Fifty-nine key microbial species are linked to and Alzheimer's disease biomarkers.
Species within the same genera, such as Bacteroides and Ruminococcus, exhibited opposing effects on cognitive health.
Akkermansia muciniphila is associated with reduced amyloid burden, potentially indicating a protective role.
Microbial pathways related to energy metabolism and neuroinflammation may mediate the relationship between gut microbiota and brain health.
Co-occurrence network analyses suggest complex interactions among gut microbes that influence neurodegeneration.
Findings challenge traditional genus-level analyses, emphasizing the importance of species-specific insights.
Simplified
BACKGROUND: Emerging evidence highlights the bidirectional communication between the gut microbiota and the brain, suggesting a potential role for in Alzheimer's disease (AD) pathology and cognitive decline. Existing literature on gut microbiota lacks species-level insights. This study investigates gut microbiota alterations in (MCI), focusing on their association with comprehensive AD biomarkers, including amyloid burden, tau pathology, neurodegeneration, and cognitive performance.
METHODS: We analyzed fecal samples from 119 individuals with MCI and 320 cognitively normal controls enrolled in the Taiwan Precision Medicine Initiative on Cognitive Impairment and Dementia cohort. Shotgun metagenomic sequencing was conducted with taxonomic profiling using MetaPhlAn4. Amyloid burden and plasma pTau181 were quantified via PET imaging and Simoa assays, respectively, while APOE genotyping was performed using TaqMan assays. Microbial diversity, differential abundance analysis, and correlation mapping with neuropsychological and neuroimaging measures were conducted to identify gut microbiota species signatures associated with MCI and AD biomarkers.
RESULTS: We identified 59 key microbial species linked to MCI and AD biomarkers. Notably, species within the same genera, such as Bacteroides and Ruminococcus, showed opposing effects, while Akkermansia muciniphila correlated with reduced amyloid burden, suggesting a protective role. Functional profiling revealed microbial pathways contributing to energy metabolism and neuroinflammation, mediating the relationship between gut microbes and brain health. Co-occurrence network analyses demonstrated complex microbial interactions, indicating that the collective influence of gut microbiota on neurodegeneration.
CONCLUSIONS: Our findings challenge genus-level microbiome analyses, revealing species-specific modulators of AD pathology. This study highlights gut microbial activity as a potential therapeutic target to mitigate cognitive decline and neurodegeneration.
Key numbers
59
Key Microbial Species Identified
Identified through differential abundance analysis in patients.
320
Cognitively Normal Controls
Included in the study alongside 119 patients.
119
Participants
Analyzed alongside 320 cognitively normal controls.
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Declarations. Ethics approval and consent to participate: Ethical approval was obtained from the Far Eastern Memorial Hospital Research Ethics Committee (110065-F) and the Institutional Review Board of Cardinal Tien Hospital (CTH-110-2-1-014) in accordance with the Declaration of Helsinki. All participants provided informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
