A compartmental model for simulating the gut-brain axis in gastric function regulation.

Area of Science:

• Physiology
• Computational Biology
• Neuroscience

Background:

• Gastric function is intricately regulated by the gut-brain axis, involving the vagal and enteric nervous systems (ENS).
• The parasympathetic pathway promotes digestion, while the sympathetic pathway inhibits it, demonstrating complex neural coordination.

Purpose of the Study:

• To develop a novel, computationally efficient mathematical model of the gut-brain axis.
• To simulate vagal and ENS pathways and their impact on gastric function.
• To enhance understanding of gut-brain axis regulation in gastric processes.

Main Methods:

• A three-compartment model representing the stomach (fundus, antrum, pyloric sphincter).
• Incorporation of passive stress and dynamic stomach geometry.
• Modeling of motor and sensory neuron activity, neurotransmitter release (Michaelis-Menten with Hill coefficient), and sympathetic response.
• Linking afferent and efferent firing rates to close the gut-brain axis feedback loop.

Main Results:

• Simulation results align with physiological observations of digestive activity.
• Demonstrated inhibitory effects during sympathetic responses and excitatory effects (e.g., gastric emptying) during parasympathetic responses.
• Observed increased interstitial cells of Cajal activity at high gastric volumes and decreased gastric emptying rates with high-calorie liquids due to pyloric sphincter regulation.

Conclusions:

• The model's flexibility allows for future integration of new signaling pathways.
• Its computational efficiency supports potential applications in closed-loop, model-based control for vagal stimulation therapies.
• The model provides a valuable tool for studying gastrointestinal disorders and gut-brain axis regulation.