The microbial metabolite isovaleric acid aggravates gelatinase‐mediated periodontal tissue destruction via the NF‐κB signaling pathway

Periodontitis is a chronic inflammatory disease characterized by the destruction of periodontal tissues, with oral bacteria as the progressive frontier. Isovaleric acid, an important short-chain fatty acid, is a substance produced by oral bacteria during the breakdown of protein-rich foods. By comparing saliva samples from healthy individuals and patients with periodontal diseases, we found that isovaleric acid levels were 2‒3 times higher in patients with inflamed or damaged periodontal tissue. In this study, we assessed the effects of isovaleric acid on periodontal tissues by injecting isovaleric acid into the gums of rats and treating human periodontal cells with isovaleric acid. We found that isovaleric acid worsened periodontal tissue damage and accelerated bone loss. This process worked through NF-κB signaling pathway activation, which increased the activity and expression of gelatinases, enzymes that break down periodontal tissues. These findings increase our understanding of the possible involvement of isovaleric acid in the development of periodontitis. Targeting isovaleric acid metabolism may provide new approaches for the treatment or prevention of periodontitis.