Raimondi Ilaria, Izzo Luca, Tunesi Marta, Comar Manola, Albani Diego, Giordano Carmen
Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milan, Italy.
SSD of Advanced Translational Microbiology, IRCCS "Burlo Garofolo", Department of Medical Sciences (DMS), University of Trieste, Trieste, Italy.
Front Bioeng Biotechnol. 2020 Jan 10;7:435. doi: 10.3389/fbioe.2019.00435. eCollection 2019.
We are accumulating evidence that intestinal microflora, collectively named gut microbiota, can alter brain pathophysiology, but researchers have just begun to discover the mechanisms of this bidirectional connection (often referred to as microbiota-gut-brain axis, MGBA). The most noticeable hypothesis for a pathological action of gut microbiota on the brain is based on microbial release of soluble neurotransmitters, hormones, immune molecules and neuroactive metabolites, but this complex scenario requires reliable and controllable tools for its causal demonstration. Thanks to three-dimensional (3D) cultures and microfluidics, engineered in models could improve the scientific knowledge in this field, also from a therapeutic perspective. This review briefly retraces the main discoveries linking the activity of gut microbiota to prevalent brain neurodegenerative disorders, and then provides a deep insight into the state-of-the-art for modeling of the brain and the blood-brain barrier (BBB), two key players of the MGBA. Several brain and BBB microfluidic devices have already been developed to implement organ-on-a-chip solutions, but some limitations still exist. Future developments of organ-on-a-chip tools to model the MGBA will require an interdisciplinary approach and the synergy with cutting-edge technologies (for instance, bioprinting) to achieve multi-organ platforms and support basic research, also for the development of new therapies against neurodegenerative diseases.
我们正在积累证据，表明肠道微生物群（统称为肠道菌群）能够改变大脑病理生理学，但研究人员才刚刚开始探索这种双向联系（通常称为微生物群-肠道-脑轴，MGBA）的机制。关于肠道菌群对大脑产生病理作用，最值得注意的假说是基于微生物释放可溶性神经递质、激素、免疫分子和神经活性代谢产物，但这一复杂情况需要可靠且可控的工具来进行因果论证。得益于三维（3D）培养和微流控技术，在模型中构建的工程化手段能够增进该领域的科学认知，从治疗角度来看亦是如此。本综述简要回顾了将肠道菌群活性与主要大脑神经退行性疾病相联系的主要发现，然后深入探讨了用于模拟大脑和血脑屏障（BBB）的最新技术进展，这两者是MGBA的两个关键要素。已经开发了几种大脑和血脑屏障微流控装置来实现芯片器官解决方案，但仍然存在一些局限性。未来用于模拟MGBA的芯片器官工具的发展将需要跨学科方法以及与前沿技术（例如生物打印）协同合作，以实现多器官平台并支持基础研究，这对于开发针对神经退行性疾病的新疗法也具有重要意义。
