The Motivation Behind the Research
Antibiotics like doxycycline are the standard treatment for Lyme disease, but 10-20% of patients continue to experience symptoms long after treatment ends. We still don’t understand why some symptoms stick around. One hypothesis is that changes in the gut microbiome might lead to a dysregulated immune response that contributes to ongoing symptoms.
The gut microbiome is a community of trillions of microbes in the digestive tract that support digestion, regulate the immune system, influence metabolism, and even affect brain function and mood. Dysbiosis, or disturbance of this balance, can have a significant impact on health.
To investigate this connection, Global Lyme Alliance (GLA) funded Dr. Ilhem Messaoudi at the University of Kentucky to study how Lyme disease and its treatment impact the gut and immune system over time in a primate model. Understanding how these systems interact could help identify better ways to support patients through and after treatment.
What Did the Researchers Do?
Researchers used a species of macaques whose gut microbiome and immune system are similar to humans. Their controlled diets and environments help keep microbiomes stable, which is difficult in human studies. Macaques were assigned to one of three groups:
One group was intentionally left untreated after infection to study the natural course of Lyme disease, which cannot be done ethically in people.
What Were the Key Findings?
Importantly, both infected and treated animals lost certain gut bacteria that produce butyrate, a compound produced mainly by gut bacteria when they ferment dietary fiber. Butyrate plays a crucial role in gut and overall health. However, no large changes in the immune response were observed except that levels of CXCL13, a molecule linked to immune cell activity, were significantly increased during infection and dropped after antibiotic treatment.
Implications
This study suggests that Lyme disease itself, not just antibiotics, can cause changes in gut bacteria. However, it is unclear how long these changes last and whether they could impact long-term health. Are certain bacterial losses driving or contributing to persistent symptoms in some patients? Could restoring these bacteria help people feel better? These important questions remain unanswered and warrant more research.
Final Thoughts on Antibiotic Use
Even though antibiotics can cause shifts in the gut microbiome, they are necessary to treat Lyme disease and prevent serious health risks. Patients should never stop or avoid antibiotics without consulting their healthcare provider.
A Note on Animal Research
This study was conducted under strict ethical oversight at an accredited primate research center. All animals received balanced nutrition, environmental enrichment, and housing that met or exceeded U.S. federal animal welfare standards.
Publication: Napier EG, Cinco IR, Wagner SB, Stuart EV, Qiao Q, Taylor J, Stevenson B, Messaoudi I. Borreliosis and doxycycline treatment disrupt gut microbiota and immune responses in nonhuman primates. mBio. 2025 Jun 27:e0143725. doi: 10.1128/mbio.01437-25
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