Neurodegenerative diseases: the crucial role of the gut

A new contribution to the understanding of neurodegenerative diseases comes from a study carried out by Francesca Terrin and coordinated by Nicoletta Plotegher e Luisa Dalla Valle, of the Department of Biology of the University of Padua. The research was published in the Journal of Biomedical Science.
The study suggests that some neurodegenerative processes may originate from intestinal inflammation, which can subsequently involve the central nervous system.

The role of BSSG

The research focused on BSSG, β-sitosterol β-D-glucoside, a glycosylated sterol of plant origin found in some foods. The molecule had already been associated with ALS-PDC, the Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex observed in the population of the island of Guam, but its mechanism of toxicity had not yet been clarified.
“Through the use of two animal models, zebrafish and mouse, we demonstrated how chronic exposure to BSSG induces an early marked state of intestinal inflammation, which appears much earlier than the onset of signs of neurodegeneration”, explains Francesca Terrin.

Inflammation, intestinal alterations and dysbiosis

The inflammation is accompanied by increased expression of genes involved in inflammatory processes, alterations to the mucosa, and impairment of intestinal motility and function. Preliminary analyses also suggest that BSSG may promote a condition of dysbiosis, namely an imbalance in the normal bacterial flora.

The glucocorticoid receptor

A central aspect of the study concerns the possible molecular mechanism responsible for these effects. “Using transgenic and mutant zebrafish lines, we observed that the molecule appears to interfere with the glucocorticoid receptor, an important regulator of the body’s anti-inflammatory responses”, states Luisa Dalla Valle.
This interference could reduce the receptor’s ability to limit inflammation, promoting the persistence of an intestinal inflammatory state.

The gut-brain axis

The results support the hypothesis that intestinal inflammation may precede neurodegeneration and strengthen the possible involvement of the gut-brain axis in the pathogenesis of these diseases.
This bidirectional communication system links the intestine to the central nervous system through neural, immune and metabolic pathways. Chronic inflammation, alterations of the intestinal barrier and dysbiosis may compromise its balance and promote neuroinflammatory and neurodegenerative processes. 

New research perspectives

“This work identifies the intestine as a possible starting point of BSSG-induced neurodegenerative processes and helps to redefine the understanding of the early stages of ALS-PDC”, concludes Nicoletta Plotegher.
Although based on animal models, the study highlights the role of intestinal homeostasis in neurodegenerative diseases and opens up new perspectives for preventive and therapeutic strategies aimed at protecting the gut-brain axis.