Antibiotic Exposure and Periodontal Susceptibility: A Risk-Modifying Hypothesis

Systemic antibiotics are among the most widely prescribed therapeutic agents worldwide, and their effects on host–microbe equilibrium extend well beyond the infection for which they are intended. Periodontitis is conventionally framed as a biofilm-initiated, host-mediated inflammatory disease, although recent work has shifted this framework toward microbial homeostasis as a regulator of periodontal stability. We hypothesize that antibiotics are not direct etiologic agents of periodontitis but instead act as risk-modifying factors that lower the threshold at which plaque-mediated inflammation progresses to destructive disease. We propose that this effect may operate through several mechanisms: broad-spectrum or repeated exposure could deplete protective commensals and narrow microbial diversity, creating ecological space for opportunistic and pathogenic taxa; antibiotics may also alter host neutrophil function, cytokine profiles, and antimicrobial peptide regulation and may interfere with the osteoblastic and osteoclastic dynamics governing alveolar bone remodelling; and antibiotic-induced gut dysbiosis may propagate systemic inflammatory signals that further modulate periodontal susceptibility. To evaluate this hypothesis, we synthesize the available clinical, epidemiological, and experimental data across four converging axes—oral microbial ecology, immune regulation, alveolar bone remodelling, and the gut–oral axis—and identify the predictions the hypothesis generates and the evidence gaps it exposes. We emphasize that no clinical study has yet demonstrated a causal link between antibiotic exposure and periodontitis; the framework advanced here is therefore intended to inform antimicrobial stewardship in dentistry and to define a research agenda for determining whether antibiotic exposure constitutes a clinically meaningful modifier of periodontal disease susceptibility.