Abdol Samat Hanis Nabilah, Razali Nurul Nadirah, Mahadzir Hazlina, Tengku Muhammad Tengku Sifzizul, Ling King-Hwa, Mansor Nur Izzati, Abidin Shahidee Zainal
Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus 21030, Terengganu, Malaysia.
Department of Medicine, Hospital Canselor Tuanku Muhriz, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia.
Int J Mol Sci. 2025 Sep 12;26(18):8905. doi: 10.3390/ijms26188905.
Alzheimer's disease (AD) represents a major global health challenge, characterised by progressive neurodegeneration that leads to cognitive decline. Inflammation is a key factor in the pathogenesis of AD, affecting both neuroinflammation and systemic inflammation. In AD, neuroinflammation is marked by the activation of microglia and the release of pro-inflammatory cytokines, which exacerbate neuronal damage and cognitive deficits. Systemic inflammation further compromises the blood-brain barrier (BBB), increasing its permeability and permitting the entry of inflammatory molecules and immune cells into the brain, thereby advancing the disease's hallmark features. Recent studies have elucidated the influence of gut microbiota dysbiosis on AD and inflammation. This imbalance is thought to be associated with alterations in the concentrations of short-chain fatty acids (SCFAs) and bile acids, which can modulate neuroinflammation and contribute to AD pathology. Additionally, imbalances in neurotransmitters resulting from gut microbiota dysbiosis can further disrupt brain function and facilitate AD progression. This review provides an overview of the hypothesis that systemic and central nervous system (CNS) inflammation, together with gut-microbiota dysbiosis, may interact to influence the development and progression of AD.
阿尔茨海默病（AD）是一项重大的全球健康挑战，其特征是导致认知能力下降的进行性神经退行性变。炎症是AD发病机制中的一个关键因素，影响神经炎症和全身炎症。在AD中，神经炎症以小胶质细胞的激活和促炎细胞因子的释放为特征，这会加剧神经元损伤和认知缺陷。全身炎症进一步损害血脑屏障（BBB），增加其通透性，使炎症分子和免疫细胞进入大脑，从而加剧该疾病的标志性特征。最近的研究阐明了肠道微生物群失调对AD和炎症的影响。这种失衡被认为与短链脂肪酸（SCFAs）和胆汁酸浓度的改变有关，它们可以调节神经炎症并导致AD病理。此外，肠道微生物群失调导致的神经递质失衡会进一步破坏脑功能并促进AD进展。本综述概述了一种假说，即全身和中枢神经系统（CNS）炎症与肠道微生物群失调可能相互作用，影响AD的发生和发展。
