Hoon Je Seong Younghwa Baek Siwoo Lee Hee-Jeong Jin ^*

• Korea Institute of Oriental Medicine (KIOM), Daejeon, Republic of Korea

Sleep quality is a vital determinant of human health as sleep disorders are associated with cognitive deficits, and chronic sleep deprivation is associated with a broad range of health complications. Previous studies on the association between the gut microbiome and sleep quality have been constrained by small sample sizes or have focused on specific sleep disorders, thus yielding inconsistent results. Herein, we investigated the relationship between microbial composition and sleep quality in a cohort of 159 Koreans. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI), determined through a self-administered questionnaire. Gut microbiome analyses were performed using 16S rRNA amplicons. We found no direct correlation between microbial alpha diversity metrics and sleep; however, we identified differences in beta diversity among sleep quality groups (with a PSQI score >5 indicating poor sleep quality and PSQI ≤5 indicating good sleep quality). We also found differential microbial signatures (Bacteroides, Prevotella 9, and Faecalibacterium) among the groups. Furthermore, functional metabolic pathway profiles revealed significant linear correlations of the L-arginine and L-tryptophan biosynthetic pathways as well as 4-aminobutanoate degradation with sleep status. In particular, Faecalibacterium prausnitzii, which harbors these metabolic pathways, showed differences between sleep quality groups and a linear association with sleep quality scores and was thus identified as the species most strongly associated with sleep status. This study provides a significant advance in our understanding of the relationship between gut microbiota and sleep regulation. The current findings provide a basis for further research into potential therapeutic strategies for sleep disorders targeting the gut microbiome.