Recently, cognitive impairments (CI) and behavioral abnormalities in patients with amyotrophic lateral sclerosis (ALS) have been reported. However, the underlying mechanisms have been poorly understood. In the current study, we explored the role of gut microbiota in CI of ALS patients. We collected fecal samples from 35 ALS patients and 35 healthy controls. The cognitive function of the ALS patients was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen. We analyzed these samples by using 16S rRNA gene sequencing as well as both untargeted and targeted (bile acids) metabolite mapping between patients with CI and patients with normal cognition (CN). We found altered gut microbial communities and a lower ratio of Firmicutes/Bacteroidetes in the CI group, compared with the CN group. In addition, the untargeted metabolite mapping revealed that 26 and 17 metabolites significantly increased and decreased, respectively, in the CI group, compared with the CN group. These metabolites were mapped to the metabolic pathways associated with bile acids. We further found that cholic acid and chenodeoxycholic acid were significantly lower in the CI group than in the CN group. In conclusion, we found that the gut microbiota and its metabolome profile differed between ALS patients with and without CI and that the altered bile acid profile in fecal samples was significantly associated with CI in ALS patients. These results need to be replicated in larger studies in the future.
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机译：最近，肌萎缩侧索硬化症 （ALS） 患者的认知障碍 （CI） 和行为异常已有报道。然而，人们对其潜在机制知之甚少。在目前的研究中，我们探讨了肠道菌群在 ALS 患者 CI 中的作用。我们收集了 35 名 ALS 患者和 35 名健康对照者的粪便样本。使用 Edinburgh 认知和行为 ALS 筛查评估 ALS 患者的认知功能。我们通过使用 16S rRNA 基因测序以及 CI 患者和认知正常 （CN） 患者之间的非靶向和靶向 （胆汁酸） 代谢物图谱来分析这些样本。我们发现与 CN 组相比，CI 组的肠道微生物群落发生了变化，厚壁菌门/拟杆菌门的比例较低。此外，非靶向代谢物映射显示，与 CN 组相比，CI 组分别有 26 和 17 种代谢物显著增加和减少。这些代谢物被映射到与胆汁酸相关的代谢途径。我们进一步发现 CI 组的胆酸和鹅去氧胆酸显著低于 CN 组。总之，我们发现伴 CI 和不伴 CI 的 ALS 患者的肠道菌群及其代谢组谱不同，粪便样本中胆汁酸谱的改变与 ALS 患者的 CI 显著相关。这些结果需要在未来更大规模的研究中复制。
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