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.

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