The microbiota-gut-brain axis in mild cognitive impairment and Alzheimer's disease: a scoping review of human studies

Alison Warren, The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Zan Wynia, Milken Institute of Public Health, Department of Global Health, The George Washington University, Washington, District of Columbia, USA.
Patrick G. Corr, The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Mershad Fahim Devin, The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Zeynep Celikkol, The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Lindsey Gordon, The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Mina Farah, The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Michaela Karam, The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Daniel Villarreal, The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Scott A. Jackson, The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Leigh A. Frame, The Frame-Corr Laboratory, Department of Clinical Research and Leadership, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.

Document Type

Journal Article

Publication Date

1-1-2026

Journal

Alzheimer's & dementia : the journal of the Alzheimer's Association

Volume

22

Issue

1

DOI

10.1002/alz.71023

Keywords

Alzheimer's disease; Mediterranean; biomarkers; cognition disorder; cognitive dysfunction; diet; dysbiosis; gastrointestinal microbiome; metagenomics; microbiota; microbiota–gut–brain axis; mild cognitive impairment; neuroinflammation; probiotics; short‐chain fatty acids; systematic review as topic

Abstract

Alzheimer's disease (AD) is projected to become the highest-burden neurological disorder globally. Mounting evidence implicates the gut microbiome in AD pathogenesis. This scoping review of gut microbiomes in mild cognitive impairment (MCI) and AD included dietary and probiotic interventions. We included original research and systematic reviews/meta-analyses. Animal and non-English studies were excluded. We searched PubMed, Scopus, and Cochrane Library through February 2023. Using Arksey and O'Malley's framework and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-Extension for Scoping Reviews (ScR) checklist, we screened 4751 articles, with 58 meeting predefined inclusion criteria. Our results demonstrated that gut dysbiosis was frequently reported in MCI and AD, including increased Pseudomonadota and Actinomycetota in AD and reduced diversity in some cases. Probiotic and dietary interventions showed promise in modulating cognition and microbiota, inconsistently. Emerging evidence links dysbiosis to cognitive decline; however, methodological heterogeneity and limited follow-up impede causal inference. Research should prioritize standardized protocols, functional microbiome analysis, and longitudinal human studies to clarify therapeutic potential. HIGHLIGHTS: Gut dysbiosis is a common feature of MCI and AD, with phylum-level microbial shifts frequently observed. Pseudomonadota and Actinomycetota are enriched in AD across multiple human studies. Beneficial genera like Faecalibacterium and Roseburia are consistently reduced in MCI and AD in a small number of studies. Probiotic and dietary interventions are promising to modulate the microbiota-cognition axis. More longitudinal human studies are needed to assess causal microbiome relationships.

Department

Clinical Research and Leadership

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