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Gut-Brain Axis

Gut-Brain Axis

The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such as...

Neural Regulation

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Gastric Motility

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Gastric motility is the coordinated contraction and relaxation of stomach muscles that convert ingested food into chyme, a semi-liquid substance ready for further digestion in the intestines. The process begins with the vagus nerve inducing the relaxation of the smooth muscles in the fundus and body of the stomach, allowing these regions to expand and accommodate up to approximately 1.5 liters of food and liquid.
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Hormonal Regulation

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Digestive activity regulation hinges on three primary components. Activation is prompted by a multitude of mechanical and chemical indicators, primarily detected by receptors within the stomach and intestines' walls. These receptors predominantly respond to factors such as mechanical stretching of the organ walls, changes in pH and osmolarity, and the presence of digesting materials and their by-products.
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Enteric Nervous System: Regulation of GI Motor Activity

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

Shannon Q Fernandes¹, Mayuresh V Kothare¹

¹Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, PA, United States.

Frontiers in Physiology

|June 19, 2026

Summary

This study presents a new mathematical model of the gut-brain axis, simulating neural pathways to understand gastric regulation. The model accurately reflects physiological responses, showing potential for treating gastrointestinal disorders.

Keywords:

autonomic nervous system compartmental modeling framework computationally inexpensive model gut-brain axis vago-vagal loop

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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.