Untargeted metabolomics of saliva in caries-active and caries-free children in the mixed dentition

Abstract

ObjectiveTo compare the differences in salivary metabolites between caries-active and caries-free children in the mixed dentition, and explore their correlation with caries status.MethodsThe study involved 20 children (aged 8–9 years) in the mixed dentition, including 10 caries-active (aged 8.6 ± 0.49years) and 10 caries-free children(aged 8.5 ± 0.5years), with a male/female ratio of 1:1. The saliva samples were collected from all children. Metabolite extraction, LC-MS/MS-based untargeted metabolomics, qualitative and semi-quantitative analysis and bioinformatics analysis were performed to identify differential metabolites between the two sample groups. The differential metabolites identified were further analyzed in an attempt to find their correlations with caries status.ResultsIn the positive ion mode, a total of 1606 molecular features were detected in the samples of the two groups, 189 of which were differential metabolites when comparing the caries-active group with the caries-free group, including 104 up-regulated and 85 down-regulated metabolites. In the negative ion mode, a total of 532 molecular features were detected in the samples of two groups, 70 of which were differential metabolites when comparing the caries-active group with the caries-free group, including 37 up-regulated and 33 down-regulated metabolites. In the positive ion mode, two of the top 5 up-regulated differential metabolites were found in and annotated to specific metabolic pathways, whereas in the negative ion mode, only one of the top 5 up-regulated differential metabolites was found in and annotated to specific metabolic pathways. In both the positive and negative ion modes, the top 5 down-regulated differential metabolites were both annotated to the metabolic pathways. KEGG pathway enrichment analysis of differential metabolites showed that histamine and arachidonic acid identified in the positive ion mode, as well as succinate and L-histidine identified in the negative ion mode were enriched in the top 3 significantly altered pathways.ConclusionThe enriched differential metabolites including histamine, L-histidine and succinate were correlated with the presence of dental caries, but their role in the caries process needs to be further investigated.

Critical Factors in Sample Collection and Preparation for Clinical Metabolomics of Underexplored Biological Specimens

“…Given the richness and metabolic response it provides, saliva samples have been used in screening for diagnosis and monitoring T2DM [ 148 , 149 , 150 ], neurological diseases (such as Alzheimer’s [ 151 ] and schizophrenia [ 152 ]), and some types of cancers (such as oral, breast, cerebral, colorectal, and gastric cancers) [ 153 , 154 , 155 ]. It is the ideal biofluid for studying oral diseases including periodontitis [ 156 , 157 ] and dental caries [ 158 , 159 ]. Recently, it has been applied to SARS-CoV-2 detection, diagnosing the coronavirus disease [ 160 ].…”