Exposure to bacteria that mimics gluten can confuse the immune system and trigger coeliac disease, Melbourne scientists have shown for the first time.
The results raise the possibility of using probiotics or developing a vaccine to prevent the disease, which affects nearly 400,000 Australians and 70,000 New Zealanders.
Some of the suspect bacteria live naturally in our guts – which might explain why people with coeliac disease can still suffer even after eliminating gluten from their diet.
"This is the first time we have shown a potential mechanism for why the microbiome may be involved in the initiation of this disease," says Hugh Reid, the Monash University researcher who led the multi-institute study.
The study also has big-picture implications. If bacteria have proteins that mimic gluten, they probably have proteins that mimic lots of things people are allergic to. Could it be that bacteria and viruses trigger many common autoimmune conditions?
Coeliac disease occurs when the body's immune system begins reacting to gluten, a protein found in wheat, rye, and barley.
When someone with the disease eats gluten, their immune system misidentifies it as a foreign invader. It mounts a huge immune response in the gut, trying to "kill" the gluten – which can lead to bloating, diarrhea and intestinal damage.
About 50 percent of people carry genes that make them susceptible to coeliac disease, but these people are not born allergic to gluten. Only one in 70 with the genes ever develops it.
It seems they come across some sort of trigger as children, activating the condition before their immune system has fully matured. Scientists have long suspected mimics are to blame.
A small number of viruses and bacteria produce protein fragments that look almost identical to parts of gluten – "molecular mimics", scientists call them.
The team used molecular databases to assemble a set of protein fragments produced by bacteria that looked near-identical to gluten. They ended up with about 20, many produced by species that live naturally – and harmlessly – within our gut.
Then researchers at the Walter and Eliza Hall Institute took blood from people with coeliac disease, and exposed the immune cells to the gluten mimics the team had found.
Immediately, the immune cells went on the attack – just as if they had spotted a molecule of gluten. "It's a case of mistaken identity," says Dr. Reid.
To confirm the results, they used the Synchrotron, a 200-meter-long tube buried under the Melbourne suburb of Clayton that shoots out light 1 million times brighter than the sun, to take a high-resolution molecular photograph of the bacterial protein fragments as they reacted with immune-system molecules.
The images looked identical to the way the gluten fragments reacted with the same molecules. "That nailed it," says Dr. Reid.
The team's paper, published in Nature Structural and Molecular Biology, is the smoking gun for the molecular mimic theory, but there are lots of questions still to be answered.
The big one: if these mimic-bacteria live in many people's guts, why doesn't everyone with susceptible genes get coeliac disease?
The answer may have to do with the number of bacteria, Dr. Reid says.
The immune system might happily tolerate a small number of mimic bacteria living in our guts. But if there are too many, it might go on the attack.
It might then remember that attack – our immune systems are designed to remember viruses and bacteria they come across - and mount an offensive whenever it sees a similar molecule. Like gluten.
That would explain why studies have shown children who develop coeliac disease tend to have abnormal microbiomes.
Using antibiotics, which kill off healthy gut bugs and open space for other ones to thrive, is also linked to developing coeliac disease.
Perhaps this allows the number of mimic bateria to grow high enough to trigger the disease?
"There are a lot of questions that are not answered by this," says Dr Reid. "But we have paved the way for developing strategies for preventing this disease.
"We could vaccinate people against this particular bacteria, potentially, or use probiotics."
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