Introduction

Early diagnosis of periodontitis by means of a rapid, accurate and non-invasive method is highly desirable to reduce the individual and epidemiological burden of this largely prevalent disease.

Objectives

The aims of the present systematic review were to examine potential salivary metabolic biomarkers and pathways associated to periodontitis, and to assess the accuracy of salivary untargeted metabolomics for the diagnosis of periodontal diseases.

Methods

Relevant studies identified from MEDLINE (PubMed), Embase and Scopus databases were systematically examined for analytical protocols, metabolic biomarkers and results from the multivariate analysis (MVA). Pathway analysis was performed using the MetaboAnalyst online software and quality assessment by means of a modified version of the QUADOMICS tool.

Results

Twelve studies met the inclusion criteria, with sample sizes ranging from 19 to 130 subjects. Compared to periodontally healthy individuals, valine, phenylalanine, isoleucine, tyrosine and butyrate were found upregulated in periodontitis patients in most studies; while lactate, pyruvate and N-acetyl groups were the most significantly expressed in healthy individuals. Metabolic pathways that resulted dysregulated are mainly implicated in inflammation, oxidative stress, immune activation and bacterial energetic metabolism. The findings from MVA revealed that periodontitis is characterized by a specific metabolic signature in saliva, with coefficients of determination ranging from 0.52 to 0.99.

Conclusions

This systematic review summarizes candidate metabolic biomarkers and pathways related to periodontitis, which may provide opportunities for the validation of diagnostic or predictive models and the discovery of novel targets for monitoring and treating such a disease (PROSPERO CRD42020188482).

中文翻译：

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用于牙周病诊断的唾液代谢组学：具有方法学质量评估的系统评价

介绍

通过快速、准确和非侵入性的方法对牙周炎进行早期诊断是非常需要的，以减少这种普遍流行的疾病的个体和流行病学负担。

目标

本系统评价的目的是检查与牙周炎相关的潜在唾液代谢生物标志物和途径，并评估唾液非靶向代谢组学诊断牙周病的准确性。

方法

系统地检查了从 MEDLINE (PubMed)、Embase 和 Scopus 数据库中确定的相关研究的分析方案、代谢生物标志物和多变量分析 (MVA) 的结果。通路分析是使用 MetaboAnalyst 在线软件进行的，并通过 QUADOMICS 工具的修改版本进行质量评估。

结果

12 项研究符合纳入标准，样本量从 19 到 130 名受试者不等。与牙周健康个体相比，大多数研究发现牙周炎患者的缬氨酸、苯丙氨酸、异亮氨酸、酪氨酸和丁酸盐上调；而乳酸、丙酮酸和N-乙酰基在健康个体中的表达最为显着。导致失调的代谢途径主要与炎症、氧化应激、免疫激活和细菌能量代谢有关。MVA 的研究结果表明，牙周炎的特征在于唾液中的特定代谢特征，其决定系数范围为 0.52 至 0.99。

结论

本系统综述总结了与牙周炎相关的候选代谢生物标志物和途径，这可能为验证诊断或预测模型以及发现监测和治疗此类疾病的新目标提供机会 (PROSPERO CRD42020188482)。