A retrospective study on blood microbiota as a marker for cognitive decline: implications for detecting Alzheimer's disease and amnestic mild cognitive impairment in Republic of Korea.

Objectives: This study aimed to investigate the relationship between blood microbiota, specifically bacterial DNA, and cognitive decline in individuals with subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI). The objective was to identify potential microbial signatures that could serve as biomarkers for cognitive deterioration.

Methods: Forty-seven participants were recruited, including 13 with aMCI, 20 with SCD, and 14 normal cognition (NC). Blood samples were collected, and microbial DNA was analyzed using 16S rRNA sequencing on the Illumina MiSeq platform. Bioinformatics analyses-including α- and β-diversity measures and differential abundance testing (using edgeR)-were employed to assess microbial diversity and differences in bacterial composition among groups. Logistic regression models were used to evaluate the predictive impact of the microbiota on cognitive decline.

Results: Microbial diversity differed significantly between groups, with NC exhibiting the highest α-diversity. Both the aMCI and SCD groups showed reduced diversity. Taxa such as Bacteroidia, Alphaproteobacteria, and Clostridia were significantly decreased in the aMCI group compared to NC (p<0.05). In contrast, Gammaproteobacteria increased significantly in the aMCI group compared to both NC and SCD, indicating progressive microbial changes from SCD to aMCI. No significant differences were found between the NC and SCD groups.

Conclusion: Distinct bacterial taxa-particularly the increase in Gammaproteobacteria along with decreases in Bacteroidia, Alphaproteobacteria, and Clostridia-are associated with the progression of cognitive decline. These findings suggest that blood microbiota could serve as potential biomarkers for the early detection of aMCI. However, the small sample size and the lack of control for confounding factors such as diet and medication limit the findings. Larger studies are needed to validate these results and further explore the role of microbiota in neurodegeneration.