Tailoring the biomarkers of Alzheimer’s disease using a gut microbiome-centric approach: Preclinical, clinical, and regulatory perspectives

IF 12.4 1区 医学 Q1 CELL BIOLOGY
Siya Sharma , Bushra Bashir , Kaustubh Ajit Kolekar , Anuradha Acharya , Mukta Gupta , Radheshyam Jena , Sukriti Vishwas , Jaskiran Kaur , Gaurav Gupta , Popat S. Kumbhar , Deepshikha Patle , MVNL Chaitanya , Monica Gulati , Sachin Kumar Singh
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Abstract

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, poses significant therapeutic challenges due to its complex etiology and limited treatment options. Traditional pharmacotherapies targeting amyloid-β (Aβ) and cholinergic pathways offer modest benefits and are often associated with adverse effects. Emerging evidence implicates gut dysbiosis and the gut–brain axis in the pathogenesis and progression of AD. This review explores the multifactorial pathophysiology of AD and evaluates the therapeutic potential of gut-based interventions such as probiotics, prebiotics, synbiotics, metabiotics, postbiotics, and fecal microbiota transplantation (FMT) in mitigating disease pathology. Emphasis has also been given on role of miRNA released from FMT in management of AD. Preclinical and clinical studies demonstrate that these strategies can restore microbial homeostasis, reduce neuroinflammation, enhance gut barrier integrity, and improve cognitive outcomes. The regulatory aspects with use of probiotics based products and FMT is also highlighted. The modulation of neuroimmune, neuroendocrine, and neural pathways through microbiota-derived metabolites offers a promising avenue for AD management. Despite encouraging findings, further research is needed to address interindividual microbiome variability, delivery challenges, and the requirement for large-scale, randomized trials. Personalized gut-targeted approaches may open new horizons for the prevention and treatment of AD.
使用以肠道微生物组为中心的方法定制阿尔茨海默病的生物标志物:临床前,临床和监管观点
阿尔茨海默病(AD)是一种进行性神经退行性疾病,由于其复杂的病因和有限的治疗选择,给治疗带来了重大挑战。针对淀粉样蛋白-β (Aβ)和胆碱能途径的传统药物治疗提供适度的益处,并且通常伴有副作用。新出现的证据表明,肠道生态失调和肠-脑轴在AD的发病和进展中起作用。本文探讨了阿尔茨海默病的多因素病理生理学,并评估了基于肠道的干预措施,如益生菌、益生元、合成菌、代谢菌、后益生菌和粪便微生物群移植(FMT)在减轻疾病病理方面的治疗潜力。FMT释放的miRNA在AD治疗中的作用也得到了重视。临床前和临床研究表明,这些策略可以恢复微生物稳态,减少神经炎症,增强肠道屏障完整性,改善认知结果。还强调了使用益生菌产品和FMT的监管方面。通过微生物衍生代谢物调节神经免疫、神经内分泌和神经通路为阿尔茨海默病的治疗提供了一条有前途的途径。尽管有令人鼓舞的发现,但需要进一步的研究来解决个体间微生物组的可变性、给药挑战以及对大规模随机试验的需求。个性化的肠道靶向方法可能为阿尔茨海默病的预防和治疗开辟新的视野。
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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
期刊介绍: With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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