Medeiros Destynie, McMurry Kristina, Pfeiffer Melissa, Newsome Kayla, Testerman Todd, Graf Joerg, Silver Adam C, Sacchetti Paola
Department of Biology, University of Hartford, West Hartford, CT, United States.
Neuroscience Program, Department of Biology, University of Hartford, West Hartford, CT, United States.
Front Neurosci. 2024 Mar 6;18:1309075. doi: 10.3389/fnins.2024.1309075. eCollection 2024.
The lack of affordable and effective therapeutics against cognitive impairment has promoted research toward alternative approaches to the treatment of neurodegeneration. In recent years, a bidirectional pathway that allows the gut to communicate with the central nervous system has been recognized as the gut-brain axis. Alterations in the gut microbiota, a dynamic population of trillions of microorganisms residing in the gastrointestinal tract, have been implicated in a variety of pathological states, including neurodegenerative disorders such as Alzheimer's disease (AD). However, probiotic treatment as an affordable and accessible adjuvant therapy for the correction of dysbiosis in AD has not been thoroughly explored. Here, we sought to correct the dysbiosis in an AD mouse model with probiotic supplementation, with the intent of exploring its effects on disease progression. Transgenic 3xTg-AD mice were fed a control or a probiotic diet ( and ) for 12 weeks, with the latter leading to a significant increase in the relative abundance of . Cognitive functions were evaluated via Barnes Maze trials and improvements in memory performance were detected in probiotic-fed AD mice. Neural tissue analysis of the entorhinal cortex and hippocampus of 10-month-old 3xTg-AD mice demonstrated that astrocytic and microglial densities were reduced in AD mice supplemented with a probiotic diet, with changes more pronounced in probiotic-fed female mice. In addition, elevated numbers of neurons in the hippocampus of probiotic-fed 3xTg-AD mice suggested neuroprotection induced by probiotic supplementation. Our results suggest that probiotic supplementation could be effective in delaying or mitigating early stages of neurodegeneration in the 3xTg-AD animal model. It is vital to explore new possibilities for palliative care for neurodegeneration, and probiotic supplementation could provide an inexpensive and easily implemented adjuvant clinical treatment for AD.
缺乏针对认知障碍的经济有效的治疗方法推动了对神经退行性疾病治疗替代方法的研究。近年来，一种允许肠道与中枢神经系统进行通信的双向途径已被确认为肠-脑轴。肠道微生物群是存在于胃肠道中的数万亿微生物的动态群体，其改变与多种病理状态有关，包括神经退行性疾病如阿尔茨海默病（AD）。然而，益生菌治疗作为一种可负担且可及的辅助疗法来纠正AD中的菌群失调尚未得到充分探索。在此，我们试图通过补充益生菌来纠正AD小鼠模型中的菌群失调，以探索其对疾病进展的影响。将转基因3xTg-AD小鼠喂食对照饮食或益生菌饮食（ 和 ）12周，后者导致 的相对丰度显著增加。通过巴恩斯迷宫试验评估认知功能，在喂食益生菌的AD小鼠中检测到记忆表现有所改善。对10个月大的3xTg-AD小鼠的内嗅皮质和海马体进行神经组织分析表明，补充益生菌饮食的AD小鼠中星形胶质细胞和小胶质细胞密度降低，在喂食益生菌的雌性小鼠中变化更为明显。此外，喂食益生菌的3xTg-AD小鼠海马体中神经元数量增加表明补充益生菌可诱导神经保护作用。我们的结果表明，补充益生菌可能有效延缓或减轻3xTg-AD动物模型中神经退行性变的早期阶段。探索神经退行性疾病姑息治疗的新可能性至关重要，补充益生菌可为AD提供一种廉价且易于实施的辅助临床治疗方法。
