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

Antimicrobial humoral response and oxidative stress response pathways were downregulated in AD transverse colon samples.

• Analysis was conducted on transverse colon samples from clinically and pathologically confirmed AD and control cases.
• Multiple immune and oxidative stress response pathways were downregulated in AD gut tissue.
• This represents the first in-depth proteomic analysis of AD transverse colon tissues.

Catabolic processes and insulin signaling pathways were upregulated in AD transverse colon samples.

• Metabolic pathways were upregulated in AD gut tissue.
• Insulin signaling was specifically identified as upregulated in AD colon samples.
• These findings were identified through proteomic analysis of transverse colon tissue.

Several complement proteins and synaptic proteins were downregulated in AD gut samples.

• Complement protein C5 was among the downregulated complement proteins identified.
• Synaptophysin was among the downregulated synaptic proteins identified.
• Synaptic protein and complement protein levels were described as 'significantly different between AD and controls.'

Amyloid beta 42 (Aβ42) was detected at higher levels in AD transverse colon samples compared to controls.

• Aβ42 levels were significantly different between AD and control gut tissue samples.
• This was detected through proteomic analysis of transverse colon tissue.
• The finding suggests peripheral Aβ42 accumulation in the gut of AD patients.

Christensenellaceae, Desulfovibrio, and Candida tropicalis amplicon sequence variants were present at higher abundance in AD gut samples.

• Microbial analysis was performed on transverse colon tissue samples.
• Christensenellaceae (bacterial family), Desulfovibrio (bacterial genus), and Candida tropicalis (fungal species) were all elevated in AD.
• Amplicon sequence variants (ASVs) were used as the unit of microbial measurement.

Streptococcus, Lachnospiraceae, Blautia, and Nakaseomyces were lower in abundance in AD gut samples.

• These microbial taxa spanned both bacterial genera/families and fungal genera (Nakaseomyces).
• Lachnospiraceae is a bacterial family previously associated with gut health.
• Blautia is a bacterial genus within Lachnospiraceae associated with beneficial gut functions.

Bacterial composition in the transverse colon correlated with AD clinical variables including plaque and tangle burden.

• Microbial composition was associated with AD clinical variables such as amyloid plaque burden and neurofibrillary tangle burden.
• Cases were clinically and pathologically confirmed AD and control cases.
• In general, bacterial composition correlated with multiple AD clinical variables.