Deciphering the molecular communications along the gut-brain axis can help in understanding the pathophysiology of neurodegenerative diseases and exploiting the gut microbiome for therapeutics. However, gut microbes and their metabolites have a multifaceted role in mediating both brain physiology and neurodegenerative pathology. There is a lack of understanding of how and when this role is tipped in neurodegenerative diseases and what are those contributing factors, both at local (gut) and distal (neuronal) levels, that drive this imbalance. Here we have reviewed the gut microbiome and its metabolites in the context of the gut-brain axis and summarized how different factors such as gut-microbial diversity, their metabolites, the role of the native immune system and the integrity of gut epithelial and blood-brain barriers are interconnected and collectively define the involvement of gut-microbiome in neurodegenerative pathologies. It also underlines the need for multidisciplinary tools and animal models to simultaneously reflect on many of these factors and to better correlate with clinical observations and data obtained from human biopsies and fecal samples. Harnessing the gut-brain axis will herald a paradigm shift in medicine for neurodegenerative diseases and aging, emphasizing the significance of the microbiome in the broader spectrum of health and disease.

中文翻译：

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逆向工程肠脑轴和微生物组代谢组学，以实现神经退行性疾病的共生/致病平衡。


破译沿肠脑轴的分子通讯有助于了解神经退行性疾病的病理生理学，并利用肠道微生物组进行治疗。然而，肠道微生物及其代谢物在介导脑生理学和神经退行性病理学方面具有多方面的作用。对于这种作用如何以及何时在神经退行性疾病中发挥作用，以及在局部（肠道）和远端（神经元）水平上导致这种不平衡的因素是什么，人们缺乏了解。在这里，我们在肠-脑轴的背景下回顾了肠道微生物组及其代谢物，并总结了不同因素，如肠道-微生物多样性、它们的代谢物、天然免疫系统的作用以及肠道上皮和血脑屏障的完整性是如何相互关联的，并共同定义了肠道微生物组在神经退行性病理学中的参与。它还强调了多学科工具和动物模型的必要性，以同时反映其中的许多因素，并更好地与临床观察和从人类活检和粪便样本中获得的数据相关联。利用肠脑轴将预示着神经退行性疾病和衰老医学的范式转变，强调微生物组在更广泛的健康和疾病中的重要性。