Causal Effects of Gut Microbiota on Morning Chronotype, Insomnia and Sleep Duration: A Two-Sample Mendelian Randomization Study.

BACKGROUND: The gut microbiota has been shown to be closely associated with brain function; however, whether it exerts a causal influence on sleep traits remains to be further explored. Mendelian randomization (MR) is an emerging epidemiological approach that uses whole-genome sequencing data to infer causal relationships. In this study, we conducted a two-sample MR analysis to investigate the causal effects of gut microbiota on three domains of sleep traits: morning chronotype, insomnia, and sleep duration. METHODS: Single nucleotide polymorphisms strongly associated with 196 gut microbiota taxa were selected as instrumental variables. Morning chronotype, insomnia, and sleep duration were used as outcomes. MR and sensitivity analyses were performed to assess the causal relationships between gut microbiota and sleep traits. RESULTS: Three taxa (Bifidobacteriales, Bifidobacteriaceae, and Bifidobacterium) were negatively associated with morning chronotype, while Tyzzerella 3 showed a positive causal effect on morning chronotype. Oscillibacter was negatively associated with insomnia, whereas four taxa (Negativicutes, Selenomonadales, the Clostridium innocuum group, and Lachnoclostridium) were identified as risk-increasing factors for insomnia. Lentisphaerae and Victivallaceae were positively associated with sleep duration. Actinobacteria and Alistipes had negative effects on long sleep duration, whereas Ruminiclostridium 6 was positively associated with long sleep duration. Four taxa (Victivallales, Anaerofilum, Lentisphaerae, and Lentisphaeria) were negatively associated with short sleep duration. CONCLUSIONS: Our findings suggest that specific gut microbiota taxa may be positively or negatively associated with sleep traits. These results offer new insights into the potential role of gut microbiota in sleep regulation and provide a basis for future studies aimed at understanding whether modulating microbial composition could influence sleep health.