Medical Genomic Research Center, Tehran Medical Science Islamic Azad University, Tehran, Iran.
Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Brain Res. 2024 Dec 15;1845:149242. doi: 10.1016/j.brainres.2024.149242. Epub 2024 Sep 16.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and synaptic dysfunction. Emerging evidence suggests a significant relationship between gut microbiota and brain health, mediated through the gut-brain axis. Alterations in gut microbiota composition may influence AD progression by affecting molecular pathways and miRNA interactions.
We retrieved and analyzed microarray data from 34 tissue samples of AD patients and controls (GEO accession number GSE110298). Differentially expressed genes (DEGs) with the GCS score package in R, considering a p-value < 0.05 and logFC<-1 and logFC>1 to isolate significant gene clusters. Enrichment analysis of signaling pathways and gene ontology was conducted using Enrichr, KEGG, Panther, DAVID, and shiny GO databases. Protein-protein interactions were visualized with Networkanalyst and CytoScape. Gut microbiota in 200 CE patients was analyzed using next-generation sequencing (NGS) data from gutMDisorder and GMrepo databases. miRNA interactions were evaluated using miEAA, Targetscan, MienTurnet, and miRnet databases.
Significant reductions in microbial taxa, including Clostridia (LDA score -4.878208), Firmicutes (LDA score -4.817032), and Faecalibacterium (LDA score -4.40714), were observed in AD patients. Pathway analysis highlighted the involvement of Axon guidance, ErbB, and MAPK signaling pathways in AD. Venn diagram analysis identified 619 intersecting genes in brain and gut tissues, emphasizing pathways such as Axon Guidance and Cell Cycle. miRNA analysis revealed important regulatory miRNAs, including hsa-let-7c, hsa-mir-125b-2, and hsa-mir-145, which target key transcription factors involved in AD pathology.
The study demonstrates significant dysbiosis in the gut microbiota of AD patients and underscores the potential role of gut microbiota in AD progression through altered signaling pathways and miRNA interactions. These findings highlight the need for further research into microbiota-based interventions as potential therapeutic strategies for AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是认知能力下降和突触功能障碍。新出现的证据表明，肠道微生物群与大脑健康之间存在着重要的关系，这种关系是通过肠道-大脑轴介导的。肠道微生物群组成的改变可能通过影响分子途径和 miRNA 相互作用来影响 AD 的进展。
我们从 34 名 AD 患者和对照组（GEO 注册号 GSE110298）的 34 个组织样本中检索和分析了微阵列数据。使用 R 中的 GCS 评分包对差异表达基因（DEGs）进行分析，考虑到 p 值 < 0.05，logFC<-1 和 logFC>1 以分离显著的基因簇。使用 Enrichr、KEGG、Panther、DAVID 和 shiny GO 数据库对信号通路和基因本体论进行富集分析。使用 Networkanalyst 和 CytoScape 可视化蛋白质-蛋白质相互作用。使用来自 gutMDisorder 和 GMrepo 数据库的下一代测序（NGS）数据分析了 200 CE 名患者的肠道微生物群。使用 miEAA、Targetscan、MienTurnet 和 miRnet 数据库评估 miRNA 相互作用。
AD 患者的微生物类群显著减少，包括梭菌（LDA 评分-4.878208）、厚壁菌门（LDA 评分-4.817032）和粪杆菌（LDA 评分-4.40714）。途径分析强调了 AD 中轴突导向、ErbB 和 MAPK 信号通路的参与。Venn 图分析确定了大脑和肠道组织中 619 个相交的基因，强调了轴突导向和细胞周期等途径。miRNA 分析揭示了重要的调节 miRNA，包括 hsa-let-7c、hsa-mir-125b-2 和 hsa-mir-145，它们靶向 AD 病理学中涉及的关键转录因子。
该研究表明 AD 患者的肠道微生物群存在显著的失调，并强调了肠道微生物群通过改变信号通路和 miRNA 相互作用在 AD 进展中的潜在作用。这些发现强调了需要进一步研究基于微生物群的干预措施作为 AD 的潜在治疗策略。
