The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS).
The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS).
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DOI：
10.1186/s12916-020-01885-3
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发表时间：
2021-01-20
期刊：
影响因子：
9.3
通讯作者：
McDermott CJ
中科院分区：
文献类型：
--
作者：
Boddy SL;Giovannelli I;Sassani M;Cooper-Knock J;Snyder MP;Segal E;Elinav E;Barker LA;Shaw PJ;McDermott CJ
在绘制与肌萎缩侧索硬化症（ALS）相关的遗传异常方面已经取得了很大进展，但大多数病例仍然没有已知的潜在原因。此外，即使在具有共同遗传异常的家族中，也存在显著的表型变异，这表明非遗传因素可能改变发病机制。鉴定这种疾病修饰剂是重要的，因为它们可能代表新的治疗靶点。越来越多的研究开始揭示肠道微生物组在健康和疾病中所起的作用，一些研究将异常与ALS联系起来。微生物组是指属于生活在我们体内和体外的无数不同微生物的基因，统称为微生物群。这些微生物中的大多数都存在于肠道中，它们在消化和产生包括神经递质在内的关键代谢物方面发挥着重要作用。肠道微生物群是我们身体运行环境的一个重要方面，个体间差异可能是解释ALS中不同疾病结果的关键。已经开始研究这种疾病的动物模型，以及ALS患者的肠道微生物组，揭示这些群体微生物群落的变化。目前的知识体系将在本次审查中进行总结。微生物组测序方法的进展将得到强调，因为它们的分辨率提高现在使研究人员能够进一步探索功能水平上的差异。还将考虑将肠道微生物组与神经变性联系起来的拟议机制，包括通过释放到宿主循环中的代谢物的直接影响以及对营养物质甚至药物的生物利用度的间接影响。对肠道微生物组的分析有可能为快速推进的ALS遗传学研究增加环境因素，并使研究朝着这种疾病的个性化医学迈进一步。此外，如果出现由肠道微生物群引发的上游神经毒性或神经保护的令人信服的证据，微生物群的修饰将代表疾病修饰疗法的潜在新途径。对于目前治疗选择很少的难治性疾病，进一步研究ALS微生物组至关重要。
Much progress has been made in mapping genetic abnormalities linked to amyotrophic lateral sclerosis (ALS), but the majority of cases still present with no known underlying cause. Furthermore, even in families with a shared genetic abnormality there is significant phenotypic variability, suggesting that non-genetic elements may modify pathogenesis. Identification of such disease-modifiers is important as they might represent new therapeutic targets. A growing body of research has begun to shed light on the role played by the gut microbiome in health and disease with a number of studies linking abnormalities to ALS. The microbiome refers to the genes belonging to the myriad different microorganisms that live within and upon us, collectively known as the microbiota. Most of these microbes are found in the intestines, where they play important roles in digestion and the generation of key metabolites including neurotransmitters. The gut microbiota is an important aspect of the environment in which our bodies operate and inter-individual differences may be key to explaining the different disease outcomes seen in ALS. Work has begun to investigate animal models of the disease, and the gut microbiomes of people living with ALS, revealing changes in the microbial communities of these groups. The current body of knowledge will be summarised in this review. Advances in microbiome sequencing methods will be highlighted, as their improved resolution now enables researchers to further explore differences at a functional level. Proposed mechanisms connecting the gut microbiome to neurodegeneration will also be considered, including direct effects via metabolites released into the host circulation and indirect effects on bioavailability of nutrients and even medications. Profiling of the gut microbiome has the potential to add an environmental component to rapidly advancing studies of ALS genetics and move research a step further towards personalised medicine for this disease. Moreover, should compelling evidence of upstream neurotoxicity or neuroprotection initiated by gut microbiota emerge, modification of the microbiome will represent a potential new avenue for disease modifying therapies. For an intractable condition with few current therapeutic options, further research into the ALS microbiome is of crucial importance.
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