A Distinct Microbiome Signature in Posttreatment Lyme Disease Patients

Madeleine Morrissette; Norman Pitt; Antonio González; Philip Strandwitz; Mariaelena Caboni; Alison W Rebman; Rob Knight; Anthony D'Onofrio; John N Aucott; Mark J Soloski; Kim Lewis

doi:10.1128/mBio.02310-20

A Distinct Microbiome Signature in Posttreatment Lyme Disease Patients

mBio. 2020 Sep 29;11(5):e02310-20. doi: 10.1128/mBio.02310-20.

Authors

Affiliations

¹ Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA.
² Department of Pediatrics, University of California San Diego, La Jolla, California, USA.
³ Lyme Disease Research Center, Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁴ Department of Computer Science and Engineering, University of California, San Diego, La Jolla, California, USA.
⁵ Center for Microbiome Innovation, University of California, San Diego, La Jolla, California, USA.
⁶ Antimicrobial Discovery Center, Department of Biology, Northeastern University, Boston, Massachusetts, USA k.lewis@northeastern.edu.

^# Contributed equally.

Abstract

Lyme disease is the most common vector-borne disease in the United States, with an estimated incidence of 300,000 infections annually. Antibiotic intervention cures Lyme disease in the majority of cases; however, 10 to 20% of patients develop posttreatment Lyme disease syndrome (PTLDS), a debilitating condition characterized by chronic fatigue, pain, and cognitive difficulties. The underlying mechanism responsible for PTLDS symptoms, as well as a reliable diagnostic tool, has remained elusive. We reasoned that the gut microbiome may play an important role in PTLDS given that the symptoms overlap considerably with conditions in which a dysbiotic microbiome has been observed, including mood, cognition, and autoimmune disorders. Analysis of sequencing data from a rigorously curated cohort of patients with PTLDS revealed a gut microbiome signature distinct from that of healthy control subjects, as well as from that of intensive care unit (ICU) patients. Notably, microbiome sequencing data alone were indicative of PTLDS, which presents a potential, novel diagnostic tool for PTLDS.IMPORTANCE Most patients with acute Lyme disease are cured with antibiotic intervention, but 10 to 20% endure debilitating symptoms such as fatigue, neurological complications, and myalgias after treatment, a condition known as posttreatment Lyme disease syndrome (PTLDS). The etiology of PTLDS is not understood, and objective diagnostic tools are lacking. PTLDS symptoms overlap several diseases in which patients exhibit alterations in their microbiome. We found that patients with PTLDS have a distinct microbiome signature, allowing for an accurate classification of over 80% of analyzed cases. The signature is characterized by an increase in Blautia, a decrease in Bacteroides, and other changes. Importantly, this signature supports the validity of PTLDS and is the first potential biological diagnostic tool for the disease.

Keywords: Lyme disease; diagnostics; microbial communities; microflora; tick-borne pathogens.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Anti-Bacterial Agents / therapeutic use*
Bacteria / classification
Bacteria / genetics
Bacteria / isolation & purification
Cohort Studies
Dysbiosis / etiology*
Feces / microbiology
Female
Humans
Lyme Disease / drug therapy*
Male
Microbiota / drug effects*
Middle Aged
Post-Lyme Disease Syndrome / diagnosis
Post-Lyme Disease Syndrome / microbiology*
Transcriptome

Substances

Anti-Bacterial Agents