Ecological Insights into Gut Microbiota Networks Across Cognitive States in Alzheimer's Disease.

The ecological mechanisms governing gut microbial community stability during Alzheimer's disease (AD) progression remain poorly understood. This study employed an ecological network to investigate microbial interactions and stability across cognitively normal controls (CK), individuals with mild cognitive impairment (MCI), and AD patients. We observed a stepwise decline in network complexity across groups, characterized by reduced clustering coefficients and average degree, from CK to AD. While the MCI group exhibited intermediate structural complexity, it displayed the highest vulnerability and lowest robustness, indicating a critical transitional state. Keystone taxa analysis revealed a significant shift in microbial community, with the CK network was enriched with diverse, potentially beneficial keystone taxa, whereas the AD network retained only connector species, and the MCI network showed a complete absence of keystone taxa. Cohesion analysis revealed a non-linear trajectory of microbial interactions, with negative cohesion peaking in MCI. Our findings demonstrate that cognitive decline is associated with a fundamental reorganization of the gut microbial ecosystem. This reorganization pattern reveals a resilient state in health, a vulnerable phase in MCI, and a stable yet dysbiotic configuration in AD, with keystone taxa serving as pivotal regulators of community stability. Community assembly analysis showed a shift from deterministic to stochastic processes during cognitive decline, with weakened host regulatory mechanisms. These findings advance our understanding of the gut microbial ecology in neurodegenerative disease and reveal the mechanism by which microbial communities reorganize network to maintain stability in different cognitive states.