Doxycycline for transgene control disrupts gut microbiome diversity without compromising acute neuroinflammatory response.

Autor: Koller EJ; Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Mail Stop BCM295, Houston, TX, 77030, USA., Wood CA; Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Mail Stop BCM295, Houston, TX, 77030, USA., Lai Z; Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Mail Stop BCM295, Houston, TX, 77030, USA., Borgenheimer E; Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Mail Stop BCM295, Houston, TX, 77030, USA., Hoffman KL; Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA., Jankowsky JL; Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Mail Stop BCM295, Houston, TX, 77030, USA. jankowsk@bcm.edu.; Departments of Neurology, Neurosurgery, and Molecular and Cellular Biology, Huffington Center On Aging, Baylor College of Medicine, Houston, TX, 77030, USA. jankowsk@bcm.edu.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2024 Jan 04; Vol. 21 (1), pp. 11. Date of Electronic Publication: 2024 Jan 04.
DOI: 10.1186/s12974-023-03004-4
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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