.01437-25

Funding Information

Global Lyme Alliance

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