The Causal Relationship between the Morning Chronotype and the Gut Microbiota: A Bidirectional Two-Sample Mendelian Randomization Study.

ABSTRACT

BACKGROUND: Numerous observational studies have documented an association between the circadian rhythm and the composition of the gut microbiota. However, the bidirectional causal effect of the morning chronotype on the gut microbiota is unknown. METHODS: A two-sample Mendelian randomization study was performed, using the summary statistics of the morning chronotype from the European Consortium and those of the gut microbiota from the largest available genome-wide association study meta-analysis, conducted by the MiBioGen consortium. The inverse variance-weighted (IVW), weighted mode, weighted median, MR-Egger regression, and simple mode methods were used to examine the causal association between the morning chronotype and the gut microbiota. A reverse Mendelian randomization analysis was conducted on the gut microbiota, which was identified as causally linked to the morning chronotype in the initial Mendelian randomization analysis. Cochran's Q statistics were employed to assess the heterogeneity of the instrumental variables. RESULTS: Inverse variance-weighted estimates suggested that the morning chronotype had a protective effect on Family Bacteroidaceae (ß = -0.072; 95% CI -0.143, -0.001; p = 0.047), Genus Parabacteroides (ß = -0.112; 95% CI -0.184, -0.039; p = 0.002), and Genus Bacteroides (ß = -0.072; 95% CI -0.143, -0.001; p = 0.047). In addition, the gut microbiota (Family Bacteroidaceae (OR = 0.925; 95% CI 0.857, 0.999; p = 0.047), Genus Parabacteroides (OR = 0.915; 95% CI 0.858, 0.975; p = 0.007), and Genus Bacteroides (OR = 0.925; 95% CI 0.857, 0.999; p = 0.047)) demonstrated positive effects on the morning chronotype. No significant heterogeneity in the instrumental variables, or in horizontal pleiotropy, was found. CONCLUSION: This two-sample Mendelian randomization study found that Family Bacteroidaceae, Genus Parabacteroides, and Genus Bacteroides were causally associated with the morning chronotype. Further randomized controlled trials are needed to clarify the effects of the gut microbiota on the morning chronotype, as well as their specific protective mechanisms.