Microbiome Impact on Amyloidogenesis

Abstract

Our life is closely linked to microorganisms, either through a parasitic or symbiotic relationship. The microbiome contains more than 1,000 different bacterial species and outnumbers human genes by 150 times. Worryingly, during the last 10 years, it has been observed a relationship between alterations in microbiota and neurodegeneration. Several publications support the hypothesis that amyloid structures formed by microorganisms may trigger host proteins aggregation. In this review, we collect pieces of evidence supporting that the crosstalk between human and microbiota amyloid proteins could be feasible and, probably, a more common event than expected before. The combination of their outnumbers, the long periods of time that stay in our bodies, and the widespread presence of amyloid proteins in the bacteria Domain outline a worrying scenario. However, the identification of the exact microorganisms and the mechanisms through with they can influence human disease also opens the door to developing a new and diverse set of therapeutic strategies.

Keywords: amyloid; bacteria; gut; microbiome; neurodegenerative disease; prion; probiotic.

FIGURE 1

Microbiome impact on amyloidogenesis. The gut microbiome is composed of approximately 10¹⁴ bacteria and contains 4.6⁷ bacterial genes. The prion prediction tools have measured approximately 0.3% prions per genome. In the microbiome, this can result in approximately 1.38⁵ genes coding for prion-like domains. The expression of these genes can produce a large number of polypeptide sequences with the potential to form amyloid fibrils. These aggregates may have the ability to interfere with and cross-seed human proteins. The gut and the brain are interconnected by a bidirectional axis. In addition, it has been reported that changes in microbiota composition are related to neurodegenerative diseases. Overall, the administration of probiotics could be a potential therapeutic strategy to treat these disorders.