Abstract

Objective

To characterize the gut microbiota in people with amyotrophic lateral sclerosis (ALS) relative to controls and to test the hypothesis that butyrate-producing bacteria are less abundant in the gastrointestinal tracts of people with ALS (PALS). Methods: We conducted a case–control study at Massachusetts General Hospital to compare the gut microbiota in people with ALS to that in controls. Metagenomic shotgun sequencing was performed on DNA extracted from stool samples of 66 people with ALS (PALS), 61 healthy controls (HC), and 12 neurodegenerative controls (NDC). Taxonomic metagenomic profiles were analyzed for shifts in the microbial community structure between the comparator groups using per-feature univariate and multivariate association tests. Results: The relative abundance of the dominant butyrate-producing bacteria Eubacterium rectale and Roseburia intestinalis was significantly lower in ALS patients compared to HC. Adjustment for age, sex, and constipation did not materially change the results. The total abundance of 8 dominant species capable of producing butyrate was also significantly lower in ALS compared to HC (p < 0.001). Conclusions: The levels of several butyrate-producing bacteria, which are important for gut integrity and regulation of inflammation, were lower in people with ALS compared to controls. These findings lend support to the inference that the gut microbiota could be a risk factor for ALS. Further investigations are warranted, preferably earlier in the disease with corresponding dietary collection and a longitudinal design.

中文翻译：

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肌萎缩侧索硬化患者的肠道微生物群

摘要

客观的

表征肌萎缩侧索硬化 (ALS) 患者相对于对照组的肠道微生物群，并检验 ALS (PALS) 患者胃肠道中产丁酸细菌较少的假设。方法：我们在马萨诸塞州总医院进行了一项病例对照研究，以比较 ALS 患者与对照组的肠道微生物群。对从 66 名 ALS (PALS)、61 名健康对照组 (HC) 和 12 名神经退行性对照组 (NDC) 的粪便样本中提取的 DNA 进行宏基因组鸟枪测序。使用每特征单变量和多变量关联测试分析分类宏基因组图谱以分析比较组之间微生物群落结构的变化。结果：占主导地位的丁酸产生菌的相对丰度真杆菌rectale和罗斯氏肠是在ALS患者显著低于对照HC。对年龄、性别和便秘的调整并没有实质性地改变结果。与 HC 相比，ALS 中能够产生丁酸盐的 8 个优势物种的总丰度也显着降低（p < 0.001）。结论：与对照组相比，ALS 患者的几种产丁酸盐细菌的水平较低，这些细菌对肠道完整性和炎症调节很重要。这些发现支持推论，即肠道微生物群可能是 ALS 的危险因素。有必要进行进一步的调查，最好在疾病早期进行相应的饮食收集和纵向设计。