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Updated: Aug 20, 2025

Organoid-Derived Epithelial Monolayer: A Clinically Relevant In Vitro Model for Intestinal Barrier Function
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The genetics of monogenic intestinal epithelial disorders

Stephen J Babcock1, David Flores-Marin1, Jay R Thiagarajah2

  • 1Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Enders Rm 605, 300 Longwood Ave, Boston, MA, 02115, USA.

Human Genetics
|November 24, 2022
PubMed

Insights

Congenital diarrheas and enteropathies (CoDEs) are rare genetic disorders affecting intestinal cells. While over 45 genes are linked, understanding pathophysiology and developing targeted therapies remain critical challenges.

Area of Science:

  • Gastroenterology
  • Genetics
  • Pediatrics

Background:

  • Monogenic intestinal epithelial disorders, or congenital diarrheas and enteropathies (CoDEs), are rare genetic conditions impacting intestinal epithelial cell function.
  • These disorders typically manifest in infancy with diarrhea and poor growth, necessitating intensive supportive care.
  • Over 45 genes are now implicated, highlighting rapid advancements in genetic discovery.

Purpose of the Study:

  • To provide a comprehensive overview of CoDE disorders, encompassing their history, genetics, and clinical presentations.
  • To elucidate the known pathophysiology of specific CoDE disorders.
  • To identify current challenges and future directions in the genetic and therapeutic landscape of CoDEs.

Main Methods:

  • Literature review of monogenic intestinal epithelial disorders.
  • Synthesis of information on genetics, clinical features, and pathophysiology.
  • Analysis of current management limitations and future research needs.

Main Results:

  • CoDE disorders are classified based on affected epithelial functions, structures, or development.
  • Genetic sequencing has identified over 45 causative genes, but cellular pathophysiology is often poorly understood.
  • Limited therapeutic options exist, underscoring the need for disorder-specific treatments.

Conclusions:

  • Despite genetic advances, a significant knowledge gap exists in understanding CoDE pathophysiology.
  • Urgent need for novel, targeted therapies for these rare intestinal disorders.
  • Future research should focus on elucidating cellular mechanisms to enable effective treatment development.

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