Aggregating gut: on the link between neurodegeneration and bacterial functional amyloids

Amyloids are insoluble protein aggregates with a cross-beta structure, which are traditionally associated with neurodegeneration. Similar structures, named functional amyloids, expressed mostly by microorganisms, play important physiological roles, e.g. bacterial biofilm stabilization. Using a bioinformatics approach, we identify gut microbiome functional amyloids and analyze their potential impact on human health via the gut-brain axis. The results point to taxonomically diverse sources of functional amyloids and their frequent presence in the extracellular space. The retrieved interactions between gut microbiome functional amyloids and human proteins indicate their potential to trigger inflammation, affect transport and signaling processes. We also find a greater relative abundance of bacterial functional amyloids in patients diagnosed with Parkinsons disease and specifically a higher content of the curli amyloid protein, CsgA, in Alzheimers disease patients than in healthy controls. Our results provide a rationale for the tentative link between neurodegeneration and gut bacterial functional amyloids.