The study shows that antibiotics can cause the gum‑bacteria Porphyromonas gingivalis to release more harmful LPS, which triggers inflammation. The natural antimicrobial peptide LL‑37 was the best at neutralizing this LPS and stopping inflammatory cytokines in lab tests. This suggests that adding LL‑37‑like agents could help reduce inflammation when taking antibiotics for gum issues, though such peptides aren’t yet common as supplements.

Bacterial lipopolysaccharide (LPS) release during periodontal infection is a significant component of periodontal disease. We hypothesized that some bacterial LPS release results from bacterial exposure to antibiotics. Therefore, we examined the ability of various classes of antibiotics to induce LPS release from Porphyromonas gingivalis as well as the ability of antimicrobial peptides (AMPs) to inhibit purified LPS. All antibiotics tested against P. gingivalis were able to liberate 1.9-12.9 times more LPS as compared to untreated bacteria. Among the three AMPs tested, LL-37 was found to be the most potent inhibitor of cytokine (tumor necrosis factor-alpha, interleukin-1beta, interleukin-6) production and completely neutralized purified P. ginigivalis LPS activity in the chromogenic limulus amebocyte lysate (LAL) and whole blood cytokine stimulation assays. These observations suggest that therapeutic approaches utilizing AMPs as adjuncts to neutralize released LPS should be considered.