IADR Abstract Archives
Integrated metagenome-metabolome profiling identifies new links between diabetes-mellitus and periodontitis
Objectives: Existing evidence supports the bi-directional association between type-2 diabetes mellitus (T2DM) and periodontitis. However, the mechanisms that link these two conditions are not completely understood. Hence, we aimed to characterize the interactions between the microbiome and metabolites in the oral environment to determine the association between T2DM and periodontitis using saliva as a medium.
Methods: In this case-control study, we performed nontargeted metabolic and metagenomic analyses of saliva in 39 women with T2DM (DM) and 40 women without T2DM (non-DM). Demographic and clinical data were recorded, and data were subjected to integrated bioinformatic analysis.
Results: Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) model showed distinct salivary metabolomes for DM and non-DM groups. At an FDR of <0.05 and VIP>1, 126 metabolites significantly differed between the two groups. Most of these differentiating metabolites belonged to the class of amino acids and their derivatives, with dipeptides accounting for about 65% of the identified amino acid derivatives. Like metabolomics, salivary metagenomic profiles were significantly diverse between the DM and non-DM groups at the genus level. Through integrated metagenome-metabolome analysis using weighted gene co-express network analysis (WGCNA), we identified that the module constituting majorly of amino acids and dipeptides was significantly associated with genera Porphyromonas and Bacteroides, which are more prevalent in periodontitis (r>0.4, p<0.0001).
Conclusions: The elevated level of salivary amino acids, particularly dipeptides, in T2DM may serve as a critical nutritional source for the survival and growth of periodontitis-associated pathogens. This, in turn, increases the risk of developing periodontitis among patients with diabetes. Therefore, it is imperative to break this nutrient cycle to restore a healthy oral ecosystem. Given that T2DM increases the risk for periodontitis and vice-versa, regulating salivary dipeptide could be a potential target to mitigate the progression of both conditions, leading to improved oral and systemic health.
Methods: In this case-control study, we performed nontargeted metabolic and metagenomic analyses of saliva in 39 women with T2DM (DM) and 40 women without T2DM (non-DM). Demographic and clinical data were recorded, and data were subjected to integrated bioinformatic analysis.
Results: Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) model showed distinct salivary metabolomes for DM and non-DM groups. At an FDR of <0.05 and VIP>1, 126 metabolites significantly differed between the two groups. Most of these differentiating metabolites belonged to the class of amino acids and their derivatives, with dipeptides accounting for about 65% of the identified amino acid derivatives. Like metabolomics, salivary metagenomic profiles were significantly diverse between the DM and non-DM groups at the genus level. Through integrated metagenome-metabolome analysis using weighted gene co-express network analysis (WGCNA), we identified that the module constituting majorly of amino acids and dipeptides was significantly associated with genera Porphyromonas and Bacteroides, which are more prevalent in periodontitis (r>0.4, p<0.0001).
Conclusions: The elevated level of salivary amino acids, particularly dipeptides, in T2DM may serve as a critical nutritional source for the survival and growth of periodontitis-associated pathogens. This, in turn, increases the risk of developing periodontitis among patients with diabetes. Therefore, it is imperative to break this nutrient cycle to restore a healthy oral ecosystem. Given that T2DM increases the risk for periodontitis and vice-versa, regulating salivary dipeptide could be a potential target to mitigate the progression of both conditions, leading to improved oral and systemic health.