The oral cavity has one of the most complex microbial communities in the human body, harboring over 1000 species of microorganisms (Lamont et al., 2018). This microbial ecosystem interacts dynamically and bidirectionally with the host, influencing various physiological processes. Under normal conditions, the oral microbiome and host are in a state of equilibrium. However, disruptions in this equilibrium can lead to dysbiosis, triggering inflammatory responses. Dysregulated and unresolved inflammatory responses can progress to chronic inflammation, as seen in periodontitis. Emerging research suggests that there is a strong association between periodontitis and systemic diseases (Hajishengallis, 2022; Hajishengallis & Chavakis, 2021). It is believed that in periodontitis, systemic dissemination of inflammatory mediators and oral bacteria into the bloodstream can potentially contribute to the initiation and aggravation of systemic conditions such as cancer, cardiovascular diseases, diabetes, rheumatoid arthritis, and Alzheimer's disease, via trained immunity.

Metabolism is another key player in the intricate web of oral and systemic health. On one hand, the oral microbiota actively participates in the host metabolic processes by metabolizing dietary components and producing metabolites that impact the host's metabolism (Minty et al., 2019). On the other hand, host metabolic dysfunction can alter the composition of oral microbiome, leading to oral dysbiosis (Pirih et al., 2021). Therefore, dysregulation of metabolic pathways in oral microbiome and host may contribute to the development of diseases both locally in the oral cavity and systemically throughout the body.

In the last few decades, significant advances have been made to understand the dynamic complexity of oral microbiome and its interaction with the host immune and metabolic systems and how this delicate relationship can be the major driver of health and disease not only within the oral cavity but also at distant tissues. Here, we present a three-part special issue entitled “Regulation of metabolism and inflammation: links with oral and systemic health.” Ten original articles and five reviews are collected for scientists to share recent advances in understanding host–microbial interactions, inflammation, and metabolism in periodontal disease and associated systemic diseases. Understanding this intricate relationship is essential for identifying therapeutic interventions to aid in the control and prevention of periodontal disease and its systemic comorbidities.

In this part of the special issue (Part I), five original articles are present. Two in vitro studies provide proof-of-concept evidence about how periodontal pathogens regulate host immune response. Sahingur and colleagues (Albuquerque-Souza et al., 2023) demonstrated that prolong exposure to Fusobacterium nucleatum triggers a pro-senescence response in gingival epithelia cells and impairs their reparative capacity, which may impact periodontal tissue homeostasis, thus increasing host susceptibility to periodontitis during aging. Sharma and colleagues (Settem et al., 2023) showed that Tannerella forsythia can scavenge nucleotide oligomerization domain (NOD) ligand peptidoglycan fragments secreted by F. nucleatum and dampen NOD-mediated inflammation of oral epithelial cells, which may affect innate immunity and promote microbial colonization and dysbiosis, leading to increased host susceptibility to periodontitis.

Porphyromonas gingivalis infection and disruption of microbial community homeostasis are believed to affect the progression of tumorigenesis (Gao et al., 2021). Previous studies have shown that GroEL, a heat shock protein 60 secreted by P. gingivalis, enhances migration of endothelial progenitor cells (EPCs) and promotes angiogenesis and tumor growth in animal models (Lin et al., 2015). In this special issue, Lin et al. (2023) demonstrated that GroEL-induced microRNAs accelerate tumor neovascularization and tumor growth by downregulating membrane-bound thrombomodulin expression in EPCs, and targeting specific microRNAs can reduce the effect of GroEL on tumor growth.

Emerging epidemiological and clinical evidence support the existence of a two-way relationship between periodontitis and diabetes (Stohr et al., 2021). However, the mechanisms underlying the links between these two conditions are not fully understood. Using high-resolution whole metagenomic shotgun analysis, Scapoli and colleagues (Favale et al., 2023) explored the compositional and functional profile of the subgingival microbiome in type 2 diabetics (T2D) and nondiabetics human subjects with or without periodontitis. They found that patients with different clinical conditions have different subgingival microbiome composition and that a set of dysregulated metabolic pathways is significantly enriched in the subgingival microbiome in periodontitis and/or diabetic patients. The results of this study provide evidence that dysregulated metabolic pathways in oral microbiome underlie systemic inflammation and the bidirectional relationship between T2D and periodontitis.

Along this line, the study by Xin and colleagues (Thomas et al., 2023) demonstrated that dysregulated host metabolite profile can change microbial community structure of T2D. They found that T2D mice harbor a significantly different gut microbiome compared with control mice, due to elevated levels of succinate in host circulation and tissues. Elevated levels of succinate have been found in T2D and periodontitis in both mice and human studies (Guo et al., 2022). The study suggests that targeting succinate G protein-coupled receptor (SUCNR1) signaling pathway is a promising therapeutic approach in metabolic, inflammatory, and immune disorders with elevated succinate levels, such as periodontitis and T2D.

We would like to thank all the authors for their contribution to this special issue. We hope this research topic will foster the understanding of the complex and dynamic interplay between oral microbiome, inflammation, and metabolism in oral and systemic diseases.

口腔是人体最复杂的微生物群落之一，拥有1000多种微生物（Lamont等，2018）。这种微生物生态系统与宿主动态地、双向地相互作用，影响各种生理过程。正常情况下，口腔微生物组和宿主处于平衡状态。然而，这种平衡的破坏可能导致生态失调，引发炎症反应。失调和未解决的炎症反应可能会发展为慢性炎症，如牙周炎。新兴研究表明牙周炎与全身性疾病之间存在密切关联（Hajishengallis，2022；Hajishengallis & Chavakis，2021）。据认为，在牙周炎中，炎症介质和口腔细菌向血液中的系统性传播可能通过训练有素的免疫力导致癌症、心血管疾病、糖尿病、类风湿性关节炎和阿尔茨海默氏病等全身性疾病的引发和加重。

新陈代谢是口腔和全身健康错综复杂的网络中的另一个关键因素。一方面，口腔微生物群通过代谢膳食成分并产生影响宿主代谢的代谢物，积极参与宿主代谢过程（Minty et al., 2019）。另一方面，宿主代谢功能障碍会改变口腔微生物组的组成，导致口腔菌群失调（Pirih et al., 2021）。因此，口腔微生物组和宿主代谢途径的失调可能会导致口腔局部和全身系统疾病的发生。

在过去的几十年里，人们在了解口腔微生物组的动态复杂性及其与宿主免疫和代谢系统的相互作用以及这种微妙的关系如何成为口腔健康和疾病的主要驱动因素方面取得了重大进展。也存在于远处的组织。在这里，我们提出一个由三部分组成的特刊，题为“新陈代谢和炎症的调节：与口腔和全身健康的联系”。收集了十篇原创文章和五篇评论，供科学家分享在了解牙周病和相关全身性疾病的宿主-微生物相互作用、炎症和代谢方面的最新进展。了解这种复杂的关系对于确定治疗干预措施以帮助控制和预防牙周病及其全身合并症至关重要。

本期特刊（第一部分）收录了五篇原创文章。两项体外研究提供了关于牙周病原体如何调节宿主免疫反应的概念验证证据。Sahinur 及其同事（Albuquerque-Souza 等，2023）证明，长期接触具核梭杆菌会引发牙龈上皮细胞的促衰老反应，并损害其修复能力，这可能会影响牙周组织稳态，从而增加宿主对牙周炎的易感性。老化。Sharma 及其同事 (Settem et al., 2023 ) 表明，连翘坦纳菌 ( Tannerella forsythia ) 可以清除具核梭杆菌分泌的核苷酸寡聚结构域 (NOD) 配体肽聚糖片段，并抑制 NOD 介导的口腔上皮细胞炎症，这可能会影响先天免疫并促进微生物定植和生态失调，导致宿主对牙周炎的易感性增加。

牙龈卟啉单胞菌感染和微生物群落稳态的破坏被认为会影响肿瘤发生的进展（Gao et al., 2021）。先前的研究表明，牙龈卟啉单胞菌分泌的热休克蛋白 60 GroEL在动物模型中增强内皮祖细胞（EPC）的迁移并促进血管生成和肿瘤生长（Lin et al., 2015）。在本期特刊中，林等人。( 2023 )证明GroEL诱导的microRNA通过下调EPC中膜结合血栓调节蛋白的表达来加速肿瘤新生血管形成和肿瘤生长，并且靶向特定的microRNA可以减少GroEL对肿瘤生长的影响。

新出现的流行病学和临床证据支持牙周炎和糖尿病之间存在双向关系（Stohr 等，2021）。然而，这两种情况之间联系的潜在机制尚不完全清楚。Scapoli 及其同事 (Favale et al., 2023 )使用高分辨率全宏基因组鸟枪法分析，探索了患有或不患有牙周炎的 2 型糖尿病患者 (T2D) 和非糖尿病人类受试者的龈下微生物群的组成和功能特征。他们发现，不同临床状况的患者具有不同的龈下微生物组组成，并且牙周炎和/或糖尿病患者的龈下微生物组中显着丰富了一组失调的代谢途径。这项研究的结果提供了证据，表明口腔微生物组代谢途径失调是全身炎症以及 T2D 和牙周炎之间双向关系的基础。

沿着这一思路，Xin 及其同事的研究（Thomas 等人，2023）证明，宿主代谢物谱失调可以改变 T2D 的微生物群落结构。他们发现，由于宿主循环和组织中琥珀酸水平升高，T2D 小鼠的肠道微生物组与对照小鼠显着不同。在小鼠和人类研究中都发现 T2D 和牙周炎中琥珀酸水平升高（Guo 等人，2022）。该研究表明，针对琥珀酸 G 蛋白偶联受体 (SUCNR1) 信号通路是治疗琥珀酸水平升高的代谢、炎症和免疫疾病（例如牙周炎和 T2D）的一种有前途的治疗方法。

我们要感谢所有作者对本期特刊的贡献。我们希望这个研究课题能够促进人们对口腔和全身疾病中口腔微生物组、炎症和代谢之间复杂而动态的相互作用的理解。