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Saliva metabolome and microbiome in permanent teeth caries

ABSTRACT:

Metabolites are important determinants of disease progression. In this study, we conducted a case-control study to explore permanent teeth caries-related differences in salivary metabolite profiles and related changes in the composition of the oral microbiota in 200 subjects including 100 caries-free individuals and 100 with moderate-to-severe caries with good homogeneity through widely targeted metabolomics and 16S rRNA deep sequencing technologies. We found that: 1) 822 metabolites were detectable in salivary samples from these participants, of which 4-acetamidobutyric acid and adipic acid were respectively enriched in healthy individuals and individuals with caries, exhibited the greatest area under the curve (AUC) values of > 0.970; 2) less diversity was observed in individuals with dental caries relative to caries-free individuals, and significant differences in the dominant taxa were evident between the two groups. For example, the healthy oral microbiome is enriched for Rothia aeria and Neisseria perflava, whereas Prevotella melaninogenica, Streptococcus salivarius, Streptococcus parasanguinis and Prevotella histicola, and Streptococcus mutans were enriched in individuals with caries; 3) Prevotella histicola, Oribacterium asaccharolyticum and Rothia aeria were the top 3 species being required to differentiate caries from caries free population; 4) adipic acid and 4-acetamidobutyric acid derived from microbiota and host-microbiota co-metabolism, respectively. A negative correlation was observed between the microbes enriched in caries individuals (such as Prevotella histicola) and 4-acetamidobutyric acid. Moreover, the upstream regulatory factor ALDH of 4-acetamidobutyric acid is expressed throughout the entire process of tooth development including the differentiation of tooth bud, ameloblasts and odontoblasts. Together, these results suggest that 4-acetamidobutyric acid and adipic acid are important targets for future caries-focused research, offering insight into cariogenic activity or risk assessment in moderate or severe cases.

INSTRUMENT(S): Liquid Chromatography MS - alternating - hilic, Liquid Chromatography MS - alternating - reverse phase

SUBMITTER: Shanshan Liu

PROVIDER: MTBLS4569 | MetaboLights | 2024-05-14

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS4569	Other
	FILES	Other
	a_MTBLS4569_LC-MS_alternating_hilic_metabolite_profiling.txt	Txt
	a_MTBLS4569_LC-MS_alternating_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt

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Project description:The effect of oral microbiota on the intestinal microbiota has garnered growing attention as a mechanism linking periodontal diseases to systemic diseases. However, the salivary microbiota is diverse and comprises numerous bacteria with a largely similar composition in healthy individuals and periodontitis patients. Thus, the systemic effects of small differences in the oral microbiota are unclear. In this study, we explored how health-associated and periodontitis-associated salivary microbiota differently colonized the intestine and their subsequent systemic effects by analyzing the hepatic gene expression and serum metabolomic profiles. The salivary microbiota was collected from a healthy individual and a periodontitis patient and gavaged into C57BL/6NJcl[GF] mice. Samples were collected five weeks after administration. Gut microbial communities were analyzed by 16S ribosomal RNA gene sequencing. Hepatic gene expression profiles were analyzed using a DNA microarray and quantitative polymerase chain reaction. Serum metabolites were analyzed by capillary electrophoresis time-of-flight mass spectrometry. The gut microbial composition at the genus level was significantly different between periodontitis-associated microbiota-administered (PAO) and health-associated oral microbiota-administered (HAO) mice. The hepatic gene expression profile demonstrated a distinct pattern between the two groups, with higher expression of Neat1, Mt1, Mt2, and Spindlin1, which are involved in lipid and glucose metabolism. Disease-associated metabolites such as 2-hydroxyisobutyric acid and hydroxybenzoic acid were elevated in PAO mice. These metabolites were significantly correlated with Bifidobacterium, Atomobium, Campylobacter, and Haemophilus, which are characteristic taxa in PAO mice. Conversely, health-associated oral microbiota were associated with higher levels of beneficial serum metabolites in HAO mice. The multi-omics approach used in this study revealed that periodontitis-associated oral microbiota is associated with the induction of disease phenotype when they colonized the gut of germ-free mice.

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Saliva metabolome and microbiome in permanent teeth caries

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