The accumulation of β-amyloid plaques, neurofibrillary tangles, and neuroinflammation are key hallmarks of Alzheimer's disease (AD). Reactive oxygen species (ROS) act as major triggers and amplifiers of neuroinflammatory responses, contributing to immune dysregulation and neuronal damage. Despite extensive research, no effective therapy halts or reverses AD progression, emphasizing the need for alternative preventive strategies, including the use of natural compounds.

Objectives: This study evaluated the neuroprotective effects of simulated digestive fractions (permeate fraction) of mushroom biomass (MB)-Trametes versicolor (TV), Hericium erinaceus (HE), and Pleurotus ostreatus (PO)-and key gut microbiota-derived metabolites, such as short-chain fatty acids (SCFAs) and γ-aminobutyric acid (GABA) on ROS production in human microglial cells (HMC3) and in transgenic Caenorhabditis elegans models exhibiting hyperphosphorylated Tau and β-amyloid-induced toxicity.

Results: Mushroom digestive fractions and SCFAs significantly decreased ROS levels in HMC3 cells. Moreover, mushroom digestive fractions, butyric acid, and GABA improved behavioral outcomes in C. elegans, enhancing chemotaxis and delaying paralysis. These effects were dose-dependent and varied among mushroom species and metabolites.

Conclusion: Mushroom-derived digestive fractions and microbiota-related metabolites exhibit neuroprotective activity by modulating oxidative stress and mitigating neurodegeneration-associated behaviors. Diets enriched with such MBs may support preventive strategies for neurodegenerative diseases.

Nutrients. 2025 Dec 11;17(24):3867. doi: 10.3390/nu17243867

The Trametes versicolor (Coriolus versicolor), Hericium erinaceus and Pleurotus ostreatus biomass used in this study was supplied by Mycology Research Laboratories Ltd.