Department of Otolaryngology, Head and Neck Surgery, Children's Hospital Capital Institute of Pediatrics, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100020, China.
National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing 100091, China.
Nutrients. 2023 Oct 26;15(21):4544. doi: 10.3390/nu15214544.
Various studies have highlighted the important associations between obstructive sleep apnea (OSA) and gut microbiota and related metabolites. Nevertheless, the establishment of causal relationships between these associations remains to be determined. Multiple mendelian randomization (MR) analyses were performed to genetically predict the causative impact of 196 gut microbiota and 83 metabolites on OSA. Two-sample MR was used to assess the potential association, and causality was evaluated using inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods. Multivariable MR (MVMR) was employed to ascertain the causal independence between gut microbiota and the metabolites linked to OSA. Additionally, Cochran's Q test, the MR Egger intercept test and the MR Steiger test were used for the sensitivity analyses. The analysis of the 196 gut microbiota revealed that _ () (P = 0.010) and _ (P = 0.041) were associated with an increased risk of OSA onset. Conversely, _ (P = 0.030), _ (P = 0.025), _ (P = 0.011), and _ (_) (P = 0.001) were negatively related to the risk of OSA. Among the 83 metabolites evaluated, 3-dehydrocarnitine, epiandrosterone sulfate, and leucine were determined to be potential independent risk factors associated with OSA. Moreover, the reverse MR analysis demonstrated a suggestive association between OSA exposure and six microbiota taxa. This study offers compelling evidence regarding the potential beneficial or detrimental causative impact of the gut microbiota and its associated metabolites on OSA risk, thereby providing new insights into the mechanisms of gut microbiome-mediated OSA development.
多项研究强调了阻塞性睡眠呼吸暂停（OSA）与肠道微生物群及其相关代谢物之间的重要关联。然而，这些关联之间建立因果关系仍有待确定。进行了多次孟德尔随机分析（MR），以遗传预测 196 种肠道微生物群和 83 种代谢物对 OSA 的因果影响。两样本 MR 用于评估潜在关联，使用逆方差加权（IVW）、MR-Egger 和加权中位数（WM）方法评估因果关系。多变量 MR（MVMR）用于确定肠道微生物群与与 OSA 相关的代谢物之间的因果独立性。此外，还使用 Cochran's Q 检验、MR Egger 截距检验和 MR Steiger 检验进行敏感性分析。对 196 种肠道微生物群的分析表明，（）（P = 0.010）和（P = 0.041）与 OSA 发病风险增加相关。相反，（P = 0.030）、（P = 0.025）、（P = 0.011）和（_）（P = 0.001）与 OSA 风险呈负相关。在评估的 83 种代谢物中，3-去氢肉碱、表雄酮硫酸盐和亮氨酸被确定为与 OSA 相关的潜在独立危险因素。此外，反向 MR 分析表明，OSA 暴露与六种微生物群分类群之间存在提示性关联。这项研究提供了令人信服的证据，表明肠道微生物群及其相关代谢物对 OSA 风险具有潜在的有益或有害的因果影响，从而为肠道微生物群介导的 OSA 发展机制提供了新的见解。
