Genetic correlations between Alzheimer's disease and gut microbiome genera.
Genetic correlations between Alzheimer's disease and gut microbiome genera.
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DOI：
10.1038/s41598-023-31730-5
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发表时间：
2023-03-31
影响因子：
4.6
通讯作者：
Chen, Jingchun
中科院分区：
文献类型：
--
作者：
Cammann, Davis;Lu, Yimei;Cummings, Melika J. J.;Zhang, Mark L. L.;Cue, Joan Manuel;Do, Jenifer;Ebersole, Jeffrey;Chen, Xiangning;Oh, Edwin C. C.;Cummings, Jeffrey L. L.;Chen, Jingchun
越来越多的证据表明，人类肠道微生物群的生态失调与阿尔茨海默病（AD）等神经退行性疾病通过微生物群-肠道-脑轴的神经炎症过程相关。肠道微生物群通过分泌毒素和短链脂肪酸影响大脑健康，从而调节肠道通透性和多种免疫功能。观察性研究表明，AD患者的微生物组多样性降低，这可能有助于疾病的发病机制。揭示微生物丰度的遗传基础及其对AD的影响可能表明生活方式的改变可能会降低个体患该疾病的风险。使用MiBioGen联盟最大的肠道微生物群属的全基因组关联研究，我们使用多基因风险评分（PRS）分析与PRSice-2中实施的“最佳拟合”模型，并确定发现样本中119个属与AD之间的遗传相关性（ADc 12病例/对照：1278/1293）。为了确认发现样本的结果，我们接下来在复制样本（GenADA病例/对照：799/778）中重复了PRS分析，然后对两个样本的PRS结果进行了荟萃分析。最后，我们进行了线性回归分析，以评估重要属的PRS和APOE基因型之间的相关性。在发现样本中，20种肠道微生物群属最初被鉴定为与AD病例/对照状态遗传相关。在这20个中，三个属（裂环真杆菌作为保护因子，柯林斯氏菌和韦荣氏菌作为风险因子）在复制样品中独立显著。发现和复制样本的荟萃分析证实，10个属与AD有显著相关性，其中4个属与APOE rs 429358风险等位基因显著相关，方向与AD关联中的保护/风险指定一致。值得注意的是，在两个样本中，被鉴定为AD风险因素的促炎性属柯林斯菌与APOE rs 429358风险等位基因呈正相关。总体而言，影响10个属丰度的宿主遗传因素与AD显著相关，表明这些属可作为AD治疗和干预的生物标志物和靶点。我们的研究结果强调，促炎肠道微生物群可能通过与APOE相互作用促进AD的发展。需要更大的数据集和函数研究来了解它们的因果关系。
A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer’s disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual’s risk for the disease. Using the largest genome-wide association study of gut microbiota genera from the MiBioGen consortium, we used polygenic risk score (PRS) analyses with the “best-fit” model implemented in PRSice-2 and determined the genetic correlation between 119 genera and AD in a discovery sample (ADc12 case/control: 1278/1293). To confirm the results from the discovery sample, we next repeated the PRS analysis in a replication sample (GenADA case/control: 799/778) and then performed a meta-analysis with the PRS results from both samples. Finally, we conducted a linear regression analysis to assess the correlation between the PRSs for the significant genera and the APOE genotypes. In the discovery sample, 20 gut microbiota genera were initially identified as genetically associated with AD case/control status. Of these 20, three genera (Eubacterium fissicatena as a protective factor, Collinsella, and Veillonella as a risk factor) were independently significant in the replication sample. Meta-analysis with discovery and replication samples confirmed that ten genera had a significant correlation with AD, four of which were significantly associated with the APOE rs429358 risk allele in a direction consistent with their protective/risk designation in AD association. Notably, the proinflammatory genus Collinsella, identified as a risk factor for AD, was positively correlated with the APOE rs429358 risk allele in both samples. Overall, the host genetic factors influencing the abundance of ten genera are significantly associated with AD, suggesting that these genera may serve as biomarkers and targets for AD treatment and intervention. Our results highlight that proinflammatory gut microbiota might promote AD development through interaction with APOE. Larger datasets and functional studies are required to understand their causal relationships.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
9.2
作者：
Choi, Shing Wan;O'Reilly, Paul F.
通讯作者：
O'Reilly, Paul F.
DOI：
10.1017/s0007114516001045
发表时间：
2016-07
期刊：
The British journal of nutrition
影响因子：
--
作者：
Candela M;Biagi E;Soverini M;Consolandi C;Quercia S;Severgnini M;Peano C;Turroni S;Rampelli S;Pozzilli P;Pianesi M;Fallucca F;Brigidi P
通讯作者：
Brigidi P
影响因子：
14
作者：
Gaugler, Joseph;James, Bryan;Hohman, Timothy J.
通讯作者：
Hohman, Timothy J.