Microbiota-derived β-amyloid-like peptides trigger alzheimer’s disease-related pathways in the sh-sy5y neural cell line

Here, we present the first in silico and in vitro evidence of Aβ-like peptides released from meaningful members of the gut microbiome (mostly from the Clostridiales order). Two peptides with high homology to the human Aβ peptide domain were synthesized and tested in vitro in a neuron cell-line model. Gene expression profile analysis showed that one of them induced whole gene pathways related to AD, opening the way to translational approaches to assess whether gut microbiota-derived peptides might be implicated in the neurodegenerative processes related to AD. This exploratory work opens the path to new approaches for understanding the relationship between the gut microbiome and the triggering of potential molecular events leading to AD. As microbiota can be modified using diet, tools for precise nutritional intervention or targeted microbiota modification in animal models might help us to understand the individual roles of gut bacteria releasing Aβ-like peptides and therefore their contribution to this progressive disease.

This work was supported by the Spanish “Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad” through the projects AGL2013-44039R (MINECO, FEDER, UE) and RTI2018-096339-B-I00 (MCIU/AEI/FEDER, UE); by the “Asociación Española Contra el Cáncer” by means of the project “Obtención de péptidos bioactivos contra el Cáncer Colo-Rectal a partir de secuencias genéticas de microbiomas intestinalis” (grant PS-2016); and by the Asturias Regional Plan I+D+i for research groups (FYCYT-IDI/2018/000236). H.T. acknowledges his “Severo Ochoa” predoctoral grant (BP17-55) to the Government of “Principado de Asturias”.