Several of these microorganism proteins were associated with samples from AD patients exhibiting increased disease severity, as indicated by specific downtrend and uptrend patterns in bEVs, including formate tetrahydrofolate ligase (FHS), AHCY (Fig. 3, F and G), and bacterial HSP (DnaK3), aconitate hydratase A (acnA), acyl-CoA dehydrogenase (ACAD), and phosphate-binding protein (PstS) (Fig. 3, H–K). Here, KLK4 is linked to Alzheimer disease.