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

Weifeng Lin,1,2 Yifan Yang,3 Yurong Zhu,4 Rong Pan,5 Chaonan Liu,2 Jiyang Pan2 1Department of Neurology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523000, People’s Republic of China; 2Department of Psychiatry, Sleep Medicine Center, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 3Sleep Medicine Center, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 4Department of Pathology, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523000, People’s Republic of China; 5Department of Psychology, The Third People’s Hospital of Zhaoqing, Zhaoqing, Guangdong Province, 526060, People’s Republic of ChinaCorrespondence: Jiyang Pan, Email [email protected]: 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_Lachnospira (p= 0.029) and total sleep time (p=0.016). Additionally, phenol and phenol sulphate had a negative correlation with genus_Coprococcus (p=0.0059; p=0.0059) and a positive correlation with Pittsburgh Sleep Quality Index (p=0.006; p=0.006) and Insomnia Severity Index (p=0.021; p=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.Keywords: insomnia disorder, gut microbiota, oral microbiota, serum metabolites, multi-omics, biomarkers