Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
Department of Neurology, Beijing Fengtai You'anmen Hospital, Beijing, China.
J Neurol. 2023 Dec;270(12):6021-6032. doi: 10.1007/s00415-023-11961-2. Epub 2023 Aug 29.
Gut dysbiosis and the resulting changes in the metabolites have been associated with neurological diseases. However, the relationship between the gut microbiota and sporadic Creutzfeldt-Jakob disease (sCJD) need to be clarified. The aim of this study was to evaluate the changes in the composition of gut microbiota and metabolome accompanying sCJD, and determine their correlation with disease severity.
Fecal samples were collected from 25 sCJD patients and 23 healthy controls. The composition of the fecal microbiota and metabolites was respectively analyzed by 16S ribosomal RNA sequencing and untargeted metabolomics. The correlation of gut microbiota and metabolites with MMSE, MoCA and MRC scores was analyzed.
The sCJD patients showed significant differences in the composition of gut microbiota and metabolites relative to the healthy controls. Several bacteria taxa in sCJD patients were increased at genus level, such as Turicibacter, norank_f_Christensenellaceae, Eisenbergiella, Bilophila and Holdemania. A total of 547 differential metabolites were identified between these two groups (VIP > 1, FDR p < 0.05). As per KEGG analysis, the metabolites related to the biosynthesis of phenylpropanoids, especially biochanin A, showed the most obvious decrease in the sCJD group. In addition, most metabolites involved in the pathways related to linoleic acid metabolism and steroid hormone biosynthesis were associated with MRC scale.
Our findings provide new insights into the relationship between gut microbiota and metabolites and sCJD. Some compounds, especially those related to the biosynthesis of phenylpropanoids were significantly altered in patients with sCJD, and those related to linoleic acid metabolism and steroid hormone biosynthesis might be biomarkers of evaluating disease severity.
肠道菌群失调及其导致的代谢物变化与神经退行性疾病有关。然而，肠道微生物群与散发性克雅氏病（sCJD）之间的关系尚需阐明。本研究旨在评估 sCJD 患者肠道微生物群和代谢组学的变化，并确定其与疾病严重程度的相关性。
收集 25 例 sCJD 患者和 23 例健康对照者的粪便标本。分别采用 16S 核糖体 RNA 测序和非靶向代谢组学分析粪便微生物群和代谢物的组成。分析肠道微生物群和代谢物与 MMSE、MoCA 和 MRC 评分的相关性。
sCJD 患者的肠道微生物群和代谢物组成与健康对照组相比存在显著差异。sCJD 患者中有几个细菌分类群在属水平上增加，如 Turicibacter、norank_f_Christensenellaceae、Eisenbergiella、Bilophila 和 Holdemania。这两组之间共鉴定出 547 个差异代谢物（VIP>1，FDR p<0.05）。通过 KEGG 分析，与苯丙烷类生物合成相关的代谢物，特别是大豆苷元 A，在 sCJD 组中下降最为明显。此外，与亚麻酸代谢和甾体激素生物合成途径相关的大多数代谢物与 MRC 评分相关。
我们的研究结果为肠道微生物群和代谢物与 sCJD 之间的关系提供了新的见解。一些化合物，特别是与苯丙烷类生物合成相关的化合物，在 sCJD 患者中明显改变，与亚麻酸代谢和甾体激素生物合成相关的化合物可能是评估疾病严重程度的生物标志物。
