Multi-Omics Signatures of Periodontitis and Periodontal Therapy on the Oral and Gut Microbiome

<h4>Aim</h4>To characterize the impact of periodontitis and of Steps I-II of periodontal therapy on microbiome composition, function, and metabolic output across the oral and gut environments.<h4>Methods</h4>A multi-omics analysis was performed on saliva and stool samples collected from 50 systemically healthy individuals with and without Stage III-IV periodontitis. For participants with periodontitis, samples were analyzed both at baseline and 3 months after Steps I-II of periodontal therapy. High-throughput whole metagenome sequencing was used to profile microbial taxa and functional genes, NMR-based metabolomics profiled host-microbial metabolites. Single-omic differential abundance analysis between healthy samples and periodontitis samples was performed with MaAsLin2, while analysis between pre- and post-treatment was conducted with timeOmics. Variable selection and subsequent supervised multivariate analysis to determine group-separating markers utilized multi-level sparse Partial Least Squares Discriminant Analysis (sPLS-DA) through mixOmics. KEGG pathway enrichment was analyzed using clusterProfiler, whereas multi-omic data integration was performed with multi-block Partial Least Squares regression analysis.<h4>Results</h4>Periodontitis was associated with significant compositional and functional changes in both saliva and stool, with increased abundance of pathobionts and loss of health-associated taxa in both niches. A subset of species was shared across oral and gut habitats, with detectable differences across clinical groups. As functional potential, periodontitis enriched microbial pro-inflammatory pathways (lipopolysaccharide biosynthesis, bacterial motility) and depleted beneficial short-chain fatty acid (SCFA)- and vitamin-producing functions. Metabolomic profiles revealed reduced SCFAs and amino acids in periodontitis, with elevated pro-inflammatory metabolites (succinate, trimethylamine) in both saliva and stool. Following therapy, microbial communities and their metabolic output partially reverted toward health-associated profiles, particularly in saliva. Stool samples showed subtler but consistent shifts, including a decrease in some typically oral species and decreased succinate and methylamine and restoration of amino acid and SCFA-related metabolites.<h4>Conclusions</h4>Periodontitis is associated with coordinated microbial and metabolic signatures across the oral and gut environments. Non-surgical periodontal therapy promotes partial ecological restoration in both niches, supporting the view of oral health as a modifiable target for influencing systemic microbial homeostasis.<h4>Trial registration</h4>ClinicalTrials.gov identification number: NCT04826926.