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

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.

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.

FIGURE 1

PRISMA flow diagram of study selection process. This flowchart illustrates the systematic process for identifying, screening, assessing for eligibility, and including studies in this scoping review. Initial searches from databases and registers yielded 4751 studies. Following the removal of 1529 duplicates (four manually identified, 1525 by covidence), 3222 studies were screened based on title and abstract. Of these, 2116 were excluded. A total of 1106 studies were sought for retrieval and assessed for eligibility. During full‐text review, 1047 studies were excluded for various reasons, predominantly incorrect study design (n = 763), wrong outcomes (n = 57), wrong patient population (n = 60), or full‐text unavailability (n = 69). Ultimately, 59 studies were included in this review.

FIGURE 2

Venn diagram summarizing unique and common attributes among individuals with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy controls.