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Neural Regulation01:37

Neural Regulation

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Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
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Gastric Motility01:16

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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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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 Activity01:11

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The Enteric Nervous System (ENS) plays a pivotal role in regulating gastrointestinal or GI motor activity. This complex network of nerves, deeply embedded within the gut wall, responds to changes in the gut environment and receives input from both the autonomic nervous system and the central nervous system. By doing so, the ENS operates various programs tailored to the body's nutritional status and needs.
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The gastrointestinal tract, responsible for the digestion and absorption of nutrients, is safeguarded by the intestinal barrier, which consists of secretory, physical, and immune components. At the forefront is the secretory barrier, composed of essential elements such as mucus, gut microbiota, and defense proteins. They collaborate to break down food particles, facilitate nutrient absorption, and maintain optimal gut health. These secretory components ensure the smooth functioning of the...
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Updated: Jan 16, 2026

A Gut-on-a-Chip Model to Study the Gut Microbiome-Nervous System Axis
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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, 18015, USA.

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|October 1, 2025
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Summary
This summary is machine-generated.

This study models the gut-brain axis to understand gastric regulation. The novel computational model simulates neural pathways, revealing how sympathetic and parasympathetic signals impact digestion and gastric emptying.

Keywords:
autonomic nervous systemcompartmental modeling frameworkcomputationally inexpensive modelgut-brain axisvago-vagal loop

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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.