Alterations in Gut Microbiota Are Correlated With Serum Metabolites in Patients With Insomnia Disorder.

Jing Zhou,Bairu Chen,Xiaoling Wu,Yongli Li,Zhonglin Li,Gang Li,Shewei Dou,Zhi Zou,Fengshan Yan

doi:10.3389/fcimb.2022.722662

Abstract

This study aimed to investigate insomnia-related alterations in gut microbiota and their association with serum metabolites. A total of 24 patients with insomnia disorder and 22 healthy controls were recruited. The fecal and serum samples were collected. The 16s rRNA sequencing and bioinformatics analysis were conducted to explore insomnia-related changes in the diversity, structure, and composition of the gut microbiota. UPLC-MS was performed to identify insomnia-related serum metabolites. Spearman correlation analysis was used to investigate the correlations between insomnia-related gut bacteria and the serum metabolites. Despite the nonsignificant changes in the diversity and structure of gut microbiota, insomnia disorder patients had significantly decreased family Bacteroidaceae, family Ruminococcaceae, and genus Bacteroides, along with significantly increased family Prevotellaceae and genus Prevotella, compared with healthy controls. Genus Gemmiger and genus Fusicatenibacter were dominant in patients with insomnia disorder, whereas genus Coprococcus, genus Oscillibacter, genus Clostridium XI, and family Peptostreptococcaceae were dominant in healthy controls. The UPLC-MS analysis identified 97 significantly decreased metabolites and 74 significantly increased metabolites in the serum samples of patients with insomnia disorder, compared with those of healthy controls. KEGG enrichment analysis revealed 1 significantly upregulated metabolic pathway and 16 downregulated metabolic pathways in patients with insomnia disorder. Furthermore, Spearman correlation analysis unveiled significant correlations among the altered bacteria genus and serum metabolites. Patients with insomnia disorder have differential gut microbiota and serum metabolic profiles compared with healthy controls. The alterations in gut microbiota were correlated with specific serum metabolites, suggesting that some serum metabolites might mediate gut microbiota-brain communication in the pathogenesis of insomnia disorder.

Highlights

Insomnia is a sleeping disorder characterized by difficulty in falling asleep and waking up during the night (Daley et al, 2009)
Patients with insomnia disorder showed significantly higher Insomnia Severity Index (ISI) (1.79 ± 3.07 vs. 19.54 ± 5.99, p < 0.001), Pittsburgh Sleep Quality Index (PSQI) (3.21 ± 1.89 vs. 15.87 ± 2.59, p < 0.001), Hamilton Depression Rating Scale (HAMD) (2.50 ± 2.56 vs. 19.33 ± 8.09, p
We found that genus Gemmiger and Fusicatenibacter were dominant in patients with insomnia disorder, whereas family Peptostreptococcaceae, genus Coprococcus, genus Oscillibacter, and genus Clostridium XI were dominant in healthy controls (Figure 1G)

Summary

Introduction

Insomnia is a sleeping disorder characterized by difficulty in falling asleep and waking up during the night (Daley et al, 2009). The gut-central nervous system (CNS) communication plays an important role in the development of sleeping, mood, and mental disorders (Lucas, 2018). Li et al have shown that human gut microbiota can regulate the sleep and mental states of the host and that the emotional states affect the composition of gut microbes, suggesting an important role of the brain-gut microbiota axis in human health (Li et al, 2018). 5-HT regulates sleep and mood by interacting with 5-HT1A and 5-HT2A autoreceptors, playing important roles in the development of insomnia disorder and depression (Gershon, 2013). These findings suggest that some metabolites may mediate the interaction between the brain and gut microbiota. The gut microbiota and serum metabolites involved in insomnia disorder remain largely unknown

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