Prognostic value of gut microbiome for progression from normal cognition to mild cognitive impairment within 4 years

Dysbiosis of the gut microbiome has been linked to the pathogenesis of Alzheimer`s disease (AD). How-ever, little is known about the longitudinal changes in the gut microbiome and its prognostic significance in early stages of AD, particularly in healthy individuals (HCs) who later develop mild cognitive impair-ment (MCI). Therefore, we investigated the ability of taxonomic and functional gut microbiome data from 100 HCs to predict the progression from normal cognition to MCI over a 4-year follow-up period (4yFU). Logistic regression models were built with baseline features that best discriminated between the two groups using an ANOVA type statistic. The best model for the discrimination of MCI converters was based on functional data using Gene Ontology (GO), which included 14 features. This model achieved an area under the receiver operating characteristic curve (AUROC) of 0.84 at baseline, 0.78 at 1-year follow-up (1yFU), and 0.75 at 4yFU. This functional model outperformed the taxonomic model, which included 38 genera features, in terms of descriptive performance and showed comparable efficacy to combined anal-yses integrating functional, taxonomic, and clinical characteristics. Gut microbiome algorithms have the potential to predict MCI conversion in HCs over a 4-year period, offering a promising innovative supplement for early AD prognosis.