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

Abstract

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.

Investigation of the shared biological mechanisms and common biomarker APTAF1 of sleep deprivation and mild cognitive impairment using integrated bioinformatics analysis

“…Our results regarding the impaired mitochondrial electron transport chain are consistent with those of previous studies on both SD and MCI ( Morris et al, 2021 ; Chen et al, 2022 ), thus indicating that deficiencies in energy-generating mitochondrial pathways play an important role in cognitive impairment induced by SD. In addition, among the 32 MitoDEGs involved in metabolism, 11 genes are implicated, including six in lipid metabolism (ACADL, THEM4, ACSM3, LYPLA1, TSPO, and SCP2), one in carbohydrate metabolism (HMGCL), one in amino acid metabolism (GLS2), and one in nucleotide metabolism (FHIT), ( Figure 8B ).…”

Metabolic profiles of saliva in male mouse models of chronic sleep disorders induced by psychophysiological stress

“…Chronic sleep deprivation induces oral and systemic inflammation in rats 20 . Therefore, we assessed IL-6 and IL-1β mRNA expression in control and CSD tongue tissues and antigen levels in plasma.…”

“…Salivary concentrations of amyloid-β 14 , 18 and tau 19 reflect cognitive dysfunction. Proteomic profiling has revealed that neurodegenerative and inflammatory pathways are enriched in tongue tissues from rats with chronic sleep deprivation 20 . However, the effects of CSD on salivary metabolic profiles remain unknown.…”

Oral microbiome: a doubtful predictor but potential target of cardiovascular diseases

“…In addition, sleep has been linked to alterations in oral microbiome. Recently, chronic sleep deprivation was shown to alter oral microbiome, and cause oral and systemic inflammation in rats [ 16 ]. These findings suggested that healthy lifestyles, like regular exercise and sufficient sleep, are beneficial to oral and cardiovascular health.…”