Sleep and circadian disruption reshape immune homeostasis in oral tissues: mechanistic roles of melatonin and cortisol in periodontal disease and xerostomia
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Sleep disturbance has emerged as a major modifier of immune homeostasis in chronic inflammatory diseases, yet its immunological relevance to oral tissues remains incompletely integrated. Accumulating evidence indicates that sleep and oral inflammatory diseases are linked through coordinated neuroendocrine–immune pathways, with melatonin and cortisol constituting a central circadian hormonal axis that shapes immune balance. Melatonin, predominantly secreted during the nocturnal phase, exerts antioxidant, anti-inflammatory, and immunomodulatory effects that support periodontal immune homeostasis and salivary gland function. In contrast, sleep disruption and chronic activation of the hypothalamic-pituitary-adrenal axis led to dysregulated cortisol secretion, promoting immune suppression, microbial dysbiosis, and progressive periodontal tissue breakdown. Experimental, observational, and clinical studies consistently associate poor sleep quality with suppressed melatonin rhythms, elevated cortisol levels, and increased prevalence of periodontitis and xerostomia, while sleep disorders such as obstructive sleep apnea further exacerbate oral inflammatory vulnerability through both circadian and mechanical mechanisms. Despite these associations, the causal immune pathways linking circadian hormonal dysregulation to oral disease progression remain insufficiently defined. This review synthesizes current mechanistic and clinical evidence to conceptualize the melatonin–cortisol axis as an immunoregulatory bridge between disturbed sleep and oral inflammatory disease, and discusses its implications for biomarker development and immune-informed therapeutic strategies.
Date Issued
2026-04-29
Date Acceptance
2026-04-17
Citation
Frontiers in Immunology, 2026, 17
ISSN
1664-3224
Publisher
Frontiers Media S.A.
Journal / Book Title
Frontiers in Immunology
Volume
17
Copyright Statement
©2026 Chen, Hung, Kuo, Hsu, Lee, Tsai, Majumdar and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Publication Status
Published
Article Number
1781288
Date Publish Online
2026-04-29