Publication Date
1-4-2024
Journal
Journal of Neuroinflammation
DOI
10.1186/s12974-023-03004-4
PMID
38178148
PMCID
PMC10765643
PubMedCentral® Posted Date
1-4-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Mice, Animals, Doxycycline, Mice, Transgenic, Gastrointestinal Microbiome, Lipopolysaccharides, Tetracycline, Anti-Bacterial Agents, Trans-Activators, Inflammation, Transgenes, Doxycycline, Tetracycline transactivator, Gut microbiome, Antibiotic, Neuroinflammation, Lipopolysaccharide, LPS, Amyloid, APP transgenic mouse, Transcriptome, Microglia
Abstract
The tetracycline transactivator (tTA) system provides controllable transgene expression through oral administration of the broad-spectrum antibiotic doxycycline. Antibiotic treatment for transgene control in mouse models of disease might have undesirable systemic effects resulting from changes in the gut microbiome. Here we assessed the impact of doxycycline on gut microbiome diversity in a tTA-controlled model of Alzheimer's disease and then examined neuroimmune effects of these microbiome alterations following acute LPS challenge. We show that doxycycline decreased microbiome diversity in both transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite the change in microbiome composition, doxycycline treatment had minimal effect on basal transcriptional signatures of inflammation the brain or on the neuroimmune response to LPS challenge. Our findings suggest that central neuroimmune responses may be less affected by doxycycline at doses needed for transgene control than by antibiotic cocktails at doses used for experimental microbiome disruption.