Introduction

Many diseases arise from both genetics and environmental influences.¹ A well-recognised example of this is Crohn’s Disease, a chronic inflammatory disorder in the gastrointestinal tract that commonly presents with symptoms such as abdominal pain and diarrhoea.² Around 20 to 25% of Crohn’s disease cases occur in children, and the incidence among paediatric patients continues to rise globally.¹ This article examines the genetic and environmental factors that contribute to Crohn’s disease in children. 

What is paediatric crohn’s disease?

Paediatric Crohn’s Disease is a type of Inflammatory Bowel Disease (IBD) in which the detailed disease mechanisms are still unclear.³ However, substantial evidence suggests that it results from an abnormal immune response to environmental triggers in individuals who are genetically predisposed to developing Crohn’s disease.² The disease causes chronic inflammation of the gastrointestinal tract, leading to symptoms such as:

• Growth delay
• Diarrhoea
• Tiredness
• Rectal bleeding
• Vomiting⁴

Paediatric Crohn’s Disease tends to be more severe in children under the age of six, and this younger age group is often less responsive to standard treatment options.⁴

What is the difference between Paediatric and Adult Crohn’s Disease?

Both paediatric and adult forms of Crohn’s disease involve chronic inflammation of the gastrointestinal tract, but there are a few more differences between the two, besides one presenting in children and the other in adults.³

Firstly, genetics plays a significantly larger role in the development of Crohn’s disease in children than in adults. In fact, the younger a child is, the stronger the genetic influence. Conversely, environmental influences have a greater impact on the development of Crohn’s disease in adults.³

Additionally, paediatric Crohn’s disease is typically more severe than the adult form. The symptoms reported by children are often different to those in adults and can include a delay in growth and anaemia. Children also tend to develop more extensive inflammation in the upper gastrointestinal tract than adults.³

Genetic risk factors for paediatric crohn’s disease

If Crohn’s Disease runs in the family, it greatly increases the risk of a child developing it. In addition to inheriting specific gene variants from parents, new (spontaneous) mutations can also arise due to errors in DNA replication. More than 200 genes have been identified as being associated with Crohn’s disease. A study that analysed the genetic profiles of over 1000 children with Inflammatory Bowel Disease found that affected children were more likely to carry known Crohn’s disease risk variants than healthy children. These findings provide strong evidence for a genetic contribution to the development of paediatric Crohn’s disease.⁵ 

Examples of genes associated with Paediatric Crohn’s Disease

NOD2 was first identified as a major risk gene for paediatric Crohn’s disease in 2001. The NOD2 gene encodes a bacterial sensor which is found on many immune cells. Mutations in the NOD2 gene can therefore lead to the impaired removal of bacteria, which can result in bacteria lingering and replicating in the body and triggering intestinal inflammation.⁶ These mutations also disrupt the immune system’s regulation of the gut microbiome —the community of beneficial (commensal) bacteria—leading to an imbalance that enables harmful bacteria to overgrow and promote gut inflammation.⁷

A specific mutation in the IL23R gene (encoding the IL-23 receptor) has been associated with providing protection against Crohn’s disease in children as opposed to being a risk mutation. IL23R is expressed on memory T cells, a population of immune cells involved in inflammation, and its primary function is to activate these T cells in response to immune signalling.⁸ When activated, the receptor can trigger signalling pathways which can contribute to gut inflammation.⁹ The protective IL23R variant works by reducing the amount of memory T cells being activated, thereby decreasing the inflammatory response in the gastrointestinal tract. Studies in children show that those with this variant had a lower chance of developing Crohn’s disease compared to children without it.⁸

Environmental risk factors for paediatric crohn’s disease

Whilst numerous environmental exposures can increase a child’s susceptibility to paediatric Crohn’s disease, there are also some that can reduce it. Important influences include early-life diet, breastfeeding, and prenatal exposures like maternal antibiotic use or tobacco use.³

Prenatal antibiotic and tobacco exposure

During the first twelve weeks of pregnancy, the fetal immune system begins to develop. At this critical stage, environmental exposures from the mother can have an influence on how the fetal immune system will develop. Factors such as antibiotics and tobacco smoke during pregnancy have been shown to raise the risk of paediatric Crohn’s disease in the child. These factors can affect the immune system and disrupt gut microbiota. Smoking during pregnancy has been shown to increase the risk of childhood inflammatory bowel disease by almost 50%.¹⁰

Diet 

A child’s diet plays a major role in determining their risk of Crohn’s disease. Diets high in fat and sugar, known as the western diet, increase the risk.³ Animal studies support this and have shown that high-fat diets can lead to inflammation of the intestines. Food choices can also modify the composition of the gut microbiota. For example, consuming meat more than four times per week has been linked to reduced gut bacterial diversity, which may increase susceptibility to inflammation.^11,12

However, other foods like fibre can have the opposite effect. Eating fibre-rich foods is associated with a lower risk of Crohn’s disease.³ Fibre supports gut health by serving as a fuel source for beneficial bacteria, helping maintain microbial balance and reducing inflammation.¹²

Breastfeeding 

Breastfeeding has been shown to protect against the development of paediatric Crohn’s disease.³ It shapes the infant’s gut microbiota, supports the maturation of the immune system and may reduce the risk of other immune-mediated diseases.¹³

Interaction between genetics and the environment in paediatric crohn’s disease

Genetic and environmental risk factors do not act independently; rather, they interact to influence the risk of a disease. All inflammatory bowel diseases are thought to arise from a complex interplay between inherited factors and environmental exposures. A child may inherit a mutation that makes them more susceptible, but it usually requires an environmental trigger for the disease to manifest. Think of it like the genetic mutation increases the risk of the disease, but the environmental factor pushes you to the tipping point, which causes you to actually develop the disease (like a switch). 

Twin studies strongly support this genetic–environmental interaction. Identical twins have the same DNA, but it is rare for both to develop Crohn’s disease. Their concordance rate is higher than that of non-identical twins, but still far below 100%, indicating that environmental factors must contribute significantly to disease onset.¹⁴ 

Summary

Paediatric Crohn’s Disease is a type of inflammatory bowel disease which involves the chronic inflammation of the gastrointestinal tract, with symptoms including diarrhoea, growth delay and vomiting.^2,4 Both genetics and the environment are thought to interact in the disease development, a concept supported by twin studies showing that the concordance rate in identical twins remains well below 100%.¹⁴ Key genetic contributors include mutations in genes such as NOD2 and IL23R, while important environmental influences include breastfeeding and the diet.^6,8,3 These factors influence the immune system’s function as well as the composition of the gut microbiota. 

Although the precise disease mechanisms remain unclear, current evidence supports the idea that paediatric Crohn’s disease results from a complex interaction between genetics and the environment. 

FAQs

What other types of inflammatory bowel disease are there, and what’s the difference compared to Crohn’s Disease?

The two main types of inflammatory bowel disease are Crohn’s disease (which includes paediatric Crohn’s disease) and Ulcerative Colitis. The main difference is that Ulcerative Colitis can affect any part of the colon, whereas Crohn’s disease can affect the whole gastrointestinal tract, which is anywhere from the mouth to the anus (including the colon). They both cause chronic inflammation and similar symptoms.¹⁵