Table_6_Multi-Omics Analysis Reveals the Systematic Relationship Between Oral Homeostasis and Chronic Sleep Deprivation in Rats.xlsx

Sleep disorders were associated with oral health. Inflammation has especially been thought to be a key factor in linking oral diseases and sleep deficiency. However, how chronic sleep deprivation (CSD) affects oral homeostasis, particularly oral inflammation and oral microbiota, is still unknown. This study aimed to uncover the systematic relationship between oral homeostasis and CSD in rats. The metabolomics in serum, proteomics in the tongue tissues, and microbiome analysis in the oral cavity in CSD rats were performed. Multi-omics data integration analysis was performed to uncover the systematic relationship between oral homeostasis and CSD through the weighted correlation network analysis. We found that CSD could lead to oral inflammation in rats. CSD significantly increased systemic inflammation by enhancing the serum levels of IL-1β, IL-6 and inhibiting the serum level of IL-10. Serum levels of adrenocorticotropin hormone, corticosterone, and triiodothyronine were increased in CSD rats, and the steroid hormone biosynthesis pathway was also found to be involved in the perturbation resulting from CSD, together suggesting the activation of the hypothalamic-pituitary-adrenocortical and hypothalamic‐pituitary‐thyroid axis. CSD led to changes of oral microbiota composition, and g_Acinetobacter, Candidatus Chryseobacterium massiliae, and g_Moraxella were significantly correlated with multiple proteins in bacterial invasion of epithelial cells pathway, which may partially responsible for oral inflammation resulting from CSD. The changes of proteomic profiling expression caused by CSD in tongue tissues were mainly enriched in neurodegenerative diseases pathways and immune/inflammation-related pathways. Multi-omics analysis indicated that the inflammatory response-related modules were significantly correlated with the neurodegenerative disease-related module suggesting a possible link between neurodegenerative diseases and oral inflammation. Together, CSD induced oral inflammation and subtle changes on oral microbiota. Our study is helpful to further understand the role that oral homeostasis plays in the process by which CSD affects human health and disease.

睡眠障碍与口腔健康息息相关。炎症被视作连接口腔疾病与睡眠不足的核心介导因素。然而，慢性睡眠剥夺（chronic sleep deprivation, CSD）如何影响口腔稳态，尤其是口腔炎症与口腔微生物群的稳态，目前仍未明确。本研究以大鼠为模型，旨在阐明口腔稳态与慢性睡眠剥夺之间的系统性关联。研究对慢性睡眠剥夺大鼠开展了血清代谢组学、舌组织蛋白质组学及口腔微生物组分析，并通过加权相关网络分析进行多组学数据整合，以揭示口腔稳态与慢性睡眠剥夺间的内在联系。结果显示，慢性睡眠剥夺可诱导大鼠出现口腔炎症；其通过升高血清IL-1β、IL-6水平并降低血清IL-10水平，显著加剧了全身炎症反应。慢性睡眠剥夺大鼠的血清促肾上腺皮质激素、皮质酮及三碘甲状腺原氨酸水平均显著升高，且类固醇激素生物合成通路参与了慢性睡眠剥夺引发的代谢扰动，上述结果共同提示下丘脑-垂体-肾上腺轴与下丘脑-垂体-甲状腺轴被激活。慢性睡眠剥夺会改变口腔微生物群的组成；不动杆菌属（g_Acinetobacter）、Candidatus Chryseobacterium massiliae以及莫拉氏菌属（g_Moraxella）与上皮细胞细菌侵袭通路中的多种蛋白质显著相关，这或许是慢性睡眠剥夺引发口腔炎症的部分机制。慢性睡眠剥夺导致的舌组织蛋白质组表达谱变化，主要富集于神经退行性疾病通路及免疫/炎症相关通路。多组学分析表明，炎症反应相关模块与神经退行性疾病相关模块显著相关，提示神经退行性疾病与口腔炎症之间可能存在潜在关联。综上，慢性睡眠剥夺可诱导大鼠发生口腔炎症，并引发口腔微生物群的细微改变。本研究有助于进一步阐明口腔稳态在慢性睡眠剥夺影响人类健康与疾病进程中所发挥的作用。