Associations between gut microbiota and Parkinson disease: A bidirectional Mendelian randomization analysis
Associations between gut microbiota and Parkinson disease: A bidirectional Mendelian randomization analysis
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DOI：
10.1111/ene.15848
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发表时间：
2023-05-26
影响因子：
5.1
通讯作者：
Guo, Ji-feng
中科院分区：
文献类型：
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作者：
Jiang, Li;Li, Jin-chen;Guo, Ji-feng
背景和目的帕金森病(PD)相关肠道微生物群的改变已在临床和动物研究中观察到。然而，目前尚不清楚这种联系是否反映了人类的因果关系。方法我们使用来自国际联盟MiBioGen(N=18,340)、Framingham心脏研究(N=2076)和国际帕金森病基因组学联盟(33,674例和449,056例对照)和PD发病年龄(17,996例)的汇总统计数据进行了两个样本的双向孟德尔随机抽样。遗传增加的双歧杆菌水平与帕金森病风险降低相关(优势比=0.77，95%可信区间[CI]=0.6-0.99，p=0.040)。相反，5种短链脂肪酸(SCFA)产生菌(LachnospiraceaeUCG010、瘤胃球菌UCG002、敏感梭菌1、哈利氏真细菌和芽孢杆菌)的高水平与帕金森病风险增加相关，而3种产生短链脂肪酸(SCFA)的细菌(Roseburia、瘤胃球菌UCG002和Erysipelatoclostridium)与帕金森病发病年龄较早相关。肠道5-羟色胺的产生与帕金森病起病年龄较早有关(β=-0.64，95%CI=-1.15~-0.13，p=0.013)。结论肠道菌群失调与PD之间存在双向关系，提示内源性SCFAs和5-羟色胺水平升高在PD发病机制中起重要作用。需要未来的临床研究和实验证据来解释观察到的关联，并提出新的治疗方法，如饮食益生菌补充剂。
Background and purposeParkinson disease (PD)-associated alterations in the gut microbiome have been observed in clinical and animal studies. However, it remains unclear whether this association reflects a causal effect in humans.MethodsWe performed two-sample bidirectional Mendelian randomization using summary statistics from the international consortium MiBioGen (N = 18,340), the Framingham Heart Study (N = 2076), and the International Parkinson's Disease Genomics Consortium for PD (33,674 cases and 449,056 controls) and PD age at onset (17,996 cases).ResultsTwelve microbiota features presented suggestive associations with PD risk or age at onset. Genetically increased Bifidobacterium levels correlated with decreased PD risk (odds ratio = 0.77, 95% confidence interval [CI] = 0.60-0.99, p = 0.040). Conversely, high levels of five short-chain fatty acid (SCFA)-producing bacteria (LachnospiraceaeUCG010, RuminococcaceaeUCG002, Clostridium sensustricto1, Eubacterium hallii group, and Bacillales) correlated with increased PD risk, and three SCFA-producing bacteria (Roseburia, RuminococcaceaeUCG002, and Erysipelatoclostridium) correlated with an earlier age at PD onset. Gut production of serotonin was associated with an earlier age at PD onset (beta = -0.64, 95% CI = -1.15 to -0.13, p = 0.013). In the reverse direction, genetic predisposition to PD was related to altered gut microbiota composition.ConclusionsThese results support a bidirectional relationship between gut microbiome dysbiosis and PD, and highlight the role of elevated endogenous SCFAs and serotonin in PD pathogenesis. Future clinical studies and experimental evidence are needed to explain the observed associations and to suggest new therapeutic approaches, such as dietary probiotic supplementation.