Park Rahel, Chevalier Claire, Kieser Silas, Marizzoni Moira, Paquis Arthur, Armand Stephane, Scheffler Max, Allali Gilles, Assal Frederic, Momjian Shahan, Frisoni Giovanni B
Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, Geneva, Switzerland.
Faculty of Medicine, University of Geneva, Geneva, Switzerland.
PLoS One. 2025 Sep 15;20(9):e0330251. doi: 10.1371/journal.pone.0330251. eCollection 2025.
Idiopathic normal pressure hydrocephalus (iNPH), a leading cause of reversible dementia in older adults, is marked by ventriculomegaly, gait disturbances, cognitive decline, and urinary incontinence. Emerging evidence suggests that gut dysbiosis (microbial imbalance) may influence neuroinflammation and cerebrospinal fluid dynamics, potentially contributing to glymphatic system dysfunction and ventricular enlargement. This study used shotgun metagenomics to analyze the gut microbiome in iNPH patients (n = 18) compared to healthy controls (n = 50), individuals with ventriculomegaly but no iNPH symptoms (n = 50), and Alzheimer's disease patients (n = 50). Microbiome analysis showed an enrichment of species previously linked to various disease states, such as Enterocloster bolteae and Ruminococcus gnavus, indicating general dysbiosis. In contrast, enrichment of specific taxa, including Evtepia gabavorous and Cuneatibacter sp., were specifically associated with iNPH clinical traits, pointing to possible disease-specific microbial markers. Functional analysis showed enrichment of pathways related to carbohydrate and amino acid metabolism, including the S-adenosyl-L-methionine superpathway, implicating inflammatory and immune processes. These findings suggest distinct gut microbiome signatures in iNPH, offering insights into potential gut-brain interactions that may contribute to the disorder's pathophysiology and highlighting possible targets for future therapeutic strategies.
特发性正常压力脑积水（iNPH）是老年人可逆性痴呆的主要原因，其特征为脑室扩大、步态障碍、认知衰退和尿失禁。新出现的证据表明，肠道菌群失调（微生物失衡）可能会影响神经炎症和脑脊液动力学，有可能导致类淋巴系统功能障碍和脑室扩大。本研究使用鸟枪法宏基因组学分析了iNPH患者（n = 18）的肠道微生物群，并与健康对照者（n = 50）、有脑室扩大但无iNPH症状的个体（n = 50）以及阿尔茨海默病患者（n = 50）进行了比较。微生物群分析显示，先前与各种疾病状态相关的物种有所富集，如博氏肠球菌和纤细瘤胃球菌，表明存在普遍的菌群失调。相比之下，包括加巴沃埃氏菌和楔形杆菌属在内的特定分类群的富集与iNPH临床特征有特异性关联，这表明可能存在疾病特异性的微生物标志物。功能分析显示，与碳水化合物和氨基酸代谢相关的途径有所富集，包括S-腺苷-L-甲硫氨酸超级途径，这与炎症和免疫过程有关。这些发现表明iNPH存在独特的肠道微生物群特征，为可能导致该疾病病理生理学的潜在肠-脑相互作用提供了见解，并突出了未来治疗策略的可能靶点。
