Figure 1.

GM affect the production of pathogenic proteins in the brain directly and indirectly. GM can produce lipopolysaccharide and amyloid protein, and these harmful substances enter the body and cause NDs when intestinal and blood-brain barriers are damaged. Bacterial amyloid directly cause the accumulation of pathogenic α-syn in the gut in a “cross-seeding” manner, or the intestinal AEP cleaved α-syn and Tau proteins at N103 and N368 sites, respectively, to form α-syn N103/Tau N368 complex. These pathogenic proteins then enter the brain through the vagus nerve, causing cognitive dysfunction. Bacterial amyloid and lipolysaccharide pass through the damaged intestinal barrier and blood-brain barrier to cause inflammation in the peripheral circulatory system, or cause inflammation in the brain to produce pro-inflammatory cytokines, indirectly leading to the synthesis and deposition of pathogenic amyloid proteins. LPS, lipopolysaccharide; α-syn, α-synuclein; Aβ, β-amyloid; AEP, asparagine endopeptidase; IL, interleukin; TNF-α, tumor necrosis factor-α; BAP, bacterial amyloid protein.