肠道菌群的代谢产物可用作轻度认知障碍的诊断和进展标志物。
Metabolites of intestinal fora can be used as diagnostic and progressive markers for mild cognitive impairment.
机构信息
Department of Laboratory Medicine, Shanghai Pudong New Area People's Hospital, Shanghai, China.
Department of Neurology, Shanghai Pudong New Area People's Hospital, Shanghai, China.
出版信息
Front Cell Infect Microbiol. 2024 Feb 9;14:1351523. doi: 10.3389/fcimb.2024.1351523. eCollection 2024.
PURPOSE
The aim of the work was to analyze the metabolites of the intestinal microbiota from the patients with mild cognitive impairment (MCI) and progressive MCI due to Alzheimer's disease (AD).
METHOD
Two cohorts were established. The first one included 87 subjects with 30 healthy controls (NC), 22 patients with MCI due to AD, and 35 patients with AD. The second cohort included 87 patients with MCI due to AD, who were followed up for 2 years and finally were divided into progressive MCI due to AD group (P-G) and unprogressive MCI due to AD group (U-G) according their cognitive levels. Fecal samples were collected to all patients at the baseline time point. Differential metabolites were subjected to pathway analysis by MetaboAnalyst.
RESULTS
In the first cohort, we found 21 different metabolites among the three groups (AD, MCI, and NC). In the second cohort, we identified 19 differential metabolites between the P-G and U-G groups. By machine learning analysis, we found that seven characteristic metabolites [Erythrodiol, alpha-Curcumene, Synephrine, o-Hydroxylaminobenzoate, 3-Amino-4-hydroxybenzoic acid, 2-Deoxystreptamine, and 9(S] were of characteristic significance for the diagnosis of MCI due to AD, and six metabolites (Indolelactate, Indole-3-acetaldehyde, L-Proline, Perillyl, Mesaconate, and Sphingosine) were the characteristic metabolites of early warning for the progression of MCI due to AD. D-Glucuronic acid was negatively correlated with Apolipoprotein E4 (APOE4). Perillyl alcohol was negatively correlated with all of the five biomarkers [P-tau181, Neurofilament light chain (NF-light), Aβ1-42, Aβ1-40, and glial fibrillary acidic protein (GFAP)], but Indoleacetaldehyde was positively correlated with three biomarkers (P-tau181, Aβ1-42, and GFAP). Three characteristic metabolites (3-Amino-4-hydroxybenzoate, 2-Deoxystreptamine, and p-Synephrine) were positively correlated with Aβ1-42. 2-Deoxystreptamine, 9(S)-HPOT, and Indoleacetaldehyde were positively correlated with GFAP. L-Proline and Indoleacetaldehyde were positively correlated with NF-light.
CONCLUSION
Specific metabolites of intestinal fora can be used as diagnostic and progressive markers for MCI.
目的
本研究旨在分析轻度认知障碍（MCI）和阿尔茨海默病（AD）所致进行性 MCI 患者的肠道微生物群代谢产物。
方法
建立了两个队列。第一个队列包括 87 名受试者，其中 30 名健康对照者（NC）、22 名 AD 所致 MCI 患者和 35 名 AD 患者。第二个队列包括 87 名 AD 所致 MCI 患者，对其进行了 2 年的随访，根据认知水平将其最终分为 AD 所致进行性 MCI 组（P-G）和 AD 所致非进行性 MCI 组（U-G）。在基线时间点收集所有患者的粪便样本。使用 MetaboAnalyst 对差异代谢物进行途径分析。
结果
在第一个队列中，我们在三组（AD、MCI 和 NC）中发现了 21 种不同的代谢物。在第二个队列中，我们在 P-G 和 U-G 组之间发现了 19 种差异代谢物。通过机器学习分析，我们发现七种特征代谢物[赤式-表儿茶素、α-姜黄烯、辛弗林、邻-羟基氨苯甲酸、3-氨基-4-羟基苯甲酸、2-脱氧链霉胺和 9(S]对 AD 所致 MCI 的诊断具有特征意义，六种代谢物（吲哚乳酸、吲哚-3-乙醛、L-脯氨酸、紫苏醇、丁烯二酸和鞘氨醇）对 AD 所致 MCI 进展具有早期预警特征。D-葡萄糖醛酸与载脂蛋白 E4（APOE4）呈负相关。紫苏醇与所有 5 种生物标志物[P-tau181、神经丝轻链（NF-light）、Aβ1-42、Aβ1-40 和胶质纤维酸性蛋白（GFAP)]均呈负相关，但吲哚乙醛与 3 种生物标志物（P-tau181、Aβ1-42 和 GFAP)呈正相关。三种特征代谢物（3-氨基-4-羟基苯甲酸、2-脱氧链霉胺和 p-辛弗林）与 Aβ1-42 呈正相关。2-脱氧链霉胺、9(S)-HPOT 和吲哚乙醛与 GFAP 呈正相关。L-脯氨酸和吲哚乙醛与 NF-light 呈正相关。
结论
肠道菌群的特定代谢物可作为 MCI 的诊断和进展标志物。
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