Gut proteome and microbiome alterations: Analysis of transverse colon samples from pathologically confirmed Alzheimer's disease patients.

INTRODUCTION: Alzheimer's disease (AD) has been regarded as a brain-first disorder. Emerging evidence suggests that the gut may influence central nervous system pathology, but the mechanisms remain unclear. METHODS: We conducted a proteomic and microbial analysis of transverse colon samples from clinically and pathologically confirmed AD and control cases. RESULTS: In the AD gut samples, antimicrobial humoral response and oxidative stress response were downregulated, while catabolic processes and insulin signaling were upregulated. Several complement (e.g., C5) and synaptic (e.g., synaptophysin) proteins were downregulated. Amyloid beta 42 was detected at higher levels. Christensenellaceae, Desulfovibrio, and Candida tropicalis amplicon sequence variants were higher in abundance, while Streptococcus, Lachnospiraceae, Blautia, and Nakaseomyces were lower. In general, bacterial composition correlated with AD clinical variables such as plaque and tangle burden. DISCUSSION: These findings underscore the gut's possible involvement in AD pathogenesis and provide new insights into potential biomarkers and therapeutic targets. HIGHLIGHTS: This study provides the first in-depth analysis of the proteome and microbiome in AD transverse colon tissues. Multiple immune and oxidative stress response pathways were downregulated in AD, while metabolic pathways were upregulated. Synaptic protein, complement protein, and Aβ42 levels were significantly different between AD and controls. Transverse colon microbial composition was associated with AD clinical variables.