Neurodegenerative diseases pose a major problem for developed countries, and stress has been identified as one of the main risk factors in the development of these disorders. Here, we have examined the protective properties against brain oxidative stress of two diets supplemented with 5% (
w/
w) of
Agaricus bisporus (white button mushroom) or
Agaricus bisporus brunnescens (Portobello mushroom) in mice. These diets did not modify the weight gain of the animals when compared to those fed with a regular diet, even after feeding on them for 15 weeks. The long-term modification of the microbiota after 12 weeks on the diets was investigated. At the phylum level, there was a large increase of
Verrucomicrobia and a reduction of
Cyanobacteria associated with the mushroom diets. No changes were observed in the
Firmicutes/Bacteroidetes ratio, whose stability is a marker for a healthy diet. At the family level, three groups presented significant variations. These included
Akkermansiaceae and
Tannerellaceae, which significantly increased with both diets; and
Prevotellaceae, which significantly decreased with both diets. These bacteria participate in the generation of microbiota-derived short-chain fatty acids (SCFAs) and provide a link between the microbiota and the brain. Mice subjected to restraint stress showed an upregulation of
Il-6,
Nox-2, and
Hmox-1 expression; a reduction in the enzymatic activities of catalase and superoxide dismutase; and an increase in lipid peroxidation in their brains. All these parameters were significantly prevented by feeding for 3 weeks on the
Agaricus-supplemented diets. In summary, the supplementation of a healthy diet with
Agaricus mushrooms may significantly contribute to prevent neurodegenerative diseases in the general population.
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