This project aims to elucidate the molecular mechanisms by which the gut microbial metabolite β-guanidinopropionic acid (β-GPA) alleviates hyperlipidemic periodontitis (HPD). We performed Tandem Mass Tag (TMT) based quantitative proteomic analysis on periodontal tissues from HPD model mice versus those treated with β-GPA. The goal was to identify key differentially expressed proteins and uncover the protective signaling pathways modulated by β-GPA, ultimately identifying the TLR4-MyD88 axis as a primary therapeutic target.