Department of Molecular Pathobiology of Brain Diseases, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
Department of Neurology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
J Alzheimers Dis. 2021;84(2):479-490. doi: 10.3233/JAD-215031.
Accumulating evidence show that the gut microbiota is deeply involved not only in host nutrient metabolism but also in immune function, endocrine regulation, and chronic disease. In neurodegenerative conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis, the gut-brain axis, the bidirectional interaction between the brain and the gut, provides new route of pathological spread and potential therapeutic targets. Although studies of gut microbiota have been conducted mainly in mice, mammalian gut microbiota is highly diverse, complex, and sensitive to environmental changes. Drosophila melanogaster, a fruit fly, has many advantages as a laboratory animal: short life cycle, numerous and genetically homogenous offspring, less ethical concerns, availability of many genetic models, and low maintenance costs. Drosophila has a simpler gut microbiota than mammals and can be made to remain sterile or to have standardized gut microbiota by simple established methods. Research on the microbiota of Drosophila has revealed new molecules that regulate the brain-gut axis, and it has been shown that dysbiosis of the fly microbiota worsens lifespan, motor function, and neurodegeneration in AD and PD models. The results shown in fly studies represents a fundamental part of the immune and proteomic process involving gut-microbiota interactions that are highly conserved. Even though the fly's gut microbiota are not simple mimics of humans, flies are a valuable system to learn the molecular mechanisms of how the gut microbiota affect host health and behavior.
越来越多的证据表明，肠道微生物群不仅深度参与宿主的营养代谢，还参与免疫功能、内分泌调节和慢性疾病。在神经退行性疾病（如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症）中，肠道-大脑轴，即大脑和肠道之间的双向相互作用，为病理传播提供了新途径和潜在的治疗靶点。虽然肠道微生物群的研究主要在小鼠中进行，但哺乳动物的肠道微生物群具有高度的多样性、复杂性，并且对环境变化敏感。黑腹果蝇作为一种实验室动物，具有许多优势：生命周期短、后代数量多且遗传同质、伦理问题较少、有许多遗传模型可用、维护成本低。果蝇的肠道微生物群比哺乳动物简单，通过简单的既定方法可以使其保持无菌或具有标准化的肠道微生物群。对果蝇微生物群的研究揭示了调节脑肠轴的新分子，并且已经表明，果蝇微生物群的失调会恶化 AD 和 PD 模型中的寿命、运动功能和神经退行性变。在果蝇研究中显示的结果代表了涉及肠道微生物群相互作用的免疫和蛋白质组学过程的基本部分，这些过程高度保守。尽管果蝇的肠道微生物群并不简单地模拟人类，但果蝇是一个有价值的系统，可以了解肠道微生物群如何影响宿主健康和行为的分子机制。
