{"title":"Gut microbiome synthesizes important core metabolites to prevent cognitive decline and mitigate onset and progression of Alzheimer's disease.","authors":"Nouf S Al-Abbas, Nehad A Shaer","doi":"10.1177/25424823241309024","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>This study explores how gut metabolites, produced through bacterial metabolism in the gut, influence neurological conditions like Alzheimer's disease (AD). Key metabolites such as succinate and short-chain fatty acids signal through the autonomic nervous system and can cross the blood-brain barrier, impacting central nervous system functions.</p><p><strong>Objective: </strong>The aim is to examine the role of the gut microbiota in compensating for metabolic deficiencies in AD. By analyzing wild-type (WT) and APP/PS1 mice, the study investigates how the microbiome affects key metabolic processes and whether it can slow AD progression.</p><p><strong>Methods: </strong>High-throughput sequencing data from the gut microbiomes of APP/PS1 transgenic AD model mice and age-matched WT C57BL/6 male mice were analyzed for microbial and metabolite profiles.</p><p><strong>Results: </strong>Alpha and beta diversity analyses showed differences in microbial composition between groups. Partial least squares discriminant analysis and Anosim confirmed distinct microbiome profiles in WT and APP/PS1 mice. At the genus level, <i>Vescimonas</i> was more abundant in WT mice, while <i>Odoribacter</i>, <i>Lacrimispora</i>, <i>Helicobacter</i>, <i>Bacteroides</i>, and <i>Alloprevotella</i> were more prevalent in APP/PS1 mice.</p><p><strong>Conclusions: </strong>While taxonomic differences did not directly link specific microorganisms to AD, functional analysis identified key metabolites-acetyl-CoA, glucose, succinate, lipids, choline, and acetylcholine-that may alleviate energy deficits and synaptic dysfunction. This study suggests that the microbiome may help compensate for AD-related impairments, opening avenues for microbiome-based therapies.</p>","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":"8 1","pages":"1705-1721"},"PeriodicalIF":2.8000,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863740/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Alzheimer's disease reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/25424823241309024","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Background: This study explores how gut metabolites, produced through bacterial metabolism in the gut, influence neurological conditions like Alzheimer's disease (AD). Key metabolites such as succinate and short-chain fatty acids signal through the autonomic nervous system and can cross the blood-brain barrier, impacting central nervous system functions.
Objective: The aim is to examine the role of the gut microbiota in compensating for metabolic deficiencies in AD. By analyzing wild-type (WT) and APP/PS1 mice, the study investigates how the microbiome affects key metabolic processes and whether it can slow AD progression.
Methods: High-throughput sequencing data from the gut microbiomes of APP/PS1 transgenic AD model mice and age-matched WT C57BL/6 male mice were analyzed for microbial and metabolite profiles.
Results: Alpha and beta diversity analyses showed differences in microbial composition between groups. Partial least squares discriminant analysis and Anosim confirmed distinct microbiome profiles in WT and APP/PS1 mice. At the genus level, Vescimonas was more abundant in WT mice, while Odoribacter, Lacrimispora, Helicobacter, Bacteroides, and Alloprevotella were more prevalent in APP/PS1 mice.
Conclusions: While taxonomic differences did not directly link specific microorganisms to AD, functional analysis identified key metabolites-acetyl-CoA, glucose, succinate, lipids, choline, and acetylcholine-that may alleviate energy deficits and synaptic dysfunction. This study suggests that the microbiome may help compensate for AD-related impairments, opening avenues for microbiome-based therapies.