Background/Objectives: Personalized nutrition programs enhanced with artificial intelligence (AI)-based tools hold promising potential for the development of healthy and sustainable diets and for disease prevention. This study aimed to explore the impact of an AI-based personalized nutrition program on the gut microbiome of healthy individuals. Methods: An intervention using an AI-based mobile application for personalized nutrition was applied for six weeks. Fecal and blood samples from 29 healthy participants (females 52%, mean age 35 years) were collected at baseline and at six weeks. Gut microbiome through 16s ribosomal RNA (rRNA) amplicon sequencing, anthropometric and biochemical data were analyzed at both timepoints. Dietary assessment was performed using food frequency questionnaires. Results: A significant increase in richness (Chao1, 220.4 ± 58.5 vs. 241.5 ± 60.2, p = 0.024) and diversity (Faith’s phylogenetic diversity, 15.5 ± 3.3 vs. 17.3 ± 2.8, p = 0.0001) was found from pre- to post-intervention. Following the intervention, the relative abundance of genera associated with the reduction in cholesterol and heart disease risk (e.g., Eubacterium coprostanoligenes group and Oscillobacter) was significantly increased, while the abundance of inflammation-associated genera (e.g., Eubacterium ruminantium group and Gastranaerophilales) was decreased. Alterations in the abundance of several butyrate-producing genera were also found (e.g., increase in Faecalibacterium, decrease in Bifidobacterium). Further, a decrease in carbohydrate (272.2 ± 97.7 vs. 222.9 ± 80.5, p = 0.003) and protein (113.6 ± 38.8 vs. 98.6 ± 32.4, p = 0.011) intake, as well as a reduction in waist circumference (78.4 ± 12.1 vs. 77.2 ± 11.2, p = 0.023), was also seen. Changes in the abundance of Oscillospiraceae_UCG_002 and Lachnospiraceae_UCG_004 were positively associated with changes in olive oil intake (Rho = 0.57, p = 0.001) and levels of triglycerides (Rho = 0.56, p = 0.001). Conclusions: This study highlights the potential for an AI-based personalized nutrition program to influence the gut microbiome. More research is now needed to establish the use of gut microbiome-informed strategies for personalized nutrition.

Emerging evidence suggests a potential role of gut dysbiosis in neurodegenerative disorders and, in particular, Alzheimer’s disease (AD) pathology and cognitive decline. However, the role of gut microbiome in the early prodromal stages of AD and particularly in mild cognitive impairment (MCI) remains understudied and has been mostly explored in Asian populations with no representation of European populations. To address this research gap in the literature and to suggest novel microbiome features associated with MCI, we conducted a cross-sectional study in a European population sample and profiled gut microbiota in 99 individuals without dementia through 16s ribosomal RNA (rRNA) sequencing. Individuals were categorized by cognitive status based on standard clinical criteria to cognitively normal (n = 49) or individuals with MCI (n = 50). Differential abundance through Microbiome Multivariable Associations with Linear model (MaAsLin2) and elastic net logistic regression analyses were used to identify gut microbiome features associated with MCI. MCI group was older than the CN group and age was used as covariate in the differential abundance analysis. No differences in alpha and beta diversity were found between the two groups (p > 0.05). At false discovery rate (FDR) < 0.05, we identified specific genera associated with MCI, mostly linked to short chain fatty acids (SCFAs) production (e.g., Candidatus_Soleaferrea q = 0.027, MaAsLin2 coefficient = 1.65, Sellimonas q = 0.017, MaAsLin2 coefficient = −4.45), while we highlight nominal (p < 0.05, q > 0.05) correlations of genera (e.g., Hydrogenoanaerobacterium, Subdoligranulum) with metrics of cognitive assessment. Microbiota was shown to have a fairly good discriminative capacity for MCI status (area under the curve AUC = 0.77), with Rothia genus found as the top predictor for MCI (beta coefficient [95% confidence intervals] = 0.224 [0.216–0.233]). Overall, our findings add to current knowledge reporting gut microbiome alterations in MCI by suggesting novel associated microbiome features; however, larger scale longitudinal studies are needed to further elucidate the underlying biological pathways linked to the disease.