Doxycycline induces dysbiosis in female C57BL/6NCrl mice

Abstract

ObjectiveThis study aims to demonstrate the effect of oral doxycycline on fecal microbiota of mice. Doxycycline is a common effector for control of gene expression using the tet-inducible system in transgenic mice. The effect of oral doxycycline on murine gut microbiota has not been reported. We evaluated the effect of doxycycline treatment by sequencing the V4 hypervariable region of the 16S rRNA gene from fecal samples collected during a 4 week course of treatment at a dose of 2 mg/ml in the drinking water.ResultsThe fecal microbiota of treated animals were distinct from control animals; the decreased richness and diversity were characterized primarily by Bacteroides sp. enrichment. These effects persisted when the treatment was temporarily discontinued for 1 week. These data suggest that doxycycline treatment can induce significant dysbiosis, and its effects should be considered when used in animal models that are or maybe sensitive to perturbation of the gut microbiota.Electronic supplementary materialThe online version of this article (10.1186/s13104-017-2960-7) contains supplementary material, which is available to authorized users.

<p>Sarecycline: A Review of Preclinical and Clinical Evidence</p>

“…Tetracyclines exhibit a broad-spectrum of antibacterial activity, targeting a wide range of both Gram-positive and Gramnegative bacteria, including activity against normal bacterial microflora commonly found in the human GI tract. 3,[16][17][18][19] These normal microbiota include Enterobacteriaceae, Enterococcus, and Escherichia species, of which disruption (dysbiosis) could potentially lead to sequelae associated with gastrointestinal disease, [20][21][22] but also the emergence of antibiotic-resistant strains. 23,24 Below, we summarize the main findings of the microbiological profile of sarecycline compared to other tetracyclines.…”

Confounding factors from inducible systems for spatiotemporal gene expression regulation

“…For instance, the gut microbiota play an important role in many physiological processes such as energy balance and metabolism. As expected, doxycycline significantly alters the gut microbiome after even 7 d of exposure (Boynton et al, 2017), impacting whole-body metabolic flexibility (Smith et al, 2018). If proper controls are not included in the study design, antibiotic-mediated alterations in the microbiome and subsequent wholebody metabolism, cognition, and immune function should be considered as confounding factors in animal experiments with the Tet-On/Tet-Off system.…”

Acute and long-term effects of antibiotics commonly used in laboratory animal medicine on the fecal microbiota

“…These studies add to the emerging realization that antibiotics used transiently to treat clinical signs or induce gene transcription (e.g., doxycycline-induced Tet-on Table 1 Results of one-way PERMANOVA to detect differences in fecal community structure between pre-treatment (Pre), immediately post-treatment (Post), and four weeks post-treatment (4w post) samples collected from C57BL/6NHsd mice receiving the indicated treatments ( n = 12) systems) can have profound and long-lasting effects on the GM [22,23], and potentially, the model phenotype. With this in mind, mouse models that are sensitive to the composition of the GM [24−26] are at risk of being influenced by the presence of antibiotic exposures during the study.…”