The project
The project in brief
A new synbiotic formulation made of probiotic bacteria and gamma-oryzanol will be tested in a well-established mouse model of accelerated aging (Senescence Accelerated Mouse-Prone 8, SAMP8).
The first part of the project will be dedicated to preliminary in vitro studies to determine the effect of gamma-oryzanol on probiotic bacterial strains isolated from elderly healthy people in terms of cell viability, production and protein content of secreted extracellular vesicles. Results from these assays will allow us to design a new formulation to be used in the following animal studies. We will also try to optimize the gamma-oryzanol extraction process from rice bran, which is normally considered a waste product of rice production, in order to improve its utilization as alternative source of biological active molecules.
The second part of the project will deal with in vivo experiments performed on SAMP8 mice and control SAMR1 animals. Mice will receive the formulation of probiotics and gamma-oryzanol for a period of two months and behavioral tests will be performed at the end of the treatment to check for cognitive performances. Upon mice sacrifice, neuronal morphology will be analyzed and biochemical tests will be conducted on brain and plasma to measure markers of aging and signs of Alzheimer’s disease, including levels of inflammation and oxidative stress and functionality of proteolytic systems. Furthermore, effects on lipid metabolism and on gut-brain axis components including short chain fatty acids (SCFAs), gut hormone peptides and gut microbiota composition will be evaluated.
Milestones
R1. Gamma-oryzanol exerts prebiotic activity on isolated probiotics and on human gut microbiota in vitro batch system.
R1.1 Development of a synbiotic formulation containing probiotics and proper gamma-oryzanol concentration for animal treatment.
R2. Gamma-oryzanol promotes the release of EVs from probiotic bacteria, which in turn have an enriched content of biologically active proteins that are useful in gut-brain communication.
R3. Optimization of the extraction conditions of gamma-oryzanol from rice bran. The obtained product shows a biological activity comparable to that of commercially available products.
R4. Amelioration of SAMP8 cognitive performance upon treatment. Amelioration of the aging hallmarks in the brain and plasma of treated mice with the reduction of oxidative and inflammatory markers and the restoration of proteolysis.
R5. Modulation of the gut-brain axis. Amelioration of gut dysbiosis and proper regulation of gut microbiota composition with a shift towards anti-inflammatory bacterial taxa.
R6. Proper modulation of lipid metabolism. Amelioration of blood lipid profile, hypocholesterolemic effect with a specific regulation of cholesterol homeostasis.
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