Coeliac disease triggered by bacterial exposure

Scientists from the Monash Biomedicine Discovery Institute (BDI) and ARC Centre of Excellence in Advanced Molecular Imaging have identified bacterial exposure as a potential environmental risk factor in developing coeliac disease (CD), a hereditary autoimmune-like condition that affects about one in 70 Australians. Approximately half of all Australians are born with one of two genes that cause coeliac disease, with one in 40 likely to develop the condition. People with coeliac disease must follow a lifelong gluten-free diet, as small amounts of gluten can cause health problems. While environmental factors can trigger CD in those with a genetic predisposition, exactly how that works is unclear.

Coeliac disease is caused by an aberrant reaction of the immune system to gluten, a protein which is found in grains such as wheat, rye, barley and oats, and is typically found in bread, pastries and cakes. Immune system cells, known as T cells, perceive gluten as a foreign substance and initiate action against it. The activation of T cells leads to an inflammatory response in the small intestine, causing diarrhoea, bloating and malabsorption of nutrients. If left untreated, the disease can cause serious issues such as malnutrition, osteoporosis, depression and infertility, with a small increased risk of certain forms of cancer, such as lymphoma of the small bowel.

Scientists have provided a molecular foundation for microbial exposure as a potential environmental factor in the development of coeliac disease. The results of the study have been published in the journal Nature Structural and Molecular Biology.

Researchers showed, at the molecular level, how receptors isolated from immune T cells from coeliac disease patients can recognise protein fragments from certain bacteria that mimic those fragments from gluten. Exposure to such bacterial proteins could lead to the generation of aberrant recognition of gluten by these same T cells when susceptible individuals eat cereals containing gluten.

‘Mimicry’. Artwork depicting the way bacterial proteins mimic gluten proteins, causing an immune response to coeliac disease. By artist in residence Erica Tandori, from the Rossjohn laboratory at Monash University. Image credit: Monash University.

“In coeliac disease you get aberrant reactivity to gluten and we have provided a proof of principle that there’s a link between gluten proteins and proteins that are found in some bacteria. That is, it’s possible that the immune system reacts to the bacterial proteins in a normal immune response and in so doing develops a reaction to gluten proteins because, to the immune system, they look indistinguishable — like a mimic,” said Dr Hugh Reid, co-lead researcher from Monash University.

The findings could eventually lead to diagnostic or therapeutic approaches to coeliac disease.

Top image credit: ©stock.adobe.com/au/M.studio