Gut microbiota alterations in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis

BackgroundAltered gut microbiota has been implicated in Alzheimer's disease (AD) and mild cognitive impairment (MCI), but findings across human studies are inconsistent.ObjectiveTo synthesize observational evidence on gut microbiota differences in older adults with AD or MCI compared with cognitively normal (CN) controls, and to assess the interpretive value of reported microbiome measures across disease stages.MethodsWe searched PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library for observational studies published from 1 January 2012 to 10 December 2025 reporting fecal microbiota profiles in AD, MCI, and CN adults (mean age ≥60). Random-effects meta-analysis was used for α-diversity; β-diversity and taxonomic changes were summarized narratively.ResultsTwenty-three studies were included (AD = 698, MCI = 485, CN = 1060). In AD versus CN, pooled α-diversity estimates showed no robust statistically significant differences (Shannon SMD = - 0.23, 95% CI: - 0.57 to 0.11; Chao1 SMD = -0.36, 95% CI: -0.74 to 0.02; ACE SMD = -0.38, 95% CI: -0.88 to 0.11). In MCI versus CN, differences were small and non-significant (Shannon SMD = -0.01, 95% CI: -0.18 to 0.15; Chao1 SMD = -0.17, 95% CI: -0.37 to 0.02). β-diversity and taxonomic findings more often suggested community-structure disruption and altered microbial composition in AD, whereas MCI findings were less consistent.Conclusionsα-diversity is not supported as a useful biomarker for distinguishing AD or MCI from CN aging. Community-structure and taxonomic patterns may be more informative, but heterogeneity limits interpretation. Future studies should use standardized, function-oriented, and biomarker-informed approaches to clarify AD-continuum microbiome changes.