Brain neurodegeneration is a major challenging ISSUE for todays’ research: Alzheimer’s disease (AD) is expected to reach 80 million patients worldwide in 2050 but still its main triggers are mostly unknown. Recently, many biologists, gastroenterologists and clinicians have proposed an intriguing CONCEPT referred to as microbiota-gut-brain axis (MGBA) that states that there is a connection between the brain, the gut and our intestinal microflora, the group of microorganisms that lives in our gut and that are collectively named “microbiota”. A huge amount of data indicates that microbiota affects brain functionality: a reliable, fascinating HYPOTESYS states that microbiota can trigger neurodegeneration through the MGBA, suggesting new revolutionary therapeutic approaches aimed at slowing down neurodegenerative disease progression by modulating microbiota composition with a huge beneficial IMPACT on SOCIETY worldwide. Unfortunately, the lack of a comprehensive model of the MGBA able to bridge current in vivo model complexity with the in vitro tools’ simplicity represents still a GAP that keeps researchers far from fully clarify microbiota-neurodegeneration potential mechanisms. MINERVA project has targeted this gap using an INNOVATIVE bioengineered APPROACH, to help in exploring in a completely NEW way the relation between neurodegeneration and human intestinal microflora.
MINERVA final GOAL has been to develop the first engineered multi-organ platform recapitulating in vitro the connections among the main players of the MGBA: the gut microbiota; the gut epithelium; the immune system; the blood-brain barrier; the brain.
The PLATFORM relies on three compartments, one for each component of the axis, that host multiple units of an innovative, engineered organ-on-a-chip device, developed within MINERVA project, serially interconnected in order to represent the MGBA players’ interaction.
In the “Microbiota-compartment”, human microbiota strains can be cultured and produce a mix of molecules named “secretoma” that, once transported to the “Gut-compartment”, interacts with human gut epithelial cells and cells from the immune system, that modify it as occurs in vivo, giving the so-called “metabolised secretome”. It reaches the “Brain-compartment”, that hosts a complete Blood-Brain-Barrier model followed by two human brain cell models, where neurons, astrocytes and microglia, the three main cellular populations of the brain, can be: (a) co-cultured to explore microbiota effect on brain cells interconnected as in the real tissue; (b) cultured individually to investigate microbiota impact on each cell type.
