Linking Gut Microbiota, Oral Microbiota, and Serum Metabolites in Insomnia Disorder: A Preliminary Study

Overview

Journal Nat Sci Sleep

Publisher Dove Medical Press

Date 2024 Dec 12

PMID 39664229

Authors

Weifeng Lin

Yifan Yang

Yurong Zhu

Rong Pan

Chaonan Liu

Jiyang Pan

Affiliations

Soon will be listed here.

Abstract

Purpose: Despite recent findings suggesting an altered gut microbiota in those suffering from insomnia disorder (ID), research into the gut microbiota, oral microbiota, serum metabolites, and their interactions in patients with ID is sparse.

Patients And Methods: We collected a total of 114 fecal samples, 133 oral cavity samples and 20 serum samples to characterize the gut microbiota, oral microbiota and serum metabolites in a cohort of 76 ID patients (IDs) and 59 well-matched healthy controls (HCs). We assessed the microbiota as potentially biomarkers for ID for ID by 16S rDNA sequencing and elucidated the interactions involving gut microbiota, oral microbiota and serum metabolites in ID in conjunction with untargeted metabolomics.

Results: Gut and oral microbiota of IDs were dysbiotic. Gut and oral microbial biomarkers could be used to differentiate IDs from HCs. Eleven significantly altered serum metabolites, including adenosine, phenol, and phenol sulfate, differed significantly between groups. In multi-omics analyses, adenosine showed a positive correlation with genus_ (0.029) and total sleep time (=0.016). Additionally, phenol and phenol sulphate had a negative correlation with genus (=0.0059; =0.0059) and a positive correlation with Pittsburgh Sleep Quality Index (=0.006; =0.006) and Insomnia Severity Index (=0.021; =0.021).

Conclusion: Microbiota and serum metabolite changes in IDs are strongly correlated with clinical parameters, implying mechanistic links between altered bacteria, serum metabolites and ID. This study offers novel perspective into the interaction among gut microbiota, oral microbiota, and serum metabolites for ID.

References

Huang W, Ramsey K, Marcheva B, Bass J . Circadian rhythms, sleep, and metabolism. J Clin Invest. 2011; 121(6):2133-41. PMC: 3104765. DOI: 10.1172/JCI46043. View

Gehrman P, Sengupta A, Harders E, Ubeydullah E, Pack A, Weljie A . Altered diurnal states in insomnia reflect peripheral hyperarousal and metabolic desynchrony: a preliminary study. Sleep. 2018; 41(5). PMC: 5946940. DOI: 10.1093/sleep/zsy043. View

Poon K, Ho M, Tai A, Leung M, Chan M, Lau W . Mediating roles of sleep quality and resilience in the relationships between chronotypes and mental health symptoms. Sci Rep. 2024; 14(1):5874. PMC: 10928116. DOI: 10.1038/s41598-024-56688-w. View

Zhou J, Wu X, Li Z, Zou Z, Dou S, Li G . Alterations in Gut Microbiota Are Correlated With Serum Metabolites in Patients With Insomnia Disorder. Front Cell Infect Microbiol. 2022; 12:722662. PMC: 8892143. DOI: 10.3389/fcimb.2022.722662. View

Koh A, Manneras-Holm L, Yunn N, Nilsson P, Ryu S, Molinaro A . Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. Cell Metab. 2020; 32(4):643-653.e4. PMC: 7546034. DOI: 10.1016/j.cmet.2020.07.012. View

McDonald D, Price M, Goodrich J, Nawrocki E, DeSantis T, Probst A . An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea. ISME J. 2011; 6(3):610-8. PMC: 3280142. DOI: 10.1038/ismej.2011.139. View

Walsh N, Repa L, Garland S . Mindful larks and lonely owls: The relationship between chronotype, mental health, sleep quality, and social support in young adults. J Sleep Res. 2021; 31(1):e13442. DOI: 10.1111/jsr.13442. View

Sureda A, Daglia M, Arguelles Castilla S, Sanadgol N, Nabavi S, Khan H . Oral microbiota and Alzheimer's disease: Do all roads lead to Rome?. Pharmacol Res. 2019; 151:104582. DOI: 10.1016/j.phrs.2019.104582. View

Sun T, Li M, Yu X, Liang D, Xie G, Sang C . 3MCor: an integrative web server for metabolome-microbiome-metadata correlation analysis. Bioinformatics. 2021; 38(5):1378-1384. DOI: 10.1093/bioinformatics/btab818. View

10.

Matenchuk B, Mandhane P, Kozyrskyj A . Sleep, circadian rhythm, and gut microbiota. Sleep Med Rev. 2020; 53:101340. DOI: 10.1016/j.smrv.2020.101340. View

11.

Zhang S, Bai L, Goel N, Bailey A, Jang C, Bushman F . Human and rat gut microbiome composition is maintained following sleep restriction. Proc Natl Acad Sci U S A. 2017; 114(8):E1564-E1571. PMC: 5338418. DOI: 10.1073/pnas.1620673114. View

12.

Wen T, Xie P, Yang S, Niu G, Liu X, Ding Z . ggClusterNet: An R package for microbiome network analysis and modularity-based multiple network layouts. Imeta. 2024; 1(3):e32. PMC: 10989811. DOI: 10.1002/imt2.32. View

13.

Liu M, Wang X, Wu F, Dai N, Chen M, Yu J . Variations of Oral Microbiome in Chronic Insomnia Patients with Different Tongue Features. Am J Chin Med. 2020; 48(4):923-944. DOI: 10.1142/S0192415X20500445. View

14.

Sheehan D, Lecrubier Y, Sheehan K, Amorim P, Janavs J, Weiller E . The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1999; 59 Suppl 20:22-33;quiz 34-57. View

15.

Gao L, Xu T, Huang G, Jiang S, Gu Y, Chen F . Oral microbiomes: more and more importance in oral cavity and whole body. Protein Cell. 2018; 9(5):488-500. PMC: 5960472. DOI: 10.1007/s13238-018-0548-1. View

16.

Humer E, Pieh C, Brandmayr G . Metabolomics in Sleep, Insomnia and Sleep Apnea. Int J Mol Sci. 2020; 21(19). PMC: 7583860. DOI: 10.3390/ijms21197244. View

17.

Wall R, Cryan J, Ross R, Fitzgerald G, Dinan T, Stanton C . Bacterial neuroactive compounds produced by psychobiotics. Adv Exp Med Biol. 2014; 817:221-39. DOI: 10.1007/978-1-4939-0897-4_10. View

18.

Wang Z, Wang Z, Lu T, Chen W, Yan W, Yuan K . The microbiota-gut-brain axis in sleep disorders. Sleep Med Rev. 2022; 65:101691. DOI: 10.1016/j.smrv.2022.101691. View

19.

Li Y, Zhang B, Zhou Y, Wang D, Liu X, Li L . Gut Microbiota Changes and Their Relationship with Inflammation in Patients with Acute and Chronic Insomnia. Nat Sci Sleep. 2020; 12:895-905. PMC: 7652227. DOI: 10.2147/NSS.S271927. View

20.

Smith R, Easson C, Lyle S, Kapoor R, Donnelly C, Davidson E . Gut microbiome diversity is associated with sleep physiology in humans. PLoS One. 2019; 14(10):e0222394. PMC: 6779243. DOI: 10.1371/journal.pone.0222394. View