The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, People's Republic of China.
Int J Nanomedicine. 2022 Oct 13;17:4807-4827. doi: 10.2147/IJN.S374024. eCollection 2022.
The bidirectional communication between the gut and the central nervous system mediated by gut microbiota is closely related to the occurrence and development of neurodegenerative diseases, including Alzheimer's disease (AD). Selenium (Se) has been identified as playing a role against AD. Probiotics have beneficial effects on host brain function and behavior by modulating the microbiota-gut-brain axis. Herein, we evaluated the protective effects of ATCC 393 ( ATCC 393) and selenium nanoparticles-enriched ATCC 393 ( ATCC 393-SeNPs) against D-galactose/aluminum chloride-induced AD model mice.
The Morris Water Maze (MWM) test was used to assess cognitive function of mice. The morphology and histopathological changes, antioxidant capacity and immune responses in the brain and ileum were evaluated. The alterations in intestinal permeability of the mice were determined using FITC-dextran. Gut microbiota composition was assessed using 16s rRNA sequencing.
Thirteen weeks intervention with ATCC 393 or ATCC 393-SeNPs significantly improved cognitive dysfunction, and minimized amyloid beta (Aβ) aggregation, hyperphosphorylation of TAU protein, and prevented neuronal death by modulating Akt/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway. Moreover, compared with ATCC 393, ATCC 393-SeNPs further effectively mitigated intestinal barrier dysfunction by improving antioxidant capacity, regulating immune response, restoring gut microbiota balance, and increasing the level of short-chain fatty acids and neurotransmitters, thereby inhibiting the activation of microglia and protecting brain neurons from neurotoxicity such as oxidative stress and neuroinflammation.
These findings indicated that targeting the microbiota-gut-brain axis with ATCC 393-SeNPs may have therapeutic potential for the deficits of cognitive function in the AD model mice. Thus, we anticipate that ATCC 393-SeNPs may be a promising and safe Se nutritional supplement for use as a food additive to prevent the neurodegenerative disease.
肠道微生物群介导的肠-中枢神经系统双向通讯与包括阿尔茨海默病（AD）在内的神经退行性疾病的发生和发展密切相关。硒（Se）已被确定可发挥抗 AD 作用。益生菌通过调节微生物群-肠-脑轴对宿主大脑功能和行为产生有益影响。在此，我们评估了 ATCC 393（ATCC 393）和富含硒纳米颗粒的 ATCC 393（ATCC 393-SeNPs）对 D-半乳糖/氯化铝诱导的 AD 模型小鼠的保护作用。
使用 Morris 水迷宫（MWM）测试评估小鼠的认知功能。评估大脑和回肠的形态和组织病理学变化、抗氧化能力和免疫反应。使用 FITC-葡聚糖测定小鼠的肠道通透性变化。使用 16s rRNA 测序评估肠道微生物组组成。
ATCC 393 或 ATCC 393-SeNPs 干预 13 周可显著改善认知功能障碍，通过调节 Akt/cAMP 反应元件结合蛋白（CREB）/脑源性神经营养因子（BDNF）信号通路最小化淀粉样β（Aβ）聚集、TAU 蛋白过度磷酸化以及防止神经元死亡。此外，与 ATCC 393 相比，ATCC 393-SeNPs 还通过提高抗氧化能力、调节免疫反应、恢复肠道微生物群平衡以及增加短链脂肪酸和神经递质水平，更有效地减轻肠道屏障功能障碍，从而抑制小胶质细胞的激活并保护大脑神经元免受氧化应激和神经炎症等神经毒性的侵害。
这些发现表明，针对微生物群-肠-脑轴的 ATCC 393-SeNPs 可能具有治疗 AD 模型小鼠认知功能障碍的潜力。因此，我们预计 ATCC 393-SeNPs 可能是一种有前途且安全的 Se 营养补充剂，可用作食品添加剂来预防神经退行性疾病。
