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RSPO4 is a potential risk gene of stages III–IV, grade C periodontitis through effects on innate immune response and oral barrier integrity

ABSTRACT: RSPO4 is a potential risk gene of stages III–IV, grade C periodontitis through effects on innate immune response and oral barrier integrity

PROVIDER: PRJNA922102 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23023955_1.fastq.gz	Fastqsanger.gz
	SRR23023955_2.fastq.gz	Fastqsanger.gz
	SRR23023956_1.fastq.gz	Fastqsanger.gz
	SRR23023956_2.fastq.gz	Fastqsanger.gz
	SRR23023957_1.fastq.gz	Fastqsanger.gz

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Project description:Background: This study aims to comprehensively characterize the dynamic succession of the salivary microbiome and metabolic reprogramming in type 2 diabetes mellitus (T2DM) patients across progressive stages of periodontitis (Stage I–IV) using an integrated multi-omics approach. We specifically sought to evaluate the clinical value of a salivary multi-omics-based machine learning model for the precision stratification of periodontitis severity.Methods: Unstimulated saliva samples were collected from 120 T2DM patients stratified into four groups based on periodontitis severity (Stages I–IV, n=30 per group). 16S rDNA amplicon sequencing and LC-MS untargeted metabolomics were employed to analyze microbial and metabolic profiles. Multivariate statistics, Procrustes analysis, and Random Forest algorithms were utilized to identify key features and construct diagnostic models.Results: Disease progression was characterized by a significant restructuring of the microbiome, featuring an increase in Firmicutes and enrichment of core pathogens (e.g., Porphyromonas, Treponema) in Stage IV. Metabolically, a stage-specific shift was observed from early amino acid perturbations to late-stage active proteolysis (accumulation of Pro-Pro dipeptides) and inflammatory lipid dysregulation. Notably, the abundance of Lactobacillus was significantly positively correlated with HbA1c levels and periodontal destruction. The Random Forest model based on these multi-omics signatures achieved an AUC of 0.961 for identifying Stage IV periodontitis.Conclusion: This study reveals that the progression of periodontitis in T2DM patients is associated with specific remodeling of the salivary microecosystem, mechanistically driven by pathogen-induced proteolysis and dysregulated inflammatory lipid metabolism. The significant correlation between Lactobacillus and HbA1c provides novel evidence for the oral-systemic metabolic interplay. Furthermore, the high-accuracy diagnostic model validates the potential of saliva for non-invasive disease stratification.

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RSPO4 is a potential risk gene of stages III–IV, grade C periodontitis through effects on innate immune response and oral barrier integrity

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