Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Department of Neurology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Department of Radiology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Neurobiol Dis. 2024 Apr;193:106464. doi: 10.1016/j.nbd.2024.106464. Epub 2024 Mar 5.
Neuroinflammation contributes to the pathology and progression of Alzheimer's disease (AD), and it can be observed even with mild cognitive impairment (MCI), a prodromal phase of AD. Free water (FW) imaging estimates the extracellular water content and has been used to study neuroinflammation across several neurological diseases including AD. Recently, the role of gut microbiota has been implicated in the pathogenesis of AD. The relationship between FW imaging and gut microbiota was examined in patients with AD and MCI. Fifty-six participants underwent neuropsychological assessments, FW imaging, and gut microbiota analysis targeting the bacterial 16S rRNA gene. They were categorized into the cognitively normal control (NC) (n = 19), MCI (n = 19), and AD (n = 18) groups according to the neuropsychological assessments. The correlations of FW values, neuropsychological assessment scores, and the relative abundance of gut microbiota were analyzed. FW was higher in several white matter tracts and in gray matter regions, predominantly the frontal, temporal, limbic and paralimbic regions in the AD/MCI group than in the NC group. In the AD/MCI group, higher FW values in the temporal (superior temporal and temporal pole), limbic and paralimbic (insula, hippocampus and amygdala) regions were the most associated with worse neuropsychological assessment scores. In the AD/MCI group, FW values in these regions were negatively correlated with the relative abundances of butyrate-producing genera Anaerostipes, Lachnospiraceae UCG-004, and [Ruminococcus] gnavus group, which showed a significant decreasing trend in the order of the NC, MCI, and AD groups. The present study showed that increased FW in the gray matter regions related to cognitive impairment was associated with low abundances of butyrate producers in the AD/MCI group. These findings suggest an association between neuroinflammation and decreased levels of the short-chain fatty acid butyrate that is one of the major gut microbial metabolites having a potentially beneficial role in brain homeostasis.
神经炎症是阿尔茨海默病（AD）的病理和进展的原因，即使在轻度认知障碍（MCI），即 AD 的前驱期，也可以观察到。游离水（FW）成像估计细胞外水含量，已用于研究包括 AD 在内的几种神经退行性疾病的神经炎症。最近，肠道微生物群在 AD 的发病机制中起作用。研究了 AD 和 MCI 患者的 FW 成像与肠道微生物群之间的关系。56 名参与者接受了神经心理学评估、FW 成像和针对细菌 16S rRNA 基因的肠道微生物组分析。根据神经心理学评估，他们被分为认知正常对照组（NC）（n=19）、MCI（n=19）和 AD（n=18）组。分析了 FW 值、神经心理学评估评分和肠道微生物群相对丰度之间的相关性。AD/MCI 组多个白质束和灰质区域的 FW 较高，主要是额叶、颞叶、边缘和旁边缘区域。在 AD/MCI 组中，颞叶（颞上回和颞极）、边缘和旁边缘（岛叶、海马和杏仁核）区域的 FW 值较高与神经心理学评估评分较差最相关。在 AD/MCI 组中，这些区域的 FW 值与丁酸盐产生菌 Anaerostipes、Lachnospiraceae UCG-004 和 [Ruminococcus] gnavus 组的相对丰度呈负相关，这些菌在 NC、MCI 和 AD 组中的丰度呈递减趋势。本研究表明，与认知障碍相关的灰质区域 FW 增加与 AD/MCI 组中丁酸盐产生菌丰度降低有关。这些发现表明，神经炎症与短链脂肪酸丁酸水平降低之间存在关联，丁酸是肠道微生物代谢物的主要成分之一，对大脑稳态具有潜在的有益作用。
