Assessing the causal association between sleep apnea and the human gut microbiome composition: A two-sample Mendelian randomization study.

ABSTRACT

Background: Studies have linked gut microbiota dysbiosis with sleep apnea; however, no causal relationship was found in human subjects. Finding new targets for the pathophysiology of sleep apnea might be made possible by systematically investigating the causal relationship between the human gut microbiota and sleep apnea. Methods: A two-sample Mendelian randomization analysis was conducted. The human gut microbiome composition data, spanning five taxonomic levels, were acquired from a genome-wide association study that included 18,340 participants from 24 cohorts. Genome-wide association study data for sleep apnea were obtained from the Sleep Disorder Knowledge Portal for primary analysis and the FinnGen consortium for meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results: Using inverse-variance weighted analysis, eight microbial taxa were initially found to be substantially linked with the apnea-hypopnea index. Only three microbial taxa remained significant associations with sleep apnea when combined with the FinnGen consortium (the class Bacilli B = 8.21%, 95% CI = 0.93%-15.49%; p = 0.03; the order Lactobacillales B = 7.55%, 95% CI = 0.25%-4.85%; p = 0.04; the genus RuminococcaceaeUCG009 B = -21.63%, 95% CI = -41.47% to -1.80%; p = 0.03). Conclusions: Sleep apnea may lead to gut dysbiosis as significant reductions in butyrate-producing bacteria and increases in lactate-producing bacteria. By integrating genomes and metabolism, the evidence that three microbiome species are causally linked to sleep apnea may offer a fresh perspective on the underlying mechanisms of the condition.