{"title":"Gut microbiota metabolites: potential therapeutic targets for Alzheimer’s disease?","authors":"Shanshan Zhang, Jing Lu, Ziqi Jin, Hanying Xu, Dongmei Zhang, Jianan Chen, Jian Wang","doi":"10.3389/fphar.2024.1459655","DOIUrl":null,"url":null,"abstract":"BackgroundAlzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective in preventing or mitigating the progression of AD. An increasing number of recent studies support the hypothesis that the gut microbiome and its metabolites may be associated with upstream regulators of AD pathology.MethodsIn this review, we comprehensively explore the potential mechanisms and currently available interventions targeting the microbiome for the improvement of AD. Our discussion is structured around modern research advancements in AD, the bidirectional communication between the gut and brain, the multi-target regulatory effects of microbial metabolites on AD, and therapeutic strategies aimed at modulating gut microbiota to manage AD.ResultsThe gut microbiota plays a crucial role in the pathogenesis of AD through continuous bidirectional communication via the microbiota-gut-brain axis. Among these, microbial metabolites such as lipids, amino acids, bile acids and neurotransmitters, especially sphingolipids and phospholipids, may serve as central components of the gut-brain axis, regulating AD-related pathogenic mechanisms including β-amyloid metabolism, Tau protein phosphorylation, and neuroinflammation. Additionally, interventions such as probiotic administration, fecal microbiota transplantation, and antibiotic use have also provided evidence supporting the association between gut microbiota and AD. At the same time, we propose an innovative strategy for treating AD: a healthy lifestyle combined with targeted probiotics and other potential therapeutic interventions, aiming to restore intestinal ecology and microbiota balance.ConclusionDespite previous efforts, the molecular mechanisms by which gut microbes act on AD have yet to be fully described. However, intestinal microorganisms may become an essential target for connecting the gut-brain axis and improving the symptoms of AD. At the same time, it requires joint exploration by multiple centers and multiple disciplines.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fphar.2024.1459655","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
BackgroundAlzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function, which significantly increases pain and social burden. However, few therapeutic interventions are effective in preventing or mitigating the progression of AD. An increasing number of recent studies support the hypothesis that the gut microbiome and its metabolites may be associated with upstream regulators of AD pathology.MethodsIn this review, we comprehensively explore the potential mechanisms and currently available interventions targeting the microbiome for the improvement of AD. Our discussion is structured around modern research advancements in AD, the bidirectional communication between the gut and brain, the multi-target regulatory effects of microbial metabolites on AD, and therapeutic strategies aimed at modulating gut microbiota to manage AD.ResultsThe gut microbiota plays a crucial role in the pathogenesis of AD through continuous bidirectional communication via the microbiota-gut-brain axis. Among these, microbial metabolites such as lipids, amino acids, bile acids and neurotransmitters, especially sphingolipids and phospholipids, may serve as central components of the gut-brain axis, regulating AD-related pathogenic mechanisms including β-amyloid metabolism, Tau protein phosphorylation, and neuroinflammation. Additionally, interventions such as probiotic administration, fecal microbiota transplantation, and antibiotic use have also provided evidence supporting the association between gut microbiota and AD. At the same time, we propose an innovative strategy for treating AD: a healthy lifestyle combined with targeted probiotics and other potential therapeutic interventions, aiming to restore intestinal ecology and microbiota balance.ConclusionDespite previous efforts, the molecular mechanisms by which gut microbes act on AD have yet to be fully described. However, intestinal microorganisms may become an essential target for connecting the gut-brain axis and improving the symptoms of AD. At the same time, it requires joint exploration by multiple centers and multiple disciplines.
背景阿尔茨海默病(AD)是一种神经退行性疾病,其特点是认知功能进行性下降,大大增加了患者的痛苦和社会负担。然而,很少有治疗干预措施能有效预防或缓解阿尔茨海默病的进展。最近越来越多的研究支持这样的假设,即肠道微生物组及其代谢物可能与 AD 病理学的上游调节因素有关。方法在这篇综述中,我们全面探讨了针对微生物组改善 AD 的潜在机制和目前可用的干预措施。我们的讨论围绕着 AD 的现代研究进展、肠道与大脑之间的双向交流、微生物代谢物对 AD 的多靶点调控作用以及旨在调节肠道微生物群以控制 AD 的治疗策略展开。其中,微生物代谢产物,如脂类、氨基酸、胆汁酸和神经递质,尤其是鞘磷脂和磷脂,可作为肠脑轴的核心成分,调节与AD相关的致病机制,包括β-淀粉样蛋白代谢、Tau蛋白磷酸化和神经炎症。此外,益生菌施用、粪便微生物群移植和抗生素使用等干预措施也提供了支持肠道微生物群与 AD 之间关联的证据。同时,我们提出了一种治疗 AD 的创新策略:将健康的生活方式与有针对性的益生菌和其他潜在的治疗干预措施相结合,旨在恢复肠道生态和微生物群平衡。然而,肠道微生物可能成为连接肠道-大脑轴和改善 AD 症状的重要靶点。同时,这也需要多中心、多学科的共同探索。
期刊介绍:
Frontiers in Pharmacology is a leading journal in its field, publishing rigorously peer-reviewed research across disciplines, including basic and clinical pharmacology, medicinal chemistry, pharmacy and toxicology. Field Chief Editor Heike Wulff at UC Davis is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.