Crohn's disease and the gut microbiome

Development of a microaerobic human intestinal organoid model to determine the role of the gut microbiome in Crohn’s disease

The Humane Research Trust is funding a research project to understand the role of the gut microbiome in Crohn’s disease.

Researchers at the University of East Anglia will use lab-grown human intestinal cells to better understand how the disease develops.

The findings could help reveal the causes of Crohn's disease and support the development of new treatments.

What is Crohn’s disease?

Crohn’s disease is a life-long illness in which part of the bowel becomes inflamed, affecting 120,000 people across the UK.

There is no cure for the condition. Existing treatments help patients manage the symptoms such as inflammation but often come with severe side effects. This treatment approach is also expensive; Crohn’s disease management costs the NHS around £750 million every year.

Scientists aren’t sure what the exact causes of the disease are, though studies suggest an involvement of environmental and genetic factors.

Patients may have genetic mutations that reduce the body’s ability to remove bacteria from the gut. They also tend to have less diversity in the microbial species present in the gut, a phenomenon called microbial dysbiosis.

Additionally, patients suffer with a leaky gut lining/barrier, called the intestinal epithelium. These factors compound and produce an immune response against the bacteria in the gut, resulting in chronic inflammation.

Current challenges in Crohn's disease research

Crohn's disease is a complex condition, and scientists are still trying to understand exactly what causes it.

Many studies currently use mice, but important differences between mice and humans can limit how well the results apply to people.

With human-based alternatives, there are other issues that researchers face. Researchers often use cells derived from colon cancers, but these do not have the same characteristics as the cells affected by Crohn's disease. They also lack the protective mucus layer found in the gut, which provides nutrients for many beneficial bacteria. On top of this, most gut bacteria cannot survive in oxygen-rich conditions, making them difficult to grow and study in the laboratory.

The Humane Research Trust is funding a research project at the University of East Anglia that will use a new model to overcome these challenges.

The project's lead researcher, Dr Stephanie Schüller, believes this approach could also help scientists study other bowel conditions, including ulcerative colitis, irritable bowel syndrome (IBS) and colorectal cancer.

The Trust granted the Andrew Berwitz Award to this innovative project. The award is named in honour of Andrew Berwitz, who served the charity as trustee and treasurer for 29 years.

An animal-free future for intestinal research

In the new research model, the research group will culture human stem cells in an environment mimicking the human intestine. These cells develop into miniature versions of the intestine, known as organoids, which include mucus-producing cells found in the gut.

To help gut bacteria survive, the team will use a specialised chamber that recreates the low-oxygen conditions found in the intestine. This allows the bacteria to interact with the organoids in a way that more closely reflects what happens in the human body.

The scientists will optimise the environment by making alterations to enhance the growth and maintenance of the organoids and microbiota. This includes introducing ‘continuous flow’, which is when they keep the culture medium moving through the chamber, to support long-term incubation.

Next, they will compare organoids and gut bacteria from people with Crohn's disease and healthy volunteers. By swapping the bacteria between the two groups, they can observe how disease-associated bacteria affect healthy gut tissue, and vice versa.

The team will measure changes in the bacteria, the substances they produce, the health of the gut lining and levels of inflammation. This will help them determine whether changes in gut bacteria are a cause of Crohn's disease or a consequence of it.