Systemic Effects of Oral Antibiotics in Mice: A Combined Physiological and Molecular Approach

This study investigates the systemic effects of amoxicillin and tetracycline on healthy Mus musculus (Swiss albino) mice, focusing on food intake, body weight, and hematological parameters. Over a 14-day oral treatment period, both antibiotics significantly reduced weight gain and food efficiency, with sex-specific variations: tetracycline had stronger metabolic effects in males, while amoxicillin was more impactful in females. To explore underlying mechanisms, molecular docking and MM-GBSA analyses were performed on PPAR-γ and TLR2–TIRAP complexes. Both antibiotics showed negligible binding to PPAR-γ, suggesting their metabolic effects are not receptor-mediated. In contrast, tetracycline exhibited strong and stable binding to TLR2 (ΔGbind = −27.87 kcal/mol), supported by extensive hydrogen bonding, implying potential immunomodulatory action. These findings suggest that antibiotic-induced metabolic and immune alterations are more likely driven by microbiota disruption and innate immune signaling, rather than direct metabolic receptor engagement.