Abstract
Antibiotic administration during early life has been shown to have lasting effects
on the gut microbiota, which have been linked to sustained alterations in liver metabolism
and adiposity. Recent investigations have discerned that the gut microbiota continues
to develop towards an adult-like profile during adolescence. However, the impact of
antibiotic exposure during adolescence on metabolism and adiposity is unclear. We
performed a retrospective analysis of Medicaid claims data, which revealed tetracycline
class antibiotics are commonly prescribed for the systemic treatment of adolescent
acne. Study purpose was to discern the impact of a prolonged tetracycline antibiotic
exposure during adolescence on the gut microbiota, liver metabolism, and adiposity.
Male C57BL/6T specific-pathogen-free mice were administered a tetracycline antibiotic
during the pubertal/postpubertal adolescent growth phase. Groups were euthanized at
timepoints to assess immediate and sustained antibiotic treatment effects. Antibiotic
exposure during adolescence caused lasting genera-level shifts in the intestinal bacteriome
and persistent dysregulation of metabolic pathways in the liver. Dysregulated hepatic
metabolism was linked to sustained disruption of the intestinal FXR-FGF15 axis, a
gut-liver endocrine axis that supports metabolic homeostasis. Antibiotics exposure
during adolescence increased subcutaneous, visceral, and marrow adiposity, which intriguingly
manifested following antibiotic therapy. This preclinical work highlights that prolonged
antibiotic courses for the clinical treatment of adolescent acne may have unintended
deleterious effects on liver metabolism and adiposity.
Graphical abstract
Graphical Abstract
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Article info
Publication history
Accepted:
February 16,
2023
Received in revised form:
January 24,
2023
Received:
December 16,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Funding Souces: American Society for Bone and Mineral Research (Rising Star Award) and the NIH (K08DE025337, T32DE017551, P20GM130457, P30DK123704, R01DE029637, R01AG067510)
Disclosure Statement: The authors have nothing to disclose.
Identification
Copyright
© 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
