This research study revealed that the gut microbiome of post treatment Lyme disease (PTLD) patients has a distinct signature as compared to healthy control subjects as well as to intensive care unit (ICU) patients, thereby providing objective evidence of biological abnormalities. Reliable diagnostics have been elusive for Lyme disease and there are no approved treatments for persistent illness which can include severe fatigue, pain, and cognitive difficulties that are functionally impairing. This distinct PTLD microbiome signature presents a potential novel objective Lyme disease diagnostic tool and new avenue for therapeutics.
Why was this study done?
This research study was done to determine if there was a distinct gut microbiome signature associated with post treatment Lyme disease (PTLD). Researchers at Johns Hopkins University School of Medicine, Northeastern University, and University of California San Diego teamed up to research the differences of the gut microbiomes of PTLD patients compared to healthy controls as well as to an intensive care unit (ICU) control group. Lyme disease lacks objective reliable diagnostics. A Lyme disease gut microbiome signature, if distinct from other antibiotic treated conditions, could be used as a potential novel diagnostic tool and new avenue for treatments.
How was this study done?
Through 16S rRNA gene sequencing, alterations in the gut microbiome were identified in a cohort of well-characterized PTLD patients compared to two healthy control cohorts and an ICU control cohort. The PTLD cohort is part of the John Hopkins Lyme Disease Research Center’s Study of Lyme Immunology and Clinical Endpoints (SLICE). Specifically, the stool samples were from 87 patients that met the IDSA-proposed case definition for PTLDS. To control for the generally high levels of antibiotic use that could alter the microbiome in patients with PTLD, a cohort of 123 fecal samples of intensive care unit (ICU) patients from two time points was used as a control group in addition to a healthy control group of 17 healthy donors from Northeastern University and 152 healthy donors from the American Gut. The majority of the ICU patients were on antibiotic treatment at the time of collection.
What were the major findings?
Results showed that the post treatment Lyme disease cohort had two distinct differences in microbial levels in their fecal matter compared with healthy people or intensive care unit patients. The PTLD patients had an abundance of Blautia bacteria and a decrease of Bacteroides.
What is the impact of this work?
The study shows that the gut microbiome of a cohort of patients with PTLD is distinct from the microbiomes of healthy and ICU controls. Results validate PTLD as a distinct abnormal condition and suggest that antibiotic influence alone cannot explain these changes in the microbiome. An excess of Blautia bacteria and a reduction in Bacteroides could potentially be related to persistent symptoms in Lyme disease.
Blautia blooms were found in Lyme disease patients but not in the healthy group or ICU patients. Excess blautia has also been known to be present in people with obesity, Alzheimer’s disease, and multiple sclerosis.
Bacteroides are common gut bacteria that help to regulate digestion, inflammation, and immune responses. They also produce GABA, an important neurotransmitter. Low GABA can result in increased anxiety and depression. Having low levels of bacteroides, such as found in the PTLD cohort, could be a factor contributing to the anxiety and depression experienced by many Lyme disease patients.
Evaluating the microbiome of Lyme disease patients potentially provides a novel objective diagnostic tool and a new approach for treatments.
This research was supported by
- the Steven and Alexandra Cohen Foundation
- RDRCC/P30 grant AR070254.
We also thank Marcia Daniela Villega de Flores, Thelio Sewell, Erica Mihm, and Susan Joseph from the Johns Hopkins Medicine Lyme Disease Research Center for their efforts in patient recruitment, consent, sample processing, and archiving.
We thank Daniel McDonald, scientific director of The Microsetta Initiative at UC San Diego School of Medicine, for his helpful comments on the AGP and ICU data sets and reviewing the manuscript and Gail Ackermann for her help with sample metadata.
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
mBio Sep 2020, 11 (5) e02310-20; DOI: 10.1128/mBio.02310-20