ELUCIDATING THE THERAPEUTIC MECHANISMS OF GUT MICROBIOTA METABOLITES IN PERIODONTITIS: A NETWORK PHARMACOLOGY APPROACH.

BACKGROUND

Periodontitis is a chronic inflammatory disease featured by progressive destruction of periodontal supporting tissues. Accumulating evidence indicates that gut microbiota-derived metabolites modulate periodontal inflammation via the gut-periodontal axis, yet the underlying mechanisms and therapeutic targets remain largely unknown.

METHODS

This study adopted network pharmacology to explore the regulatory mechanisms of gut microbiota metabolites in periodontitis. Periodontitis-related genes and metabolite targets were obtained from public databases. Protein-protein interaction (PPI) network, GO and KEGG enrichment analyses, and a Microbiota‑Substrate‑Metabolite‑Target (MSMT) network were constructed for systematic analysis.

RESULTS

We identified 1954 periodontitis-related genes and 43 overlapping targets. Five core hub genes (IL6, AKT1, TP53, EGFR, TNF) were screened. These targets were mainly enriched in inflammatory responses and apoptosis regulation, and key pathways included PI3K‑Akt, MAPK, IL‑17, TNF and Toll-like receptor signaling.

CONCLUSION

Gut microbiota metabolites, particularly short-chain fatty acids, exert anti-periodontitis effects by regulating core hub genes and inflammatory-immune pathways. This study reveals the gut-periodontal axis mechanism and provides potential targets for periodontitis treatment.