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Regulation of the Digestive System01:25

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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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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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Hormones regulate a significant portion of digestion through activation of the neuroendocrine system. The neuroendocrine system of digestion contains many different hormones all with multiple functions that are both, directly and indirectly, involved in digestion.
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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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Enteroendocrine cells, accounting for only 1% of stomach epithelial cells, play a significant role in digestion and are classified by their digestive hormone secretions.
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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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In Vitro and In Vivo Approaches to Determine Intestinal Epithelial Cell Permeability
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Enteroendocrine Cells Regulate Intestinal Barrier Permeability.

Jennifer G Nwako1, Sparsh D Patel1, Taevon J Roach1

  • 1Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, 111 Mason Farm Road, Molecular Biology Research Building 5341C, Chapel Hill, NC 27599.

Biorxiv : the Preprint Server for Biology
|March 31, 2025
PubMed
Summary

Enteroendocrine cells are crucial for maintaining intestinal barrier integrity. Supplementing with hormones like peptide tyrosine tyrosine (PYY) can restore barrier function, offering new therapeutic avenues for inflammatory bowel disease.

Keywords:
Enteroendocrine cellsbarrier functionintestinal organoidspeptide YYtight junctions

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Area of Science:

  • Gastroenterology
  • Cell Biology
  • Immunology

Background:

  • The intestinal epithelial barrier, maintained by tight junctions, is vital for nutrient absorption and pathogen defense.
  • Barrier dysfunction and increased permeability are hallmarks of inflammatory bowel disease (IBD).
  • Current therapies do not directly target or improve intestinal epithelial barrier function.

Purpose of the Study:

  • To investigate the potential role of enteroendocrine cells in maintaining intestinal epithelial barrier integrity.
  • To determine if enteroendocrine cells are necessary for a healthy intestinal barrier.
  • To explore therapeutic potential of enteroendocrine cell-derived hormones in restoring barrier function.

Main Methods:

  • Utilized human intestinal enteroids genetically modified for enteroendocrine cell loss.
  • Assessed barrier function using transepithelial electrical resistance and paracellular permeability assays.
  • Evaluated the localization and abundance of key junctional proteins (zona-occludens 1, occludin, claudin-2).
  • Tested the effects of peptide tyrosine tyrosine (PYY) and octreotide supplementation on barrier function.

Main Results:

  • Enteroendocrine cells were essential for maintaining barrier integrity in both stem and differentiated enteroid cultures.
  • Supplementation with PYY and octreotide rescued barrier defects in enteroendocrine-deficient enteroids.
  • Barrier improvements occurred independently of significant changes in tight junction protein levels.
  • Hormone supplementation restored barrier function under both baseline and tumor necrosis factor (TNF)-induced inflammatory conditions.

Conclusions:

  • Enteroendocrine cells play a significant, previously unappreciated role in augmenting intestinal epithelial barrier function.
  • Hormones secreted by enteroendocrine cells, such as PYY, can restore barrier integrity.
  • These findings present a novel therapeutic strategy for improving intestinal barrier function in inflammatory conditions like IBD.