Division of Biological Sciences, University of California at San Diego, La Jolla, CA, USA.
Department of Psychiatry, University of California at San Diego, La Jolla, CA, USA.
Arch Clin Neuropsychol. 2022 Feb 22;37(3):595-607. doi: 10.1093/arclin/acac008.
OBJECTIVE: The gut microbiome is a complex community of microorganisms that inhabit the gastrointestinal tract. The microbiota-gut-brain axis encompasses a bidirectional communication system that allows the gut to influence the brain via neural, endocrine, immune, and metabolic signaling. Differences in the gut microbiome have been associated with psychiatric and neurological disorders, including Alzheimer's Disease (ad). Understanding these ad-associated alterations may offer novel insight into the pathology and treatment of ad. METHOD: We conducted a narrative review of clinical studies investigating the gut microbiome in ad, organizing the results by phyla to understand the biological contributions of the gut microbial community to ad pathology and clinical features. We also reviewed randomized clinical trials of interventions targeting the microbiome to ameliorate ad symptoms and biomarkers. RESULTS: Alpha diversity is reduced in patients with ad. Within Firmicutes, taxa that produce beneficial metabolites are reduced in ad, including Clostridiaceae, Lachnospiraceae, Ruminococcus, and Eubacterium. Within Bacteroidetes, findings were mixed, with studies showing either reduced or increased abundance of Bacteroides in mild cognitive impairment or ad patients. Proteobacteria that produce toxins tend to be increased in ad patients, including Escherichia/Shigella. A Mediterranean-ketogenic dietary intervention significantly increased beneficial short-chain fatty acids and taxa that were inversely correlated with changes in ad pathological markers. Probiotic supplementation with Lactobacillus spp. and Bifidobacterium spp. improved cognitive function and reduced inflammatory and metabolic markers in patients with ad. CONCLUSIONS: The gut microbiome may provide insight into ad pathology and be a novel target for intervention. Potential therapeutics include probiotics and dietary intervention.
目的:肠道微生物组是栖息在胃肠道中的微生物的复杂群落。微生物群-肠道-大脑轴包含一个双向通讯系统,使肠道能够通过神经、内分泌、免疫和代谢信号影响大脑。肠道微生物组的差异与精神和神经疾病有关,包括阿尔茨海默病(AD)。了解这些与 AD 相关的改变可能为 AD 的病理和治疗提供新的见解。
方法:我们对研究 AD 中肠道微生物组的临床研究进行了叙述性综述,通过门分类来组织结果,以了解肠道微生物群落对 AD 病理学和临床特征的生物学贡献。我们还回顾了针对微生物组的干预措施的随机临床试验,以改善 AD 症状和生物标志物。
结果:AD 患者的α多样性降低。在厚壁菌门中,产生有益代谢物的分类群在 AD 中减少,包括梭菌科、lachnospiraceae、瘤胃球菌和真杆菌。在拟杆菌门中,研究结果喜忧参半,一些研究表明轻度认知障碍或 AD 患者的拟杆菌丰度降低或增加。产生毒素的变形菌通常在 AD 患者中增加,包括大肠杆菌/志贺氏菌。地中海-生酮饮食干预显著增加了有益的短链脂肪酸和与 AD 病理标志物变化呈负相关的分类群。补充乳杆菌属和双歧杆菌属的益生菌可改善 AD 患者的认知功能,并降低炎症和代谢标志物。
结论:肠道微生物组可能为 AD 病理学提供见解,并成为干预的新靶点。潜在的治疗方法包括益生菌和饮食干预。
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