Mafe Alice N, Büsselberg Dietrich
Department of Biological Sciences, Faculty of Sciences, Taraba State University, Main Campus, Jalingo 660101, Taraba State, Nigeria.
Weill Cornell Medicine-Qatar, Education City, Qatar Foundation, Doha Metropolitan Area, Ar-Rayyan P.O. Box 22104, Qatar.
Foods. 2025 Apr 29;14(9):1559. doi: 10.3390/foods14091559.
Neurodegenerative disorders such as Alzheimer's disease (AD), the most common form of dementia, represent a growing global health crisis, yet current treatment strategies remain primarily palliative. Recent studies have shown that neurodegeneration through complex interactions within the gut-brain axis largely depends on the gut microbiota and its metabolites. This review explores the intricate molecular mechanisms linking gut microbiota dysbiosis to cognitive decline, emphasizing the impact of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and tryptophan metabolites, on neuroinflammation, blood-brain barrier (BBB) integrity, and amyloid-β and tau pathology. The paper highlights major microbiome signatures associated with Alzheimer's disease, detailing their metabolic pathways and inflammatory crosstalk. Dietary interventions have shown promise in modulating gut microbiota composition, potentially mitigating neurodegenerative processes. This review critically examines the influence of dietary patterns, such as the Mediterranean and Western diets, on microbiota-mediated neuroprotection. Bioactive compounds like prebiotics, omega-3 fatty acids, and polyphenols exhibit neuroprotective effects by modulating gut microbiota and reducing neuroinflammation. Furthermore, it discusses emerging microbiome-based therapeutic strategies, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), as potential interventions for slowing Alzheimer's progression. Despite these advances, several knowledge gaps remain, including interindividual variability in microbiome responses to dietary interventions and the need for large-scale, longitudinal studies. The study proposes an integrative, precision medicine approach, incorporating microbiome science into Alzheimer's treatment paradigms. Ultimately, cognizance of the gut-brain axis at a mechanistic level could unlock novel therapeutic avenues, offering a non-invasive, diet-based strategy for managing neurodegeneration and improving cognitive health.
神经退行性疾病，如最常见的痴呆形式阿尔茨海默病（AD），正成为全球日益严重的健康危机，但目前的治疗策略主要仍是姑息性的。最近的研究表明，通过肠-脑轴内复杂相互作用导致的神经退行性变在很大程度上取决于肠道微生物群及其代谢产物。本综述探讨了将肠道微生物群失调与认知能力下降联系起来的复杂分子机制，强调了微生物代谢产物，包括短链脂肪酸（SCFAs）、胆汁酸和色氨酸代谢产物，对神经炎症、血脑屏障（BBB）完整性以及淀粉样β蛋白和tau蛋白病理的影响。本文重点介绍了与阿尔茨海默病相关的主要微生物群特征，详细阐述了它们的代谢途径和炎症相互作用。饮食干预已显示出调节肠道微生物群组成的前景，有可能减轻神经退行性过程。本综述批判性地研究了饮食模式，如地中海饮食和西方饮食，对微生物群介导的神经保护作用的影响。益生元、ω-3脂肪酸和多酚等生物活性化合物通过调节肠道微生物群和减轻神经炎症发挥神经保护作用。此外，本文还讨论了新兴的基于微生物群的治疗策略，包括益生菌、益生元、后生元以及粪便微生物群移植（FMT），作为减缓阿尔茨海默病进展的潜在干预措施。尽管取得了这些进展，但仍存在一些知识空白，包括微生物群对饮食干预反应的个体差异以及开展大规模纵向研究的必要性。该研究提出了一种综合的精准医学方法，将微生物群科学纳入阿尔茨海默病的治疗模式。最终，从机制层面认识肠-脑轴可能会开辟新的治疗途径，为管理神经退行性变和改善认知健康提供一种非侵入性的、基于饮食的策略。
