A 3D gut-brain-vascular platform for bidirectional crosstalk in gut-neuropathogenesis

Area of Science:

• Neuroscience
• Gastroenterology
• Biomedical Engineering

Background:

• The gut-brain axis is a complex bidirectional communication pathway.
• Existing in vitro models lack the complexity to fully represent gut-brain interactions.
• Understanding this axis is crucial for neurogastrointestinal disease mechanisms and treatments.

Purpose of the Study:

• To develop and validate a novel 3D human gut-brain-vascular microphysiological platform.
• To model circulation-mediated crosstalk between the gut and brain.
• To investigate bidirectional signaling in the gut-brain axis.

Main Methods:

• Integration of a lumenized intestinal barrier, vascular-astrocyte interactions, and brain tissue.
• Utilizing a 3D microphysiological system to mimic human gut-brain-vascular interfaces.
• Employing bacterial toxins and disease-relevant stimuli to probe signaling pathways.

Main Results:

• Demonstrated gut-to-brain signaling: bacterial toxins crossed barriers, inducing neuroinflammation and tau pathology.
• Showcased brain-to-gut feedback: stimuli from the brain compartment caused neuroinflammation and barrier disruption.
• Validated the platform's ability to model bidirectional communication and disease pathology.

Conclusions:

• The developed 3D platform accurately models human gut-brain-vascular interactions.
• The platform facilitates the study of gut-to-brain and brain-to-gut signaling mechanisms.
• This human-relevant model is valuable for dissecting neurogastrointestinal diseases and evaluating therapeutics.