Crohn’s disease is an auto-inflammatory disorder that affects the gut. People with Crohn’s disease must manage chronic pain, fatigue, and severe complications, such as intestinal blockages and ulcers. The time taken to diagnose a person with Crohn’s disease is critical in preventing the development of more severe complications.
Helmsley supports innovative research aimed at improving improves our understanding of the disease course, with the hope that these discoveries lead to future preventative therapies. Helmsley supported the Genetic, Environmental, Microbial (GEM) Project and its goal to predict a person’s risk of developing Crohn’s disease, prevent the disease before symptoms appear, and develop new treatments for those who already have the disease. Since 2008, the GEM Project has enrolled 5000 healthy first-degree relatives of people with Crohn’s disease across seven countries.
Recently the GEM project published three significant papers in the journals Clinical Gastroenterology and Hepatology and Gastroenterology. GEM researchers established the risk of developing Crohn’s disease in healthy individuals with multiple immediate family members with Crohn’s disease. They developed and validated a scoring method to assess these individuals’ risk of developing Crohn’s disease, and identified environmental factors associated with its onset.
These studies demonstrate the complex interplay of genetics and environment in shaping health and microbiomes among individuals with a family history of Crohn’s disease. Future work integrating these findings from the GEM project could bring us closer to transformative interventions in the management and prevention of Crohn’s disease.
A deeper look at their findings:
Identifying Individuals with Higher Risk of Developing the Disease
People with at least two immediate family members with Crohn’s disease are at a significantly higher risk of developing the disease. The GEM project aimed to identify differences in biomarkers between healthy individuals at high risk for developing Crohn’s disease and those with only one immediate family member affected by the disease.
The research found that healthy individuals with multiple immediate family members with Crohn’s disease were three times more likely to develop the disease. They had higher levels of gut inflammation and altered microbiomes (bacteria, viruses and fungi found in the gut) despite not yet having Crohn’s disease. Notably, both groups had the same level of genetic risk for developing Crohn’s disease, suggesting that environmental factors, such as diet or early-life exposures, likely contribute to the increased gut inflammation and altered microbiome alterations.
Assessing Risk in Individuals with Family Members with Crohn’s Disease
To enhance early detection of Crohn’s disease, GEM researchers developed a method to evaluate the risk of healthy individuals developing the disease when they have multiple immediate family members affected. This risk score employs a novel approach that incorporates various predictive biomarkers, such as gut inflammation and permeability (the ability to prevent toxins from entering the bloodstream) alongside microbial composition and activity. During validation, the model demonstrated potential for distinguishing high-risk individuals, which is essential for designing future primary prevention trials for Crohn’s disease. This score could help identify patients who may require more frequent monitoring for the development of Crohn’s disease.
Establishing Environmental Factors Associated with Crohn’s Disease Onset
The GEM Project examined whether living with three or more people or with pets, such as dogs or birds, influenced the onset of Crohn’s disease symptoms of at-risk individuals. Researchers tracked exposure to these factors from the first year of life up to age 15 in participants enrolled in the study. They found that these environmental factors induced changes in pre-disease biomarkers, such as gut permeability, gut inflammation, and microbiome composition in at-risk individuals.
For individuals at high risk, living with three or more people or a bird during early life was correlated with the development of pre-disease biomarkers. Interestingly, living with a dog was identified as a potential protective factor against developing Crohn’s disease. With further research, this finding could inform preventative strategies for those at risk.
Future research is essential to understand how these environmental factors influence the onset of Crohn’s disease and how they alter the gut biology in at-risk individuals.
Read more about the GEM project here.