Gut Microbiota, Mild Cognitive Impairment and Dementia: A Systematic Review

Background: Alterations of the gut microbiota have been increasingly implicated in the pathogenesis of dementia through mechanisms involving systemic inflammation, immune dysregulation, and gut–brain axis disruption. Clinical evidence, however, remains fragmented. Objectives: This systematic review aimed to characterize gut microbiota profiles in individuals with mild cognitive impairment (MCI) or Alzheimer’s dementia (AD), explore mechanistic associations with neurodegeneration, and evaluate the impact of microbiota-targeted interventions on cognitive outcomes. Methods: Following PRISMA 2020 guidelines and a registered protocol (PROSPERO CRD420251074832), PubMed/Medline was searched through May 2025. Eligible studies included randomized controlled trials (RCTs) and cohort and case–control studies assessing microbiota composition or interventions in participants with MCI or AD. Results: Twenty-one studies were included (1 RCT, 20 observational; sample size 22–302). Most used 16S rRNA sequencing; one used shotgun metagenomics. Across cohorts, MCI and AD patients consistently showed reduced short-chain fatty acid-producing bacteria (Faecalibacterium, Ruminococcaceae, Lachnospiraceae) and increased pro-inflammatory taxa (Escherichia/Shigella, Enterobacteriaceae, Bacteroides). Several studies reported reduced microbial diversity. Specific taxa, including Akkermansia muciniphila and Faecalibacterium, were associated with amyloid burden, hippocampal atrophy, and cognitive decline. Environmental and dietary factors influenced microbial composition and cognition. The RCT reported that probiotic supplementation improved inflammatory markers and BDNF levels, although changes in microbiota composition were inconsistent. Conclusions: Gut dysbiosis is strongly associated with cognitive impairment and markers of neurodegeneration. Modulation of the microbiota through diet and probiotics emerges as a promising avenue for dementia prevention and management, though robust longitudinal and interventional studies are needed to confirm causality and therapeutic efficacy.