The Role of Plasma Metabolites in Mediating the Effect of Gut Microbiota on Obstructive Sleep Apnea: A Two-Step, Two-Sample Mendelian Randomization Study.

Background: Recent research has increasingly underscored a significant correlation between gut microbiota and obstructive sleep apnea (OSA). Probiotics have emerged as promising adjunctive interventions for OSA. Metabolites and their related biochemical pathways have emerged as important contributors to the development of OSA. This study aimed to estimate the causal association between gut microbiota and OSA and to quantify the mediating effects of metabolites.

Methods: We employed two-step, two-sample Mendelian randomization techniques, utilizing single nucleotide polymorphisms as genetic instruments for exposures and mediators. Summary statistics were obtained from genome-wide association studies of gut microbiota (the Dutch Microbiome Project, n=7,738), plasma metabolites (the Canadian Longitudinal Study on Aging cohort, n=8,299), and OSA (FinnGen database, n=410,385). To ensure the robustness of our findings, sensitivity analyses and heterogeneity tests were systematically conducted.

Results: In the Dutch Microbiome Project, species Parabacteroides merdae, genus Faecalibacterium, species Faecalibacterium prausnitzii and species Bifidobacterium longum demonstrated a potential protective association with OSA. We included the top 10 metabolites with potential biological significance as candidate mediators. Among them, only 2-hydroxypalmitate was associated with a reduced risk of OSA. 2-hydroxypalmitate partially mediated the association between species Parabacteroides merdae and OSA, with a mediation proportion of 20.53%.

Conclusion: The study highlighted the protective effect of species Parabacteroides merdae against OSA. It also revealed the mediating role of 2-hydroxypalmitate in the relationship between species Parabacteroides merdae and OSA.