The alteration of gut microbiome and metabolism in amyotrophic lateral sclerosis patients

The alteration of gut microbiome and metabolism in amyotrophic lateral sclerosis patients
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肌萎缩侧索硬化症患者肠道微生物组和代谢的变化

DOI:
10.1038/s41598-020-69845-8
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发表时间:
2020
期刊:
影响因子:
4.6
通讯作者:
Bi Fangfang
Bi Fangfang
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zeng Qianqian;Shen Jie;Chen Kangzhi;Zhou Jinxia;Liao Qiao;Lu Ke;Yuan Jiao;Bi Fangfang

文献摘要

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肌萎缩侧索硬化症(amyotrophiclateralsclerosis,ALS)是一种严重的神经退行性疾病,常伴有严重的瘫痪甚至死亡,其发病机制尚不清楚,目前尚无有效的治疗方法。越来越多的证据表明肠道微生物群与各种神经系统疾病之间存在联系。因此,为了探索肠道微生物组在ALS中的潜在作用,招募了20名诊断为可能或明确ALS的患者和20名健康对照,并收集了他们的粪便排泄物。16S rDNA序列分析显示,ALS患者粪便微生物群落结构发生明显变化,与健康对照组相比,拟杆菌门水平和属水平的几种微生物表达上调,厚壁菌门水平和巨单胞菌属水平表达下调。此外,在ALS患者中观察到与代谢途径相关的基因功能降低。宏基因组学进一步证明了物种水平上微生物菌群的差异,当与代谢组学结合时,其相关代谢物也被揭示。总之,ALS患者肠道微生物群和代谢产物组成的改变为ALS的发病机制提供了更深入的见解,这些生物标志物可能被确立为值得进一步探索的潜在治疗靶点。
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied with severe paralysis or even death, while the pathogenesis of ALS is still unclear and no effective therapy exists. The accumulating evidence has indicated the association between gut microbiota and various neurological diseases. Thus, to explore the potential role of gut microbiome in ALS, 20 patients diagnosed with probable or definite ALS and 20 healthy controls were enrolled and their fecal excrements were collected. The analysis of fecal community diversity with 16S rDNA sequencing showed an obvious change in microbial structure of ALS patients, where Bacteroidetes at the phylum level and several microbes at the genus level were up-regulated, while Firmicutes at the phylum level andMegamonasat the genus level were down-regulated compared to healthy controls. Additionally, decreased gene function associated with metabolic pathways was observed in ALS patients. The metagenomics further demonstrated the discrepancies in microflora at the species level and relevant metabolites thereof were also revealed when combined with metabolomics. In conclusion, the altered composition of the gut microbiota and metabolic products in ALS patients provided deeper insights into the pathogenesis of ALS, and these biomarkers might be established as potential therapeutic targets which deserve further exploration.