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Related Concept Videos

Inflammatory Bowel Disease I: Ulcerative Colitis01:27

Inflammatory Bowel Disease I: Ulcerative Colitis

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Introduction
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
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Inflammatory Bowel Disease II: Crohn's Disease01:30

Inflammatory Bowel Disease II: Crohn's Disease

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Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
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Irritable Bowel Syndrome I: Introduction01:17

Irritable Bowel Syndrome I: Introduction

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Irritable Bowel Syndrome (IBS) is characterized by functional disturbances in the gastrointestinal system, presenting a cluster of symptoms without evident structural or biochemical abnormalities. It primarily affects the large intestine and may cause abdominal pain, bloating, excessive gas, diarrhea, constipation, or both.
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
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Chronic Bowel Disorders: Introduction01:17

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Chronic bowel diseases are a group of long-term conditions affecting the digestive tract, characterized by inflammation and damage to the gut lining. These conditions primarily include irritable bowel syndrome and inflammatory bowel disease.
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
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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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Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy01:30

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Various diagnostic tests are employed in the diagnostic process for Inflammatory Bowel Disease (IBD), particularly to differentiate between Crohn's disease and ulcerative colitis.
Diagnostic studies
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Breaking Down Barriers: Epithelial Contributors to Monogenic IBD Pathogenesis.

Jodie D Ouahed1, Alexandra Griffith1, Lauren V Collen1

  • 1Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.

Inflammatory Bowel Diseases
|January 27, 2024
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Summary

Monogenic causes of inflammatory bowel diseases (IBD) linked to intestinal barrier dysfunction are understudied. This review categorizes these genetic defects, highlighting their impact on epithelial barrier integrity and IBD development.

Keywords:
homeostasisintestinal epithelial barriermonogenic inflammatory bowel disease

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Area of Science:

  • Gastroenterology
  • Genetics
  • Immunology

Background:

  • Monogenic causes of inflammatory bowel diseases (IBD) are increasingly identified.
  • Current research prioritizes inborn errors of immunity, with less focus on genetic defects impairing the intestinal epithelial barrier.
  • Therapeutic strategies often involve immune modulation or bone marrow transplantation for IBD patients with immune disorders.

Purpose of the Study:

  • To provide a comprehensive review of monogenic causes of IBD resulting from impaired intestinal epithelial barrier function.
  • To categorize these genetic defects based on their impact on six key epithelial barrier functions.
  • To elucidate the genetic underpinnings, inheritance patterns, clinical features, and translational implications of these disorders.

Main Methods:

  • Literature review of monogenic causes of IBD affecting the intestinal epithelial barrier.
  • Categorization of genetic defects based on impaired epithelial cell organization, intrinsic functions, apoptosis/necroptosis, complement activation, signaling, and RNA degradation control.
  • Synthesis of current understanding of involved genes, inheritance patterns, IBD features, and translational research.

Main Results:

  • Monogenic defects impairing intestinal epithelial barrier function represent an underappreciated cause of IBD.
  • These defects can be grouped into six functional categories impacting epithelial integrity.
  • Impairment in any of these categories can precipitate IBD development.

Conclusions:

  • Genetic defects affecting the intestinal epithelial barrier are critical contributors to IBD pathogenesis.
  • Understanding these monogenic causes offers new avenues for diagnosis and therapeutic development.
  • Further research into these specific genetic pathways is essential for advancing IBD management.