Microbiota-Derived β-Amyloid-like Peptides Trigger Alzheimer’s Disease-Related Pathways in the SH-SY5Y Neural Cell Line

Abstract

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.

The intestinal immune system and gut barrier function in obesity and ageing

“…The same study also observed Aβ aggregation in the intestinal epithelium of patients with AD, which reinforces the importance of the gut‐brain axis in the pathogenesis of neurodegenerative diseases. In fact, a study recently has found that Aβ‐like peptides synthesized from the gut microbiota ( Clostridiales order) were actually capable of activating AD‐related pathways in neural cells in vitro , due to their homology to Aβ, although whether this phenomenon occurs in vivo remains to be seen [231]. Furthermore, it has been reported that the faecal microbiota composition of patients with AD is significantly different.…”