Dihydromyricetin Alleviates Diabetic Periodontitis By Modulating Gut Microbiota-Inflammation Axis

To explore the mechanism by which DHM alleviates diabetic periodontitis through the modulation of the gut microbiota-host inflammation axis. A diabetic periodontitis mouse model was established with streptozotocin induction, and mice were divided into a control group, diabetic periodontitis group (DP), and DHM treatment group (DP + DHM). Micro-CT assessed alveolar bone resorption, HE staining observed histopathological changes, and qRT-PCR, WB, and immunofluorescence detected inflammatory cytokine levels. 16S rRNA sequencing analyzed gut microbiota composition, and upper jaw transcriptome sequencing explored periodontal immune infiltration and key "gut-periodontal axis" pathways. DHM intervention improved alveolar bone loss in diabetic periodontitis mice, alleviating inflammation and collagen degradation in periodontal tissues. 16S sequencing showed DHM reshaped gut microbiota, enhancing SCFAs-producing bacteria, with SCFAs levels correlating with anti-inflammatory factors in periodontal tissues. Transcriptomic analysis revealed DHM activated the SCFAs-GPR43 axis, inhibiting M1 macrophage polarization, promoting the M2 phenotype, and downregulating NLRP3 activity. DHM also restored gut barrier integrity, reduced bacterial translocation, and mitigated the systemic inflammatory "secondary hit" on the periodontal microenvironment. DHM improves diabetic periodontitis through a dual "microbiota metabolism-immune reprogramming" axis. It enriches SCFAs-producing bacteria, activating GPR43-dependent anti-inflammatory signaling and reshaping macrophage phenotypes in the periodontium. Additionally, it restores the gut barrier, blocking the systemic-local inflammation cascade. This study unveils the multi-target mechanism of DHM, highlighting the interaction between gut-derived metabolites and the periodontal immune microenvironment, offering a new paradigm for cross-organ therapeutic strategies in metabolic inflammatory diseases.