阿尔茨海默病患者载脂蛋白E基因多态性与肠道菌群微生态的关系

Association between apolipoprotein E gene polymorphism and gut microbiota ecology in patients with Alzheimer disease

摘要:

目的 探讨载脂蛋白E（ApoE）基因多态性与阿尔茨海默病（AD）患者肠道菌群的关系以及粪便微生物移植（FMT）的治疗效果。方法 纳入2023年1月至2024年12月黄河三门峡医院就诊的110例AD患者。检测患者的ApoE基因型，分为ApoE4携带组（ε3/ε4和ε4/ε4，58例）与非携带组（ε3/ε3，52例）。比较2组肠道菌群（肠球菌、大肠埃希菌、乳杆菌、双歧杆菌）及短链脂肪酸（乙酸、丙酸、丁酸、异丁酸）水平。另将患者分为试验组（55例，FMT胶囊+常规药物）与对照组（55例，安慰剂胶囊+常规药物）。比较2组患者的临床症状改善情况，通过临床痴呆评定量表（CDR）、蒙特利尔认知评估量表（MoCA）、匹兹堡睡眠质量指数（PSQI）、汉密尔顿抑郁量表（HAMD）、阿尔茨海默病协作研究日常能力量表（ADCS-ADL）、布里斯托粪便分型量表（BSFS）、胃肠道症状评定量表（GSRS）进行评估。比较试验组和对照组肠道的菌群分布和肠道菌群代谢产物。结果 ApoE4携带组肠球菌、大肠埃希菌数量高于非携带组，乳杆菌、双歧杆菌及短链脂肪酸水平低于非携带组（P<0.05）。FMT治疗后，试验组临床症状评分优于对照组，肠球菌、大肠埃希菌数量低于对照组，乳杆菌、双歧杆菌及短链脂肪酸水平高于对照组（P<0.05）。结论 AD患者中ApoE4携带者存在肠道菌群失衡，FMT可改善AD症状，并调节肠道菌群。

Abstract:

Objective To investigate the association between apolipoprotein E （ApoE） gene polymorphism and gut microbiota in patients with Alzheimer disease （AD） and the therapeutic effect of fecal microbiota transplantation （FMT）.Methods A total of 110 AD patients who attended Yellow River Sanmenxia Hospital from January 2023 to December 2024 were enrolled. The ApoE genotype was determined， and the patients were divided into ApoE4 carrier group （58 patients with ε3/ε4 or ε4/ε4 genotype） and non-carrier group （52 patients with ε3/ε3 genotype）. The two groups were compared in terms of the levels of gut microbiota （Enterococcus， Escherichia coli， Lactobacillus， and Bifidobacterium） and short-chain fatty acids （acetic acid， propionic acid， butyric acid， and isobutyric acid）. In addition， the patients were divided into test group （55 patients treated with FMT capsules and conventional medications） and control group （55 patients treated with placebo capsules and conventional medications）. These two groups were compared in terms of the improvement of clinical symptoms based on Clinical Dementia Rating （CDR）， Montreal Cognitive Assessment （MoCA）， Pittsburgh Sleep Quality Index （PSQI）， Hamilton Depression Rating （HAMD）， Alzheimer’s Disease Cooperative Study Activities of Daily Living （ADCS-ADL）， Bristol Stool Form Scale （BSFS）， and Gastrointestinal Symptom Rating Scale （GSRS）. The distribution of gut microbiota and their metabolic products were also compared between the test group and the control group.Results Compared with the non-carrier group， the ApoE4 carrier group had significantly higher numbers of Enterococcus and Escherichia coli， significantly lower numbers of Lactobacillus and Bifidobacterium， and significantly lower levels of short-chain fatty acids （P<0.05）. After FMT treatment， compared with the control group， the test group had significantly better clinical symptom scores， significantly lower numbers of Enterococcus and Escherichia coli， significantly higher numbers of Lactobacillus and Bifidobacterium， and significantly higher levels of short-chain fatty acids （P<0.05）.Conclusions ApoE4 carriers among AD patients exhibit gut microbiota dysbiosis， and FMT can improve the symptoms of AD and regulate gut microbiota.