Age-Dependent Resilience of the Wild-Derived Murine Gut Microbiome in Response to Subtherapeutic Antibiotic Exposure

Abstract

Recent advances in microbial research have revealed the crucial role that the gut microbiome plays in maintaining host health across a multitude of physiological systems, especially during early life maturation. Correspondingly, these studies indicate that antibiotic prescriptions administered to infants, which disrupt the development of a healthy microbiome, often have immediate and lasting consequences for host health. While these investigations are important, this thesis explores an underappreciated source of prolonged and unavoidable antibiotic exposure: environmental antibiotic pollution. As this crisis continues to escalate globally, it is crucial to investigate how exposure to subtherapeutic concentrations of antibiotics—similar to those measured in polluted waterways—impacts the gut microbiome, especially in early life. To address this pressing gap in existing literature, early-life (4.29 – 11.14 weeks old) and mid-life (17.29 – 35.14 weeks old) wild-derived mice were subjected to a seven-day treatment of low-concentration ampicillin, and changes to their gut microbiota were analyzed from fresh fecal samples. We found that exposure to subtherapeutic concentrations of ampicillin had a significant but transient impact on species richness (α-diversity) and a persistent impact on microbial community composition (β-diversity) in both the early-life and mid-life murine gut microbiome. Crucially, early-life mice younger than eight weeks were particularly susceptible to antibiotic-induced perturbation and largely unable to recover either species richness or composition upon discontinuation of treatment, suggesting that early-life antibiotic exposure before maturation may pose a critical threat to host health. Our results highlight the pressing risk that the global rise in antibiotic pollution poses to wildlife health. Further research should work to confirm the applicability of these findings to the human gut microbiome and investigate the impact of antibiotic pollution on comorbidities associated with early-life gut dysbiosis, like systemic inflammation, immune dysregulation, and antimicrobial resistance.