唾液多组学特征对2型糖尿病伴慢性牙周炎的辅助评估价值

Value of salivary multi-omics profiles for the adjunctive assessment of type 2 diabetes mellitus with chronic periodontitis

  • 摘要:
    目的 探讨唾液微生态及代谢特征对2型糖尿病(T2DM)伴慢性牙周炎辅助评估的价值。
    方法 纳入2023至2025年于常州市第一人民医院口腔科、内分泌科就诊的80例慢性牙周炎患者,分为单纯慢性牙周炎组(CP组,40例)和合并T2DM的牙周炎组(DM-CP组,40例)。记录所有参与者的牙周临床参数菌斑指数(PLI)、龈沟出血指数(SBI)、探诊深度(PD)和附着丧失(AL)及全身血糖代谢指标空腹血糖(FBG)和糖化血红蛋白A1c(HbA1c)。采集非刺激性全唾液样本后,分别运用16S rRNA测序和液相色谱-质谱联用(LC-MS)代谢组学技术进行微生物组学与代谢组学分析。
    结果 DM-CP组PLI(P = 0.007)、PD(P < 0.001)、HbA1cP < 0.001)及FBG(P < 0.001)均高于CP组;校正年龄和性别后,T2DM状态仍与PD加深(β = 0.766,P < 0.001)和PLI升高(β = 0.330,P = 0.008)相关。16S rRNA测序显示,DM-CP组唾液菌群丰富度降低,链球菌属等相对丰度升高,β多样性差异具有统计学意义(P = 0.001)。LC-MS分析显示2组代谢谱存在差异,差异代谢物主要富集于类固醇激素生物合成、胆汁分泌等通路,神经激肽A等在DM-CP组丰度较高。部分特征菌属和代谢物与PD、HbA1c相关。探索性随机森林模型显示,微生物组-代谢组联合模型的曲线下面积为0.941(95%CI:0.799~1.000,灵敏度为1.00,特异度为0.78),数值上高于单一微生物组或代谢组,但差异均无统计学意义(均P > 0.05)。
    结论 T2DM可能影响慢性牙周炎患者的唾液微生态及代谢特征。唾液微生物组与代谢组联合特征对T2DM合并慢性牙周炎具有一定辅助评估价值,可为其临床无创筛查提供参考。

     

    Abstract:
    Objective To investigate the value of salivary microbial and metabolic profiles for the adjunctive assessment of chronic periodontitis accompanied by type 2 diabetes mellitus (T2DM).
    Methods Eighty patients with chronic periodontitis who were treated at the Departments of Stomatology and Endocrinology of Changzhou First People’s Hospital between 2023 and 2025 were enrolled. They were divided into a chronic periodontitis-alone group (CP group, n = 40) and a chronic periodontitis with T2DM group (DM-CP group, n = 40). Periodontal clinical parameters, including plaque index (PLI), sulcus bleeding index (SBI), probing depth (PD) and attachment loss (AL), as well as systemic glycemic indices, including fasting blood glucose (FBG) and glycated hemoglobin (HbA1c), were recorded for all participants. Unstimulated whole-saliva samples were collected and subjected to microbiome and metabolome analyses using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, respectively.
    Results PLI (P = 0.007), PD (P < 0.001), HbA1c (P < 0.001) and FBG (P < 0.001) were higher in the DM-CP group than in the CP group. After adjustment for age and sex, T2DM status remained associated with greater PD (β = 0.766, P < 0.001) and a higher PLI (β = 0.330, P = 0.008). The 16S rRNA gene sequencing results showed reduced salivary microbial richness and increased relative abundances of genera such as Streptococcus in the DM-CP group, with a statistically significant difference in β-diversity between the two groups (P = 0.001). LC-MS analysis revealed distinct metabolic profiles between the two groups. The differential metabolites were mainly enriched in pathways such as steroid hormone biosynthesis and bile secretion, and metabolites such as neurokinin A were more abundant in the DM-CP group. Several characteristic bacterial genera and metabolites were associated with PD and HbA1c. The exploratory random forest model showed that the AUC of the microbiome metabolome combined model was 0.941(95%CI: 0.799-1.000), with a sensitivity of 1.00 and a specificity of 0.78. Although the AUC was numerically higher than that of the microbiome-only or metabolome-only models, the differences were not statistically significant (both P > 0.05).
    Conclusions T2DM may affect the salivary microbial and metabolic profiles of patients with chronic periodontitis. The combined salivary microbiome and metabolome features have value for the adjunctive assessment of chronic periodontitis with T2DM and may provide a reference for noninvasive clinical screening.

     

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