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Related Concept Videos

Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
Dysbiosis of the Gut Microbiota01:18

Dysbiosis of the Gut Microbiota

The human gut microbiome includes a diverse array of microbial species, including beneficial commensals and opportunistic pathogens, which interact to support host health. These microbes contribute to essential functions such as nutrient metabolism, immune system modulation, and maintenance of intestinal barrier integrity. However, disruptions to this equilibrium—referred to as dysbiosis—can have widespread physiological consequences.Dysbiosis is often characterized by reduced microbial...
Inflammatory Bowel Disease II: Crohn's Disease01:30

Inflammatory Bowel Disease II: Crohn's Disease

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 transmural...
Inflammatory Bowel Disease I: Ulcerative Colitis01:27

Inflammatory Bowel Disease I: Ulcerative Colitis

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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...
Inflammatory Bowel Disease II: Ulcerative Colitis01:20

Inflammatory Bowel Disease II: Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
Chronic Bowel Disorders: Introduction01:17

Chronic Bowel Disorders: Introduction

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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Chronic Salmonella Infection Induced Intestinal Fibrosis
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Interleukin23 Receptor Genetic Variants Associate With Crohn's Disease Risk and Microbiome Changes in Healthy

Haim Leibovitzh1, Anna Neustaeter1, Sun-Ho Lee1

  • 1Division of Gastroenterology and Hepatology, Temerty Faculty of Medicine, Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association
|May 28, 2026
PubMed
Summary

Genetic risk score for Interleukin-23 receptor (IL23-R) variants increases Crohn's disease (CD) risk and alters gut microbiome in healthy relatives. This IL23R-GRS identifies individuals for monitoring or preventive therapies.

Keywords:
Gut MicrobiotaHealthy Relatives of Patients With Crohn’s DiseaseInterleukin23 ReceptorIntestinal Permeability

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07:34

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Published on: December 16, 2021

Area of Science:

  • Genetics
  • Gastroenterology
  • Microbiome Research

Background:

  • Single nucleotide polymorphisms (SNPs) in IL23-R are linked to Crohn's disease (CD).
  • IL-23 pathway is implicated in intestinal barrier function and gut microbiome composition.
  • Investigating IL23-R variants in healthy first-degree relatives (FDRs) can reveal early disease predictors.

Purpose of the Study:

  • To determine if IL23-R genetic variants predict CD risk in healthy FDRs.
  • To assess the influence of IL23-R variants on gut barrier function and microbiome composition.
  • To explore potential clinical applications of IL23R genetic risk score (IL23R-GRS).

Main Methods:

  • Utilized genotypic data from 3,055 healthy FDRs in the CCC-GEM cohort.
  • Generated a weighted IL23R-GRS from seven CD-associated IL23R SNPs.
  • Assessed intestinal permeability (n=1,698) and microbiome profiling (n=2,523); analyzed CD onset risk using Cox models.

Main Results:

  • A high IL23R-GRS was associated with a 1.67-fold increased CD risk (p=0.044), independent of subclinical inflammation.
  • No association was found between high IL23R-GRS and intestinal permeability (p=0.84).
  • High IL23R-GRS correlated with altered microbiome composition, including decreased Faecalibacterium and increased Akkermansia (q<0.1).

Conclusions:

  • High IL23R-GRS predicts increased CD risk in healthy FDRs.
  • IL23R-GRS is linked to gut microbial alterations but not intestinal permeability.
  • IL23R-GRS may aid in identifying high-risk individuals for targeted monitoring or preventive strategies.