Intermittent fasting alleviates periodontitis by enhancing gingival epithelial barrier through Bnip3 inhibition
Periodontitis is a chronic inflammatory disease characterized by progressive destruction of tooth-supporting tissues. Although intermittent fasting is known to improve overall health and reduce inflammation, its impact on periodontitis remains unclear. Here, using a ligature-induced periodontitis mouse model combined with an intermittent fasting regimen, we found that an optimal intermittent fasting protocol alleviated alveolar bone loss and periodontal inflammation, while concurrently enhancing gingival epithelial barrier integrity. This protection was independent of major oral microbial remodeling. Transcriptomic analysis of gingival tissue identified BCL2/adenovirus E1B interacting protein 3 (Bnip3) as a key host target downregulated by IF. Functionally, knockdown of BNIP3 in human oral keratinocytes rescued lipopolysaccharide-induced mitochondrial dysfunction and reduced epithelial permeability. Crucially, inhibition of gingival Bnip3 in vivo recapitulated the protective effects of intermittent fasting against periodontitis. Collectively, our findings establish intermittent fasting as a potential novel strategy for periodontitis management and identify Bnip3 as a promising therapeutic target.