Dai Chun-Ling, Liu Fei, Iqbal Khalid, Gong Cheng-Xin
Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY 10314, USA.
Int J Mol Sci. 2022 Dec 3;23(23):15230. doi: 10.3390/ijms232315230.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that eventually leads to dementia and death of the patient. Currently, no effective treatment is available that can slow or halt the progression of the disease. The gut microbiota can modulate the host immune system in the peripheral and central nervous system through the microbiota-gut-brain axis. Growing evidence indicates that gut microbiota dysbiosis plays an important role in the pathogenesis of AD, and modulation of the gut microbiota may represent a new avenue for treating AD. Immunotherapy targeting Aβ and tau has emerged as the most promising disease-modifying therapy for the treatment of AD. However, the underlying mechanism of AD immunotherapy is not known. Importantly, preclinical and clinical studies have highlighted that the gut microbiota exerts a major influence on the efficacy of cancer immunotherapy. However, the role of the gut microbiota in AD immunotherapy has not been explored. We found that immunotherapy targeting tau can modulate the gut microbiota in an AD mouse model. In this article, we focused on the crosstalk between the gut microbiota, immunity, and AD immunotherapy. We speculate that modulation of the gut microbiota induced by AD immunotherapy may partially underlie the efficacy of the treatment.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，最终会导致患者痴呆和死亡。目前，尚无有效的治疗方法能够减缓或阻止该疾病的进展。肠道微生物群可通过微生物-肠道-脑轴调节外周和中枢神经系统中的宿主免疫系统。越来越多的证据表明，肠道微生物群失调在AD的发病机制中起重要作用，调节肠道微生物群可能代表一种治疗AD的新途径。靶向β淀粉样蛋白（Aβ）和tau蛋白的免疫疗法已成为治疗AD最有前景的疾病修饰疗法。然而，AD免疫疗法的潜在机制尚不清楚。重要的是，临床前和临床研究强调，肠道微生物群对癌症免疫疗法的疗效有重大影响。然而，肠道微生物群在AD免疫疗法中的作用尚未得到探索。我们发现，在AD小鼠模型中，靶向tau蛋白的免疫疗法可调节肠道微生物群。在本文中，我们重点关注肠道微生物群、免疫和AD免疫疗法之间的相互作用。我们推测，AD免疫疗法诱导的肠道微生物群调节可能是该治疗疗效的部分基础。
