A Compartmental Model for Simulating the Gut-Brain Axis in Gastric Function Regulation.

Area of Science:

• Computational biology and neuroscience
• Physiology of the gastrointestinal tract
• Mathematical modeling of biological systems

Background:

• Gastric function is intricately regulated by the gut-brain axis, involving the vagal and enteric nervous systems (ENS).
• The parasympathetic pathway stimulates digestion, while the sympathetic pathway inhibits it, demonstrating complex neural coordination.
• Existing models lack detailed simulation of dynamic gastric geometry and passive stress.

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 effects on gastric function, including dynamic geometry.
• To enhance understanding of gut-brain axis regulation for potential therapeutic applications.

Main Methods:

• A three-compartment mathematical model representing the stomach (fundus, antrum, pyloric sphincter).
• Incorporation of the Michaelis-Menten equation with a Hill coefficient (MMEHC) for neurotransmitter release.
• Modeling of motor neurons, sensory inputs (chemo- and mechanoreceptors), and sympathetic response, linked via fitted curves.

Main Results:

• Simulations align with physiological observations, showing digestive inhibition during sympathetic response and excitation (gastric emptying) during parasympathetic response.
• Interstitial Cells of Cajal (ICC) activity amplitude increases at very high gastric volumes during gastric emptying.
• Gastric emptying rates decrease with high-calorie liquids due to pyloric sphincter regulation.

Conclusions:

• The developed model accurately simulates gut-brain axis regulation of gastric function.
• The model shows potential for studying gastrointestinal disorders and informing vagal-based therapies.
• Dynamic changes in stomach geometry and passive stress are crucial factors in gastric regulation.