The correlation and gut microbial characteristics in the whole spectrum of Alzheimer’s disease: a systematic review and meta-analysis

Background Gut dysbiosis is hypothesized to be a potential pathological mechanism in patients across the Alzheimer’s disease (AD) spectrum. Nevertheless, despite growing interest, existing findings remain largely inconsistent. Purpose This systematic review and meta-analysis aimed to compare the composition of gut microbiota (GM) between patients with mild cognitive impairment (MCI) or AD and healthy controls (HC). Methods PubMed, Embase, MEDLINE and Web of science were searched from January 2022 to November 2025. Eligible studies included observational studies and pre-intervention arms of interventional trials reporting GM abundance in AD spectrum patients vs. HC. Two reviewers independently screened articles, extracted data, and assessed bias risk. Effect sizes were pooled using an inverse-variance weighted random-effects model. Results Twenty studies (1,025 HC and 456 AD spectrum patients) were analyzed. AD patients demonstrated reduced GM diversity vs. HC cohort. The abundances of Megamonas and Bacteroides were elevated in AD patients, while Firmicutes and Proteobacteria were reduced. When stratified by clinical stage, Fusobacteria and Lactobacillus abundances showed gradient shift from MCI to AD. Conclusion Individuals within the AD spectrum exhibit altered GM abundance, with these differences influenced by clinical stage. The present study did not identify any significant trends; it reports only findings that have been statistically substantiated.